Respiratory Diseases

DISEASES OF THE UPPER AIRWAY

These disorders are characterized by inspiratory dyspnea. The increased resistance to airflow caused by upper airway obstructions often creates audible inspiratory noise and results in referred airway sounds through the tracheobronchial apparatus. Sounds that have been “referred” to the lower airway from an upper airway obstruction may be misinterpreted as lower airway in origin unless the upper airway is examined and the trachea ausculted in such cases. If the respiratory sounds can be heard without a stethoscope, they are most likely originating from the upper respiratory tract. The upper airway examination should include detection of airflow from both nostrils, close examination of soft tissues of the head, and oral examination if necessary. Severe upper airway obstruction can cause open mouth breathing and head extension as the affected cow tries to decrease the resistance to airflow (Figure 4-1 ).

Figure 4-1.

Open mouth breathing and neck extension in adult Holstein with retropharyngeal abscessation and pain associated with iatrogenic trauma.

Mechanical or Obstructive Diseases

Congenital

Etiology and Signs.

Congenital disorders including pharyngeal cysts of respiratory epithelial origin, nasal cysts, cystic nasal conchae, skull anomalies, laryngeal malformations, and branchial cysts have been observed in calves and adult cows. Inspiratory dyspnea with audible snoring sounds or stertorous breathing is a sign common to most of these problems. The condition may be present at birth or is most often observed within the first few months of life. The degree of dyspnea associated with these abnormalities tends to be progressive as a result of either enlargement of the lesion (cyst) or worsening upper airway edema and swelling from the mechanical overwork associated with respiratory efforts to move air through an airway narrowed by malformations.

Diagnosis.

Specific diagnosis requires physical examination, including visual inspection of the nares and oral cavity, endoscopy, and skull radiographs (Figure 4-2 ). In addition, aspiration for cytology and cultures may be indicated for cystic lesions. Most cystic lesions will be secondarily infected.

Figure 4-2.

Radiograph of a conchal cyst in a 6-month-old heifer.

Treatment.

Method of treatment depends on the specific lesions found. Cystic conditions may be the most treatable because surgical removal offers some hope of being curative. Simple drainage or drainage with cautery of cystic lesions is not likely to be successful. Therefore referral of such cases to veterinary surgeons experienced in upper airway surgery is recommended so that complete excision of the secretory epithelium can be completed. Other conditions such as laryngeal malformations and skull anomalies have a poor prognosis.

Regardless of cause, symptomatic or supportive treatment may be necessary before diagnostic procedures are performed in calves with severe dyspnea, lest the stress of examination or endoscopy induce anoxia. A tracheostomy should be considered to allow safe diagnostic manipulation. Misinterpreting anoxic patient struggling as wildness requiring additional physical restraint is a frequent, and potentially fatal, error in judgment made by inexperienced clinicians. When a dyspneic animal struggles during examination, usually it is anoxic, frightened, and extremely anxious. All restraint of the head and neck should be relaxed, and the animal should be allowed to “get its breath.” Continued restraint during these situations will result in asphyxiation of the animal.

Although the prognosis for congenital lesions varies with the specific diagnosis, generally it is guarded to poor.

Acquired

Etiology and Signs.

Acquired mechanical or obstructive lesions of the upper airway may occur in calves or adult cattle. Most of the lesions represent enlargement or inflammation of tissues and structures external to the airway itself. Impingement into the upper airway by soft tissue masses such as pharyngeal abscesses, retropharyngeal cellulitis, necrotic laryngitis, pyogranulomatous swellings (e.g., wooden tongue), enlarged lymph nodes, neoplasms, foreign bodies, or enlarged maxillary sinuses compose the majority of lesions. Pharyngeal abscesses and necrotic laryngitis are probably the most common acquired causes of obstruction. Pharyngeal abscesses and retropharyngeal cellulitis may occur following traumatic injury to the mouth when an animal is treated with oral medication or may arise in calves with no history of pharyngeal trauma.

Regardless of cause, progressive inspiratory dyspnea is the primary sign observed in affected cattle. Fever may be present with pharyngeal abscesses or chronic maxillary sinusitis. Unilateral nasal discharge or reduced airflow from one nostril may be present with maxillary sinusitis or unilateral neoplasms of the nasal pharynx or maxillary sinus. Lymphadenopathy may be present as a primary sign in neoplastic conditions, such as juvenile lymphosarcoma and adult lymphosarcoma (Figure 4-3, Figure 4-4 ), or as a secondary sign, in cases of soft tissue infections. Unilateral Horner's syndrome and progressive exophthalmos have been observed in slow-growing adenocarcinomas of respiratory epithelial origin in the nasal pharynx (Figure 4-5 ). Cattle with unilateral nasal obstruction often show more obvious respiratory signs during hot weather. One cow with Horner's syndrome would demonstrate open mouth breathing on hot days because of the nasal mucosal vasodilation and edema (Figure 4-6 ). A fetid odor may exist on the breath caused by chronic inflammation or tumor necrosis in some cattle. The owner may report a progressive course of stertorous breathing eventually leading to open mouth breathing. Inflammatory lesions often have a more acute course than neoplasms, but this is a generality rather than a rule. Obvious external swelling may be present in certain conditions such as chronic maxillary sinusitis, pharyngeal or retropharyngeal abscesses, and lymphosarcoma.

Figure 4-3.

Juvenile lymphosarcoma in a 4-month-old Milking Shorthorn calf presented because of inspiratory dyspnea.

Figure 4-4.

Adult Holstein with lymphosarcoma mass in the pharyngeal area that caused inspiratory dyspnea.

Figure 4-5.

Aged Jersey cow with an adenocarcinoma of respiratory epithelial origin. The mass caused reduced airflow through the left nasal passage, left-sided Horner's syndrome, and exophthalmos. The eyelids have been sutured together to protect the eye.

Figure 4-6.

Open mouth breathing in a 5-year-old cow with unilateral Horner's disease (etiology unknown). The cow had no respiratory difficulties during the winter months.

Diagnosis.

A complete physical examination followed by manual and visual inspection of the oral cavity is the first diagnostic procedure. Relative equality of airflow and the odor of the breath should be evaluated at the nostrils. If chronic maxillary sinusitis is suspected, the upper premolar and molar teeth should be examined closely for abnormalities.

Endoscopy should be performed in an effort to identify a specific lesion or the anatomic region of impingement of tissue into the airway. When performing endoscopy in a calf or cow with severe upper airway dyspnea, most of the mucosal surfaces (e.g., soft palate, larynx, and respiratory pharynx) will be edematous from exertional or labored respiratory efforts. This edema should not be misinterpreted as the causative lesion (see video clips 3 to 5).

Skull radiographs may be necessary if physical examination and endoscopy fail to identify a lesion. Radiographs are helpful for definitive diagnosis of sinusitis, nasal or sinus cyst, and for identifying the location of soft tissue masses such as abscesses or tumors. In addition, radiographs would help to identify abscessed tooth roots in cases of chronic maxillary sinusitis and metallic foreign bodies.

Diagnostic ultrasonography, if available, may help in the assessment of soft tissue swellings. This technique also has been used to locate retropharyngeal abscesses and nonmetallic foreign bodies so that external drainage may be performed safely.

In the case of obvious or palpable swellings of the head or pharynx, aspirates for cytology and culture are indicated. Similarly, biopsies for histopathology are indicated for solid masses or enlarged lymph nodes.

Treatment and Prognosis.

Treatment is most successful when external compression of the upper airway can be cured through treatment of an inflammatory lesion. Pharyngeal or retropharyngeal abscesses should be drained with liberal incisions that avoid vital structures. Internal drainage is preferred unless the abscess is close to the skin surface. External drainage is technically difficult in deep pharyngeal abscesses located more than a few centimeters below the skin surface. Vagus nerve damage, salivary duct laceration, and acute cellulitis are potential complications associated with opening the abscess. If drainage is not liberal, abscesses tend to recur. If recurrence is obvious, culture and sensitivity coupled with drainage through multiple sites are indicated. Daily flushing of the drainage sites is important. Systemic antibiotics should be administered for 1 to 2 weeks following drainage; Arcanobacterium pyogenes (A. pyogenes) and Fusobacterium spp. are the most common organisms cultured, so penicillin is the most commonly used antibiotic.

Chronic maxillary sinusitis should be treated by trephination of the sinus, removal of any teeth that have infected roots, daily flushing of the sinus with dilute disinfectants or sterile saline, and appropriate systemic antibiotics for 1 to 2 weeks.

In general, neoplasms have a hopeless prognosis, and the animal should not be treated. Juvenile lymphosarcoma often causes upper airway dyspnea via enlarged pharyngeal lymph nodes. Occasional adult-form lymphosarcoma cases have one or more very large (10 to 20 cm diameter) pharyngeal or mediastinal lymph nodes that will cause dyspnea. Lymphosarcoma usually results in death within 1 to 6 months of diagnosis. Adenocarcinomas originating in the respiratory pharynx in older cattle (i.e., more than 8 years of age) may have an insidious but progressive course over months to years. Therefore unlike cattle with lymphosarcoma, these animals may be allowed to survive for some time to deliver another calf or to undergo superovulation and embryo transfer. Only if the animal stops eating, develops severe respiratory distress, or is suffering from exposure damage from an exophthalmic eye will euthanasia be necessary. Cattle affected with primary squamous cell carcinoma, metastatic squamous cell carcinoma, or osteosarcoma originating in a sinus, bone, or periocular location occasionally may have enough tumor mass or lymph node metastases to develop inspiratory dyspnea. Cattle with squamous cell carcinomas frequently have a fetid breath odor from the primary tumor and should not be made to suffer unduly.

Inflammatory Diseases

Allergic Rhinitis

Also called summer snuffles, allergic rhinitis occurs primarily in cattle turned out on pasture in the spring and summer. Affected cows do not act ill but have a heavy bilateral nasal discharge and nasal pruritus. This condition also has been described as a familial problem in a group of Holstein-Angus cattle. Affected cattle may rub their nose so frequently that foreign bodies may be trapped in the nasal cavity, and significant self-induced trauma may ensue.

Granulomatous Rhinitis

Diffuse nasal granulomas are uncommon in dairy cattle in the northeastern United States. Rhinosporidium is the most common cause of granulomas that are observed. The granulomas develop on the nasal mucosa through the turbinate region, and as they enlarge, the nasal airway is progressively compromised. Therefore signs include a progressive inspiratory dyspnea, nasal discharge, and pruritus.

Frequently epistaxis is reported by the owner. Inspection at the nares with the aid of a focal light source allows observation of the tan or brown granulomatous masses in the nasal region. Endoscopy further defines the lesion. Biopsy for tissue culture and histopathology is indicated to determine the exact cause of the nasal granulomas.

Treatment consists of sodium iodide solution intravenously (IV; 30 g/450 kg once or twice at 24-hour intervals), followed by 30 g of organic iodide powder orally each day until signs of iodism occur.

Granulomas Caused by Actinobacillus lignieresii or Actinomyces bovis

Etiology and Signs.

Actinobacillus lignieresii granulomas within the nasal cavity usually are unilateral masses within the external nares and appear as red, raised, fleshy masses that bleed easily and look very similar to Rhinosporidium granulomas (Figure 4-7, A and B ). Signs include a progressively enlarging mass in one nostril and inspiratory dyspnea as the lesion enlarges to occlude the nostril completely. The granulomas may originate at the site of nose-lead lesions of the mucosa near the nasal septum or at other mucosal sites of soft tissue injury from foreign bodies or fibrous feed. Progressive inspiratory dyspnea and nasal discharge are found in patients having granulomas deeper in the nasal cavity, larynx, pharynx, or trachea. Actinomyces bovis was responsible for multiple tracheal granulomas in a cow treated at our clinic.

Figure 4-7.

A, Necropsy specimen of nasal turbinate region showing Rhinosporidium granulomas. B, Actinobacillus nasal granuloma in a Holstein cow.

Diagnosis.

Granulomas can be confused with tumors on gross inspection. Therefore diagnosis requires biopsy for histopathology and tissue culture. Sulfur granules may be observed grossly on cut surfaces of these granulomas and suggest the diagnosis. Although usually found near the external nares, granulomas caused by A. lignieresii or A. bovis could occur anywhere in the upper airway or trachea because these opportunists reside in the oral cavity and pharynx. When soft tissue infection occurs following injury to the mucosa, both organisms produce similar granulomas. Endoscopy and radiographs are necessary to identify granulomas at locations other than the external nares.

Treatment.

Treatment for granulomas caused by A. lignieresii consists of excisional biopsy to debulk the mass to the level of nasal mucosa and sodium iodide therapy until iodism is observed. Usually this requires IV sodium iodide (30 g/450 kg) initially and at 2- to 3-day intervals for several treatments, or oral organic iodide (30 g/450 kg) daily following the initial IV dose. Cryosurgery has been used successfully on these granulomas following debulking. In severe or recurrent cases, antibiotic therapy may be necessary in addition to sodium iodide. Penicillin and ampicillin have been used to treat infection caused by A. lignieresii. Whenever possible, an antibiotic should be selected based on organism culture and sensitivity results. Usually the prognosis is good.

Granulomas caused by A. bovis are much more difficult to treat because this organism is poorly responsive to sodium iodide therapy. Treatment with penicillin (22,000 U/kg intramuscularly [IM], once a day), in conjunction with sodium iodide, may be effective. Surgical debulking of soft tissue granulomas also is indicated. The prognosis for those with lesions caused by A. bovis is guarded because of the limited clinical knowledge regarding treatment of this organism, and many owners may not treat for a sufficient time.

Frontal Sinusitis

Etiology and Signs.

Frontal sinusitis in calves and adult cattle may be acute or chronic. Acute frontal sinusitis is more common and usually follows sharp dehorning techniques. Calves and cattle dehorned by laypeople are most at risk because of nonsterile equipment and techniques. Signs of acute sinusitis include fever (103.0 to 106.0° F/39.4 to 41.1° C), unilateral or bilateral mucopurulent nasal discharge, depression, and headache pain characterized by partially closed eyes, extended head and neck, head pressing or resting the muzzle on support structures (interestingly cattle with severe skeletal pain can often be found pressing their muscle against an object, which suggests this must be a pain relief point), and sensitivity to palpation on percussion of the sinus. When acute sinusitis follows recent dehorning, purulent drainage or heavy scabs may be observed at the wound in the cornual portion of the sinus. A multitude of bacteria such as A. pyogenes, Pasteurella multocida, Escherichia coli, and anaerobes may contribute to acute frontal sinus infection. Tetanus is another possible complication of acute frontal sinusitis if wound debris or scabs occlude the cornual opening to allow an anaerobic environment.

Chronic frontal sinusitis does not develop until months to years following dehorning and may be completely unassociated with dehorning because it occasionally occurs in animals dehorned by noninvasive techniques, polled animals, or animals with horns. Ascending respiratory tract infections, as in other species, are a cause of chronic frontal sinusitis and usually are caused by P. multocida. Chronic frontal sinusitis associated with old dehorning complications such as low-grade infection, bony skull fragments, or sequestra typically is associated with infection by A. pyogenes or mixed infections that may include A. pyogenes, P. multocida, anaerobes, or miscellaneous gram-negative organisms. Signs of chronic frontal sinusitis include gradual loss of condition and production that may be constant or intermittent; unilateral nasal discharge usually is observed, again as a persistent or intermittent complaint. Additional signs include head pressing, an extended head and neck, partially closed eyes, or resting of the muzzle on inanimate objects, all of which signal headache or pain. Intermittent or consistent fever is present. Bony expansions of the sinus may occur, causing asymmetric facial distortion—especially in cattle that do not have significant nasal discharge because of occlusion or obstruction of the ethmoidal meatus opening into the nasal cavity. In fact, some cattle will have intermittent bony swelling of the sinus that becomes less apparent during times of sinus drainage with subsequent nasal discharge. Palpation or percussion of the frontal bone overlying the affected sinus causes pain, and the patient is extremely apprehensive when the examiner approaches the head. Bony expansion of the sinus may result in ipsilateral exophthalmos and decreased air movement through the ipsilateral nasal passage (Figure 4-8 ). Neurologic complications, including septic meningitis, dural abscesses, and pituitary abscesses, are possible in neglected cases as a result of erosion of the bony sinus. Tetanus is another potential complication. Occasionally cattle with chronic frontal sinusitis have developed orbital cellulitis, pathologic exophthalmos, or facial abscesses from infectious destruction of the postorbital diverticula of the sinus, allowing soft tissue infection of the orbit (Figure 4-9 ).

Figure 4-8.

Chronic frontal sinusitis in a mature bull. The bull died from septic meningitis caused by the sinusitis.

Figure 4-9.

Orbital cellulitis, exophthalmos, and facial abscesses secondary to extension of chronic frontal sinusitis into the orbital soft tissue.

Diagnosis.

In acute cases, diagnosis is based on signs, history, and palpation and percussion of the sinus. Ancillary data are limited to bacterial culture and susceptibility testing to ensure proper antibiotic selection.

Diagnosis of chronic cases may be possible based only on clinical signs coupled with palpation and percussion of the sinus in selected cases. When mature animals are affected, however, it is important to rule out neoplasia and other differentials. Skull radiographs are helpful when available. Drilling into the sinus with a Steinmann's pin and collection of purulent material for cytology and bacterial cultures will confirm the diagnosis (Figure 4-10 ). Sedation and local anesthesia allow this procedure to be performed with minimal patient discomfort.

Figure 4-10.

Sinus trephination with Steinmann pin to facilitate sample collection in a bull with chronic sinusitis. Note caudal trephination flap that has already been made in the dehorning site to facilitate sinus lavage.

Treatment.

In those with acute frontal sinusitis, treatment requires cleansing of cornual wounds, lavage of the sinus with saline or saline and mild disinfectant solutions, and appropriate systemic antibiotics for 7 to 14 days. Penicillin usually suffices, but selection of a systemic antibiotic is better based on culture and susceptibility testing. Tilting the patient's head to allow the sinus to fill and then twisting the head to empty the sinus facilitate lavage and drainage. Systemic analgesics such as aspirin or flunixin meglumine greatly aid patient comfort. The prognosis is good.

Treatment of chronic frontal sinusitis requires trephination of the sinus at two sites to allow lavage and drainage. One site is at the cornual portion of the sinus, and the second is located over the affected sinus approximately 4.0 cm from midline and on a transverse line connecting the caudal bony orbits (Figure 4-11, A and B ). A third site caudodorsal to the rim of orbit and medial to the temporal ridge has been recommended, but we have found this site to be dangerous because it occasionally results in orbital soft tissue infection as compromised softened bone is penetrated. Further caution regarding trephination of the sinus should be practiced in animals less than 2 years of age because the rostral and medial rostral portions of the sinus may not be developed in younger animals. Attempts to establish rostral-medial drainage in these animals may risk invasion of the calvarium. Drains may be placed to communicate the two trephine sites and prevent premature closure of the wounds. Trephine holes should be at least 2.0 to 2.5 cm in diameter or they will close prematurely. Liquid pus is a positive prognostic sign, and pyogranulomatous or solid tissue in the sinus is a grave prognostic sign. Antibiotic selection must be based on culture and susceptibility testing and should be continued for 2 to 4 weeks. Analgesics such as oral aspirin are used to improve the patient's comfort.

Figure 4-11.

A, Trephination sites surgically created to treat chronic frontal sinusitis in a 4-year-old Holstein cow. B, Trephination sites surgically created to treat chronic frontal sinusitis in a 3-year-old Holstein bull.

Prognosis is fair to good with appropriate therapy as described above unless neurologic signs have been observed. Neurologic signs and orbital cellulitis constitute severe and usually fatal complications of chronic frontal sinusitis. On several occasions, especially in animals less than 18 months of age, Dr. Rebhun performed enucleation successfully to allow orbital drainage necessitated by severe orbital cellulitis and ocular proptosis in addition to trephination of the affected sinus. Long-term wound care, antibiotics, and nursing are essential if treatment is elected for such complicated cases.

Laryngeal Edema

Laryngeal edema secondary to bracken fern intoxication has been described in calves. Termed the “laryngitic” form, this response leads to progressive dyspnea without obvious signs of hemorrhage as expected in older animals affected with bracken fern toxicity. Laryngeal edema has also occurred following vaccination of cattle, assumingly as part of an adverse immune response. Cattle with persistent upper airway obstruction and dyspnea caused by conditions associated with the soft tissues of the retropharynx and/or larynx may develop laryngeal edema as a secondary complication.

Necrotic Laryngitis (Calf Diphtheria)

Etiology and Signs.

Necrotic laryngitis represents an atypical site of infection by the anaerobe Fusobacterium necrophorum, the organism responsible for calf diphtheria. Calf diphtheria is an infection of the soft tissue in the oral cavity following mucosal injury caused by sharp teeth in calves of 1 to 4 months of age. Calves affected with calf diphtheria usually have abscesses in the cheek region, have mild salivation, and may refuse solid feed (Figure 4-12 ). The infection spreads among calves fed from common utensils or those in such close contact that they may lick one another. When the larynx becomes infected in the atypical form of this disease, the affected calf develops a progressive inspiratory dyspnea. Low-grade fever (103.0 to 104.5° F/39.44 to 40.28° C) may be present along with a painful short cough that is observed when the calf attempts to drink or eat. As the condition worsens over several days, both inspiratory and expiratory dyspnea may be apparent, but the inspiratory component always will be worse. A necrotic odor may be present on the breath.

Figure 4-12.

Typical cheek abscess observed in calf diphtheria.

Audible inspiratory efforts are heard. Harsh sounds of airway turbulence will be heard when a stethoscope is placed over the larynx; these sounds will be referred down the tracheobronchial tree to confuse auscultation of the lower airway.

Diagnosis.

Endoscopy is helpful in confirming the diagnosis. In some calves, the lesions can be seen by using an oral speculum, but endoscopy is much easier and less stressful for the patient. If the calf is in extreme dyspnea or is anoxic or cyanotic, a tracheostomy should be performed before endoscopy. The larynx will be found to be uniformly swollen and may appear to have cartilaginous deformities in chronic cases (Figure 4-13 ). The laryngeal opening always is narrowed, and mucosal necrosis will be present in acute cases. Chronic cases may have laryngeal deformity and airway narrowing, but the necrotic, infected cartilage may be covered by normal mucosa (see video clips 6 to 8).

Figure 4-13.

Endoscopic view of laryngeal deformity and profoundly narrow laryngeal airway in a 3-month-old Holstein calf that had necrotic laryngitis and chronic laryngeal cartilage infection caused by F. necrophorum.

Treatment.

Long-term therapy is required because infection of cartilaginous structures usually exists. Acute cases should be treated with penicillin (22,000 U/kg IM, twice daily). A tracheostomy is essential for treatment of calves that have severe dyspnea. This will provide a patent airway and rest the infected larynx from further exertional irritation while the infection is controlled. The prognosis for acute cases is fair.

Chronic cases have a poor prognosis because laryngeal deformity and cartilaginous necrosis or abscesses within the laryngeal cartilage already have developed. Treatment is similar to that described for acute cases but should be extended to 14 to 30 days in patients valuable enough to warrant treatment, or the necrotic cartilage should be surgically removed or debrided. A tracheostomy may be necessary for the reasons listed above, and some clinicians recommend concurrent treatment with sodium iodide in the hope of penetrating the deep-seated infection of cartilage. A. pyogenes frequently contributes to or replaces F. necrophorum as the causative organism in chronic infections because these two organisms are synergistic. For valuable cattle with the chronic form, referral to an expert surgeon familiar with the tracheolaryngostomy technique described by Gasthuys should be considered.

Tracheal Obstruction

Tracheal obstruction is not common but may occur from either intraluminal obstruction such as infectious bovine rhinotracheitis (IBR) infection or from extraluminal obstruction caused by abscess or lymphosarcoma or as a result of proliferative callus on the first ribs in calves (Figure 4-14 ). Congenital tracheal stenosis independent of rib injury has also been reported to occur within the cervical or thoracic portions of the trachea.

Figure 4-14.

Radiograph of a 2-month-old calf with tracheal compression caused by callus formation on the first rib.

Diagnosis is generally easy if endoscopy and radiographs can be used to support the clinical examination. Most calves with tracheal obstruction resulting from proliferative rib callus are several weeks of age when respiratory signs develop and have a history of dystocia at birth.

Treatment for intraluminal inflammatory obstruction would include nebulization with acetylcysteine, inhalational ceftiofur, and an appropriate bronchodilator (ipratropium inhaler and/or aminophylline or atropine systemically). Repair of the tracheal compression caused by proliferative callus formation has been described, but the procedure is technically difficult, and because of the young age of the animals, the prosthesis needs to be removed to permit normal growth of the trachea.

DISEASES OF THE LOWER AIRWAY

Bacterial Bronchopneumonia

This remains the most important cause of fatal respiratory disease in dairy calves and adult cattle. Virulent strains of Mannheimia haemolytica and Histophilus somni are primary pathogens capable of causing acute infections of the lower airway and lung parenchyma. These organisms do not always require the help of environmental and management stressors or other infectious agents to cause pneumonia. Chronic lower airway infections by P. multocida and A. pyogenes may cause pneumonia in calves either previously infected or coinfected with viral or Mycoplasma pathogens of the respiratory tract or in animals stressed by shipment, poor management, or ventilation insufficiencies. Chronic suppurative pneumonia in acute cattle may be the result of previous aspiration pneumonia; a combination of P. multocida, A. pyogenes, Fusobacterium, and Mycoplasma sp. are frequently cultured. Aspiration pneumonia associated with these same bacterial pathogens may also be observed in calves with white muscle disease, calves fed via an inappropriately large opening on the nipple of milk feeding bottles, premature calves with inadequately developed protective reflexes of the glottis, and calves with retropharyngeal diseases that interfere with normal upper airway reflexes. It is imperative for the bovine practitioner to understand the causes, predisposing factors, treatment, control, and prevention of these pathogens. In addition, it must be emphasized that the only way to diagnose and control contagious respiratory disease in cattle is to know the exact identity of the pathogens and predisposing causes. This can be accomplished only by careful history, thorough physical examination, collection of appropriate samples, and collaboration with a diagnostic laboratory capable of identifying all known bovine respiratory pathogens. The five major bacterial pathogens of the bovine lower airways currently are M. haemolytica, P. multocida, Mycoplasma spp., H. somni, and A. pyogenes. They will be discussed separately. Although other organisms may be involved, they seldom cause herd problems and will not be discussed.

Mannheimia haemolytica

Etiology and Signs.

M. haemolytica is a gram-negative rod that may be a normal inhabitant of the upper airway but is not cultured from the upper airway of normal cattle as frequently as P. multocida. Several properties of M. haemolytica contribute to its pathogenicity. These include a capsule that provides defense against phagocytosis; production of an exotoxin (leukotoxin) lethal to alveolar macrophages, monocytes, and neutrophils; cell wall–derived endotoxin that helps to initiate complement and coagulation cascades; and the ability to reside in the upper airway among other nonpathogenic serotypes and then convert and/or overgrow under stressful stimuli to a pathogenic serotype, A1, that is more virulent. The cytotoxicity of the leukotoxin is associated with its ability to bind and interact with B2 integrin leukocyte function-associated antigen 1. Currently M. haemolytica is a leading cause of death as a result of respiratory infection in dairy cattle and calves in most areas of the United States. This organism is a primary pathogen not always needing assistance from other viral or Mycoplasma agents to establish lower airway infection, although it is well demonstrated that bovine herpesvirus 1 (BHV1) infection can activate genes that will increase leukotoxin binding, cytotoxicity to bovine mononuclear cells, and the severity of M. haemolytica infection. When a virus such as IBR, bovine respiratory syncytial virus (BRSV), or bovine virus diarrhea virus (BVDV) does infect a herd, mortality will be greatly increased if M. haemolytica bronchopneumonia is superimposed. In this situation, the bacteria may cause death because the viral infection compromises mechanical and cellular defense mechanisms. Mortality may approach 30% to 50% when a virulent M. haemolytica infection is superimposed on a preexisting viral infection (e.g., BHV1 or BVDV) in a herd. Cattle that are stressed are at great risk of M. haemolytica pneumonia because stress triggers both activation of the organism to a more virulent form, permits greater colonization of the virulent strain, and compromises the host defense mechanisms. Thus M. haemolytica is frequently isolated as the cause of “shipping fever pneumonia” associated with shipment of cattle, transport of cattle to shows, or recent purchase of replacement animals. Classic signs of pneumonia generally develop 1 to 2 weeks following any of these stresses. The morbidity and mortality percentages tend to be much greater for M. haemolytica pneumonia outbreaks than if P. multocida is found as the cause of shipping fever.

A great deal of variation in pathogenicity and antibiotic resistance exists for various isolates of M. haemolytica. Therefore the veterinarian must accept the fact that signs produced by these types will vary from mild to severe. Mild infections or less pathogenic M. haemolytica may mimic P. multocida with respect to clinical signs and response to therapy, whereas severe infections may be so drastic as to cause death within hours of the first clinical signs. In rare instances the death can be so peracute that toxicity is expected. A less pathogenic form has been seen causing high fever in recently fresh cows, all of which had a remarkably quick recovery following treatment with ceftiofur.

Signs of acute M. haemolytica pneumonia include fever, depression, anorexia, markedly decreased milk production, salivation, nasal discharge, moist painful cough, and rapid respirations (Figure 4-15 ). The fever may be as high as 108.0° F (42.22° C) but usually ranges between 104.0 and 107.0° F (40.0 to 41.67° C). Auscultation of the lungs reveals moist or dry rales in the anterior ventral lung fields bilaterally. Bronchial tones indicative of consolidation in the ventral lung fields are observed much more frequently than with acute P. multocida infections (Figure 4-16 ). Pleuritic friction sounds may be ausculted in some cases because of stretching or compression of fibrinous adhesions between the parietal and visceral pleura. The dorsal lung fields may sound normal on auscultation of animals with mild to moderate M. haemolytica pneumonia. In more severe cases, however, the dorsal lung may be forced to overwork because of the ventral lung consolidation. This overwork creates interstitial edema or bullous emphysema on occasion, and these pathologic changes cause the dorsal lung to be abnormally quiet on auscultation. Auscultation of the trachea will reveal coarse rattling or bubbling sounds caused by the inflammatory exudate free in the trachea. Palpation of the intercostal regions over the pneumonic lung causes the animal pain. Occasional cases will have an accumulation of transudative or exudative pleural fluid in the ventral thorax unilaterally or bilaterally that will cause a total absence of sounds when auscultation is performed.

Figure 4-15.

Calf affected with M. haemolytica pneumonia showing anxious expression, extended head and neck to minimize upper airway resistance, and ventral edema caused by both albumin loss into the severely infected lungs and gravitational edema.

Figure 4-16.

Thoracic radiograph of calf affected with severe M. haemolytica pneumonia. Cranioventral consolidation is highlighted by air bronchograms. Such lesions give rise to bronchial tones when the affected region of the lung is ausculted.

More severe or neglected cases may show open mouth breathing (Figure 4-17 ), anxious expression, subcutaneous emphysema secondary to tracking of air from bullae rupture in the dorsal lung field, and have harsh bronchial tones ventrally with inaudible lung sounds dorsally. Respiratory dyspnea is marked in such cases and affects both inspiratory and expiratory components, with the expiratory component being the most obvious. An audible grunt or groan may accompany each expiratory effort, and the animals are reluctant to move because of hypoxia and painful pleuritis.

Figure 4-17.

Cow affected with severe M. haemolytica pneumonia showing open mouth breathing, pulmonary edema froth at muzzle, anxious expression, dehydration, and extended head and neck to maintain a “straight line” upper airway.

A peracute rapidly consolidating form of M. haemolytica bronchopneumonia occasionally has been observed over the past 10 years in the northeastern United States and has resulted in high morbidity and mortality within affected herds. The causative M. haemolytica has proven extremely resistant to antibiotics. In some instances, it was resistant to all antibiotics approved for use in dairy cows. Signs in acutely affected cattle include high fever (106.0 to 108.0° F/41.11 to 42.22° C), marked depression, salivation, increased respiratory rate (60 to 120 breaths/min), complete anorexia and milk cessation, reluctance to move, absence of rales when the ventral lungs are ausculted, profound bronchial tones bilaterally that indicate consolidation of 25% to 75% of the ventral pulmonary parenchyma (Figure 4-18 ), and quiet or inaudible sounds in the dorsal lungs where the remaining pulmonary tissue has been subjected to extreme mechanical and physiologic stress to maintain gas exchange. Subcutaneous emphysema and pulmonary edema are common sequelae in these cattle. Ventral abdominal pain can be elicited in the cranial abdomen as a result of the fibrinous pleuritis present. This pain and absence of rumen activity coupled with the other signs have caused many veterinarians to confuse the initial case of rapidly consolidating pneumonia as peritonitis caused by hardware or perforating abomasal ulcer. The major reason for this error is the absence of rales with this form of M. haemolytica. Therefore we have had to “retrain” our ears to auscult carefully for bronchial tones versus normal or harsh vesicular sounds. Careless auscultation of air sounds in the ventral lung field may not discriminate between bronchial tones and vesicular sounds. Acute infection with this form of M. haemolytica will result in progressive dyspnea and death in 12 to 48 hours unless the veterinarian is fortunate enough to choose as the first treatment an antibiotic to which the organism is susceptible.

Figure 4-18.

Necropsy view of lungs affected by peracute rapidly consolidating M. haemolytica pneumonia. Consolidation exists over 80% to 90% of the lung parenchyma, and fibrin is obvious on the visceral pleura. The clinical course of the disease was 36 hours.

Diagnosis.

As with P. multocida pneumonia, accurate diagnosis of M. haemolytica bronchopneumonia requires culture of the organisms from tracheal wash specimens collected from acute, untreated cattle (Figure 4-19 ) or postmortem cultures of lung and lymph node specimens. Because mortality is greater for M. haemolytica than P. multocida, autopsy specimens often are the source of diagnostic material.

Figure 4-19.

A cow being restrained with two halters in preparation of a transtracheal wash. This method of restraint helps keep the head and neck straight during the procedure.

Once it is apparent that the disease is epidemic in the herd, the veterinarian should obtain appropriate cultures via tracheal washings or fresh lung tissue at necropsy from several animals so that the delay in accurate diagnosis and bacterial susceptibility to antibiotics is as short as possible.

Tracheal wash, nasopharyngeal swab, or autopsy specimens also should be cultured and/or antigen tested for viral pathogens, H. somni, and Mycoplasma sp. Serum for viral titers should be collected from several acute cases so that it may be compared with convalescent serum titers in the future, if the animals survive. In this way, some viral agents that are difficult to culture, such as BRSV, may be identified as primary or contributing causes of the respiratory outbreak. Having collected these samples for culture, antigen testing, and seroconversion, the veterinarian will now have a basis, albeit retrospective, to identify the pathogens involved and attribute the disease to M. haemolytica alone or combined with other pathogens. This will be of importance for future preventive measures.

Gross pathology specimens show a bilateral fibrinous bronchopneumonia with 25% to 75% or more of the lungs involved. The distribution is anterior ventral in all cases, and the affected lung is firm, meaty, friable, and discolored. Usually fibrin is present on both the visceral and parietal pleura. Increased amounts of yellow or yellow-red pleural fluid are found frequently. In acute cases with advanced pulmonary parenchymal consolidation or in chronic cases, the dorsal lung may have bullous emphysema or interstitial edema present.

A complete blood count (CBC) from acutely infected cattle usually will show leukopenia characterized by a neutropenia with a left shift as neutrophils move to the site of severe infection. Fibrinogen values are elevated.

Radiographs or ultrasonography is only of value for prognosing an individual valuable calf or cow. An estimation of degree of consolidation and subsequent abscess formation may be aided by these techniques and allow accurate prediction of outcome. However, these techniques seldom are necessary given the physical signs present.

Treatment.

Broad-spectrum antibiotics constitute the major therapeutic defenses against M. haemolytica pneumonia. Once again, the veterinarian is forced to use “best guess” judgment when selecting an initial antibiotic in such cases. Following collection of appropriate diagnostic samples, antibiotic therapy should commence immediately. Because life-threatening signs usually appear in at least some of the affected cattle, the veterinarian is more likely to select broad-spectrum antibiotics immediately. The current popular antibiotics for cows and calves are shown in Table 4-1 . Even when the causative bacterial organism is known, antibiotic therapy may be unable to cure the patient for a variety of reasons, such as the chosen antibiotic does not reach adequate tissue levels in the lung; the organism is resistant to the antibiotic; the organism is sensitive in vitro but in vitro inhibitory concentrations do not occur in the cow as a result of the dose, frequency of dosage, or other pharmacologic considerations; the drug may not be able to penetrate consolidated tissue or work in purulent tissue; and in vitro susceptibility tests may not reflect in vivo success of an antibiotic against a specific organism—thus the Kirby-Bauer disc assay has been criticized as too gross compared with mean inhibitory or bactericidal concentration tests that can give a concentration of drug that inhibits or kills an organism. This mean inhibitory concentration then can be compared with known achievable blood and tissue levels of the antibiotic in the cow to determine likelihood of successful treatment. The pathology may be irreversible or viral, and Mycoplasma or A. pyogenes pathogens may coexist to complicate the treatment plan. Textbook charts that quote percentages of isolates sensitive to various antibiotics are seldom helpful because both geographic differences in strains and temporal resistance patterns occur. Appropriate withdrawal times for any antibiotic selected for milk and slaughter residues must be known and observed and may shape decisions by the producer as to which antibiotic is chosen so that an immediate slaughter option is maintained.

TABLE 4-1.

Dosages and Frequencies of Administration for Selected Antibiotics for Initial Therapy

Antibiotic	Dose	Frequency	Age
Ceftiofur	2.2 mg/kg *IM/IV +/or− aerosolution	Once or twice daily	Adult cattle and replacement heifers
Oxytetracycline HCI alone or in combination with sulfadimethoxine	11 mg/kg IV	Twice daily; use only in well-hydrated cattle	Adult cattle and replacement heifers
Florfenicol	20 mg/kg IM (neck only)	Every 48 hr	Replacement heifer
Erythromycin	5.5 mg/kg	Twice daily	Nonlactating cattle
Ampicillin	11.0-22.0 mg/kg	Twice daily	Adult cattle and replacement heifers
Enrofloxacin (Other fluoroquinolones available in some countries)	2.2-5.0 mg/kg*†	Once daily, Europe only	Adult cattle and replacement heifers
Tilmicosin	10 mg/kg SQ	Every 3 days	Replacement heifer
Tulathromycin	2.5 mg/kg SQ	Once or repeat in 5 days	Nonlactating dairy cattle

^*Often used at higher dosages, but no objective data are available about efficacy of higher dosages.

^†Prohibited in dairy cattle in the United States.

The industry continues to seek the “silver bullet”—a magic antibiotic that will cure all cases of Mannheimia pneumonia. This silver bullet would take away the need for diagnostic work or preventive medicine, excuse management techniques that predispose to pneumonia, and of course would only be available through veterinarians. As a profession, we persist in overuse of every new antibiotic that becomes available. We ask these antibiotics to do things that cannot be done while ignoring older time-tested antibiotics. The silver bullet does not and will not exist.

Improvement in response to appropriate antibiotic therapy will appear as better attitude and appetite and a decreasing fever within 24 hours. A decrease of 2° F or more should be considered clinically indicative of improvement. The body temperature continues to decrease into the normal range over 48 to 72 hours in most cases that have been treated with appropriate antibiotics. Depending on which antibiotic is used, a minimum of 3 days of antibiotic treatment is often required, and more often 5 to 7 days of continuous therapy are necessary and less likely to result in recurrence.

Antiinflammatory medications are used by many veterinarians in conjunction with antibiotic therapy, as discussed under P. multocida pneumonia. If corticosteroids are used as part of initial therapy, we believe that 20 mg of dexamethasone or a comparable dose of prednisone for an adult cow is the maximum. This should not be used more than once, and it should not be used at all in pregnant cattle. Currently in our clinic, we do not use any corticosteroids in the treatment of M. haemolytica pneumonia. Flunixin meglumine or other nonsteroidal antiinflammatory drugs (NSAIDs) are sound therapeutic agents for use in those with M. haemolytica pneumonia for the first 1 to 3 days of therapy. Excessive dosage of NSAIDs or prolonged treatment with these agents should be avoided. Once again, aspirin is the safest drug for this purpose (at a dosage of 240 to 480 grains orally, twice daily for an adult cow or 25 grains/100 lb body weight twice daily for calves). Flunixin meglumine at 0.50 to 1.0 mg/kg is the most commonly recommended and only approved NSAID for treating bovine pneumonia and has been documented to improve clinical outcomes when combined with antibiotics compared with antibiotic treatment alone.

Antihistamines such as tripelennamine (1 mg/kg twice or thrice daily) are less commonly used these days but are still used by many experienced clinicians as supportive therapy. Atropine may be a useful adjunct in advanced cases showing marked dyspnea, open mouth breathing, or pulmonary edema. Atropine is used at 2.2 mg/45 kg body weight IM or subcutaneously (SQ), twice daily to decrease bronchial secretions and to act as a mild bronchodilator.

In severe cases, dehydration may be a complication because of toxemia and fever causing depression of appetite and water consumption. In addition, some cattle are so dyspneic that they are unable to take time to drink, lest they become more hypoxic. Any IV fluid therapy that excessively expands the intravascular volume may cause or worsen existing pulmonary edema, and the fluid volume administered must be appropriate. Administrating fluids through a stomach tube is safer regarding pulmonary edema, but the procedure is very stressful to an already hypoxic animal. Clinical judgment is required for these decisions, and in most cases, it is best to hope that antibiotic therapy will improve the animal within 24 to 48 hours so that the cow or calf may hydrate itself through adequate water consumption. Adequate water, salt, and small amounts of fresh feeds should be used to promote appetite.

Any management or ventilation deficiencies should be remedied immediately, and fresh air is of the utmost importance. It is better that the animals be in the cold fresh air than in a poorly ventilated or drafty but warm enclosure. The worst environmental effects occur when cattle develop M. haemolytica pneumonia during hot, humid weather because the additional respiratory effort to encourage heat loss complicates existing hyperpnea. Intranasal oxygen is beneficial for affected cattle being treated in a hospital.

Prognosis always is guarded until signs of clinical improvement are obvious. Cattle improving within 24 to 72 hours have a good prognosis, whereas those that take more than 72 hours have a greater risk of chronic lung damage or abscessation.

Following endemic Mannheimia or Pasteurella infection in groups of calves, Drs. King and Rebhun observed occasional calves that developed peracute respiratory distress and dyspnea as a result of proliferative pneumonia 2 to 4 weeks after recovering from confirmed Mannheimia/Pasteurella pneumonia. At autopsy, resolving anterior ventral pneumonia from the previous Mannheimia/Pasteurella infection is observed in anterior ventral lung fields, and the remainder of the lung is diffusely firm, heavy, and wet. Histopathology confirms proliferative pneumonia. Viral cultures, fluorescent antibody (FA) procedures, and serology have been negative for other pathogens, including BRSV, which also may cause a delayed-effect hypersensitivity pneumonia but with different lesions. Following observation of a number of these secondary proliferative pneumonia cases in the necropsy room, they were able to recognize clinically and treat several calves with this problem. The calves had a history of being part of a pneumonia outbreak 2 to 4 weeks previously, then apparently recovering. A sudden onset of extreme dyspnea in one recovered calf typifies the clinical situation. Signs include mild fever, open mouth breathing, and diffusely quiet lungs. Treatment consists of atropine (2.2 mg/45 kg twice daily), furosemide (25 mg/45 kg once or twice daily), broad-spectrum antibiotics, and box stall rest in a well-ventilated area. Response to therapy is slow, but survivors gradually improve over 7 to 10 days.

Pasteurella multocida

Etiology and Signs.

P. multocida is a gram-negative normal inhabitant of the upper airway of cattle and calves. The normal defense mechanisms of the lower airway prevent colonization of the lung by P. multocida via physical, cellular, and secretory defenses in the healthy state. P. multocida is, however, a likely opportunist any time lower airway defense mechanisms are compromised. Chemical damage to mucociliary clearance, such as is caused by ammonia fumes in poorly ventilated barns, may allow P. multocida the opportunity to colonize the lower airway. P. multocida also is found in mixed infections of the lung along with H. somni, A. pyogenes, Mycoplasma sp., and various respiratory viruses of cattle. Fusobacterium and other anaerobic organisms may also be present with chronic suppurative pneumonia in adult cattle.

The strains of P. multocida isolated from the lungs of cattle or calves frequently are sensitive to many antibiotics, including penicillin. This is in definite contrast to M. haemolytica, in which antibiotic resistance is much more probable. This difference will be important regarding treatment and prevention of P. multocida pneumonia.

The signs of acute P. multocida pneumonia include fever, depression, mild to severe anorexia, moist cough, increased rate and depth of respiration, and a decrease in milk production commensurate with the degree of anorexia. The fever ranges from 103.5 to 105.5° F (39.72 to 40.83° C) in most cases. Moist and dry rales will be ausculted in the anterior ventral lung field bilaterally and are classical findings in acute cases. Usually the dorsal lung fields are normal. Nasal discharge may be serous or mucopurulent in nature and is more apparent in calves than adult cows. The acute disease may occur in calves and cows of any age but tends to be more common in weaned calves and other grouped animals. When seen in younger animals, the acute disease usually is indicative of poor ventilation, excessive ammonia fumes, failure of passive transfer of immunoglobulins, and/or part of a diarrhea/pneumonia complex. All these predisposing factors are common in dairy calves placed in veal operations or other indoor group housing facilities. P. multocida has been found as the cause of neonatal septicemia in calves receiving inadequate colostrum. These septicemic calves may show signs of meningitis, septic uveitis, septic arthritis, and mucopurulent nasal and ocular discharge (Figure 4-20 ) in addition to the typical signs of acute P. multocida pneumonia.

Figure 4-20.

Neonatal calf with P. multocida septicemia. In addition to pneumonia, signs included fever, hypopyon, and mucopurulent nasal and ocular discharges.

Acute P. multocida pneumonia tends to occur as either an infectious epidemic or endemic disease in groups of housed calves or adult cattle and may affect 10% to 50% of the animals within a group. It is one of the causes of “enzootic pneumonia” in calves, but this is not the preferred term because it gives little information as to the exact cause of pneumonia. During an acute outbreak, the degree of apparent illness and auscultable degree of pneumonia will vary greatly among affected cattle or calves. If only one animal in a group is infected, predisposing causes or stress unique to that animal should be sought when establishing a history (e.g., recent purchase, recent calving, possibility of BVDV-persistent infection [Figure 4-21 ], transport to a show, sale, or poor ventilatory management).

Figure 4-21.

A 3-year-old Jersey bull at a stud facility developed P. multocida pneumonia without any environmental stress factors. The bull was later proven to be persistently infected with BVDV, which likely resulted in immunosuppression.

Chronic pneumonia resulting from P. multocida causes signs similar to the acute disease, but bronchial tones indicative of consolidation frequently are limited to the anterior ventral lung fields. The abnormal area may be missed unless the stethoscope is pushed under the shoulder and the calf or cow forced to take a deep breath. In calves this can be accomplished most easily by holding the mouth and nose shut for a short period (Figure 4-22 ). Animals affected with chronic pneumonia may have marked exacerbation of dyspnea and an increased respiratory rate ($60 breaths/min) if housed in poorly ventilated areas or where the environmental temperature exceeds 70.0° F (21.1° C). A. pyogenes is a common secondary invader in lungs chronically infected with P. multocida. Following acute epidemic P. multocida pneumonia, occasional affected animals may show signs of chronic pneumonia.

Figure 4-22.

An easy method of properly auscultating the lungs in calves. To make the calf breathe deeply, the calf is backed into a corner and one hand is placed over the mouth and nose until the calf struggles, at which time the calf is allowed to breathe. Alternatively, in adult cows a plastic garbage bag can be used over the cow's nose and mouth to force deep breathing.

Diagnosis.

P. multocida pneumonia may be suspected after obtaining the appropriate history from the cow's owner and finding typical signs complete with anterior ventral pneumonia and bilateral auscultable rales. However, confirmation requires culture of P. multocida from tracheal wash samples or autopsy specimens of acute, untreated affected animals. Neutrophils predominate the white blood cell components of the tracheal wash fluid, and gram-negative rods may be observed intracellularly in acute cases. The hemogram may show a degenerative left shift typical of acute infection in cattle or may be normal in mild cases. Chronic cases ($2 weeks) may have neutrophilia, and adult cattle may show hyperglobulinemia in the serum.

Gross pathology of fatal acute cases includes bilateral anterior ventral pneumonia with the affected portion of lung being firm and discolored red or blue (Figure 4-23 ). Palpation of the firm affected lung is the key to gross pathologic diagnosis. Fibrin may coat the surface of the parietal or visceral pleura but tends to be less than that observed with M. haemolytica. Chronic cases will show similar firm, pneumonic lung parenchyma but often have bronchiectasis and pulmonary abscesses.

Figure 4-23.

Necropsy findings in a calf that was affected with severe cranioventral pneumonia caused by P. multocida.

Radiographs seldom are necessary but may be helpful for individual chronically infected calves or mature cattle to identify abscesses and degree of consolidation for prognostic purposes. Ultrasound examination will help define the severity of lung involvement.

Treatment.

Antimicrobials and changes in husbandry or management constitute the integral components of effective therapy for P. multocida pneumonia. Many antibiotics have been used, including penicillin, ampicillin, erythromycin, and tetracycline. Sulfa drugs (trimethoprim-sulfa has been used in calves because it can be mixed with milk to bypass the forestomachs) also have been effective when administered either alone or in combination with antibiotics such as penicillin or tetracycline. Ceftiofur, a broad-spectrum cephalosporin, has been approved for use in Pasteurella pneumonia in cattle and has proven to be very effective. Tilmicosin (a macrolide) and florfenicol are also effective but currently not approved for use in adult dairy cattle. The practicing veterinarian must start antibiotic therapy without knowing results of cultures and antibiotic sensitivity tests. Therefore initial treatment is based on previous experience, geographic differences in antibiotic sensitivity, and economic factors. Animals that are febrile, anorectic, and dyspneic require treatment. Other animals that have mild fever and depression but continue to eat and do not act very ill may not require treatment. Individual or small groups of sick animals may be treated empirically if fatalities are not anticipated. However, if an epidemic situation is apparent, it always is best to do transtracheal washes from several animals before any treatment. Having done this, the veterinarian may start empiric therapy assured that definitive antibiotic sensitivity results will be forthcoming in 3 days. Thus if the animals fail to respond to the initial choice of antibiotic, a specific antibiotic may be selected based on the sensitivity results as soon as these are available.

Penicillin, tetracycline, florfenicol, ampicillin, or ceftiofur may be selected for initial therapy. Dosages and frequency of administration are listed in Table 4-1. Regardless of the antibiotic selected, all treated cattle should have temperature and attitudes recorded daily so that 24- and 48-hour evaluations can be assessed. A trend of decreasing temperature into the normal range should proceed at 1 to 2° F per day when an effective antibiotic is used; the attitude, appetite, and degree of dyspnea should improve along with the return to normal body temperature. Hjerpe has done extensive work in feedlot cattle to estimate probable efficacies of various antibiotics in pneumonia outbreaks. This material is an excellent reference, but the veterinarian must remember that geographic variations in bacterial serotypes and antibiotic susceptibility exist and that antibiotic resistance is likely to increase in years to come. Individual treatment generally is easier for dairy animals than beef animals. Antibiotics such as tetracycline, sulfa drugs, and tylosin have been added to feed and water to treat large groups of calves or heifers. This method may be utilized if the animals are not too sick to eat or drink. If affected cattle are completely off feed, this method is ineffective. When faced with an obvious epidemic, the veterinarian may choose to divide the animals requiring treatment into three groups—each group consisting of animals with mild, moderate, and severe signs. Each group then could be treated with a different antibiotic. Twenty-four hours after initial treatment, each group would be evaluated for relative degrees of improvement and all sick animals given the antibiotic that resulted in the most improved group.

Many practitioners use antiinflammatory agents in conjunction with antimicrobial therapy. The goals of antiinflammatory medications are to reduce fever, block specific parts or mediators of the inflammatory cycle, counteract endotoxins released by the cell wall of the causative gram-negative organisms, and result in symptomatic improvement through better appetite and attitude. The two general groups of drugs include corticosteroids and NSAIDs, such as aspirin and flunixin meglumine. Corticosteroids have a marked antiinflammatory and antipyretic activity that often leads to a “steroid euphoria” with resultant improved attitude and appetite within 24 hours. Although corticosteroids have these positive effects and also block several parts of the inflammatory cycle, they are dangerous if used repeatedly or in high dosages. Corticosteroids may reduce some of the chemotactic factors and lysosomal enzymes that cause a vicious cycle of increasing inflammation in the lung and tend to stabilize small vessels. However, they also partially or completely inhibit macrophage activation and antimicrobial peptide expression, which are serious detriments to the defense mechanisms of the lower airway. If the veterinarian elects to use corticosteroids, one treatment of low-dose (10 to 20 mg/450 kg) dexamethasone may be given as part of the initial therapy and should not be used thereafter. This treatment cannot be used in pregnant cows because of the abortifacient qualities of dexamethasone. Corticosteroids have potent antipyretic properties, and this may lead to a false sense of security because the veterinarian may assume that the proper antibiotic has been used based on a decreasing fever 24 hours following treatment when in fact the antibiotic has not been effective and fever will return 24 to 48 hours later. I do not recommend the use of corticosteroids for bacterial pneumonia.

NSAIDs are safer than corticosteroids in the treatment of bacterial bronchopneumonia in cattle but are not without some disadvantages. Advantages include blockage of some prostaglandin-mediated inflammation within the lung, antiendotoxin effects, and antipyretic activity. Disadvantages include inability to gauge response to specific antibiotics based on body temperature alone as a result of the artificial decrease in fever caused by NSAIDs, and the possibility of toxicity manifested by abomasal ulceration or renal damage if treatment is excessive in frequency, dosage, or duration. Aspirin may be the safest of the NSAIDs and is given at 240 to 480 grains orally, twice daily for an adult animal, and flunixin meglumine at 0.50 to 1.0 mg/kg IV, once or twice daily may be the most effective. Occasionally aspirin and flunixin meglumine have caused abomasal ulceration when administered for a prolonged time to sick cattle. Renal toxicity also is a risk—especially in a dehydrated animal in which the cytoprotective and vascular effects of prostaglandins are essential during reduced renal perfusion. I prefer flunixin when NSAID therapy is selected, but similar to corticosteroids, these drugs are adjuncts, not essentials, for the treatment of bronchopneumonia caused by P. multocida.

Bronchodilators such as aminophylline have been used in cattle with pneumonia but do not appear to be beneficial clinically except when given by constant infusion to calves with respiratory distress. Atropine given parenterally or ipratropium by inhalation may be effective bronchodilators. If albuterol could be used in cattle, it might be beneficial because this drug has been shown in other species to act not only as a bronchodilator but also to improve mucociliary clearance. Parasympatholytic bronchodilators have been shown to be more effective in calves than sympathomimetic drugs.

Antihistamines are used as adjunctive therapy in bovine bronchopneumonia by many practitioners. Drugs such as tripelennamine hydrochloride (1 mg/kg IM or SQ, twice or thrice daily) are believed to improve the animal's attitude and appetite. These symptomatic observations may be valid, but because histamine has not been shown to be one of the major inflammatory mediators in Pasteurella pneumonia, no scientific evidence exists to justify the use of these drugs.

The recognition and correction of management problems or ventilation deficiencies may be as important, if not more so, than any of the previous pharmaceuticals when treating endemic P. multocida pneumonia. Because the organism primarily is an opportunist that gains access to the lower airway following insults to the physical, cellular, or secretory defense mechanisms, predisposing causes should be sought and corrected. In calves, poor ventilation, crowding, and poor husbandry relating to excessive ammonia fumes may be sufficient to allow P. multocida to descend from its normal habitat of the upper airway and colonize the lungs. Examples include changeable temperature and humidity when calves are grouped during the indoor housing season (especially fall, spring, and during winter thaws), broken fans, failure to clean large pens when calves have been in groups for weeks to months, lungworms, and drafts that the confined calves cannot escape. Fresh air is vital to recovery and should be provided even if it means allowing the animals access to outside air in inclement weather.

In adult cattle, all these factors above apply, but ventilation deficiencies predominate. In modern free stall facilities, transition cow management practices that add greater stress to an already changeable/stressful period appear to greatly impact the acquisition of acute pneumonia and progression to chronic disease. Frequent pen moves, overstocking, poor ventilation, and concurrent metabolic disease alongside some of the treatments and therapeutic practices used by producers all substantially increase the chances for postpartum respiratory disease to become a herd problem. Bronchopneumonia caused by P. multocida alone usually is a management problem. Although it certainly is recognized that previous viral infection or mixed infections (e.g., Mycoplasma) could and do predispose to P. multocida pneumonia in calves and cattle, it must be emphasized that management factors are very important. Secondary P. multocida pneumonia, such as that following viral respiratory infection, will be discussed in conjunction with viral diseases. Failure of cattle affected with P. multocida pneumonia to respond to appropriate antibiotic therapy based on culture and susceptibility results should alert the veterinarian to the fact that (1) P. multocida is not the only agent involved in the epidemic (i.e., a virus or Mycoplasma also may be present or was present—therefore viral isolation, paired serology, and so forth are indicated); (2) the predisposing management or ventilation problems have not been corrected; and (3) lungworms should be ruled out.

Vaccinations are included in the prevention section and are discussed on pages 107-109.

Histophilus somni

Etiology and Signs.

With increasing frequency, H. somni has been identified as a pathogen of the lower airway in dairy cattle. It is occasionally identified as the cause of herd outbreaks of pneumonia in dairy cattle or calves in the northeastern United States. H. somni may be the only pathogen isolated or may be found in conjunction with Mycoplasma spp. or Pasteurella pneumonia in cattle. Although H. somni occasionally is isolated from the upper airway of normal cattle, this gram-negative organism is more commonly isolated in clinical pneumonia patients. A shift in the normal upper airway bacterial flora or stress activation of latent H. somni in the upper airway may contribute to lower airway infection.

The pathogenicity of H. somni and Pasteurella organisms is attributed to several characteristics: (1) an endotoxin derived from the cell wall lipopolysaccharides, (2) exotoxins that are lethal or damaging to alveolar macrophages, neutrophils, and vascular endothelium, and (3) chemotactic factors and possible hemolysins common to H. somni and other bacteria that act as inflammatory mediators. Vasculitis is a predominant feature of H. somni pathology. H. somni–stimulated platelets have also been shown to contribute to endothelial cell damage, which may play a role in pathogenesis of the vasculitis and thrombosis. In addition, H. somni has a propensity to cause disease in the heart muscle and sometimes the central nervous system.

The signs of H. somni bronchopneumonia in calves and adult cattle are indistinguishable from moderate to severe P. multocida pneumonia or mild to moderate M. haemolytica pneumonia. Affected animals have fever (103.5 to 106.6° F/39.72 to 41.44° C), an increased respiratory rate (40 to 80 breaths/min), depression, nasal discharge, occasional salivation, painful cough, and decreased milk production proportional to the degree of anorexia observed. Dyspnea may be marked in some cases, and these cattle will show anxiety and reluctance to move. Neurologic signs or septicemia caused by H. somni observed in feedlot animals is less common in dairy cattle and calves. If, however, any cattle develop neurologic signs during an outbreak of bronchopneumonia in a herd or group of calves, H. somni should be strongly suspected as the cause of the illness.

Auscultation of the lungs typically identifies bilateral anterior ventral pneumonia characterized by moist and dry rales with bronchial tones indicative of ventral consolidation identified in up to 50% of the cases. Tracheal rales may be ausculted as a result of the heavy mucopurulent exudate found in the trachea. Palpation of the intercostal spaces overlying the pneumonic regions may be painful to the animal.

Diagnosis.

Because the signs usually are identical to those of Pasteurella pneumonia, the veterinarian should collect appropriate samples (tracheal washes for culture and bacterial sensitivities or autopsy cultures from lung and lymph nodes) and institute therapy. A failure of response to standard broad-spectrum antibacterial therapy typifies H. somni pneumonia. Usually an exact diagnosis as to etiology has to await culture and sensitivity results from diagnostic samples. CBCs are variable and nonspecific, with either a degenerative or regenerative left shift observed and elevated fibrinogen levels. Acute and convalescent serum may be helpful retrospectively if the diagnostic laboratory utilized for testing has the capability to establish H. somni titers.

Postmortem specimens will show anteroventral firm areas of pneumonia bilaterally. Fibrin may be apparent in the visceral and parietal pleura occupying the areas of pneumonia. In some cases, red blotches or hemorrhage is apparent. White microabscesses may be observed also.

Treatment.

Although H. somni apparently is sensitive in vitro to many antibiotics including penicillin, clinical results in vivo are discouraging. Ampicillin is the drug of choice for H. somni pneumonia in calves and adult cattle. Ampicillin is used at 11 to 22 mg/kg twice daily by injection for 3 to 7 days in most cases. Cephalosporins also may be effective. Enrofloxacin reportedly has good efficacy against Histophilus sp. but currently is not approved for use in dairy cattle in the United States.

Response to ampicillin or other effective antibiotics will be manifested by a progressive decrease in body temperature to the normal range over 24 to 72 hours. For this reason, the treating veterinarian may find it best not to use NSAIDs or corticosteroids in H. somni pneumonia because these drugs decrease the temperature artificially through antipyretic effects and interfere with interpretation of appropriate antibiotic selection.

Just as in Pasteurella bronchopneumonia, ventilation or management factors that predispose to altered lower airway defense mechanisms should be corrected immediately. The prognosis is fair to good unless severe pneumonia and marked dyspnea are present.

Arcanobacterium pyogenes Chronic Suppurative Pneumonia

Etiology and Signs.

A. pyogenes is a gram-positive coccobacillus that acts as a ubiquitous opportunist capable of establishing chronic pyogenic infections virtually anywhere in the cow's body. In the lung, it is a secondary invader that usually only establishes infection following suppression of host physical, cellular, or secretory defense mechanisms. Physical factors such as inhalation pneumonia also may allow A. pyogenes to infect the lung, and viral, bacterial, or Mycoplasma agents may precede infection with A. pyogenes. Immunosuppression caused by acute or persistent infection with BVDV has been followed by A. pyogenes pneumonia in calves and adult cows. Similarly, calves affected with bovine leukocyte adhesion deficiency (BLAD) frequently suffered A. pyogenes pneumonia. Pulmonary infection is aided by the proteases and hemolysins that the organism produces. These factors contribute to tissue necrosis and inflammatory events that perpetuate the organism's existence. Fusobacterium and other pathogenic anaerobic organisms may be found concurrently with A. pyogenes, P. multocida, and Mycoplasma spp.

Signs are indicative of chronic or recurrent infection, the hallmark of A. pyogenes pneumonia. The history usually indicates illness of at least 1 week's duration or recurrent episodes of pneumonia over weeks to months. There may only be one (usually adult cattle) or a few animals (usually calves) affected out of a group or herd. In adult dairy cattle, it is common for clinical signs to develop following freshening (Figure 4-24 ). In some cases, there may be severe subcutaneous emphysema over the dorsum, suggesting a rupture of diseased alveoli associated with calving as a cause of the pneumomediastinum, subcutaneous emphysema, and sometimes pneumothorax. Although this should be considered in cattle with dorsal emphysema following calving, similar emphysema may be found sometimes in apparently healthy cattle following calving and of course in cattle with interstitial pneumonia. Affected animals may show low-grade fever (103.0 to 105.0° F/39.44 to 40.56° C), rapid respiratory rate (40 to 100 breaths/min), dyspnea characterized by exaggerated inspiratory and especially expiratory efforts (particularly when stressed), head and neck extension when lying down, cough, nasal discharge (Figure 4-25 ), rough hair coat, poor body condition, depression, inappetence, or decreased milk production. Some cattle maintain normal respiratory rates but exhibit the other signs. Chronic suppurative pneumonia should always be considered a differential for the “poor doing” cow. Auscultation of the lungs reveals moist and dry rales in the ventral 25% to 50% of both lungs in calves and one or both lungs in adult cattle, bronchial tones indicative of consolidation in the ventral lung fields, and coarse tracheal rales caused by a thick mucopurulent airway exudate. High environmental temperatures, high humidity, and poor ventilation exacerbate the clinical signs. A fetid smell may be present following a cough if anaerobic bacteria are present. Auscultation during rebreathing, paying close attention to the cranioventral lung fields under the triceps musculature for the presence of bronchial tones indicative of consolidation, is important when investigating possible cases of mild to moderate chronic suppurative bronchopneumonia.

Figure 4-24.

A 5-year-old cow with cough and respiratory distress following calving 5 days earlier. The cow had chronic suppurative pneumonia with acute onset of respiratory signs associated with stress of calving.

Figure 4-25.

A mature Holstein cow presented to the hospital for poor production and weight loss. Although respiratory rate was within normal limits, the cow coughed after rising, had slight head and neck extension when lying down, and, as seen in this photo, had small and intermittent purulent nasal discharge. P. multocida, A. pyogenes, and Mycoplasma spp. were cultured from a tracheal wash. The cow improved dramatically following tetracycline therapy.

Diagnosis.

History and physical signs are very suggestive of A. pyogenes pneumonia, but specific diagnosis requires culture of the organism from tracheal wash samples or lung tissue. There may only be one or a few animals affected with signs of chronic pneumonia following a preceding herd endemic of pneumonia caused by other organisms. Chronic or recurrent cases are referred to as “lungers” by some farmers.

Radiographs or ultrasonography of the thorax is helpful in establishing a prognosis because lung abscesses, bronchiectasis, and consolidation (sometimes remarkably severe in a single lobe) (Figure 4-26 ) are common in the affected lung (see video clip 9).

Figure 4-26.

Radiograph of a cow with chronic suppurative pneumonia and a dramatic lobar consolidation.

A CBC may show neutrophilia or be normal. Serum globulin often is in the high range of normal or elevated ($5.0 g/dl), especially in adult cattle. The animal should be screened for persistent infection with BVDV via buffy coat viral isolation. Gross autopsy of fatal cases reveals anterior ventral consolidation with areas of purulent bronchiectasis and multiple pulmonary abscesses (Figure 4-27 ).

Figure 4-27.

Necropsy view of cut section from the cranioventral lung region of a calf showing bronchiectasis and pulmonary abscesses typical of chronic A. pyogenes pneumonia.

Treatment.

Treatment is frustrating, and the prognosis is poor for pneumonia caused by A. pyogenes. Other causative organisms such as P. multocida, M. haemolytica, Mycoplasma, and/or Fusobacterium also may be cultured from the tracheal wash sample. Penicillin is the drug of choice and should be given at 22,000 U/kg twice daily for 7 to 30 days. Although penicillin is effective against A. pyogenes in vitro, the pulmonary in vivo infection should be likened to an abscess because of the heavy accumulation of A. pyogenes pus in areas of bronchiectasis or encapsulated lung abscesses. If another pathogen, in addition to A. pyogenes, is isolated from the tracheal wash sample, appropriate antibiotic therapy should be selected for this organism as well. Ceftiofur, ampicillin, and tetracyclines are other commonly used therapies. Clinical treatment frequently results in short-term improvement followed by relapse when the animal is stressed or subjected to high environmental temperatures, humidity, or poor ventilation. Signs of improvement will be indicated by normal rectal temperature, improved respiratory function, and improvement in overall body condition and attitude. Many affected animals eventually succumb to the infection or are culled because of poor condition and production.

Mycoplasma Pneumonia

Etiology and Signs.

Several types of Mycoplasma organisms, including Mycoplasma dispar, M. bovis, and Mycoplasma bovirhinus, have been isolated from the lungs of calves and cattle with pneumonia. In addition, Ureaplasma organisms and occasional isolates of Mycoplasma bovigenitalium have been found from lower airway infections in cattle. M. dispar and M. bovis probably are the two major types identified. The organisms may be normal inhabitants of the upper airway in some cattle. Experimentally, Mycoplasma spp. have caused pneumonia in calves when introduced into the lower airway. This pneumonia is characterized by peribronchiolar and peribronchial lymphoid hyperplasia and purulent bronchiolitis. Lesions usually are limited to the anterior ventral tips of the lung lobes, and the associated clinical signs are mild. Gross inspection at necropsy reveals ventral areas of lung lobes that are red-blue and firm, appear almost as atelectatic areas, and ooze purulent material from the airways on cut sections. Mycoplasma pneumonia has been described as a “cuffing pneumonia” because lymphoid hyperplasia appears around the airways and expands with time. Mycoplasma organisms have several properties that contribute to their pathogenicity, including inhibition of the mucociliary transport mechanism (at least in humans); they cause some degree of humoral and cell-mediated immunosuppression in calves; and they avoid phagocytosis by attaching to ciliated epithelium above the level of alveolar macrophages.

At our clinic, Mycoplasma frequently is isolated from acute and chronic calf pneumonia outbreaks and may be involved in up to 50% of chronic calf pneumonia endemics that we investigate. However, Mycoplasma sp. seldom is the only pathogen isolated in these outbreaks, and H. somni, P. multocida, and M. haemolytica usually are isolated as well. Because Mycoplasma appears ubiquitous on many farms, we wonder whether the Mycoplasma infection has been present in the calves' lungs for a long time and contributes to impaired host defense against bacterial and viral pathogens or whether the Mycoplasma infection is acute along with the other pathogens. In herds with Mycoplasma pneumonia, Mycoplasma frequently can be isolated from almost all adult cows and calves—most of which appear healthy. Therefore the ubiquitous nature of the organism makes it nearly impossible for calves on these farms not to be infected. The subsequent low grade pneumonia and defense mechanism compromise caused by the Mycoplasma infection may precede the onset of clinical pneumonia caused by bacterial and viral pathogens. How significant Mycoplasma sp. is to the entire problem is difficult to determine, but we believe it increases the risk of calfhood pneumonia. In addition to pneumonia, M. bovis may also cause otitis media, mastitis, and arthritis once it becomes established in a herd. Some of the spread is likely from feeding infected milk. Effective control measures for Mycoplasma when it is ubiquitous on a premise are challenging and made more so because effective vaccines are not available. In endemic herds, the feeding of waste milk is a known risk factor for transmission of the organism to calves, and this practice should be actively discouraged. Pasteurization will remove the risk of Mycoplasma spread by this means but only makes economic sense on larger dairies or heifer-rearing operations.

Signs of pure Mycoplasma pneumonia may be very mild. In several calf and heifer outbreaks of pure Mycoplasma pneumonia, the only signs observed were coughing induced by stress or movement of the animals, a slight increase in the respiratory rate (40 to 60 breaths/min), and low grade fever (103.5 to 105.0° F/39.72 to 40.56° C). Most affected animals continued to eat and experienced only mild depression. Owners reported observing a slight mucopurulent nasal discharge in the animals in the mornings that disappeared after the animals became active, ate, and licked their noses clean. Tracheal washes grew pure cultures of Mycoplasma, and no other pathogens were identified by bacterial cultures, viral isolation, or retrospective paired serology. Pure Mycoplasma is the exception rather than the rule because, in our clinic, Mycoplasma usually is isolated in conjunction with other pathogens in the majority of pneumonia outbreaks in which it is involved. Signs of pneumonia in these instances are identical to those described for the specific bacterial or viral agents isolated. The Mycoplasma component does not have any unique clinical features except for its association with otitis media and arthritis, and perhaps that affected animals sometimes respond poorly to specific antibiotic therapy directed against the bacterial pathogen. When this occurs, a contributory viral or Mycoplasma infection should be suspected.

Diagnosis.

This is totally dependent on culture of the organism from tracheal wash or necropsy samples. In pure Mycoplasma pneumonia, fatalities are rare, but typical Mycoplasma pneumonia gross lesions appear as red-blue firm areas in the anterior ventral lung. These areas resemble atelectatic areas but are firm, and pus may be expressed from the airways within these firm areas on a cut section. Histopathology demonstrates the “cuffing pneumonia” previously described.

In most instances in which Mycoplasma is merely one component of infection, gross necropsy lesions are typical of the other pathogens—usually anterior ventral consolidating bronchopneumonia typical of Mannheimia, Pasteurella, or Histophilus infection or abscessation caused by A. pyogenes. Occasionally Mycoplasma is isolated from lungs showing typical lesions of BRSV, BVDV, or other viral infections.

Treatment.

Treatment for Mycoplasma pneumonia may be unnecessary in some pure Mycoplasma infections because the cattle do not appear extremely ill. In pure infections, oxytetracycline hydrochloride (11 mg/kg once or twice daily) is most frequently used. Erythromycin (5.5 mg/kg twice daily), tilmicosin (10 mg/kg SQ), tulathromycin (2.5 mg/kg SQ)or florfenicol (20 mg/kg IM in the neck) may provide effective therapy in some cases, but in vitro testing found widespread resistance to these antibiotics. Enrofloxacin or other fluoroquinolones are reported to be the most effective antibiotic against Mycoplasma, but these are not approved for use in dairy cattle in the United States. Because affected animals usually continue to eat, chlortetracycline or oxytetracycline (Terramycin, Pfizer) added to the feed in therapeutic levels may provide effective therapy for groups of weaned calves or heifers.

When Mycoplasma is isolated along with P. multocida, M. haemolytica, A. pyogenes, Fusobacterium sp., or H. somni, antibacterial therapy should primarily address the bacterial pathogen. If the Pasteurella or Histophilus isolate is sensitive to tetracycline or erythromycin, choosing one of these drugs may provide efficacy against both the bacteria and Mycoplasma. Fortunately, if treatment is directed against the bacterial pathogens and ventilation or management factors are corrected, the calves recover and the Mycoplasma may not require specific therapy.

At our clinic, we have investigated several chronic heifer and postweaning calf pneumonia problems in which Mycoplasma and P. multocida or Mycoplasma and H. somni have coexisted. These problems have been very difficult to solve. In these herds, the Mycoplasma seems to be ubiquitous and seems to infect calves very early in life. Calf hutches and individual rearing of calves may not be effective in preventing Mycoplasma infection in some of these herds, but calf hutches do seem to prevent bacterial infection in the calves. Therefore as soon as the calves are grouped following weaning, a pneumonia outbreak is caused by both bacterial and Mycoplasma components. Every new group seems to be affected, and attempts at prevention appear futile. Isolation of calves to a separate farm following immediate removal from their dams may be the only solution. Other recommendations for prevention of Mycoplasma infection in calves include avoiding feeding Mycoplasma bovis– infected milk, using separate feed buckets and bottles for every calf, and preventing calves from direct contact with other cattle.

Viral Diseases of the Respiratory Tract

Infectious Bovine Rhinotracheitis

Etiology and Signs.

IBR (also known as BHV1, or “red nose”) is an infection of the upper airway and trachea caused by BHV1. Infection may assume many forms in cattle, including respiratory, conjunctival, or infectious pustular vulvovaginitis affecting the caudal reproductive tract, infectious balanoposthitis of the male external genitalia, endemic abortions, and the neonatal septicemic form characterized by encephalitis and focal plaque necrosis of the tongue. Bovine herpesvirus 5 (BoHV5) may also cause outbreaks of encephalitis in young stock. The respiratory form of BHV1 is the most common and may occur alone or coupled with the conjunctival form. DNA variants of BHV1 initially described correlated to specific system disease, but recent genomic mapping has found no basis for these divisions. Abortions may occur in association with any of the forms of the disease, either during the acute disease or in the ensuing weeks following an endemic. Each infected herd seems to have one predominant clinical form of the disease, but occasional animals may also show signs of other forms during an endemic. Recent work suggests that genetic factors may play a role in the relative resistance of cattle to IBR virus and that this resistance may be mediated by type 1 interferon genotypes.

Like many other herpes viruses, IBR virus is capable of recrudescence when previously infected cattle harboring latent virus infection are stressed by infectious diseases, shipment, or corticosteroids. Immunity from natural infection or vaccination is short lived and probably does not exceed 6 to 12 months. Respiratory disease caused by IBR is associated with high morbidity but low mortality in susceptible animals. Fatalities seldom result from primary or recurrent IBR infections unless secondary bacterial bronchopneumonia, especially M. haemolytica, or concurrent viral infection with BVDV or BRSV occurs. (These viruses are discussed further in this section.) The IBR virus compromises the physical and cellular components of the lower airway defense mechanism by damaging mucociliary transport and the mucus layer and directly infecting alveolar macrophages. Therefore combination infections may result in high mortality because of multiple compromises of the lower airway host defense and possible immunosuppression—especially with concurrent BVDV infection. As stated previously, BHV1 infection up-regulates genes that activate receptors for the leukotoxin of M. haemolytica and contribute to the severity of that disease.

Because most dairy cattle and calves currently are vaccinated for IBR, owners and veterinarians sometimes overlook or fail to consider the possibility of IBR infection during acute respiratory outbreaks or herd abortions. However, the confusing array of bovine vaccines available to laypeople, outdated or mishandled vaccines, and inadvertent failure to vaccinate individual groups or herds of cattle still predispose to acute outbreaks of IBR.

The clinical signs of IBR-respiratory form include high fever of 105.0 to 108.0° F (40.56 to 42.22° C); depression; anorexia; rapid respiration (40 to 80 breaths/min); heavy serous nasal discharge that becomes a thick mucopurulent discharge during the first 72 hours of infection; a painful cough; a dried necrotic crusting of the muzzle; white plaques visible in the nasal mucosa, mucosa of the nasal septum (Figure 4-28 ), and sometimes on the external nares and muzzle (Figure 4-29 ); occasional mucosal ulceration of the muzzle and oral mucosa; coarse tracheal rales caused by mucopurulent exudate or diphtheritic membranes in the larynx and trachea; and referred sounds and rales from the upper airway heard over both lung fields (especially in the area of the major bronchi). Although bronchitis and bronchiolitis occasionally have been observed, most cases do not have pulmonary pathology unless secondary bacterial bronchopneumonia occurs. Bacterial bronchopneumonia usually occurs within 7 to 10 days following acute IBR infection in those instances in which bacteria complicate the viral infection. Devastating mortality may occur in stressed, recently transported or purchased animals that develop IBR infection concurrent with BVDV infection, BRSV infection, or virulent strains of M. haemolytica bronchopneumonia. In outbreaks in adult herds, the disease seems to cause the most severe signs in first-calf heifers and may severely affect their future milk production during the remainder of the first lactation.

Figure 4-28.

Classical IBR plaques on the mucosa overlying the nasal septum of a Holstein. The view is through the right nares, and a penlight is present in the right lower corner of the photo.

Figure 4-29.

Plaques from IBR on the mucosa and mucocutaneous junction of the right nares region in a Holstein.

Affected animals show signs for 7 to 14 days and recover after this time unless secondary infection occurs. Abortions may occur during the acute infection or in the subsequent 4 to 8 weeks. Although fetal mortality can occur at any stage of gestation, most abortions occur in cows in the second or third trimester of pregnancy. Direct fetal infection or stress and high fever may contribute to the abortions. The conjunctival form sometimes coexists with the respiratory form and is characterized by unilateral or bilateral severely inflamed conjunctiva and serous ocular discharge that becomes mucopurulent within 2 to 4 days. In addition, multifocal white plaques composed of lymphocytes and plasma cells appear grossly on the palpebral conjunctiva (Figure 4-30 ). Some cattle also have corneal edema in the peripheral cornea, but ulcerations do not occur (also see Chapter 13). BHV1 has a similar synergistic (increased pathogenicity) effect with Moraxella bovis in the eye as with M. haemolytica in the lung. Calves with the encephalitic form of IBR may demonstrate necrotic plaques on the ventral surface of the tongue or proximal gastrointestinal tract at autopsy (Figure 4-31 ).

Figure 4-30.

Multifocal white plaques on the palpebral conjunctiva of a Holstein affected with the conjunctival form of IBR.

Figure 4-31.

White plaque on the tongue of a neonatal calf infected with IBR.

Diagnosis.

Usually the diagnosis of IBR is based on physical examination when characteristic signs and pathognomonic nasal mucosal plaques are present. Laboratory confirmation is possible by FA techniques during the acute stage (lesions less than 7 days are best). Scrapings of mucosal lesions and the white plaques in the nasal mucosa should be positive in almost all acute cases. In addition, viral isolation is possible during this time. Paired serum (acute and convalescent, 14 to 21 days later) samples provide another means of positive diagnosis. One word of caution, however—individual sick cows with septic mastitis, septic metritis, bacterial pneumonia, and so forth may show typical IBR plaques as a result of recrudescence of latent virus of natural or live vaccine origin during their illness. A diagnosis of primary IBR should not be made in these cattle, although the plaque represents the only manifestation of BHV1 disease seen in such immunocompromised animals; importantly, they may be a contagious risk for in-contact and naive animals.

Necropsy of fatal IBR cases will show diffuse inflammation, necrosis, ulceration, and diphtheritic membranes throughout the nasal passages, larynx, and trachea (Figure 4-32 ). Characteristic white plaques will be visible in the inflamed nasal mucosa and sometimes in other areas of the nasopharynx or trachea. Oral mucosal ulceration sometimes occurs. Secondary bacterial bronchopneumonia or superimposed viral infections may mask some IBR lesions.

Figure 4-32.

Severe mucosal necrosis involving larynx and trachea of a cow that died from IBR. Although fatal cases of pure IBR are rare, the pathology presented highlights the damage to the physical defense mechanisms of the lower airway that predisposes to secondary bacterial pneumonia.

(Photo courtesy Dr. John M. King.)

Bovine Respiratory Syncytial Virus

Etiology and Signs.

BRSV has become one of the most important respiratory pathogens in dairy calves and adult cattle in the past 20 years. The virus certainly may have been present for much longer, but new diagnostic procedures, increased technology in virology, and recognition of the virus and its pathophysiology have heightened awareness of this disease. The virus is a pneumovirus within the paramyxovirus family and is distinctly different from the bovine syncytial virus (BSV), which is a spumavirus in the retrovirus family. There is no current evidence that the BSV is a pathogen in cattle. Respiratory disease caused by BRSV was first reported in Europe during the 1970s and has been recognized throughout the United States in the 1980s in endemic form in beef and dairy cattle. Experimental and natural diseases have been reported, and it is now accepted that BRSV is likely the cause of many poorly defined epidemics heretofore diagnosed as “atypical interstitial pneumonia” in calves and cattle. It also is likely that BRSV infection has proceeded, and predisposed cattle to, severe bacterial bronchopneumonia but gone undiagnosed because of overwhelming bacterial lesions.

The virus produces a humoral antibody response, which is helpful both for diagnosis and epidemiological surveys. Based on surveys completed in several regions of the United States, BRSV infection appears common in cattle because 50% or more of cattle surveyed have titers to BRSV. The virus has caused sporadic clinical disease in dairy cattle and calves and probably has gone undiagnosed frequently. Outbreaks of BRSV may be limited to calves, affect only adult cows, or can involve all animals in a herd. Morbidity is high, but mortality as a result of BRSV infection is much lower unless secondary bacterial bronchopneumonia ensues. The virus apparently does not infect alveolar macrophages but may damage physical defense mechanisms of the lower airway, such as mucociliary transport, and may lead to antigen-antibody complexes that subsequently engage complement and result in damage to the lower airway. Although experimental reproduction of the clinical disease has not been consistently successful in challenge studies, there have been recent studies that help explain the pathogenesis of the disease further. Two- to 6-month-old calves have been successfully infected and have marked production of inflammatory cytokines (tumor necrosis factor, interleukin 6, and interferon); these are thought to help promote viral clearance but may have a pathogenic role in causing airway obstruction. Previous work suggests that BRSV alters macrophage function sufficiently to short cycle and depress responsiveness of lymphocytes. In any event, interstitial pneumonia, secondary bacterial pneumonia, airway obstruction, and pneumothorax are very common following BRSV infection. Many unexplained facets of BRSV infection persist despite the proliferation of research on the virus. For example, BRSV infection often arises in herds that appear to have excellent management and have not purchased new cattle, shipped and returned existing cattle, or stressed animals in any apparent way. Where did the infection come from in these herds? Was it latent in a recovered animal, or was it introduced by regular visitors to the farm? Cattle are thought to be the reservoir, but it has not yet been shown how or why the virus activates, replicates, and spreads to cause all clinical epidemics.

Fortunately, because of increased awareness of BRSV in cattle, bovine practitioners are beginning to suspect the disease based on clinical signs and routinely seek virus identification, histopathologic confirmation of the virus, or serologic confirmation when acute epidemics of respiratory disease occur in cattle.

The signs of acute BRSV range from inapparent to fulminant. In most outbreaks, acute BRSV infection causes high morbidity in the affected group within several days to 1 week. Clinical signs include high fever (104.0 to 108.0° F/40.0 to 42.22° C); depression, anorexia, and decreased milk production; salivation and serous or mucoid nasal discharge; degree of dyspnea varies from simple increased respiratory rate (40 to 100 breaths/min) to open mouth breathing; and in all but the most mild outbreaks, a percentage of the affected cattle will have subcutaneous emphysema palpable under the skin of the dorsum, especially near the withers (Figure 4-33 ). Auscultation of the lungs in acute cases may reveal a wide range of sounds. Increased bronchovesicular sounds, bronchial tones, fine crepitation caused by emphysema, and rales (usually as a result of secondary bacterial bronchopneumonia) have been described. In New York, practitioners have found the lungs may auscult as diffusely very quiet or almost inaudible in acutely affected cattle in some outbreaks. This has been a very important sign and initially appears in contrast to the outward signs of dyspnea displayed by these cattle. However, the relative deficit of airway sounds fits the existing pathology because pneumothorax and/or diffuse interstitial edema and emphysema compress the small airways and cause the lungs to be quieter than one would expect (Figure 4-34, Figure 4-35 ). This is the same phenomenon that occurs in proliferative pneumonia in which the alveoli and small airways are obliterated or reduced in size. If secondary bacterial pneumonia occurs, bronchial tones or rales are heard in the anterior ventral lung region, and the dorsal and caudal lungs become quieter because of mechanical overwork, increasing the degree of edema and emphysema. Dyspnea will be severe in such cases, and affected animals usually show open mouth breathing and an audible grunt or groan with each expiration. This dyspnea is more obvious if affected animals are stressed by handling or being made to move. Despite the high fevers and respiratory distress, affected cattle frequently do not look septic (e.g., severe depression, scleral injection) as with acute overwhelming bacterial pneumonia.

Figure 4-33.

A mature cow representative of a herd outbreak with BRSV infection. This cow had respiratory distress and severe subcutaneous emphysema over the chest, back, and face (notice indentation of the halter on the face).

Figure 4-34.

A, A 4-month-old calf with respiratory distress and pneumothorax caused by BRSV. B, Radiograph of the pneumothorax is shown. C, Radiograph of another calf on the farm infected with BRSV showing a large bullae in the lung., Top of lung;, diaphragm.

Figure 4-35.

Cut section of lung at necropsy of a fatal case of BRSV pneumonia. Interstitial edema and emphysema are apparent.

(Photo courtesy Dr. John M. King.)

A biphasic disease may occur in some cattle with BRSV infection. The first stage or phase of the disease is characterized by mild or more serious signs as described above. The affected animals apparently improve over the next few days only to develop peracute severe respiratory distress several days to several weeks after their initial improvement. Because these animals initially appeared to have mild disease and responded to treatment, this secondary phase is entirely unexpected. Secondary acute dyspnea is thought to reflect an immune-mediated disease caused by hypersensitivity and/or a severe Th2 response in the lower airway and lung parenchyma and is frequently fatal.

Diagnosis.

The signs of BRSV infection in calves or cattle may be suggestive of the diagnosis, especially when acute onset, high fever, and subcutaneous emphysema are found in several affected animals. These signs are rarely seen in calves younger than 6 weeks, but calves aged 2 to 6 months seem to be most commonly affected. Auscultation of the lungs in acute cases may be helpful if the lungs sound diffusely quiet despite obvious severe dyspnea. The veterinarian must be cautious in diagnosing BRSV based only on the finding of subcutaneous emphysema or pneumothorax in some animals. Any severe pneumonia (especially other interstitial pneumonias or severe consolidating bronchopneumonia) can also cause subcutaneous emphysema because the only remaining normal lung tissue (dorsal or caudal lung fields) is overworked to the point at which emphysema and interstitial edema are likely. Therefore subcutaneous emphysema may be suggestive of but not pathognomonic for BRSV. As with most of the diseases discussed thus far, laboratory confirmation is the only definitive means to confirm a diagnosis of BRSV. Viral cultures from tracheal wash fluid or necropsy specimens are indicated but often are not rewarding because BRSV is quickly cleared from the respiratory tract or a rapidly developing secretory antibody neutralizes the virus within the respiratory tract. The best results are from viral cultures or FA testing taken in the very early stages of the disease and quickly transported unfrozen to a diagnostic laboratory equipped with appropriate cell cultures. FA techniques may be used for tracheal wash samples, nasopharyngeal smears, and necropsy specimens of infected lung. Serology is helpful in establishing a diagnosis of BRSV because a marked humoral antibody titer occurs in response to the infection. Baker and Frey emphasize that antibody titers may increase early after acute infection and often peak before 2 weeks postinfection. Therefore collection of serum on day 1 and day 14 is very important when evaluating seroconversion. The same authors state that young calves may have titers derived from colostrum. These titers, indicative of passive immunity, are not protective against BRSV infection. Thus older calves, heifers, or adult animals are better populations to sample. Necropsy specimens may be very helpful in establishing a diagnosis. This is especially true if death has been acute and secondary bacterial pneumonia has not yet developed to somewhat mask the pulmonary lesions caused by BRSV. In pure BRSV infection, diffuse edema and emphysema may be present (see Figure 4-35). In addition, focal firm areas of pneumonia will be palpable throughout the entire lung. Lesions are not limited to any one area of lung tissue. If secondary bacterial bronchopneumonia coexists with BRSV, the anterior ventral lung fields usually are dark colored, firm, fibrin covered, and consolidated (Figure 4-36 ). In this instance, typical BRSV lesions of emphysema, edema, and scattered palpably firm areas will be found in the lung caudal and dorsal to the consolidated areas.

Figure 4-36.

Necropsy view of lungs from a fatal case of BRSV combined with secondary M. haemolytica. This combination of pathogens killed 30 of the 55 heifers in the group within 10 days during inclement winter weather.

Several times at our clinic, we have obtained Pasteurella or Mannheimia isolates from tracheal wash specimens in BRSV outbreaks before BRSV was confirmed by the diagnostic laboratory. Cattle in these herd outbreaks failed to respond, or responded unusually slowly, when placed on antibiotics chosen for their specific Pasteurella/Mannheimia isolate. This poor clinical response is a signal that another pathogen is contributing to the herd problem. Subsequent laboratory procedures may identify the causative virus, but viral cultures often lag behind bacterial culture and sensitivities. Despite the clinical frustrations and economic consequences, the veterinarian must show reasonable patience when requesting confirmation of viral diseases. It is best to make personal contact with the laboratory, explain the seriousness of the outbreak, provide appropriate samples, and ascertain the appropriate time required for viral isolation, FA techniques, or titers.

Treatment.

Therapy for acute BRSV infection is symptomatic and supportive. Broad-spectrum antibiotics are indicated to counteract or discourage bacterial bronchopneumonia and should be initiated following collection of tracheal wash samples from acutely infected calves or cattle. Ceftiofur is initially used in most dairy animals until tracheal wash cultures have been completed. Once cultures are completed, specific antibacterial therapy may be instituted if bacterial pathogens are isolated.

NSAIDs may be helpful in acute BRSV infections. Aspirin or flunixin may be used in the same dosages mentioned previously. Corticosteroids have been recommended for treatment of BRSV infections in calves. Whereas calves or nonpregnant cattle with respiratory distress but minimal evidence of sepsis may receive some benefit from these drugs in diminishing the pulmonary pathology created by the BRSV, in a few cases a dramatic improvement in clinical signs can be observed. They certainly can predispose to secondary infections and abortions, and their use should be selective. Antihistamines also have been recommended for treatment of BRSV and may be used (tripelennamine hydrochloride at a dosage of 1 mg/kg IM, twice daily).

Any cattle that develop the second phase or second stage of BRSV infection, which appears as a hypersensitivity reaction, should receive antiinflammatory medication in addition to broad-spectrum antibiotics. The peracute onset and extreme dyspnea exhibited by these animals is usually fatal; therefore heroic therapeutic measures are indicated. Several drugs may be indicated, and clinical judgment will determine which drugs will be used. For an adult cow with this form of the disease, drugs that may be considered and their dosages follow:

1. Broad-spectrum antibiotics	Based on previous herd tracheal wash results
2. Dexamethasone	10 to 20 mg once daily (except in pregnant animals) IM or IV
3. Antihistamine	Tripelennamine hydrochloride 1 mg/kg IM twice daily
4. Atropine	0.048 mg/kg IM or SQ twice daily
5. NSAID	(e.g., flunixin 1 mg/kg IM or IV every 12 or 24 hours, aspirin 240 to 480 grains twice daily)
6. Furosemide	250 mg (if severe pulmonary edema is present) IV or IM once or twice daily

Intranasal oxygen (10 to 15 L/min) is usually used in our hospital and will often decrease the respiratory rate and effort. Nebulization with corticosteroids and antibiotics can be helpful, but a bronchodilator should be administered either before beginning the nebulization or at the same time. Systemic atropine and/or inhaled ipratropium and/or aminophylline (2 to 4 mg/kg every 12 hours) as a constant rate infusion can be used. In animals that develop pneumothorax, evacuation of free air from the pleural space can offer significant improvement. The complete mediastinum of cattle often confines pneumothorax to one hemithorax, but bilateral disease or severe unilateral lung collapse caused by pneumothorax may necessitate evacuation. Details regarding specific treatment of pneumothorax are given later in this chapter.

In summary, the veterinarian must allow for a wide range of severity in BRSV outbreaks. In some mild outbreaks, no animals will require treatment. On the other hand, severe outbreaks complicated by pneumothorax (Figure 4-37 ), emphysema, and/or bacterial pathogens may result in 10% to 30% mortality despite heroic treatment efforts. Vaccination will be discussed later, but the literature on BRSV vaccination is confusing, with some articles showing protection from inactivated or modified live vaccines, others demonstrating no protection from inactivated vaccines, and a few suggesting an adverse immune response on exposure to the virus. Most recently protection from challenge infection was good following the intranasal administration of a MLV vaccine marketed for parenteral administration.

Figure 4-37.

Radiograph of a yearling heifer with pneumothorax associated with BRSV infection. Note the unilateral lung collapse and “silhouetting” of great vessels, indicating concurrent pneumomediastinum.

Parainfluenza-3

Etiology and Signs.

Parainfluenza-3 (PI₃) virus is capable of infecting the bovine respiratory tract and predisposing infected animals to more severe pneumonia when subsequently exposed to bacterial pathogens such as M. haemolytica. After experimental inoculation, the virus infects the upper and lower airways of calves with subsequent damage to ciliated epithelial cells, mucus layer, mucociliary transport, and infection of alveolar macrophages. As bronchitis and bronchiolitis ensue, purulent exudate fills some small airways. Despite this pathology, PI₃ infection is a mild disease unless complicated by secondary bacterial agents. Based on serologic surveys, most cattle probably have been exposed to PI₃ infection as calves. We seldom identify PI₃ in bovine respiratory outbreaks in dairy calves or cows in the northeastern United States. This may result from the fact that most dairy animals are vaccinated against this virus.

The signs of PI₃ infection include fever (104.0 to 107.0° F/40.00 to 41.67° C), depression, anorexia, nasal and ocular serous discharge, increased respiratory rate (40 to 80 breaths/min), tracheal rales, and occasional rales in the lower lung fields. Fatalities are uncommon, and recovery should occur over 7 days.

The signs of PI₃ complicated by bacterial pneumonia are simply those of a moderate to severe bacterial bronchopneumonia as previously described under the various bacterial pathogens. Response to specific treatment for the bacterial bronchopneumonia, however, would be less prompt and complete than anticipated for bacterial infection alone.

Diagnosis.

The clinical signs of PI₃ infection in calves or cattle are not specific enough to allow definitive diagnosis. Therefore culture of the organism from acutely infected calves via tracheal wash, nasopharyngeal swabs, or necropsy specimens is necessary to identify this organism. Paired serum samples also are helpful because humoral antibody production is anticipated following infection. Isolation attempts may be fruitless if samples are not collected early in the course of the disease.

Fatal cases usually are complicated by secondary bacterial pneumonia—especially M. haemolytica or P. multocida. Therefore gross pathology lesions suggest bacterial bronchopneumonia, and a diagnosis of PI₃ is easily missed unless the veterinarian requests viral isolation and obtains paired serum samples from surviving animals.

Treatment.

Treatment must address the frequent secondary bacterial pneumonia. There are no characteristic clinical signs to allow veterinarians to diagnose PI₃ specifically.

Bovine Virus Diarrhea Virus

BVDV is one of the major pathogens of dairy cattle and may cause a wide range of lesions or clinical syndromes. This pestivirus from the Flaviviridae family causes fever, mucosal erosions, diarrhea, abortions or reproductive failure, congenital anomalies, persistent infection of fetuses infected during 40 to 120 days of gestation, and many other signs. The disease will be discussed fully in Chapter 6. However, BVDV has been incriminated as a “respiratory virus” in cattle, and certain strains certainly can be isolated from the lower airway and alveolar macrophages of infected cattle. Some BVDV strains (genotypes 1a and 1b and biotype noncytopathogenic) are more commonly found in the lungs of cattle and are frequently associated with respiratory disease outbreaks. All strains of BVDV are immunosuppressive and predispose infected cattle to bacterial or other viral pneumonia. Naive cattle exposed to type 2 strain may develop severe interstitial pneumonia, thrombocytopenia, bone marrow necrosis, diarrhea, and acute death sometimes without having mucosal erosions. Additionally, a persistently infected calf or cow may suddenly develop bacterial pneumonia without other predisposing factors, and this scenario should always be considered as a possible reason for a single case of bacterial pneumonia in a herd.

During acute BVDV infection, high fevers occur in affected cattle early in the course of the disease. These cattle may show no other signs—no diarrhea, no mucosal lesions—and merely appear depressed and febrile at 106.0 to 108.0° F (41.11 to 42.22° C). Because the high fever necessitates increased physiologic heat loss, some cows have mild increases in their respiratory rate (40 to 60 breaths/min), but the lungs are normal on auscultation or may have slightly increased bronchovesicular sounds. These cattle are merely in the early stages of acute BVDV infection, and unless a superimposed bacterial infection develops, clinical pneumonia may not occur. If the animal seroconverts and responds to the BVDV in a normal fashion, no other signs may develop. Some cattle will progress from this early stage of fever with no other signs to blatant mucosal lesions and diarrhea 7 to 14 days following the original onset of fever. This situation has been observed in natural outbreaks and with experimental BVDV infection with certain strains of BVDV in naive cattle. Most cattle with BVDV have mild pulmonary lesions or normal lungs grossly and histologically unless an opportunistic bacterial pneumonia has developed. Naive cattle infected with the type 2 strain may die with severe interstitial pneumonia.

Acute BVDV infection causes profound immunosuppression in affected animals for 7 to 14 days or until they recover. Research documents the negative effects that BVDV infection has on neutrophil, macrophage, and lymphocyte function. Humoral and cell-mediated lymphocyte functions are depressed during acute BVDV infection. Leukopenia in the peripheral blood is a well-known feature of acute BVDV infection in cattle. Although naive or susceptible cattle fully recover immune function following the development of adequate humoral antibody against BVDV, they are very susceptible to secondary infection during the acute BVDV infection and associated immunosuppression. Alveolar macrophages are frequently infected with BVDV, which would be expected to have a direct negative effect on lung protection against invading bacteria. Therefore the results are devastating if a cow or group of cows acutely infected with BVDV has the bad fortune to become infected with P. multocida, M. haemolytica, or H. somni pneumonia at the same time. Bacterial bronchopneumonia may progress rapidly because host defense mechanisms are negligible. In addition, cattle may die so quickly from severe pneumonia that necropsy identifies bacterial pneumonia as the cause of death. The existence of BVDV infection will only be confirmed if viral isolation or immunohistochemistry is performed, some affected cows develop signs of mucosal disease, or some fatalities demonstrate typical BVDV lesions as well as bacterial pneumonia at necropsy.

This situation most often develops in assembled groups of heifers or replacement heifers that are naive to BVDV and have lost maternal antibodies and subsequently encounter BVDV via a persistently infected animal. Other management-related stresses, transportation, pen reorganization, poor ventilation, and so on may also contribute to the development of bacterial pneumonia during concurrent BVDV infection.

In summary, BVDV by itself rarely causes major respiratory disease except for type 2 infections in naive cattle, which may cause interstitial pneumonia and acute death sometimes without the typical upper gastrointestinal tract lesions. Type 1 strains are commonly isolated from the lower airway and more recently pulmonary macrophages in BVDV outbreaks, and play a potentially important role in the bovine respiratory disease complex. Acute BVDV infection (any strain) may result in transient immunosuppression that predisposes to severe respiratory infections in cattle concurrently exposed to other respiratory pathogens. This immunosuppressive effect is not limited to the respiratory tract and certainly would contribute to drastic illness if a cow acutely infected with BVDV encountered septic mastitis, metritis, or salmonellosis.

Other Viruses

Several other viruses, including adenoviruses (types 3 and 7), rhinoviruses, and coronaviruses, have been shown experimentally to be potential pathogens of the bovine respiratory tract. Clinically there are no pathognomonic features of these viruses. Except for coronaviruses, diagnostic laboratories seldom identify these viruses in outbreaks of infectious respiratory disease in cattle or calves. The role coronavirus plays in the bovine respiratory disease complex is not clear. Coronavirus is commonly found in outbreaks, either acute or endemic, but can also be commonly found in healthy animals. It may be important if the farmer describes a “pneumonia-enteritis” complex in 1- to 8-week-old calves. The respiratory isolate is very similar to the enteric isolate.

Control and Prevention of Infectious Respiratory Diseases in Dairy Cattle*

The control of acute or chronic endemic respiratory disease within groups of calves or adult cattle consists of four components:

• 1.Definitive diagnosis of the causative agent(s)
• 2.Specific medical therapy
• 3.Correction of management, environmental, or ventilation deficiencies that contribute to or perpetuate the respiratory disease
• 4.Preventive medicine, including management techniques and vaccination

Most of these points have been addressed in the discussion of treatment for each of the infectious agents in this section. Field outbreaks of respiratory disease may be limited to individual groups such as weaned calves, breeding age heifers, milking cows, and dry cows, or may involve all animals on the premises. When only one group is affected, the veterinarian should try to determine what management, environmental, or ventilation conditions might have predisposed this group to infection. It also is necessary to elicit information from the owner such as vaccination history, previous outbreaks of respiratory disease, recent purchase of animals, recent movement of resident animals to shows, and other facts that may help to explain how the respiratory infection may have become established in a group of animals or the entire herd.

In the northeastern United States, calves housed indoors have a notoriously high incidence of pneumonia. This may be seen in calves of all ages or only in postweaning calves. The most common age for pneumonia in calves is 1 to 6 months. Infection may occur in every group of calves placed in a certain housing condition on the farm or only in calves kept in the main dairy barn. This type of high morbidity calf pneumonia has been termed “enzootic pneumonia,” but this is a poor term because it does not help elucidate a specific etiology. The term has gained acceptance because it is often more indicative of management and ventilation deficiencies than a specific primary etiology. Respiratory viruses, bacteria, and Mycoplasma may be involved separately or in combination in these outbreaks. Although P. multocida and M. haemolytica are the most common bacteria found in such outbreaks, H. somni is also found in a small proportion of herd problems.

Chronic or recurrent pneumonia caused by bacterial pathogens other than Mycoplasma in milk-fed calves is best controlled by the use of calf hutches (Figure 4-38 ). Many farms have also had good success with plastic hoop houses or curtain-sided barns with transparent roofs. Calves should be removed from the dam and calving pen as quickly as possible, aided in drying, and fed 4 quarts of colostrum before being moved to the hutch or calf barn. When the environment is managed in this way, most bacterial and viral pneumonias will be prevented, primarily by ensuring good ventilation that dilutes potential pathogens. Mycoplasma may be a herd problem even with good environmental management. Feeding of contaminated colostrum or waste milk is thought to be the primary means of transmitting Mycoplasma to young calves. Aerosol spread may subsequently occur to calves housed with or very near infected calves. Use of colostrum replacer, milk replacer, and pasteurization of waste milk are all alternatives to prevent exposure of young calves. Recent studies of heat-treating colostrum have shown that heating to less than pasteurization temperatures is very effective in killing important calf pathogens without damaging the immunoglobulins. Heating to 140° F (60° C) for 30 minutes eliminates M. bovis from colostrum. Standard pasteurization procedures have been used to successfully treat waste milk before feeding it to calves and are becoming common on larger dairies.

Figure 4-38.

Plywood calf hutches with calves tethered.

The major objection to the use of calf hutches by dairy farmers is the increased labor required to feed calves outdoors and the necessity to work outside in inclement winter weather. Both of these factors have probably contributed to the increased use of hoop houses and barns on larger dairies where employees care for calves. Regardless of the selected housing type, we recommend it be unheated and well ventilated. Calves have increased caloric requirements at low environmental temperatures and thus require additional milk or milk replacer. A rough estimate of the increase in energy needs is 50% at 20° F (27° C) and 100% at 25° F (221° C). Calves may be fed more volume twice a day or be fed an additional time at midday to meet these needs. The choice of bedding material influences the energy balance of the calf, with deep straw providing the greatest insulation benefit, wood shavings intermediate, and shredded paper the least. Despite the disadvantages to labor, calves reared in hutches appear to be at least risk of respiratory infection.

Cattle housed in tie stall barns are predisposed to infectious pneumonia where marked environmental temperature and humidity fluctuations occur during the indoor housing season. Late fall and early spring, as well as winter thaws, are the times most likely to vary widely in temperature and humidity. Increased humidity and ammonia accumulate in areas with inadequate ventilation. Ammonia dissolves in the suspended water vapor and is an irritant to the respiratory epithelium. Exhaled bacteria and viruses are included in microscopic droplets of moisture. Prevention of respiratory infections in these settings requires improvement in the ventilation to dilute the pathogens and remove the irritants. There is a wealth of information on techniques for designing or retrofitting appropriate ventilation systems available from agricultural engineers through the extension services of each state. If the walls or ceiling accumulate condensation or the odor of ammonia in the barn is noticeable, there is inadequate ventilation. Normally the inside temperature in these barns in winter should not exceed 50° F (10° C). All modern free stall barns in cold climates are now curtain-sided and can be adjusted according to weather conditions in the winter to allow adequate fresh air entry for removal of humidity and ammonia. A temperature gradient of only a few degrees between inside and outside temperatures is adequate to drive the necessary air exchanges for maintaining air quality inside the barn.

Whenever possible, prevention of infectious respiratory diseases in dairy cattle is more desirable than control measures. Prevention consists both of effective vaccination programs and management designed to reduce the probability of infectious respiratory disease. Currently, effective vaccines are available for IBR, PI₃, and BVDV. Vaccines against H. somni and P. multocida, although available, have not been proven to be of any benefit. Newer vaccines against M. haemolytica that are based on leukotoxins of this bacterium have been proven beneficial in reducing morbidity and mortality in feedlot cattle. No comparable data have been published for dairy cattle, but by extension a benefit is probable if mannheimiosis were to occur. Vaccination strategies for herds should be individually determined and include the assessment of risk for all age groups. Closed herds in isolated settings have a much lower risk of contagious pathogens than herds that continuously purchase animals or exhibit cattle. Regardless, primary immunization requires two doses of vaccine and is best done at an early age. Optimal response to vaccines occurs after the waning of colostrally derived antibodies. Thus current recommendations are to begin the primary series at about 3 months of age with the second dose administered 2 to 4 weeks later. Recent research indicates the greatest response to immunization against IBR and BVDV occurs if the first two doses are a killed product and the subsequent booster is a modified live vaccine. All major vaccine producers offer combination products with options of killed virus or modified live virus that provide the four viral components in a single injection. The M. haemolytica leukotoxoids are usually a distinct product. Subsequent boosters are administered at frequencies that correspond to the perceived risk and usually at times or ages that offer some convenience to management. The duration of immunity following proper vaccination is mostly not known for each of the components of the routinely used products. Thus recommendations for low-risk herds may be annual revaccination of the entire herd, whereas high-risk herds may be given boosters two or three times per year. Alternatively, in many large herds adults are vaccinated in conjunction with the lactation cycle. For example, a modified live booster is given at 30 days in milk, and killed boosters are given at 120 and 240 days of gestation.

There have been recommendations in the face of endemic respiratory disease in calves to hyperimmunize young calves against viral and bacterial diseases by repeated vaccination at 2-week intervals. To date, there is no evidence this strategy has any merit. Rather, the environmental and management ideas discussed above are more likely to provide health and economic returns to the herd. Another widely used strategy for undifferentiated respiratory disease of recently weaned calves is metaphylaxis of the at-risk group. Current practice in many dairies is to wean a group of calves and move them within 1 week or so to group housing. This change, particularly when more than 10 calves in a group are moved at one time, seems to be a trigger for respiratory disease. Control has been achieved in many herds with mass medication at the time of a move with a single injection of a long-acting antibiotic such as oxytetracycline, tilmicosin, tulathromycin, or florfenicol or by feeding chlortetracycline and sulfamethazine pellets for 5 to 7 days. Herds that practice a more gradual assembly of large groups of calves or that simply have fewer calves seem to be at much lower risk for this problem.

As of this writing, there is a commercial vaccine available for M. bovis that has not yet been proven efficacious. Regulatory methods in the United States require that vaccines be safe and induce an immune response measured by the production of specific antibodies. Unfortunately, efficacy in preventing the target disease is not a requirement. Thus there are vaccines available for respiratory pathogens such as P. multocida and H. somni that appear to provide no benefit to the calf or cow. Efforts will no doubt continue to develop new immunization products with greater safety, efficacy, and efficiency. Veterinarians are encouraged to remain abreast of these new developments because new knowledge and technologies may make our current practices obsolete.

Parasitic Pneumonia

Dictyocaulus viviparus

Etiology and Signs.

Dictyocaulus viviparus is the lungworm of cattle and causes parasitic pneumonia and bronchiolitis in calves and adult cattle. This parasite has a direct life cycle, so infection merely requires management factors that allow a buildup of the parasite in the environment and ingestion of the infective larvae by naive cattle.

Adult lungworms reside in the trachea and bronchi. Eggs produced by female adults hatch either in the trachea or before being passed in the feces. The progression to the infective third stage larvae requires only 5 days, and the larvae are then ingested during consumption of contaminated grass in a pasture or bedding in heavily contaminated box stalls. Ingested larvae traverse the intestinal wall to reside in mesenteric lymph nodes, moult to the fourth stage, and within 1 week migrate to the lungs through lymphatics or blood vessels. The final fifth stage is reached after the larvae arrive in the bronchioles. The prepatent period is approximately 4 weeks because this period is required for the larvae to mature to egg-laying adults.

Signs of primary infection include varying degrees of dyspnea, a characteristic deep and moist cough, and moist rales or crackles heard over the entire lung field. Coughing is more severe than with most other bovine pneumonias. Diffuse rales rather than rales limited to the anterior ventral lung fields are an important sign that differentiates lungworm from bacterial pneumonias. Severely affected calves or cows will show “heave”-like breathing with visible expiratory and inspiratory effort. In some cases, emphysema is present when heavy airway exudate results in extreme mechanical respiratory efforts. Fever (103.0 to 106.0° F/39.44 to 41.11° C) may be present in some cases, as opportunistic bacteria such as P. multocida invade the damaged lower airway and establish a secondary bacterial bronchopneumonia. Fever also may be present simply from exertion involved in breathing during warm weather or in poorly ventilated barns. Usually several animals in a group or the entire herd will show signs. Affected cattle will continue to eat unless severe dyspnea or coughing interferes with their ability to ingest feed. In those cases with severe dyspnea, frequent coughing, marked expiratory efforts, and open mouth breathing are noted.

In addition to the above signs of primary infection, veterinarians should be aware of the reinfection or acute larval migration syndrome that occurs in adult cattle with endemic D. viviparus. Although age-related immunity to D. viviparus exists in adult cattle in endemic areas, this immunity may be incomplete or may not be able to overcome heavy challenge. Although most ingested larvae are killed or fail to mature in previously infected cattle, heavy exposure apparently allows large numbers of larvae to reach the lungs and cause respiratory signs through either an immune-mediated means and/or from migration of large numbers of larvae into the lung. Signs usually develop 14 to 16 days following exposure to contaminated pastures. Coughing that is frequent and deep, as well as an increased respiratory rate, characterizes the syndrome. Milk production decreases acutely in affected cattle. Rales may not be present. Fecal examinations are usually negative for Dictyocaulus because the disease is a result of the L4 migration into the lung.

Diagnosis.

In primary infections, the diagnosis is aided by history, physical examination findings, laboratory or postmortem confirmation, and knowledge of the life cycle of the parasite.

The characteristic deep moist cough and moist rales ausculted throughout the entire lung are the most significant clinical signs—especially if found in a majority of the cattle within a group. As with any parasitic disease, some affected animals (“weak sisters”) will display more blatant signs than others, but most within the group will be affected. History may be very helpful if animals have been placed on pasture recently or confined by group housing (heifers) to pens having a base consisting of several months of manure accumulation.

Baermann's technique performed on fresh manure is indicated for specific diagnosis but is of limited value in prepatent and postpatent infections. Therefore Baermann's technique and tracheal washes should be performed on several animals. If larvae are found using Baermann's technique, the diagnosis is confirmed as a patent infection. In prepatent infections, tracheal wash samples may identify parasites, rule out other causes of pneumonia, and allow cytologic confirmation of eosinophilic inflammation typical of parasitic bronchitis/pneumonia. In postpatent infections, tracheal wash cytology indicates eosinophilic inflammation and may suggest chronic inflammation. Eosinophilic tracheal wash should be highly suggestive of parasitic pneumonia (Figure 4-39 ).

Figure 4-39.

Wright-Giemsa stain of tracheal wash from a cow representative of a herd problem of chronic cough and decreased production. Lungworms (D. viviparous) were found to be the cause of the disease. The large number of eosinophils on this 403 slide is highly suggestive of lungworm infection.

Necropsy findings in fatal infections vary with the stage of infection. In early prepatent infections, microscopic examination of bronchial exudate may be necessary to identify larvae, whereas in later prepatent infections, the larvae are obvious if the airways are properly opened and inspected. Eosinophilic bronchitis may be confirmed by histopathology. Patent infections are obvious because large numbers of mature parasites up to 8.0 cm in length are found in the airways (Figure 4-40 ). Secondary anterior ventral bacterial bronchopneumonia may be present, and interstitial emphysema is observed in occasional severe cases. In postpatent infections, chronic bronchitis, bronchiectasis, and secondary bronchiolitis obliterans may be observed.

Figure 4-40.

Necropsy specimen of trachea from fatal lungworm infection in a calf showing hundreds of D. viviparous lungworms.

(Photo courtesy Dr. John Perdrizet.)

The reinfection syndrome is characterized by clinical signs of severe coughing in the majority of cattle following their introduction to infected pastures. Tracheal wash samples will reveal eosinophilic inflammation. Baermann's technique results will be negative. Necropsy lesions in the reinfection syndrome consist of small greenish-gray subpleural nodules, green exudate occluding small airways, and occasional green tinting of the interlobular septa. Histologically, eosinophils predominate, but lymphocytes, plasma cells, macrophages, and giant cells may be observed within the airways.

Treatment.

Treatment of primary D. viviparus infection consists of an anthelmintic to destroy the parasite and, when necessary, antibiotic therapy to control secondary bacterial infection of the lower airway.

Levamisole phosphate (8 mg/kg body weight, SQ or orally), fenbendazole (5 mg/kg orally), albendazole (10 mg/kg orally), and ivermectin (0.2 mg/kg SQ) all have been recommended as treatments for primary D. viviparus infection. Levamisole has been very effective in our clinic but is no longer approved for use in dairy cattle, so fenbendazole would now be the first choice of treatment. Affected cattle should not be allowed back on infected pastures, and confined cattle should be removed from infected manure packs until the pens can be cleaned completely of manure and bedding.

Because the most common secondary bacterial invader is P. multocida, bacterial bronchopneumonia may be treated with tetracycline, ceftiofur, ampicillin, or penicillin. Secondary bacterial pneumonia may mask the presence of lungworms in calves or heifers. Such animals frequently appear to improve temporarily while on antibiotic therapy but then quickly relapse when antibiotics are withdrawn. Antibiotic therapy in these instances may cause resolution of fever and improved attitude but will not alleviate coughing or severe dyspnea. Only when further diagnostics are pursued in live patients or necropsies are performed in fatal cases will the true diagnosis be obtained and effective treatment instituted.

Although the reinfection syndrome appears to be an immune-mediated disorder, affected cattle appear to respond rapidly to levamisole injections according to Breeze. Without treatment, continued coughing and production losses persist in the affected animals for weeks.

Control.

Control of D. viviparus infections requires management decisions regarding contaminated pastures. Because infective larvae have been shown to survive winter conditions, pastures should not be grazed in the early spring. Before being pastured, yearling heifers should be treated with anthelmintics effective against D. viviparus, and all animals should be treated routinely with anthelmintics at monthly intervals if the animals are to be placed on contaminated pastures. Moisture promotes survival and activity of infective larvae. Highlighting this fact, clinical lungworm infections in the northeastern United States are observed primarily during wet summers. Whenever possible, extreme care and additional anthelmintic treatment are indicated during wet summers and when animals are pastured in swampy, low-level endemic areas.

Ascaris lumbricoides

Etiology and Signs.

Although reported rarely, Ascaris lumbricoides, the swine ascarid, has been identified as a natural and experimental cause of pneumonia in cattle. Exposure of susceptible cattle to large numbers of larvae occurs when the cattle are placed in bedded pens, corrals, or poor quality pastures previously used by pigs.

Clinical signs consisting of elevated temperature, elevated respiratory and heart rate, marked dyspnea, coughing, and an expiratory grunt develop 7 to 14 days after the cattle are exposed to ascarid ova. Auscultation of the lungs may reflect interstitial changes of pulmonary edema and emphysema. Therefore initial increased bronchovesicular sounds may be replaced by decreased sounds as further interstitial pathology and emphysema ensue. The clinical course lasts 10 to 14 days in most cases and occasionally may be fatal.

One experimental infection suggested that initial exposure to ascarid larvae resulted in very mild signs, whereas reexposure resulted in pronounced signs. This may imply an immune-mediated cause or component to the severe interstitial pneumonia.

Diagnosis.

Diagnosis of this disease is difficult unless historical information leads to suspicion of exposure to A. lumbricoides ova. A tracheal wash sample may demonstrate an eosinophilic inflammatory pattern. Definitive diagnosis requires identification of the parasite or histopathology to study the larvae and associated interstitial pneumonia.

Treatment.

Treatment is nonspecific and supportive in the hope that the normal life cycle of the parasite will eliminate the larvae. Prevention involves avoidance of environments used by swine.

Caudal Vena Caval Thrombosis

Etiology and Signs.

Caudal vena caval thrombosis results in a variety of clinical respiratory syndromes in cattle. Septic thromboemboli originating from an abscess at the hilus of the liver shower the caudal vena cava, right heart, and pulmonary arterial circulation. Although most cattle do not show signs of illness when the shower occurs, some cattle experience acute death from massive pulmonary infarction or have an acute onset of profound respiratory distress at the time of a thromboembolic episode. Those cattle that have inapparent seeding of the pulmonary arteries or survive an acute respiratory distress episode caused by thromboemboli may eventually develop dyspnea, hemoptysis, and anemia. Epistaxis is the most common clinical sign observed in those cows with hemoptysis.

The pathogenesis of caudal vena caval thrombosis starts in the forestomach or abomasum and involves inflammatory or ulcerative mucosal lesions that allow bacterial seeding of the portal circulation with subsequent formation of liver abscesses. Therefore rumenitis, ruminal acidosis, abomasal ulcers, and similar disorders predispose to the condition. This same pathogenesis is responsible for “sawdust livers” in feedlot beef animals, but in dairy cattle, the abscesses usually are larger and fewer in number. Many dairy cattle have only one abscess. The location is much more important than the number of abscesses, however, because only those at the hilus of the liver or adjacent to the post cava represent significant risk (Figure 4-41 ). F. necrophorum or A. pyogenes are the most common organisms isolated from liver abscesses in dairy cattle. Most cattle with liver abscesses show no clinical signs of illness unless an abscess erodes into the vena cava or multiple large abscesses develop. This disease occurs sporadically in heifers and adult cattle but is rare in calves. This may be the result of calves being fed less intensive diets than heifers or lactating animals.

Figure 4-41.

Multiple hepatic abscesses that were an incidental finding at postmortem in an adult dairy cow. Abscesses, although multiple, were small and located well away from the hilus. No evidence of embolic showering to other sites was evident at postmortem.

In caudal vena caval thrombosis, erosion of a liver abscess into the vena cava with formation of a septic venous thrombosis instigates the clinical disease, and the affected cow may show one of the following syndromes.

Sudden Death Syndrome

Acute rupture of a liver abscess into the caudal vena cava may result in massive thromboemboli to the right heart and pulmonary artery thrombosis, pulmonary infarction, exotoxemia or endotoxemia, and anoxia. Sudden death may result, and this syndrome represents one of the more common causes of acute death in adult dairy cattle. This sudden death may represent a hypersensitivity reaction following a previous clinically inapparent thromboembolic episode; however, sudden rupture of a large hilar abscess into the caudal vena cava or embolic movement of an existing large septic thrombus may cause enough direct pulmonary infarction to cause death without the need for a previous sensitizing episode. F. necrophorum toxins have also been shown to aggregate cattle platelets, and this may play some role in the development of thrombosis.

Acute Respiratory Distress Syndrome

This syndrome appears in one animal within a group or herd. The affected cow has peracute onset of respiratory distress, fever, labored breathing, and increased respiratory and heart rates. Pulmonary edema, subcutaneous emphysema, and open mouth breathing also may be observed. Auscultation of the thorax generally reveals reduced airway sounds resulting from pulmonary edema, pulmonary infarction, and bullous emphysema brought on by exertional respiratory efforts. Rales may be ausculted in some instances, but in general, the lungs are quieter than expected given the obviously labored respirations. The key to diagnosis is the fact that only one animal is affected with severe lower airway disease, and to the owner's knowledge, this cow has had no unique stress or previous problems.

Hemoptysis, Epistaxis, Chronic Pneumonia, Anemia Syndrome

This classic syndrome is associated with caudal vena caval thrombosis in cattle and results from singular or multiple episodes of thromboembolism from the hilar liver abscess and subsequent septic thrombosis residing in the caudal vena cava. Septic thromboemboli create pulmonary abscesses at their endpoint in pulmonary arteries, and aneurysms develop proximal to each of these abscesses within the affected pulmonary arteries. Because the pulmonary arterial branches in cattle course close to bronchi, eventual enlargement of the abscesses predisposes to their rupture into airways. Sudden discharge of purulent material into the airway creates septic bronchopneumonia followed immediately by minor or major hemorrhage from the arterial aneurysm now communicating directly into the airway. This hemorrhage may be sufficient to result in hemoptysis and subsequent epistaxis. Affected cattle are unthrifty and frequently have been treated for recurrent bronchopneumonia characterized by fever (103.0 to 106.0° F/39.44 to 41.11° C), increased respiratory rate, as well as rales, crackles, or wheezes within localized areas of the lung. Some affected cattle develop endocarditis caused by the septic thrombus in the caudal vena cava remaining as a source of chronic bacteremia through the right heart and pulmonary arteries.

Epistaxis or hemoptysis may be slight and intermittent or may be profound, acute, and result in sudden death (Figure 4-42 ). Epistaxis associated with coughing and chronic bronchopneumonia in dairy cattle indicates an extremely guarded prognosis because of the irreversible nature of the pathology in caudal vena caval thrombosis. Other signs such as ascites, generalized visceral edema, and diarrhea are possible if the thrombosis occludes the caudal vena cava and results in portal hypertension. Right heart failure and a chronic passive congestion of the liver may also develop in some chronic cases.

Figure 4-42.

Massive pulmonary hemorrhage and acute death in a 3-year-old Holstein cow with hepatic-pulmonary abscesses. The cow was calving when the hemorrhage occurred.

Diagnosis of Sudden Death Syndrome

The diagnosis of caudal vena caval thrombosis requires careful necropsy when sudden death results. Generally affected animals have appeared completely healthy before death. Only one animal is affected in the herd, and the suddenness of death precludes physical examination or ancillary laboratory data. Necropsy will reveal a hilar liver abscess with rupture into the caudal vena cava (Figure 4-43 ). The lungs may show bullous emphysema, pulmonary edema, pulmonary infarction, and pulmonary arterial thrombosis.

Figure 4-43.

Necropsy specimen from a cow that died from rupture of a hilar liver abscess into the post cava. The site of rupture into the post cava is apparent as a rough-edged crater highlighted against the intima of the vein. The purulent remnants of the abscess appear to the left of the crater.

(Photo courtesy Dr. John King.)

Diagnosis of Acute Respiratory Distress Syndrome

Sudden onset of respiratory distress in a single cow within a herd raises an index of suspicion of acute caudal vena caval thrombosis. History and physical examination should exclude other causes of severe lower airway disease and acute respiratory distress. An elevated serum globulin (.5.0 g/dl) further raises the index of suspicion but cannot confirm the diagnosis. Chest radiographs, although not widely available in practice, are very helpful to the diagnosis because they usually demonstrate focal or multifocal pulmonary infarction and densities resulting from septic emboli, diffuse pulmonary edema, and bullous emphysema. In field situations, the affected cow is treated symptomatically and gradually may improve over 5 to 10 days. Subsequently, however, these animals usually develop hemoptysis, epistaxis, anemia, and chronic pneumonia typical of the classic signs associated with caudal vena caval thrombosis. The average lag phase between improvement from the acute syndrome and the onset of epistaxis is 3 to 6 weeks.

Diagnosis of Classical Caudal Vena Caval Thrombosis with Epistaxis, Hemoptysis, Anemia, and Chronic Bronchopneumonia

This form remains the most common clinical syndrome of caudal vena caval thrombosis. Elevated heart rate, increased respiratory rate, auscultable rales, persistent or recurrent fever, anemia, and hemoptysis are frequent signs. The owner may have observed epistaxis on several occasions or only once (Figure 4-44, Figure 4-45 ). Some affected cattle bleed out acutely with few premonitory signs. A heart murmur caused by anemia or endocarditis may be present. Generalized edema of the hind parts, ventrum, udder, and ascites may be present in some animals. If edema is generalized, diarrhea caused by gastrointestinal edema is observed. Frequently serum globulin is elevated (.5.0 g/dl), and a neutrophilic leukocytosis may be present in the hemogram. Thoracic radiographs or ultrasonography are helpful in identifying distinct pulmonary abscesses, and occasionally the causative thrombus may be lodged in the caudal vena cava and identified on thoracic radiographs. Transabdominal ultrasound in the right eighth through eleventh intercostal spaces can also be useful to identify liver abscesses and allows visualization of the hilus and abdominal caudal vena cava close to the hilus. Endoscopy will help confirm the origin of hemorrhage in the lower airway and will allow collection of tracheal wash material for cytology and culture.

Figure 4-44.

Slight epistaxis that was intermittently observed in a cow with caudal vena caval thrombosis (CVCT).

Figure 4-45.

Severe epistasis and hemoptysis in a Holstein with caudal vena caval thrombosis (CVCT) that survived for 3 months after initial diagnosis of CVCT.

Treatment

Therapy for caudal vena caval thrombosis causing acute respiratory distress is symptomatic and includes:

• Broad-spectrum antibiotics such as oxytetracycline, cephalosporins, or penicillin to control septic thromboemboli. F. necrophorum and A. pyogenes are the primary organisms found in these abscesses.

• Furosemide (250 to 500 mg IM, twice daily per adult animal) if pulmonary edema is present.

• Atropine (2.2 mg/45 kg body weight SQ, twice daily) as a supportive bronchodilator and to dry bronchial secretions.

• Aspirin or another NSAID in standard dosages as an antiinflammatory drug. Initially flunixin meglumine may be used (250 to 500 mg/450 kg body weight) to counteract possible endotoxemia.

If improvement is observed, the animal should be maintained on long-term penicillin in the hope that the septic thromboemboli may be sterilized. Rifampin may be added to improve antibiotic penetration, but this represents extra-label drug use and is expensive. Prognosis is poor because a large thrombus tends to persist in the caudal vena cava, and constant or intermittent embolic showers are likely to continue. Few cattle have survived long term.

Treatment of caudal vena caval thrombosis with classic signs of pneumonia, epistaxis, hemoptysis, and anemia seldom is worthwhile because of the extensive pathology that exists. Valuable cattle may be treated with long-term penicillin (22,000 U/kg IM, twice daily) and aspirin (240 to 480 grains/450 kg body weight orally, twice daily). Penicillin is the antibiotic of choice, given the causative organisms, and aspirin may be safe for long-term use in an effort to discourage further platelet aggregation and thrombosis. Once epistaxis has been observed and confirmed to originate from the lower airway, prognosis is extremely guarded. Attempted therapy may be worthwhile in extremely valuable cattle in the hope that only a few pulmonary arterial abscesses have developed, giving the cow a chance to survive. However, it is rare for a cow with well-defined signs of caudal vena caval thrombosis to survive.

Control.

Prevention or control of caudal vena caval thrombosis in cattle involves nutritional changes. Highly acidic diets that predispose to clinical or subclinical rumenitis and abomasal ulceration have to be tempered by buffers, prefeeding hay before high energy grains such as high moisture corn, or by feeding total mixed rations. Dairy rations should not be fed to yearling or bred heifers. High production herds are most at risk for rumenitis and abomasal ulceration secondary to intensive feeding of high-energy acid diets. Most cattle with liver abscesses are asymptomatic, and those having hilar abscesses probably suffered initiation of pathophysiology months to years before the onset of clinical signs. When more than an occasional case of caudal vena caval thrombosis appears in a herd, immediate evaluation of the herd's nutritional program is in order. One cow in a herd with caudal vena caval thrombosis is unfortunate but a common clinical problem. More than one cow in the same herd with caudal vena caval thrombosis, however, signals a potential serious economic loss and requires changes in the feeding program. Evaluation of the herd for subacute rumen acidosis is indicated under these circumstances and is described in Chapter 5.

Inhalation Pneumonia

Etiology and Signs.

Inhalation pneumonia occurs when feed materials, milk, or medications enter the trachea and the animal fails to clear the airways of the material, and septic bronchopneumonia ensues. In calves, white muscle disease and iatrogenic inhalation pneumonia are the two most common causes. White muscle disease caused by selenium/vitamin E deficiency may affect the tongue, muscles of mastication, or muscles involved in swallowing and predispose to inhalation of milk or milk replacer as the affected calf tries to drink. Iatrogenic inhalation pneumonia in calves follows inadvertent intubation of the trachea with stomach tubes or esophageal feeders or, more commonly, from use of abnormally large holes on the end of nipple bottles. Nipple bottles used to feed calves should only drip milk when the bottle is turned upside down. Prematurity or dysmaturity may also predispose to inhalation pneumonia as a result of incompletely developed laryngeal protective reflexes. Inhalation pneumonia also may follow pharyngeal trauma by stomach tubes, esophageal feeders, or balling guns, resulting in dysphagia or neurogenic swallowing deficits. Crude or neophytic use of stomach tubes, feeders, and balling guns by laypeople causes most iatrogenic inhalation pneumonia.

In adult cattle, milk fever (parturient hypocalcemia) is the most common cause of inhalation pneumonia. The severely hypocalcemic cow not only is recumbent but also may lie in lateral recumbency and thus become bloated. Regurgitation of rumen ingesta may lead to inhalation because the cow's semicomatose state prevents her clearing the regurgitated ingesta from her pharynx and airway. Pharyngeal trauma caused by stomach tubes, magnet retrievers, and balling guns may injure vagal nerve branches traversing the pharynx. This neurogenic injury may lead to dysphagia and to defective eructationand regurgitation, and may predispose to inhalation pneumonia. Inadvertent intubation of the trachea during attempts at stomach tubing by an unskilled person creates a significant risk of inhalation in adult cattle as in calves. Choke, although rare in dairy cattle today, certainly represents a significant predisposing cause of inhalation pneumonia as well. Cattle that have choked on vegetables or feedstuff should be assessed carefully for early signs of inhalation pneumonia.

Neurologic disease constitutes another potential cause of inhalation pneumonia in cattle. Listeriosis and other diseases that affect the cranial nerves involved in deglutition, mastication, and swallowing food predispose to inhalation pneumonia, although our experience is that aspiration pneumonia associated with Listeriosis has rarely caused a clinical problem. Botulism represents an intoxication that may lead to inhalation pneumonia secondary to dysphagia.

Signs of inhalation vary with the relative volume and content of the inhaled material. For example, inadvertent administration of a large volume of fluid into the trachea results in immediate signs of dyspnea, respiratory distress, cyanosis, and repeated coughing. The affected calf or cow will expel some of the material from the nose or mouth as a frothy liquid before dying within minutes to hours. Smaller volumes of milk (calves with white muscle disease) or feed inhaled into the lower airway cause a septic or gangrenous pneumonia as the microorganisms contained in the causative material proliferate. In this instance, signs are progressive in nature and consist of a fever poorly responsive to antibiotics, dyspnea and rapid respirations, rales or bronchial tones in the anterior ventral lung fields (unless the animal was in lateral recumbency at the time of inhalation, in which case the major portion of the pathology may occur in one lung), and failure of response to antibiotic therapy. Rather than groups of animals being affected, as is typical with contagious pneumonia, only individual animals tend to be affected with inhalation pneumonia. However, when groups of calves are affected with white muscle disease, several calves may be affected with inhalation pneumonia at the same time.

Individual cattle with inhalation of rumen ingesta secondary to milk fever or other problems develop a progressive gangrenous pneumonia with fever, dyspnea, and toxemia. Rapid consolidation of affected lung tissue occurs, and bronchial tones and rales may be ausculted—usually in the cranioventral lung fields. Broad-spectrum antibiotic therapy is effective only if the amount of ingesta inhaled was relatively small. In most instances, the course is one of progressive deterioration over several days, ending in death. Sometimes inhalation of saliva or small amounts of water or feed as a result of dysphagia is treatable with broad-spectrum antibiotic therapy. We have had the best results with cattle that develop some degree of inhalation pneumonia secondary to dysphagia induced by pharyngeal trauma. Because the amount of inhaled material usually is unknown, treatment is indicated unless the animal shows profound dyspnea and cyanosis.

Treatment.

Therapy for inhalation pneumonia incorporates broad-spectrum antibiotics directed against the microbes normally present in the material inhaled. Nonsteroidal antiinflammatory drugs also would be indicated for supportive therapy. Antibiotic therapy should be continued at least 2 weeks if symptomatic improvement occurs. Persistent fever, depression, dyspnea, and toxemia are negative signs and generally signal a fatal outcome.

Prevention.

Inhalation of certain necrotizing or nonabsorbable chemicals (e.g., mineral oil) is uniformly fatal, and treatment is not indicated. Prevention of inhalation pneumonia can be practiced only when the problem is anticipated and is largely a matter of common sense. Therefore withdrawing feed from animals suffering from choke, dysphagia, and other known problems may be helpful. Prompt treatment of milk fever or other diseases that may prevent a cow from maintaining sternal recumbency is important in preventing aspiration pneumonia. Management practices such as routine or therapeutic drenching of postparturient cattle should only be performed by laypeople who have been properly trained and provided with appropriate equipment. The feeding of milk to weak, premature, or dysmature calves should also be predicated on common sense and an awareness that normal protective airway reflexes may be overcome by impatient feeding practices (e.g., enlarging holes in nipples) or by allowing these calves to nurse with the head and neck hyperextended or dorsiflexed, as appears to be their instinctive habit. Feeding from buckets or a bottle with the head and neck in a neutral position parallel to the ground can lessen the risk of inhalation.

Thermal and Chemical Damage to the Lower Airway

Etiology and Signs.

Barn fires and occasionally grass fires in pastures are responsible for thermal and smoke injury to the respiratory tract in cattle. Chemical damage may be mild, as a result of common gases such as ammonia, or severe, as in accidental exposure to anhydrous ammonia.

Thermal damage resulting from excessive heat and smoke inhalation has been well described for comparative species. The pathophysiology involves heat-induced edema and necrosis of the mucosal lining, pulmonary edema and congestion, destruction of the mucociliary apparatus, hyaline membrane formation, and filling of the small airways with proteinaceous fluid, sloughing tissue in the form of diphtheritic membranes, hyaline membranes, and inflammatory cell debris (Figure 4-46 ). Pathology tends to be progressive with increasing dyspnea as small airway occlusion develops hours to days following the original thermal and smoke insult. Therefore it is difficult to estimate the severity of the lesions immediately following the fire. Dyspnea characterized by an increased respiratory rate may be the only sign. Cattle with obvious facial burns, muzzle burns, or diphtheritic crusts in the nasal cavity should be suspected of having suffered significant smoke inhalation. Pulmonary edema is an early sign of severe thermal damage and suggests that subsequent pathology with hyaline membrane formation will follow. Other signs in severely affected animals include cough, tachypnea, wheezing, cyanosis, and stridor. In severe cases, respiratory distress will develop 1 to 24 hours following initial injury, and bacterial bronchopneumonia may develop within 1 to 4 days in cattle that survive the initial thermal injury. Carbon monoxide poisoning is a common cause of death for animals at the time of the fire or shortly thereafter.

Figure 4-46.

Postmortem specimen of trachea from cow that had died from smoke inhalation during a barn fire. Note the severe tracheal mucosal erosions and diphtheritic damage.

Chemical damage resulting from high environmental concentrations of ammonia largely reflects poor management or inadequate ventilation within an enclosure. Excessive buildup of manure and urine without adequate ventilation will allow ammonia fumes to damage the physical defense mechanisms of the lower airway. Secondary bacterial pneumonias are the most common sequelae to this problem, and this topic has been discussed under bacterial pneumonias.

We have also observed a progressive increase in respiratory rate in some hospitalized cattle that have their bedding changed frequently and are kept in deeply bedded stalls for 2 weeks or more. This has occurred in all seasons of the year and does not seem to be simply temperature related. There is no coughing, and tracheal washes have not revealed a cause for the tachypnea. If the cows are put outside, the respiratory rates return to normal in 1 to 3 days.

Anhydrous ammonia is an extremely dangerous chemical that is widely used in agriculture today. It is used as a source of nonprotein nitrogen for forages and fertilization of various crops. The chemical seeks out water when it comes in contact with vegetable matter or tissue. Accidental exposure to anhydrous ammonia can be lethal to animals or humans who come in contact with the material. Because of the intense water affinity of the chemical, anhydrous ammonia seeks moist tissues such as the eye and respiratory tract. As a result of this contact, moist tissue rapidly desiccates followed by necrosis as the chemical dehydrates the tissue. Corneal edema, epithelial necrosis, and corneal stromal burns immediately develop in the eyes. The mucosa of the respiratory tract is burned, and following dehydration, sloughs and diphtheritic membranes fill the airways, leading to hypoxia or suffocation. Pulmonary edema develops rapidly, and death may occur peracutely or be delayed hours or days. Secondary bacterial pneumonias are possible if the animal survives the initial chemical injury.

Insecticides that are fogged into barns for fly control occasionally may induce chemical damage or sensitivity to the lower airway. The exact mechanism of action is not fully understood, but tachypnea, coughing, and mild dyspnea may be observed.

Diagnosis.

The diagnosis of thermal or chemical injury is made by the history and physical examination findings. Ancillary information seldom is necessary. Endoscopy and thoracic radiographs may provide prognostic information for valuable animals but seldom are used in practice.

Treatment.

Major treatment considerations for acute thermal injury of the airway include adequate oxygenation and establishment of an adequate airway. If laryngeal edema is so severe as to result in respiratory distress, a tracheostomy may be necessary. A tracheostomy should not be performed unless severe upper respiratory distress is present because the procedure further predisposes to secondary bacterial bronchopneumonia in burn patients. Oxygen administration is indicated if acute dyspnea suggests possible carbon monoxide poisoning.

Judicious dosages of furosemide (25 to 50 mg/45 kg body weight) may be necessary if pulmonary edema is present. Use of corticosteroids for acute pulmonary distress caused by thermal injury is controversial. Steroids have been proposed as initial therapy to “short cycle” parts of the vicious cycle of inflammation because they decrease mediators of inflammation, stabilize inflamed vasculature, and decrease edema of the upper and lower airway. If steroids are used, they should be given immediately rather than waiting for the subsequent pathology and respiratory distress that will follow thermal injury in the following 1 to 24 hours. Dosages vary but may be as high as 0.1 to 1.0 mg/lb dexamethasone as a one-time treatment. Abortifacient properties of the drug need to be considered before it is used on pregnant animals, and a significant risk associated with the use of steroids in the form of possible secondary bronchopneumonia also must be considered before dexamethasone's use. Dr. Rebhun commented that he had treated some barn fire victims with dexamethasone but that the results were hard to interpret. In one valuable yearling bull, a high dose of corticosteroids was used initially without respiratory consequences, but the bull developed a left displacement of the abomasum within 24 hours of treatment. The cause/effect relationship of the exogenous source of corticosteroids on the displacement never was confirmed but certainly was suspicious. NSAIDs may be used at regular dosages without the additional risks presented by corticosteroids. However, NSAIDs probably do not block the ongoing pathophysiology of lower airway disease corticosteroids. Prophylactic systemic antibiotics are reported not to influence the subsequent development of bacterial bronchopneumonia. Some literature regarding usage in humans discourages the use of prophylactic antibiotics for fear of allowing resistant strains of bacteria to emerge in the lower airway. In cattle, especially valuable ones, broad-spectrum antibiotics usually are used on a prophylactic basis, although no controlled data support their use. Tetracyclines may help decrease inflammation via their inhibitory effect on metalloproteinases. Disadvantages of tetracyclines would be that they are bacteriostatic and many commensal organisms may be resistant to the drug. If used, practitioners should be aware of their potential to cause nephrotoxicity, particularly in hemodynamically challenged patients. If tracheostomies or tracheal washes are performed, extreme care should be taken to minimize iatrogenic introduction of pathogens into the respiratory tract. As in thermal skin injury, Pseudomonas sp. and other opportunists are the major bacteria to invade damaged tissue.

Nebulization with antibiotics, bronchodilators, corticosteroids, acetylcysteine, and/or surfactant has also been used in affected cattle. Acetylcysteine has anticollagenase and antioxidant effects via its glutathione-promoting properties.

In chemical injury resulting from anhydrous ammonia, exposed animals and the entire environment should be sprayed with water to destroy residual fumes. Emergency personnel and fire companies should be summoned immediately so that gas masks and protective clothing are available for people spraying water in the area and repairing the leak. All humans in the area should move upwind and leave the area until the leak and fumes have been controlled. Cattle exposed but still alive should not be stressed and should be allowed access to as much fresh air as possible. No specific treatment is possible. Symptomatic treatment may include furosemide, prophylactic antibiotics, or oxygen therapy. Animals with chemically injured eyes should have topical antibiotic ointments and atropine ointments applied to the eyes several times daily.

Mycotic Pneumonia

Etiology and Signs.

Mycotic or fungal pneumonia usually results from embolic dissemination of fungal organisms from other infected organs such as the rumen, abomasum, or mammary gland. Immunosuppression and immunosuppressive drugs (corticosteroids) predispose to fungal infection, as does intensive antibiotic therapy, which may deplete the bacterial flora and promote fungal growth. Lactic acid indigestion (toxic rumenitis) remains one of the leading causes of mycotic pneumonia. Pathophysiology evolves from chemical rumenitis to bacterial rumenitis and subsequent mycotic rumenitis—especially if the affected cow has been treated with antibiotics. Embolic infection of the lungs ensues as a result of seeding of the portal circulation and liver from the primary ruminal infection. Similarly fungal pneumonia has been observed as a sequela to severe septic mastitis in dairy cattle. Intensive antibiotic therapy and overzealous use of corticosteroids predisposed these animals to mycotic infections that became septicemic from the udder and then involved the lungs. Although Aspergillus spp. are the most common fungal organisms identified, theoretically any yeast or fungus could be causative.

Signs are nonspecific but consist of persistent fever unresponsive to antibiotics (104.0 to 108.0° F/40.0 to 42.2° C), increased respiratory rate, and variable abnormal lung sounds in one or both lungs. Rales and increased or decreased bronchovesicular sounds may be heard in individual cases. A primary site of severe infection such as the mammary gland, forestomach, or uterus usually is apparent, and the respiratory signs may be disregarded or difficult to identify. Multiple organ failure and neurologic signs frequently coexist or develop because of the fungal septicemia. Occasional cases of disseminated fungal disease with fungal pneumonia can be seen in septicemic calves or calves with severe enteritis that have received extensive antibiotic and/or corticosteroid treatment.

Diagnosis.

Diagnosis is difficult and at best may only be suspected before the death of the individual. Tracheal washings may identify the organisms during cytology or culture procedures but also may be disregarded as evidence of upper airway contamination of the tracheal wash sample.

Gross and histologic pathology confirms the diagnosis. Discolored multifocal areas of pneumonia are present grossly (Figure 4-47 ), and hyphae are identified by histopathology.

Figure 4-47.

Necropsy specimen showing mycotic hepatitis (left) and pneumonia (right) secondary to lactic acid indigestion. Mycotic lesions appear similar to “targets” with red centers and pale peripheries.

Treatment.

No successful treatment has been described for mycotic pneumonia in cattle, and the primary infection coupled with mycotic pneumonia or mycotic septicemia usually is fatal.

Prevention.

Although intensive antibiotic therapy is necessary for certain infections in dairy cattle, practitioners should be aware that chronic localized infections in the udder, uterus, or gastrointestinal tract that are treated with long-term antibiotics may predispose to yeast or fungal overgrowth and potential embolic spread. Repeated IV therapy by practitioners or laypeople using drugs from multidose vials also may lead to direct mycotic septicemia, such as occurs occasionally in human abusers of IV drugs.

High or repeated dosages of exogenous corticosteroids are to be condemned in dairy cattle and may represent the most dangerous drugs currently predisposing to fungal infections. There are few, if any, dise/ases in dairy cattle that require high doses of corticosteroids for effective therapy. Corticosteroid use as initial therapy for severe infectious/inflammatory diseases should not be repeated. The low dosages of corticosteroids (10 to 20 mg of dexamethasone) utilized by many veterinarians as daily treatment for ketosis generally are safe if limited to 3 to 7 days and not used in cattle with severe infections such as septic mastitis, septic metritis, pneumonia, or toxic rumenitis.

Space-Occupying Masses in the Thorax, Lung Parenchyma, or Lower Airway

Etiology and Signs.

Space-occupying thoracic masses involving the lung parenchyma, visceral or parietal pleura, or other structures in the thorax cause subtle or marked progressive dyspnea and may cause signs similar to congestive heart failure. Other clinical signs vary with specific lesions; for example, fever unresponsive to antibiotics would be present in cattle affected with thoracic abscesses or pleuritis, whereas fever may not be present in thoracic or mediastinal neoplasia.

Inflammatory lesions include thoracic abscesses and pleuritis (Figure 4-48 ). Thoracic abscesses usually are unilateral and result in detectable absence of lung sounds in the affected ventral hemithorax. Ipsilateral heart sounds may be absent or muffled, whereas contralateral heart sounds are louder than normal and accentuated by the displaced heart's proximity to the contralateral thoracic wall. Fever unresponsive to antibiotics, progressive dyspnea, venous distention and pulsation of the jugular and mammary veins, ventral edema, and a reluctance to move are other signs observed in cattle affected with thoracic abscesses. Etiology of thoracic abscesses sometimes is unknown, but penetration of the thorax by reticular foreign bodies and localized enlarging pulmonary abscesses from previous pneumonia have been confirmed at autopsy in several fatal cases. Previous history of pneumonia or hardware disease may suggest etiology in certain cases, but a specific etiology seldom is determined in surviving cattle. A. pyogenes is the organism isolated from most thoracic abscesses.

Figure 4-48.

Sonogram of the thorax of a cow with septic pleuritis. The white echogenic spots in the black fluid suggest anaerobic infection and gas production.

Pleuritis is rare in dairy cattle except when it accompanies severe consolidating bronchopneumonia of bacterial origin. As in other species, fever, progressive dyspnea, absence of lung sounds in the ventral thorax (unilateral or bilateral), and thoracic pain are typical. Although a fibrinous pleuritis is most common in cattle, when large amounts of pleural fluid are present, venous distention and apparent pulsations may be present in the jugular and mammary veins. Rare cases of pleuritis resulting from rupture of a parenchymal pulmonary abscess into the pleural space, penetrating thoracic wounds or foreign bodies associated with traumatic reticuloperitonitis, erosion of the diaphragm by an abscess associated with hardware or perforating abomasal ulcer, and rupture of the esophagus secondary to chronic choke or trauma also have been observed.

Pleural effusion may also occur as part of a nonseptic or septic pericarditis syndrome. We have had some cases of pericarditis/pleuritis in which the cause could not be determined. In one cow with fibrinous pericarditis (based on ultrasound appearance and a mixed cell type [neutrophils, lymphocytes, plasma cells] pericardial and pleural fluid cytology), there was a complete cure following pericardial injection of corticosteroids in addition to systemic antibiotics. Another cow had pleural effusion as a result of right heart failure caused by pulmonary hypertension. Although severe pleural effusion is not common in cattle with right heart failure, it may occur.

Seromas and hematomas may develop following trauma to the thoracic wall. These masses occasionally extend into the thorax itself. In these instances, apparent rupture or leakage of the seroma through the parietal pleura occurs. These seromas and hematomas may be associated with rib fractures or traumatic injuries at the costochondral junctions (Figure 4-49 ). Signs include progressive dyspnea, increased respiratory rate, venous distention and pulsation, normal temperature, absence of lung sounds ventrally in the affected hemithorax, absence or muffling of heart sounds in the affected hemithorax, and loud pounding heart sounds in the contralateral hemithorax caused by cardiac displacement.

Figure 4-49.

Mature Holstein with thoracic seroma or transudate secondary to traumatic injury at the costochondral region of the left thorax. Forty liters of transudative fluid have just been removed from the left hemithorax via thoracocentesis. The cow made a complete recovery.

Diaphragmatic hernias may cause dyspnea and absence of cardiopulmonary sounds in the affected thoracic area. Bloat is commonly observed in cattle having diaphragmatic hernia because the reticulum is usually the herniated organ.

Neoplastic masses may occur in the pulmonary parenchyma, pleura, lymph nodes, or thymus. Cardiac neoplasms will be discussed with other cardiac diseases. Thymic lymphosarcoma may be the most obvious neoplasm within this group. Thymic lymphosarcoma is recognized in cattle between 4 and 24 months of age and causes progressive dyspnea, bloat, or both. Swelling is obvious in the distal ventral cervical area and extends into the thoracic inlet. Some thymic lymphosarcoma masses are soft, fluid-like swellings on palpation (Figure 4-50 ), whereas others are firmer. Compression of the trachea and esophagus results in dyspnea and interference with eructation that varies with the size of the mass. Compression of the trachea, causing respiratory distress, may also occur in adult cattle with enzootic lymphosarcoma. Adult lymphosarcoma may cause tumor formation in the thorax as a result of lymph node, pleural, cardiac, and occasionally pulmonary involvement. Signs vary depending on the tumor numbers, size, and other organs affected. Occasionally lymphosarcoma patients will have fever caused by tumor necrosis, and this may be a misleading sign. Severe pleural effusion with many neoplastic lymphocytes may occur. The pleural effusion caused by lymphoma is often grossly discolored, having a bloody appearance.

Figure 4-50.

Thymic lymphosarcoma in a 6-month-old calf presented because of worsening dyspnea and intermittent bloat.

Primary pulmonary tumors of epithelial origin described as papillary adenomas have been observed in young cattle at slaughter. These were reported as benign, multicentric tumors because metastases were not observed. Signs were not reported because these were incidental findings during slaughter inspection. Several case reports have documented malignant neoplasms such as bronchiolar adenocarcinoma in older cows showing signs of progressive dyspnea. Dr. Rebhun documented one older cow and one bull with massive pulmonary adenocarcinomas that resulted in progressive dyspnea, weight loss, and reduced lung sounds. Mesotheliomas originate from the pleura and tend to be multiple. They may enlarge collectively to create signs of progressive dyspnea, decreased lung sounds caused by massive pleural effusion, weight loss, and eventually lead to death.

Tuberculosis, although rare in dairy cattle because of regulatory control efforts, should be remembered as a potential cause of progressive dyspnea, coughing, weight loss, and signs of pneumonia. Enlarged thoracic lymph nodes associated with the infection may result in esophageal compression and bloat or obvious respiratory distress from tracheal compression.

Diagnosis.

Diagnosis of space-occupying lesions in the thorax requires careful auscultation to detect differences in lung and heart sounds in each hemithorax.

Abscesses, seromas, or masses occupying one hemithorax will elevate the ipsilateral lung and push the heart toward the opposite hemithorax. Therefore in the affected hemithorax, lung sounds will be absent ventrally, and heart sounds will be muffled or absent. Auscultation of the opposite hemithorax will reveal uniformly increased bronchovesicular sounds and a loud “pounding” heart beat caused by the proximity of the heart to the thoracic wall on this side. Thoracic percussion also may be helpful in detecting the area of involvement. Because cattle affected with these problems often have increased central venous pressure as a result of impaired venous return, they may be confused with heart failure patients. An incomplete physical examination may lead to an erroneous diagnosis such as endocarditis or pericarditis if the examiner only auscults one hemithorax.

Once a lesion has been identified, further diagnostics are indicated. Thoracic radiographs and ultrasonography are indicated if a complete diagnostic workup is to be performed. Blood work may be helpful in the case of thoracic abscesses in that serum globulin usually is elevated ($5.0 g/dl) and neutrophilia may be present. The most direct diagnostic aid remains thoracocentesis with a suitable needle. Although a 5.0-cm needle will enter the pleural space of cattle, it is seldom long enough to invade the capsule of an encapsulated abscess or seroma. Therefore an 8.75-cm, 18-gauge needle is preferred for initial thoracocentesis through the lower fifth or sixth intercostal space on the affected hemithorax. If fluid or pus is obtained, the material is submitted for cytology and culture. If no fluid is obtained, biopsy of a mass lesion may be indicated.

Similarly, if thymic lymphosarcoma is suspected, aspirates for cytology or biopsies (True-Cut biopsy needle, Baxter Healthcare Corp., Valencia, CA) are indicated to allow definitive diagnosis. As previously mentioned, some thymic lymphosarcoma patients have a misleading fluctuant mass that appears fluid filled. Aspirate attempts yield no fluid, however, and biopsy will confirm the diagnosis. Juvenile cattle affected with thymic lymphosarcoma usually are negative for bovine leukemia virus when their serum is tested by agar gel immunodiffusion or radioimmunoassay.

Pleuritis or pleural effusion may be unilateral or bilateral. Careful auscultation and percussion should lead to suspicion of free pleural fluid because lung sounds usually are absent in the ventral aspect of the affected hemithorax. Dyspnea may be marked in cattle with large accumulations of pleural fluid. Pleural fluid does not displace the heart, as occurs in those with unilateral thoracic masses or abscesses. Therefore heart sounds are audible bilaterally and may appear to radiate caudodorsally by sound conduction through the pleural fluid. Pleural fluid must be differentiated from anterior ventral pulmonary consolidation. Bronchial tones usually are heard in consolidated regions of lungs, whereas absence of sounds is more typical of pleural fluid. Thoracocentesis is indicated to confirm pleural fluid accumulation; any sampled fluid should be analyzed using cytology and culture to differentiate infections from neoplastic or other causes. Ultrasonography and thoracic radiographs, if available, would help in the management of a valuable cow affected with this problem. Ultrasonography is an extremely valuable tool for evaluating pleural disease in cattle. As more portable equipment becomes available, an ultrasound machine may be used with increased frequency as part of the evaluation for sick cows. Ultrasonography can quickly determine whether there is pleural effusion, abscessation, consolidation, or pleural surface masses. It can also be used as an aid for collection of samples via needle or biopsy. If available, thoracic radiographs are helpful to confirm or deny diaphragmatic hernia.

Thoracic tumors involving the lung parenchyma, pleura, or thoracic lymph nodes are difficult to diagnose unless thoracic radiographs and ultrasonography are available. Signs vary, and dyspnea and progressive weight loss occur despite symptomatic treatment. Thoracic lymphosarcoma may be suspected based on physical signs involving other sites or lymph nodes becoming obviously enlarged. A bovine leukemia virus agar gel immunodiffusion or enzyme-linked immunoabsorbent assay (ELISA) will be positive in most cows with clinical lymphosarcoma. This does not confirm a diagnosis but does add to the index of suspicion if lymphosarcoma is suspected. Bloat and tracheal compression may occur if mediastinal masses or lymphadenopathy become severe. Thoracocentesis may offer the best means of diagnosis in these unusual tumors because exfoliative cytology may help identify the tumor and allow proper prognosis.

Treatment.

Therapy of unilateral thoracic abscesses and seromas involves drainage of the lesions through the thoracic wall. Because A. pyogenes is the usual causative organism of thoracic abscesses, a thick capsule often is present. Once the location of the abscess is confirmed by thoracocentesis, a large-bore (20 to 28 French) chest trochar is placed into the abscess cavity (Figure 4-51 ). The chest trochar is sutured in place, and the affected cow is started on penicillin (22,000 IU/kg, twice daily). Where ultrasonography is available, it may be used to confirm pleural adhesions between parietal pleura and the abscess, allowing subsequent surgical thoracotomy coupled with rib resection to afford even more efficient drainage and exploration of the cause of the abscess. Complete drainage is the key to successful treatment. Lavage of saline or antibiotic and saline solutions through the indwelling trochar also has been used in some cases. Irritating solutions such as iodine products are contraindicated, however.

Figure 4-51.

Yearling heifer with an encapsulated A. pyogenes abscess in the right hemithorax. A chest trochar has been placed to facilitate drainage.

Cattle with seromas that are drained in this manner subsequently have a good prognosis. Abscesses require long-term antibiotic therapy and complete evacuation/drainage. Therefore the affected cow must be of substantial value to justify the medical expenses and associated loss of milk sales for several weeks. Cattle affected with thoracic abscesses may lose significant body condition during early treatment, but absence of fever, decreased venous distention, increased appetite, weight gain, and a return to normal thoracic sounds on auscultation are all signs of improvement.

Treatment for pleuritis and pleural fluid requires drainage of the fluid and appropriate antibiotic therapy to control associated pneumonia. If pleural fluid is caused by effusion from neoplastic conditions, treatment is rarely indicated. Hardware perforations of the diaphragm may result either in frank pleuritis with pleural fluid accumulation, thoracic abscess, or diaphragmatic hernia. When A. pyogenes predominates, a thick-walled thoracic abscess develops, resulting in chronic disease. If a mixed infection develops and a fluid pleuritis that is not encapsulated results, the affected cow has an acute disease with large amounts of septic pleural fluid free in the pleural space.

Surprisingly few cattle with bacterial bronchopneumonia develop clinically significant pleural fluid accumulation. Nonetheless, pneumonia remains the most common cause of pleural fluid accumulation. Diagnosis of pleural fluid accumulation unilaterally or bilaterally in a cow affected with severe pneumonia dictates drainage of this fluid. Pleural effusion associated with bronchopneumonia will result in fever unresponsive to antibiotics and marked dyspnea. Drainage is provided by daily thoracocentesis or continuous drainage until negligible quantities of pleural fluid are obtained. Appropriate systemic antibiotics should be selected based on culture and susceptibility results and maintained for at least 1 week beyond the last thoracocentesis.

Pneumothorax

Etiology and Signs.

Dyspnea accompanied by increased respiratory rate and effort coupled with absence of bronchovesicular sounds in the dorsal lung fields unilaterally or bilaterally characterizes pneumothorax or bullous emphysema. Dyspnea may range from mild to severe. Some adult cattle appear very painful with pneumothorax. When severe dyspnea is present, open mouth breathing and expiratory groan suggest a bilateral problem. Subcutaneous emphysema may be observed in some affected cattle. Pneumoretroperitoneum may be documented in some cattle with pneumothorax on rectal examination.

Auscultation of the affected hemithorax reveals increased bronchovesicular sounds in the ventral lung fields and absence of lung sounds dorsally. Body temperature is normal unless exertion, high environmental temperatures, or pulmonary inflammation leads to pyrexia. Severe exertion during parturition, exertion during restraint for treatment or surgery, penetrating thoracic wounds, or pharyngeal/laryngeal injury causing a pneumomediastinum that ruptures into the chest may cause pneumothorax. Primary pulmonary pathology associated with chronic bronchopneumonia and emphysematous bullae formation is the most common cause of pneumothorax in cattle. Fever may be present if primary pulmonary inflammation (BRSV, severe bacterial bronchopneumonia, acute bovine pulmonary emphysema [ABPE], among others) contributed to emphysema and resultant pneumothorax. BRSV is the most common infectious agent associated with pneumothorax in cattle. In these inflammatory diseases, auscultation of the ventral lung fields helps to define etiology. Ultrasonography may be helpful in diagnosing the pneumothorax (there is no normal sliding of the dorsal air line) and determining the cause (e.g., lung abscess).

Diagnosis.

Auscultation and percussion suggest the diagnosis. Pneumothorax must be differentiated from bullous emphysema and pulmonary edema. Radiographs or ultrasonography will confirm the diagnosis but may not be available. If history, auscultation, and percussion suggest the diagnosis, thoracic puncture and vacuum evacuation of free air should be attempted through the dorsal ninth or tenth intercostal space. The presence of free air confirms the diagnosis, and airway sounds should return to the dorsal thorax following evacuation of free air. Tracheal wash samples for cytology and culture may be necessary to assess lower airway infection or inflammation.

Treatment.

Therapy requires evacuation of air from the affected hemithorax and treatment of any primary problem such as pneumonia, puncture wounds, and so forth. Cattle with pneumothorax resulting from bacterial pneumonia have a guarded prognosis. Rapid improvement in the dyspnea should be anticipated when pneumothorax is the major problem. The clinician must remember that, except in exogenous puncture of the thorax, pneumothorax originates from damaged pulmonary tissue that has “leaked” air. Simple evacuation of the free air in the thorax will improve the affected animal temporarily but does not guarantee the problem will not recur. Owners need to be instructed to watch the patient carefully for recurrence of dyspnea if the damaged lung continues to leak. Most cattle, however, respond to one or two evacuations of the thorax. A technique for continuous drainage has been described by Dr. Peek in cattle that requires hospitalization and confinement.

Pneumomediastinum

Etiology and Signs.

Pneumomediastinum most often accompanies severe pulmonary parenchymal diseases that result in emphysema and bullae formation. Subsequent leakage of air into the mediastinum occurs. Several of the causes of pneumothorax mentioned previously are also potential causes of pneumomediastinum. Pneumomediastinum is most common in postpartum cows. In some cases there is old pulmonary pathology predisposing to the pneumomediastinum, whereas other cases may simply result from the exertion of calving. Signs may be mild or impossible to separate from those caused by the primary pulmonary pathology. Mild dyspnea, subcutaneous emphysema, and bilateral muffled heart sounds are present in most instances. The muffled heart sounds are the only constant findings and are caused by air insulation of the cardiac sounds. The subcutaneous emphysema is mostly on the dorsum of the cow as the air migrates along the aorta and through the lumbar fascial planes. It can also be felt rectally along the aorta.

Diagnosis.

Subcutaneous emphysema in a postpartum cow is highly suggestive of pneumomediastinum. The presence of bilateral heart sound muffling requires differentiation of this condition from pericarditis. This differentiation is aided by obvious pulmonary pathology coupled with an absence of signs of heart failure in most cases. If physical examination findings cannot definitely differentiate these problems, ultrasonography and radiographs are indicated. Pericardiocentesis is not indicated as an initial procedure because it may subject the patient to unnecessary risks. Thoracic radiographs demonstrate a very clear cardiac and aortic shadow because surrounding air highlights these tissues.

Treatment.

Specific treatment for pneumomediastinum is not required unless the cow has labored breathing and a probable pneumothorax. Therefore therapy should be directed against any primary pulmonary pathology in addition to oxygen, bronchodilator, and antitussive therapy.

Noninfectious Causes of Acute Respiratory Distress in Cattle

Acute respiratory distress in cattle may occur with a variety of noninfectious pathologic changes. Some causes have well-documented pathophysiology, whereas others are more poorly defined and controversial. Terminology varies tremendously among pathologists and clinicians, resulting in much confusion regarding these disorders. Most acute diseases discussed here require gross or microscopic pathology to enable positive diagnosis. The clinician cannot differentiate most of these diseases based on physical examination alone. Textbook descriptions have confused the issue by using different synonyms and eponyms to characterize the problem.

Fortunately, as a collected group of respiratory problems, these diseases are uncommon and much less important than infectious causes of respiratory diseases in dairy cattle. Therefore they will be described individually as best as possible in this section. The reader should realize that the nomenclature of these diseases has changed in the past and is likely to change in the future. Specific therapy is addressed where indicated.

Acute Bovine Pulmonary Edema and Emphysema (Atypical Interstitial Pneumonia, Fog Fever)

Etiology and Signs.

This acute disease of cattle develops within 2 weeks of the time cattle are moved to lush pasture. The exact composition of the pasture does not seem important because grasses, alfalfa, turnips, kale, and rape all have been incriminated. Similarly Perilla mint and moldy sweet potatoes may cause identical syndromes. Although not as well documented, we have seen similar clinical and pathological outbreaks associated with grass silages and ryegrass pastures. Affected cattle develop acute, severe respiratory distress characterized by reluctance to move, open mouth breathing, pulmonary edema, tachypnea, and hyperpnea. Temperatures are normal to slightly elevated unless environmental temperatures are very high.

The transformation of ingested L-tryptophan to indole acetic acid is followed by decarboxylation to 3-methylindole, which is the toxic metabolite of tryptophan. Following absorption of 3-methylindole into the systemic circulation from the rumen, the mixed function oxidase system metabolizes the chemical producing pneumotoxicity in Clara cells and type 1 pneumocytes. Experimental studies have confirmed that 3-methylindole is the toxic metabolite of tryptophan involved in ABPE. Calves seldom are affected, but adult animals over 2 years of age in good body condition appear most at risk.

Fortunately the disease is rare in dairy cattle in the United States because pasture management is more stringent and pasturing is practiced less commonly in confinement herds than in the beef industry. Dairy practitioners should be aware of ABPE but may never see a herd outbreak of this disease.

Signs.

Profound dyspnea, reluctance to move, auscultable evidence of interstitial pneumonia (rhonchi and rales) in the ventral lung field, and quiet lungs dorsally secondary to emphysema and edema characterize the condition. Subcutaneous emphysema may be observed. Morbidity may approach 50%, and mortality quotes range from 25% to 50%.

Diagnosis and Treatment.

Diagnosis is by history, clinical signs, and pathologic study of the lungs from fatal cases. Treatment is seldom helpful, although a variety of drugs have been used in an effort to save badly affected animals. Simple movement or mild restraint may be fatal to these anoxic animals. Therefore treatment is controversial and empiric. Furosemide (0.5 to 1.0 mg/kg) may lessen pulmonary edema. Atropine (0.048 mg/kg or 1/30 grain/100 lb body weight twice daily), antihistamines, NSAIDs, vitamins A and E, and cortisone all have been used with varying anecdotal results. Animals that are rested, removed from the pasture, and not severely affected usually recover in 1 to 2 weeks. Some cattle may fall into the category of “chronic lungers,” this being caused by proliferation of type 2 pneumocytes and pulmonary fibrosis.

Prevention.

Prevention is the best treatment and may be accomplished by feeding susceptible cattle monensin (200 mg/head/day) starting several days before they are introduced to lush pasture and for 7 to 10 days following being placed on that pasture. These drugs inhibit the metabolism of tryptophan to 3-methylindole.

Proliferative Pneumonia

Etiology and Signs.

Proliferative pneumonia is another form of acute respiratory distress observed in dairy cattle. This condition occasionally has been observed to cause high morbidity within a herd but usually affects only one or a few cattle within a group. Acute onset of dyspnea characterized by hyperpnea, tachypnea, an occasional cough, open mouth breathing, and pulmonary edema is observed (Figure 4-52 ).

Figure 4-52.

Holstein with acute severe dyspnea and open mouth breathing because of proliferative pneumonia.

The term proliferative pneumonia derives from the characteristic gross pathology consisting of heavy, firm, wet lung that is diffusely affected. Histologic study of these lungs reveals obliteration of alveolar space by proliferating type 2 pneumocytes and interstitial edema.

The gross pathology and histopathology are characteristic. Unfortunately affected cattle show signs common to many diseases characterized by acute respiratory distress. Clinical signs include low-grade fever (103.0 to 104.0° F/39.44 to 40.00° C), which may range higher (105.0 to 106.0° F/40.56 to 41.11° C) as a result of exertion and environmental factors. Auscultation of the lungs reveals diffuse reduction of airway sounds over the entire thorax. Proliferation of type 2 pneumocytes within the alveoli and interstitial edema contribute to the reduced lower airway sounds. Therefore although the affected cow has severe lower airway dyspnea, the lungs are very quiet on auscultation.

Other diseases, such as ABPE, diffuse pulmonary edema, acute dyspnea associated with embolic showering from a caudal vena caval thrombosis, nitrogen dioxide inhalation, and other causes of acute respiratory distress could lead to similar signs.

Not only is the disease difficult to diagnose accurately but also the exact cause or causes remain unknown. Nitrogen gases have been incriminated, and the disease has similarities to silo filler's disease caused by nitrogen dioxide (NO₂). However, calves and adult cattle that develop proliferative pneumonia frequently have not been exposed to silo gas or other environmental nitrogen gases. Other proposed etiologies include metabolites such as 3-methylindole (the cause of ABPE); Perilla ketone (Perilla frutescens or purple mint), which has been related to acute respiratory distress in cattle, sheep, rats, and mice and causes pneumotoxicity through preformed toxins absorbed from the rumen into the bloodstream; and moldy sweet potato toxicity, which is caused by 4-ipomeanol and related metabolites elaborated by the fungus Fusarium solaria from ipomeamarone and 4-hydroxymyoparone produced by the infected host potato. Once again, the 4-ipomeanol is pneumotoxic to Clara cells and alveolar epithelial cells after metabolic conversion by a cytochrome P450–dependent mixed function oxidase system.

The question remains—are all of these individual toxicities completely separate entities in cattle? It seems that the disease known as proliferative pneumonia may be a composite of these toxicities or may be caused by a yet-to-be-determined toxin common to the environment of dairy cattle.

Another form of pathologically confirmed proliferative pneumonia has been observed in dairy calves following previous infection with and recovery from Pasteurella or Mannheimia pneumonia. The disease occurs in a single animal among a group of calves affected by Pasteurella or Mannheimia pneumonia 2 to 4 weeks previously that had seemingly recovered. This single animal develops an acute severe respiratory distress syndrome with tachypnea, hyperpnea, elevated heart rate, open mouth breathing, fever (103.0 to 106.0° F/39.44 to 41.11° C), and pulmonary edema and may have an expiratory grunt. The animal is reluctant to move and may become cyanotic if stressed. The degree of respiratory effort makes it impossible to determine whether the pyrexia is caused by inflammation or exertion. The lungs are very quiet on auscultation and have reduced sounds throughout all fields. If the previous pneumonia resulted in consolidation of anterior ventral lung lobes, bronchial tones may be heard ventrally and reduced sounds elsewhere. Usually both lungs are involved, but occasionally one lung has much more serious lesions. Unless treated quickly and intensively, the calf dies within 24 hours. Gross necropsy reveals diffusely heavy, wet, firm lungs with evidence of resolved or resolving anterior ventral pneumonia (Figure 4-53 ). Bacterial products resulting in a delayed hypersensitivity reaction are thought to be the cause of this problem. The 2- to 4-week interval between earlier signs of typical Pasteurella/Mannheimia pneumonia and subsequent acute proliferative pneumonia, as well as pathologic lesions, differentiate this syndrome from the “relapse” respiratory distress sometimes observed in BRSV infections. In addition, paired serum samples do not support BRSV as the cause.

Figure 4-53.

Necropsy specimen of lungs from a calf with acute proliferative pneumonia superimposed on resolving cranioventral bronchopneumonia.

(Photo courtesy Dr. John King.)

Diagnosis and Treatment.

Treatment of proliferative pneumonia is controversial because only lung biopsy or necropsy can confirm the clinical entity at hand. Lung biopsy via a Tru-Cut biopsy needle is a useful diagnostic step to aid diagnosis and treatment in valuable animals. Thoracic radiographs, if available, will demonstrate a diffuse pulmonary edema and mixed alveolar-interstitial pattern. Dr. King has recommended therapy with 1 g of atropine/1000 lb body weight daily IM or SQ. The mechanism of action is unknown, but in instances where endemic proliferative pneumonia has been confirmed by necropsy study, this therapy apparently has been beneficial to affected herdmates. When proliferative pneumonia is confirmed or strongly suspected, the following therapy is suggested:

• Remove affected cattle from any source of toxic plants, nitrogen gases, or fumes; for example, if the only affected cows are confined near a silo chute or manure pit, move them. Affected cattle should be moved only when their ventilation and environment need to be improved. Otherwise, any movement constitutes a severe stress.

• Furosemide (0.5 to 1.0 mg/kg or 25 to 50 mg/100 lb body weight by injection once or twice daily) for the first 2 days of therapy if hydration status allows.

• Atropine (0.048 mg/kg or 1/30 grain [2.2 mg] per 100 lb body weight twice daily).

• Dexamethasone (10 to 20 mg once daily) for 3 days unless the affected cow is pregnant.

• Broad-spectrum antibiotics for 5 to 7 days to protect against secondary bacterial pneumonia.

Respiratory Distress in Newborn Calves

Etiology, Pathophysiology, and Signs.

This is a relatively common occurrence and may result from aspiration of meconium, congenital heart disease, white muscle disease, fetal lung pathology (e.g., herpes infection), or more commonly from dysmaturity/immaturity of the lung such as surfactant deficiency. It is especially common in premature, cloned, or in vitro fertilized calves (Figure 4-54 ). Some calves born as early as 6 weeks prematurely may have relatively normal pulmonary function, but this would be unusual. The abnormal compliance causes poor air exchange, hypoxia, pulmonary hypertension, and eventually right heart failure.

Figure 4-54.

A newborn clone calf with hypoxemia being treated with intranasal oxygen.

Diagnosis.

Calves should develop a fairly normal respiratory pattern within the first hour after life, whereas newborn calves with respiratory distress syndrome (RDS) will have labored breathing that does not improve with time. There may be other signs of prematurity (e.g., small size, abnormally fine hair coat) in premature calves. Cloned calves may also have abnormally large umbilical vessels. Lung sounds are diffusely harsh and generally do not have rales. The heart rate will be high, but loud murmurs are usually absent unless the respiratory distress is caused by a congenital heart defect. An arterial sample can be collected from the brachial artery to confirm the severity of the hypoxemia. In some cases, the CO₂ will be elevated, and this can be confirmed by a venous sample (.45 mm Hg). If the CO₂ is elevated in a rapidly breathing calf, the PaO₂ will be extremely low. Pulse oximetry is useful in calves to confirm the hypoxemia and for monitoring therapy. A chest radiograph will reveal diffuse underinflation of the lung and parenchymal collapse. Some premature calves will have moderate to severe respiratory acidosis, hypercapnia, and hypoxemia but because of inappropriate/underdeveloped central responses will appear eupneic or only slightly tachypneic. Periodic assessment of preferably arterial blood gases, or at the very least venous blood pH and CO₂ tension, in the first day or two of life in premature calves is therefore recommended.

Treatment.

Treatment must be early and vigorous if there is hope for survival. Vitamin E and selenium should be given IM. Intranasal oxygen must be administered and the calf given prophylactic antibiotics. One dose of corticosteroid (10 mg of dexamethasone) is often given and empirically does seem to help, especially following meconium aspiration. Although it is proven that corticosteroids given to cattle in the last 2 weeks of gestation improve lung function at birth in cesarean-derived calves, there is limited proof that postnatal-administered steroids will similarly accelerate lung maturation. It may be that postnatal-administered steroids, if they help at all, are inhibiting oxidative lung damage in the hypoxic calf. If surfactant is available, it should be given to the calf via intratracheal instillation via a tube, less commonly by direct injection, or it can be nebulized. Commercially prepared surfactant is preferred, but we have collected surfactant from healthy donor cows by bronchoalveolar lavage using 100 ml of sterile saline and then using the top (foamy) part of the collection for intratracheal administration or nebulization. We have also nebulized the affected calves with acetylcysteine while they were being administered an aminophylline drip. The aminophylline not only serves as a bronchodilator but also has antiinflammatory properties and helps maintain diaphragm strength. Fluids (crystalloids and colloids such as plasma) may be given IV as a continuous drip if needed. We have also administered thyrotropin releasing factor and/or thyroxin in hopes of increasing surfactant production. If pulmonary gas exchange cannot be sufficiently improved with the above and the owners request further treatment, the calf can be placed on a mechanical ventilator, but this is expensive. It is sometimes more difficult to keep calves quiet on a ventilator as compared with foals. Cloned calves with ascites and enlarged umbilical vessels seldom survive even when placed on the ventilator. Persistent pulmonary hypertension causes progression of right heart failure and sometimes reversion to fetal circulation patterns. Nitric oxide (ratio NO to oxygen 5 1:9) can be administered through the oxygen line in hopes of decreasing the pulmonary hypertension (Figure 4-55 ). The chronic hypoxia results in acidosis and multiple organ failure.

Figure 4-55.

A 2-day-old calf with pulmonary hypertension receiving oxygen and nitric oxide.

Other Less Common Causes of Respiratory Distress

Silo Filler's Disease (Nitrogen Dioxide Poisoning)

Etiology and Signs.

NO₂, a heavy yellow gas produced by anaerobic fermentation of fresh silage, may cause the same lower airway damage in cattle exposed to fumes as in humans. Because the gas is heavier than air, it lies on top of recently ensiled material—especially corn silage—and seeks out lower locations such as silo chutes. The major risk to farmers occurs when workers enter a silo chute or silo without first starting the blower in the silo loader to “wash out” NO₂. Cattle confined next to the silo chute are most at risk and may receive chronic low exposure toxicity or severe acute toxicity. Gaseous NO₂ seeks water that allows it to convert to nitric acid, which damages tissues. In the respiratory tract, nitric acid causes acute injury similar to anhydrous ammonia and subsequent obliterative bronchiolitis and interstitial fibrosis.

Affected cattle that have been chronically exposed to NO₂ have a chronic dry cough and increased respiratory rate greater than 40 breaths/min but few other symptoms. Cattle suffering acute severe exposure have a moist cough, more severe dyspnea (increased rate and effort), and pulmonary edema.

Diagnosis.

Careful observation and history may be the key to diagnosis because the signs are nonspecific. Lung biopsy or necropsy is the only absolute means of diagnosis.

Treatment.

Corticosteroids may be used judiciously in affected cattle. Cattle are very sensitive to dexamethasone, and 10 to 20 mg/day for several days would be appropriate therapy. Risk of secondary infection and abortifacient properties of dexamethasone need to be considered. Atropine and furosemide may also be indicated.

Farmer's Lung—Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)

Etiology and Signs.

Hypersensitivity pneumonitis may occur in cattle and result in respiratory distress or chronic respiratory disease. In humans, many specific inhalant antigens may cause similar symptoms, but frequently Micropolyspora faeni and related organisms are incriminated. Wet hay that ferments excessively remains the biggest cause of this condition in farmers and cattle. The resultant dusty, moldy hay releases tremendous numbers of spores when bales are opened into the face of humans and animals. Large round bales also have been observed to cause the problem occasionally. A delayed hypersensitivity reaction is suspected.

Signs of acute experimental exposure include a sudden decrease in appetite and milk production, coughing, cranioventral pulmonary rales bilaterally, and transient fever. In natural cases, chronic cough without obvious illness remains the most common sign when this disease has been recognized in the northeastern United States. Usually more than 50% of the herd is affected, and herd production decreases 10% to 25% because affected cattle cough enough to interfere with normal consumption of feed. Auscultation of the lungs may reveal a few wheezes or may be normal. Signs lessen but do not stop entirely when animals are fed outdoors or go to pasture. Confinement and feeding the causative hay indoors accentuate the signs. Mortality is rare, but occasionally severe chronic cases have developed right heart failure. With the feeding of total mixed rations and the reduction in lifespan of dairy cattle in the United States, this disease has become less common. However, sporadic cases continue to be seen, not so much as a herd issue, but as an individual, older multiparous cow problem on traditional stanchion and tie stall farms.

Diagnosis.

Diagnosis can be aided by history, observation, lack of profound illness in affected cattle, and high morbidity. Tracheal wash samples suggest lymphocytic inflammation with macrophages, lymphocytes, and some plasma cells. The serum of affected cattle may be analyzed for precipitins to M. faeni and other human antigens. When positive, this is suggestive but not definitive evidence because many normal cattle have positive antibodies.

Lung biopsy also may be a very helpful diagnostic aid if the value of the affected cow precludes necropsy. Necropsy inspection of the affected lungs reveals gray spots indicative of lymphocyte accumulations around small airways in the interstitium. Histopathology shows infiltration of lymphocytes and plasma cells in the interalveolar septa. Provocative testing utilizing the hay in question provides subjective causative evidence. Lungworms definitely should be ruled out by Baermann's technique, tracheal wash cytology, and necropsy, if necessary.

Treatment and Control.

Because a large percentage of the herd may be affected, corticosteroids do not represent a wise treatment. Corticosteroids benefit acutely affected cattle or severe recurrent cases but cannot be used on a wide scale. Changes in management constitute both treatment and prevention. Feeding hay outside may give some relief, especially if the bales are opened several minutes or more before the cows being allowed access to the hay. Wetting the hay may be helpful. If economics allow, getting rid of the hay is the best policy and may solve the problem. Farmers who consistently make poor quality hay should be encouraged to consider haylage or at least including hay additives during harvesting that inhibit mold growth. Humans working with causative hay should consider the use of surgical masks or protective face masks to prevent symptoms of farmer's lung in themselves.

Bronchiolitis Obliterans

Etiology and Signs.

This poorly described condition is observed occasionally in individual animals. A dry cough is the predominant sign in affected cattle, and Fox highlights the magnitude of the cough by quoting farmers who call only because the cow “coughs so hard she causes the milking machine to fall off.” Auscultation of the lungs may reveal wheezes or abnormally quiet lung sounds. Although hyperpnea and tachypnea are present in addition to the dry cough, the affected cow does not otherwise appear ill.

The cause is unknown but probably involves chronic exposure to toxic gases, 3-methylindole, allergens, or other proposed causes of acute respiratory distress in cattle. The chronic damage that ensues may result in bronchiolitis obliterans—a pathologic diagnosis.

Diagnosis.

Lung biopsy or histopathology following necropsy is required for definitive diagnosis.

Treatment.

Dexamethasone often gives some relief to affected animals when administered judiciously at 10 to 20 mg/day. Appropriate contraindications should be considered.

Fibrosing Alveolitis

Etiology and Signs.

This is a chronic debilitating respiratory disease of mature cattle. Affected cattle do not act ill but have an obvious increased respiratory rate and effort, as well as obvious coughing. Moist or dry rales may be ausculted over the entire lung field. Morbidity is low, but subsequent mortality is high because the disease is chronic and progressive.

The cause is unknown and may simply be the result of chronic exposure to some of the pneumotoxic materials previously discussed in this section. Chronic exposure to 3-methylindole, NO₂ or other gases, antigens known to cause hypersensitivity pneumonia, or unknown factors may result in diffuse fibrosis of the alveoli.

Diagnosis.

Gross inspection of the lungs at necropsy reveals diffuse pale, heavy, firm lungs. The lobules are white and fleshy. Obliteration of alveolar air space by type 2 pneumocytes, macrophages, and other cells histopathologically explain the antemortem dyspnea. Lung biopsy is indicated if necropsy is not an option.

Treatment.

No treatment is likely to be successful, but antiinflammatory drugs may be tried.

Anaphylaxis and Milk Allergy

Etiology and Signs.

Respiratory distress often accompanies anaphylaxis induced by exogenous antigens such as vaccines, antibiotics, local anesthetics and feedstuffs, or endogenous antigens such as alpha-casein in milk.

In susceptible animals, signs usually develop within minutes following injection of biologics or antibiotics and consist of urticaria, edema of mucocutaneous junctions, and respiratory distress. Signs may be mild, with urticaria predominating, or severe, with collapse quickly following initial signs. Laryngeal edema may occur and be progressive over many hours. Certain biologics have been incriminated more than others in this regard. Antibiotic-induced anaphylaxis has been observed as a result of penicillin, tetracycline, sulfas, and other antibiotics. Penicillin may cause respiratory distress from a true anaphylaxis (usually hives accompany the respiratory distress) or as part of the procaine reaction. Biologics that cause an anaphylactic reaction in more than an occasional cow should be avoided unless suitable alternatives are not available. Many apparent anaphylactic crises may in fact be the result of endotoxins in certain biologics and cattle of certain genetic lines being more susceptible to such vaccine reactions.

Affected cattle appear apprehensive and restless, and their hair stands on end. The heart rate elevates, hives may develop, and frequent attempts to urinate and defecate may alternate with restless treading on the limbs. Dyspnea may be inapparent or obvious, with pulmonary edema, hyperpnea, and respiratory stertor. Cyanosis, cold clammy skin, and hypotensive collapse ensue in severe cases.

Milk allergy occurs most commonly in Channel Island breeds but may occur in any breed. The onset of signs may follow drying a cow off or a reduction in milking frequency to “bag” a cow for a show. Any delay in the normal milking interval may trigger this reaction in cattle sensitized to their own alpha-casein. The signs may be mild or severe as previously described. Hives, edema of mucocutaneous junctions, and respiratory signs develop to varying degrees.

A unique syndrome of collapse has been observed by many practitioners in cattle injected with concentrated vitamin E/selenium products. The reaction is observed within minutes of the IM injection, and collapse and dyspnea are the only signs. It is not known whether this represents anaphylaxis, accidental intravascular administration, or specific toxicity. Most cases recover, but fatal outcomes may appear in 10% to 20% of the cases.

Diagnosis.

History and physical signs suffice for diagnosis.

Treatment.

Treatment is commensurate with the severity of disease and consists of drugs such as epinephrine, antihistamines, corticosteroids, and furosemide. Recommended dosages for adult cattle include:

• Epinephrine (1/1000 concentration), 2 to 10 ml IM or SQ; 2 to 4 ml can be given IV in severe cases

• Tripelennamine HCl, 1 mg/kg IM or SQ

• Furosemide, 0.5 to 1.0 mg/kg IM (if pulmonary edema is present)

• Dexamethasone, 20 to 40 mg IV or IM if the cow is not pregnant

• Flunixin meglumine, 1.1 mg/kg IM

For milk allergy, immediate milking out is indicated along with other symptomatic therapy (above) if the cow shows a serious allergic reaction.

In most cases, one treatment suffices, but in cattle with severe pulmonary edema or urticaria, several treatments at 8- to 12-hour intervals may be necessary for complete resolution.