Acute Bronchitis

Acute bronchitis refers to a clinical syndrome distinguished by a relatively brief, self-limited inflammatory process of large and mid-sized airways not associated with evidence of pneumonia on chest radiography. It is characterized by a dry or productive cough of less than 3 weeks' duration, is most prevalent in winter, and is primarily caused by viruses. This definition does not pertain to acute exacerbations of chronic bronchitis, a clinical syndrome also frequently associated with viral infection but in which bacteria play a more important role (see Chapter 67). It should also be distinguished from acute bronchiolitis, a clinical syndrome involving small airways most closely linked to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infection in infants (see Chapters 160 and 161).

Acute cough is one of the most common reasons for physician visits in all age groups.¹ Incidence data may be imprecise because symptoms overlap considerably with those of the common cold, pneumonia, and asthma. Estimates from the National Health Interview Survey of U.S. households have found that overall, 5% of persons annually report physician-diagnosed acute bronchitis, with highest rates during the winter months and in those younger than age 5 years.² Studies from the United Kingdom have reported similar rates of 54 per 1000 persons, ranging from 36 per 1000 in younger men to 225 per 1000 in those older than 85 years of age.3, 4

Microbial etiology

Despite failing to uncover a specific pathogen in most case series, acute bronchitis is believed to be most commonly caused by a wide range of viruses (Table 66-1 ). Approximately 10% or less of cases are attributed to bacterial pathogens, principally Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis. However, the recent increase in pertussis cases among adolescents and adults should be considered when evaluating illnesses. The relative proportion of cases caused by different pathogens varies according to age and the season studied but, importantly, is also influenced by the diagnostic methods used. Molecular tests, rather than standard culture, identify a greater number and wider range of viral pathogens, especially in adults, in whom many illnesses represent reinfection with common pediatric viruses (RSV, hMPV, parainfluenza viruses) or infections with newly discovered pathogens such as parainfluenza 4 and bocavirus.5, 6, 7, 8 Many of these infections in adults are associated with low virus shedding.6, 7 Furthermore, at presentation to a physician, virus shedding may have already ceased. Influenza A and B viruses are most closely associated with winter outbreaks of acute bronchitis in both children and adults because of a high relative incidence of infection and the efficiency of influenza virus to infect and damage bronchiolar epithelial cells.3, 8, 9, 10 Although cough associated with most coronavirus and rhinovirus infections is commonly caused by postnasal congestion, these agents, including recently identified strains of rhinovirus and coronavirus, including severe acute respiratory syndrome, can infect the lower airway, causing acute bronchitis.11, 12, 13, 14 The higher temperature of lower airways was considered inhospitable to rhinovirus replication; however, recent evidence has convincingly documented virus presence in bronchiolar epithelial cells, although cytopathology is less than that with influenza virus infection.¹³ Although found less frequently than other viruses in the general population, adenoviruses, including the recently identified adenovirus type 14, and adenovirus types 4 and 7, are important causes of bronchitis in military recruits.8, 15 Enteroviruses, primarily echovirus and coxsackievirus, can cause acute bronchitis. Simultaneous infection with two or more viruses occurs in 10% to 30% of cases, as is frequently the case with bocavirus infection. Worldwide, measles virus remains an important respiratory tract pathogen causing cough during the early prodromal phase; especially vulnerable are malnourished children in developing countries lacking resources for vaccination.¹⁶ Although herpes simplex virus is commonly identified in respiratory secretions of patients with respiratory illness and is generally considered to be clinically insignificant, it has been associated on occasion with acute hemorrhagic tracheobronchitis in normal persons and has been described in critically ill intubated adults.¹⁷ Although occasionally involving the lower airways, infection with human papillomavirus types 6 and 11 produces symptoms of hoarseness, stridor, and chronic cough.¹⁸

TABLE 66-1.

Viral and Bacterial Causes of Acute Bronchitis

PATHOGEN	SEASONALITY	COMMENTS
Influenza viruses	Winter	Local epidemics last 6-8 wk during which clinical illness of cough and fever has high predictive value; laboratory diagnosis readily available; early neuraminidase inhibitor therapy effective
Rhinoviruses	Fall and spring	Most frequent cause of common cold syndrome; immunity is serotype specific
Coronaviruses	Winter to spring	Causes common cold syndrome; newer strains are difficult to culture and require RT-PCR for diagnosis
Adenoviruses	Year-round, winter epidemics	High attack rates in closed populations such as persons living in military barracks or college dormitories; serotype-specific immunity
Respiratory syncytial virus (RSV)	Late fall to early spring	Attack rates approach 75% in neonates, 3%-5% in adults; associated with wheezing in all age groups; rapid antigen test accurate in children but requires culture or RT-PCR to diagnose in adults
Human metapneumovirus (hMPV)	Winter to early spring	Associated with wheezing in adults and in infants; difficult to isolate in tissue culture and often requires RT-PCR
Parainfluenza viruses	Fall to winter	Similar to RSV and hMPV, parainfluenza viruses primarily pediatric pathogens but can cause severe acute disease in some adults
Measles virus	Year-round	Can cause respiratory disease in malnourished children; illness causes transient immune suppression
Mycoplasma pneumoniae	Year-round, fall outbreaks	Long incubation period (10-21 days) results in staggered epidemic pattern in families; nonproductive persistent cough typical; diagnosed by IgM serology; treated with macrolide, quinolone, or tetracycline antibiotics
Chlamydia pneumoniae	Year-round	Associated with sinusitis; diagnosis by RT-PCR not readily available
Bordetella pertussis	Year-round	Severe illness in nonimmunized children; illness milder in partially immune adults can be associated with prolonged cough; adults often reservoir for epidemics; early therapy with antibiotics can reduce spread

RT-PCR, reverse-transcriptase polymerase chain reaction.

Mycoplasma pneumoniae, C. pneumoniae, and Bordetella pertussis are the bacteria most associated with acute bronchitis, implicated in perhaps 10% of cases.³ Cough caused by these agents, especially B. pertussis, may persist in some cases for several months. Recently, Bordetella holmesii has been recognized as a cause of pertussis syndrome (see Chapter 232). In a recent acellular pertussis vaccine trial in adults, the incidence of pertussis was 0.7% in the placebo group.¹⁹ However, the number of cases in adults has been increasing in recent years, attributed to incomplete vaccine uptake as well as failure of the vaccine to induce durable immunity.²⁰ This has resulted in a recommendation to provide a vaccine booster dose to adults and pregnant women (see Chapter 321). Bordetella bronchiseptica, a canine pathogen, can occasionally cause disease in humans, especially those who are immunocompromised.²¹ Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis (formerly Branhamella catarrhalis) have not been conclusively demonstrated to cause acute bronchitis, despite their implication in postviral pneumonia and chronic bronchitis. Although many viruses enhance bacterial adherence to respiratory epithelial cells in vitro, the actual incidence of postviral bacterial infection in clinical situations has not been well defined.

Pathogenesis

The pathogenesis of acute bronchitis is the result of a combination of direct cytopathology of the pathogen and host immune response. Because cell tropism and pathogenic mechanisms vary for each of the viruses, it is not surprising that the location and extent of cytopathology in the airways also varies. Histopathologic changes in the airways during infection are best characterized for influenza virus.10, 11, 22, 23 In a recent autopsy series of 47 children with fatal influenza, submucosal congestion, hemorrhage, mononuclear cell infiltration, and epithelial necrosis were noted in 50% of cases.²³ Similar findings have been reported in adults, along with occlusion of airways by desquamated necrotic debris.²² In less severe influenza, bronchoscopic examination reveals only mild inflammatory changes.²⁴ RSV has also been demonstrated to infect terminal bronchiolar lining cells with extensive debris occluding the lumen in infants, but similar data are lacking in adults.²⁵ Rhinovirus, which is primarily associated with upper respiratory common cold symptoms, produces patchy infection of bronchial epithelial cells up to 15 days after experimental challenge.¹³

There is ample evidence that immune responses contribute significantly to disease pathogenesis in acute bronchitis. The innate immune response, characterized by virus-induced release of proinflammatory cytokines and chemokines by respiratory epithelial cells and immune cells, contributes to systemic and local symptoms. Early after infection with influenza, type I interferons, tumor necrosis factor, and interleukin-6 can be detected.²⁶ In experimental influenza virus infection, symptoms correlate temporally with the kinetics of cytokine secretion.²⁷ Cytokine induction by rhinovirus may also explain the important role that this virus plays in asthma episodes.²⁸ The immune response is thought likely to be responsible for the prolonged airway hyperreactivity that can be demonstrated for up to 6 weeks after influenza or RSV infection in normal adults.²⁹ Among the bacterial causes of acute bronchitis, B. pertussis is unique in that its expression of toxins may play a role in clinical symptoms, including the prolonged characteristic cough. However, a defined and specific pertussis “cough” toxin has not yet been identified.

Clinical Manifestations

In most children and adults, acute bronchitis begins with signs and symptoms typical of the common cold syndrome. Nasal congestion, rhinitis, sore throat, malaise, and low-grade fever typical of the common respiratory viral pathogens are noted first, followed shortly by the onset of cough, which becomes the dominant sign in acute bronchitis. In mild cases, the illness lasts only 7 to 10 days, whereas in others, cough may persist for up to 3 weeks or longer. Wheezing is not uncommon with acute bronchitis; in one study from the Netherlands, 37% of patients with acute bronchitis ultimately were diagnosed with asthma.³⁰ Disease severity and dominance of various symptoms may vary according to the specific pathogen. Fever is more common and higher with influenza or adenovirus infection, compared with rhinovirus or RSV infection at all ages. In contrast, RSV- or hMPV-infected persons are more likely to wheeze than influenza virus–infected patients.7, 31

Various host factors such as age, underlying medical conditions, immune status, and environmental factors such as second-hand smoke exposure can influence clinical presentation and illness severity. Older patients and those with underlying cardiopulmonary conditions infected with influenza, RSV, or hMPV remain ill for an average of 16 to 17 days, in contrast to younger persons whose illness lasts an average of 7 to 10 days.6, 7, 31 In M. pneumoniae infection, cough can be particularly persistent and irritating, often with minimal phlegm, causing severe chest discomfort.

Diagnosis

Acute bronchitis should be suspected in any person with an acute respiratory tract illness in which cough is the dominant complaint. Patient evaluation begins with a careful history, including identification of underlying chronic obstructive pulmonary disease or asthma, which may require specific therapy. Taking note of the season and the presence of influenza or other circulating viruses in the community is important. During community outbreaks of influenza, the presence of an acute illness with fever and cough can have a predictive value of 79% in young healthy persons.³² Among hospitalized older persons with acute respiratory tract illness, similar clinical parameters increase the odds of influenza approximately threefold.³³ Exposure to environmental irritants should be sought, especially in the absence of typical upper respiratory tract symptoms. Travel history or exposure to ill family members or close contacts may provide useful information about the incubation period and thus the etiology. M. pneumoniae, with an incubation period of 7 to 21 days, will progress slowly through the family in contrast to influenza with its 2- to 4-day incubation period and close clustering of illnesses. Recent vaccination does not eliminate influenza from consideration, especially in older persons in whom protective efficacy is poor.6, 34 Prolonged cough longer than 4 weeks, with or without paroxysms or vomiting, should suggest B. pertussis, even among vaccinated adolescents and adults, because immunity is not durable.19, 20

Physical examination should be attentive to signs of pneumonia, because a primary goal of evaluation is to discriminate acute bronchitis from pneumonia. A concern for clinicians is the occurrence of bacterial infection that can follow viral respiratory tract infection. This is best exemplified by the severe bacterial pneumonias that followed influenza infection during the 1918 H1N1 and 1957 H2N2 pandemics. Similarly, one report described bacteremic S. pneumoniae pneumonia in long-term care patients after antecedent parainfluenza virus infections.³⁵ Despite concerns about postviral bacterial pneumonia, several large studies have indicated that only approximately 7% of patients diagnosed with acute bronchitis will have radiographic evidence of pneumonia.³⁶ Combinations of signs and symptoms or overall clinical judgment is imprecise, with a sensitivity of only 23%.37, 38 One study has found that in the absence of any vital sign abnormality, radiographic evaluation could be safely omitted.³⁷ Standard laboratory tests, such as white blood cell count or inflammatory markers such as serum C-reactive protein, do not reliably discriminate viral from bacterial infection.³⁸ However, recent studies from Europe have suggested that a serum procalcitonin level below 0.1 ng/mL may be a more reliable indicator of patients with a variety of acute respiratory syndromes, including acute bronchitis, that do not require antibiotic therapy.39, 40 Procalcitonin, the prohormone of calcitonin, is synthesized by a variety of tissues in response to bacterial infection to a greater extent than to viral infections.

Ultimately, etiologic diagnosis requires laboratory confirmation. Rapid antigen detection in nasopharyngeal swabs is relatively sensitive for influenza virus in all age groups, as it is for RSV in infants. Identification of other viral pathogens requires tissue culture or reverse-transcriptase polymerase chain reaction (RT-PCR) assay. The latter is especially useful in older adults because culture for many of the most prevalent viruses (RSV, hMPV, coronaviruses, parainfluenza viruses) is insensitive in adults.5, 6, 7 Diagnosis of M. pneumoniae rests on demonstrating pathogen-specific IgM in serum or with RT-PCR assay. B. pertussis diagnosis can be made by serology, RT-PCR assay, or culture. C. pneumoniae is difficult to diagnose and requires RT-PCR assay or serology. Because of the large number of potential pathogens that can cause acute bronchitis, newer rapid multiplex RT-PCR assays could provide useful diagnostic information in managing acute bronchitis.

Therapy

Therapy for patients with acute bronchitis is generally symptomatic, directed at relief of troublesome upper respiratory symptoms, cough, and wheezing. As noted, acute bronchitis and asthma can present with similar manifestations, and therapy directed toward bronchospasm may be required. Several approaches to controlling acute cough have included narcotic cough suppressants, expectorants, antihistamines, decongestants, and β₂-agonists.41, 42 Reviews of randomized controlled trials have not clearly concluded that they are beneficial. In a placebo-controlled double-blind trial in experimental rhinovirus infection, the combination of ibuprofen (400 mg) plus chlorpheniramine (12 mg), administered every 12 hours for 4.5 days, reduced cough significantly, although the effect was optimal when combined with an intranasal antiviral compound (interferon-α).⁴³

After their introduction after 1940, antibacterial agents were rapidly embraced for treatment of acute bronchitis; currently, 60% to 80% of patients receive antibiotics for this diagnosis.44, 45 However, empirical antibacterial therapy for acute bronchitis without regard for demonstrated pathogen-specific therapy has repeatedly been shown to provide no benefit for most patients.⁴⁶ However, acute bronchitis remains one of the five most frequently cited rationales for excessive antibiotic use in outpatients. Acute bronchitis and other acute respiratory syndromes (otitis media, sinusitis, pharyngitis, upper respiratory tract infections) account for approximately 75% of ambulatory prescriptions in the United States.¹ Current guidelines, endorsed by a number of national societies, including the Infectious Diseases Society of America, do not recommend the routine use of antibiotics for uncomplicated acute bronchitis in otherwise normal persons.⁴⁷ Various strategies to reduce antibiotic use, including patient and physician education or delayed prescription filling, can reduce antibiotic use by approximately 50%.48, 49 Recent randomized controlled studies using levels of serum procalcitonin to guide therapy in acute respiratory infections, including acute bronchitis, have also demonstrated that antibiotic use can be partly reduced without adversely affecting outcome.39, 40 If a specific viral diagnosis can be confirmed using a rapid RT-PCR test, perhaps physicians would be more willing to forego antibiotic treatment. Even patients with documented M. pneumoniae or C. pneumoniae infection may not benefit from specific therapy with macrolides or quinolones in the absence of pneumonia. In adults and adolescents, early therapy for infection with B. pertussis with macrolides or tetracyclines is indicated to prevent transmission, although the clinical findings early in infection are indistinguishable from viral causes of bronchitis.

It may be useful to seek a specific diagnosis of influenza during community outbreaks, because specific treatment with neuraminidase inhibitors active against influenza A and B strains can reduce the duration of illness when administered early in its course. In one study of adults with influenza, subsequent antibacterial use was 11% in zanamivir-treated patients compared with 17% in placebo-treated controls.⁵⁰ However, bacteriologic and radiologic confirmation of bacterial pneumonia was not sought in this study.

Prevention

Preventive measures to reduce transmission of agents known to cause acute bronchitis should be limited to standard respiratory and contact precautions when a specific etiology is unknown. Immunization against specific pathogens, such as influenza and pertussis, is of benefit and can reduce the incidence of symptomatic infection with these agents (see Chapter 321).