Spontaneous pneumothorax in a dog with interstitial pulmonary fibrosis and ruptured bullae

Abstract

Canine interstitial pulmonary fibrosis has been described in dogs, almost exclusively in terrier breeds. Here, we present a unique case of spontaneous pneumothorax in a Labrador Retriever that was presented to an emergency clinic in severe respiratory distress. Despite resuscitation efforts, the animal died and was submitted for autopsy, which revealed severely collapsed lungs bilaterally and bullae along the pleural surface, with at least one ruptured bulla observed grossly. Histopathology of the lung revealed coalescing areas of interstitial fibrosis throughout most of the lung tissue examined. A pan-herpesvirus PCR assay was negative on fresh lung tissue. Based on our findings, we propose that the fibrosis and bullae developed sequentially, and the fibrotic interstitium likely decreased the elasticity in the respective alveoli, leading to increased alveolar wall tension in normal alveoli, which caused the formation of bullae. Our case adds to the body of literature regarding canine interstitial lung disease by describing a unique presentation of canine idiopathic interstitial fibrosis in a non-terrier breed.

Canine idiopathic pulmonary fibrosis has been described and defined as septal fibrosis within the lung with an unknown cause. ² The syndrome has been described almost exclusively in West Highland White Terriers, although there are rare reports of a very similar syndrome in other canine breeds.^2,3,6,8 Interstitial fibrosis is the primary finding in such cases, with only mild-to-moderate mononuclear inflammation observed in the affected areas of lung. ¹⁰ The progressive nature of the fibrosis often leads to respiratory failure. There are no proven curative treatments for canine idiopathic pulmonary fibrosis. Instead, treatment is aimed at reducing the severity of clinical signs, such as exercise intolerance and cough, often with the use of corticosteroids. ⁵ Unfortunately, due to the slow and progressive nature of lesion development, clinical signs are often slow to develop and may go unnoticed by animal owners, resulting in animals being presented for veterinary care when already in advanced stages of pulmonary fibrosis.

A reportedly 4.5-y-old female Labrador Retriever was presented to an after-hours veterinary emergency clinic in severe respiratory distress. The dog was drooling and gasping for air with its neck flexed, giving the clinical impression that the animal had choked on a treat that was given by the owner shortly before the clinical signs began. On physical examination, no objects were observed lodged in the oropharyngeal cavity or appreciated on external palpation of the throat. The tongue and gingiva were severely cyanotic. Throughout the clinical assessment period, the animal experienced several bouts of cardiopulmonary arrest and was successfully resuscitated. Radiographically, there was severe bilateral collapse of the lungs consistent with pneumothorax ( Fig. 1A ). A thoracentesis was performed that withdrew an estimated several hundred mL of air, but the clinician did not appreciate negative pressure being achieved at any point. The animal died shortly thereafter despite a fourth attempt to resuscitate.

Figure 1.

Radiographic and gross autopsy images from a dog with interstitial pulmonary fibrosis, ruptured bullae, and spontaneous pneumothorax. A. Right lateral thoracic radiographic image obtained at the emergency clinic after the dog was presented with acute respiratory distress. Both lungs are severely collapsed. Arrowheads outline the more caudal aspect of the collapsed lungs. A large portion of the thorax contains air and appears anechoic (black areas indicated by stars), consistent with pneumothorax. B. The lung is diffusely collapsed and is relatively uniform dark-red. C. Variably sized, tan bullae protrude from the pleural surface of the lung. One of the larger bullae had ruptured, creating a loose piece of tissue (white arrow) that exposed the underlying expanded cavity within the parenchyma (asterisk). While dissecting the lung, it was common to hear the release of air when the smaller bullae were incised (red arrows).

The animal was submitted to the Nebraska Veterinary Diagnostic Center (Lincoln, NE, USA) the following day for an autopsy and diagnostic workup. The carcass weighed 28.2 kg and was in adequate postmortem condition. Upon opening the carcass, the diaphragm was displaced caudally into the abdomen. When the diaphragm was incised, a large amount of air exited the thoracic cavity, causing the diaphragm to become flaccid. The lungs were severely collapsed bilaterally and diffusely dark-red ( Fig. 1B ). Present mostly along the caudal margin and lateral surface of the left caudal lung lobe were tan, pinpoint to ~0.8-cm bullae ( Fig. 1C ). The portions of lung adjacent to or underlying the bullae were moderately firm, whereas the areas without bullae were softer, consistent with atelectasis. One of the larger bullae had ruptured, exposing the lung parenchyma to the pleural cavity. While dissecting the remainder of the lung, remaining intact bullae contained a moderate amount of air that caused them to deflate upon incision with an audible release of air in some cases. No gross lesions were appreciated during the remainder of the autopsy, which included examination of the integument, oral cavity, eyes, trachea, heart, liver, spleen, kidneys, and the entire gastrointestinal tract.

Three pieces of lung were examined histologically, including samples from 1) a severely affected portion of the left caudal lobe, 2) an area along the periphery of the grossly abnormal pleural surface, and 3) a normal-appearing portion of the adjacent parenchyma from the same lobe. In sections of lung, most of the overall architecture (estimated at 50–80% depending on the slide examined) was disrupted due to marked expansion of the interstitium by thick bands of mature collagen ( Fig. 2 ). Excessive collagen was also observed along the pleural surface as well as surrounding airways and blood vessels of various sizes. Alveoli with septa that were expanded by collagen were often lined by hyperplastic type II pneumocytes. The interstitial fibrosis was not a diffuse process but instead was present as coalescing areas with variably sized interspersed areas of relatively normal alveoli (Fig. 2A). The areas with a more normal interstitium had variable degrees of atelectasis, ranging from fairly mild to severe. The overall amount of fibrosis was substantially more severe in areas near the bullae, but abnormal interstitial fibrosis was present in all sections of lung examined.

Figure 2.

Marked expansion of the interstitium due to extensive fibrosis within a section of lung from a dog with ruptured bullae and spontaneous pneumothorax. A. Areas of extensive septal fibrosis are adjacent to areas with normal-appearing alveoli (stars). In the areas with fibrosis, alveoli are often lined by a single layer of hyperplastic type II pneumocytes (arrows). H&E. B. A trichrome stain highlights the amount of collagen (stained blue) in the alveolar septa.

Equine multinodular pulmonary fibrosis (EMPF) is strongly associated with equine herpesvirus 5 infection in horses.^1,12 Given the gross and histologic similarities between our case and EMPF, a pan-herpesvirus PCR assay was performed to evaluate herpesvirus as a potential cause of the fibrosis. Briefly, nucleic acid was extracted from lung tissue and used as a template for nested PCR of consensus pan-herpesvirus targeting the DNA polymerase gene, as described previously.^7,11 Additionally, a consensus pan-gammaherpesvirus nested PCR assay was performed targeting the glycoprotein B gene, as described previously. ⁴ No herpesvirus nucleic acid was detected in the lung sample from our case.

Canine idiopathic pulmonary fibrosis has been described in the literature, with the vast majority of cases being in West Highland White Terriers.^2,3,6,8 To our knowledge, idiopathic pulmonary fibrosis with ruptured bullae and acute, severe pneumothorax has not been described previously in a Labrador Retriever as we retrieved no such cases when searching Google, PubMed, Web of Science, and CAB Direct using the search terms “canine idiopathic pulmonary fibrosis”, “interstitial”, “lung”, “dog”, “Labrador”, “bullae”, “pneumothorax”, and “ILD” together, or in different combinations. We found no evidence of herpesvirus nucleic acid in the lungs of this animal, which is consistent with the findings in a study in 28 West Highland White Terriers with canine idiopathic pulmonary fibrosis in which no herpesvirus nucleic acid was amplified in any of the cases. ⁹

We propose that the combination of pulmonary lesions in our case is related and that progressive interstitial fibrosis preceded bulla formation. Fibrosis was observed throughout a large portion of the lung parenchyma, but even in areas that were severely affected, fibrosis was multifocal. That is, there were normal alveolar septa between and near foci of extensive fibrosis. We propose that these normal alveolar septa would have maintained normal elasticity during inspiration, whereas alveolar septa immediately adjacent to or within areas of septal fibrosis had decreased elasticity. During inspiration, the differences in elasticity between affected and unaffected alveolar walls may have resulted in a disproportionate distribution of inspiratory airflow to the more compliant alveoli. This would increase the mechanical strain on the alveolar walls, potentially beyond normal structural limits, resulting in alveolar rupture and the formation of bullae.

The owners of the animal in our case had not appreciated any exercise intolerance, although the dog was housed mostly indoors, and her level of physical activity was uncertain. Canine idiopathic pulmonary fibrosis should be considered as a differential diagnosis by clinicians and diagnosticians in dogs that are presented with chronic progressive exercise intolerance, acute respiratory distress due to pneumothorax, or both.