Chronic idiopathic pulmonary fibrosis in five dogs

Five dogs presented with chronic and progressive pulmonary illness characterized by progressive dyspnea, exercise intolerance, and significant inspiratory crackles on auscultation. Radiographically, there was a widespread and diffuse interstitial lung pattern with varying degrees of bronchial involvement. Histopathological changes included thickened alveolar septa, interstitial fibrosis, and pneumocyte hyperplasia. Based on the clinical, radiographic, and histopathological changes, a diagnosis of idiopathic pulmonary fibrosis was made. Idiopathic pulmonary fibrosis is a chronic disease characterized by inflammation and fibrosis of the pulmonary interstitium and peripheral airspaces, which has been poorly characterized in the dog.     

Thoracic high resolution CT using the modified VetMousetrap™ device is a feasible method for diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers

Canine idiopathic pulmonary fibrosis is a chronic, progressive interstitial lung disease particularly prevalent in West Highland White Terriers. In the present prospective pilot study, we evaluated the feasibility of modified VetMousetrap? device in high resolution CT to detect idiopathic pulmonary fibrosis in West Highland White Terriers. Twelve awake West Highland White Terriers with canine idiopathic pulmonary fibrosis and 24 clinically healthy West Highland White Terriers were scanned using a helical dual slice scanner utilizing VetMousetrap? device without or with minimal chemical restraint with butorphanol. Three evaluators blindly assessed the images for image quality and the presence of canine idiopathic pulmonary fibrosis related imaging findings such as ground glass opacity and reticular opacities. Additionally, the attenuation of the lung was quantified with ImageJ software using histogram analysis of density over the lung fields. Computed tomography was successfully completed and motion artifact ranked in statistical analysis barely noticeable to mild in all dogs. The agreement between imaging findings and clinical status was very good with overall κ value 0.91 and percentage of agreement of 94%. There was also very good intraobserver (κ_range = 0.79‐0.91) and interobserver agreement (κ = 0.94). Moderate to severe ground glass opacity was present in all affected dogs. In the ImageJ analysis, a significant difference in lung attenuation between the study groups was observed. We conclude that modified VetMousetrap? device is applicable in diagnosing canine idiopathic pulmonary fibrosis in awake West Highland White Terriers avoiding anesthetic risk in these often severely hypoxic patients.     

RADIATION PNEUMONITIS IN THREE DOGS

Radiation pneumonitis developed within the radiation treatment field in three dogs with soft tissue sarcomas located on or adjacent to the thoracic wall. Radiographic signs compatible with a diagnosis of radiation pneumonitis developed from one (n = 2 dogs) to two (n = 1 dog) months after completion of therapy. The initial radiographic sign was an alveolar infiltrate in all three dogs. At subsequent examinations at variable time periods after treatment, radiographic findings included: bronchiectasis (n = 3 dogs), alveolar infiltrate (n = 2 dogs), decreased lung volume (n = 2 dogs), and unstructured interstitial opacification (n = 1 dog). Necropsy examination of one dog at fourteen months after the completion of radiotherapy showed evidence of pulmonary fibrosis within the irradiated lung. Necropsy examination of the second dog did not show any evidence of radiation induced changes. It is possible that histopathologic examination did not include irradiated lung. No clinical signs that could be attributed to the radiation pneumonitis were observed in any dog. It appears that approximately 25% of the lung can be safely irradiated to high doses, if indicated, in order to deliver an adequate dose of radiation to a primary tumor site.     

Use of keyhole lung biopsy for diagnosis of interstitial lung diseases in dogs and cats: 13 cases (1998-2001)

OBJECTIVE: To characterize interstitial lung diseases (ILDs) and evaluate use of keyhole lung biopsy for diagnosis of ILDs in dogs and cats. DESIGN: Retrospective study. ANIMALS: 11 dogs and 2 cats. PROCEDURE: Medical records of dogs and cats undergoing keyhole lung biopsy to confirm ILDs were reviewed. Signalment, clinical signs, results of thoracic radiography and other respiratory diagnostic tests, postoperative complications, and patient outcome were analyzed. RESULTS: Clinical respiratory signs included cough, tachypnea, exercise intolerance, and hemoptysis. Thoracic radiographic abnormalities included interstitial, alveolar, and bronchointerstitial patterns and multiple discrete pulmonary nodules. Lung biopsy and histologic examination revealed interstitial pulmonary fibrosis, bronchiolitis obliterans with organizing pneumonia, or unclassified lesions. Outcome after biopsy included no response to treatment, euthanasia, partial or complete remission while receiving medication, and cure. CONCLUSIONS AND CLINICAL RELEVANCE: Recognition and classification of ILDs in dogs and cats are likely to be important in guiding appropriate treatment and providing accurate prognostic information. Ancillary respiratory diagnostic tests are beneficial in ruling out infectious and neoplastic disorders that may mimic ILDs; however, their present use in the diagnosis of ILDs is limited. Results suggest that keyhole lung biopsy is an effective means for obtaining a specimen for histologic diagnosis in dogs and cats with ILDs.     

Chronic renal failure in dogs: a comparative clinical and morphological study of chronic glomerulonephritis and chronic interstitial nephritis.

Chronic renal disease is an important clinical problem in dogs. Until recently, diffuse renal fibrosis with chronic renal failure has been attributed mainly to chronic interstitial nephritis, itself considered to be the end stage of acute leptospiral nephritis. A clinical and morphological analysis of eight cases of chronic glomerulonephritis is described and a comparison made with eight dogs suffering from severe chronic interstitial nephritis. Clinically and biochemically, the two diseases were virtually indistinguishable, both resulting in uraemia. A possible distinguishing feature of chronic interstitial nephritis was the anaemia which was absent from chronic glomerulonephritis cases. Morphologically, the two diseases appeared to be distinguishable on three grounds; the pattern and severity of fibrosis, the degree of fibrin deposition and the immunofluorescence findings.     

Chronic pulmonary interstitial fibrosis in a blue-fronted Amazon parrot (Amazona aestiva aestiva)

A 30-yr-old blue-fronted Amazon parrot (Amazon aestiva aestiva) was presented to the clinic with a history of sneezing more often during the last 2 mo. Physical examination revealed only a mild nasal discharge. Complete hematologic and plasma biochemical examination showed no abnormalities. Computerized tomography (CT) of the complete bird showed generalized lung alterations consistent with lung fibrosis. Two lung biopsies were taken. The results of the histologic examination of the biopsies confirmed the tentative CT diagnosis of pulmonary interstitial fibrosis. To our knowledge this is the first reported case of chronic pulmonary interstitial fibrosis diagnosed by means of a lung biopsy in an avian species. The histologic characteristics are discussed and compared with those of human idiopathic pulmonary fibrosis.     

IMAGING DIAGNOSIS—PULMONARY ALVEOLAR PROTEINOSIS IN A DOG

A young dog was presented for cyanosis and right heart failure. Radiographic and CT characteristics included right heart/pulmonary artery enlargement, hepatomegaly, abdominal effusion, and severe, generalized air‐space filling. Focal increased opacities were present in the peripheral lung, as were multiple pulmonary blebs and bullae. Echocardiographic findings were consistent with cor pulmonale and pulmonary hypertension. Bronchoscopic findings were consistent with chronic inflammation. Pulmonary alveolar proteinosis (PAP) was confirmed at necropsy. Pulmonary alveolar proteinosis is an interstitial lung disease that results in accumulation of phospholipoproteinaceous material and should be included as a differential diagnosis for dogs with these clinical and imaging characteristics.     

Diffuse alveolar injury in two dogs

Proliferative interstitial pneumonia of undetermined cause was diagnosed in 2 dogs. The clinical signs in both dogs consisted primarily of acute onset, rapid breathing, and raspy lung sounds. Radiography revealed a diffuse increase in pulmonary alveolar density. In both dogs, the primary pathologic process was diffuse alveolar pneumocyte injury, and the pulmonary lesions were similar. Proliferation of type II pneumocytes (some of which were atypical mononucleated, and others multinucleated) was a prominent feature of the interstitial pneumonia. Because of the atypical features of some pneumocytes in such cases, biopsy findings may suggest a neoplastic process. Proliferative interstitial pneumonia should be included in the differential diagnosis of a diffuse pulmonary disease that is poorly responsive to medical treatment.     

IMAGING DIAGNOSIS—COMPUTED TOMOGRAPHY OF TRACTION BRONCHIECTASIS SECONDARY TO PULMONARY FIBROSIS IN A PATTERDALE TERRIER

An 8‐year‐old, Patterdale terrier was referred for evaluation of tachypnoea, exercise intolerance, and weight loss. Computed tomographic images showed pneumomediastinum, diffuse pulmonary ground glass opacity, and marked dilatation of peripheral bronchi, but no evidence of thickened bronchial walls. The histopathologic diagnosis was diffuse pulmonary interstitial fibrosis, type II pneumocyte hyperplasia, and bronchiectasis. The lack of evidence of primary bronchitis supported a diagnosis of traction bronchiectasis. Traction bronchiectasis can occur as a sequela to pulmonary fibrosis in dogs.     

Chronic pulmonary disease in West Highland white terriers.

This paper describes the clinical features, and diagnostic findings of a chronic respiratory condition in 29 West Highland white terriers. Typically, the dogs were coughing chronically, had dyspnoea and tachypnoea of varying severity, and had deteriorated progressively over months to years. The mean (sem) survival time in months from the clinical signs being first noted by the owners was 17.9 (2.3). Most cases had a combination of respiratory signs, but coughing was the predominant sign in 18 cases. Inspiratory crackles were audible on chest auscultation in 28 cases, 10 of which were also wheezing. Rhonchi were the predominant sound in the remaining case. The main radiographic changes were mild to severe increased Interstitial markings in all cases, with additional bronchial markings in 14 of the dogs. Right-sided cardiomegaly (cor pulmonale) was recorded in 15. Bronchoscopic findings in 17 of the dogs were either normal or involved a mild airway mucoid reaction in eight. Chronic mucosal changes were observed in eight, but in two this finding was equivocal. Dynamic changes to the lumen of the airway were present in seven cases. No significant haematological or biochemical changes could be detected in 20 cases, but four cases were hypercholestrolaemic. A histopathological assessment of four cases revealed alveolar septal fibrosis to be the predominant change. Prednisolone, with or without bronchodilators, was the most commonly used therapy, and the response was variable. The condition appears to be associated with significant pulmonary interstitial fibrosis of unknown aetiology and has clinical similarities to idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) in human beings.     

Lung Injury Leading to Respiratory Distress Syndrome in Young Dalmatian Dogs

A progressive pulmonary disease resulting in severe respiratory failure and death in an average of 3 weeks was diagnosed in 11 young Dalmatian dogs. The dogs were from 4 litters, all genetically related by a common ancestor. The initial clinical signs were tachypnea and noisy respiration. Respiratory distress developed shortly before death and was characterized by strenuous and rapid respirations, along with cyanosis and vomiting. On blood gas analysis, there were severe arterial hypoxemia, hypercapma, and marked alveolar-arterial oxygen difference. Radiographically, a diffuse pattern of alveolar, interstitial, and peribronchial densities was observed in the lungs. Most dogs developed pneumomediastinum and gastroesophageal intussusception in the terminal phase of the disease. There was no response to treatment with antibiotics, corticosteroids, diuretics, or oxygen. At necropsy, the lungs were wet, heavy, and relatively airless. Absence of 1 kidney in 2 dogs and severe internal hydrocephalus in 2 dogs were additional necropsy findings. Pulmonary histopathology included metaplasia and atypia of the alveolar and bronchiolar epithelium, a nonpurulent inflammatory reaction characterized mainly by mononuclear cells and macrophages, eosinophilic hyaline membrane formation, and focal pulmonary fibrosis. The histological manifestations were typical of acute lung injury. Clinically, the findings were consistent with adult respiratory distress syndrome (ARDS), except for the relatively long course. No known risk factors for ARDS, such as trauma, toxin exposure, infection, or endotoxemia could be identified. The relationship of the other abnormalities (ie, renal aplasia, hydrocephalus) to the pulmonary disease also remains obscure. An inherited defect is suspected, because segregation analysis of the 4 litters suggests autosomal recessive inheritance.     

PULMONARY MINERALIZATION IN FOUR DOGS WITH CUSHING'S SYNDROME

The clinical and imaging features of four dogs with Cushing's syndrome and pulmonary mineralization are reviewed. Three dogs presented with a primary complaint of respiratory distress/dyspnea. Three dogs had pituitary dependent Cushing's syndrome, while the remaining one dog had iatrogenic Cushing's syndrome. Each dog had clinical features typical for Cushing's syndrome. Two of the dogs were euthanized due to progressive hypoxemia. In each dog, the serum calcium, phosphorous, blood urea nitrogen and creatinine were normal.
A generalized increase in unstructured interstitial pulmonary opacity with diffuse mineralization was noted on thoracic radiographs of all dogs. In one dog, an ill-defined nodular interstitial pattern of mineralization was present. Delayed bone phase scintigraphy using ^99mTechnetium methylene diphosphonate documented generalized pulmonary uptake in two dogs. ^99mTechnetium labeled microaggregated albumin lung perfusion scans were normal in these two dogs. ^99mTc-MDP scintigraphy can provide useful information in diagnosing pulmonary mineralization in Cushingoid dogs.     

Interstitial lung disease in West Highland White Terriers

Progressive respiratory failure and pulmonary fibrosis in West Highland White Terriers (WHWT) is an apparently genetic disorder of unknown pathogenesis. This study characterizes the light microscopic, ultrastructural, and immunohistochemical features of affected WHWT in comparison with lesions in usual interstitial pneumonia (UIP) of humans. Lesions in WHWT were confined to the expansion of the interstitial space of alveolar septa by extracellular matrix (ECM) determined to be mixtures of type-I and -III collagens. Features of UIP such as intra-alveolar fibroblastic foci, subpleural distribution, and honeycombing were not observed in six WHWT. Comparison with normal dogs showed no apparent increase in septal myofibroblasts. Ultrastructually, the ECM in alveolar septa consisted of large aggregates of periodic collagen filaments underlying alveolar capillaries that were surrounded by thick bands of amorphous to fine fibrillar matrix. This study suggests that chronic pulmonary disease of WHWT is a result of aberrant collagen regulation.     

Surfactant Protein C in Canine Pulmonary Fibrosis

Background: Canine pulmonary fibrosis (CPF) occurs most commonly in West Highland White Terriers. The differing incidences of CPF among dog breeds suggest that genetic factors contribute to its pathophysiology. Pulmonary fibrosis in humans is associated with mutations in the gene coding for lung surfactant protein C (SP-C) ( SFTPC ).
Hypothesis/Objectives: To investigate the histopathologic changes and SP-C composition and genetic structure in dogs with CPF.
Animals: Five dogs with PF, 2 dogs with other lung diseases, and 3 healthy dogs.
Methods: Lung tissue from dogs with clinically suspected CPF and 5 control cases was analyzed histopathologically. Bronchoalveolar lavage fluid (BALF) collected postmortem from 3 terriers with histopathologically confirmed pulmonary fibrosis and the 5 controls were analyzed by Western blots, and the exons of SFTPC were sequenced for 2 dogs with PF and 1 dog with other lung disease.
Results: SP-C could not be detected in BALF of 1 dog with PF, although SP-B was present. A mutation was detected in SFTPC exon 5 of this dog. From 2 dogs with PF and in all 5 control dogs SP-B and SP-C were detected in BALF.
Conclusions: Taken together, the results indicate that canine and human lung fibrosis share histopathologic features and that analysis of SP-C and its gene in a larger set of dogs with PF is warranted.     

Comparative study of chronic kidney disease in dogs and cats: Induction of myofibroblasts

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, α-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The α-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.     

Pulmonary Abnormalities in Dogs with Leptospirosis

Background: Leptospirosis in dogs is a multiorgan disease affecting mostly kidneys and liver. Objectives: The objective was to characterize prevalence, clinical, and radiological features and outcome of dogs with leptospirosis and pulmonary abnormalities. Animals: Fifty dogs with leptospirosis. Methods: Medical records of dogs diagnosed with leptospirosis at the Small Animal Clinic, Berlin, were reviewed. Diagnosis was based on microscopic agglutination test, blood or urine polymerase chain reaction, and histopathology. Based on clinical and/or radiological signs, patients were grouped into dogs with lung abnormalities (group 1) or without (group 2). Severity of respiratory distress was scored as mild to moderate (grade 1) or severe (grade 2). Thoracic radiographs were scored based on pulmonary changes and location as grade 1 (caudal interstitial pattern), 2 (generalized mild to moderate reticulonodular interstitial pattern), or 3 (generalized severe reticulonodular interstitial pattern with patchy alveolar consolidations). Results of CBC and biochemistry were compared between groups. Results: Thirty‐five dogs had radiological pulmonary changes (grade 1: 5; grade 2: 14; grade 3: 16); 31 of them had pulmonary distress (grade 1: 13, grade 2: 18). Sixty‐seven percent of the dogs with dyspnea grade 2 were mainly euthanized because of respiratory distress. Fifteen percent of the dogs with dyspnea grade 1 and 21% without clinical respiratory signs were euthanized because of acute renal failure or sepsis. Conclusions and Clinical Importance: In 70% of dogs with leptospirosis pulmonary changes were detected. Lung involvement represented a severe complication causing increased case fatality depending on the severity of respiratory distress.     

Chronic idiopathic pulmonary fibrosis in a West Highland white terrier

A 9-year-old, spayed, female West Highland white terrier was presented with a chronic cough, lethargy, and exercise intolerance. Thoracic radiographic findings were consistent with a marked interstitial lung pattern. Idiopathic pulmonary fibrosis, a disease anecdotally linked to this breed, was diagnosed on postmortem examination.     

The Efficacy of Mechanical Abrasion and Talc Slurry as Methods of Pleurodesis in Normal Dogs

OBJECTIVE: To determine the efficacy of mechanical abrasion and talc slurry as methods for pleurodesis in normal dogs. STUDY DESIGN: Experimental study. ANIMALS OR SAMPLE POPULATION: Ten normal beagle dogs. METHODS: Group I dogs had mechanical abrasion (MA) of the pulmonary and costal pleurae performed in one hemithorax with a dry gauze sponge with a median sternotomy approach. Group II dogs had 100 mL of a 1 g talc slurry (TS) administered into one hemithorax through a tube thoracostomy. Administration of the TS was visualized by using video thoracoscopy. All dogs were evaluated at 2, 10, 20, and 30 days postoperatively by means of thoracic radiography and ultrasonographic thoracic wall measurement. The dogs were euthanatized 30 days postoperatively and a gross necropsy was performed. Hemithoraces were assigned a pleurodesis score (0-4) and an obliteration grade (0-6). Tissues were collected for histopathologic examination of pulmonary pleura, costal pleura, and pleural adhesions. Pulmonary and costal pleurae were graded for the degree of fibrosis (0-4). RESULTS: Obliteration grade and costal pleural fibrosis score were significantly higher for the treated sides in the MA dogs compared with the TS dogs. MA Dogs: Mechanical abrasion dogs had pleurodesis, obliteration, and pleural fibrosis scores that were greater on the treated side than the untreated side, however, the differences were not statistically significant. Only two MA dogs had firm adhesion of the pulmonary pleura to the costal pleura in portions of the cranial and middle lung lobes in the treated hemithorax. Thoracic wall surface area covered with adhesions was 15% and 21% in each of these two dogs. The median pulmonary pleural fibrosis score of all MA dogs for the treated hemithorax was 3 compared to 0 on the untreated side. TS Dogs: There was no statistical difference for pleurodesis scores and obliteration grades between the treated and untreated sides. No dogs showed evidence of pulmonary to costal pleural adhesions. Histopathology showed talc crossover into the untreated side in all five dogs. Median pulmonary fibrosis score of the treated hemithorax was 1 compared with 0 on the untreated side. CONCLUSIONS: Neither method of pleurodesis produced sufficient pleural adhesions to obliterate the pleural space. It is possible that the degree of pulmonary pleural fibrosis present in MA dogs may be sufficient to limit air leakage from pulmonary blebs and bullae resulting in successful treatment of spontaneous pneumothorax.     

Clinical, bronchoscopic, histopathologic, diagnostic imaging, and arterial oxygenation findings in West Highland White Terriers with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, interstitial lung disease primarily affecting West Highland White Terriers (WHWTs). Objective: To describe the clinicopathological and diagnostic imaging features in WHWTs with IPF. Animals: Twelve WHWTs with IPF and 14 healthy control WHWTs. Method: Prospective study. Clinical signs and findings of physical examination, blood and arterial blood gas analyses, radiography, high‐resolution computed tomography (HRCT), bronchoscopy and bronchoalveolar lavage (BAL) of IPF dogs were obtained and compared with controls. Histopathologic changes in IPF dogs were evaluated. Results: Mean partial pressure of oxygen was significantly lower in IPF (mean ± SD, 65.5 ± 15.4 mmHg) than in controls (99.1 ± 7.8 mmHg, P<.001). The alveolar‐arterial oxygen gradient was significantly higher in IPF (50.1 ± 17.3 mmHg) than in controls (17.5 ± 4.9 mmHg, P<.001). In HRCT, ground glass opacity (GGO) was detected in all IPF dogs, traction bronchiectasis in 4, and honeycombing in 1. Bronchoscopic airway changes were noted in all IPF dogs. On BAL fluid (BALF) cytology, the total cell count (TCC) was higher in IPF dogs, and the numbers but not the percentages of macrophages, neutrophils, and mast cells were increased. On histopathology, multifocal or diffuse interstitial fibrosis, type II pneumocyte hyperplasia, prominent intraalveolar macrophages, distortion of alveolar architecture, and emphysematous change were detected. Conclusion and Clinical Importance: IPF causes substantial hypoxemia. In HRCT, GGO is a consistent finding. IPF dogs have concurrent airway changes and an increase in BALF TCC.