Factors influencing the response to therapy in dogs with eosinophilic bronchopneumopathy.

OBJECTIVES: Canine eosinophilic bronchopneumopathy (EBP) is a poorly understood disease characterized by chronic inflammation of the lower airways. To date, factors affecting the course of the disease are largely unknown. The objective of this study was to investigate the influence of clinical, laboratory, and environmental factors on therapeutic outcome in dogs with EBP. MATERIAL AND METHODS: Environmental and housing conditions, course of disease, and response to treatment were evaluated using a standardized questionnaire for owners of 29 dogs diagnosed with EBP from 3 different veterinary referral centers in Germany. Data of diagnostic tests (hematology, radiographs, bronchoalveolar-lavage-fluid-(BALF) cytology) were retrospectively obtained from medical records. The influence of the different factors was assessed using Fisher's-exact-test and Mann-Whitney-U- or Kruskal-Wallis-test. RESULTS: The proportion of neutrophilic granulocytes in BALF-cytology was significantly higher in dogs with persistent clinical signs compared to dogs that achieved clinical remission (p=0.029). Duration of clinical signs before treatment was significantly longer in dogs with persistent clinical signs (16±12 months) compared to dogs that achieved clinical remission (6±7 months) (p=0.017). CONCLUSION: Early diagnosis and therapy have a decisive influence on the success of treatment. CLINICAL RELEVANCE: Dogs with respiratory signs suspicious for EBP should be evaluated in a timely manner to increase the likelihood of clinical remission with an early start of therapy.

Topographical distribution and radiographic pattern of lung lesions in canine eosinophilic bronchopneumopathy.

OBJECTIVES: To evaluate the radiographic lung pattern and topographical distribution in canine eosinophilic bronchopneumopathy. MATERIALS AND METHODS: Medical records were retrospectively reviewed for dogs diagnosed with eosinophilic bronchopneumopathy. Lateral thoracic radiographs were examined for the presence of increased radiopacity, classification of pattern, topography of lung changes (cranioventral, perihilar, caudodorsal, caudoventral) and severity of pulmonary lesions. RESULTS: Forty-four cases were identified with the Labrador retriever being the most commonly affected breed; there was a mean age of 5 years and an equal gender distribution. Coughing was the most common clinical sign. Circulating eosinophilia was present in 39% of dogs, with a mean peripheral eosinophilia of 5.1×109 cells/L and a mean bronchoalveolar lavage fluid eosinophilia of 40%. Eighty percent of dogs had an abnormal lung pattern in at least one of the four lung fields; the remaining had normal thoracic radiographs. The most common patterns were a bronchial and a bronchointerstitial pattern, with 41 and 89% distribution to the caudodorsal lung field, respectively. CLINICAL SIGNIFICANCE: A bronchial and bronchointerstitial pattern are the most common radiographic lung patterns seen in canine eosinophilic bronchopneumopathy with these patterns most frequently topographically distributed to at least the caudodorsal lung field. Furthermore, within the caudodorsal lung field, a bronchointerstitial pattern predominates. This radiographic and topographical finding may allow eosinophilic bronchopneumopathy to take precedence on a differential diagnoses list before confirmatory bronchoalveolar lavage fluid sampling.

Clinical features and long-term follow-up of 70 cases of canine idiopathic eosinophilic lung disease.

BACKGROUND: Canine idiopathic eosinophilic lung disease (ELD) is sparsely documented in the literature. METHODS: Clinical presentation and outcome of dogs diagnosed with ELD (eosinophilic bronchitis or eosinophilic bronchopneumonia) were reviewed. Subgroups were made based on chronicity of clinical signs and findings of thoracic imaging: NCI (no changes in thoracic imaging), BRON (bronchial/peribronchial pattern), INT (bronchointerstitial/interstitial/alveolar). RESULTS: Seventy cases were included. There were more young to adult, crossbreed and female dogs. Compared with the other two groups NCI dogs showed lower bronchoalveolar lavage fluid eosinophilic pleocytosis and absence of circulating eosinophilia, bronchiectasis or death due to respiratory disease. All dogs responded clinically to corticosteroids. Median treatment duration was four months. Remission (no clinical signs after treatment discontinuation for >one month) and long-term remission (>six months) was achieved in 60 per cent, and 51 per cent of patients, respectively. Relapse occurred in 26 per cent of cases after remission but was rare (3 per cent) after long-term remission. The one-year, two-year and four-year survival to death due to respiratory disease was 98 per cent, 97 per cent and 91 per cent, respectively. CONCLUSION: Prognosis and initial clinical response for ELD was generally good although achievement of long-term remission was only seen in 51 per cent of dogs. Different outcomes based on chronicity of signs, corticosteroid dose, thoracic imaging abnormalities and other clinical variables were not appreciated.

Eosinophilic bronchitis, eosinophilic granuloma, and eosinophilic bronchopneumopathy in 75 dogs (2006-2016).

BACKGROUND: Eosinophilic lung disease is a poorly understood inflammatory airway disease that results in substantial morbidity. OBJECTIVE: To describe clinical findings in dogs with eosinophilic lung disease defined on the basis of radiographic, bronchoscopic, and bronchoalveolar lavage fluid (BAL) analysis. Categories included eosinophilic bronchitis (EB), eosinophilic granuloma (EG), and eosinophilic bronchopneumopathy (EBP). ANIMALS: Seventy-five client owned dogs. METHODS: Medical records were retrospectively reviewed for dogs with idiopathic BAL fluid eosinophilia. Information abstracted included duration and nature of clinical signs, bronchoscopic findings, and laboratory data. Thoracic radiographs were evaluated for the pattern of infiltrate, bronchiectasis, and lymphadenomegaly. RESULTS: Thoracic radiographs were normal or demonstrated a bronchial pattern in 31 dogs assigned a diagnosis of EB. Nine dogs had intraluminal mass lesions and were bronchoscopically diagnosed with EG. The remaining 35 dogs were categorized as having EBP based on radiographic changes, yellow green mucus in the airways, mucosal changes, and airway collapse. Age and duration of cough did not differ among groups. Dogs with EB were less likely to have bronchiectasis or peripheral eosinophilia, had lower total nucleated cell count in BAL fluid, and lower percentage of eosinophils in BAL fluid compared to dogs in the other 2 groups. In contrast to previous reports, prolonged survival (>55 months) was documented in dogs with EG. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with eosinophilic lung disease can be categorized based on imaging, bronchoscopic and BAL fluid cytologic findings. Further studies are needed to establish response to treatment in these groups.

Bronchoalveolar lavage fluid lymphocytosis in 104 dogs (2006-2016).

BACKGROUND: Bronchoalveolar lavage (BAL) fluid cytology and culture are used to characterize respiratory diseases in dogs. Little is known about disorders associated with increased numbers of lymphocytes in BAL fluid. OBJECTIVE: To evaluate duration of clinical signs and detection of specific respiratory diagnoses in dogs with BAL lymphocytosis. ANIMALS: One-hundred four client-owned dogs evaluated for respiratory signs. METHODS: Medical records of dogs that had >300 cells/µL and >20% lymphocytes on a differential cell count of BAL fluid between January 1, 2006, and January 1, 2016, were reviewed retrospectively. Cases were evaluated for the duration of clinical signs and respiratory diagnoses, including aspiration injury, infectious or inflammatory respiratory disease, and airway collapse. RESULTS: Dogs ranged in age from 0.5 to 16 years (median, 7.9 years) and had a median body weight of 11.4 kg (range, 2.0-42.7 kg). Eosinophilic lung disease was documented in 13 of 104 dogs (Group 1) and airway neutrophilia associated with infectious or inflammatory disease was found in 59 of 104 dogs (Group 2). Lymphocytosis alone in BAL fluid was described in 32 dogs (Group 3). Duration of cough did not differ among groups, but airway collapse was significantly more common in dogs with solitary lymphocytosis than in those with other types of inflammation. CONCLUSIONS AND CLINICAL IMPORTANCE: Lymphocytosis in BAL fluid is common in dogs and, in many cases, likely represents a common response to airway injury, independent of the type or duration of insult. It is unknown whether airway collapse leads to lymphocytosis or if the inflammatory process causes airway collapse.

Reflux aspiration in lungs of dogs with respiratory disease and in healthy West Highland White Terriers.

BACKGROUND: Gastroesophageal reflux and microaspiration (MA) of gastric juice are associated with various human respiratory diseases but not in dogs. OBJECTIVE: To detect the presence of bile acids in bronchoalveolar lavage fluid (BALF) of dogs with various respiratory diseases. ANIMALS: Twenty-seven West Highland White Terriers (WHWTs) with canine idiopathic pulmonary fibrosis (CIPF), 11 dogs with bacterial pneumonia (BP), 13 with chronic bronchitis (CB), 9 with eosinophilic bronchopneumopathy (EBP), 19 with laryngeal dysfunction (LD), 8 Irish Wolfhounds (IWHs) with previous BPs, 13 healthy WHWTs, all privately owned dogs, and 6 healthy research colony Beagles METHODS: Prospective cross-sectional observational study with convenience sampling of dogs. Bile acids were measured by mass spectrometry in BALF samples. Total bile acid (TBA) concentration was calculated as a sum of 17 different bile acids. RESULTS: Concentrations of TBA were above the limit of quantification in 78% of CIPF, 45% of BP, 62% of CB, 44% of EBP, 68% of LD, and 13% of IWH dogs. In healthy dogs, bile acids were detected less commonly in Beagles (0/6) than in healthy WHWTs (10/13). Concentrations of TBA were significantly higher in CIPF (median 0.013 µM, range not quantifiable [n.q.]-0.14 µM, P < .001), healthy WHWTs (0.0052 µM, n.q.-1.2 µM, P = .003), LD (0.010 µM, n.q.-2.3 µM, P = .015), and CB (0.0078 µM, n.q.-0.073 µM, P = .018) groups compared to Beagles (0 µM, n.q.). CONCLUSION AND CLINICAL IMPORTANCE: These results suggest that MA occurs in various respiratory diseases of dogs and also in healthy WHWTs.

Detection of specific bacterial agents by quantitative PCR assays in the bronchoalveolar lavage fluid of dogs with eosinophilic bronchopneumopathy vs. dogs with chronic bronchitis and healthy dogs.

In humans, Mycoplasma pneumoniae and Bordetella pertussis infections are suggested to trigger or exacerbate asthma. Whether Mycoplasma or Bordetella are associated with chronic inflammatory bronchial diseases in dogs has not been investigated. The aim of this study was to assess detection rates of Mycoplasma canis (M. canis), M. cynos and Bordetella bronchiseptica (Bb), in dogs with eosinophilic bronchopneumopathy (EBP) and chronic bronchitis (CB), compared with healthy dogs. Specific quantitative PCR (qPCR) analysis for M. canis, M. cynos and Bb were retrospectively performed on bronchoalveolar lavage fluid (BALF) collected from 24 dogs with EBP, 21 dogs with CB and 15 healthy dogs. Possible associations between qPCR results and age, BALF cytology or clinical severity scores (CSS) in dogs with EBP were investigated. There was no difference in M. canis, M. cynos and Bb detection rates in dogs with EBP (n=6, n=2 and n=6, respectively) and dogs with CB (n=2, n=2 and n=2, respectively) compared with control dogs (n=4, n=2 and n=2, respectively). In dogs with EBP, the proportion that were qPCR-positive for Bb was higher in dogs with higher CSS (P=0.014) and BALF from Bb-positive dogs had higher percentage of neutrophils (P<0.001). Among dogs that were qPCR-positive for Bb, moderate to high loads were only detected in dogs with EBP. M. canis and M. cynos detection was not associated with EBP or CB; higher Bb loads were only present in dogs with EBP and high CSS. A possible cause and effect relationship between Bb infection or load and EBP remains unclear and requires further investigation.

Long-term follow-up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy.

BACKGROUND: Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described. OBJECTIVES: Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy. METHODS: Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test. RESULTS: Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism. CLINICAL SIGNIFICANCE: Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment.

Elevation of serum surfactant protein-A with exacerbation in canine eosinophilic pneumonia.

A 7-year-old female spayed Labrador Retriever was admitted to our hospital, because of cough with sputum. She was diagnosed as having canine eosinophilic pneumonia (CEP) based on blood eosinophilia, bronchial pattern and infiltrative shadow observed on thoracic radiography, bronchiolar obstruction and air-space consolidation predominantly affecting the right caudal lung lobe, as revealed by computed tomography (CT), predominant eosinophils in CT-guided fine needle aspiration and the clinical course. She exhibited a good response to steroid therapy, and the cough disappeared. The serum surfactant protein (SP)-A level increased with the aggravated symptom and decreased markedly with improvement compared with the C-reactive protein level and the number of eosinophils. We propose that serum SP-A level is a good biomarker in CEP.

Computed tomographic findings in 15 dogs with eosinophilic bronchopneumopathy.

Eosinophilic bronchopneumopathy is a disease characterized by the infiltration of the lung and bronchial mucosa by eosinophils. The aim of the present study was to describe the CT findings in a large series of dogs with confirmed diagnosis of eosinophilic bronchopneumopathy. Computed tomographic scans of 15 dogs with confirmed diagnosis of eosinophilic bronchopneumopathy were evaluated retrospectively by two boarded radiologists who reached a consensus. Abnormalities were identified in 14/15 (93%) dogs, including pulmonary parenchymal abnormalities in 14/15 (93%) dogs, bronchial wall thickening in 13 (87%) dogs, which was considered marked in eight (53%), plugging of the bronchial lumen by mucus/debris in 11 (73%) dogs, and bronchiectasis in nine (60%) dogs. Pulmonary nodules were identified in 5/15 (33%) dogs including one dog with a mass. All dogs with a nodular lung pattern had additional abnormalities. Lymphadenopathy was present in 10 dogs (67%). Lesions associated with eosinophilic bronchopneumopathy are variable and heterogeneous and encompass a wider variety of computed tomographic features than reported previously. Computed tomographic images were abnormal in the majority of affected dogs, hence CT is a useful modality to characterize the nature and distribution of thoracic lesions in dogs with eosinophilic bronchopneumopathy.

Correlation of bronchoalveolar eosinophilic percentage with airway responsiveness in cats with chronic bronchial disease.

OBJECTIVES: To retrospectively assess the relationship between bronchoalveolar lavage fluid analysis and lung function parameters as assessed by means of barometric whole body plethysmography and airway responsiveness testing in cats with chronic bronchial disease and to evaluate the potential application of barometric whole body plethysmography and airway responsiveness testing to distinguish between eosinophilic and non-eosinophilic bronchitis. METHODS: Twelve cats presented for chronic bronchial disease with complete bronchoalveolar lavage fluid and barometric whole body plethysmography data were identified. Cats were retrospectively assigned to eosinophilic bronchitis or non-eosinophilic bronchitis groups on the basis of bronchoalveolar lavage fluid eosinophil percentage (threshold 17%). Airway responsiveness was quantified by calculating the concentration of carbachol-inducing bronchoconstriction (C-Penh-300), defined as a 300% increase of basal enhanced pause (Penh). RESULTS: Log Penh was significantly higher and C-Penh-300 significantly lower in eosinophilic bronchitis cats compared to non-eosinophilic bronchitis cats (P=0·031 and P=0·032, respectively). Bronchoalveolar lavage fluid eosinophil percentage was moderately correlated with log Penh (P=0·012, r=0·70) and showed a weak inverse correlation with C-Penh-300 (P=0·047, r=-0·58). CLINICAL SIGNIFICANCE: This study provides supportive evidence of a correlation between airway eosinophilic inflammation and plethysmographic measures of bronchoconstriction and airway responsiveness. Further investigation of the use of barometric whole body plethysmography to differentiate between forms of chronic bronchial disease in cats is indicated.

Eosinophilic pulmonary granulomatosis in a young dog with prolonged remission after treatment.

A two-year-old Jack Russell terrier was presented for evaluation of chronic cough and exercise intolerance. Previous treatment with antibiotics and glucocorticoids had only partially ameliorated the clinical signs. During investigation, hypoxaemia, peripheral eosinophilia and an eosinophilic bronchoalveolar lavage fluid were noted. Thoracic radiographs revealed two ovoid clearly delineated soft-tissue opacities, one in the caudal segment of the left cranial lung lobe (diameter 26 mm) and the other in the right cranial lung lobe (diameter 20 mm). These findings were verified by computed tomography, which identified an additional smaller lesion (diameter 16 mm) dorsally in the right caudal lobe. Ultrasound-guided fine-needle aspiration samples confirmed the diagnosis of eosinophilic pulmonary granulomatosis and treatment with prednisolone and azathioprine was initiated. Within 1 month, granulomas were no longer detectable radiographically. All medication was discontinued after 7 months and currently, after 2·5 years, the dog remains free of clinical signs. To the authors' knowledge this is the first case report to describe prolonged remission from idiopathic canine eosinophilic pulmonary granulomatosis.

Cuterebrid myiasis (Diptera: Oestridae) in captive ring-tailed lemurs (Lemur catta) at a South Carolina zoo.

In September 2008, two ring-tailed lemurs (Lemur catta), comprising a mother-daughter pair, at the Greenville Zoo, Greenville, South Carolina, USA, were diagnosed with cuterebrid myiasis (Diptera: Oestridae) subsequent to sudden death of the adult lemur. On necropsy, a single bot warble was discovered in the subcutis of the axillary region. Histopathology revealed a severe eosinophilic bronchopneumonia. The juvenile lemur was inspected and found to have warbles on three separate dates in late September. One representative bot fly larva was identified as a Cuterebra sp. that normally infests lagomorphs in the southeastern United States. Cuterebrid myiasis is rarely reported in lemurs and has not been previously associated with pneumonia or death in these animals.

Diffuse cylindrical bronchiectasis due to eosinophilic bronchopneumopathy in a dog.

A miniature pinscher-cross was evaluated for chronic coughing. Computed tomography and bronchoscopy revealed severe, diffuse, cylindrical bronchiectasis secondary to eosinophilic bronchopneumopathy. Computed tomography is the gold standard for diagnosis of bronchiectasis in humans, and should be further investigated in dogs as a means of characterizing severity and pattern of disease.

Idiopathic chronic eosinophilic pneumonia in 7 horses.

BACKGROUND: Idiopathic chronic eosinophilic pneumonia of horses is incompletely described. OBJECTIVES: To describe the physical examination, clinicopathologic, histopathologic, and radiographic features and response to corticosteroid treatment of idiopathic chronic eosinophilic pneumonia of horses. ANIMALS: Seven horses with eosinophilic pneumonia. METHODS: Retrospective, descriptive study. RESULTS: Anamnesis, clinical signs, and clinicopathologic and radiologic findings in 7 adult horses with histologically confirmed eosinophilic pneumonia were reviewed. The horses were examined for signs of chronic respiratory disease. The horses ranged in age from 8 to 20 years. Significant findings on physical examination included tachypnea and abnormal respiratory sounds. Thoracic radiography revealed severe diffuse interstitial patterns of increased pulmonary density in all horses. There was a predominance of eosinophils in bronchoalveolar lavage fluid (BALF), and 6 of 7 horses had peripheral blood eosinophilia. Lung biopsies revealed eosinophilic infiltrates in all horses. Dexamethasone was administered to 3 horses and resulted in short-term clinical improvement in all three. CONCLUSIONS AND CLINICAL IMPORTANCE: A diagnosis of idiopathic eosinophilic pneumonia should be considered in horses with a history of chronic pulmonary disease, diffuse interstitial pattern of increased pulmonary density on thoracic radiographs, and a predominance of eosinophils in BALF. Horses with this condition may show a temporary response to treatment with dexamethasone.

Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a first case report.

BACKGROUND: Eosinophilic bronchitis is a recently described, relatively benign condition in humans that is characterized by a corticosteroid-responsive chronic cough and sputum eosinophilia without the abnormalities of airway function seen in asthma. The exact cause of this condition is currently unknown, however has been associated with various occupational exposures in humans. It has also been reported to progress to irreversible airway obstruction. This disease has been reported in dogs and horses, but not in non-human primates. METHODS: Gross examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta, which died of severe non-responsive respiratory distress revealed that the lungs were markedly inflated and moist. RESULTS: Hematoxylin and eosin-stained sections from the lungs contained widespread accumulation of eosinophils, sloughed epithelial cells, and mucus centered around bronchioles and adjacent airways. There was no evidence of mast cell infiltration of peribronchiolar smooth muscle, goblet cell hyperplasia, or basement membrane thickening. CONCLUSIONS: This ruled out recurrent episodes as would be expected in asthma, favoring the diagnosis of an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic bronchitis-like features in a M. mulatta.

Clinical alterations and mRNA levels of IL-4 and IL-5 in bronchoalveolar cells of horses with transient pulmonary eosinophilia.

The aim of this study was to assess clinical signs and altered pulmonary cell expression of cytokines related to eosinophil kinetics in horses with pulmonary eosinophilia. Pulmonary eosinophilia was detected by bronchoalveolar lavage (BAL) in a group of standardbreds in training. Horses had detailed clinical examination, bronchoscopy, endobronchial biopsy and BAL on three occasions at approximately 6 month intervals. During the second sampling period BAL eosinophils were significantly elevated (p>0.010), with five horses having from 5% to 37% eosinophils in BAL. Neither detailed clinical examination parameters nor gene expression of IL-4 and IL-5 mRNA (real-time-PCR) were associated with BAL eosinophilia. Pulmonary eosinophilia abated without treatment apart from deworming. It appears that pronounced lung eosinophilia in horses can be transient, abate without specific treatment, and in this instance, lack correlation to upregulation of expression of either IL-4 or IL-5.

Effects of cyproheptadine and cetirizine on eosinophilic airway inflammation in cats with experimentally induced asthma.

OBJECTIVE: To determine whether oral administration of cyproheptadine or cetirizine blocks the action of serotonin and histamine, respectively, and results in diminished eosinophilic airway inflammation in cats with experimentally induced asthma. ANIMALS: 9 cats in which asthma was experimentally induced through exposure to Bermuda grass allergen (BGA) during a 3-month period. PROCEDURES: Cats were randomized to receive monotherapy with each of 3 treatments for 1 week: placebo (flour in a gelatin capsule, PO, q 12 h), cyproheptadine (8 mg, PO, q 12 h), or cetirizine (5 mg, PO, q 12 h). A 1-week washout period was allowed to elapse between treatments. Prior to and following each 1-week treatment period, blood and bronchoalveolar lavage fluid (BALF) samples were collected. The percentage of eosinophils in BALF was evaluated to determine treatment efficacy. Serum and BALF BGA-specific immunoglobulin contents and plasma and BALF histamine concentrations were determined via ELISAs. Plasma and BALF serotonin concentrations were measured by use of a fluorometric method. RESULTS: The mean +/- SD percentage of eosinophils in BALF did not differ significantly among treatment groups (placebo, 40 +/- 22%; cyproheptadine, 27 +/- 16%; and cetirizine, 31 +/- 20%). Among the treatment groups, BGA-specific immunoglobulin content and histamine and serotonin concentrations were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: In cats with experimentally induced asthma, cyproheptadine and cetirizine were not effective in decreasing airway eosinophilic inflammation or in altering several other measured immunologic variables. Neither cyproheptadine nor cetirizine can be advocated as monotherapy for cats with allergen-induced asthma.