Vasoproliferative process resembling pulmonary capillary hemangiomatosis in a cat.

BACKGROUND: Pulmonary capillary hemangiomatosis is a rare, vascular obstructive disorder that uniformly causes pulmonary arterial hypertension. Clinically, pulmonary capillary hemangiomatosis is indistinguishable from primary pulmonary arterial hypertension and histology is required for definitive diagnosis. The distinctive histologic feature of pulmonary capillary hemangiomatosis is non-malignant extensive proliferation of capillaries in the alveolar septae. Vasodilator treatment of humans with primary arterial hypertension due to pulmonary capillary hemangiomatosis can result in fatal acute pulmonary edema. Computed tomography is thus critical to discern pulmonary capillary hemangiomatosis from other causes of pulmonary arterial hypertension prior to vasodilator therapy. This is the first report of a vasoproliferative process resembling pulmonary capillary hemangiomatosis in the feline species. CASE PRESENTATION: A 15-year-old, male castrated, domestic shorthair cat presented for persistent labored breathing presumptively due to congestive heart failure despite treatment with diuretics for 7 days. Echocardiography showed evidence of hypertrophic cardiomyopathy with severe pulmonary hypertension; however, a normal sized left atrium was not consistent with congestive heart failure. Thoracic computed tomography was performed and showed evidence of diffuse ill-defined nodular ground glass opacities, enlarged pulmonary arteries, and filling defects consistent with pulmonary thromboembolism. The cat acutely decompensated after a single dose of sildenafil and was euthanized. Histopathology of the lungs showed severe multifocal alveolar capillary proliferation with respiratory bronchiolar infiltration, marked type II pneumocyte hyperplasia and multifocal pulmonary arterial thrombosis. CONCLUSION: This is the first description in a cat of a vasoproliferative disorder resembling pulmonary capillary hemangiomatosis complicated by multifocal pulmonary arterial thrombosis. Inspiratory and expiratory ventilator-driven breath holds with angiography revealed lesions predominantly characterized by ground glass opacification and vascular filling defects with absence of air trapping. The results from this report suggest that, as in humans, the cat can develop a pulmonary capillary hemangiomatosis-like disease in which vasodilator therapy to address pulmonary hypertension may lead to fatal pulmonary edema.

Long-term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma.

BACKGROUND: Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. OBJECTIVE: To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. METHODS: Cats with chronic, experimentally induced asthma received six intravenous infusions of MSCs (0.36-2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. RESULTS: There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. CONCLUSIONS AND CLINICAL RELEVANCE: When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic asthma.

Lung ultrasound nodule sign for detection of pulmonary nodule lesions in dogs: Comparison to thoracic radiography using computed tomography as the criterion standard.

Thoracic radiography (TR), the most common screening test for pulmonary metastases in dogs, can fail to detect small lesions <3 mm. Lung ultrasonography (LUS) is a widely available imaging modality capable of detecting peripheral nodules but is underutilized for this purpose. Thoracic computed tomography (CT) is the criterion standard for diagnosis of lung metastases and nodular disease but is less practical for a variety of reasons. We hypothesized that LUS would be more sensitive but less specific at detecting nodules consistent with metastatic pulmonary disease in dogs compared to TR, using CT as the criterion standard. This was a masked, single-center prospective study of 62 client-owned dogs evaluated for respiratory signs or pulmonary metastatic neoplasia screening using TR, LUS and CT. Dogs were included if metastatic pulmonary disease was a differential. All imaging modalities were scored as having nodules (yes/no) and other types of pathologic lesions were recorded. Sensitivity (Se), specificity (Sp) and positive (LR+) and negative likelihood ratios (LR-) were determined for TR and LUS. For TR, Se and Sp were 64% and 73%, and LR+ and LR- were 2.37 and 0.49, respectively. For LUS, Se and Sp were 60% and 65% and LR+ and LR- were 1.71 and 0.62, respectively. The results of the study indicate that LUS had a similar Se to TR, with both modalities missing nodules when used for screening. The low Sp and LR- suggests caution should be used when assuming TR and LUS rule out the presence of nodules.

Comparison between thoracic ultrasonography and thoracic radiography for the detection of thoracic lesions in dairy calves using a two-stage Bayesian method.

Infectious bronchopneumonia is a lower respiratory tract disease with major economic consequences in dairy calves. Thoracic radiography (TR) and thoracic ultrasonography (TUS) are two imaging diagnostic procedures available in bovine medicine for identifying thoracic lesions. However, no study has investigated whether one of these tests is superior to the other or if they provide comparable results for the detection of thoracic lesions in calves. The objective of this study was therefore to estimate and to compare the performances of TUS and TR for the detection of thoracic lesions in dairy calves. A prospective cross-sectional study was performed in a hospital setting. A total of 50 calves (≥7 days old; ≤100 kg; standing; pCO2 ≥ 53 mmHg; any reason of presentation) were enrolled. Every calf underwent TUS and TR. Only calves with thoracic lesions on TUS and/or TR were controlled by thoracic computed tomography (CT) (the gold standard). Calves without lesions were not controlled by CT. A two-stage Bayesian framework was used. The sensitivities (Se) and specificities (Sp) of both tests individually and used in series or parallel were estimated. The Se and Sp of TUS were 0.81 (95 % BCI (Bayesian Credible Interval): 0.65; 0.92) and 0.90 (95 % BCI: 0.81; 0.96), respectively. The Se and Sp of TR were 0.86 (95 % BCI: 0.62; 0.99) and 0.89 (95 % BCI: 0.67; 0.99), respectively. This study did not reveal any differences between both tests. Using TUS and TR in series was more specific than using both tests in parallel. The performances of TUS alone were not different from the performances of both tests in series or in parallel. In conclusion, TUS and TR were equivalent in detecting thoracic lesions in this study. Using TUS alone allowed an accurate detection of thoracic lesions in dairy calves. Further studies enrolling a larger sample (> 400 calves) and allowing adequate power to be achieved would be necessary to confirm these results.

Aerodigestive disorders in dogs evaluated for cough using respiratory fluoroscopy and videofluoroscopic swallow studies.

Aerodigestive diseases, hybrid disorders representing a pathologic link between respiratory and alimentary tracts, may manifest with respiratory signs without gastrointestinal signs. These are underdiagnosed in dogs due to poor clinical recognition and diagnostic limitations. We hypothesize that a subset of dogs presenting for cough without gastrointestinal signs would have occult aerodigestive disorders identified using videofluoroscopic swallow study (VFSS). Data were retrospectively obtained from 31 client-owned dogs presenting for cough, with thoracic radiographs, and a VFSS between April 2015 and December 2017. Exclusion criteria were cough of cardiac origin or gastrointestinal signs within 6 months. Swallow study parameters included pharyngeal/esophageal motility, laryngeal obstruction/defects, penetration-aspiration, reflux, excessive aerophagia, megaesophagus (ME), lower-esophageal sphincter achalasia-like syndrome (LES-AS), and sliding hiatal hernia (HH). The median (interquartile range) duration of cough was 4 (2-8) months. Thoracic radiographs were unremarkable in 11 dogs, with aspiration pneumonia suspected in seven. In 25/31 dogs (81%), VFSS abnormalities were detected and some dogs had more than one defect: pharyngeal (n=10) or esophageal hypomotility (n=10), reflux (n=9), penetration-aspiration (n=8), excessive aerophagia (n=6), laryngeal obstruction (n=3), ME (n=3), HH (n=2), and LES-AS (n=1). A respiratory disorder causing cough was identified in 17 dogs with VFSS abnormalities (laryngeal obstruction/defect and airway disease including chronic or eosinophilic bronchitis, tracheal/mainstem bronchial collapse, bronchiectasis, and bronchomalacia). An alimentary disorder identified on VFSS in absence of a discrete respiratory disorder causing cough was diagnosed in eight dogs. In conclusion, canine aerodigestive disorders can manifest as cough without alimentary signs. VFSS is a useful diagnostic to determine the contribution of esophageal/gastrointestinal pathology in dogs with cough.

Pulmonary hypertension secondary to respiratory disease and/or hypoxia in dogs: Clinical features, diagnostic testing and survival.

Pulmonary hypertension (PH) is associated with substantial morbidity and if untreated, mortality. The human classification of PH is based on pathological, hemodynamic characteristics, and therapeutic approaches. Despite being a leading cause of PH, little is known about dogs with respiratory disease and/or hypoxia (RD/H)-associated PH. Therefore, our objectives were to retrospectively describe clinical features, diagnostic evaluations, final diagnoses and identify prognostic variables in dogs with RD/H and PH. In 47 dogs identified with RD/H and PH, chronic airway obstructive disorders, bronchiectasis, bronchiolar disease, emphysema, pulmonary fibrosis, neoplasia and other parenchymal disorders were identified using thoracic radiography, computed tomography, fluoroscopy, tracheobronchoscopy, bronchoalveolar lavage, and histopathology. PH was diagnosed using transthoracic echocardiography. Overall median survival was 276.0 days (SE, 95% CI; 216, 0-699 days). Dogs with an estimated systolic pulmonary arterial pressure (sPAP) ≥47mmHg (n=21; 9 days; 95% CI, 0-85 days) had significantly shorter survival times than those <47mmHg (n=16; P=0.001). Estimated sPAP at a cutoff of ≥47mmHg was a fair predictor of non-survival with sensitivity of 0.78 (95% CI, 0.52-0.94) and specificity of 0.63 (95% CI, 0.38-0.84). Phosphodiesterase-5 (PDE5) inhibitor administration was the sole independent predictor of survival in a multivariable analysis (hazard ratio: 4.0, P=0.02). Canine PH is present in a diverse spectrum of respiratory diseases, most commonly obstructive disorders. Similar to people, severity of PH is prognostic in dogs with RD/H and PDE5 inhibition could be a viable therapy to improve outcome.

Carotid Endothelial VCAM-1 Is an Early Marker of Carotid Atherosclerosis and Predicts Coronary Artery Disease in Swine.

OBJECTIVE: The aim was to determine if endothelial VCAM-1 (eVCAM-1) expression in the common carotid artery (CCA) would correlate with predictive markers of atherosclerotic disease, would precede reduction of markers of endothelial cell function and would predict coronary artery disease (CAD). METHODS AND RESULTS: Carotid arterial segments (bifurcation, proximal and distal CCA) were harvested from 14 and 24 month-old male castrated familial hypercholesterolemic (FH) swine, a model of spontaneous atherosclerosis. Quantification of local expression of eVCAM-1, intimal macrophage accumulation, oxidative stress, intima-media (I/M) ratio, intima-media thickness (IMT), endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) in selected regions of the carotids revealed a relationship between local inflammation and atheroscle-rotic plaque progression. Importantly, inflammation was not uniform throughout the CCA. Endo-thelial VCAM-1 expression was the greatest at the bifurcation and increased with age. Finally, eV-CAM-1 best estimated the severity of CAD compared to blood levels of glucose, hypercholestero-lemia, carotid IMT, and p-eNOS. CONCLUSION: Our data suggested that eVCAM-1 was closely associated with atherosclerotic plaque progression and preceded impairment of EDD. Thus, this study supported the use of carotid VCAM-1 targeting agents to estimate the severity of CAD.