Clinicopathologic features,comorbid diseases,and prevalence of pulmonary hypertension in dogs with bronchomalacia

BackgroundReports of clinicopathologic features of bronchomalacia (BM) differ because of inconsistent definitions and frequent prevalence of comorbid cardiopulmonary disease. Pulmonary hypertension (PH) secondary to BM is poorly described.ObjectivesDogs with BM will be older but of any somatotype, and increased expiratory effort, ≥1 comorbid disease, and PH will be more common than in dogs without BM.AnimalsClient‐owned dogs (n = 210) evaluated for respiratory signs.MethodsMedical records of dogs with paired inspiratory: expiratory‐breath‐hold computed tomography, tracheobronchoscopy, or both between January 2016 and December 2019 were retrospectively reviewed. Comparisons between dogs with and without BM using Mann‐Whitney rank sum or χ ² tests (P < .05 significant were made). Because of high numbers of variables, criteria with high prevalence (>25%) were identified (n = 10) for univariate analysis (P < .005 significant). Significant variables were submitted for multivariate analysis.ResultsBronchomalacia was identified in 41% of dogs of all sizes/somatotypes; 38% were >10 kg. All dogs with BM had ≥1 comorbid cardiopulmonary disorder. Dogs with BM were significantly older (P < .001), smaller (P < .001), and were more likely diagnosed with tracheal or mainstem bronchial collapse (P < .001) or bronchiectasis (P < .001). Multivariate analysis confirmed associations with age, tracheal or mainstem bronchial collapse, and bronchiectasis. In dogs with BM, PH was more prevalent.Conclusions and Clinical ImportanceAlthough significantly more common in older, smaller dogs, BM occurs in dogs of all sizes and in all instances with comorbidities. Echocardiography should be considered in dogs with BM to identify PH.     

Secretoglobin and Transferrin Expression in Bronchoalveolar Lavage Fluid of Horses with Chronic Respiratory Disease

Background

Lower expression of secretoglobin and transferrin has been found in the bronchoalveolar lavage fluid (BALF) of a small number of horses with experimentally induced signs of recurrent airway obstruction (RAO) compared to healthy controls.

Hypothesis/Objectives

Secretoglobin and transferrin BALF expression will be similarly decreased in horses with naturally occurring clinical signs of RAO and in horses with experimentally induced clinical signs of RAO as compared to healthy controls and intermediate in horses with inflammatory airway disease (IAD).

Animals

Recurrent airway obstruction‐affected and control horses were subjected to an experimental hay exposure trial to induce signs of RAO. Client‐owned horses with a presumptive diagnosis of RAO and controls from the same stable environments were recruited.

Methods

Pulmonary function and BALF were evaluated from control and RAO‐affected research horses during an experimental hay exposure trial (n = 5 in each group) and from client‐owned horses (RAO‐affected horses, n = 17; IAD‐affected horses, n = 19; healthy controls, n = 5). The concentrations of secretoglobin and transferrin in BALF were assessed using Western blots.

Results

Naturally occurring and experimentally induced RAO horses had similar decreases in BALF transferrin expression, but secretoglobin expression was most decreased in naturally occurring RAO. Secretoglobin and transferrin expression were both lower in BALF of RAO‐affected horses than in IAD‐affected and control horses.

Conclusions and Clinical Importance

Secretoglobin and transferrin expression is decreased in BALF of RAO‐affected horses after both experimental and natural exposure. Secretoglobin and transferrin likely play clinically relevant roles in the pathophysiology of RAO, and may thus be used as biomarkers of the disease.     

Quantification of nasal airflow resistance in English bulldogs using computed tomography and computational fluid dynamics

Stenotic nares, edematous intranasal turbinates, mucosal swelling, and an elongated, thickened soft palate are common sources of airflow resistance for dogs with brachycephalic airway syndrome. Surgery has focused on enlarging the nasal apertures and reducing tissue of the soft palate. However, objective measures of surgical efficacy are lacking. Twenty‐one English bulldogs without previous surgery were recruited for this prospective, pilot study. Computed tomography was performed using conscious sedation and without endotracheal intubation using a 128 multidetector computed tomography scanner. Raw multidetector computed tomography data were rendered to create a three‐dimensional surface mesh model by automatic segmentation of the air‐filled nasal passage from the nares to the caudal soft palate. Three‐dimensional surface models were used to construct computational fluid dynamics models of nasal airflow resistance from the nares to the caudal aspect of the soft palate. The computational fluid dynamics models were used to simulate airflow in each dog and airway resistance varied widely with a median 36.46 (Pa/mm)/(l/s) and an interquartile range of 19.84 to 90.74 (Pa/mm)/(/s). In 19/21 dogs, the rostral third of the nasal passage exhibited a larger airflow resistance than the caudal and middle regions of the nasal passage. In addition, computational fluid dynamics data indicated that overall measures of airflow resistance may significantly underestimate the maximum local resistance. We conclude that computational fluid dynamics models derived from nasal multidetector computed tomography can quantify airway resistance in brachycephalic dogs. This methodology represents a novel approach to noninvasively quantify airflow resistance and may have utility for objectively studying effects of surgical interventions in canine brachycephalic airway syndrome.     

Pharmacokinetics of a modified,compounded theophylline product in dogs

Theophylline is a commonly used bronchodilator drug for treatment of chronic canine bronchitis, but no formulations validated in dogs are currently available. An oral, modified and compounded theophylline product (MCT), which could fulfil this need, is available through a USP‐compliant, veterinary compounding pharmacy; however, its pharmacokinetic properties are unknown. The aim of this study was to determine the pharmacokinetics of MCT. Plasma drug concentrations were measured in seven healthy, fed dogs after single doses of intravenous aminophylline (8.6 mg/kg theophylline equivalent) and oral MCT (10 mg/kg). Systemic bioavailability of the MCT was 96.2 ± 32.9%. MCT times to maximum concentration, mean absorption time and terminal half‐life were 8.85 ± 3.63, 6.95 ± 3.42, and 8.67 ± 1.62 hr, respectively. Based on simulations of 10 mg/kg and 12‐hr dosing, steady‐state plasma theophylline concentrations are expected to exceed the minimum therapeutic concentration for 71.7 ± 35.6% of the dosing interval. Overall, the MCT product investigated showed similar pharmacokinetic characteristics compared to previously validated extended‐release theophylline products. An oral dose of 10 mg/kg q 12 hr is likely an appropriate dosage to begin therapy; however, therapeutic drug monitoring may be warranted because of inter‐individual variation.     

Investigating the Link between Particulate Exposure and Airway Inflammation in the Horse

Inhalant exposure to airborne irritants commonly encountered in horse stables is implicated in the pathogenesis of inflammatory airway disease (IAD) and recurrent airway obstruction (RAO), non‐infectious, inflammatory pulmonary disorders that impact the health and performance of horses across all equine disciplines. IAD and RAO have overlapping clinical, cytological, and functional manifestations of the pulmonary response to organic dust and noxious gases encountered in the barn environment. Study of these diseases has provided important but incomplete understanding of the effect of air quality upon the respiratory health of horses. In this review, the principles of particulate exposure assessment, including health‐related aerosol size fractions and size‐selective sampling, the factors influencing air quality in equine environments, and the effect of air quality on the equine respiratory tract are discussed. The objective of this review is to provide the reader with a summary of the most common chronic inflammatory airway diseases in the horse and the principles of air sampling that are essential to the planning, interpretation, and assessment of equine respiratory health‐related exposure studies.     

Effect of long-term fluticasone treatment on immune function in horses with heaves

Background: Corticosteroids currently are the most effective pharmacological treatment available to control heaves in horses. Systemically administered corticosteroids have been shown to alter immune response in horses, humans, and other species. Aerosolized administration theoretically minimizes systemic adverse effects, but the effect of inhaled corticosteroids on immune function has not been evaluated in horses. Objectives: To evaluate the effects of prolonged administration of inhaled fluticasone on the immune system of heaves‐affected horses. Animals: Heaves‐affected horses were treated with inhaled fluticasone (n = 5) for 11 months or received environmental modifications only (n = 5). Methods: Prospective analysis. Clinical parameters and CBC, lymphocyte subpopulations and function, and circulating neutrophil gene expression were sequentially measured. Primary and anamnestic immune responses also were evaluated by measuring antigen‐specific antibodies in response to vaccination with bovine viral antigen and tetanus toxoid, respectively. Results: No clinical adverse effects were observed and no differences in immune function were detected between treated and untreated horses. Conclusions and Clinical Importance: The treatment of heaves‐affected horses with inhaled fluticasone at therapeutic dosages for 11 months has no significant detectable effect on innate and adaptive (both humoral and cell‐mediated) immune parameters studied. These results suggest that prolonged administration of fluticasone would not compromise the systemic immune response to pathogens nor vaccination in adult horses.     

Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance

Reasons for performing study: Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. Objective: To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. Methods: Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airway endoscopy. Relationships between horse demographics, resting endoscopic findings, treadmill intensity and implementation of head and neck flexion during exercise with exercising endoscopic findings were examined. Results: Dynamic upper airway obstructions were observed in 72% of examinations. Head and neck flexion was necessary to obtain a diagnosis in 21 horses. Pharyngeal wall collapse was the most prevalent upper airway abnormality, observed in 31% of the examinations. Complex abnormalities were noted in 27% of the examinations. Resting laryngeal dysfunction was significantly associated with dynamic arytenoid collapse and the odds of detecting intermittent dorsal displacement of the soft palate (DDSP) during exercise in horses with resting DDSP was only 7.7%. Exercising endoscopic observations were different from the resting observations in 54% of examinations. Conclusions: Dynamic upper airway obstructions were common in nonracing performance horses with respiratory noise and/or poor performance. Resting endoscopy was only helpful in determining exercising abnormalities with recurrent laryngeal neuropathy. Potential relevance: This study emphasises the importance of exercising endoscopic evaluation in nonracing performance horses with abnormal respiratory noise and/or poor performance for accurate assessment of dynamic upper airway function.     

Efficacy of oral prednisolone and dexamethasone in horses with recurrent airway obstruction in the presence of continuous antigen exposure

Reasons for performing study: Orally administered prednisolone and dexamethasone are used commonly in the treatment of recurrent airway obstruction (RAO) in horses. However, the efficacy of prednisolone in improving pulmonary function during continuous antigen exposure has not been evaluated critically and there is little evidence supporting the efficacy of low‐dose oral dexamethasone in the same conditions. Hypothesis: Oral prednisolone and dexamethasone improve pulmonary function in RAO under conditions of continuous antigen exposure, and dexamethasone is more effective than prednisolone at commonly used dosages. Methods: Using a randomised crossover design, prednisolone (2 mg/kg bwt) and dexamethasone (0.05 mg/kg bwt) were administered per os, s.i.d. for 7 days, to 7 horses during clinical exacerbation of the disease. Maximal difference in transpulmonary pressure (ΔP_L), lung resistance (R_L) and elastance (E_L) were measured before and after 3 and 7 days of treatment. Results: Prednisolone and dexamethasone improved pulmonary function significantly. However, the improvement was of greater magnitude after 3 and 7 days of treatment with dexamethasone compared to prednisolone. Also, after 7 days of treatment with dexamethasone, ΔP_L and R_L were not different from values obtained when horses were on pasture, while all 3 pulmonary function parameters remained different from pasture values after prednisolone treatment. Conclusions: Both corticosteroids improve pulmonary function, in spite of continuous antigen exposure. However, oral dexamethasone at 0.05 mg/kg bwt is more effective than prednisolone at 2 mg/kg bwt in the treatment of RAO. Potential relevance: Prednisolone was shown, for the first time, to our knowledge, to improve the pulmonary function of horses with RAO in the presence of continuous antigen exposure. This study also demonstrates the efficacy of low‐dose oral dexamethasone in reversing airway obstruction in these conditions.