Effects of positive end-expiratory pressure and 30% inspired oxygen on pulmonary mechanics and atelectasis in cats undergoing non-bronchoscopic bronchoalveolar lavage.

Objectives The objective of this study was to determine if modification of inspired oxygen concentration or positive end-expiratory pressure (PEEP) would alter bronchoalveolar lavage (BAL)-induced changes in pulmonary mechanics or atelectasis, as measured using ventilator-acquired pulmonary mechanics and thoracic CT. Methods Six experimentally asthmatic cats underwent anesthesia and non-bronchoscopic BAL, each under four randomized treatment conditions: 100% oxygen, zero PEEP; 30% oxygen, zero PEEP; 100% oxygen, PEEP 2 cmH2O; and 30% oxygen, PEEP 2 cmH2O. Pulse oximetry was used to estimate oxygen saturation (SpO2). Ventilator-acquired pulmonary mechanics and thoracic CT scans were collected prior to BAL and at 1, 5 and 15 mins post-BAL. Results While receiving 100% oxygen, no cat had SpO2 <91%. Some cats receiving 30% oxygen had decreased saturation immediately post-BAL (mean ± SD 70.8 ± 31%), but 6/8 of these had SpO2 >90% by 1 min later. There was a significant increase in airway resistance and a decrease in lung compliance following BAL, but there was no significant difference between treatment groups. Cats receiving no PEEP and 30% oxygen conserved better aeration of the lung parenchyma in BAL-sampled areas than those receiving no PEEP and 100% oxygen. Conclusions and relevance Alterations in pulmonary mechanics or atelectasis may not be reflected by SpO2 following BAL. The use of 30% inspired oxygen concentration failed to show any significant improvement in pulmonary mechanics but did diminish atelectasis. In some cats, it was also associated with desaturation of hemoglobin. The use of PEEP in this study did not show any effect on our outcome parameters. Further studies using higher PEEP (5-10 cmH2O) and intermediate inspired oxygen concentration (40-60%) are warranted to determine if they would confer clinical benefit in cats undergoing diagnostic BAL.

Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of feline asthma.

OBJECTIVES: Feline allergic asthma is a chronic inflammatory disorder of the lower airways that may manifest with acute, life-threatening clinical signs. Tachykinins released from sensory nerves and immune cells binding neurokinin (NK)-1, NK-2 and NK-3 receptors have been implicated in asthma pathogenesis. Maropitant, an NK-1 receptor antagonist, blocks neuroimmune pathways and may be a viable treatment option for cats in asthmatic crisis. Using an experimental chronic allergic feline asthma model, we hypothesized that a single dose of maropitant given immediately after allergen challenge would blunt clinical signs, airway hyperresponsiveness (AHR) and airway eosinophilia. METHODS: Cats (n = 7) induced to have an asthmatic phenotype using Bermuda grass allergen (BGA) were enrolled in a prospective, placebo-controlled crossover design study. Cats randomly received maropitant (2 mg/kg SC) or placebo (saline SC) immediately post-BGA challenge, followed 12 h later by pulmonary mechanics testing and measurement of airway eosinophils. After a 2 week washout, cats were crossed-over to the alternate treatment. Study endpoints included subjective clinical scoring systems post-BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine and collection of bronchoalveolar lavage fluid to quantify airway eosinophilia. Data were analyzed using a Mann-Whitney rank sum test with P <0.05 considered significant. RESULTS: A single injection of maropitant failed to diminish clinical composite score (P = 0.902), visual analogue scale scoring (P = 0.710), AHR (P = 0.456) or airway eosinophilia (P = 0.165) compared with placebo. CONCLUSIONS AND RELEVANCE: A single injection of maropitant given immediately post-allergen challenge was ineffective at blunting clinical signs, AHR and airway eosinophilia, and cannot be recommended as treatment for feline status asthmaticus.

The TRPV1 receptor agonist capsaicin is an ineffective bronchoprovocant in an experimental model of feline asthma.

OBJECTIVES: Airway hyper-responsiveness (AHR), a key feature of feline asthma, can be measured using bronchoprovocation testing. Limitations of both direct and indirect bronchoprovocants evaluated to date in experimental feline asthma have led to a search for a more specific indirect bronchoprovocant (ie, one which relies on existing inflammatory cells or activated neural pathways in diseased but not healthy airways). We hypothesized that capsaicin, a transient receptor potential cation channel subfamily V member 1 agonist, would lead to dose-responsive increases in airway resistance as measured by ventilator-acquired pulmonary mechanics in experimentally asthmatic cats. METHODS: Five cats induced to have asthma using Bermuda grass allergen (BGA) were studied. Twenty-four hours after aerosol challenge of BGA, cats were anesthetized and underwent neuromuscular blockade for ventilator-acquired pulmonary mechanics. Cats were monitored with pulse oximetry for hemoglobin desaturation. Parameters recorded on a breath-by-breath basis on the ventilator included airway resistance (Raw) and compliance. Saline at baseline and 10-fold increasing concentrations of capsaicin (0.4-4000.0 µM) were aerosolized for 30 s and data collected for 4 mins between doses. The intended endpoint of the study was a doubling in baseline airway resistance, halving of compliance or oxygen desaturation <75%. RESULTS: All cats completed the trial, reaching the highest dose of capsaicin without reaching any of the aforementioned endpoints. No biologically significant alteration in any other pulmonary mechanics parameter was noted. CONCLUSIONS AND RELEVANCE: Capsaicin does not appear to be an effective bronchoprovocant in a feline asthma model.