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Practical Relevance: Feline inflammatory airway diseases, including (but not limited to) asthma, chronic bronchitis and bronchiectasis, are common and incurable disorders. These diseases require lifelong therapy and may result in substantial morbidity and, in some cases, mortality. Goals of therapy include reduction or resolution of clinical signs and the underlying pathologic processes driving those clinical signs. Inhalational therapy has the advantage of topical delivery of drugs to target tissues at higher doses with fewer systemic effects than oral medications. There are multiple options for delivery devices, and proper selection and training on the use of these devices - including acclimation of the cat to the device - can maximize therapeutic efficacy., Aim: As inhalational therapy is uncommonly used by many veterinarians and owners, this review article provides a foundation on the selection and use of devices and inhalant medications for specific feline inflammatory airway diseases. Cats present a unique challenge with respect to the use of inhalers, and easy-to-follow steps on acclimating them to the devices are provided. The review also discusses the mechanics of inhalational therapy and helps clarify why certain medications, such as albuterol (salbutamol), fluticasone or budesonide, are chosen for certain diseases. The ultimate aim is that the practitioner should feel more comfortable managing common airway diseases in cats., Evidence Base: In compiling their review, the authors searched the veterinary literature for articles in English that discuss inhalational therapy in cats, and which focus primarily on inhaled glucocorticoids and bronchodilators. While most literature on inhalational therapy in cats is based on experimental feline asthma models, there are some studies demonstrating successful treatment in cats with naturally occurring inflammatory airway disease.

Objectives: The aim of this study was to evaluate the results of serum allergen-specific IgE testing in cats with a clinical diagnosis of asthma and to determine if the number of allergens with positive IgE reactivity and magnitude of positive IgE responses would be associated with the severity of clinical signs or airway eosinophilia., Methods: Medical records from 2008 to 2018 were retrospectively reviewed. Inclusion required a diagnosis of feline asthma based on consistent clinicopathologic features and bronchoalveolar lavage (BAL) cytology with >10% eosinophils; additionally, cats needed to have the results of serum allergen-specific IgE tests., Results: Eighteen cases satisfied the inclusion criteria. Median age was 5 years and the most common presenting clinical sign was cough (n = 10/18). Most cats lived exclusively indoors (n = 13/18). The median percentage of BAL eosinophils was 47%. Serum allergen-specific IgE testing supported an underlying allergic etiology in 14/18 (78%) cats, with all but one having polysensitization. The severity of clinical signs and magnitude of airway eosinophilia did not correlate with the degree of positive IgE reactivity., Conclusions and Relevance: This study identified a strong association between the identification of allergen-specific IgE and cats with asthma, and the majority of these cats were polysensitized. However, larger numbers of allergens with positive IgE reactivity or magnitude of IgE reactivity were not significantly associated with clinical severity or airway eosinophilia. Knowledge of positive allergen-specific IgE results could guide allergen avoidance, regardless of the magnitude of IgE reactivity.

Objectives: The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental feline asthma model., Methods: Allergic asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after asthma induction. Infusions contained 2 × 10 6 , 4 × 10 6 , 4.7 × 10 6 , 1 × 10 7 and 1 × 10 7 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally asthmatic cats (combined with placebo-treated cats), and six healthy, non-asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays., Results: Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal <17%). Diminished airway hyper-responsiveness was noted in all MSC-treated compared with placebo-treated cats at day 133 (dose of methacholine to double baseline airway resistance: MSC-treated median 22.9 mg/ml [range 6.4-64.0]; individual placebo-treated cats 1.1 and 5.0 mg/ml). Lung attenuation (mean ± SEM MSC-treated -865 ± 12 Hounsfield units [HU]; untreated asthmatics -820 ± 11 HU; P = 0.004) and bronchial wall thickening scores (median [interquartile range] MSC-treated 0 [0-1.5]; untreated asthmatic 11.6 [7.3-27.3]; P = 0.010) were significantly reduced in MSC-treated vs untreated asthmatic cats, consistent with decreased airway remodeling at month 9. No clear immunologic mechanisms by which MSCs act were determined., Conclusions and Relevance: MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced asthmatic cats. Results warrant additional investigation of MSC therapy for asthma in cats., (© The Author(s) 2015.)

Objectives: Feline allergic asthma is a common chronic lower airway disease characterized by clinical signs attributed to eosinophilic inflammation, airway hyper-responsiveness (AHR) and airway remodeling. Tachykinins released from sensory nerves and immune cells bind neurokinin-1 (NK-1) receptors in the lung. The resultant neurogenic airway inflammation has been implicated in asthma pathogenesis. In mouse models and spontaneous human asthma, NK receptor antagonists reduce bronchospasm and inflammation. We hypothesized that chronic administration of maropitant, an NK-1 receptor antagonist, would decrease clinical signs of asthma, AHR and eosinophilic inflammation in experimentally asthmatic cats., Methods: Cats (n = 6) induced to have asthma using Bermuda grass allergen (BGA) were enrolled in a randomized, prospective, placebo-controlled crossover design study. Cats received either oral maropitant (2 mg/kg) or placebo q48h for 4 weeks; following a 2 week washout, cats were crossed-over to the alternate treatment. Study endpoints included subjective clinical scoring systems after BGA challenge, ventilator-acquired pulmonary mechanics to assess AHR after bronchoprovocation with methacholine, and collection of bronchoalveolar lavage fluid to quantify airway eosinophilia. Statistical analysis was performed using a Mann-Whitney rank sum test with P <0.05 considered significant., Results: Administration of maropitant for 1 month in experimentally asthmatic cats produced no significant difference in clinical scoring scheme (P = 0.589 and P = 1.0), AHR (P = 0.818) or airway eosinophilia (P = 0.669) compared with placebo., Conclusions and Relevance: Chronic administration of maropitant was ineffective at blunting clinical signs, AHR and airway eosinophilia in experimental feline asthma and thus cannot be recommended as a novel treatment for this disorder., (© ISFM and AAFP 2015.)

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., (© ISFM and AAFP 2015.)

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., (© ISFM and AAFP 2014.)

Nebulized lidocaine may be a corticosteroid-sparing drug in human asthmatics, reducing airway resistance and peripheral blood eosinophilia. We hypothesized that inhaled lidocaine would be safe in healthy and experimentally asthmatic cats, diminishing airflow limitation and eosinophilic airway inflammation in the latter population. Healthy (n = 5) and experimentally asthmatic (n = 9) research cats were administered 2 weeks of nebulized lidocaine (2 mg/kg q8h) or placebo (saline) followed by a 2-week washout and crossover to the alternate treatment. Cats were anesthetized to measure the response to inhaled methacholine (MCh) after each treatment. Placebo and doubling doses of methacholine (0.0625-32.0000 mg/ml) were delivered and results were expressed as the concentration of MCh increasing baseline airway resistance by 200% (EC200Raw). Bronchoalveolar lavage was performed after each treatment and eosinophil numbers quantified. Bronchoalveolar lavage fluid (BALF) % eosinophils and EC200Raw within groups after each treatment were compared using a paired t-test (P <0.05 significant). No adverse effects were noted. In healthy cats, lidocaine did not significantly alter BALF eosinophilia or the EC200Raw. There was no difference in %BALF eosinophils in asthmatic cats treated with lidocaine (36±10%) or placebo (33 ± 6%). However, lidocaine increased the EC200Raw compared with placebo 10 ± 2 versus 5 ± 1 mg/ml; P = 0.043). Chronic nebulized lidocaine was well-tolerated in all cats, and lidocaine did not induce airway inflammation or airway hyper-responsiveness in healthy cats. Lidocaine decreased airway response to MCh in asthmatic cats without reducing airway eosinophilia, making it unsuitable for monotherapy. However, lidocaine may serve as a novel adjunctive therapy in feline asthmatics with beneficial effects on airflow obstruction.

Management of feline chronic lower airway disease focuses on controlling clinical signs and decreasing airway inflammation. This retrospective study evaluated the correlation between the resolution of clinical signs in cats with lower airway disease receiving oral glucocorticoids with the resolution of inflammation based on bronchoalveolar lavage fluid (BALF) cytology. Ten cats diagnosed with lower airway disease based on characteristic clinical signs and inflammatory BALF cytology received oral glucocorticoids for at least 3 weeks. They were required to have resolution of clinical signs and BALF collected while asymptomatic and still receiving glucocorticoids. Cats received prednisolone or prednisone (average dose of 1.8±0.2mg/kg daily) for 35.7±5.5 days. Three cats had resolution of clinical signs and lacked inflammatory BALF cytology; seven had persistent inflammatory BALF cytology despite resolution of clinical signs. Given that subclinical inflammation during high-dose glucocorticoid treatment was common, current recommendations to taper therapy based on resolution of clinical signs should be re-evaluated., (Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Bronchoalveolar lavage fluid (BALF) collection is a valuable respiratory diagnostic procedure in cats. This study evaluated effects of BALF storage on total nucleated cell counts (TNCCs) and differential cell counts (DCC), cell morphology, and cytological diagnosis. Forty-five research cats with neutrophilic, eosinophilic, and mixed inflammation, and healthy controls were enrolled. BALF samples were processed within 1h (baseline) or stored at 4°C (4C24) or room temperature (RT24) for 24h, or 4°C (4C48) or room temperature (RT48) for 48h before processing. Stored BALF at RT48 had decreased TNCC compared to baseline. The RT24 and RT48 samples had greater eosinophil % and the RT24, 4C48, and RT48 samples had decreased neutrophil % compared with baseline. Cellular morphology deteriorated in all stored samples. Storage resulted in a change in cytological diagnosis in up to 57% of stored samples. We conclude that cytological analysis of BALF in cats should be performed promptly for optimal results., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

N-acetylcysteine (NAC), a mucolytic and antioxidant, is speculated to cause bronchoconstriction in cats when delivered via aerosol. We hypothesized that in cats with experimental asthma, aerosol delivery of NAC (400mg cumulative dose) via an endotracheal tube would increase airflow limitation as measured by ventilator-acquired mechanics. After endotracheal drug delivery, airway resistance and inspiratory plateau pressure (Pplat) measurements were obtained in six mechanically ventilated asthmatic cats. Results demonstrated significantly increased airway resistance (P=0.0007) compared with aerosolized saline control; Pplats were not significantly different (P=0.059). All cats exhibited at least one adverse effect: excessive airway secretions (n=3), spontaneous cough (n=2), unilateral strabismus (n=1) and post-anesthetic death (n=1). No adverse reactions were noted with saline aerosol; cough was noted in one cat with methacholine challenge. In conclusion, airway resistance and adverse reactions were documented in all cats after NAC aerosol delivery. Further studies must be performed to evaluate if it is an effective mucolytic and/or antioxidant in cats and to determine if bronchodilator pre-treatment will negate NAC-induced bronchoconstriction., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Immunoglobulin E (IgE) plays an important role in defense against parasitic infections as well as allergy. Knowledge of serum total IgE concentrations may have value in diagnosis and prognostication of various disorders; however, to date, no studies have reported feline serum total IgE concentrations. We hypothesize that serum total IgE concentrations will be greater in spontaneously parasitized and asthmatic cats compared to healthy pet cats. Healthy (n=10), parasitized (10) and asthmatic cats (eight) had measurement of serum total IgE by ELISA. Data were analyzed using a t-test with P<0.05 considered significant. Serum total IgE was higher in parasitized (mean±SEM, 328.4±123.8μg/ml; P<0.028) and asthmatic cats (85.5±19.5μg/ml; P<0.047) compared to healthy cats (45.9±19.6μg/ml). However, serum total IgE had poor discriminatory capability between diseased and healthy cats. In conclusion, this assay can detect small quantities of feline serum total IgE, which may be beneficial in future studies of parasitism or allergic disease., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the effects of a cysteinyl-leukotriene-1 (cys-LT(1)) receptor antagonist, zarfirlukast, during feline endotoxemia. Six adult, sexually intact male cats received either placebo or zarfirlukast (10mg, PO) and endotoxin (2 μg/kg/h q 6h) in a cross-over design. Rectal temperature, heart rate, systolic arterial blood pressure, plasma tumor necrosis factor (TNF) activity, interleukin (IL)-6 concentration and urine cys-LT to creatinine ratio were evaluated. The rectal temperature, plasma TNF activity and IL-6 concentrations were significantly higher and systolic arterial blood pressure and heart rate significantly lower after endotoxin infusion. Cats treated with zafirlukast had a significantly higher blood pressure at 4h (P=0.002) compared to placebo. Urine cys-LT to creatinine ratio was significantly greater in the cats treated with zafirlukast compared to placebo (P=0.02). Zafirlukast administration ameliorated the acute hypotensive response to endotoxin in cats, but failed to significantly alter rectal temperature, heart rate or production of TNF and IL-6., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Directed, effective therapies for feline sepsis are needed to reduce the high morbidity and mortality associated with this disease. We investigated the anti-endotoxin effects of polymyxin B (PMB) in a blinded, placebo controlled fashion, both ex vivo in a feline whole blood culture system and in vivo, using a low-dose endotoxin infusion in cats. Serial measures of systemic inflammation, and hemodynamic stability, were compared between groups. Ex vivo, PMB significantly decreased lipopolysaccharide-induced tumor necrosis factor (TNF) production from whole blood. PMB (1mg/kg over 30min) demonstrated anti-endotoxin effects in vivo, including decreased peak plasma TNF activity (P<0.001) and increased white blood cell count (P=0.019), with no adverse effects. Given the apparent safety and anti-endotoxin effects of PMB in this endotoxemia model, a carefully designed, randomized, blinded, placebo controlled clinical trial evaluating the use of PMB in naturally occurring Gram-negative feline sepsis should be considered., (Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Cats with inflammatory bronchial disease are usually treated with glucocorticoid (GC) drugs to reduce airway inflammation. Inhalant GC delivery can preserve airway effects while systemic effects are minimized. An appropriate dosage regimen for inhaled GC in cats has not been investigated. A blinded, randomized, cross-over study design was used to investigate the ability of three different dosages of the inhalant GC fluticasone propionate delivered by metered dose inhaler to ameliorate eosinophilic airway inflammation in cats with experimentally induced allergic airway inflammation. Further, suppression of the hypothalamic-pituitary-adrenal axis (HPAA) at each dose was assessed. Fluticasone administered at dosages of 44, 110, or 220 microg q 12h reduced airway eosinophilia by 74%, 82%, or 81%, respectively (no difference). None of the dose regimens tested caused HPAA suppression. We conclude that a twice daily dosage of 44 microg fluticasone should be evaluated for the management of cats with naturally occurring inflammatory bronchial disease., (Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Inhaled medications have proven effective and well tolerated in cats, and inhaled insulin has been used successfully for the management of diabetes mellitus in humans. Thus, we hypothesize that delivery of aerosolized regular insulin can lower blood glucose in healthy cats. Five adult cats were administered aerosolized 0.9% saline (IS), regular insulin intravenously (IV) 0.5 U/kg, and aerosolized regular insulin 15 U/kg (I15) and 25 U/kg (I25) and blood glucose was evaluated. Mean blood glucose was significantly lower at 15, 30 and 45 min in the I25 and IV groups compared to baseline. Similarly, the IV and I25 groups had a significantly greater maximal percent change in blood glucose than the IS group. Significantly more cats developed severe hypoglycemia (<50 mg/dl; 2.7 mmol/l) in the IV and I25 groups than in the IS group. Results of this study demonstrate that aerosolized insulin can effectively lower blood glucose concentrations in healthy cats.