Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma

Bullone, Michela; Vargas, Amandine; Elce, Yvonne; Martin, James G.; Lavoie, Jean‐Pierre

doi:10.1038/s41598-017-09414-8

Cited by 46 publications

(78 citation statements)

References 63 publications

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“…In IAD, mixed/neutrophilic and eosinophilic inflammation may be present . Similar to human asthma, RAO and IAD respond to beta‐adrenergic agonists in combination with inhaled or systemic corticosteroids …”

Section: Asthma/obstructive Airway Disease In Other Mammalian Speciesmentioning

confidence: 99%

“…In IAD, mixed/neutrophilic and eosinophilic inflammation may be present 91. Similar to human asthma, RAO and IAD respond to beta-adrenergic agonists in combination with inhaled or systemic corticosteroids 92,93. Pathologically, RAO is associated with airway remodeling, increased airway mucus and epithelial mucous metaplasia, ASM hypertrophy, and subepithelial collagen deposition.…”

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confidence: 99%

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Modeling asthma: Pitfalls, promises, and the road ahead

Rosenberg

Druey

2018

Journal of Leukocyte Biology

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Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource.

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Section: Asthma/obstructive Airway Disease In Other Mammalian Speciesmentioning

confidence: 99%

mentioning

confidence: 99%

Modeling asthma: Pitfalls, promises, and the road ahead

Rosenberg

Druey

2018

Journal of Leukocyte Biology

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“…There is strong evidence that corticosteroid therapy does not normalize airway neutrophilia without environmental modifications, even after treatment periods of up to 6 months, when corticosteroid treatment is combined with measures to improve air quality an improvement in clinical signs, improvement in airway neutrophilia and inflammatory cytokine expression is observed in horses with severe asthma . It is possible that longer treatment periods are required to achieve resolution of airway neutrophilia following prolonged exposure to poor ambient air quality.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of dexamethasone, salbutamol, and reduced respirable particulate concentration on aerobic capacity in horses with smoke‐induced mild asthma

Bond

Greco‐Otto

MacLeod

et al. 2020

Veterinary Internal Medicne

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Background Mild asthma in horses decreases racing performance and impairs gas exchange. The efficacy of treatment on performance is unknown. Hypothesis Treatment targeting lung inflammation improves V˙O2peak in horses with mild asthma. Animals Thoroughbred polo horses (n = 12) with smoke‐induced mild asthma. Horses were exposed to increased ambient particulate matter (35.51 μg/m3 [PM2.5]; day mean, centrally measured) from day −33 to 0, from bushfire smoke (natural model). Methods Prospective, randomized, placebo‐controlled, double‐blinded clinical trial. All horses completed 3 V˙O2peak tests, measuring aerobic and anaerobic variables: day 0 ‐baseline; day 16 ‐after dexamethasone (20 mg IM q24h; DEX, n = 6) or saline treatment (SALINE, n = 6), under improved ambient PM2.5 concentrations (7.04 μg/m3); day 17‐15‐30mins after inhaled salbutamol (1500 μg). Bronchoalveolar lavage and mucus scoring were performed on day −8 and day 20. Linear mixed effects models were used to examine the effects of timepoint and treatment group on BAL differential cell counts, mucus scores, aerobic and anaerobic variables. Results Horses’ mucus scores improved significantly from day −8 to 20 by 1.27 ± .38 (P = .01). There was a significant increase in V˙O2peak of 15.5 ± 4.0 mL(min.kg)−1 from day 0 to 17 (P = .002), representing an average (mean) increase in V˙O2peak of 13.2%. There was no difference in V˙O2peak between treatment groups (SALINE versus DEX) at any timepoint. Conclusions and Clinical Importance This study highlighted the key role of improved air quality on functionally important airway inflammation. Evidence provided is central to increasing owner compliance regarding improved air quality for the treatment and prevention of mild asthma.

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“…The β 2 ‐agonists usually used in veterinary clinical practice may also induce tachyphylaxis leading to a refractory response to repeated doses of adrenergic agonists . Thus, combinations of anti‐inflammatory medicines and bronchodilators may optimise the control of disease by reducing the doses of individual drugs and the risk of adverse events .…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

Calzetta

Crupi

Roncada

et al. 2019

Equine Veterinary Journal

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Summary Background Airway obstruction is the main trait of severe equine asthma that affects respiratory function and elicits detrimental effects on clinical presentation. Only few and underpowered clinical studies have investigated the impact of improvement in lung function induced by bronchodilators on the clinical signs of asthma‐affected horses. Objectives To identify the minimal important difference (MID) in lung function elicited by bronchodilator leading to a meaningful improvement in clinical signs. Study design Pairwise meta‐analysis and meta‐regression analysis. Methods Literature searches were performed for studies that investigated the effect of bronchodilator therapy on lung function and clinical condition of asthmatic horses. The relationship between the change in lung function variables and clinical score was analysed via random‐effect meta‐regression. One‐point change of the Improved clinically Detectable Equine Asthma Scoring System (IDEASS) score was used to identify the MID. Results A significant (P<0.05) relationship was found between the changes in IDEASS score and maximum change in transpulmonary pressure (ΔPplmax) or pulmonary resistance (RL). Since only the model resulting for RL passed through the origin (Y‐intercept when X = 0: −0.31, 95% CI −0.75 to 0.14), this variable was used to identify the MID correlated with a meaningful improvement in clinical signs. The resulting MID value was a change in RL of 0.63 cm H2O/L/s (95% CI 0.33–0.94), representing the slope of meta‐regression model (high quality of evidence). Main limitations No long‐term studies investigated the effect of bronchodilator agents on both lung function and clinical signs in asthmatic horses. Conclusions In conclusion, bronchodilator pharmacotherapy in equine asthma elicits clinically meaningful effect when RL increases ≥1 cm H2O/L/s, a value indicating the MID. Assessing the MID based on change in RL may improve the quality of evidence and the scientific impact of future clinical trials as it extends beyond the simple, and limiting, evaluation of statistical significance.

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Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma

Cited by 46 publications

References 63 publications

Modeling asthma: Pitfalls, promises, and the road ahead

Modeling asthma: Pitfalls, promises, and the road ahead

Efficacy of dexamethasone, salbutamol, and reduced respirable particulate concentration on aerobic capacity in horses with smoke‐induced mild asthma

Clinical efficacy of bronchodilators in equine asthma: Looking for minimal important difference

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