Despite substantial research efforts to improve the treatment and outcome of horses with asthma, glucocorticoids (GC) remain the cornerstone of drug treatment of this prevalent disease. The high efficacy of GC to relieve airway obstruction explains their extensive use despite potential deleterious effects. However, much is yet to be uncovered concerning GC use in horses with asthma, including the comparative efficacy of the different drugs, the determination of minimal effective doses and the mechanisms underlying their variable modulation of airway inflammation. The objectives of this structured review were to report and compare the plethora of effects of the various GC used in asthmatic horses with a focus on impact on lung function, airway inflammation, and bronchial remodeling. Adverse effects are also briefly described, with an emphasis on those that have been specifically reported in horses with asthma. Ultimately, we aimed to highlight gaps in the literature and to identify future research areas.

Background Tamoxifen, a selective estrogen receptor modulator, decreased airway neutrophilia and improved clinical signs in an experimental model of equine asthma, and induced neutrophilic apoptosis in vitro. Hypothesis/Objectives Tamoxifen reduces airway neutrophilia and improves lung function in severe asthmatic horses. Animals Twelve severe asthmatic horses from a research herd. Methods Randomized controlled blinded study design. The effects of a 12‐day oral treatment with tamoxifen (0.22 mg/kg, q24h) or dexamethasone (0.06 mg/kg, q24h) on lung function, endoscopic tracheal mucus score and bronchoalveolar lavage fluid cytology were compared. Results Tamoxifen significantly improved the pulmonary resistance (R_L; mean reduction of 1.15 cm H₂O/L/s [CI: 0.29‐2.01, P = .007] on day 13), but had no effect on the other variables evaluated. Dexamethasone normalized lung function (mean reduction of R_L of 2.48 cm H₂O/L/s [CI: 1.54‐3.43, P < .0001] on day 13), without affecting airway neutrophilia. Conclusions and Clinical Importance Results of this study do not support the use of tamoxifen at the dose studied as an antineutrophilic medication in the treatment of asthmatic horses in chronic exacerbation.

Neutrophilic inflammation is believed to contribute to the airway obstruction and remodelling in equine asthma. Azithromycin, an antibiotic with immunomodulatory properties, reduces pulmonary neutrophilia and hyper‐responsiveness in human asthmatics and decreases airway remodelling in rodent models of asthma. It was therefore hypothesised that azithromycin would improve lung function, mucus accumulation and central airway remodelling by decreasing luminal neutrophilia in severe equine asthma. The effects of a 10‐day treatment with either azithromycin or ceftiofur, an antimicrobial without immune‐modulating activity, were assessed using a blind, randomised, crossover design with six severe asthmatic horses in clinical exacerbation. Lung function, tracheal mucus accumulation, tracheal wash bacteriology, bronchial remodelling, airway neutrophilia and mRNA expression of proinflammatory cytokines (interleukin (IL)‐8, IL‐17A, IL‐1β, tumour necrosis factor‐α) in bronchoalveolar lavage fluid were evaluated. Azithromycin decreased the expression of IL‐8 (P=0.03, one‐tailed) and IL‐1β (P=0.047, one‐tailed) but failed to improve the other variables evaluated. Ceftiofur had no effect on any parameter. The reduction of neutrophilic chemoattractants (IL‐8, IL‐1β) justifies further efforts to investigate the effects of a prolonged treatment with macrolides on airway neutrophilia and remodelling. The lack of efficacy of ceftiofur suggests that severe equine asthma should not be treated with antibiotics at first‐line therapy.

Extracellular vesicles (EVs) contribute to intercellular communication through the transfer of their rich cargo to recipient cells. The EVs produced by LPS-stimulated neutrophils from healthy humans and horses increase airway smooth muscle (ASM) proliferation, but the roles of neutrophil EVs in asthma are largely unexplored. The aim of this study was to determine whether neutrophil-derived EVs isolated during the remission or exacerbation of asthma influence ASM proliferation differentially. Peripheral blood neutrophils were collected during remission and exacerbation in eight horses affected by severe asthma. The cells were cultured (±LPS), and their EVs were isolated by ultracentrifugation and characterized by laser scattering microscopy and proteomic analysis. The proliferation of ASM co-incubated with EVs was monitored in real time by electrical impedance. Two proteins were significantly upregulated during disease exacerbation in neutrophil EVs (MAST4 and Lrch4), while LPS stimulation greatly altered the proteomic profile. Those changes involved the upregulation of neutrophil degranulation products, including proteases known to induce myocyte proliferation. In agreement with the proteomic results, EVs from LPS-stimulated neutrophils increased ASM proliferation, without an effect of the disease status. The inhalation of environmental LPS could contribute to asthma pathogenesis by activating neutrophils and leading to ASM hyperplasia.

Background: Standard thoracic auscultation suffers from limitations, and no systematic analysis of breath sounds in asthmatic horses exists. Objectives: First, characterize breath sounds in horses recorded using a novel digital auscultation device (DAD). Second, use DAD to compare breath variables and occurrence of adventitious sounds in healthy and asthmatic horses. Animals: Twelve healthy control horses (ctl), 12 horses with mild to moderate asthma (mEA), 10 horses with severe asthma (sEA) (5 in remission [sEA−], and 5 in exacerbation [sEA+]). Methods: Prospective multicenter case-control study. Horses were categorized based on the horse owner-assessed respiratory signs index. Each horse was digitally auscultated in 11 locations simultaneously for 1 hour. One-hundred breaths per recording were randomly selected, blindly categorized, and statistically analyzed. Results: Digital auscultation allowed breath sound characterization and scoring in horses. Wheezes, crackles, rattles, and breath intensity were significantly more frequent, higher (P < .001, P < .01, P = .01, P < .01, respectively) in sEA+ (68.6%, 66.1%, 17.7%, 97.9%, respectively), but not in sEA− (0%, 0.7%, 1.3%, 5.6%) or mEA (0%, 1.0%, 2.4%, 1.7%) horses, compared to ctl (0%, 0.6%, 1.8%, −9.4%, respectively). Regression analysis suggested breath duration and intensity as explanatory variables for groups, wheezes for tracheal mucus score, and breath intensity and wheezes for the 23-point weighted clinical score (WCS23). Conclusions and Clinical Importance: The DAD permitted characterization and quantification of breath variables, which demonstrated increased adventitious sounds in sEA+. Analysis of a larger sample is needed to determine differences among ctl, mEA, and sEA− horses.