Sophie Mainguy-Seers

Objective: To evaluate potential relationships between sex, asthma severity, and tracheal diameter in adult horses through the use of thoracic radiography. Methods: This was a retrospective case-control study of horses that underwent thoracic radiography at the Université de Montréal from 2018 through 2024. Horses were classified as control, mild/moderate asthma, or severe asthma (SEA) according to the latest consensus statement on equine asthma. To account for radiographic magnification and body size, standardized ratios of tracheal diameter relative to the fifth thoracic vertebral body length and aortic diameter were calculated. The effects of disease status, sex, and their interaction were analyzed using a 2-way ANOVA and Tukey multiple-comparisons test, with results presented as mean [SD] and 95% confidence intervals (CI) of the difference for significant pairwise comparisons. Results: 189 horses were included. The trachea-to-fifth thoracic vertebral body length ratio differed by disease status, with an interaction between sex and disease, as SEA mares had a lower ratio (0.7 [SD, 0.1]) than SEA geldings (0.8 [SD, 0.1]; 95% CI, 0.03 to 0.2), control mares (0.8 [SD, 0.1]; 95% CI, 0.05 to 0.3), and mild/moderate asthma mares (0.8 [SD, 0.1]; 95% CI, 0.03 to 0.2). The trachea-to-aorta ratio was influenced by disease status as it was lower in SEA horses than in controls. Absolute tracheal diameter was affected by disease status and sex, with an interaction between both factors, with SEA mares exhibiting the narrowest trachea. Conclusions: Tracheal diameter is influenced by both sex and asthma status in horses. Clinical Relevance: Whether this sex-related difference in tracheal diameter influences lung mechanics and exercise capacity remains to be investigated.

Background: During clinical remission of severe equine asthma (SEA), affected animals can be challenging to distinguish from healthy horses. In humans, the degree of bronchodilation achieved with a β ₂ ‐adrenergic bronchodilator is helpful in differentiating asthmatics from healthy subjects. Objective: To determine whether the response to an inhaled bronchodilator improves the sensitivity of oscillometry in detecting subclinical airway obstruction in horses with asthma. Study Design: In vivo experiments. Methods: Nine control university‐owned horses and 10 SEA horses in remission from a research herd were studied in the main sub‐study. Oscillometry was performed at baseline, 8, and 30 min after the inhalation of a β ₂ ‐adrenergic bronchodilator. Whole‐breath and within‐breath resistance (R) and reactance from 3 to 7 Hz were compared. Data were analysed with two‐way ANOVAs. Results: At baseline, the inspiratory reactance at 3 Hz was significantly higher in the healthy control group (0.014 ± 0.007 kPa/L/s) compared to the asthma remission group (0.003 ± 0.01 kPa/L/s, p = 0.01). The R3/R7 ratio, a variable representing the frequency‐dependence of airway obstruction, was improved at 30 min in both groups (from 0.77 ± 0.08 to 0.68 ± 0.06 kPa/L/s in the control group [ p = 0.003] and from 0.76 ± 0.09 to 0.69 ± 0.10 kPa/L/s in the SEA group [ p = 0.01]). Similarly, the bronchodilator produced comparable improvements in pulmonary reactance in both groups. Main Limitations: The small number of horses. Conclusion: Only within‐breath analysis with oscillometry distinguished horses with SEA in remission from control horses. Salbutamol administration did not improve this discrimination, as the magnitude of bronchodilation was similar in both groups.

Background: Airway dysfunction in severe equine asthma (SEA) often results in early retirement or euthanasia of affected horses. Exercise‐induced bronchodilation occurs in horses with SEA after intense treadmill exercise, but the effects of a lighter, field‐applicable, training regimen remain largely unexplored. Objectives: To evaluate the impact of submaximal aerobic exercise on airway obstruction during exacerbation of SEA. Study Design: The preliminary phase explored the effects of a 25‐min standardised exercise on the lung function of eight SEA horses. As notable bronchodilation occurred, the results were confirmed in a randomised controlled crossover protocol comparing the effect of the same standardised exercise on lung function with that of an equal duration turnout. Methods: Lung function was assessed by standard lung mechanics before and 15 min after the interventions (turnout and walk/trot lungeing exercise). To compare exercise‐induced bronchodilation with that of a potent bronchodilator in the main study, salbutamol was administered after the turnout intervention only, and lung function was measured again 5 min later. Data were analysed with t tests, Wilcoxon tests, and mixed‐effects models. Results: In the preliminary phase, exercise led to a mean 50% reduction in pulmonary resistance. This was confirmed in the main study, where pulmonary resistance decreased from 2.6 (2.1–3.3) to 1.3 cm (0.8–2.2) H ₂ O/L/s after exercise ( p = 0.006), whereas it remained unchanged after the turnout intervention. Following salbutamol administration after the turnout, lung function was comparable to that of the lunged horses, suggesting that the extent of exercise‐induced bronchodilation was similar to that achieved with a β2‐adrenergic agonist. Main Limitations: The small number of aged horses, the lack of blinding, and the focus on the short‐term effects of exercise restrict the generalisability of the results. Conclusions: The rapid and potent bronchodilation achieved through brief aerobic exercise supports the investigation of a training program's impact on the management of SEA.

OBJECTIVE: In severe equine asthma, structural remodeling of the airways ultimately leads to bronchial wall thickening and airflow obstruction. Increased bronchial vascularization has been described in horses affected by the severe form of the disease, but whether it contributes to bronchial remodeling in milder forms of asthma remains to be determined. In a blinded, retrospective case-control study, we evaluated the presence of bronchial angiogenesis in horses with mild and moderate equine asthma (MEA) and its correlation to airway smooth muscle remodeling. METHODS: Endobronchial biopsies from the Equine Respiratory Tissue Biobank collected between August 14, 2014, and May 31, 2019, from 9 horses with MEA and 7 healthy controls were studied. The vascular basement membrane was identified by immunohistochemistry, allowing the measurement of the number of bronchial vessels, vascular area, and mean vessel size by histomorphometry. The correlations between angiogenic parameters, airway smooth muscle (ASM) remodeling features, and airway neutrophilia were studied. RESULTS: No differences between groups were observed for the angiogenic parameters evaluated. The number of vessels was correlated to ASM cell proliferation in MEA horses (Spearman r = 0.73) but not in controls. Airway neutrophilia correlated negatively with mean vessel size in horses with MEA (Pearson r = −0.83) but not in control horses. CONCLUSIONS: Major changes in bronchial vascularization do not occur in central airways in MEA. CLINICAL RELEVANCE: Contrary to previous findings in horses with severe equine asthma, angiogenesis is not a prominent feature of MEA, but it might be associated with ASM remodeling.

Vitamin D deficiency is associated with asthma development and severity of symptoms in humans, but whether the same occurs in horses is unknown. We aimed to determine whether the serum vitamin D levels differ in horses with asthma compared to control animals and, secondarily, to explore clinical, respiratory, and environmental parameters associated with its concentration in equids in a retrospective cross-sectional study. The total serum vitamin D (25(OH)D) was measured by radioimmunoassay in 45 serum samples from the Equine Respiratory Tissue Biobank (15 control animals, 14 horses with mild or moderate asthma (MEA), and 16 horses with severe asthma (SEA)). Descriptive clinical and environmental parameters, bronchoalveolar lavage fluid cytology, and lung function data were extracted. There was no difference in serum 25(OH)D levels between healthy controls, horses with MEA, and horses with SEA (respectively, means of 57.9 ± 11.6, 55.6 ± 20.0, and 64.6 ± 14.5 nmol/L; p = 0.3), suggesting that this micronutrient does not play a major role in equine asthma pathophysiology.

Background: Salbutamol and hyoscine butylbromide (HBB) are commonly used bronchodilators in horses with severe asthma (SA). Objective: To compare the bronchodilation potency, duration, and adverse effects of salbutamol and HBB in SA. Animals: Six horses in exacerbation of SA. Methods: The effects of inhaled salbutamol (1000 μg) and HBB (150 mg, IV) were compared in a randomized, blinded, crossover experiment. Lung function, intestinal borborygmi and heart rate were assessed before and sequentially until 180 minutes after drug administration, and analyzed with 2-way repeated-measures ANOVA and Dunnett's multiple comparison tests. Results: Both treatments caused a similar improvement in lung function. Pulmonary resistance and reactance returned to baseline values within 30 minutes after HBB administration, whereas salbutamol improved reactance until 180 minutes (mean improvement at 180 minutes of 0.040 Kpa/L/s, 95% CI = 0.004 to 0.076; P = .02 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.028 to 0.045; P = .98 for HBB for the resistance at 3 Hz and of 0.040 Kpa/L/s, 95% CI = 0.007 to 0.074; P = .01 for salbutamol and of 0.009 Kpa/L/s, 95% CI = −0.024 to 0.042; P = .97 for HBB for the reactance at 7 Hz). From 5 to 30 minutes after HBB administration, the heart rate accelerated (mean increase of 3.3 beats per minute, 95% CI = −6.6 to 13.1; P = .92 for salbutamol, and of 13.0 beats per minute, 95% CI = 3.6 to 22.4; P = .002 for HBB at 30 minutes) and the gut sounds decreased (mean reduction of 1.3, 95% CI = −0.1 to 2.8; P = .09 for salbutamol and of 2.8 for the gastrointestinal auscultation score, 95% CI = 1.4 to 4.3; P < .0001 for HBB at 30 minutes). Conclusions and Clinical Importance: Both drugs have a similar bronchodilator potency but with a longer duration for salbutamol. Gastrointestinal and cardiovascular effects were noted only with HBB, suggesting the preferential use of salbutamol to relieve bronchoconstriction in horses with asthma.

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.

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.

While the prevalence of asthma is higher in boys than in girls during childhood, this tendency reverses at puberty, suggesting an effect of sex hormones on the disease pathophysiology. Fluctuations of asthma severity concurring with the estrus cycle are reported in women, but this phenomenon has never been investigated in mares to date. The objective of this exploratory study was to determine whether the estrus cycle modulates airway obstruction in severe equine asthma (SEA). Five mares with SEA during exacerbation of the disease were studied. The whole breath, expiratory and inspiratory resistance, and reactance were compared during the follicular and luteal phases of the estrus cycle. The reproductive tract was evaluated by rectal palpation, ultrasound, and serum progesterone levels. The inspiratory resistance and reactance improved during the luteal phase of the estrus cycle, and variation in progesterone levels and the dominant follicle size correlated with several lung function parameters. The fluctuation of airway dysfunction during the estrus cycle is noteworthy as deterioration of the disease could perhaps be expected and prevented by horse owners and veterinarians. Further studies are required to determine if the equine species could be a suitable model to evaluate the effects of sex hormones on asthma.

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.