Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, St-Hyacinthe, QC, J2S 2M2, Canada.
Laboratoire de Sciences Judiciaires Et de Médecine Légale, Ministère de La Sécurité Publique, Montreal, QC, H2K 3S7, Canada.
Sci Rep. 2022 Jan 10;12(1):446. doi: 10.1038/s41598-021-03955-9.
Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. Macrolide add-on therapy can improve the quality of life and the exacerbation rate in refractory cases, possibly with greater effectiveness in neutrophilic phenotypes. The mechanisms leading to these beneficial effects are incompletely understood and whether macrolides potentiate the modulation of bronchial remodeling induced by inhaled corticosteroids (ICS) is unknown. The objective of this study was to determine if adding azithromycin to ICS leads to further improvement of lung function, airway inflammation and bronchial remodeling in severe asthma. The combination of azithromycin (10 mg/kg q48h PO) and inhaled fluticasone (2500 µg q12h) was compared to the sole administration of fluticasone for five months in a randomized blind trial where the lung function, airway inflammation and bronchial remodeling (histomorphometry of central and peripheral airways and endobronchial ultrasound) of horses with severe neutrophilic asthma were assessed. Although the proportional reduction of airway neutrophilia was significantly larger in the group receiving azithromycin, the lung function and the peripheral and central airway smooth muscle mass decreased similarly in both groups. Despite a better control of airway neutrophilia, azithromycin did not potentiate the other clinical effects of fluticasone.
哮喘的皮质激素抵抗与中性粒细胞炎症和疾病的严重表现有关。大环内酯类药物附加治疗可以改善难治性病例的生活质量和恶化率，在中性粒细胞表型中可能更有效。导致这些有益效果的机制尚不完全清楚，并且大环内酯类药物是否增强吸入皮质激素（ICS）诱导的支气管重塑的调节尚不清楚。本研究的目的是确定在严重哮喘中添加阿奇霉素是否会导致肺功能、气道炎症和支气管重塑的进一步改善。在一项随机盲法试验中，将阿奇霉素（10 mg/kg q48h PO）与吸入氟替卡松（2500 µg q12h）联合应用与单独使用氟替卡松进行了比较，评估了严重中性粒细胞性哮喘马的肺功能、气道炎症和支气管重塑（中央和外周气道的组织形态计量学和支气管内超声）。尽管接受阿奇霉素治疗的组气道中性粒细胞增多的比例显著更大，但两组的肺功能以及外周和中央气道平滑肌质量均相似地降低。尽管对气道中性粒细胞增多的控制更好，但阿奇霉素并没有增强氟替卡松的其他临床效果。
