Effects of azithromycin on bronchial remodeling in the natural model of severe neutrophilic asthma in horses

Sophie Mainguy-Seers,Pierre Hélie,Alvaro G Bonilla,Francis Beaudry,Roxane Boivin,Sheila Pourali Dogaheh,James G Martin,Jean-Pierre Lavoie

doi:10.1038/s41598-021-03955-9

Sophie Mainguy-Seers, Pierre Hélie + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-03955-9

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Abstract

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.

Highlights

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease
The administration of azithromycin has beneficial effects on some features of asthma, whether these favorable properties extend to the airway architectural changes has not been assessed in natural models of asthma
The improvement of lung function and bronchial remodeling obtained with fluticasone were not potentiated by the macrolide, refuting the initial hypothesis

Summary

Introduction

Steroid resistance in asthma has been associated with neutrophilic inflammation and severe manifestations of the disease. 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. The release of inflammatory mediators with the propensity to damage airway architecture, such as e lastase[7] and neutrophil extracellular traps[10], partly explains why neutrophils are deemed harmful Whether these leukocytes are causative or bystanders in the natural history of asthma is speculative. Results of studies from species naturally affected by asthma may possibly better translate to humans[25]

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