Sputum microbe community alterations induced by long-term inhaled corticosteroid use are associated with airway function in chronic obstructive pulmonary disease patients based on metagenomic next-generation sequencing (mNGS)

Abstract

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Objective: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD) patients as a treatment option. However, ICS may also increase the risk of pneumonia and alter the composition of airway microbiota. In clinical application, the overuse of ICS exists pervasively and may potentially lead to adverse effects. Whether the long-term use of ICS confers enough benefit to COPD patients to justify its use so far remains unknown. Therefore, this study employed a single-center retrospective cohort study to compare alterations in airway function and the sputum microbial community structure between COPD patients who had undergone either long-term or short-term treatment with ICS.Methods: Sixty stable COPD patients who had used ICS were recruited and classified into the long-term use group (more than 3 months) and short-term use group (less than 3 months). The demographic features and clinical information of the subjects were investigated and their sputum samples were collected and subjected to metagenomic next-generation sequencing (mNGS).Results: The study found that compared with short-term ICS use, long-term ICS use did not further improve the clinical airway function, decrease the number of acute exacerbations, or decrease hospital readmission. In terms of sputum microbiota, the long-term use of ICS significantly altered the beta diversity of the microbial community structure (p < 0.05) and the top three phyla differed between the two groups. At the genus level, long-term ICS induced higher relative abundances of Abiotrophia, Schaalia, Granulicatella, Mogibacterium, Sphingobium, and Paraeggerthella compared to short-term ICS use. Additionally, alpha diversity was positively associated with clinical airway indicators (pre-bronchodilatory FEV1 and pre-bronchodilatory FVC) in the long-term ICS group. The relative abundances of Rothia, Granulicatella, Schaalia, and Mogibacterium genera had positive correlations with the eosinophil % (of all white blood cells). Conclusion: This study reveals the effect of long-term and short-term ICS use on sputum microbiota among COPD patients and provides a reference for the appropriate application of clinical ICS treatment in COPD patients.

Keywords

• chronic obstructive pulmonary disease
• inhaled corticosteroids
• sputum microbiota
• airway function
• metagenomic next-generation sequencing