Sputum Microbiome, Potentially Pathogenic Organisms, and Clinical Outcomes in Japanese Patients with COPD and Moderate Airflow Limitation: The Prospective AERIS-J Study.

Background: In Western studies, lung microbiome changes are reported in patients with chronic obstructive pulmonary disease (COPD) and are associated with poorer outcomes, but similar studies in Asian patients or those with less severe COPD are limited.

Methods: The Acute Exacerbation and Respiratory InfectionS in COPD Japan (AERIS-J; jRCT1080224632/NCT03957577) was a prospective, non-interventional study to evaluate sputum microbiome diversity at baseline and after 12 months (V2; exploratory analysis), in patients aged 40-80 years with stable COPD (June 2019-June 2022). Baseline sputum potentially pathogenic organisms (PPOs) were identified. Blood cell counts and COPD Assessment Test (CAT) scores were collected at baseline and COPD symptoms measured over 12 months using the Evaluating Respiratory Symptoms in COPD and EXAcerbations of Chronic pulmonary disease Tool, collected by eDiary.

Results: Patients (N=63) had a mean age of 72.8 years, and percent predicted post-bronchodilator forced expiratory volume in 1 second was 58.3%; 92% were male. Across 62 baseline sputum samples, microbiome composition was similar between 16S rRNA/metagenomic datasets. Patients graded Global Initiative for Chronic Obstructive Lung Disease (GOLD) III versus GOLD I/II had minimal differences in their microbial taxonomic profile and no differences in microbial diversity (Wilcoxon P=0.71). Alpha diversity (Shannon index) positively correlated with blood basophils (rho=0.41; P=0.0019) and negatively correlated with CAT score (rho=0.36; P=0.0069). Alpha diversity and sputum (rho: -0.0637; P=0.7836) or blood (rho: 0.1739; P=0.2043) eosinophils were not correlated. No difference in alpha (P=0.5) or beta (P=0.3) diversity or Operational Taxonomic Unit (Anosim R=-0.024; P=0.892) was observed between PPO-positive or -negative sputum.

Conclusion: A less diverse microbiome correlated with poorer health status and lower blood basophils in patients with COPD and moderate airflow limitation. There was no relationship between PPO presence and microbiome diversity.