The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction

Author:

Chen Yen-Fu1,Hou Hsin-Han2,Chien Ning3,Lu Kai-Zen4,Lin Chieh-Hua5,Liao Yu-Chieh6,Lor Kuo-Lung7,Chien Jung-Yien4,Chen Chung-Ming7,Chen Chung-Yu1,Cheng Shih-Lung8,Wang Hao-Chien Wang4,Hsueh Po-Ren9,Yu Chong-Jen10

Affiliation:

1. National Taiwan University Hospital, Yun-Lin Branch

2. Graduate Institute of Oral Biology, College of Medicine, National Taiwan University

3. Department of Medical Imaging, National Taiwan University Cancer Center

4. Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University

5. Big Data Center, China Medical University Hospital

6. Institute of Population Health Sciences, National Health Research Institutes

7. Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University

8. Division of Thoracic Medicine, Far Eastern Memorial Hospital

9. Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University

10. Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch

Abstract

Abstract Background Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them with those diagnosed with chronic obstructive pulmonary disease (COPD). Results In this prospective, observational study conducted in Taiwan, we enrolled patients diagnosed with either bronchiectasis or COPD. Bronchoalveolar lavage samples were collected for 16S rRNA gene sequencing to analyze the lung microbiome and assess inflammatory markers. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis accompanied by FAO, as confirmed by spirometry. We found that patients with bronchiectasis, whether with FAO or not, had similar microbiome profiles, characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from the microbiomes of COPD patients which exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted notable differences in clinical features, inflammatory profiles, and slight variations in the microbiome between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion Bronchiectasis patients with FAO exhibit greater disease severity and a lung microbiome more akin to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns, reinforcing their potential role in disease progression and exacerbations in bronchiectasis with FAO.

Publisher

Research Square Platform LLC

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