Microbiological characteristics of the lower airway in adults with bronchiectasis: a prospective cohort study

Abstract

Background: Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis.

Methods: We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up.

Results: We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p < 0.001) with the time to the next exacerbation in bronchiectasis.

Conclusion: We have revealed the pathogenic microbial spectrum in lower airways and the negative correlation of PPM colonization with the time to the next exacerbation in bronchiectasis. These results suggested that pathogens contribute to the progression of bronchiectasis.

Keywords: Pseudomonas aeruginosa; Bronchiectasis; Metagenomic next-generation sequencing.

Fig. 1

The design of the study was illustrated in the flow chart

Fig. 2

Clinical utility of mNGS for lower airway pathogen identification. A Microbial findings in the exacerbation cohort using mNGS, conventional microbiological tests (CMTs), or their combination. The left side represents the number of samples with microorganism detection by mNGS and CMTs, or their combination. The right side represents the number of patients with pathogen detection by mNGS and CMTs, or their combination. B Positive and negative rates of pathogen detection by culture, CMTs, and mNGS in the etiology confirmed and unknown groups. C Patients’ etiology and diagnosis. The left side shows the percentage of patients with known or unknown etiology, while the right side indicates the number of patients with known etiology diagnosed via mNGS, CMTs, and clinical manifestations. D Comparison of culture, CMTs, and mNGS relative to a composite reference standard (CRS). Sensitivity, specificity, and accuracy values are displayed below each table

Fig. 3

The pathogenic index of potential pathogenic microorganisms (PPMs) negatively correlates with the time to next exacerbation. A The composition of top 20 bacterial species measured by mNGS in the lower airways in bronchiectasis patients at exacerbation onset and stable state. B Pearson’s analysis of correlation of adjusted pathogenic index (API) with the time to next exacerbation in bronchiectasis patients with or without PPMs colonization