Sputum Microbiome and clinical outcomes of Asthma-Bronchiectasis Overlap: A Prospective Cohort Study

<bold>Background:</bold> Co-existing bronchiectasis and asthma (Asthma-Bronchiectasis Overlap, ABO) is common in clinical practice. <bold>Objective:</bold> To investigate the microbiome of patients with ABO (including its subtypes) compared with bronchiectasis and asthma alone, and determine the relevance with clinical characteristics, inflammatory endotype and exacerbation risks. <bold>Methods:</bold> This was a prospective cohort study conducted between May 2018 and August 2023. We recruited patients with ABO (N=99), asthma (N=61) and bronchiectasis (N=87). At baseline (steady-state), patients underwent comprehensive clinical assessments and sputum collection. We profiled microbiome via 16S rRNA sequencing. Patients were followed-up to record exacerbation events. <bold>Results:</bold> Baseline Shannon-Wiener diversity index of airway microbiome was significantly lower in ABO than in asthma but higher than in bronchiectasis. Pseudomonadaceae and Rothia were genera that best discriminated ABO from asthma and bronchiectasis. Microbial composition correlated significantly with bronchiectasis severity and airflow limitation. During follow-up, low bacterial diversity with sputum eosinophilia or high bacterial diversity without sputum eosinophilia was associated with a significantly shorter time to the first exacerbation (both P<0.05). <bold>Conclusion:</bold> Integrated microbial profiling could help identify the molecular underpinnings of ABO, which when evaluated along with eosinophilic inflammatory endotyping, can inform future risk of AE and personalized management of ABO.