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Endotyping Chronic Obstructive Pulmonary Disease, Bronchiectasis, and the "Chronic Obstructive Pulmonary
Jeffrey T-J Huang1, Erin Cant2, Holly R Keir2
1Division of Systems Medicine and.
American Journal of Respiratory and Critical Care Medicine
|April 18, 2022
Summary
Patients with the COPD-bronchiectasis association exhibit distinct sputum microbiome and proteome profiles, characterized by neutrophilic inflammation and Gram-negative infections. These findings help differentiate this condition from chronic obstructive pulmonary disease (COPD) alone.
Area of Science:
- Respiratory Medicine
- Microbiome Research
- Proteomics
Background:
- Bronchiectasis and chronic obstructive pulmonary disease (COPD) frequently co-occur, forming the
Purpose of the Study:
- Investigate sputum microbiome and proteome in COPD, bronchiectasis, and their association.
- Identify distinct endotypes for targeted treatment strategies.
Main Methods:
- 16S rRNA sequencing and label-free proteomics on sputum samples.
- Validation in an independent cohort using targeted inflammatory markers, mucins, and bacterial culture.
Main Results:
- Partial separation of microbiome and proteome profiles between COPD and COPD-bronchiectasis association groups.
- COPD-bronchiectasis association shows higher Proteobacteria, MUC5AC, and neutrophil degranulation pathway proteins.
- COPD exhibits higher MUC5B, peptidase inhibitors, commensal taxa, and microbiome diversity.
- Overlapping profiles observed between COPD-bronchiectasis association and bronchiectasis groups.
Conclusions:
- The COPD-bronchiectasis association is characterized by neutrophilic inflammation, specific mucin expression patterns (MUC5AC), and Gram-negative infections.
- Five distinct endotypes identified with unique inflammatory, mucin, and microbiological features.
- Findings validated in an independent cohort, supporting distinct disease traits.
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