Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study

Hayoung Choi; Soorack Ryu; Holly Keir; Yan Hui Giam; Alison Dicker; Lidia Perea; Hollian Richardson; Jeffrey Huang; Erin Cant; Francesco Blasi; Jennifer Pollock; Michal Shteinberg; Simon Finch; Stefano Aliberti; Oriol Sibila; Amelia Shoemark; James Chalmers

doi:10.1183/13993003.congress-2023.PA383

Abstract

Introduction: Inflammation is believed to be central to the pathophysiology of bronchiectasis. This study aimed to perform inflammatory endotyping in bronchiectasis and examine the validity of identified inflammatory clusters by comparing the microbiome profiles and exacerbation risk among endotypes of bronchiectasis.
Methods: Patients with stable bronchiectasis were enrolled at three European centres. K-means cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Sputum microbiome composition was determined through 16S rRNA amplicon sequencing. Endotypes were compared for their risk of exacerbations over 12 months follow-up.
Results: 199 patients were enrolled, and using cluster analysis, four endotypes were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2 inflammation), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). In the sputum microbiome, Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more dominant in clusters 2 and 3 than in clusters 1 and 4. Although the four clusters were indistinguishable by clinical characteristics at baseline, patients in clusters 2 (rate ratio [RR] 1.53, 95% CI 1.19–1.97) and 3 (RR 1.46, 95% CI 1.02–2.09) were at higher risk of exacerbation and severe exacerbation over 12 months follow-up compared to cluster 1.
Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

Original language	English
Article number	PA383
Number of pages	1
Journal	European Respiratory Journal
Volume	62
Issue number	67
DOIs	https://doi.org/10.1183/13993003.congress-2023.PA383
Publication status	Published - Sept 2023
Event	European Respiratory Society (ERS) 2023: International Congress - Allianz MiCo, Milan, Italy Duration: 9 Sept 2023 → 13 Sept 2023 https://www.ersnet.org/congress-and-events/congress/venue-hotel-and-travel-information/venue/

Keywords

Inflammation
Bronchiectasis
Mirobiome/Microbiota

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10.1183/13993003.congress-2023.PA383

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Choi, H., Ryu, S., Keir, H., Giam, Y. H., Dicker, A., Perea, L., Richardson, H., Huang, J., Cant, E., Blasi, F., Pollock, J., Shteinberg, M., Finch, S., Aliberti, S., Sibila, O., Shoemark, A., & Chalmers, J. (2023). Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study. European Respiratory Journal, 62(67), Article PA383. https://doi.org/10.1183/13993003.congress-2023.PA383

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title = "Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study",

abstract = "Introduction: Inflammation is believed to be central to the pathophysiology of bronchiectasis. This study aimed to perform inflammatory endotyping in bronchiectasis and examine the validity of identified inflammatory clusters by comparing the microbiome profiles and exacerbation risk among endotypes of bronchiectasis. Methods: Patients with stable bronchiectasis were enrolled at three European centres. K-means cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Sputum microbiome composition was determined through 16S rRNA amplicon sequencing. Endotypes were compared for their risk of exacerbations over 12 months follow-up. Results: 199 patients were enrolled, and using cluster analysis, four endotypes were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2 inflammation), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). In the sputum microbiome, Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more dominant in clusters 2 and 3 than in clusters 1 and 4. Although the four clusters were indistinguishable by clinical characteristics at baseline, patients in clusters 2 (rate ratio [RR] 1.53, 95\% CI 1.19{\textendash}1.97) and 3 (RR 1.46, 95\% CI 1.02{\textendash}2.09) were at higher risk of exacerbation and severe exacerbation over 12 months follow-up compared to cluster 1. Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.",

keywords = "Inflammation, Bronchiectasis, Mirobiome/Microbiota",

author = "Hayoung Choi and Soorack Ryu and Holly Keir and Giam, \{Yan Hui\} and Alison Dicker and Lidia Perea and Hollian Richardson and Jeffrey Huang and Erin Cant and Francesco Blasi and Jennifer Pollock and Michal Shteinberg and Simon Finch and Stefano Aliberti and Oriol Sibila and Amelia Shoemark and James Chalmers",

note = "Copyright {\textcopyright}the authors 2023; European Respiratory Society (ERS) 2023 : International Congress, ERS 2023 ; Conference date: 09-09-2023 Through 13-09-2023",

year = "2023",

month = sep,

doi = "10.1183/13993003.congress-2023.PA383",

language = "English",

volume = "62",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "67",

url = "https://www.ersnet.org/congress-and-events/congress/venue-hotel-and-travel-information/venue/",

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Choi, H, Ryu, S, Keir, H, Giam, YH, Dicker, A, Perea, L, Richardson, H , Huang, J , Cant, E, Blasi, F, Pollock, J, Shteinberg, M, Finch, S, Aliberti, S, Sibila, O, Shoemark, A & Chalmers, J 2023, 'Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study', European Respiratory Journal, vol. 62, no. 67, PA383. https://doi.org/10.1183/13993003.congress-2023.PA383

TY - JOUR

T1 - Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis

T2 - European Respiratory Society (ERS) 2023

AU - Choi, Hayoung

AU - Ryu, Soorack

AU - Keir, Holly

AU - Giam, Yan Hui

AU - Dicker, Alison

AU - Perea, Lidia

AU - Richardson, Hollian

AU - Huang, Jeffrey

AU - Cant, Erin

AU - Blasi, Francesco

AU - Pollock, Jennifer

AU - Shteinberg, Michal

AU - Finch, Simon

AU - Aliberti, Stefano

AU - Sibila, Oriol

AU - Shoemark, Amelia

AU - Chalmers, James

PY - 2023/9

Y1 - 2023/9

N2 - Introduction: Inflammation is believed to be central to the pathophysiology of bronchiectasis. This study aimed to perform inflammatory endotyping in bronchiectasis and examine the validity of identified inflammatory clusters by comparing the microbiome profiles and exacerbation risk among endotypes of bronchiectasis. Methods: Patients with stable bronchiectasis were enrolled at three European centres. K-means cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Sputum microbiome composition was determined through 16S rRNA amplicon sequencing. Endotypes were compared for their risk of exacerbations over 12 months follow-up. Results: 199 patients were enrolled, and using cluster analysis, four endotypes were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2 inflammation), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). In the sputum microbiome, Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more dominant in clusters 2 and 3 than in clusters 1 and 4. Although the four clusters were indistinguishable by clinical characteristics at baseline, patients in clusters 2 (rate ratio [RR] 1.53, 95% CI 1.19–1.97) and 3 (RR 1.46, 95% CI 1.02–2.09) were at higher risk of exacerbation and severe exacerbation over 12 months follow-up compared to cluster 1. Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

AB - Introduction: Inflammation is believed to be central to the pathophysiology of bronchiectasis. This study aimed to perform inflammatory endotyping in bronchiectasis and examine the validity of identified inflammatory clusters by comparing the microbiome profiles and exacerbation risk among endotypes of bronchiectasis. Methods: Patients with stable bronchiectasis were enrolled at three European centres. K-means cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers. Sputum microbiome composition was determined through 16S rRNA amplicon sequencing. Endotypes were compared for their risk of exacerbations over 12 months follow-up. Results: 199 patients were enrolled, and using cluster analysis, four endotypes were defined according to their inflammatory profiles: cluster 1 (milder neutrophilic inflammation), cluster 2 (mixed-neutrophilic and type 2 inflammation), cluster 3 (most severe neutrophilic), and cluster 4 (mixed-epithelial and type 2). In the sputum microbiome, Proteobacteria and Pseudomonas at phylum and genus levels, respectively, were more dominant in clusters 2 and 3 than in clusters 1 and 4. Although the four clusters were indistinguishable by clinical characteristics at baseline, patients in clusters 2 (rate ratio [RR] 1.53, 95% CI 1.19–1.97) and 3 (RR 1.46, 95% CI 1.02–2.09) were at higher risk of exacerbation and severe exacerbation over 12 months follow-up compared to cluster 1. Conclusion: Bronchiectasis inflammatory endotypes are associated with distinct microbiome profiles and future exacerbation risk.

KW - Inflammation

KW - Bronchiectasis

KW - Mirobiome/Microbiota

UR - https://www.ersnet.org/congress-and-events/congress/venue-hotel-and-travel-information/venue/

U2 - 10.1183/13993003.congress-2023.PA383

DO - 10.1183/13993003.congress-2023.PA383

M3 - Meeting abstract

SN - 0903-1936

VL - 62

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 67

M1 - PA383

Y2 - 9 September 2023 through 13 September 2023

ER -

Inflammatory Endotypes, Microbiome and Exacerbation Risk in Bronchiectasis: A European Multicentre Study

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