Inflammatory Endotype Associated Airway Microbiome in COPD Clinical Stability and Exacerbations - A Multi-Cohort Longitudinal Analysis
| Autor: | Wang, Zhang, Locantore, Nicholas, Haldar, Koirobi, Ramsheh, Mohammadali Yavari, Beech, Augusta S, Ma, Wei, Brown, James R, Tal-Singer, Ruth, Barer, Michael R, Bafadhel, Mona, Donaldson, Gavin C, Wedzicha, Jadwiga A, Singh, Dave, Wilkinson, Tom M A, Miller, Bruce E, Brightling, Christopher E |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Wang, Z, Locantore, N, Haldar, K, Ramsheh, M Y, Beech, A S, Ma, W, Brown, J R, Tal-Singer, R, Barer, M R, Bafadhel, M, Donaldson, G C, Wedzicha, J A, Singh, D, Wilkinson, T M A, Miller, B E & Brightling, C E 2021, ' Inflammatory Endotype Associated Airway Microbiome in COPD Clinical Stability and Exacerbations-A Multi-Cohort Longitudinal Analysis ', American Journal of Respiratory and Critical Care Medicine . https://doi.org/10.1164/rccm.202009-3448OC |
| Popis: | RATIONALE: Understanding the role of airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.OBJECTIVES: To understand the association of airway microbiome with neutrophilic and eosinophilic COPD at stability and exacerbations.METHODS: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 COPD patients recruited at four UK sites in BEAT-COPD, COPDMAP and AERIS cohorts. The microbiome was analyzed using COPDMAP and AERIS as discovery dataset and BEAT-COPD as validation dataset.RESULTS: The airway microbiome in neutrophilic COPD was heterogeneous with two primary community types differentiated by the predominance of Haemophilus. The Haemophilus-predominant subgroup had elevated sputum IL-1b and TNFa and was relatively stable over time. The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic. Patients in this state at stability were susceptible to greatest microbiome shifts during exacerbations. This subgroup can temporally switch to both neutrophilic-Haemophilus-predominant and eosinophilic states which were otherwise mutually exclusive. Time-series analysis on the microbiome showed the temporal trajectories of Campylobacter and Granulicatella were indicative of intra-patient switches from neutrophilic to eosinophilic inflammation, and in track with patient sputum eosinophilia over time. Network analysis revealed distinct host-microbiome interaction patterns between neutrophilic-Haemophilus-predominant, neutrophilic-balanced-microbiome and eosinophilic subgroups.CONCLUSIONS: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies. Neutrophilic and eosinophilic COPD are inter-changeable in some patients. Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time. |
| Databáze: | OpenAIRE |
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