Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort
Posted on 2020-03-31 - 03:42
Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking. Methods Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years. We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits. Results Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates. Virus infection was strongly associated with exacerbation events (P < 5E-20). Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation. Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event. Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung. Conclusions This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations. It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Bouquet, Jerome; Tabor, David E.; Silver, Jonathan S.; Nair, Varsha; Tovchigrechko, Andrey; Griffin, M. Pamela; et al. (2020). Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4912785.v1
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (9)
JB
Jerome Bouquet
DT
David E. Tabor
JS
Jonathan S. Silver
VN
Varsha Nair
AT
Andrey Tovchigrechko
MG
M. Pamela Griffin
ME
Mark T. Esser
BS
Bret R. Sellman
HJ
Hong Jin
KEYWORDS
exacerbation phenotypesVirus infectionmicrobiome analysis methods3 yearsdrug developmentCzech Republicmulticenter COPD cohort Abstract Background Chronicdisease stageMethods Two-hundredmulticenter assessmentfollow-up visitslung sensitizationmicrobiome diversityCOPD patientsimpact exacerbation ratesguide future patient management applicationsCOPD exacerbationsUSAmicrobiotaRNA gene sequencing1179 sputum samplesexacerbation eventsacid detection16 SMicrobial burdendisease progression