TY - JOUR
T1 - Lung microbiota predict clinical outcomes in critically ill patients
AU - Dickson, Robert P.
AU - Schultz, Marcus J.
AU - van der Poll, Tom
AU - Schouten, Laura R.
AU - Falkowski, Nicole R.
AU - Luth, Jenna E.
AU - Sjoding, Michael W.
AU - Brown, Christopher A.
AU - Chanderraj, Rishi
AU - Huffnagle, Gary B.
AU - Bos, Lieuwe D. J.
AU - Study group members AMC, null
AU - Lagrand, Wim K.
AU - Horn, Johanna
N1 - BASIC Consortium Group members: Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands: F. M. de Beer, L. D. Bos, T. A. Claushuis, G. J. Glas, J. Horn, A. J. Hoogendijk, R. T. van Hooijdonk, M. A. Huson, M. D. de Jong, N. P. Juffermans, W. A. Lagrand, T. van der Poll, B. Scicluna, L. R. Schouten, M. J. Schultz, K. F. van der Sluijs, M. Straat, L. A. van Vught, L. Wieske, M. A. Wiewel, and E. Witteveen.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Rationale: Recent studies have revealed that, in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of altered lung bacteria in critical illness is unknown. Objectives: To determine if clinical outcomes of critically ill patients are predicted by features of the lung microbiome at the time of admission. Methods: We performed a prospective, observational cohort study in an ICU at a university hospital. Lung microbiota were quantified and characterized using droplet digital PCR and bacterial 16S ribosomal RNA gene quantification and sequencing. Primary predictors were the bacterial burden, community diversity, and community composition of lung microbiota. The primary outcome was ventilatorfree days, determined at 28 days after admission. Measurements and Main Results: Lungs of 91 critically ill patients were sampled using miniature BAL within 24 hours of ICU admission. Patients with increased lung bacterial burden had fewer ventilator-free days (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88), which remained significant when the analysis was controlled for pneumonia and severity of illness. The community composition of lung bacteria predicted ventilator-free days (P = 0.003), driven by the presence of gutassociated bacteria (e.g., species of the Lachnospiraceae and Enterobacteriaceae families). Detection of gut-associated bacteria was also associated with the presence of acute respiratory distress syndrome. Conclusions: Key features of the lung microbiome (bacterial burden and enrichment with gut-associated bacteria) predict outcomes in critically ill patients. The lung microbiome is an understudied source of clinical variation in critical illness and represents a novel therapeutic target for the prevention and treatment of acute respiratory failure.
AB - Rationale: Recent studies have revealed that, in critically ill patients, lung microbiota are altered and correlate with alveolar inflammation. The clinical significance of altered lung bacteria in critical illness is unknown. Objectives: To determine if clinical outcomes of critically ill patients are predicted by features of the lung microbiome at the time of admission. Methods: We performed a prospective, observational cohort study in an ICU at a university hospital. Lung microbiota were quantified and characterized using droplet digital PCR and bacterial 16S ribosomal RNA gene quantification and sequencing. Primary predictors were the bacterial burden, community diversity, and community composition of lung microbiota. The primary outcome was ventilatorfree days, determined at 28 days after admission. Measurements and Main Results: Lungs of 91 critically ill patients were sampled using miniature BAL within 24 hours of ICU admission. Patients with increased lung bacterial burden had fewer ventilator-free days (hazard ratio, 0.43; 95% confidence interval, 0.21-0.88), which remained significant when the analysis was controlled for pneumonia and severity of illness. The community composition of lung bacteria predicted ventilator-free days (P = 0.003), driven by the presence of gutassociated bacteria (e.g., species of the Lachnospiraceae and Enterobacteriaceae families). Detection of gut-associated bacteria was also associated with the presence of acute respiratory distress syndrome. Conclusions: Key features of the lung microbiome (bacterial burden and enrichment with gut-associated bacteria) predict outcomes in critically ill patients. The lung microbiome is an understudied source of clinical variation in critical illness and represents a novel therapeutic target for the prevention and treatment of acute respiratory failure.
KW - Acute respiratory distress syndrome
KW - Lung injury
KW - Lung microbiome
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85080041449&partnerID=8YFLogxK
U2 - https://doi.org/10.1164/rccm.201907-1487OC
DO - https://doi.org/10.1164/rccm.201907-1487OC
M3 - Article
C2 - 31973575
SN - 1073-449X
VL - 201
SP - 555
EP - 563
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 5
ER -