Serum bilirubin and chronic obstructive pulmonary disease (COPD): a systematic review

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7 Scopus citations


Background: Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV1), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality. Methods: MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle–Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality—Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE. Results: Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV1) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV1/FVC ratio) (4 studies). Conclusion: Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes. PROSPERO registration: CRD42019145747.

Original languageEnglish (US)
Article number33
JournalBMC Pulmonary Medicine
Issue number1
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This research was supported by the National Institutes of Health’s (NIH) National Heart, Lung and Blood Institute (NHLBI) Grant T32 HL007741-26A1 (DMM) and in part by the National Center for Advancing Translational Sciences (NCATS) Grants KL2TR002492 and UL1TR002494 (AKB). This material is also the result of work supported with resources of the Minneapolis VA Health Care System. The funding body had no role in the design of the study, the collection, analysis, and interpretation of the data, or writing the manuscript.

Publisher Copyright:
© 2021, The Author(s).


  • Antioxidants
  • Bilirubin
  • Pulmonary disease, chronic obstructive
  • Systematic review


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