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

Abstract

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.

Candidate gene prioritization for chronic obstructive pulmonary disease using expression information in protein–protein interaction networks

“…For the first ranked candidate gene, UGT1A1, its low expression was found to play a protective role in COPD since several studies has found that the enzyme uridine diphosphate glucuronosyltransferase polypeptide 1A1, encoded by gene UGT1A1, was responsible for clearing bilirubin from the blood, whereas higher bilirubin concentrations were associated with a lower risk of acute exacerbations of COPD [ 21 – 23 ]. The serum levels of BDNF (Rank: 2) (but not concentrations of platelets in the peripheral blood) were significantly elevated at all stages of COPD as compared to controls [ 24 ].…”

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B

“…Bilirubin is cleared by the liver, and elevated levels usually indicate a liver disorder. However, bilirubin is also a potent antioxidant ( 21 ). The role of elevated total bilirubin levels in the PPC-treated patients with CHB is unclear.…”

Chronic obstructive pulmonary disease risk assessment tools: is one better than the others?

“…Vitamin D deficiency has been associated with greater FEV 1 decline, although the drivers behind this association remain to be elucidated [61 ▪ ]. Low alanine amino-transferase levels (<11 IU) have been associated with poor survival following a COPD exacerbation requiring hospitalization [62 ▪ ], while higher bilirubin may be associated with better COPD outcomes [63 ▪ ]. A distinct airway mycobiome profile characterized by dominance of Aspergillus, Curvularia, and Penicillium has been associated with high mortality and frequent exacerbations [64 ▪▪ ].…”