Serum Bilirubin and Disease Progression in Mild COPD

Chest. 2015 Jul;148(1):169-175. doi: 10.1378/chest.14-2150.


Background: COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown.

Methods: Serum bilirubin was measured in 4,680 smokers aged 35 to 60 years old with mild to moderate airflow limitation. The relationship of serum bilirubin to postbronchodilator FEV₁ and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained.

Results: Serum bilirubin was positively related to FEV₁ (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV₁ when adjusted for baseline demographics, pack-years smoked, and baseline measures of lung function (P = .01). Additionally, serum bilirubin was negatively associated with risk of death from coronary heart disease (P = .03); however, the relationships between bilirubin and other mortality end points were not statistically significant (P > .05).

Conclusions: Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV₁ and less annual decline in FEV₁. Bilirubin was also associated with less coronary heart disease mortality. These data support the hypothesis that bilirubin has a protective effect on COPD disease progression, possibly through its antioxidant actions. Bilirubin may prove useful as an easily accessible and readily available blood-based COPD biomarker.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bilirubin / blood*
  • Cohort Studies
  • Disease Progression*
  • Female
  • Forced Expiratory Volume / physiology
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Smoking
  • Spirometry
  • Time Factors


  • Bilirubin