Scott Apperley1, Hye Yun Park2, Daniel T Holmes3, S F Paul Man4, Donald Tashkin5, Robert A Wise6, John E Connett7, Don D Sin8. 1. Department of Medicine, Pulmonary Division, University of British Columbia, Vancouver, BC, Canada. 2. UBC James Hogg Research Centre and the Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC, Canada; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Seoul, South Korea. 3. Department of Pathology, University of British Columbia, Vancouver, BC, Canada. 4. Department of Medicine, Pulmonary Division, University of British Columbia, Vancouver, BC, Canada; UBC James Hogg Research Centre and the Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC, Canada. 5. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 6. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 7. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN. 8. Department of Medicine, Pulmonary Division, University of British Columbia, Vancouver, BC, Canada; UBC James Hogg Research Centre and the Institute for Heart and Lung Health, St. Paul's Hospital, Vancouver, BC, Canada. Electronic address: don.sin@hli.ubc.ca.
Abstract
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.
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.
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