Association Between Serum Total Bilirubin Level and Lung Function Decline in Patients with COPD: Results from a Pooled Study

Abstract

Background Serum total bilirubin has been reported to have antioxidant properties against chronic respiratory diseases. The objective of our study is to evaluate the association of total bilirubin (TB) with annual lung function decline in COPD patients with different GOLD stages. Methods This study used pooled data from two observational and prospective cohorts of 612 COPD patients whose TB levels were measured at baseline. The associations between TB and postbronchodilator FEV 1 , FEV 1 pred, FVC, FVCpred, FEV 1 /FVC, and the rate of their decline were all determined using linear regression models in the total population and strata of GOLD stages. Results Serum TB was positively related to FEV 1 and FVC in the total group (β 0.02, 95% CI 0.001~0.02, P = 0.025 and β 0.02, 95% CI 0.002~0.03, P = 0.022, respectively). Additionally, TB was inversely associated with the annual decline in FEV 1 and FEV 1 pred (β 4.91, 95% CI 1.68~8.14, P = 0.025 and β 0.21, 95% CI 0.06~0.36, P = 0.022, respectively) when adjusted for multivariables. After stratification, the significant associations merely persisted in COPD patients with GOLD 2 and GOLD 3–4. Conclusion Increased TB level was related to less annual decline in FEV 1 as well as FEV 1 pred in moderate-to-severe COPD but not mild COPD, which indicated the different status of TB in different COPD severity and the possible role as potential biomarker merely in moderate-to-severe COPD. Future researches to determine whether TB could be served as biomarker for COPD and the mechanisms should be focused on some target patients with a certain disease severity.

Serum Bilirubin Levels and Disease Severity in Patients with Pneumoconiosis

“…Recently, a relationship between serum bilirubin and lung function decline has been demonstrated in patients with chronic obstructive pulmonary disease [ 29 ]. Apperley S et al [ 30 ] suggested that serum bilirubin is associated with forced expiratory volume in 1 s in patients with mild chronic obstructive pulmonary disease.…”

Bilirubin-associated single nucleotide polymorphism (SNP) and respiratory health outcomes: a mendelian randomization study

“…Bilirubin, the main metabolic end-product of heme degradation, is a potent anti-oxidant that scavenges peroxyl radicals and inhibits membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is a large intracellular source of reactive oxygen species. [ 6 , 7 ] We and others have demonstrated in large observational studies that higher serum bilirubin concentrations are associated with lower risk of AECOPD [ 8 , 9 ], slower rate of lung function decline [ 10 , 11 ], and lower all-cause mortality. [ 12 ] In a recent systematic review we found that higher serum bilirubin concentrations may be associated with decreased mortality, lower risk of AECOPD, reduced incidence of COPD diagnosis, and improved lung function.…”