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 FEV₁, FEV₁pred, FVC, FVCpred, FEV₁/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 FEV₁ 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 FEV₁ and FEV₁pred (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 FEV₁ as well as FEV₁pred 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.

Keywords:

• total bilirubin
• COPD
• lung function
• GOLD stage
• decline

Abbreviations

TB, total bilirubin; COPD, chronic obstructive pulmonary disease; GOLD, the Global Initiative for Chronic Lung Disease; mMRC, Modified Medical Research Council dyspnea; BMI, body mass index; FVC, forced vital capacity; FVC, %predicted, the ratio of FVC to its predicted value; FEV₁, forced expiratory volume in the first second; FEV₁,%predicted, the ratio of FEV₁ to its predicted value; FEV₁/FVC, the ratio of FEV₁ to FVC; ANOVA, analysis of variance; SD, standard deviation; CI, confidence interval; CVD, cardiovascular disease; ECOPD, the early COPD; HO-1, oxygenase-1.

Data Sharing Statement

The datasets used and analyzed in this study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

The original two studies were performed in line with the principles of the Declaration of Helsinki. All the participants from two studies gave written informed consent and two studies were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No.2013-37 and No. 2018-53 respectively).

Acknowledgments

The authors thank for the contributions of all the subjects who agreed to donate their information for analysis. Besides, the authors thank Bijia Lin, Shaodan Wei and Xiaopeng Ling (State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Nanshan Medicine Innovation Institute of Guangdong Province) for their help in collecting the data.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All the authors declare they have no real or potential competing interests in this work.

Additional information

Funding

The study was funded by The Nature Key Research and Development Program (2016YFC1304101), the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01s155), the independent project of the State Key Laboratory of Respiratory Diseases (SKLRD-QN-201913), the National Science Foundation of China (81970045), and Zhong Nanshan Medical Development Foundation of Guangdong Province (ZNSA-202003, ZNSA-2020012, ZNSA-2020013).