Association Between Serum Total Bilirubin and COPD: Results from a Cross-Sectional Study and a Bidirectional Mendelian Randomization Analysis

Dai, Caili; Wang, Z; Yang, Huajing; Xiao, Shan; Xu, Jun‐Fa; Deng, Zhishan; Wu, Fan; X, Wen; Zheng, Yuzhen; Liu, Lu; Zhao, Ningning; Huang, Peiyu; Zhou, Yumin; Ran, Pixin

doi:10.2147/clep.s353389

Cited by 4 publications

(1 citation statement)

References 35 publications

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“…The inverse relationship of TBIL with COPD risk was fairly consistent with several prospective studies ( 8 , 34 ). However, a bidirectional Mendelian randomization analysis showed no causal relation between TBIL and COPD ( 35 ). Although higher TBIL levels within the normal range have been demonstrated to decrease the risk of cardiovascular disease through antioxidant and anti-inflammatory effects ( 36 ), the underlying mechanism for the protective effects of TBIL in COPD progression is unclear.…”

Section: Discussionmentioning

confidence: 99%

Circulating liver function markers and the risk of COPD in the UK Biobank

Guan

Wan

et al. 2023

Front. Endocrinol.

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ObjectiveTo investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD).MethodsWe leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05).ConclusionWe observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.

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Section: Discussionmentioning

confidence: 99%

Circulating liver function markers and the risk of COPD in the UK Biobank

Guan

Wan

et al. 2023

Front. Endocrinol.

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

et al. 2023

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Background Observational studies have shown an association between higher bilirubin levels and improved respiratory health outcomes. Targeting higher bilirubin levels has been proposed as a novel therapeutic strategy in COPD. However, bilirubin levels are influenced by multiple intrinsic and extrinsic factors, and these observational studies are prone to confounding. Genetic analyses are one approach to overcoming residual confounding in observational studies. Objectives To test associations between a genetic determinant of bilirubin levels and respiratory health outcomes. Methods COPDGene participants underwent genotyping at the baseline visit. We confirmed established associations between homozygosity for rs6742078 and higher bilirubin, and between higher bilirubin and decreased risk of acute respiratory events within this cohort. For our primary analysis, we used negative binomial regression to test associations between homozygosity for rs6742078 and rate of acute respiratory events. Results 8,727 participants (n = 6,228 non-Hispanic white and 2,499 African American) were included. Higher bilirubin was associated with decreased rate of acute respiratory events [incidence rate ratio (IRR) 0.85, 95% CI 0.75 to 0.96 per SD increase in bilirubin intensity]. We did not find significant associations between homozygosity for rs6742078 and acute respiratory events (IRR 0.94, 95% CI 0.70 to 1.25 for non-Hispanic white and 1.09, 95% CI 0.91 to 1.31 for African American participants). Conclusions A genetic determinant of higher bilirubin levels was not associated with better respiratory health outcomes. These results do not support targeting higher bilirubin levels as a therapeutic strategy in COPD.

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High indirect bilirubin levels as an independent predictor of postoperative myasthenic crisis: a single-center, retrospective study

Sun,

Ruan,

Zhang

et al. 2024

Front. Neurol.

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BackgroundThymectomy is an efficient and standard treatment strategy for patients with myasthenia gravis (MG), postoperative myasthenic crisis (POMC) is the major complication related to thymectomy and has a strongly life-threatening effect. As a biomarker, whether the bilirubin level is a risk factor for MG progression remains unclear. This study aimed to investigate the association between the preoperative bilirubin level and postoperative myasthenic crisis (POMC).MethodsWe analyzed 375 patients with MG who underwent thymectomy at Tangdu Hospital between January 2012 and September 2021. The primary outcome measurement was POMC. The association between POMC and bilirubin level was analyzed by restricted cubic spline (RCS). Indirect bilirubin (IBIL) was divided into two subgroups based on the normal upper limit of IBIL, 14 μmol/L.ResultsCompared with non–POMC group, IBIL levels were significantly higher in patients with POMC. Elevated IBIL levels were closely associated with an increased risk of POMC (p for trend = 0.002). There was a dose-response curve relationship between IBIL levels and POMC incidence (p for non–linearity = 0.93). However, DBIL levels showed a U-shaped association with POMC incidence. High IBIL level (≥14 μmol/L) was an independent predictive factor for POMC [odds ratio = 3.47, 95% confidence interval (CI): 1.56–7.8, p = 0.002]. The addition of high IBIL levels improved the prediction model performance (net reclassification index = 0.186, 95% CI: 0.039–0.334; integrated discrimination improvement = 0.0345, 95% CI: 0.005–0.065).ConclusionHigh preoperative IBIL levels, especially those exceeding the normal upper limit, could independently predict the incidence of POMC.

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Association Between Serum Total Bilirubin and COPD: Results from a Cross-Sectional Study and a Bidirectional Mendelian Randomization Analysis

Cited by 4 publications

References 35 publications

Circulating liver function markers and the risk of COPD in the UK Biobank

Circulating liver function markers and the risk of COPD in the UK Biobank

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

High indirect bilirubin levels as an independent predictor of postoperative myasthenic crisis: a single-center, retrospective study

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