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Serum Bilirubin and Disease Progression in Mild COPD.

ABSTRACT: 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.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 FEV? and rate of FEV1 decline over 3 to 9 years was determined using regression modeling. Total and disease-specific mortality were also ascertained.Serum bilirubin was positively related to FEV? (P < .001). Serum bilirubin was also negatively related to the annual decline in FEV? 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).Bilirubin is inversely related to COPD disease severity and progression. Higher serum bilirubin concentration was associated with a higher FEV? and less annual decline in FEV?. 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.

SUBMITTER: Apperley S

PROVIDER: S-EPMC4493872 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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Serum Bilirubin and Disease Progression in Mild COPD.

Apperley Scott S Park Hye Yun HY Holmes Daniel T DT Man S F Paul SFP Tashkin Donald D Wise Robert A RA Connett John E JE Sin Don D DD

Chest 20150701 1

<h4>Background</h4>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.<h4>Methods</h4>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 dec ...[more]

PMID: 25539285

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Project description:Background: Previous studies have suggested that serum total bilirubin (STB) levels are associated with heightened chronic kidney disease (CKD) and mortality in both the general population and nephropathy patients. However, these results remain inconsistent. The aim of our study was to investigate whether STB was a predictor for progression of CKD and mortality by meta-analysis. Methods: We performed a systematic literature search in PubMed, Web of Science, MEDLINE, EMBASE, Google Scholar, and Cochrane Library's database up to June 30, 2019. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were extracted for the highest vs. lowest category STB levels within the physiological range, and a random-effects model was applied to calculate the dose-response relationships. A pooled hazard ratio (HR) was used to investigate the association between STB levels and mortality in dialysis patients. Results: A total of 16 studies, wherein participants were followed from 21 months to 7 years, were eligible for inclusion in the study. For the categorized STB, 11 studies with 41,188 participants were identified and analyzed. Patients with the highest STB levels were associated with a lower risk of CKD (RR = 0.64; 95% CI 0.55-0.73) compared to those with the lowest STB levels. Furthermore, based on seven studies, a pooled RR of 0.89, 95% CI (0.80-0.99) was observed for the continuous STB levels (per 0.2 mg/dL increase). Four studies that included 51,764 participants illustrated that there was no association between STB levels and all-cause mortality (HR = 0.77; 95% CI 0.42-1.41). A prominent negative linear relationship (X2 = 14.70; P = 0.0001) was found between STB levels and risk of CKD. Subgroup analyses showed that there were no significant differences in the subgroup adjustment factor except for sample size. Conclusions: Elevated STB levels within a physiological range are associated with lower risk of CKD regardless of the study characteristics and coincide with a liner dose-response relationship. However, whether high STB levels are a protective factor against mortality remains inconclusive. Large-scale randomized controlled trails are needed to target STB levels for predicting renal outcomes.

Project description:IntroductionClinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart.Methods and analysisSOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ?45?and ?80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ?1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and peripheral muscle mass by CT imaging).Ethics and disseminationThe Institutional Ethics Committee from Pontificia Universidad Católica de Chile has approved the study protocol and signed informed consent will be obtained from all participants. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations.Trial registration numberNCT03026439.

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Serum Bilirubin and Disease Progression in Mild COPD.

Publications

Serum Bilirubin and Disease Progression in Mild COPD.

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