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Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations.

ABSTRACT: Bilirubin is a potent anti-oxidant and higher serum concentrations of bilirubin have been associated with better lung function, slower lung function decline, and lower incidence of chronic obstructive pulmonary disease (COPD). We sought to determine whether elevated bilirubin blood concentrations are associated with lower risk for acute exacerbations of COPD (AECOPD).We performed a secondary analyses of data in the Simvastatin for Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE) and the Azithromycin for Prevention of Exacerbations of COPD (MACRO) studies. We used time-dependent multivariable Cox proportional hazards analyses, using bilirubin concentrations prior to first AECOPD as the exposure variable and time to first AECOPD as the outcome variable. STATCOPE was used for model development, with validation in MACRO.In STATCOPE (n = 853), higher bilirubin was associated with a lower but statistically insignificant hazard for AECOPD, (adjusted hazard ratio [aHR] 0.89 per log10 increase [95%CI: 0.74 to 1.09; p = 0.26]). In the validation MACRO study (n = 1018), higher bilirubin was associated with a significantly lower hazard for AECOPD (aHR 0.80 per log10 increase [95%CI: 0.67 to 0.94; p = 0.008]).Bilirubin may be a biomarker of AECOPD risk and may be a novel therapeutic target to reduce AECOPD risk.ClinicalTrials.gov NCT01061671 (registered 02 February 2010) and ClinicalTrials.gov NCT00325897 (registered 12 May 2006).

SUBMITTER: Brown KE

PROVIDER: S-EPMC5655988 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations.

Brown Kirstin E KE Sin Don D DD Voelker Helen H Connett John E JE Niewoehner Dennis E DE Kunisaki Ken M KM

Respiratory research 20171024 1

<h4>Background</h4>Bilirubin is a potent anti-oxidant and higher serum concentrations of bilirubin have been associated with better lung function, slower lung function decline, and lower incidence of chronic obstructive pulmonary disease (COPD). We sought to determine whether elevated bilirubin blood concentrations are associated with lower risk for acute exacerbations of COPD (AECOPD).<h4>Methods</h4>We performed a secondary analyses of data in the Simvastatin for Prevention of Exacerbations in ...[more]

PMID: 29065885

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Project description:Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 ?g/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

Dataset Information

Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations.

Publications

Serum bilirubin and the risk of chronic obstructive pulmonary disease exacerbations.

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