Abstract
BACKGROUND: 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).
METHODS: 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.
RESULTS: 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]).
CONCLUSIONS: Bilirubin may be a biomarker of AECOPD risk and may be a novel therapeutic target to reduce AECOPD risk.
TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01061671 (registered 02 February 2010) and ClinicalTrials.gov NCT00325897 (registered 12 May 2006).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 179 |
| Number of pages | 1 |
| Journal | Respiratory research |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 24 2017 |
Bibliographical note
Funding Information:DDS has received advisory board honoraria, research funding and speaking fees from AstraZeneca, meeting honoraria and research funding from Boehringer Ingelheim, research funding from Merck Frosst, and advisory board honoraria from Novartis. DEN has received consulting fees from GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca. KEB, HV, JEC, and KMK declare no competing interests.
Funding Information:
Study supported by National Heart, Lung, and Blood Institute awards to COPD Clinical Research Network sites: U10 HL074407, U10 HL074408, U10 HL074409, U10 HL074416, U10 HL074418, U10 HL074422, U10 HL074424, U10 HL074428, U10 HL074431, U10 HL074439, U10 HL074441. Study also supported by Canadian Institutes for Health Research.
Keywords
- Bilirubin
- Biomarker
- Chronic obstructive
- Pulmonary disease