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Table 1 Associations between serum bilirubin and clinically relevant outcomes

From: Serum bilirubin and chronic obstructive pulmonary disease (COPD): a systematic review

First author, year Measure Outcome Model covariates
Apperly 2015 [13] Logistic regression of relationship between bilirubin quintile and mortality OR of mortality in quintile 1 vs 5 (reference) 1.15 (95% CI 0.80–1.65; p = 0.32)
OR of respiratory mortality in quintile 1 vs 5 (reference) 1.59 (95% CI 0.50–5.11; p = 0.58)
Age, sex, BMI, race, and pack-years smoked
Brown 2017 [19] Time dependent multivariable Cox proportional hazards analysis for time to first AECOPD STATCOPE (development and calibration): aHR per log(10) increase in bilirubin = 0.89 (95% CI 0.74–1.09; p = 0.26)
MACRO (validation): aHR per log(10) increase in bilirubin = 0.80 (95% CI 0.67–0.94; p = 0.008)
Treatment assignment, sex, race, BMI, chronic bronchitis, supplemental O2 use, SGRQ score, inhaler use, steroid or antibiotic use in last year
Treatment assignment, sex, race, BMI, bronchitis, supplemental O2 use, SGRQ score, inhaler use, steroid or antibiotic use in last year
Horsfall 2011 [17] Poisson regression between overall mortality and bilirubin levels
Poisson regression between diagnosis of COPD and bilirubin levels
Men: aIRR per 0.1 mg/dL increase in bilirubin 0.97 (95% CI 0.97–0.98; p < 0.001)
Women: aIRR per 0.1 mg/dL increase in bilirubin 0.97 (95% CI 0.96–0.98; p < 0.001)
Men: aIRR per 0.1 mg/dL increase in bilirubin 0.94 (95% CI 0.93–0.95; p < 0.001)
Women: aIRR per 0.1 mg/dL increase in bilirubin 0.94 (95% CI 0.92–0.95; p < 0.001)
Age, BMI, systolic blood pressure, smoking status, alcohol intake, social deprivation score
Treatment assignment, sex, race, BMI, bronchitis, supplemental O2 use, SGRQ score, inhaler use, steroid or antibiotic use in last year
Lee 2018 [22] Modified Poisson regression for risk of COPD in high vs low bilirubin aRR 1.17 (95% CI 0.80–1.71; p = 0.431) Age, sex, BMI
Leem 2019 [27] Cox regression model for mortality
Linear mixed model and generalized estimating equations for number of exacerbations per year, 6 MW, CAT, and SGRQ
HR = 1.60 (95% CI 0.65–3.97; p = 0.311)
# Exacerbations/year: β = 0.62 (SE 0.18; p = 0.001)
6 MW: β = 20.5 (SE 12.2; p = 0.094)
CAT: β = 0.4 (SE 1.2; p = 0.746)
SGRQ: β = 2.9 (SE 2.5; p = 0.261)
age, sex, BMI, Smoking, baseline FEV1
Milevoj Kopcinovic 2016 [29] Bilirubin in COPD vs controls by Mann–Whitney or t-test 6.4 (IQR 5.2–8.3) vs 7.1 (IQR 5.5 to 10.9); p = 0.102 No difference so not included in additional analysis
Wei 2015 [28] Bilirubin in COPD vs controls by one-way ANOVA No significant difference, values not reported None
  1. OR odds ratio, BMI body mass index, aIRR adjusted incidence rate ratio, HR hazard ratio, FEV1 forced expiratory volume in 1 s, 6MW 6 min walk, CAT COPD assessment test, SGRQ St. George’s Respiratory Questionnaire, AECOPD acute exacerbation of COPD, aHR adjusted hazard ratio, CI confidence interval, SE standard error, STATCOPE Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD, MACRO Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease