Serum Bilirubin and Risk of Respiratory Disease and Death

Horsfall, Laura; Rait, Greta; Walters, Kate; Swallow, Dallas M.; Pereira, Stephen P.; Nazareth, Irwin; Petersen, Irene

doi:10.1001/jama.2011.124

Cited by 194 publications

(202 citation statements)

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“…These associations are also reported in individuals with Gilbert syndrome (9,10). Several findings suggest preventive effects of unconjugated bilirubin (UCB) on cancer development, showing that the prevalence and incidence of lung and colon cancer is reduced with increasing circulating UCB concentrations (7,11). Recently, a possible protective role of the UGT1A1 Ã 28 allele on colorectal cancer (CRC) was detected and patients with CRCs had lower serum bilirubin levels than controls (10).…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models

Wallner

Antl

Rittmannsberger

et al. 2013

Cancer Prevention Research

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The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared to matched controls. Seventy-six individuals (age-and sex-matched) were allocated into Gilbert syndrome (UCB !17.1 mmol/L; n ¼ 38) or control groups (UCB < 17.1 mmol/L; n ¼ 38). In addition, 40 Gunn rats were used to support the results of the human trial. Single-cell gel electrophoresis (SCGE) assay measuring standard conditions (strand breaks, apurinic/apyrimidinic sites) and formamidopyrimidine glycosylase (FPG)-sensitive sites was conducted in human peripheral blood mononuclear cells (PBMC) and rat PBMCs, colon, and hepatocytes. Furthermore, urinary 8-oxo-2 0 -deoxyguanosine (8oxodGuo, DNA oxidation) and 8-oxoguanosine (8oxoGuo, RNA oxidation) were measured in humans. The Gilbert syndrome and Gunn rat groups had significantly higher UCB levels (P < 0.001) than the corresponding controls. No further differences in damage to DNA or RNA were detected between the two groups, except higher strand breaks (PBMCs) in Gunn rats when compared with controls. However, when demographic effects were analyzed, lower 8oxodGuo concentrations were detected in the human group with a BMI !25 kg/m 2 (1.70 AE 0.67 vs. 1.38 AE 0.43 nmol/mmol creatinine, P < 0.05), although this group showed lower UCB levels than normal weight subjects. This study suggests that the disease preventative effect of UCB is unrelated to DNA oxidation/strand breaks in human and animal models of hyperbilirubinaemia. Cancer Prev Res; 6(10); 1056-63. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 90%

“…Importantly, epidemiologic evidence suggests a preventive role for bilirubin in disease development, specifically in regard to cardiovascular disease and cancer (7,8). These associations are also reported in individuals with Gilbert syndrome (9,10).…”

Section: Introductionmentioning

confidence: 99%

Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models

Wallner

Antl

Rittmannsberger

et al. 2013

Cancer Prevention Research

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“…• Relatively higher levels of bilirubin were associated with a lower risk of pulmonary disease and all-cause mortality (23). Bilirubin possesses anti-oxidant, anti-inflammatory, and anti-proliferative effects (24).…”

Section: Other Candidate Biomarkers In Copdmentioning

confidence: 99%

Chronic Obstructive Pulmonary Disease Biomarkers

Beiko¹,

Strange²

2016

Eurasian J Pulmonol

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Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD) and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD) continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

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“…The antioxidant properties of this enzyme are mediated largely via intracellular generation of free bilirubin, which functions physiologically to inhibit certain NADPH oxidase complexes [43][44][45][46]. Intriguingly, in a massive prospective study in the UK, serum levels of bilirubin at baseline were found to correlate inversely with risk for both COPD and lung cancer, after controlling for smoking habit [47]. Likewise, in a case -control study, serum free bilirubin was lower in patients with COPD than without [48].…”

Section: Complementary Protection From Spirulina?mentioning

confidence: 99%

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

Mf¹

2016

J Nutr Food Sci

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Evidence has accumulated over the last twenty years that smokers who frequently ingest fish are at lower risk for both chronic obstructive pulmonary disease (COPD) and lung cancer. Plasma phospholipid levels of DHA, but not EPA, have been reported to correlate inversely with risk for COPD in smokers, suggesting that DHA may be primarily responsible for the apparent protection afforded to lungs of smokers by fish consumption. Meanwhile, evidence is emerging that certain metabolites of DHA -including 4 -hydroxy hexenal (4-HHE), 17 -oxo -DHA, and resolvin D1 -can activate Nrf2 -mediated transcription of heme oxygenase -1 and other antioxidant / cytoprotective enzymes. Since the oxidant stress imposed by cigarette smoke exposure could be expected to promote peroxidation of membrane DHA and hence boost production of 4 -HHE, DHA in lung membranes may in effect up-regulate the protective feedback mechanism whereby oxidative stress provokes Nrf2 -mediated induction of cytoprotective enzymes. DHA can also give rise to the autacoid resolvin D1, which, via activation of a receptor, suppresses NFkappaB activation and the consequent production of pro-inflammatory cytokines. Resolvin D1 can also inhibit macrophage NADPH oxidase and promote an anti-inflammatory M2 phenotype in lung macrophages. Not surprisingly, inhalation of resolvin D1 has a marked anti-inflammatory impact on the lungs of mice exposed to tobacco smoke. These considerations help to rationalize the epidemiology linking fish consumption to lung health, and suggest that smokers who can't or won't quit their habit would be well advised to consume fish or DHA supplements regularly. Higher intakes of fruits and vegetables -likely in part because many of these contain Nrf2 -activating phytochemicals -likewise are associated with lower risk for COPD, and can be recommended for smokers.Keywords: COPD; Lung cancer; Fish; Docosahexaenoic acid (DHA); 4 -hydroxy hexenal; Nrf2; Resolvin D1 Fish Consumption May Protect Smokers from COPDLimited but nonetheless compelling epidemiology has linked heavy dietary consumption of fresh fish to marked decreases in risk for lung cancer and chronic obstructive pulmonary disease (COPD) among smokers. The first key evidence in this regard emerged in 1994. Shahar et al.[1] studied subjects enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study, who had received a dietary assessment and a physical exam including lung spirometry, and had been questioned regarding lung symptoms [1]. COPD was defined by three separate criteria: self -reported symptoms of chronic bronchitis, physician diagnosis of emphysema, and via spirometry (FEV1 < 65% of predicted value). When risk for COPD was compared between the first and fourth quartiles of estimated daily intake of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), relative risk for COPD in the fourth quartile (mean omega-3 intake 480 mg) after appropriate multivariate adjustments was found to be 0.66 (95% CI 0.52 -0.85), 0.31 (CI 0.18 -0.52), and 0.50 (CI 0.32...

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Serum Bilirubin and Risk of Respiratory Disease and Death

Abstract: Among patients with normal-range bilirubin levels in primary care practices, relatively higher levels of bilirubin were associated with a lower risk of respiratory disease and all-cause mortality.

Cited by 194 publications

References 31 publications

Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models

Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models

Chronic Obstructive Pulmonary Disease Biomarkers

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

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