Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP–lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.

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