Complement C3 and allergic asthma: A cohort study of the general population.
Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration was associated with high risk of asthma hospitalisations and exacerbations.We prospectively assessed the risk of asthma hospitalisations in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608, and rs448260 determining levels of complement C3. Risk of asthma exacerbations was further assessed in 2248 individuals with allergic asthma.The multivariable adjusted hazard ratio of asthma hospitalisations was 1.23(95% confidence interval 1.04-1.45) for individuals in the highest tertile(>1.19 g·L-1) of plasma complement C3 compared with those in the lowest tertile(<1.03 g·L-1). The C3 rs448260 genotype was associated with risk of asthma hospitalisations with an observed hazard ratio of 1.17(1.06-1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE(p for trends ≤6·10-9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count(p=3·10-4) and level of IgE(p=3·10-4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbations was 1.69(1.06-2.72) for individuals in the highest plasma complement C3 tertile(>1.24 g·L-1) versus the lowest(<1.06 g·L-1).In conclusion, high concentration of plasma complement C3 was associated with high risk of asthma hospitalisations in the general population and with high risk of asthma exacerbations in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.