High concentrations of plasma complement C3 may be associated with an increased risk for asthma hospitalizations in the general population and with a high risk for asthma exacerbations in patients with allergic asthma, according to an analysis published in the European Respiratory Journal.

Researchers analyzed a prospective study of the general population residing in Greater Copenhagen, Denmark — the Copenhagen General Population Study (CGPS) — that was originally conducted between 2003 and 2013.

In the current analysis, investigators sought to test the hypothesis that high plasma complement C3 levels are linked to a high risk for asthma exacerbations and for hospitalizations for asthma. Of a total of 101,029 individuals from CGPS, the risk for asthma hospitalizations was evaluated using baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608, and rs448260 to establish levels of complement C3. Additionally, the risk for asthma exacerbations was evaluated in a total of 2248 persons with allergic asthma.

Continue Reading

Allergic asthma was defined as asthma with <10 pack-years of smoking, a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) above the lower limit of normal, and the reporting of allergy. Further, asthma was defined as an affirmative response to the question “Do you have asthma?” Allergy was self-reported based on the CGPS questionnaire if the respondent reported asthma, eczema, or hay fever as a reaction to food, medication, animal hair, grass, flowers, or other allergens.

Results demonstrated that the multivariable adjusted hazard ratio (HR) of asthma hospitalizations was 1.23 (95% CI, 1.04-1.45) for those persons in the highest tertile (ie, >1.19 g/L) of plasma complement C3, compared with those in the lowest tertile (<1.03 g/L). The C3 rs448260 genotype was associated with a risk for asthma hospitalizations (HR, 1.17; 95% CI, 1.06-1.28) for the CC genotype compared with the AA genotype.

Additionally, high levels of plasma complement C3 were linked to increased levels of blood eosinophils and immunoglobulin E (IgE; P for trends ≤6∙10-9); however, only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (P =3∙10-4) and IgE level (P =3∙10-4). In patients with allergic asthma, the multivariable adjusted incidence rate ratio for asthma exacerbation risk was 1.69 (95% CI, 1.06-2.72) in those in the highest plasma complement C3 tertile (>1.24 g/L) vs those in the lowest plasma complement C3 tertile (<1.06 g/L).

The investigators concluded that the findings suggest a causal role played by the complement system in the severity of asthma and in an individual’s predisposition to asthma exacerbations.


Vedel-Krogh S, Rasmussen KL, Nordestgaard BG, Nielsen SF. Complement C3 and allergic asthma: a cohort study of the general population. Eur Respir J. Published online August 18, 2020. doi:10.1183/13993003.00645-2020