Circulating CC16, immune response to Mycoplasma pneumoniae and lung function: a population-based, multi-cohort study

Background: Sufficient levels of club cell secretory protein (CC16) are essential to protect against lung function impairments. Experimental studies have demonstrated that CC16 modulates inflammatory responses and protects against airway hyperresponsiveness following Mycoplasma pneumoniae (Mp) infection. Individuals with asthma have low CC16 levels and increased susceptibility to Mp infection. Here we determine whether low CC16 and Mp seropositivity have combined effects on lung function deficits predisposing to airflow limitation, particularly in asthma. Methods: Serum levels of CC16 and IgG antibodies against Mp (MpIgG) were measured in adult participants from cohorts BAMSE, MAAS, LSC, and TESAOD. Participants were then stratified into four groups: normal CC16/MpIgG-, normal CC16/MpIgG+, low CC16/MpIgG-, low CC16/MpIgG+. Associations between these groups and lung function (FEV₁ and FEV₁/FVC) were assessed by linear regression, adjusting for covariates. Meta-analyzed estimates were calculated. Results: Low CC16 was associated with decreased lung function in the total population, but no combined effects of CC16 and MpIgG were observed. Among asthmatic participants, the low CC16/MpIgG + group had remarkably lower FEV₁/FVC z-scores (−0.84, CI: 1.29, −0.38) compared to the reference group, and Mp seropositivity was associated with significant deficits in FEV₁/FVC z-scores among those with low CC16 (−0.60, CI: 1.08, −0.12), but not among those with normal CC16 (−0.10, CI: 0.56, 0.36). Conclusion: This suggests that individuals with asthma with low levels of CC16 combined with a history of Mp infection may be more susceptible to deficits in FEV₁/FVC, the hallmark of airflow limitation, emphasizing the need for prospective studies designed to test this hypothesis.