Deficits in circulating Club cell secretory protein (CC16) levels are strongly and independently associated with asthma, especially asthma with frequent symptoms, from childhood through mid-adult life, according to a study in the American Journal of Respiratory and Critical Care Medicine.
Lowered levels of CC16, a major anti-inflammatory protein circulating in airways, has been associated with poorer lung function. Although research suggests CC16 deficits may be a possible biomarker in chronic obstructive pulmonary disease, it is unclear whether a deficit in CC16 is associated with asthma. Researchers therefore sought to characterized the longitudinal relationship between circulating CC16 and asthma, using data from 3 independent, prospective birth cohorts: the Tucson Children’s Respiratory Study (TCRS), the Swedish Barn/children, Allergy, Milieu, Stockholm, Epidemiological survey (BAMSE), and the UK Manchester Asthma and Allergy Study (MAAS). The researchers also explored whether CC16 levels in early childhood predicted the course of asthma in adulthood.
The study cohort included participants from the 3 birth cohorts who had corresponding CC16 and asthma data for analysis, which amounted to:
- 814 participants from TCRS (49% male; 22% with parental asthma; 16% with maternal smoking during pregnancy);
- 2547 participants from BAMSE (47% male; 22% with parental asthma; 12% with maternal smoking during pregnancy); and
- 745 from MAAS (55% male; 30% with parental asthma; 29% with maternal smoking during pregnancy).
Circulating CC16 levels were measured with enzyme-linked immunoassay (ELISA). Active asthma was defined as having physician-diagnosed asthma with active symptoms (at least 1 asthma attack or wheeze occurrence during the previous year). Persistence of symptoms was defined as having active symptoms in at least 50% of follow-up surveys with available data.
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[T]hese findings support a possible protective role of CC16 in asthma and warrant future studies to investigate systematically the potential use of this protein in risk stratification and as a therapeutic target in asthma.
Circulating CC16 levels were inversely related to active asthma, according to generalized estimating equations models from childhood to adult life, after adjustment for survey year, sex, race-ethnicity, parental asthma, and childhood atopy. The associations were consistent among all groups. A 1-SD reduction in CC16 concentrations increased the odds for active asthma by 20% (meta-analyzed adjusted OR [adjOR] 1.20; 95% CI, 1.12-1.28; P <.0001).
The association between CC16 and active asthma was more pronounced among those with frequent symptoms; risk for asthma with frequent symptoms increased by 40% for each 1-SD reduction in CC16 levels (meta-analyzed adjusted relative risk ratio [adjRRR] 1.40; 95% CI, 1.24-1.57; P < .0001), and the risk for asthma with infrequent symptoms was substantially smaller although statistically significant.
The low CC16 tertile was strongly associated with an increased risk for persistence of frequent symptoms after adjustment for sex, baseline symptom frequency, and childhood atopy (adjusted meta-analyzed OR 3.72; 95% CI, 1.78-7.76; P <.0001).
Study limitations include the relatively small number of children with asthma included in the analyses of prediction of symptom persistence. Also, variation in blood collection protocols and sample type may have affected comparability among the cohorts.
“Together with existing evidence for a causal relationship, these findings support a possible protective role of CC16 in asthma and warrant future studies to investigate systematically the potential use of this protein in risk stratification and as a therapeutic target in asthma,” stated the study authors.
