Potential Determinants of Progression from Cough-Variant Asthma to Classic Asthma in Children: Evidence, Mechanisms, and Clinical Research Gaps.

OBJECTIVE

To synthesize current evidence on host and environmental factors potentially associated with progression of cough variant asthma (CVA) to classic asthma in children, with explicit distinction between direct evidence from pediatric CVA cohorts and indirect evidence extrapolated from general asthma or adult studies, and to identify research gaps for future investigation.

DATA SOURCES: PubMed, EMBASE, and Web of Science were searched for studies examining CVA progression, risk factors, and mechanisms in pediatric populations.

STUDY SELECTIONS: Original research articles, meta-analyses, and systematic reviews investigating genetic susceptibility, atopy, airway hyperresponsiveness, medication adherence, diet, psychological stress, respiratory infections, allergen exposure, and indoor air pollution in relation to CVA-to-classic asthma progression in children aged <18 years were included.

RESULTS

Atopy and airway hyperresponsiveness carry the most consistent evidence. Poor medication adherence is the most readily modifiable risk factor. Environmental triggers include respiratory viral infections (particularly rhinovirus), allergen exposure, and indoor air pollution. These factors converge on Th2-biased immunity, epithelial barrier dysfunction, neuroimmune interactions, and epigenetic reprogramming. A nomogram integrating clinical variables and biomarkers achieved AUCs of 0.929 and 0.914 in training and validation cohorts, respectively, but validated prediction tools for CVA progression remain unavailable.

CONCLUSION

Early identification of high-risk children through integrated clinical and biomarker assessment, combined with comprehensive management targeting modifiable risk factors, remains the most rational approach to symptom control, exacerbation prevention, and preservation of lung function; whether this delays progression awaits validation in pediatric interventional trials.