Cystic Fibrosis-Asthma Overlap Syndrome: Current Understanding and Future Directions.Pediatr Pulmonol 2026 Jun; 61(6):e71682.PP
BACKGROUND
Cystic fibrosis-asthmaoverlap syndrome (CFAOS) has high incidence in people with CF (pwCF) yet remains poorly defined, hindering both diagnosis and treatment. Asthmatic type2 (T2) inflammation (eosinophilia, elevated IgE, and increased IL-4/IL-5/IL-13), identifies an endo type within the CF community with accelerated disease progression and increased mortality. However, diagnostic criteria for asthma in the general population are less useful inpwCF due to overlapping phenotypes generated by chronic inflammation and structural lung disease. Therapeutically, the lack of standardized CFAOS diagnostic criteria has led to the heterogenous use of asthma-directed therapies, with inconsistent benefits.
OBJECTIVE
This review summarizes current CFAOS diagnostic and therapeutic approaches, explores the role of T2 inflammation in CFpathophysiology, and identifies critical research priorities for defining clinically meaningful subgroups and optimizing treatment strategies.
METHODS
We conducted a comprehensive literature search of peer-reviewed publications on the PubMed database related to asthma diagnosis and treatment, markers of T2 inflammation in samples from pwCF, CFAOS.
RESULTS
Emerging evidence suggests that CFTR deficiency in immune cells enhances their responsiveness to T2 stimuli. Combined with individual genetic and environmental contexts that also drive T2 inflammation,this could explain the higher incidence of asthma in pwCF. There is a critical need to better identify asthma in pwCF and transition to using bio markers to select those who would benefit from targeted asthma biologic therapies.
