Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency

Summary Common variable immunodeficiency (CVID) is a common primary immune deficiency, caused by undefined defects in lymphocyte function, and is treated routinely by immunoglobulin substitution. CVID complications include airway disease (AD) and interstitial lung disease (ILD). It was not known if AD and ILD in CVID have a common immunological aetiology and should be considered separate features of the same disease, or as distinct syndromes that require specialized monitoring and treatment. We used high‐resolution computed tomography (CT) to diagnose AD or ILD in paediatric CVID patients. Spirometry and body plethysmography did not differentiate between ILD and AD. Patients with AD ( n  = 11, 20%) developed more pneumonias while children with ILD ( n  = 8, 15%) showed immune dysregulation characterized by autoimmune complications, more severe memory B cell reduction and expansion of non‐naive cytotoxic T cells. In conclusion, ILD and AD in CVID have dissimilar clinical and immunological characteristics, suggesting distinct aetiology requiring tailored monitoring and treatment of these patient subgroups.