Pulmonary Rehabilitation in Inborn Errors of Immunity with Bronchiectasis: A Narrative Review with Implications for...

Bronchiectasis is the most frequent chronic structural lung complication of inborn errors of immunity (IEI) and a major driver of morbidity and mortality, even in patients receiving immunoglobulin replacement. Pulmonary rehabilitation (PR), comprising airway clearance, physical activity training and self-management education, is recommended for bronchiectasis in international and national guidelines, yet its evidence base was generated largely in populations in which immunodeficiency was neither characterised nor analysed separately. This narrative review, written from the combined perspectives of clinical immunology and cardiopulmonary rehabilitation, synthesises evidence on rehabilitation in IEI-associated bronchiectasis and considers its relevance to populations with high rates of consanguinity, such as those of the Middle East and North Africa, where autosomal recessive and combined IEIs are over-represented; Saudi Arabia is used as an illustrative example. Evidence specific to IEI is sparse. A single underpowered pilot randomised study (n = 34) of home-based moderate-intensity physical activity in primary immunodeficiency found no between-group difference in infection rates, while observational studies consistently document impaired functional capacity, prominent fatigue, reduced health-related quality of life, and heightened airway and systemic inflammation. Trials of PR in bronchiectasis show short-term gains in functional capacity and quality of life, but none of the trials we examined reported outcomes by aetiology, and no paediatric trials exist. No study has evaluated PR in the IEI categories that predominate in high-consanguinity regions, such as chronic granulomatous disease and the hyper-IgE syndromes, although cohorts from these regions report pulmonary complications as a leading cause of death. Because PR is individually tailored and has a favourable safety profile, its core benefits, including gains in muscle function and cardiorespiratory fitness, are likely to apply regardless of aetiology; the main uncertainties concern how to deliver it safely and how to evaluate it, given that withholding PR from control groups may be unethical. We outline the immunological rationale for rehabilitation in IEI, propose an integrated immunology-rehabilitation care model with personalised delivery, including home-based and tele-rehabilitation to limit cross-infection, and set out a prioritised research agenda that includes pragmatic trial designs, IEI-stratified analyses and immunological endpoints.