Bronchiectasis in Inborn Errors of Immunity: Prevalence, Predictors, and Cardiopulmonary Complications in a Genetically Characterized Cohort.

PURPOSE: Bronchiectasis poses a serious but incompletely defined burden in patients with inborn errors of immunity (IEI). We determined its prevalence, independent predictors, and cardiopulmonary complications in a genetically characterized IEI cohort to inform care in this vulnerable population.

METHODS

We conducted a cross-sectional analysis of patients enrolled in a National Institutes of Health prospective IEI protocol (2018-2024) who had undergone whole exome or genome sequencing and chest computed tomography (CT). Bronchiectasis was radiologically confirmed, excluding traction bronchiectasis. Predictors were identified by multivariable logistic regression. Cardiopulmonary outcomes included spirometry, lung volumes, diffusing capacity, six-minute walk distance, pulmonary hypertension by echocardiography, and mortality.

RESULTS

Of 229 enrolled patients, 131 were eligible, representing 31 distinct IEIs. Median age at first chest CT was 20 years (IQR 10-33). The most common CT finding was pulmonary nodules (55%). Bronchiectasis prevalence was 27% (95% CI 20-35%). Independent predictors were older age at first CT (aOR 1.04, 95% CI 1.01-1.08), combined immunodeficiency affecting cellular and humoral immunity (aOR 4.30, 95% CI 1.42-14.54), predominantly antibody deficiencies (aOR 5.83, 95% CI 1.66-22.26), and diseases of immune dysregulation (aOR 7.56, 95% CI 1.07-52.72). Patients with bronchiectasis had greater cardiopulmonary impairment across all measured domains and higher mortality (15% vs. 3%; P = 0.046).

CONCLUSIONS

Bronchiectasis is common across IEI diagnostic classes and carries substantial cardiopulmonary morbidity and excess mortality. Older age at first chest CT and specific IUIS classes, particularly predominantly antibody deficiencies and diseases of immune dysregulation, independently predict bronchiectasis, identifying patients who would benefit most from early pulmonary surveillance.

TRIAL PROTOCOL: NCT03394053.