Introduction: Pulmonary manifestations are the major cause of morbidity and mortality in patients with inborn errors of immunity (IEI). Early recognition and treatment may improve outcome yet requires sensitive diagnostic methods. Multiple-breath washout (MBW) is already established for the assessment of cystic fibrosis (CF) lung disease including the detection of early lung involvement prior to clinical signs and symptoms.

Aims and objectives: The aim of this study was to compare MBW and spirometry in patients with IEI and CF as well as healthy controls (HC) and to evaluate the sensitivity of lung clearance index (LCI) to detect IEI lung disease.

Methods: Patients were recruited from our pediatric and adult immunodeficiency outpatient clinics. In addition, control groups of CF patients and HC were included. Nitrogen-MBW measurement and spirometry were performed with the study participants.

Results: In total, 342 participants (114 IEI, 114 CF, 114 HC) with a median (range) age of 21.0 (3.7-76.9) years were included. LCI (p<0.001) and FEV1 z-score (p<0.001) differed significantly between the groups and had a median (interquartile range) of 7.0 (6.5-7.9) and -0.6 (-1.4-0.1) in the IEI group, 8.9 (6.8-14.2) and -1.1 (-2.7--0.3) in the CF group and 6.5 (6.2-6.9) and -0.1 (-0.8-0.5) in the HC group. Nineteen (20.7%) of 92 IEI patients and 35 (33.3%) of 105 CF patients had an elevated LCI but a normal FEV1 z-score.

Conclusion: We demonstrated that LCI is sensitive to detect early lung disease in patients with IEI. Future studies will investigate longitudinal measurements as well as the correlation with radiological imaging methods in different subgroups of IEI patients.