Abstract Rationale Inborn errors of immunity (IEIs) are inherited disorders that often cause chronic lung disease in up to 40% of affected individuals, driven by recurrent infections and immune-mediated inflammation1. Early identification of pulmonary involvement in people with IEIs (pwIEIs) is essential to reduce both morbidity and mortality2. However, current screening methods for lung disease have significant limitations. Spirometry lacks the sensitivity to detect early or regional changes in lung function, while common imaging modalities involve ionizing radiation exposure. To address this gap, we evaluated pulmonary ventilation using hyperpolarized 129-xenon magnetic resonance imaging (XeMRI), in a diverse cohort of pwIEIs and compared these findings with spirometry and multiple-breath nitrogen washout (MBW). Methods MBW and XeMRI procedures were performed during a single study visit, with spirometry data obtained from clinical records within three months. The MBW primary outcome was the lung clearance index (LCI), reflecting ventilation heterogeneity3. The XeMRI primary outcome measure was the ventilation defect percent (VDP) reflecting whole-lung ventilation inhomogeneity4. Z-scores for spirometry and MBW measures were calculated using Global Lung Function Initiative reference equations5,6, while VDP z-scores were derived from normative equations developed by the XeMRI Clinical Trials Consortium7. One-tailed Spearman correlations were conducted between z-scored VDP, FEV1 and LCI2.5. Results A total of 18 pwIEIs (3F/15M; median age 22.8 years Q1-Q3: 15.9 - 36.9) were included. Median (Q1-Q3) values were: FEV1 = −0.1 (−0.7 - 0.7), LCI2.5 = 1.3 (0.5 - 2.5), and VDP = 0.8 (0.5 - 2.5). Abnormal outcomes (z −1.65 for FEV1; z 1.65 for LCI2.5 and VDP) occurred in 3/17 (16.7%) for FEV1, 8/18 (44.4%) for LCI2.5, and 6/18 (33.3%) for VDP. Abnormal VDP showed strongest concordance with LCI2.5 (5/6), compared with FEV1 (2/5). Both lung function measures showed significant correlations with VDP: a negative association with FEV1 (r = −0.5466, p = 0.0126), and a positive association with LCI2.5 (r = 0.7445, p = 0.0002). The negative association between FEV1 and LCI2.5 was not significant. Conclusions XeMRI−derived VDP correlates with sensitive lung health measures, such as LCI, and can detect subtle pulmonary involvement in pwIEIs that may be missed by standard tests. However, its clinical applicability has yet to be evaluated. REFERENCES: (1) Patrawala P, J Clin Immunol 2020; (2) Manson D, Ped Radiol 1997; (3) Busack B, ERJ 2023; (4) Rayment J, ERJ 2019; (5) Bowerman C, AJRCCM 2022; (6) Ramsey K, ERJ 2024; (7) Bdaiwi A, AJRCCM 2025. This abstract is funded by: BC Children’s Research Institute
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