C73-21 Novel Functional Measures Reflect Structural Lung Abnormalities in Inborn Errors of Immunity

Rationale

Inborn errors of immunity (IEIs) are inherited conditions marked by recurrent infection and immune-driven inflammation frequently leading to chronic lung disease¹. These pulmonary complications can develop silently over time, progressing to irreversible damage without sensitive surveillance and timely intervention². Although computed tomography (CT) is the most sensitive modality for detecting early lung abnormalities3, cumulative radiation exposure limits its suitability for longitudinal monitoring, particularly in radiosensitive IEIs4. We therefore evaluated two novel non-radiographic techniques, hyperpolarized 129Xe magnetic resonance imaging (XeMRI) and multiple-breath nitrogen washout (MBW), and evaluated their relationships with CT-based structural scores in a diverse cohort of people with IEIs (pwIEI).

Methods

MBW and XeMRI were performed during a single visit, with CT and spirometry data collected from clinical records within three months. Primary functional outcomes were the lung clearance index (LCI2.5) from MBW and ventilation defect percent (VDP) from XeMRI, reflecting whole-lung ventilation inhomogeneity5,6. Z-scores for FEV1, LCI2.5 and VDP were derived from reference equations7-9. CT severity was evaluated using a modified version of an existing semi-quantitative scoring system for radiologic manifestations in common variable immunodeficiency10. This tool assessed both the severity and extent of nine distinct radiologic airway and interstitial findings commonly seen in IEI-related lung disease. Two-tailed Spearman correlations were evaluated for CT scores with z-scored FEV₁, LCI2.5, and VDP.

Results

A total of 16 pwIEIs (2F/14M; median age 18 years [Q1-Q3: 12-38]) were included. Median (Q1-Q3) values were: FEV1 = −0.46 (-1.60-0.45), LCI2.5=1.11 (0.46-2.98), VDP=0.83 (0.52-2.77), and CT score=34.5 (18.0-51.5) Abnormal outcomes (z < −1.65 for FEV1; z > 1.65 for LCI2.5 and VDP) occurred in 3/14 (21.4%) for FEV1, 6/15 (40.0%) for LCI2.5, and 5/14 (35.7%) for VDP. LCI2.5 and VDP were significantly correlated with CT scores: LCI2.5 (rs = −0.90, p < 0.0001), and VDP (rs=0.70, p = 0.004; Figure 1). FEV1 was not significantly associated with CT scores.

Conclusions

LCI and VDP correlated with CT-based structural assessments in pwIEIs, suggesting a relationship between subtle structural abnormalities and early functional impairment. MBW and XeMRI can be considered for radiation-sparing tools for longitudinal monitoring in pwIEIs.REFERENCES: (1) Patrawala ClinImmunol 2020; (2) Manson PedRadiol 1997; (3) Touw PedAllergyImmunol 2010; (4) Beyls ClinImmunol 2025; (5) Busack ERJ 2023; (6) Rayment ERJ 2019; (7) Bowerman AJRCCM 2022; (8) Ramsey ERJ 2024; (9) Bdaiwi AJRCCM 2025; (10) vandeVen Chest 2010.

This abstract is funded by: BC Children’s Hospital Childhood Diseases Theme