Multiple-breath washout to detect lung disease in patients with inborn errors of immunity

Leonie M Busack; Stephanie Thee; Yvonne Liu; Christine Allomba; Niklas Ziegahn; Apolline Tosolini; Charlotte O Pioch; Alexandra N Schnorr; Bent R Fuhlrott; Olga Staudacher; Mirjam Völler; Eva Steinke; Leif G Hanitsch; Jobst Röhmel; Volker Wahn; Renate Krüger; Marcus A Mall; Horst von Bernuth; Mirjam Stahl

doi:10.1183/23120541.01019-2023

Multiple-breath washout to detect lung disease in patients with inborn errors of immunity

ERJ Open Res. 2024 Mar 11;10(2):01019-2023. doi: 10.1183/23120541.01019-2023. eCollection 2024 Mar.

Authors

Leonie M Busack¹, Stephanie Thee^{1

2}, Yvonne Liu¹, Christine Allomba¹, Niklas Ziegahn¹, Apolline Tosolini¹, Charlotte O Pioch¹, Alexandra N Schnorr¹, Bent R Fuhlrott¹, Olga Staudacher¹, Mirjam Völler^{1

3}, Eva Steinke^{1

2

3}, Leif G Hanitsch^{2

4

5}, Jobst Röhmel^{1

2

3}, Volker Wahn¹, Renate Krüger¹, Marcus A Mall^{1

2

3}, Horst von Bernuth^{1

2

5

6}, Mirjam Stahl^{1

2

3}

Affiliations

¹ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
² Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
³ German Center for Lung Research, associated partner site, Berlin, Germany.
⁴ Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁵ Berlin Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁶ Department of Immunology, Labor Berlin-Charité Vivantes GmbH, Berlin, Germany.

Abstract

Background: Pulmonary manifestations are the major cause of morbidity and mortality in patients with inborn errors of immunity (IEI). New and more sensitive diagnostic methods can potentially lead to earlier recognition and treatment of IEI lung disease and improve outcome. The aim of this study was to compare multiple-breath washout (MBW) and spirometry in patients with IEI and cystic fibrosis (CF) as well as healthy controls (HC) and to evaluate the sensitivity of lung clearance index (LCI) to assess lung disease in IEI.

Methods: IEI patients (n=114) were recruited from our paediatric and adult immunodeficiency outpatient clinics and compared to age-matched CF patients (n=114) and HC (n=114). MBW measurements and spirometry were performed in the study participants, and MBW testing was repeated after 63-707 days in IEI patients (n=70).

Results: The LCI was significantly higher in IEI patients than in HC (p<0.001) and significantly lower than in CF patients (p<0.001). The forced expiratory volume in 1 s (FEV₁) z-score was significantly lower in IEI patients than in HC (p<0.01) and significantly higher than in CF patients (p<0.01). LCI and FEV₁ z-score correlated moderately negatively in the total cohort, the IEI group and the CF 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. After a median of 364 days, the median LCI of 70 IEI patients increased significantly by 0.2.

Conclusion: MBW is useful to detect lung disease in IEI and is more sensitive than spirometry.