Lung function trajectories in common variable immunodeficiencies: An observational retrospective multicenter study

Helena Buso; Davide Firinu; Renato Finco Gambier; Riccardo Scarpa; Giulia Garzi; Valentina Soccodato; Giulia Costanzo; Andrea G Ledda; Nicolò Rashidy; Ilaria Bertozzi; Stefania Nicola; Giulio Tessarin; Mauro Ramigni; Cinzia Piovesan; Fabrizio Vianello; Andrea Vianello; Stefano Del Giacco; Vassilios Lougaris; Luisa Brussino; Mark G Jones; Isabella Quinti; Carlo Agostini; Marcello Rattazzi; Cinzia Milito; Francesco Cinetto

doi:10.1016/j.jaci.2024.10.037

Lung function trajectories in common variable immunodeficiencies: An observational retrospective multicenter study

J Allergy Clin Immunol. 2024 Nov 19:S0091-6749(24)01230-2. doi: 10.1016/j.jaci.2024.10.037. Online ahead of print.

Authors

Helena Buso¹, Davide Firinu², Renato Finco Gambier¹, Riccardo Scarpa¹, Giulia Garzi³, Valentina Soccodato³, Giulia Costanzo⁴, Andrea G Ledda⁴, Nicolò Rashidy⁵, Ilaria Bertozzi¹, Stefania Nicola⁵, Giulio Tessarin⁶, Mauro Ramigni⁷, Cinzia Piovesan⁷, Fabrizio Vianello⁸, Andrea Vianello⁹, Stefano Del Giacco⁴, Vassilios Lougaris⁶, Luisa Brussino⁵, Mark G Jones¹⁰, Isabella Quinti³, Carlo Agostini¹, Marcello Rattazzi¹, Cinzia Milito³, Francesco Cinetto¹

Affiliations

¹ Department of Medicine, DIMED, University of Padova, Padova, Italy; Internal Medicine 1, Ca' Foncello University Hospital, AULSS2, Treviso, Italy.
² Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy. Electronic address: davide.firinu@unica.it.
³ Department of Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
⁴ Department of Medical Sciences and Public Health, University of Cagliari, Monserrato, Italy.
⁵ Department of Medical Sciences, University of Torino & Mauriziano Hospital, Torino, Italy.
⁶ Department of Clinical and Experimental Sciences, Paediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, University of Brescia, Brescia, Italy.
⁷ Epidemiology Service, AULSS2, Treviso, Italy.
⁸ Hematology Unit, Department of Medicine, University of Padova, Padova, Italy.
⁹ Department of Cardio-Thoracic, Respiratory Pathophysiology Division, University of Padova, Padova, Italy.
¹⁰ Clinical and Experimental Sciences & NIHR Southampton Biomedical Research Centre, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

PMID: 39566607
DOI: 10.1016/j.jaci.2024.10.037

Abstract

Background: Respiratory disease is a frequent cause of morbidity and mortality in common variable immunodeficiencies (CVIDs); however, lung function trajectories are poorly understood.

Objective: We sought to determine lung physiology measurements in CVIDs, their temporal trajectory, and their association with clinical and immunologic parameters.

Methods: This retrospective study from 5 Italian centers included patients with CVIDs who had longitudinal pulmonary function tests (PFTs) and chest computed tomography scan available. Applying the European Respiratory Society/American Thoracic Society 2021 standard, PFTs were expressed as percentile value within the normal distribution of healthy individuals, with the 5th percentile identified as lower limit of normal (LLN). The association of lung function with clinical and immunologic parameters was investigated.

Results: The study included 185 patients with CVIDs; 64% had at least 1 lung comorbidity (bronchiectasis: 41%; granulomatous interstitial lung diseases: 24%). At first spirometry, median FEV₁ was 3.07 L (interquartile range: 2.40-3.80 L), at the 32nd percentile (6th-61st percentile), and median forced vital capacity (FVC) was 3.70 L (interquartile range: 3.00-.54 L), at the 29th percentile (7th-49th percentile). Of patients, 23% had FEV₁ < LLN, and 21% had FVC < LLN. Switched-memory B cells <2% were associated with both FEV₁ < LLN (odds ratio 7.58) and FVC < LLN (odds ratio 3.55). In 112 patients with at least 5 years of PFTs, we found no significant difference between measured and predicted annual decline of FEV₁ (25.6 mL/year vs 20.7 mL/year) and FVC (15.6 mL/year vs 16.2 mL/year).

Conclusions: In our study, lung volumes of the majority of patients with CVIDs were in the lower third of normal distribution of healthy individuals. After diagnosis, rate of lung decline was not accelerated.

Keywords: B cell subtypes; Common variable immunodeficiencies; Global Lung Function Initiative (GLI); bronchiectasis; chronic obstructive pulmonary disease (COPD); granulomatous lymphocytic interstitial lung disease (GLILD); pulmonary function tests.