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

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.