Integrating Clinics, Laboratory, and Imaging for the Diagnosis of Common Variable Immunodeficiency-Related Granulomatous–Lymphocytic Interstitial Lung Disease

Abstract

BackgroundGranulomatous–lymphocytic interstitial lung disease (GLILD) is a distinct clinic-radio-pathological interstitial lung disease (ILD) that develops in 9% to 30% of patients with common variable immunodeficiency (CVID). Often related to extrapulmonary dysimmune disorders, it is associated with long-term lung damage and poorer clinical outcomes. The aim of this study was to explore the potential use of the integration between clinical parameters, laboratory variables, and developed CT scan scoring systems to improve the diagnostic accuracy of non-invasive tools.MethodsA retrospective cross-sectional study of 50 CVID patients was conducted in a referral unit of primary immune deficiencies. Clinical variables including demographics and comorbidities; analytical parameters including immunoglobulin levels, lipid metabolism, and lymphocyte subpopulations; and radiological and lung function test parameters were collected. Baumann’s GLILD score system was externally validated by two observers in high-resolution CT (HRCT) scans. We developed an exploratory predictive model by elastic net and Bayesian regression, assessed its discriminative capacity, and internally validated it using bootstrap resampling.ResultsLymphadenopathies (adjusted OR 9.42), splenomegaly (adjusted OR 6.25), Baumann’s GLILD score (adjusted OR 1.56), and CD8+ cell count (adjusted OR 0.9) were included in the model. The larger range of values of the validated Baumann’s GLILD HRCT scoring system gives it greater predictability. Cohen’s κ statistic was 0.832 (95% CI 0.70–0.90), showing high concordance between both observers. The combined model showed a very good discrimination capacity with an internally validated area under the curve (AUC) of 0.969.ConclusionModels integrating clinics, laboratory, and CT scan scoring methods may improve the accuracy of non-invasive diagnosis of GLILD and might even preclude aggressive diagnostic tools such as lung biopsy in selected patients.

Common and uncommon CT findings in CVID related GL-ILD: correlations with clinical parameters, therapeutic decisions and potential implications in the differential diagnosis

“…Nodules were divided in small and large, based on their dimension (≤ 10 mm or > 10 mm [22]), de ning the amount (≤ 3 or > 3), the density (solid, ground glass, both), the presence of halo sign around solid nodules or inner calci cations. Small nodules preferential distribution (perilymphatic, centrilobular, random) was also recorded.…”

“…Two thoracic radiologists of 7 and 20 years for experience (NL and MPB) reviewed the literature to de ne a score that could describe CT ndings in both GL-ILD and lung diseases to be considered in differential diagnosis [11][12][13][14][15][17][18][19][20][21][22].…”

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in Common Variable Immunodeficiency (CVID)

“…CVID is a group of immunologic diseases, characterized by lowered IgG, and associated with lowered IgA and/or IgM, and reduced antibody response to infections [ 1 ]. Immunoglobulin replacement therapy proved its value by tackling infectious diseases, which has led to a significant decrease of the morbidity and mortality in CVID patients.…”

Raised Serum Markers of T Cell Activation and Exhaustion in Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency

“…However, it is not clear if different entities of CVID-related ILD, also within the term GLILD, represent different pathological processes or variations within a disease spectrum. GLILD can often be distinguished radiologically from other ILDs by CT findings, and is characterized by reticulation, bronchial wall thickening, pulmonary nodules, and ground glass opacities [ 14 – 16 ].…”