Managing Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders: e-GLILDnet International Clinicians Survey.

Annick A J M Van De Ven,Véronique Meignin,Isabella Quinti,Antje Prasse,Siobhan O Burns,Marion Malphettes,Tiago M Alfaro,Børre Fevang,Stephen Jolles,Daiana Stolz,Joseph Jacob,Alexandra Robinson,Klaus Warnatz,Tomas Milota,Joris Van Montfrans,John R Hurst,Alison M Condliffe,Andrew R Gennery,Filomeen Haerynck,Ulrich Baumann,Anne Bergeron,Elisabetta Renzoni

doi:10.3389/fimmu.2020.606333

Abstract

BackgroundGranulomatous–lymphocytic interstitial lung disease (GLILD) is a rare, potentially severe pulmonary complication of common variable immunodeficiency disorders (CVID). Informative clinical trials and consensus on management are lacking.AimsThe European GLILD network (e-GLILDnet) aims to describe how GLILD is currently managed in clinical practice and to determine the main uncertainties and unmet needs regarding diagnosis, treatment and follow-up.MethodsThe e-GLILDnet collaborators developed and conducted an online survey facilitated by the European Society for Immunodeficiencies (ESID) and the European Respiratory Society (ERS) between February–April 2020. Results were analyzed using SPSS.ResultsOne hundred and sixty-one responses from adult and pediatric pulmonologists and immunologists from 47 countries were analyzed. Respondents treated a median of 27 (interquartile range, IQR 82–maximum 500) CVID patients, of which a median of 5 (IQR 8–max 200) had GLILD. Most respondents experienced difficulties in establishing the diagnosis of GLILD and only 31 (19%) had access to a standardized protocol. There was little uniformity in diagnostic or therapeutic interventions. Fewer than 40% of respondents saw a definite need for biopsy in all cases or performed bronchoalveolar lavage for diagnostics. Sixty-six percent used glucocorticosteroids for remission-induction and 47% for maintenance therapy; azathioprine, rituximab and mycophenolate mofetil were the most frequently prescribed steroid-sparing agents. Pulmonary function tests were the preferred modality for monitoring patients during follow-up.ConclusionsThese data demonstrate an urgent need for clinical studies to provide more evidence for an international consensus regarding management of GLILD. These studies will need to address optimal procedures for definite diagnosis and a better understanding of the pathogenesis of GLILD in order to provide individualized treatment options. Non-availability of well-established standardized protocols risks endangering patients.

Highlights

Common variable immunodeficiency (CVID) disorders are the most prevalent symptomatic primary immunodeficiency (PID) conditions, characterized by hypogammaglobulinemia together with an increased susceptibility to infections and/or, in a minority of patients, clinically significant immune dysregulation [1]
With generally efficacious administration of immunoglobulin substitution and antimicrobial agents, immune dysregulation imposes the heaviest burden on morbidity and mortality of CVID patients
Lung involvement is very common in CVID disorders and typically has two not mutually exclusive entities: structural abnormalities such as bronchial wall thickening, air trapping and bronchiectasis that can arise as complications of recurrent bronchopulmonary infections; and interstitial lung disease (ILD) including parenchymal and interstitial abnormalities that are considered to be driven by intrinsic CVID-related immune dysregulation

Summary

Introduction

Common variable immunodeficiency (CVID) disorders are the most prevalent symptomatic primary immunodeficiency (PID) conditions, characterized by hypogammaglobulinemia together with an increased susceptibility to infections and/or, in a minority of patients, clinically significant immune dysregulation [1]. Lung involvement is very common in CVID disorders and typically has two not mutually exclusive entities: structural abnormalities such as bronchial wall thickening, air trapping and bronchiectasis that can arise as complications of recurrent bronchopulmonary infections; and interstitial lung disease (ILD) including parenchymal and interstitial abnormalities (ground glass opacities, nodules and consolidation) that are considered to be driven by intrinsic CVID-related immune dysregulation. This ILD in CVID disorders is commonly referred to as granulomatous-lymphocytic interstitial lung disease or GLILD.

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