GLILD Diagnosed in Children and Young Adults With Common Variable Immunodeficiency (pGLILD)

Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) Diagnosed in Children and Young Adults With Common Variable Immunodeficiency

8 to 22% of patients with common variable immunodeficiency (CVID) will develop Granulomatous Lymphocytic Interstitial Lung Disease (GLILD), which has emerged as a major cause of mortality. Little is known about GLILD in children and young adults. The aim of this study was to describe the clinical, functional, radiological and pathological features of children and young adults diagnosed with GLILD.

Study Overview

• Status: Unknown
• Conditions: GLILD in a Population of Children and Young Adults

Detailed Description

Variable common immunodeficiency (VCID) encompasses a heterogeneous group of primitive immunodeficiencies, with variable clinical and immunological settings, but globally characterized by hypogammaglobulinemia with significant reduction of Immunoglobulin G levels, often associated with a decrease in Immunoglobulin A and/or Immunoglobulin M levels, coupled with inability to produce antibodies in response to infection and/or immunization. VCID is the most common primary immunodeficiency, with an estimated prevalence between 1/10,000 and 1/50,000. With the introduction of high-dose, intravenous or subcutaneous immunoglobulins, number of infections, along with morbidity and induced mortality, has declined sharply in recent years. Conversely, non-infectious complications, such as autoimmune manifestations, inflammatory bowel diseases, enteropathies, hepatitis, lung disease and lymphoproliferation (up to lymphoma), increased considerably, reaching 70% of patients.

Granulomatous Lymphocytic Interstitial Lung Disease is a non-infectious complication that can occur during the evolution of VCID and which is usually the pulmonary manifestation of a systemic polyclonal lymphoproliferative disease. GLILD contained both granulomatous and lymphoproliferative histopathologic patterns such as lymphocytic interstitial pneumonia , follicular bronchiolitis, and lymphoid hyperplasia. In recent series, approximately 8 to 22% of patients develop GLILD in VCID, and this complication is associated with increased mortality.

Although there are now more studies conducted in the adult population, those in the pediatric population are only currently case report. To the best of our knowledge, very little data is available on this specific lung disease in the pediatric and young adults population.

• Study Type: Observational
• Enrollment (Anticipated): 24

Contacts and Locations

• Study Contact: Name: Fanny FOUYSSAC; Phone Number: 0033383154532; Email: f.fouyssac@chru-nancy.fr
• Study Contact Backup: Name: Mathilde JOUGLET; Phone Number: 0033383154532; Email: m.jouglet@chru-nancy.fr

Study Locations

• France
  • Besançon, France, 25030
    • Recruiting
    • CHU Besançon
    • Contact: Nathalie CHEIKH; Email: ncheikh@chu-besancon.fr
  • Bordeaux, France, 33000
    • Recruiting
    • CHRU Bordeaux
    • Contact: Nathalie ALADJIDI; Email: nathalie.aladjidi@chu-bordeaux.fr
  • Dijon, France, 21000
    • Recruiting
    • CHRU Dijon Bourgogne
    • Contact: Claire BRIANDET; Email: claire.briandet@chu-dijon.fr
  • Montpellier, France, 34295
    • Recruiting
    • CHU Montpellier
    • Contact: Eric JEZIORSKI; Email: e-jeziorski@chu-montpellier.fr
  • Nancy, France, 54500
    • Recruiting
    • CHRU Nancy
    • Contact: Fanny FOUYSSAC; Phone Number: 003383154532; Email: f.fouysac@chru-nancy.fr
    • Contact: Mathilde Jouglet; Phone Number: 003383154532; Email: mathilde.jouglet@hotmail.fr
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker Enfants Malades
    • Contact: Felipe SUAREZ; Email: felipe.suarez@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Children and young adults, aged from 0 to 25 years-old
• with a diagnosis of Common Variable Immunodeficiency (marked decrease in IgG, at least less than -2 SD compared to the mean for age; associated with a decrease of at least one of the Immunoglobulin M or Immunoglobulin A isotypes, , absence of iso-haemagglutinins and/or poor vaccine response, with other defined causes of hypogammaglobulinemia excluded)
• GLILD suspected according to the lung biopsy or CT chest

Description

Inclusion Criteria:

• patient aged to 0 to 25 years old (at the diagnosis of GLILD)
• diagnosed with a primary immunodeficiency syndrome "Common Variable Immunodeficiency" like, according to the 1999 American and European Societies for Immunodeficiency criteria
• Suspected with GLILD (Granulomatous Lymphocytic Interstitial Lung Disease

Exclusion Criteria:

• pulmonary diseases caused by other causes such as infectious or hypersensitivity pneumonitis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung biopsy	Number of patients suspected of GLILD with lung biopsy whose characteristics corresponds to those defined by the British Lung Foundation	from 1998 to july 2018

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical symptomatology	Number of patients suspected of GLILD with significant clinical symptomatology	from 1998 to july 2018
Immunology	Number of patients suspected of GLILD with a particular immunological profile	from 1998 to july 2018
Pulmonary function tests	Number of patients suspected of GLILD with restrictive syndrome and/or carbon monoxide diffusion capacity alteration (Pulmonary Function Tests)	from 1998 to july 2018
CT chest in GLILD	Number of patients suspected of GLILD with radiological characteristics corresponding to those defined by the British Lung foundation	from 1998 to july 2018
Broncho-alveolar lavage	Number of patients suspected of GLILD with significant alteration of Broncho-alveolar Lavage	from 1998 to july 2018
GLILD Management	Number of patients suspected of GLILD who received a treatment for this indication	from 1998 to july 2018

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Fanny FOUYSSAC, CHRU Nancy

Publications and helpful links

General Publications

• Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004 Aug;114(2):415-21. doi: 10.1016/j.jaci.2004.05.057.
• Park JH, Levinson AI. Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol. 2010 Feb;134(2):97-103. doi: 10.1016/j.clim.2009.10.002. Epub 2009 Nov 8.

Helpful Links

• British Lung Foundation

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): September 15, 2018

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: children; GLILD; Common variable immunodeficiency
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency
• Other Study ID Numbers: PSS2017/p-GLILD-FOUYSSAC/NK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No