Clinical trial NCT03648567: GLILD Diagnosed in Children and Young Adults With Common Variable Immunodeficiency
Official title: Granulomatous-Lymphocytic Interstitial Lung Disease (GLILD) Diagnosed in Children and Young Adults With Common Variable Immunodeficiency
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: GLILD in a Population of Children and Young Adults
Keywords: GLILD
Common variable immunodeficiency
children
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2018-08-27
Enrollment: 24
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Lung biopsy
timeFrame: from 1998 to july 2018
Secondary outcomes:
measure: Clinical symptomatology
timeFrame: from 1998 to july 2018
measure: Immunology
timeFrame: from 1998 to july 2018
measure: Pulmonary function tests
timeFrame: from 1998 to july 2018
measure: CT chest in GLILD
timeFrame: from 1998 to july 2018
measure: Broncho-alveolar lavage
timeFrame: from 1998 to july 2018
measure: GLILD Management
timeFrame: from 1998 to july 2018
Other outcomes:
Locations:
city: Besançon
country: France
facility: Chu Besancon
city: Bordeaux
country: France
facility: CHRU Bordeaux
city: Dijon
country: France
facility: Chru Dijon Bourgogne
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHRU Nancy
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
Study officials:
affiliation: CHRU Nancy
name: Fanny FOUYSSAC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.