Study details

Interstitial Lung Disease: A Study From Infancy to Elderly Including Relatives

RaDiCo-ILD2

Ongoing study

The primary objective of the RaDiCo-ILD2 cohort is to describe the phenotypic characteristics of pediatric and adult patients with idiopathic interstitial pneumonias (IIP), other chronic fibrosing interstitial lung diseases with a progressive phenotype, or interstitial lung disease associated with systemic sclerosis (SSc-ILD), as well as of their relatives, throughout the study period. These data will make it possible to describe the natural history of the different forms of IIP in patients, and to assess the penetrance of known genetic variants and the prevalence of IIP among relatives of patients carrying mutations in genes involved in telomere regulation, in particular TERT, TERC, RTEL1, PARN, TINF2 and DKC1, as well as in any other genes identified subsequently.

In patients with IIP, other chronic fibrosing interstitial lung diseases with a progressive phenotype, or SSc-ILD, the research also aims to identify the genetic factors involved in disease onset and progression, to investigate the extent to which environmental factors and comorbidities may influence disease severity and course, and to identify and validate biomarkers for disease diagnosis and progression. It also aims to assess the impact of SARS-CoV-2 on disease progression.

In relatives of mutation carriers, the study aims to determine and characterize the association between carrying a mutation and developing interstitial lung disease, and to assess the frequency and characteristics of extrapulmonary manifestations specific to the mutations studied, in particular hepatic, hematological, immunological and cutaneous involvement, and their association with the presence of the mutation. It also aims to assess the frequency and characteristics of pulmonary and extrapulmonary conditions suspected of being associated with these mutations, in particular pulmonary emphysema, infertility, cancers and osteoporosis, as well as their association with mutation status.

Finally, the research aims to compare the characteristics of relatives according to the status of each condition, to identify the respective risk factors of the most frequent conditions, in particular interstitial lung disease, mutation-specific extrapulmonary manifestations and suspected pulmonary and extrapulmonary conditions, and to describe the chronological course of abnormalities, notably through a 5-year reassessment of mutation carriers who were initially healthy and asymptomatic.

The RaDiCo-ILD2 cohort results from the requalification and extension of the RaDiCo-PID cohort, which was initially dedicated to diffuse interstitial lung diseases (PID) in children and adults. It is an observational, longitudinal, multicenter study, conducted both retrospectively and prospectively, dedicated to idiopathic interstitial pneumonias (IIP), chronic fibrosing interstitial lung diseases with a progressive phenotype (PF-ILD) and interstitial lung diseases associated with systemic sclerosis (SSc-ILD). It includes pediatric and adult patients, as well as first-degree relatives of patients with familial pulmonary fibrosis carrying mutations in telomere-related genes. Patients already enrolled in the RaDiCo-PID cohort continue their follow-up within RaDiCo-ILD2, in the same database.

This research aims to better characterize the natural history and the clinical and biological features of the different forms of interstitial lung disease over time. In patients, the data collected include family history, clinical and biological parameters, imaging data, pulmonary function tests, any pathological examinations, assessment of other organ functions, and treatments. For incident patients, data are collected at enrollment and then annually during follow-up. For prevalent patients, data available since diagnosis or the first measurement may be collected retrospectively and then completed during follow-up.

The research also aims to study the genetic and environmental factors and comorbidities that may be associated with disease onset, severity and progression. It includes the identification and validation of candidate biomarkers for diagnosis and progression, notably MMP7, SP-A, SP-D, KL-6 and MUC5B, as well as the assessment of the impact of SARS-CoV-2, particularly with regard to diagnostic procedures, symptoms, medical management and treatments.

In first-degree relatives of patients carrying a mutation in a telomere-related gene, the study aims to assess the association between mutation status and the development of interstitial lung disease. It also makes it possible to study the frequency and characteristics of mutation-specific extrapulmonary manifestations, in particular hematological and immunological, hepatic and cutaneous involvement. Certain pulmonary and extrapulmonary conditions that may be associated with these mutations are also studied, notably pulmonary emphysema, infertility, osteopenia or osteoporosis, and cancers.

The cohort thus includes pediatric and adult patients, as well as relatives of patients carrying genetic mutations. The data collected notably include demographic, clinical, biological, genetic, radiological and pulmonary function data, as well as information on treatments, comorbidities and environmental factors. Questionnaires are also used to assess quality of life, respiratory symptoms and their impact, notably the SF-36, the SF-10, the St George's Respiratory Questionnaire (SGRQ), the L-PF Symptoms, the L-PF Impacts and the K-BILD.

The cohort will thus provide longitudinal data to better understand the natural history and course of interstitial lung diseases, to identify the genetic, environmental and clinical factors associated with their development and progression, and to better characterize the pulmonary and extrapulmonary manifestations related to mutations in telomere-related genes. The results will contribute to improving knowledge of these rare lung diseases and to improving their diagnosis, follow-up and management.

Rare Diseases Interstitial Lung Diseases Diffuse Interstitial Lung Diseases Cohort Pulmonology Idiopathic interstitial pneumonias (IIP) Chronic fibrosing interstitial lung diseases with a progressive phenotype (PF-ILD) Telomeres Quality of life Genetics scleroderma-associated interstitial lung diseases(SSc-ILD)

Internal medicine Medical genetics Paediatrics Pulmonary medicine Radiology and nuclear medicine Rheumatology

Other interstitial pulmonary diseases Idiopathic pulmonary fibrosis Systemic sclerosis with lung involvement

Socio-demographic and economic determinants Socio-demographic and economic determinants: Employment Socio-demographic and economic determinants: Housing Socio-demographic and economic determinants: Education level Socio-demographic and economic determinants: Age Environmental determinants Environmental determinants: Other Behavioral determinants Behavioral determinants: Addiction Biological determinants Biological determinants: Genetic predisposition Biological determinants: Sex Other

Active or passive smoking; exposure to materials or substances such as silica, asbestos, clay and wood; place of residence and type of housing.

Clinical and laboratory data and biomarkers studied in the context of the characterization and progression of interstitial lung diseases, including laboratory tests, pulmonary function data, and the identification and validation of biomarkers for diagnosis and progression.

Yes

France

Oui

Comité de Pilotage :
Vincent Cottin, Nadia Nathan, Hilario Nunes, Raphaël Borie, et RaDiCo.
Comité Scientifique :
Vincent Cottin, Nadia Nathan, Hilario Nunes, Stéphane Jouneau, Lidwine Wemeau, Raphaël Borie, Bruno Crestani, Jacques Cadranel, Philippe Bonniaud, Jean-Christophe Dubus, Martine Reynaud-Gaubert, Raphaël Hindre, et RaDiCo.

Oui

Filière de santé maladies rares, RespiFIL, Maladies respiratoires rares ; Fondation du Souffle.

Individus

Etude observationnelle

Cohorte

Autre

Oui

Caractéristiques cliniques et biologiques des pneumopathies interstitielles idiopathiques (IIP), des pneumopathies interstitielles fibrosantes chroniques à phénotype progressif (PF-ILD) et des pneumopathies interstitielles associées à la sclérodermie systémique (SSc-ILD), évaluées au cours du temps chez les patients pédiatriques et adultes.

Les critères d’évaluation secondaires portent sur l’identification des facteurs génétiques impliqués dans l’initiation et la progression de la maladie, l’évaluation de l’influence des facteurs environnementaux et des comorbidités sur la sévérité et l’évolution de la maladie, ainsi que l’identification et la validation de biomarqueurs candidats au diagnostic et à la progression de la maladie, notamment MMP7, SP-A, SP-D, KL-6 et MUC5B. Ils comprennent également l’évaluation de l’impact du SARS-CoV-2 sur l’évolution de la maladie, notamment selon les modalités de diagnostic, les symptômes, les prises en charge médicales et les traitements. Chez les apparentés de patients porteurs d’une mutation, les critères comprennent l’évaluation de la relation entre les mutations et le développement d’une pneumopathie interstitielle diffuse, ainsi que la fréquence et les caractéristiques des atteintes extra-pulmonaires spécifiques aux mutations, notamment hématologiques, immunologiques, hépatiques et cutanées. Sont également évaluées la fréquence et les caractéristiques des atteintes pulmonaires et extra-pulmonaires suspectées d’être associées aux mutations, notamment l’emphysème pulmonaire, l’infertilité, l’ostéopénie ou l’ostéoporose et les cancers.