Genetics of the Combined Pulmonary Fibrosis and Emphysema Syndrome

Study Overview
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Brief Summary
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The combined pulmonary fibrosis and emphysema syndrome (CPFE) individualized by our group in 2005 is characterized by an often severe dyspnea, almost exclusive male predominance, and often major, profound impairment of gas exchange contrasting with preserved lung volumes and absence of airflow obstruction, and a high risk of pre-capillary pulmonary hypertension responsible for increased mortality. Almost all patients are smokers or ex-smokers. There are some arguments in favor of genetic abnormalities in this syndrome of unknown etiology (other than smoking) including short telomeres and mutations in the telomerase complex genes. There are also emphysematous lesions, in patients with familial pulmonary fibrosis, with mutations in the SFTPC gene (surfactant protein C), and reported cases of CPFE syndrome with SFTPC mutation. No large genetic studies have been conducted to date in the CPFE syndrome. Our main hypothesis is that the proportion of subjects with short telomeres is higher among patients with CPFE syndrome than in subjects of similar age with idiopathic pulmonary fibrosis but without emphysema. It has previously been shown that mutations in the telomerase TERT or TERC genes are mostly found in people whose telomeres are abnormally short. The investigators propose to use that test to identify patients most likely carrying a mutation, and to seek, among them, the mutations in the TERT or TERC telomerase genes. The objective of the study is to compare the proportion of patients with short telomeres in the group of patients with CPFE syndrome to that of other patients (with idiopathic pulmonary fibrosis without emphysema, or with emphysema without fibrosis).

Official Title
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Genetics of the Combined Pulmonary Fibrosis and Emphysema Syndrome

Conditions
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Combined Pulmonary Fibrosis and Emphysema Syndrome, Pulmonary Fibrosis, Emphysema, Healthy Subjects

Intervention / Treatment
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* Genetic: Genetic analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 80 years old. Patient with Idiopathic Pulmonary Fibrosis Or Patient with emphysema Or Patient with combined pulmonary fibrosis and emphysema syndrome Or Patient reporting no chronic lung disease Exclusion Criteria: Other causes of interstitial lung disease or context: Connective Pneumonia drug Pneumoconiosis Sarcoidosis histiocytosis, lymphangioleiomyomatosis, etc. Refusal to participate in the study or to sign the consent Inability to give informed about the information Woman breastfeeding or pregnant No coverage for Social Security Deprivation of Civil Rights

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Combined pulmonary fibrosis and emphysema syndrome<br>Genetic analysis on patients with combined pulmonary fibrosis and emphysema syndrome. | Genetic: Genetic analysis<br>* One part of these patients is already included in a cohort: for them the blood sample will be centralized and then analyzed. The other part of these patients will be recruited during the study: for them intervention will be blood samples for further genetic analysis.<br>|
| Other: Pulmonary fibrosis<br>Genetic analysis on patients with pulmonary fibrosis. | Genetic: Genetic analysis<br>* One part of these patients is already included in a cohort: for them the blood sample will be centralized and then analyzed. The other part of these patients will be recruited during the study: for them intervention will be blood samples for further genetic analysis.<br>|
| Other: Emphysema<br>Genetic analysis on patients with emphysema. | Genetic: Genetic analysis<br>* One part of these patients is already included in a cohort: for them the blood sample will be centralized and then analyzed. The other part of these patients will be recruited during the study: for them intervention will be blood samples for further genetic analysis.<br>|
| Other: Healthy subject<br>Genetic analysis on healthy subject. | Genetic: Genetic analysis<br>* One part of these patients is already included in a cohort: for them the blood sample will be centralized and then analyzed. The other part of these patients will be recruited during the study: for them intervention will be blood samples for further genetic analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Telomere length | The primary endpoint is the percentage of patients with telomere length less than the 10th percentile of the age range for each type of patient | At inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mutation of the telomerase complex genes evaluated by gene sequencing. | Frequency of the telomerase complex mutations measured by the percentage of patients having at least one mutation of the complex. | At inclusion | 
| Mutations in the gene encoding the SFTPC evaluated by gene sequencing | Frequency of mutations in the gene encoding the SFTPC surfactant protein C measured by the percentage of patients having at least one mutation of the complex | At inclusion | 
| Patients characteristics evaluated by clinical examination | Comparison of each type of patients with controls | At inclusion | 
| Genetic profile evaluated by gene sequencing. | Description of the mutations found, relations with the phenotype | At inclusion | 
| Total mortality evaluated by phone call contact | 6 months after inclusion, patients will be contacted to know their clinical status. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary fibrosis, syndrome, genetic, emphysema