Genetics of the Combined Pulmonary Fibrosis and Emphysema Syndrome (GENES-SEF)

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).

Study Overview

• Status: Completed
• Conditions: Emphysema; Pulmonary Fibrosis; Healthy Subjects; Combined Pulmonary Fibrosis and Emphysema Syndrome
• Intervention / Treatment: Genetic: Genetic analysis

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hôpital pneumologique et cardiovasculaire Louis Pradel, HCL
  • Grenoble, France, 38 043
    • Hôpital Albert Michallon, CHU de Grenoble
  • Saint-Etienne, France, 42055
    • Hôpital Nord, CHU de Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Combined pulmonary fibrosis and emphysema syndrome; Genetic analysis on patients with combined pulmonary fibrosis and emphysema syndrome.	Genetic: Genetic analysis; 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.
Other: Pulmonary fibrosis; Genetic analysis on patients with pulmonary fibrosis.	Genetic: Genetic analysis; 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.
Other: Emphysema; Genetic analysis on patients with emphysema.	Genetic: Genetic analysis; 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.
Other: Healthy subject; Genetic analysis on healthy subject.	Genetic: Genetic analysis; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Vincent COTTIN, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2015
• Primary Completion (Actual): December 6, 2018
• Study Completion (Actual): December 6, 2018

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: May 7, 2015
• First Posted (Estimated): May 8, 2015

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: genetic; emphysema; pulmonary fibrosis; syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pathological Conditions, Signs and Symptoms; Syndrome; Pulmonary Fibrosis; Emphysema; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Genetic Techniques; Genetic Services; Diagnostic Services; Genetic Testing
• Other Study ID Numbers: 2013.819