GEN-FPF: Genetic Exploration of Familial Pulmonary Fibrosis (GEN-FPF)

Unravelling the Genetic Basis of Familial Pulmonary Fibrosis: A Next-Generation Sequencing Approach to Fibrogenesis and Surfactant Disorder Genes

Pulmonary fibrosis (PF) is a progressive lung disease marked by tissue scarring and impaired breathing. Familial pulmonary fibrosis (FPF) makes up 10-20% of PF cases and shares features with idiopathic PF (IPF), but the genetic causes of FPF are not fully understood.

This study focuses on uncovering the genetic basis of FPF by analyzing families with multiple affected members. It targets genes involved in fibrogenesis and surfactant disorders, as familial cases often appear earlier and progress more rapidly than sporadic ones.

Understanding FPF genetics could:

1. Identify new genetic markers for early diagnosis and prognosis.
2. Improve genetic counseling and preventive strategies for affected families.
3. Reveal therapeutic targets for personalized treatments.
4. Highlight shared molecular pathways between familial and idiopathic PF, potentially benefiting a broader patient group.

In summary, the study aims to deepen our understanding of FPF genetics to improve diagnosis, counseling, and treatment for both familial and idiopathic forms of pulmonary fibrosis.

Study Overview

• Status: Recruiting
• Conditions: Familial Pulmonary Fibrosis

Detailed Description

observational study , longitudinal retrospective

• Study Type: Observational
• Enrollment (Estimated): 126

Contacts and Locations

• Study Contact: Name: Ilaria Campo, PhD; Phone Number: +39 0382 501007; Email: i.campo@smatteo.pv.it

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Recruiting
      • Fondazione IRCCS Policlinico San Matteo
      • Contact: Ilaria Campo; Phone Number: +39 0382 501007; Email: i.campo@smatteo.pv.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population includes individuals diagnosed with familial pulmonary fibrosis (FPF) and their first-degree relatives (affected and unaffected), as well as a comparison cohort of idiopathic pulmonary fibrosis (IPF) patients.

Participants will be recruited from two Italian centers:

SC Pneumologia, Fondazione IRCCS Policlinico San Matteo (Pavia) Azienda Ospedaliero Universitaria Careggi (Florence)

Description

Inclusion Criteria:

Diagnosis of Familial Pulmonary Fibrosis (FPF):

At least two individuals from the same family (first-degree relatives) diagnosed with pulmonary fibrosis based on clinical, radiological, or histopathological criteria (e.g., HRCT pattern consistent with usual interstitial pneumonia, UIP).

Definite or probable FPF diagnosis, according to international classification criteria and verified family history of disease.

Age:

Adults aged 18 years or older at the time of enrollment.

Informed Consent:

Ability and willingness to provide written informed consent (or consent provided by a legally authorized representative).

Willingness to participate in genetic testing, clinical evaluations, and longitudinal follow-up.

Availability of Family Members:

Affected family members with pulmonary fibrosis willing to provide blood samples and clinical information.

Unaffected first-degree relatives willing to participate in genetic testing and family history documentation.

Idiopathic Pulmonary Fibrosis (IPF) Cohort:

Individuals with a confirmed diagnosis of idiopathic pulmonary fibrosis (IPF) according to ATS/ERS 2018 criteria, enrolled as a comparative (non-familial) cohort.

Exclusion Criteria:

Non-Familial Pulmonary Fibrosis:

Individuals with isolated, sporadic pulmonary fibrosis (without a family history) who are not part of the defined IPF control group.

Other Significant Pulmonary Diseases:

Presence of pulmonary diseases unrelated to fibrosis (e.g., chronic obstructive pulmonary disease, asthma, cystic fibrosis, or active pulmonary infection).

Refusal or Withdrawal of Consent:

Individuals unwilling to provide or maintain informed consent for participation, genetic testing, or long-term data use.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
FPF; Familial Pulmonary Fibrosis
IPF; idiopathic pulmonary fibrosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Type of Pathogenic or Likely Pathogenic Variants Identified by Next-Generation Sequencing (NGS)	dentification and classification of genetic variants detected in genes associated with familial pulmonary fibrosis (FPF) and surfactant metabolism (e.g., SFTPC, SFTPA2, ABCA3, MUC5B). Variants will be classified according to ACMG guidelines and reported as counts and frequencies in the study population.	within 24 months of participant enrollment

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 25, 2025
• First Submitted That Met QC Criteria: November 24, 2025
• First Posted (Actual): November 26, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: GEN-FPF

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