Clinical Genetics and Screening for Idiopathic Pulmonary Fibrosis

Clinical Genetics and Screening for Idiopathic Pulmonary Fibrosis

Background:

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of interstitial lung disease. Between 2% and 20% of patients with IPF have a family history of the disease, which is considered the strongest risk factor. Therefore, genetic testing has been increasingly considered as a potential tool to identify patients at risk of developing IPF.

According to some studies, genetic testing (particularly of MUC5B and TERT mutations) could be useful to rapidly identify unidentified and/or asymptomatic individuals (in families as well as in the general population) who have interstitial lung anomalies (ILA) that may indicate a initial stage of pulmonary fibrosis. Finding efficient screening methods and associated targeted treatments for IPF may be essential to improving the prognosis and quality of life of those suffering from this disease.

Objectives of the study:

The study involves two populations of study subjects:

• patients with FPF and sporadic IPF
• first-degree relatives of patients with FPF and sporadic IPF (biological relatives, not spouses)

The primary objective is to determine the prevalence rates of interstitial lung abnormalities in at-risk relatives of patient with IPF and FPF.

Study design:

Multicenter, cross-sectional study without drug and without device conducted in two major Italian tertiary referral hospitals.

The entire project is expected to last 24 months.

Criteria for PATIENTS:

Inclusion Criteria:

1. patients aged ≥18 years when signing the informed consent
2. diagnosis of IPF based on 2022 ATS/ERS/JRS/ALAT Guidelines as confirmed by the investigator based on chest HRCT scan and if available surgical lung biopsy
3. diagnosis of FPF defined as the presence of fibrotic ILD in at least two members of the same biological family
4. at least one 1st degree relative >40 years of age.

Exclusion Criteria:

1. patients with Interstitial Lung Diseases other than Idiopathic Pulmonary Fibrosis, including but not limited to patients with granulomatous lung disease, autoimmune/collagen vascular disease associated interstitial lung disease, and drug induced interstitial lung disease
2. unwilling or unable to sign informed consent

Criteria for FIRST DEGREE BIOLOGICAL RELATIVES:

Inclusion Criteria:

a. subjects aged ≥40 years

Exclusion Criteria:

1. previous diagnosis of IPF
2. a history of severe or poorly controlled anxiety, severe or poorly controlled depression according to the opinion of the investigators, suicidal ideation, or other psychiatric illness requiring hospitalization
3. unwilling or unable to sign informed consent 400 first-degree relatives of participating patients will be recruited