Familial Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis (IPF), Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder), Progressive Pulmonary Fibrosis, Telomere Disease
Conditions
Keywords
PROGRESSIVE PULMONARY FIBROSIS, INTERSTITIAL LUNG DISEASE, TELOMERE DISORDER, FAMILIAL PULMONARY FIBROSIS, IDIOPATHIC PULMONARY FIBROSIS
Brief summary
The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study is a prospective, multicenter, observational cohort study designed to investigate familial pulmonary fibrosis (FPF) within the Italian population.
Detailed description
Familial pulmonary fibrosis (FPF) is a genetically driven subset of fibrosing interstitial lung diseases (ILDs) characterised by heterogeneous phenotypes, variable clinical trajectories, and limited evidence to guide prognosis and treatment. Although antifibrotic therapies are effective in idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), data in FPF, particularly from European populations, remain scarce. The SHIFT (Hereditary Influences on Pulmonary Fibrosis Trajectories) study aims to prospectively characterize disease progression, treatment response, and outcomes in a national Italian cohort. SHIFT is a prospective, multicenter, observational cohort study enrolling adults (≥18 years) with ILD on high-resolution computed tomography and genetic findings consistent with FPF. Participants are recruited from specialized ILD referral centers across Italy and followed every 6 months for up to 5 years. Diagnostic attribution is standardized through multidisciplinary discussion using a structured confidence framework. All treatments are prescribed according to routine clinical practice. The primary endpoint is annual relative decline in forced vital capacity (FVC). Secondary endpoints include longitudinal changes in diffusing capacity (DLCO), treatment effectiveness and safety, mortality, transplant-free survival, cancer incidence, and genotype-phenotype and genotype-treatment response associations. Longitudinal data will be analyzed using mixed-effects models, and time-to-event outcomes using survival methods. Multivariable analyses and sensitivity analyses will address confounding.
Interventions
None listed
Sponsors
Istituto Clinico Humanitas
University of Siena
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Ospedale San Paolo
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A HRCT scan consistent with ILD diagnosis * Age over 18 years old * A genetic test proved variant or a polymorphism consistent with a diagnosis of FPF * Ability to give informed consent for the inclusion in the study
Exclusion criteria
* Patients unable to perform pulmonary function tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| annual relative FVC decline over the observation period | Annual for 5 years | The annual relative decline is defined as the difference between the final and the initial FVC value divided by the initial value, and it will be calculated for each year and for the entire follow-up period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| relative reduced annual FVC decline when compared to FPF patients treated with immunomodulator agents and FPF patients not treated in a 5-years period of FU. | 5 years | relative reduced annual FVC decline when compared to FPF patients treated with immunomodulator agents and FPF patients not treated in a 5-years period of FU. |
| mortality | 5 years | mortality |
| Annual relative DLCO decline | 5 years | Annual relative DLCO decline: The annual relative decline is defined as the difference between the final and the initial DLCO value divided by the initial value, and it will be calculated for each year and for the entire follow-up period. |
| incidence of lung and non-lung cancer | 5 years | incidence of lung and non-lung cancer |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORFrancesco Amati, MD
Humanitas Research Hospital IRCCS, Rozzano-Milan
Outcome results
None listed