Hereditary Influences on Pulmonary Fibrosis Trajectories (SHIFT)

An Observational, Prospective, Multicenter Study on Hereditary Influences on Pulmonary Fibrosis Trajectories

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Idiopathic Pulmonary Fibrosis (IPF); Familial Pulmonary Fibrosis; Telomere Disease; Progressive Pulmonary Fibrosis; Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)

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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

Study Locations

• Italy
  • Italy
    • Rozzano, Italy, Italy, 20089
      • Francesco Amati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with ILDs discussed in the multidisciplinary discussion to define FPF. Cases discussed will be documented using a standard CRF that detailed complete medical history including genetic test, physical examination, laboratory test results, pulmonary function test (PFT) results and, eventually, lung biopsy results and/or bronchoalveolar lavage (BAL) results.

Pre-MDD diagnoses will be based on the referring pulmonologist's diagnosis and current consensus classification for ILDs.

Post-MDD diagnosis will be classified according to Ryerson confidence terminology, with "confident diagnosis" reserved for >90% clinical likelihood or a provisional diagnosis which was categorized as "high confidence" (70-89% likelihood) or "low confidence" (51-69% likelihood). Patients with less than 50% diagnostic confidence level post-MDD will be categorized as "unclassifiable ILD".

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Familial pulmonary fibrosis; Eligible participants will be adults (≥18 years) with ILD documented on HRCT and with a positive genetic test, defined as the presence of rare variants or susceptibility polymorphisms consistent with the diagnosis of FPF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
annual relative FVC decline over the observation period	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.	Annual for 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
mortality	mortality	5 years
Annual relative DLCO decline	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.	5 years
incidence of lung and non-lung cancer	incidence of lung and non-lung cancer	5 years

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas
• Collaborators: Fondazione Policlinico Universitario Agostino Gemelli IRCCS; University of Siena; Ospedale San Paolo
• Investigators: Principal Investigator: Francesco Amati, MD, Humanitas Research Hospital IRCCS, Rozzano-Milan

Publications and helpful links

General Publications

• Zhang D, Newton CA. Familial Pulmonary Fibrosis: Genetic Features and Clinical Implications. Chest. 2021 Nov;160(5):1764-1773. doi: 10.1016/j.chest.2021.06.037. Epub 2021 Jun 26.
• Borie R, Kannengiesser C, Antoniou K, Bonella F, Crestani B, Fabre A, Froidure A, Galvin L, Griese M, Grutters JC, Molina-Molina M, Poletti V, Prasse A, Renzoni E, van der Smagt J, van Moorsel CHM. European Respiratory Society statement on familial pulmonary fibrosis. Eur Respir J. 2023 Mar 16;61(3):2201383. doi: 10.1183/13993003.01383-2022. Print 2023 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): December 1, 2034
• Study Completion (Estimated): December 1, 2034

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: IDIOPATHIC PULMONARY FIBROSIS; PROGRESSIVE PULMONARY FIBROSIS; INTERSTITIAL LUNG DISEASE; TELOMERE DISORDER; FAMILIAL PULMONARY FIBROSIS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: Prot. Nr.721/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No