Molecular Diagnosis of Idiopathic Interstitial Pneumonias: a Prospective Study

NCT03836417 | Completed DMC

• 1 other identifier: 6156
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Molecular diagnosis of idiopathic interstitial pneumonias is an innovative way to potentially improve the diagnostic accuracy of surgical lung biopsies (SLBs), introducing molecular classifiers of idiopathic pulmonary fibrosis (IPF) vs. non-specific interstitial pneumonia (NSIP) vs. chronic hypersensitivity pneumonitis (CHP). The investigators hypothesize that pre-defined gene expression profiles previously identified on large lung explants can still be identified and reproducible on smaller, clinically available surgical lung biopsies (SLBs), and can be used to increase diagnostic accuracy during multi-disciplinary discussion. The investigators also hypothesize that the expression level of individual, preselected genes that accurately differentiate IPF from NSIP and CHP on lung explants can be reproduced on SLBs. The investigators will isolate RNA from SLBs obtained from patients with IIP and perform microarray analysis to verify the reproducibility of gene expression profiles on SLBs. Individual genes expression levels will be determined by RT-PCR. The diagnosis will be determined by MDD and further validated by prospective follow-up of patients for a period of 3 years. The investigators will assess the impact of molecular diagnostic techniques on interobserver agreement during multi-disciplinary discussion. The investigators will prospectively follow the clinical course of patients after SLB for a period of 3 years to validate the diagnosis, and asses the diagnostic accuracy of molecular techniques.

Conditions

Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Nonspecific Interstitial Pneumonia

Outcome Measures

Primary Outcomes (1)

• Reproducibility of gene expression profiles on surgical lung biopsies

  Proportion of patients (% of the total) with reproducible predefined gene expression profiles of either IPF or NSIP on surgical lung biopsy.

  February 2019-January 2022

Secondary Outcomes (2)

• Prognostic impact of gene expression profiles of IPF and NSIP

  February 2019-January 2025

• Prognostic impact of selected genes expression levels

  February 2019-January 2025

Study Arms (1)

Idiopathic interstitial pneumonias

Patients with idiopathic interstitial pneumonias undergoing surgical lung biopsy

Diagnostic Test: Microarray analysis

Interventions

Microarray analysis DIAGNOSTIC_TEST

Microarray analysis to identify gene expression profiles that distinguish IPF from NSIP

Idiopathic interstitial pneumonias

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

After ruling out known causes (connective tissue disease; occupational, environmental or domestic exposures; drug-induced lung toxicity) of interstitial lung disease, patients being referred for a surgical lung biopsy to clarify the diagnosis of IIP (IPF vs. NSIP) will be recruited in the study.

You may qualify if:

• Chronic interstitial lung disease not caused by connective tissue disease, drug-induced toxicity or environmental occupational or domestic exposures. These criteria equal to a diagnosis of idiopathic interstitial pneumonia (IIP).
• High resolution chest CT scan not consistent with an idiopathic pulmonary fibrosis pattern, therefore requiring a surgical lung biopsy to clarify the exact diagnosis of IIP.
• No contraindications to undergo a surgical lung biopsy (advanced disease stage; significant cardiac disease; significant obesity; or associated pulmonary hypertension).
• Patient able to provide informed consent.

You may not qualify if:

• Chronic interstitial lung disease caused by connective tissue disease, drug-induced toxicity or environmental occupational or domestic exposures.
• High resolution chest CT scan consistent with an idiopathic pulmonary fibrosis pattern, therefore not requiring a surgical lung biopsy.
• Contraindications to undergo a surgical lung biopsy (advanced disease stage; significant cardiac disease; significant obesity; or associated pulmonary hypertension).

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Western University, Canada: collaborator

Study Sites (1)

London Health Science Centre

London, Ontario, N6A 5W9, Canada

Location

Related Publications (3)

• Cecchini MJ, Hosein K, Howlett CJ, Joseph M, Mura M. Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis. Respir Res. 2018 Aug 15;19(1):153. doi: 10.1186/s12931-018-0857-1.

  PMID: 30111332 BACKGROUND

• Mura M, Anraku M, Yun Z, McRae K, Liu M, Waddell TK, Singer LG, Granton JT, Keshavjee S, de Perrot M. Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis. Chest. 2012 Mar;141(3):661-673. doi: 10.1378/chest.11-0449. Epub 2011 Aug 11.

  PMID: 21835902 BACKGROUND

• Mura M, Porretta MA, Bargagli E, Sergiacomi G, Zompatori M, Sverzellati N, Taglieri A, Mezzasalma F, Rottoli P, Saltini C, Rogliani P. Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Eur Respir J. 2012 Jul;40(1):101-9. doi: 10.1183/09031936.00106011. Epub 2012 Jan 12.

  PMID: 22241745 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Lung tissue biopsies

MeSH Terms

Conditions

Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis

Interventions

Transcriptome

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Transcription, Genetic; Biochemical Phenomena; Chemical Phenomena; Gene Expression; Genetic Phenomena; Genetic Structures

Study Officials

• Marco Mura, MD, PhD

  Western University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: February 11, 2019
• Study Start: June 28, 2019
• Primary Completion: October 17, 2024
• Study Completion: October 17, 2024
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)