The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS): description of the protocol for a multicentre prospective observational cohort study identifying biomarkers of progressive fibrotic lung disease

Fasihul Khan, Iain Stewart, Lucy Howard, Tricia M McKeever, Steve Jones, Glenn Hearson, Rebecca Braybrooke, Colin Edwards, Gisli Jenkins, Gauri Saini, Fasihul Khan, Iain Stewart, Lucy Howard, Tricia M McKeever, Steve Jones, Glenn Hearson, Rebecca Braybrooke, Colin Edwards, Gisli Jenkins, Gauri Saini

Abstract

Introduction: The Its Not JUST Idiopathic pulmonary fibrosis Study (INJUSTIS) is a multicentre, prospective, observational cohort study. The aims of this study are to identify genetic, serum and other biomarkers that may identify specific molecular mechanisms, reflecting disease endotypes that are shared among patients with progressive pulmonary fibrosis regardless of aetiology. Furthermore, it is anticipated that these biomarkers will help predict fibrotic activity that may identify patterns of disease behaviour with greater accuracy than current clinical phenotyping.

Methods and analysis: 200 participants with the multidisciplinary team confirmed fibrotic lung disease (50 each of rheumatoid-interstitial lung disease (ILD), asbestosis, chronic hypersensitivity pneumonitis and unclassifiable ILD) and 50 idiopathic pulmonary fibrosis participants, recruited as positive controls, will be followed up for 2 years. Participants will have blood samples, lung function tests, quality of life questionnaires and a subgroup will be offered bronchoscopy. Participants will also be given the option of undertaking blinded home handheld spirometry for the first 3 months of the study. The primary end point will be identification of a biomarker that predicts disease progression, defined as 10% relative change in forced vital capacity (FVC) or death at 12 months.

Ethics and dissemination: The trial has received ethical approval from the National Research Ethics Committee Nottingham (18/EM/0139). All participants must provide written informed consent. The trial will be overseen by the INJUSTIS steering group that will include a patient representative, and an independent chairperson. The results from this study will be submitted for publication in peer-reviewed journals and disseminated at regional and national conferences.

Trial registration number: NCT03670576.

Keywords: asbestos induced lung disease; hypersensitivity pneumonitis; interstitial fibrosis.

Conflict of interest statement

Competing interests: CE is an employee and shareholder of patientMpower. RGJ reports grants from GlaxoSmithKline, UK Medical Research Council, Biogen, Galecto, MedImmune; as well as personal fees from Boehringer Ingelheim, Galapagos, GlaxoSmithKline, Heptares, MedImmune, Roche and Pulmatrix outside the submitted work; served as consultant for NuMedii and Pliant; a trustee for charities Action for Pulmonary Fibrosis and the British Thoracic Society.

Figures

Figure 1
Figure 1
Legend – participant flow through the study.
Figure 2
Figure 2
Directed acyclic graph (DAG) illustrates proposed model of causal inference and minimal sufficient adjustment sets (confounders; red) for estimating the direct effect of biomarker expression profiles (exposure; green) on disease progression (outcome; blue). Image generated using DAGitty.net environment. QoL, quality of life. BMI, body mass index; ILD, interstitial lung disease.

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