Optimising Screening for Early Disease Detection in Familial Pulmonary Fibrosis

Study Overview
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Brief Summary
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In this study the prognostic value of the current screening parameters for familial pulmonary fibrosis (FPF) will be investigated by looking at the screenings of 200 first-degree relatives of patients with FPF. Also insight in the natural history of early FPF, and the necessary interval between screenings visits will be investigated.

Detailed Description
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Familial pulmonary fibrosis (FPF) is a fatal lung disease that is often not diagnosed until a significant portion of the lung function is lost. Median survival after diagnosis is 3 to 5 years. As treatment can only slow down lung function decline, early disease detection is essential to provide timely therapeutic support. As first-degree relatives of patients with FPF are at high risk of developing pulmonary fibrosis as well, a screening protocol has been put in place. However, the value of current screening parameters to detect early asymptomatic disease as well as the optimal interval between screening appointments are unknown. A prospective study into the prognostic value of these screening markers in the target population and the appropriate clinical setting is needed to develop an evidence-based screening protocol. There will be an emphasis on easily operable parameters that may allow for redirection of (part of the) screening activities to the general practice in the future.

Official Title
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Optimising Screening for Early Disease Detection in Familial Pulmonary Fibrosis

Conditions
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Pulmonary Fibrosis Idiopathic Familial

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic first-degree relative of patients with familial pulmonary fibrosis (FPF) Exclusion Criteria: A previous diagnosis of interstitial lung disease (ILD) Minors (aged <18 years) Pregnant Note: woman who are pregnant at the start of the study or at the time of the HRCT are not allowed to participate. If a participant gets pregnant at a later stage during the study, she will not be excluded from the study. To be able to account for a potential effect of pregnancy during data analysis, female participants can be asked if they are pregnant at every visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characteristics of participants | Difference in age, sex, body weight, smoking history and comorbidities between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Forced Vital Capacity (FVC) | Difference in forced vital capacity (FVC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) | Difference in haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Total lung capacity (TLC) | Difference in total lung capacity (TLC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Biomarker levels | Difference in Krebs von den Lungen 6 (KL6), chemokine (C-C motif) ligand 18 (CCL18), surfactant protein-D (SP-D), matrix metalloproteinase 7 (MMP7) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Oxygen saturation in 6-minute walk test (6MWT) | Difference in oxygen saturation (rest in %), oxygen saturation (after 6MWT in %), oxygen saturation (nadir in %) and oxygen saturation (difference between rest and nadir in %) (all continuous variables) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Distance (meters) in 6-minute walk test (6MWT) | Difference in distance covered (in meters) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| MUC5B genotype | Difference in MUC5B genotype (all discrete variables) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Patient reported cough score | Difference in visual analogue scale (VAS) for cough (scores between 0-100, with 100 being the worst) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Patient reported dyspnea score | Difference in medical research council (MRC) (scores between 0-5, with 5 being the worst) between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Clubbing | Difference in presence of digital clubbing between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 
| Crackles | Difference in inspiratory crackles during lung auscultation between the group with ILD changes and the group without ILD changes present on enrollment HRCT | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Vital Capacity (FVC) | Difference in forced vital capacity (FVC) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) | Difference in haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Total lung capacity (TLC) | Difference in total lung capacity (TLC) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Biomarker levels | Difference in KL6, CCL18, SP-D and MMP7 over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Genotype | Difference in MUC5B genotype over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Oxygen saturation in 6-minute walk test (6MWT) | Difference in oxygen saturation (rest in %), oxygen saturation (after 6MWT in %), oxygen saturation (nadir in %) and oxygen saturation (difference between rest and nadir in %) (all continuous variables) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Distance (meters) in 6-minute walk test (6MWT) | Difference in distance covered (in meters) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Patient reported cough score | Difference in visual analogue scale (VAS) for cough (scores between 0-100, with 100 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Patient reported dyspnea score | Difference in medical research council (MRC) (scores between 0-5, with 5 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Digital clubbing | Difference in presence of digital clubbing over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Crackles | Difference in inspiratory crackles during lung auscultation over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Patient reported fatigue | Difference in fatigue assessment scale (FAS) (scores range from 10-50, with 50 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 
| Patient reported health status | Difference in EuroQol 5D-5L (EQ-5D-5L) (comprises of a score in five levels, level 1-5 with 5 being the worst, and a visual analoque scale ranging from 0-100 with 100 being the best) and the over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary Fibrosis, Familial, Screening, Asymptomatic, Family members, First-degree