Pulmonary Fibrosis Idiopathic Familial
Conditions
Keywords
Pulmonary Fibrosis, Familial, Screening, Asymptomatic, Family members, First-degree
Brief summary
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
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.
Interventions
None listed
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
Boehringer Ingelheim
St. Antonius Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient reported dyspnea score | Baseline | 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 |
| Patient reported cough score | Baseline | 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 |
| Distance (meters) in 6-minute walk test (6MWT) | Baseline | Difference in distance covered (in meters) between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| MUC5B genotype | Baseline | Difference in MUC5B genotype (all discrete variables) between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| Crackles | Baseline | Difference in inspiratory crackles during lung auscultation between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| Clubbing | Baseline | Difference in presence of digital clubbing between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| Characteristics of participants | Baseline | 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 |
| Forced Vital Capacity (FVC) | Baseline | Difference in forced vital capacity (FVC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) | Baseline | 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 |
| Total lung capacity (TLC) | Baseline | Difference in total lung capacity (TLC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT |
| Biomarker levels | Baseline | 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 |
| Oxygen saturation in 6-minute walk test (6MWT) | Baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient reported health status | 2 years | 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 |
| Digital clubbing | 2 years | 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 |
| Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) | 2 years | 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 |
| Total lung capacity (TLC) | 2 years | 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 |
| Forced Vital Capacity (FVC) | 2 years | 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 |
| Biomarker levels | 2 years | 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 |
| Genotype | 2 years | 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 |
| Oxygen saturation in 6-minute walk test (6MWT) | 2 years | 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 |
| Distance (meters) in 6-minute walk test (6MWT) | 2 years | 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 |
| Patient reported cough score | 2 years | 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 |
| Patient reported dyspnea score | 2 years | 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 |
| Crackles | 2 years | 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 |
| Patient reported fatigue | 2 years | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relatedness | Baseline | In case multiple members of the same family are included in the study |
| Additional blood based markers | 2 years | Additional blood based markers as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between these blood based markers in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT |
| Total bilirubin | 2 years | Total bilirubin (umol/l) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between total bilirubin in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT |
| Liver function tests | 2 years | Liver function tests (consisting of: ASAT (U/l), ALAT (U/l), alkaline phosphatase (U/l), Gamma-glutamyl transpeptidase (U/l)) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between these liver function tests in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT |
| Creatinin | 2 years | creatinin (umol/l) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between creatinin in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT |
| Blood count | 2 years | Blood count (Consisting of; hemoglobin (mmol/l), erythrocytes (x10\^12/l), mean corpuscular volume (fl), red cell distribution width (%), thrombocytes (x10\^9/l), leukocytes (x10\^9/l)) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between bloodcount in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT |
Countries
Netherlands
Contacts
Primary ContactJan Grutters, Prof.
Backup ContactMartijn Maus, MD
Outcome results
None listed