Early identification of progressive pulmonary fibrosis Precision Medicine for more Oxygen - ILD extensio
- Conditions
- 'Insterstitial Lung disease' 'lung fibrosis'100386861000381610024967
- Registration Number
- NL-OMON56954
- Lead Sponsor
- Amsterdam UMC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 450
To be eligible to participate in this study, subjects must meet all of the
following criteria:
Arm 1
- IPF/FPF diagnosis (non-stratified) within 1 year prior to screening, based on
the guidelines set by ATS/ERS/JRS/ALAT (Raghu et al., 2022)(Zhang & Newton,
2021). A chest HRCT should have been performed within 12 months prior to
screening, meeting the minimum requirements for IPF diagnosis by
multidisciplinary consultation consensus in the ILD-expertise center based on
HRCT or HRCT and lung biopsy if available. If no HRCT is available prior to
screening, it can be performed at the screening;
- Meeting all of the following criteria during the screening period:
1. FVC >=45% predicted for normal.
2. FEV1/FVC >=0.7.
3. DLco corrected for Hb >=40% predicted of normal.
- Able to provide written informed consent as approved by the independent
ethics committee;
- Able to undergo a CT scan and perform pulmonary function testing;
- Age >18 years and <80 years;
- Understanding the Dutch or English language.
Arm 2
- Fibrotic ILD diagnosis based on the ATS/ERS/JRS/ALAT guidelines, classified
into one of the four defined subgroups (chronic/fibrotic HP, iNSIP, CTD-ILD, or
unclassifiable ILD; non-stratified)(Raghu et al., 2020; Ryerson et al., 2013;
Shao et al., 2021; Travis et al., 2013). A chest HRCT should have been
performed within 12 months prior to screening, meeting the minimum requirements
for fILD diagnosis by multidisciplinary consultation consensus in the
ILD-expertise center based on HRCT or HRCT, serologic markers (e.g.,
antibodies, biomarkers), and/or BALF/ung biopsy (if available). If no HRCT is
available prior to screening, it can be performed at the screening;
- Minimum of 10% involvement of the lung parenchyma on HRCT and signs of
fibrosis, defined as traction bronchiectasis/bronchiolectasis, lobar volume
loss, and/or honeycombing (investigator-determined);
- Meeting all of the following criteria during the screening period:
1. FVC >=45% predicted for normal.
2. FEV1/FVC >=0.7.
3. DLco corrected for Hb >=40% predicted of normal.
- Able to provide written informed consent as approved by the independent
ethics committee;
- Able to undergo a CT scan and perform pulmonary function testing;
- Age >18 years and <80 years;
- Understanding the Dutch or English language.
Criteria BAL candidates Arm 2/ f-ILD-group:
- BAL at diagnosis available;
- Progression after 1 year of follow-up;
- No contra-indications for performing BAL e.g. allergies;
- Performance of BAL is low-risk estimated by clinical physician.
Arm 3
- ILA is defined according to the current guidelines set by the Fleischner
Society (Hatabu et al., 2020). A chest HRCT should have been performed within
12 months prior to screening, meeting the minimum requirements for ILA
diagnosis by multidisciplinary consultation consensus in the ILD-expertise
center based on HRCT only or HRCT and lung biopsy if available.
- Meeting all of the following criteria during the screening period:
1. FVC >=45% predicted for normal.
2. FEV1/FVC >=0.7.
3. DLco corrected for Hb >=40% predicted of normal.
- Able to provide written informed consent as approved by the independent
ethics committee;
- Able to undergo a CT scan and perform pulmonary function testing;
- Age >18 years and <
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
Arm 1
- Combined pulmonary fibrosis and emphysema (CPFE) is defined by the
coexistence of pulmonary fibrosis and emphysema, as described in the latest
paper by Cottin et al. (2022). To meet the criteria for CPFE on high-resolution
computed tomography (HRCT), patients must exhibit: emphysema of any subtype,
characterized by well-demarcated areas of low attenuation delimited by a very
thin wall (<1 mm) or no wall, involving at least 5% of the total lung volume
and lung fibrosis of any subtype (Cottin et al., 2022).
- Chronic obstructive lung disease (COPD) with an FEV1/FVC <70%;
- Uncontrolled severe asthma;
- Active malignancy, except for squamous cell carcinoma of the skin, low-risk
breast cancer, and low-risk prostate cancer;
- Pregnancy or lactating.
Arm 2
- Combined pulmonary fibrosis and emphysema (CPFE) is defined by the
coexistence of pulmonary fibrosis and emphysema, as described in the latest
paper by Cottin et al. (2022). To meet the criteria for CPFE on high-resolution
computed tomography (HRCT), patients must exhibit: emphysema of any subtype,
characterized by well-demarcated areas of low attenuation delimited by a very
thin wall (<1 mm) or no wall, involving at least 5% of the total lung volume
and lung fibrosis of any subtype (Cottin et al., 2022).
- Chronic obstructive lung disease (COPD) with an FEV1/FVC <70%;
- Uncontrolled severe asthma;
- Active malignancy, except for squamous cell carcinoma of the skin, low-risk
breast cancer, and low-risk prostate cancer;
- Pregnancy or lactating.
Arm 3
- Combined pulmonary fibrosis and emphysema (CPFE) is defined by the
coexistence of pulmonary fibrosis and emphysema, as described in the latest
paper by Cottin et al. (2022). To meet the criteria for CPFE on high-resolution
computed tomography (HRCT), patients must exhibit: emphysema of any subtype,
characterized by well-demarcated areas of low attenuation delimited by a very
thin wall (<1 mm) or no wall, involving at least 5% of the total lung volume
and lung fibrosis of any subtype (Cottin et al., 2022).
- Chronic obstructive lung disease (COPD) with an FEV1/FVC <70%;
- Uncontrolled severe asthma;
- Active malignancy, except for squamous cell carcinoma of the skin, low-risk
breast cancer, and low-risk prostate cancer;
- Medical history with pulmonary related auto-immune diseases;
- Family history with familial fibrosis (FPF);
- Pregnancy or lactating.
Additional exclusion criteria for the subgroups (n=60):
- In a subgroup of participants from arm 2 (n=30) and arm 3 (n=30), who undergo
an (additional) immunological bronchoalveolar lavage (iBAL) procedure,
participants with absolute contra-indications to undergo bronchoscopy with iBAL
will be excluded. Absolute-contra-indications are allergies to lidocaine,
midazolam, or xylometazoline, acute myocardial ischemia, and hemodynamic
instability in accordance with the protocol Bronchoscopy with immunological BAL
(in Dutch: Bronchoscopie met immunologische B.A.L) of the Amsterdam UMC (added
in Appendix 15.2).
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Pulmonary function test.<br /><br>- Inflammatory and Fibrosis Extent assessed by High-resolution Computed<br /><br>Tomography (HRCT) analyzed by using artificial intelligence software.<br /><br>- Biomarkers related to pulmonary fibrosis will be measured in plasma and<br /><br>serum.<br /><br>- Peripheral Blood Mononuclear Cell (PBMC) populations in blood.<br /><br>- Exhaled breath analysis including volatile organic compounds (VOCs) analysis<br /><br>by gas chromatography-mass spectrometry (GC-MS). </p><br>
- Secondary Outcome Measures
Name Time Method <p>- Disease-relevant questionnaires.<br /><br>- Genomics, epigenomics, and transcriptome analysis in blood.<br /><br>- Biomarkers related to pulmonary fibrosis will be measured in bronchoalveolar<br /><br>lavage fluid (BALF), if it has been collected at clinical grounds or has been<br /><br>performed in the subgroups.<br /><br>- Lung tissue will be analyzed with histochemical techniques if available from<br /><br>clinical context e.g., diagnostic biopsies or lung explants.<br /><br>- A subgroup of participants will be sampled using a ReCIVA breath analyzer<br /><br>from Owlstone and using a PExA instrument from PExA.<br /><br>- External exposome analyses of thephysical/chemical environment.<br /><br>- Biomarkers related to pulmonary fibrosis will be measured in a 24-hour urine<br /><br>collection.<br /><br>- Metabolome analyses in urine and blood.<br /><br>- Microbiome analyses in stool and nasal swabs. </p><br>