Clinical trial NCT04680832: Exhaled Breath Analysis Using eNose Technology as a Biomarker for Diagnosis and Disease Progression in Fibrotic ILD
Official title: Exhaled Breath Analysis Using eNose Technology as a Biomarker for Diagnosis and Disease Progression in Fibrotic Interstitial Lung Disease
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Pulmonary Fibrosis
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2020-12-23
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with ILD

Brief summary: The ILDnose study a multinational, multicenter, prospective, longitudinal study in outpatients with pulmonary fibrosis. The aim is to assess the accuracy of eNose technology as diagnostic tool for diagnosis and differentiation between the most prevalent fibrotic interstitial lung diseases. The value of eNose as biomarker for disease progression and response to treatment is also assessed. Besides, validity of several questionnaires for pulmonary fibrosis is investigated.

Detailed description: Patients will be included in the study after signing written informed consent. eNose measurements will take place before or after a routine outpatient clinic visit at the same location as the regular visit, ensuring minimal inconvenience for patients. First, patients will be asked to rinse their mouth thoroughly with water three times. Subsequently, exhaled breath analysis will be performed in duplicate with a 1-minute interval. An eNose measurement consists of five tidal breaths, followed by an inspiratory capacity maneuver to total lung capacity, a five second breath hold, and subsequently a slow expiration (flow \<0.4L/s) to residual volume. The measurements are non-invasive and will cost approximately 5-10 minutes in total, including explanation and informed consent procedure. There are no risks associated with this study and the burden for patients is minimal.

After the measurement, patients will complete a short survey about questions relevant for the data analysis (food intake in the last two hours, smoking history, medication use, comorbidities, and symptoms of respiratory infection). In addition, patients will complete the L-PF questionnaire and the Global Rating of Change scale (GRoC). The L-PF questionnaire consists of 21 questions on a 5-point Likert scale about the impact of pulmonary fibrosis on quality of life, and takes about 3 minutes to complete. The GRoC consists of one question on a scale from -7 to 7: were there any changes in your quality of life since your last visit? Symptoms (cough and dyspnea) will be scored on a 10 cm VAS scale from -5 to 5.

Next to eNose measurements, demographic data and physiological parameters of patients will be collected from the medical records at baseline, month 6, and month 12. Parameters such as age, gender, diagnosis, time since diagnosis, comorbidities, medication, pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO)), laboratory parameters (i.e. auto-immune antibodies), HRCT pattern, BAL results and if applicable also genetic mutations, will be recorded and stored in an electronic case report form. These parameters will be collected as part of routine daily care, patients will not undergo any additional tests for study purposes. HRCT scans will be re-analysed centrally by an experienced ILD thoracic radiologist. Mortality and lung function parameters will also be collected at 24 months, if this information is available.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of fibrotic ILD, as discussed in a multidisciplinary team meeting (50% incident patients and 50% prevalent patients). Patients are classified as 'incident' if they received a diagnosed in a multidisciplinary team meeting within the past six months. Patients will be required to have fibrosis on a HRCT scan \<1 year before enrollment in the study defined as reticular abnormality with traction bronchiectasis, with or without honeycombing, as determined by a radiologist. No minimum extent of fibrosis will be required.

Exclusion Criteria:

* Alcohol consumption ≤ 12 hours before the measurement
* Physically not able to perform eNose measurement

Primary outcomes:
measure: Diagnostic accuracy for IPF - CHP
timeFrame: Baseline
measure: AUC for IPF - CHP
timeFrame: Baseline
measure: AUC for IPF - iNSIP
timeFrame: Baseline
measure: Diagnostic accuracy for IPF - iNSIP
timeFrame: Baseline
measure: AUC for IPF - IPAF
timeFrame: Baseline
measure: Diagnostic accuracy for IPF - IPAF
timeFrame: Baseline
measure: Diagnostic accuracy for IPF - CTD-ILD
timeFrame: Baseline
measure: AUC for IPF - CTD-ILD
timeFrame: Baseline
measure: Diagnostic accuracy for IPF - unclassifiable ILD
timeFrame: Baseline
measure: AUC for IPF - unclassifiable ILD
timeFrame: Baseline
measure: Diagnostic accuracy for CHP - iNSIP
timeFrame: Baseline
measure: AUC for CHP - iNSIP
timeFrame: Baseline
measure: Diagnostic accuracy for CHP - IPAF
timeFrame: Baseline
measure: AUC for CHP - IPAF
timeFrame: Baseline
measure: Diagnostic accuracy for CHP - CTD-ILD
timeFrame: Baseline
measure: AUC for CHP - CTD-ILD
timeFrame: Baseline
measure: Diagnostic accuracy for CHP - unclassifiable ILD
timeFrame: Baseline
measure: AUC for CHP - unclassifiable ILD
timeFrame: Baseline
measure: Diagnostic accuracy for iNSIP - IPAF
timeFrame: Baseline
measure: AUC for iNSIP - IPAF
timeFrame: Baseline
measure: Diagnostic accuracy for iNSIP - CTD-ILD
timeFrame: Baseline
measure: AUC for iNSIP - CTD-ILD
timeFrame: Baseline
measure: Diagnostic accuracy for iNSIP - unclassifiable ILD
timeFrame: Baseline
measure: AUC for iNSIP - unclassifiable ILD
timeFrame: Baseline
measure: Diagnostic accuracy for IPAF - CTD-ILD
timeFrame: Baseline
measure: AUC for IPAF - CTD-ILD
timeFrame: Baseline
measure: Diagnostic accuracy for IPAF - unclassifiable ILD
timeFrame: Baseline
measure: AUC for IPAF - unclassifiable ILD
timeFrame: Baseline
measure: Diagnostic accuracy for CTD-ILD - unclassifiable ILD
timeFrame: Baseline
measure: AUC for CTD-ILD - unclassifiable ILD
timeFrame: Baseline
measure: Disease progression
timeFrame: 12 months after inclusion
measure: Disease progression
timeFrame: 24 months after inclusion
measure: Diagnostic accuracy of disease progression
timeFrame: 6 months after inclusion
measure: Diagnostic accuracy of disease progression
timeFrame: 12 months after inclusion
measure: Diagnostic accuracy of disease progression
timeFrame: 24 months after inclusion
measure: Worsening of respiratory symptoms (cough and/or dyspnea)
timeFrame: 12 months after inclusion
measure: Mortality
timeFrame: 12 months after inclusion
measure: Mortality
timeFrame: 24 months after inclusion
measure: Therapeutic effect
timeFrame: 6 months after start therapy
measure: Therapeutic effect
timeFrame: 12 months after start therapy
Secondary outcomes:
measure: L-PF evaluation
timeFrame: 6 months after inclusion
measure: L-PF evaluation
timeFrame: 6 months after inclusion
measure: L-PF evaluation
timeFrame: 12 months after inclusion
measure: L-PF evaluation
timeFrame: 12 months after inclusion
measure: L-PF evaluation
timeFrame: 24 months after inclusion
measure: L-PF evaluation
timeFrame: 24 months after inclusion
measure: GRoC evaluation
timeFrame: 6 months after inclusion
measure: GRoC evaluation
timeFrame: 6 months after inclusion
measure: GRoC evaluation
timeFrame: 12 months after inclusion
measure: GRoC evaluation
timeFrame: 12 months after inclusion
measure: GRoC evaluation
timeFrame: 24 months after inclusion
measure: GRoC evaluation
timeFrame: 24 months after inclusion
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Lyon
country: France
facility: University Lyon 1, Louis Pradel hospital, Lyon. FranceService de pneumologie, hôpital Louis Pradel
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: London
country: United Kingdom
facility: Royal Brompton Hospital
Study officials:
affiliation: Erasmus Medical Center
name: Marlies S Wijsenbeek, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: