Exhaled Breath Analysis Using eNose Technology as a Biomarker for Diagnosis and Disease Progression in Fibrotic ILD

Not Applicable

Recruiting

• Conditions: Pulmonary Fibrosis
• Interventions: Diagnostic Test: Electronic nose

• Registration Number: NCT04680832
• Lead Sponsor: Erasmus Medical Center

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.

Study Timeline

• Study Start: 2020-11-01
• Study First Submitted: 2020-12-11
• Study First Submitted QC: 2020-12-17
• Study First Posted: 2020-12-23
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-18
• Last Update Posted: 2024-03-19
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ILD patients	Electronic nose	Patients diagnosed with one of the most prevalent fibrotic ILDs: IPF, CHP, CTD-ILD, iNSIP, IPAF, and unclassifiable ILD (defined as unclassifiable disease at the time of the first MDT).

Primary Outcome Measures

Name	Time	Method
AUC for IPAF - CTD-ILD	Baseline	AUC for differentiating IPAF from CTD-ILD
AUC for IPF - CHP	Baseline	AUC for differentiating IPF from CHP
Diagnostic accuracy for iNSIP - CTD-ILD	Baseline	Accuracy for differentiating iNSIP from CTD-ILD
AUC for CTD-ILD - unclassifiable ILD	Baseline	AUC for differentiating CTD-ILD from unclassifiable ILD
Mortality	24 months after inclusion	Deceased subjects
AUC for IPF - iNSIP	Baseline	AUC for differentiating IPF from iNSIP
AUC for IPF - IPAF	Baseline	AUC for differentiating IPF from IPAF
Diagnostic accuracy for IPF - CHP	Baseline	Accuracy for differentiating IPF from CHP
Diagnostic accuracy for IPF - IPAF	Baseline	Accuracy for differentiating IPF from IPAF
AUC for IPF - CTD-ILD	Baseline	AUC for differentiating IPF from CTD-ILD
Diagnostic accuracy for CHP - IPAF	Baseline	Accuracy for differentiating CHP from IPAF
AUC for CHP - CTD-ILD	Baseline	AUC for differentiating CHP from CTD-ILD
Diagnostic accuracy for CHP - unclassifiable ILD	Baseline	Accuracy for differentiating CHP from unclassifiable ILD
AUC for iNSIP - IPAF	Baseline	AUC for differentiating iNSIP from IPAF
Diagnostic accuracy for IPF - iNSIP	Baseline	Accuracy for differentiating IPF from iNSIP
Diagnostic accuracy for IPF - CTD-ILD	Baseline	Accuracy for differentiating IPF from CTD-ILD
Diagnostic accuracy for IPAF - unclassifiable ILD	Baseline	Accuracy for differentiating IPAF from unclassifiable ILD
Diagnostic accuracy of disease progression	24 months after inclusion	Relating disease progression (based on FVC decline, CT scan and/or symptoms) to change in eNose values
Diagnostic accuracy for IPF - unclassifiable ILD	Baseline	Accuracy for differentiating IPF from unclassifiable ILD
AUC for CHP - iNSIP	Baseline	AUC for differentiating CHP from iNSIP
AUC for CHP - IPAF	Baseline	AUC for differentiating CHP from IPAF
Diagnostic accuracy for CHP - CTD-ILD	Baseline	Accuracy for differentiating CHP from CTD-ILD
Diagnostic accuracy for iNSIP - IPAF	Baseline	Accuracy for differentiating iNSIP from IPAF
AUC for iNSIP - CTD-ILD	Baseline	AUC for differentiating iNSIP from CTD-ILD
Diagnostic accuracy for iNSIP - unclassifiable ILD	Baseline	Accuracy for differentiating iNSIP from unclassifiable ILD
Diagnostic accuracy for CTD-ILD - unclassifiable ILD	Baseline	Accuracy for differentiating CTD-ILD from unclassifiable ILD
Worsening of respiratory symptoms (cough and/or dyspnea)	12 months after inclusion	Worsening of respiratory symptoms (cough and/or dyspnea) measured on a visual analogue scale (0-10, 0 no symptoms, 10 most severe symptoms)
AUC for IPF - unclassifiable ILD	Baseline	AUC for differentiating IPF from unclassifiable ILD
Diagnostic accuracy for CHP - iNSIP	Baseline	Accuracy for differentiating CHP from iNSIP
AUC for CHP - unclassifiable ILD	Baseline	AUC for differentiating CHP from unclassifiable ILD
AUC for iNSIP - unclassifiable ILD	Baseline	AUC for differentiating iNSIP from unclassifiable ILD
Diagnostic accuracy for IPAF - CTD-ILD	Baseline	Accuracy for differentiating IPAF from CTD-ILD
AUC for IPAF - unclassifiable ILD	Baseline	AUC for differentiating IPAF from unclassifiable ILD
Disease progression	24 months after inclusion	FVC decline in combination with worsening of respiratory symptoms (cough and/or dyspnea) and/or progressive fibrosis on CT scan
Therapeutic effect	12 months after start therapy	Relating start of anti-fibrotic medication to change in eNose values

Secondary Outcome Measures

Name	Time	Method
GRoC evaluation	24 months after inclusion	Relating Longitudinal changes in score of Global Rating of Change Scale to lung function values
L-PF evaluation	24 months after inclusion	Relating Longitudinal changes in score of L-PF questionnaire to lung function values

Trial Locations

Locations (4)

University Lyon 1, Louis Pradel hospital, Lyon. FranceService de pneumologie, hôpital Louis Pradel; 🇫🇷 Lyon, France

Thoraxklinik Heidelberg; 🇩🇪 Heidelberg, Germany

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Royal Brompton Hospital; 🇬🇧 London, United Kingdom