Cardiorespiratory Diagnostic Study (CARES)

A Longitudinal Observational Study to Investigate the Patterns of Change in the Tidal Breathing CO2 Waveform, Measured Using the N-Tidal C Handset, in Patients With COPD Compared to Patients With Other Common Cardiorespiratory Conditions

This study uses a new breathing device called 'N-Tidal C' handset which measures breathing patterns. Investigators have found that people with cardiac and respiratory illnesses breathe out a gas, called carbon dioxide (CO2), in a different way to healthy people. The pattern of breathed out CO2 (the waveform) varies according to the underlying health of the user's lungs. Monitoring these changes may help doctors to more accurately diagnose and monitor the most common and serious respiratory conditions.

Study Overview

• Status: Completed
• Conditions: Healthy; Bronchiectasis; Anemia; Asthma; Lung Cancer; Interstitial Lung Disease; COPD; Long COVID; Upper Respiratory Disease; Congestive Cardiac Failure
• Intervention / Treatment: Device: N-Tidal C handset

Detailed Description

Chronic Obstructive Pulmonary Disease (COPD) is among the most prevalent respiratory conditions, and in the top five causes of death worldwide. However, mis-diagnosis rates are high (both under- and over- diagnosis), owing to the lack of a simple, reliable and specific diagnostic test. In addition, COPD is often diagnosed late in the natural history of the disease, which misses the opportunity for early intervention, with early treatment and health-behaviour changes (smoking cessation).

Spirometry, the current gold standard for diagnosis, is unreliable (technique-dependent), crude (measures airflow), and non-specific (multiple respiratory conditions can produce similar patterns on spirometry). It also relies on proper administration by specially trained members of staff. As a result, spirometry is often (a) not performed before a speculative diagnosis of COPD is made, and (b) performed poorly, resulting in poor-quality information on which to base a respiratory diagnosis.

There is therefore a need for a simple, reliable, robust and accurate test for diagnosing COPD which is non-operator dependent, and non-technique dependent.

Currently, capnography is invasive, expensive and can only be recorded in specialist centres via a nasal cannula and micro-stream sampling of expired carbon dioxide in the intensive care setting. The N-Tidal C (NTC) handset, a new (CE-marked), hand-held, wireless device has been developed to monitor the user's Tidal Breathing CO2 (TBCO2) waveforms at rest, during normal tidal breathing. This device can be safely operated in the home environment, has a battery life of weeks, and has an isolated, disposable, breath pathway that isolates an individual's breath from the rest of the device, making it safe to reuse between patients after the outer casing has been decontaminated using a 3-stage disinfection process.

The N-Tidal technology has the potential to offer new insights into lung physiology (above and beyond those currently available from spirometry and lung function testing), and early evidence from TidalSense's previous clinical studies suggests that the TBCO2 data could be used to fingerprint and diagnose COPD.

• Study Type: Observational
• Enrollment (Actual): 744

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B19 1BP
      • Modality Partnership

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from among the primary care patient population served by the Modality (GP) partnership. Participants will either be healthy (no underlying cardiorespiratory diagnoses) or have one of the following conditions: COPD, asthma, congestive cardiac failure (heart failure), bronchiectasis (including cystic fibrosis), anaemia, lung cancer (including mesothelioma), pulmonary fibrosis, long COVID, an upper airway obstruction disorder, pulmonary embolism, pulmonary hypertension, extrinsic allergic alveolitis.

Participants will deliberately be recruited from a wide range of demographic backgrounds, to provide diversity of: age, gender, geographic location and ethnicity.

Description

Inclusion Criteria:

• Age > 18 years
• Healthy volunteer (with no previous or current chronic cardiorespiratory diagnoses)

One of the following cardiorespiratory diagnoses:

• COPD (GOLD 1, 2, 3 / A, B, C)*
• Asthma (mild to moderate, not labelled as severe)*
• Congestive cardiac failure*
• Anaemia (with at least 50% of participants recruited having no history of chronic cardiorespiratory conditions)*
• Bronchiectasis (acquired or genetic, e.g. cystic fibrosis or other primary ciliary dyskinesias)*
• Lung cancer (including rare types e.g. mesothelioma)*
• Interstitial Lung Disease (including pulmonary fibrosis pneumoconiosis, asbestosis, sarcoidosis, amyloidosis)*
• Long COVID*
• Upper airway obstruction disorder*
• [Active pulmonary hypertension]
• [Extrinsic Allergic Alveolitis]
• [Active pulmonary embolism]

Exclusion Criteria:

• Participants who, in the opinion of the chief investigator, or their delegate, are unlikely to comply with the requirements of the study;
• Diagnosis of neuromuscular disorders;
• Concurrent diagnosis of cardiorespiratory conditions (other than those listed in the inclusion criteria above) that, in the opinion of the chief investigator, would impact the conduct of the study
• Participants who are acutely unwell, e.g. active exacerbation, very short of breath e.g. severe COPD (GOLD 4 / D) or end-stage IPF.
• Inability to give written informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

10

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Obstructive Pulmonary Disease; 245 participants - GOLD 1, 2, 3 / A, B, C	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Asthma; 55 participants - Mild to moderate, not labelled as severe.	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Congestive cardiac failure; 55 participants	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Anaemia; 55 participants - with at least 50% of participants recruited having no history of chronic cardiorespiratory conditions	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Bronchiectasis; 55 participants - Acquired or genetic, e.g. cystic fibrosis or other primary ciliary dyskinesias	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Lung cancer; 55 participants - including rare types e.g. mesothelioma	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Interstitial Lung Disease; 55 participants - including pulmonary fibrosis pneumoconiosis, asbestosis, sarcoidosis, amyloidosis	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Long COVID; 55 participants	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Upper airway obstruction disorder; 55 participants	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.
Healthy; 55 participants - with no previous or current chronic cardiorespiratory diagnoses	Device: N-Tidal C handset; Participants are to use the 'N-Tidal C' handset every day for 14 days. This will ideally be two times a day (once in the morning and once in the evening, before using any regular inhalers). Each breath record requires the participant to breathe through the mouthpiece for 75 seconds in a relaxed manner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath records from participants with Chronic Obstructive Pulmonary Disease (COPD)	Tidal Breathing CO2 waveform data from 245 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 6860 records	12 months from First Patient First Visit (FPFV)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath records from Healthy volunteers (no previous or current cardiorespiratory diagnoses)	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Asthma	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Congestive cardiac failure	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Anaemia	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Bronchiectasis	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Lung cancer	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Interstitial Lung Disease	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Long COVID	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)
Breath records from participants with Upper airway obstruction disorder	Tidal Breathing CO2 waveform data from 55 participants collected using the N-Tidal C Handset. Each participant delivering 2 x breath records per day for 14 days = 1540 records	12 months from First Patient First Visit (FPFV)

Collaborators and Investigators

• Sponsor: TidalSense
• Collaborators: National Institute for Health Research, United Kingdom; Innovate UK
• Investigators: Principal Investigator: Zishan Ali, MBBS BSc, Modality Partnership; Principal Investigator: Elango Vijaykumar, MBBS, FRCG, Modality Partnership

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: June 3, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Disease Attributes; Bronchial Diseases; Chronic Disease; Post-Infectious Disorders; COVID-19; Heart Failure; Bronchiectasis; Lung Diseases; Lung Diseases, Interstitial; Respiration Disorders; Respiratory Tract Diseases; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: G001-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No