Using Exercise-testing to Explore Patient Differences in Severe Asthma

NCT05733143 | Active Not Recruiting

• 2 other identifiers: B22/23320351
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational pilot study is to use exercise-testing to assess patients with severe asthma who have high levels of breathlessness and compare them to other groups of patients with low levels of breathlessness. We will compare the background and overall fitness levels in all groups. This may provide new knowledge to why these patients remain breathless despite being on treatment with low levels of inflammation. The main question we aim to answer is: "How are these patients different compared to patients who respond to treatment?" We will look at reasons why patients with low levels of inflammation in their lungs are still breathless despite being on treatment. Participants will be required to take part in a 6-month study were they will firstly attend a "study visit" and a 6 month follow up. At the study visit participants will be consented and required to:

• Complete questionnaires on their symptoms
• Provide information on their background
• Undergo a physical examination
• Provide blood and urine samples for specific testing for asthma and future investigations
• Perform breathing tests
• Undergo an exercise-test on a treadmill During this study, researchers will compare this group will to participants who are similar but whose symptoms respond to treatment. We will also look at other groups of asthma patients who have who have different levels of inflammation in their lungs to see if there are any differences. We predict, these patients will have a different background and features to those whose symptoms respond to treatment.

Conditions

Asthma

Keywords

asthma; Cardiopulmonary exercise stress testing

Outcome Measures

Primary Outcomes (1)

• OBJECTIVES AND OUTCOME MEASURES

  The outcomes of this study are purely exploratory. We will describe maximal exercise tolerance and limiting factors at peak exercise in distinct patient groups with severe asthma using the physiological parameters derived from CPEST.

  6 months

Other Outcomes (1)

• EXPLORATORY ANALYSIS

  6 MONTHS

Study Arms (4)

Symptom high/T2-biomarker low (20 participants)

\[ACQ≥ 1.5 FeNO\<20 ppb AND blood eosinophil count\<150 cells/µL\]. During the study visit patients will undergo the following; COVID Lateral flow test (24 and 48 hours prior to assessment visit), Informed consent, Medical history and baseline demographics, vital Signs measurements, Weight/Height/BMI, Medication review, Concomitant medication check including technique, medical adherence, and self-management plan, Physical examination, Urine pregnancy test (If relevant), HADS score for depression, HADS score for anxiety, ACQ-5, Mini-AQLQ (QoL), St Georges Respiratory Questionnaire (SGRQ), Nijmegen hyperventilation score, BORG score, WHO Physical Global Activity Questionnaire (GPAQ), Haematology (FBC), Bio-banked samples: EDTA and urine(Eicosanoids), Spirometry, FeNO, Exercise test (CPEST) At 6 month follow up, in routine clinical care, participants will complete the same assessments. They will not be required to provide samples for biobanking or perform a repeat CPEST.

Other: cardiopulmonary exercise stress test (CPEST)

Symptom low/T2-biomarker high (20 participants)

\[ACQ\<1.5 AND FeNO≥20 ppb AND blood eosinophil count≥150 cells/µL\] During the study visit patients will undergo the following; COVID Lateral flow test (24 and 48 hours prior to assessment visit), Informed consent, Medical history and baseline demographics, vital Signs measurements, Weight/Height/BMI, Medication review, Concomitant medication check including technique, medical adherence, and self-management plan, Physical examination, Urine pregnancy test (If relevant), HADS score for depression, HADS score for anxiety, ACQ-5, Mini-AQLQ (QoL), St Georges Respiratory Questionnaire (SGRQ), Nijmegen hyperventilation score, BORG score, WHO Physical Global Activity Questionnaire (GPAQ), Haematology (FBC), Bio-banked samples: EDTA and urine(Eicosanoids), Spirometry, FeNO, Exercise test (CPEST) At 6 month follow up, in routine clinical care, participants will complete the same assessments. They will not be required to provide samples for biobanking or perform a repeat CPEST.

Other: cardiopulmonary exercise stress test (CPEST)

Symptom low/T2-biomarker low (12 participants)

\[ACQ\<1.5 AND FeNO\<20 ppb AND blood eosinophil count\<150 cells/µL\] During the study visit patients will undergo the following; COVID Lateral flow test (24 and 48 hours prior to assessment visit), Informed consent, Medical history and baseline demographics, vital Signs measurements, Weight/Height/BMI, Medication review, Concomitant medication check including technique, medical adherence, and self-management plan, Physical examination, Urine pregnancy test (If relevant), HADS score for depression, HADS score for anxiety, ACQ-5, Mini-AQLQ (QoL), St Georges Respiratory Questionnaire (SGRQ), Nijmegen hyperventilation score, BORG score, WHO Physical Global Activity Questionnaire (GPAQ), Haematology (FBC), Bio-banked samples: EDTA and urine(Eicosanoids), Spirometry, FeNO, Exercise test (CPEST) At 6 month follow up, in routine clinical care, participants will complete the same assessments. They will not be required to provide samples for biobanking or perform a repeat CPEST.

Other: cardiopulmonary exercise stress test (CPEST)

Symptom high/T2-biomarker high (12 participants)

\[ACQ≥ 1.5 AND FeNO≥20 ppb AND blood eosinophil count≥150 cells/µL\] During the study visit patients will undergo the following; COVID Lateral flow test (24 and 48 hours prior to assessment visit), Informed consent, Medical history and baseline demographics, vital Signs measurements, Weight/Height/BMI, Medication review, Concomitant medication check including technique, medical adherence, and self-management plan, Physical examination, Urine pregnancy test (If relevant), HADS score for depression, HADS score for anxiety, ACQ-5, Mini-AQLQ (QoL), St Georges Respiratory Questionnaire (SGRQ), Nijmegen hyperventilation score, BORG score, WHO Physical Global Activity Questionnaire (GPAQ), Haematology (FBC), Bio-banked samples: EDTA and urine(Eicosanoids), Spirometry, FeNO, Exercise test (CPEST) At 6 month follow up, in routine clinical care, participants will complete the same assessments. They will not be required to provide samples for biobanking or perform a repeat CPEST.

Other: cardiopulmonary exercise stress test (CPEST)

Interventions

cardiopulmonary exercise stress test (CPEST) OTHER

The study is observational and purely exploratory. We will utilise cardiopulmonary exercise stress testing to assess levels of fitness and causes for symptoms in proposed groups.

Symptom high/T2-biomarker high (12 participants); Symptom high/T2-biomarker low (20 participants); Symptom low/T2-biomarker high (20 participants); Symptom low/T2-biomarker low (12 participants)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will aim to look at and sample phenotypically different groups of asthma patients who are symptom high and low with with either low or high biomarkers.

You may qualify if:

• All participating patients will be attending the Regional Severe Asthma Service of Belfast Trust and will be:
• Age ≥ 18 and ≤ 80 years at screening visit
• Able and willing to provide written informed consent and to comply with the study protocol
• Severe asthma confirmed after assessment by an asthma specialist as per GINA guidelines (1)
• Diagnosed with asthma at least 12 months prior to screening and on GINA Step 4/5 treatment including those who are on biologic therapy
• On optimal medical management as determined by clinician

You may not qualify if:

• Any absolute contraindication to CPEST (Acute myocardial infarction (3-5 days), unstable angina uncontrolled arrhythmia causing symptoms or haemodynamic compromise, syncope, active endocarditis, acute myocarditis/pericarditis, symptomatic severe aortic stenosis, uncontrolled heart failure, suspected dissecting or leaking aortic aneurysm, uncontrolled asthma, arterial desaturation at rest on room air \<85%) (15)
• Acute exacerbation requiring oral corticosteroids in previous 4 weeks before first visit
• History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the participant's full participation in the study, in the opinion of the investigator
• Treatment with an investigational agent within 30 days of assessment (or five half-lives of the investigational agent, whichever is longer)
• Female participants who are pregnant or lactating
• Other clinically significant medical disease or uncontrolled concomitant disease despite treatment that is likely, in the opinion of the investigator, to impact the patient's ability to participate in the study

Sponsors & Collaborators

• Queen's University, Belfast: lead
• Belfast Health and Social Care Trust: collaborator

Study Sites (1)

Queen's University Belfast

Belfast, Northern Ireland, United Kingdom

Location

Related Publications (1)

• McNicholl DM, Megarry J, McGarvey LP, Riley MS, Heaney LG. The utility of cardiopulmonary exercise testing in difficult asthma. Chest. 2011 May;139(5):1117-1123. doi: 10.1378/chest.10-2321. Epub 2011 Feb 3.

  PMID: 21292756 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Haematology \[5ml\] (haemoglobin, haematocrit, platelet count, red blood cell count, white blood cell count, percent and absolute differential count. Samples for Biomarkers: The following will be collected on the day of Cardiopulmonary exercise stress testing for exploration of biomarkers and stored for future research. These biomarkers can include, but are not limited to, plasma biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways in severe asthma. * Plasma: 10 ml EDTA collection tube resulting in \~5 ml plasma stored as 0.5 ml aliquots for plasma measures of biomarkers related to asthmatic airway inflammation, corticosteroid signalling and putative inflammatory pathways in severe asthma * Urine sample: urinary eicosanoids

MeSH Terms

Conditions

Asthma

Interventions

Exercise Test

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Officials

• Liam G Heaney, MD

  Queens University Belfast

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Respiratory Medicine

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: February 17, 2023
• Study Start: July 18, 2023
• Primary Completion: November 1, 2025
• Study Completion: November 30, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)