Bronchial HyperreactivityNCT02343419
Diagnostic Utility of Different Airway Resistance Assessment Techniques in the Methacholine Challenge Test
A study testing Methacholine Challenge Test in people with Bronchial Hyperreactivity and Abnormal Respiratory Airway Resistance, run by Medical University of Warsaw at 1 site in Poland.
Trial summary
The aim of the study is to compare standard spirometric evaluation of methacholine challenge test with plethysmographic, interrupter technique and forced oscillation technique (FOT) evaluation of the airways resistance. The study group will consist of patients referred for methacholine challenge test. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Bronchial Hyperreactivity, Abnormal Respiratory Airway Resistance
- What is being tested?
- Methacholine Challenge Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 sitePoland
- Study dates
- Nov 2014to May 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- presence of asthma symptoms without confirmation of diagnosis by standard methods
- dyspnea and/or cough of unknown etiology
Who cannot join
- FEV1 <1.2 L or <60% of predicted value
- acute heart failure
- myocardial infarction in last 3 months
- transient ischaemic attack or stroke in last 3 months
- aneurysms
- methacholine allergy
Show all 10Show fewer
- pregnant and lactating women
- administration of β2-mimetic, anticholinergic agent or theophylline before methacholine challenge test in 6, 8 and 24 hours, respectively
- respiratory tract infection in last 6 weeks
- patient inability to cooperate
Trial locations and contacts
1 site in 1 country.
Poland1 site
Department of Internal Medicine, Pneumonology and Allergy, Medical University of Warsaw
Warsaw, Masovian Voivodeship, 02-097
About this study
Official title: Diagnostic Utility of Different Airway Resistance Assessment Techniques in the Evaluation of Bronchial Hyperreactivity by Methacholine Challenge Testing
The aim of the study is to compare standard spirometric evaluation of methacholine challenge test with plethysmographic, interrupter technique and forced oscillation technique (FOT) evaluation of the airways resistance.
The study group will consist of patients referred for methacholine challenge test. All patient will undergo spirometric, plethysmographic, interrupter technique and FOT examinations - before and after inhalation of aerosols. Patients will also undergo the measurement of nitric oxide concentration in exhaled air and laboratory tests, including: blood count, measurement of serum C-reactive protein, sodium, potassium, creatinine, immunoglobulin E and N-Terminal pro-brain natriuretic peptide (NT-proBNP) concentration.
The investigators intend to assess, if plethysmographic, and/or interrupter, and/or FOT measurement of bronchial reactivity can replace standard spirometric assessment. Plethysmography, interrupter technique and FOT are much more easier to perform for patients. Furthermore, those two techniques are less dependent on patient's motivation and cooperation ability. Thus, usage of FOT, interrupter technique and/or plethysmography in bronchial hyperreactivity testing could make methacholine challenge test more comfortable and available for more patients. The investigators are also going to analyze the relationship between exhaled nitric oxide and functional indices of bronchial hyperreactivity.
Read the detailed description
Bronchial hyperreactivity is defined as the increased respiratory tract responsiveness to multiple stimuli, which results in bronchial muscles constriction and bronchial lumen narrowing. Bronchial hyperreactivity is a hallmark of asthma, however it may also be present in other diseases, e.g. chronic obstructive pulmonary disease (COPD). Methacholine challenge test is one of the bronchial reactivity assessment methods. Methacholine acts directly on bronchial smooth muscles receptors and causes bronchoconstriction. Bronchial reactivity is increased in the presence of active inflammation. Methacholine challenge testing is commonly performed in patients with symptoms suggestive of asthma and negative result of spirometry reversibility test. The measurement of methacholine concentration which causes 20% forced expiratory volume at one second (FEV1) decrease in post-inhalation spirometry (PC20) is a standard method of hyperreactivity evaluation. However, above method could be used among patients who are able to perform acceptable spirometry. Furthermore, results of spirometry might be influenced by level of compliance and motivation of patients. Moreover, whereas spirometric methacholine challenge test has high negative predictive values, its positive predictive value is relatively low. Thus, diagnostic utility of other pulmonary function tests should be assessed in methacholine challenge test evaluation.
In plethysmography airway resistance is performed during tidal breathing. The increase of specific airway resistance of 200% and the decrease of specific airway conductance of 40% after methacholine inhalation, respectively, are proposed as a cut-off levels for bronchial hyperreactivity diagnosis.
In forced oscillation technique (FOT), sinusoidal oscillations are emitted by membrane into airway lumen and airway resistance is calculated on the basis of changes in air flow induced by oscillations. The increase of resistance and decrease of reactance in FOT are typical for bronchoconstriction.
Finally, also interrupter technique (IT) allows for airway resistance assessment during tidal breathing. In IT, airway resistance is calculated on the basis of mouth pressure measured directly after airway occlusion and airflow measured directly before occlusion.
The aim of the study is to compare standard spirometric evaluation of methacholine challenge test with plethysmographic, interrupter technique and forced oscillation technique (FOT) evaluation of the airways resistance.
All patient will undergo:
- clinical examination
- measurement of nitric oxide concentration in exhaled air
- spirometric, plethysmographic, interrupter technique and FOT examinations - before inhalation and after inhalation of aerosols
- following laboratory tests: blood count, measurement of serum C-reactive protein (CRP), sodium, potassium, creatinine, immunoglobulin E and NT-proBNP concentration
Patients will be provided with written and spoken information about study protocol. Written informed consent will be obtained from every patient.
- Being tested
- Methacholine Challenge Test
- Keywords
- Bronchial Hyperreactivity, Bronchial Provocation Tests, Methacholine Chloride, Respiratory Function Tests, Spirometry, Airway Resistance, Plethysmography
- Medical subject headings
- Bronchial Hyperreactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methacholine Challenge TestOther
Forced oscillation technique test, plethysmography, interrupter technique test and spirometry will be performed in a row before any intervention and after inhalation of aerosols - normal saline, followed by increasing concentrations of methacholine: 0.03 mg/ml; 0.06 mg/ml; 0.125 mg/ml; 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml, 2 mg/ml, 4 mg/ml, 8 mg/ml, 16 mg/ml.
In case of FEV1 decrease of ≥ 20% of the initial value methacholine challenge test will be ceased and patient will be administered 200 µg of salbutamol in inhalation. Then, pulmonary function tests will be performed after 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Bronchial challenge test | Experimental | Patients will undergo Methacholine Challenge Test assessed by forced oscillation technique (FOT), plethysmography, interrupter technique and spirometry. Receives: Other: Methacholine Challenge Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
The concentration of methacholine inducing a 20% fall in FEV(1) from post-diluent baseline [PC(20)]
In case of FEV1 decrease of > 20% from baseline PC (20) will be calculated by logarithmic interpolation.
Measured: up to 2 hours
Secondary outcomes (13)
Change in FOT resistance and reactance from post-diluent baseline after inhalating consecutive methacholine aerosols
Airway resistance and reactance will be measured by FOT after inhalating methacholine aerosols until FEV(1) fall of >20% from baseline
Measured: within 6 minutes after methacholine aerosol inhalation
Change in plethysmographic airway resistance from post-diluent baseline after inhalating consecutive methacholine aerosols
Airway resistance will be measured by plethysmography after inhalating methacholine aerosols until FEV(1) fall of >20% from baseline
Measured: within 6 minutes after methacholine aerosol inhalation
Change in interrupter airway resistance from post-diluent baseline after inhalating consecutive methacholine aerosols
Airway resistance will be measured by interrupter technique after inhalating methacholine aerosols until FEV(1) fall of >20% from baseline
Measured: within 6 minutes after methacholine aerosol inhalation
Change in FEV(1) from from post-diluent baseline after inhalating consecutive methacholine aerosols
FEV (1) will be measured by spirometry after inhalating methacholine aerosols until FEV(1) fall of >20% from baseline
Measured: within 6 minutes after methacholine aerosol inhalation
Assessment of the difficulty level of FOT
Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test
Measured: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of plethysmography
Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test
Measured: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of interrupter technique
Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test
Measured: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of spirometry
Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test
Measured: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Duration of the bronchial resistance assessment by FOT
Duration of each pulmonary function test will be measured
Measured: During methacholine challenge test (up to 2 hours)
Duration of the bronchial resistance assessment by plethysmography
Duration of each pulmonary function test will be measured
Measured: During methacholine challenge test (up to 2 hours)
Duration of the bronchial resistance assessment by interrupter technique
Duration of each pulmonary function test will be measured
Measured: During methacholine challenge test (up to 2 hours)
Duration of spirometry
Duration of each pulmonary function test will be measured
Measured: During methacholine challenge test (up to 2 hours)
Total duration of methacholine challenge test
Total duration bronchial challenge will be measured
Measured: During methacholine challenge test (up to 2 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2015 (estimated)
- Study startNov 2014
- Primary completionJan 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bronchial HyperreactivityStudies of the same condition, open and under way.
- More trials run by Medical University of WarsawThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Warsaw
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tomasz A Urbankowski, MD, Principal investigator, Department of Internal Medicine, Pneumonology and Allergy, Medical University of Warsaw
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02343419
- Sponsor's protocol ID
- PFT-DIMPA-WUM1
- Status last verified
- Nov 2016
- First submitted
- 1 Dec 2014
- Last updated
- 9 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Urbankowski T, Przybylowski T. Methacholine Challenge Testing: Comparison of FEV1 and Airway Resistance Parameters. Respir Care. 2021 Mar;66(3):449-459. doi: 10.4187/respcare.08331. Epub 2020 Nov 17.
PubMed 33203723
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnostic Utility of Different Airway Resistance Assessment Techniques in the Evaluation of Bronchial Hyperreactivity by Methacholine Challenge Testing
- ClinicalTrials.gov ID
- NCT02343419
- Acronym / sponsor ID
- PFT-DIMPA-WUM1
- Keywords
- Bronchial Hyperreactivity, Bronchial Provocation Tests, Methacholine Chloride, Respiratory Function Tests, Spirometry, Airway Resistance, Plethysmography
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Medical University of WarsawUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 22 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to compare standard spirometric evaluation of methacholine challenge test with plethysmographic, interrupter technique and forced oscillation technique (FOT) evaluation of the airways resistance.
The study group will consist of patients referred for methacholine challenge test. All patient will undergo spirometric, plethysmographic, interrupter technique and FOT examinations - before and after inhalation of aerosols. Patients will also undergo the measurement of nitric oxide concentration in exhaled air and laboratory tests, including: blood count, measurement of serum C-reactive protein, sodium, potassium, creatinine, immunoglobulin E and N-Terminal pro-brain natriuretic peptide (NT-proBNP) concentration.
The investigators intend to assess, if plethysmographic, and/or interrupter, and/or FOT measurement of bronchial reactivity can replace standard spirometric assessment. Plethysmography, interrupter technique and FOT are much more easier to perform for patients. Furthermore, those two techniques are less dependent on patient's motivation and cooperation ability. Thus, usage of FOT, interrupter technique and/or plethysmography in bronchial hyperreactivity testing could make methacholine challenge test more comfortable and available for more patients. The investigators are also going to analyze the relationship between exhaled nitric oxide and functional indices of bronchial hyperreactivity.
Detailed description
Bronchial hyperreactivity is defined as the increased respiratory tract responsiveness to multiple stimuli, which results in bronchial muscles constriction and bronchial lumen narrowing. Bronchial hyperreactivity is a hallmark of asthma, however it may also be present in other diseases, e.g. chronic obstructive pulmonary disease (COPD). Methacholine challenge test is one of the bronchial reactivity assessment methods. Methacholine acts directly on bronchial smooth muscles receptors and causes bronchoconstriction. Bronchial reactivity is increased in the presence of active inflammation. Methacholine challenge testing is commonly performed in patients with symptoms suggestive of asthma and negative result of spirometry reversibility test. The measurement of methacholine concentration which causes 20% forced expiratory volume at one second (FEV1) decrease in post-inhalation spirometry (PC20) is a standard method of hyperreactivity evaluation. However, above method could be used among patients who are able to perform acceptable spirometry. Furthermore, results of spirometry might be influenced by level of compliance and motivation of patients. Moreover, whereas spirometric methacholine challenge test has high negative predictive values, its positive predictive value is relatively low. Thus, diagnostic utility of other pulmonary function tests should be assessed in methacholine challenge test evaluation.
In plethysmography airway resistance is performed during tidal breathing. The increase of specific airway resistance of 200% and the decrease of specific airway conductance of 40% after methacholine inhalation, respectively, are proposed as a cut-off levels for bronchial hyperreactivity diagnosis.
In forced oscillation technique (FOT), sinusoidal oscillations are emitted by membrane into airway lumen and airway resistance is calculated on the basis of changes in air flow induced by oscillations. The increase of resistance and decrease of reactance in FOT are typical for bronchoconstriction.
Finally, also interrupter technique (IT) allows for airway resistance assessment during tidal breathing. In IT, airway resistance is calculated on the basis of mouth pressure measured directly after airway occlusion and airflow measured directly before occlusion.
The aim of the study is to compare standard spirometric evaluation of methacholine challenge test with plethysmographic, interrupter technique and forced oscillation technique (FOT) evaluation of the airways resistance.
All patient will undergo:
- clinical examination
- measurement of nitric oxide concentration in exhaled air
- spirometric, plethysmographic, interrupter technique and FOT examinations - before inhalation and after inhalation of aerosols
- following laboratory tests: blood count, measurement of serum C-reactive protein (CRP), sodium, potassium, creatinine, immunoglobulin E and NT-proBNP concentration
Patients will be provided with written and spoken information about study protocol. Written informed consent will be obtained from every patient.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bronchial challenge test | Experimental | Other: Methacholine Challenge TestPatients will undergo Methacholine Challenge Test assessed by forced oscillation technique (FOT), plethysmography, interrupter technique and spirometry. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- presence of asthma symptoms without confirmation of diagnosis by standard methods
- dyspnea and/or cough of unknown etiology
Key exclusion criteria (10 listed)
- FEV1 <1.2 L or <60% of predicted value
- acute heart failure
- myocardial infarction in last 3 months
- transient ischaemic attack or stroke in last 3 months
- aneurysms
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methacholine Challenge TestForced oscillation technique test, plethysmography, interrupter technique test and spirometry will be performed in a row before any intervention and after inhalation of aerosols - normal saline, followed by increasing concentrations of methacholine: 0.03 mg/ml; 0.06 mg/ml; 0.125 mg/ml; 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml, 2 mg/ml, 4 mg/ml, 8 mg/ml, 16 mg/ml. In case of FEV1 decrease of ≥ 20% of the initial value methacholine challenge test will be ceased and patient will be administered 200 µg of salbutamol in inhalation. Then, pulmonary function tests will be performed after 15 minutes. | Other | Bronchial challenge test |
Primary outcome
The concentration of methacholine inducing a 20% fall in FEV(1) from post-diluent baseline [PC(20)]
Time frame: up to 2 hours
In case of FEV1 decrease of > 20% from baseline PC (20) will be calculated by logarithmic interpolation.
13 secondary outcomes
Change in FOT resistance and reactance from post-diluent baseline after inhalating consecutive methacholine aerosols
Time frame: within 6 minutes after methacholine aerosol inhalation
Change in plethysmographic airway resistance from post-diluent baseline after inhalating consecutive methacholine aerosols
Time frame: within 6 minutes after methacholine aerosol inhalation
Change in interrupter airway resistance from post-diluent baseline after inhalating consecutive methacholine aerosols
Time frame: within 6 minutes after methacholine aerosol inhalation
Change in FEV(1) from from post-diluent baseline after inhalating consecutive methacholine aerosols
Time frame: within 6 minutes after methacholine aerosol inhalation
Assessment of the difficulty level of FOT
Time frame: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of plethysmography
Time frame: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of interrupter technique
Time frame: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Assessment of the difficulty level of spirometry
Time frame: after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)
Duration of the bronchial resistance assessment by FOT
Time frame: During methacholine challenge test (up to 2 hours)
Duration of the bronchial resistance assessment by plethysmography
Time frame: During methacholine challenge test (up to 2 hours)
Duration of the bronchial resistance assessment by interrupter technique
Time frame: During methacholine challenge test (up to 2 hours)
Duration of spirometry
Time frame: During methacholine challenge test (up to 2 hours)
Total duration of methacholine challenge test
Time frame: During methacholine challenge test (up to 2 hours)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2016.
- Derived from this study: PubMed 33203723Urbankowski T, Przybylowski T. Methacholine Challenge Testing: Comparison of FEV1 and Airway Resistance Parameters. Respir Care. 2021 Mar;66(3):449-459. doi: 10.4187/respcare.08331. Epub 2020 Nov 17.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tomasz A Urbankowski, MD principal investigator
Department of Internal Medicine, Pneumonology and Allergy, Medical University of Warsaw
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Methacholine Challenge Test in people with Bronchial Hyperreactivity and Abnormal Respiratory Airway Resistance, run by Medical University of Warsaw at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The concentration of methacholine inducing a 20% fall in FEV(1) from post-diluent baseline [PC(20)] (time frame: up to 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02343419, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2016.