Diagnostic Utility of Different Airway Resistance Assessment Techniques in the Methacholine Challenge Test

Bronchial Hyperreactivity Clinical Trial

Official title:

Diagnostic Utility of Different Airway Resistance Assessment Techniques in the Evaluation of Bronchial Hyperreactivity by Methacholine Challenge Testing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02343419
• Other study ID #: PFT-DIMPA-WUM1
• Status: Completed
• Phase: N/A
• First received: December 1, 2014
• Last updated: November 8, 2016
• Start date: November 2014
• Est. completion date: May 2016

Study information

• Verified date: November 2016
• Source: Medical University of Warsaw
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ethics Committee
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: May 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• presence of asthma symptoms without confirmation of diagnosis by standard methods

• dyspnea and/or cough of unknown etiology

Exclusion Criteria:

• 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

• pregnant and lactating women

• administration of ß2-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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Abnormal Respiratory Airway Resistance
• Bronchial Hyperreactivity

Intervention

Other:
• Methacholine Challenge Test
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.

Locations

Country	Name	City	State
Poland	Department of Internal Medicine, Pneumonology and Allergy, Medical University of Warsaw	Warsaw	Mazowieckie

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Warsaw

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measurement of nitric oxide concentration in exhaled air	Nitric oxide concentration in exhaled air will be measured once, immediately before performing methacholine challenge test	Participanst will undergo measurement of nitric oxide concentration in exhaled air immediately before bronchial challenge test, total time of measurement: approximately 10 minutes	No
Other	Laboratory tests	Following laboratory tests will be performed: blood count, measurement of serum C-reactive protein, sodium, potassium, creatinine, immunoglobulin E and NT-proBNP concentration	Patients will undergo laboratory tests once before perfoming methacholine challenge test; maximum period between the methacholine challenge test and performing laboratory tests: one month	No
Primary	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.	up to 2 hours	No
Secondary	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	within 6 minutes after methacholine aerosol inhalation	No
Secondary	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	within 6 minutes after methacholine aerosol inhalation	No
Secondary	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	within 6 minutes after methacholine aerosol inhalation	No
Secondary	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	within 6 minutes after methacholine aerosol inhalation	No
Secondary	Assessment of the difficulty level of FOT	Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test	after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)	No
Secondary	Assessment of the difficulty level of plethysmography	Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test	after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)	No
Secondary	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	after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)	No
Secondary	Assessment of the difficulty level of spirometry	Patients will receive visual analogue scale form assessing difficulty level and problems related to performing each test	after methacholine challenge test (up to 2 hours two hours from the start of the methacholine challenge test)	No
Secondary	Duration of the bronchial resistance assessment by FOT	Duration of each pulmonary function test will be measured	During methacholine challenge test (up to 2 hours)	No
Secondary	Duration of the bronchial resistance assessment by plethysmography	Duration of each pulmonary function test will be measured	During methacholine challenge test (up to 2 hours)	No
Secondary	Duration of the bronchial resistance assessment by interrupter technique	Duration of each pulmonary function test will be measured	During methacholine challenge test (up to 2 hours)	No
Secondary	Duration of spirometry	Duration of each pulmonary function test will be measured	During methacholine challenge test (up to 2 hours)	No
Secondary	Total duration of methacholine challenge test	Total duration bronchial challenge will be measured	During methacholine challenge test (up to 2 hours)	No