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

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.

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.

Eligibility Criteria:
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 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