Determining the Optimal Adenosine Provocation Test (impact)

Asthma is a frequently occurring inflammatory lung disease that affects the whole bronchial tree including the small airways (<2mm). Since the introduction of the solution hydrofluoroalkane (HFA) technology it is possible to generate medication with small particles of approximately 1-2 μm, and therefore to reach the small airways. However, at this moment the investigators have no reliable instruments to identify the asthmatic subjects who particularly benefit from treatment with inhaled small particles. Recently the investigators research group investigated whether provocation with small and large particles AMP is able to identify responders and non-responders to treatment with small and large particles of inhaled corticosteroids. This provocation technique gave promising results but needs further optimization. The aim of this study is to determine the optimal particle size of dry powder adenosine to assess small airway involvement in asthma. Secondary, to provide insight in the associations between the standard test, executed with nebulized AMP, and the new test, executed with dry powder Adenosine.

This is a cross-over study. The study population consists of 10 non-smoking asthma patients in the age of 18-65 years who have a PC20 metacholine value ≤4.9mg/ml. Participating subjects perform 6 provocation tests in randomized order: one test with nebulized methacholine, one test with nebulized AMP, four times dry powder adenosine provocation test. (small particles with inhaled with a slow flow, small particles inhaled with a fast flow, large particles inhaled with a slow flow, large particles inhaled with a fast flow)

Provocation tests with adenosine dry powder and nebulized AMP (adenosine-5'monophosphate). The AMP provocation test is a standard test and consists of 14 doubling concentrations in a range of 0.04mg/ml to 320mg/ml. The aerosols will be inhaled during tidal breathing for 2 minutes. The dry powder adenosine also consists of 14 doubling steps with doses in a range of 0.01mg to 20mg.

Provocation tests with adenosine dry powder and nebulized AMP (adenosine-5'monophosphate). The AMP provocation test is a standard test and consists of 14 doubling concentrations in a range of 0.04mg/ml to 320mg/ml. The aerosols will be inhaled during tidal breathing for 2 minutes. The dry powder adenosine also consists of 14 doubling steps with doses in a range of 0.01mg to 20mg.

The R5-R20 is measured with the IOS. This a method to determine the resistance of the small airways. The R5-R20 is measured during each provocation test after each provocative step.

Small airway reaction is measured during each provocation test. The Visits will take place in a period of 6 weeks.

The total airway reaction to provocation with adenosine, reflected by the decline in FEV1 (PD20/ PC20 values)

We want to compare the different PD20/PC20 values of the three dry powder adenosine provocation test and with the nebulized AMP provocation test. The lung function is measured after each provocative step to determine the point of 20% decline in FEV1. The provocation test is ended after the last step or is ended prematurely when there is a 20% fall of FEV1 compared to baseline

Lung function is measured during each provocation test. All visits take place in a period of 6 weeks.

Inclusion Criteria: A doctor's diagnosis of asthma Age: 18-65 years PC20 AMP < 320 mg/ml Non-smoker Steroid naive or steroids have been stopped 4 weeks before entry into the baseline period Exclusion Criteria: Recent exacerbation asthma (<2 months) or upper respiration tract infection (<2 weeks) Severe airway obstruction at baseline, FEV1pred< 50% or < 1.2L Diagnosis of COPD or any other pulmonary disease that could influence the study results as judged by the investigator Pregnancy or lactating women. (i.e. women of childbearing potential who do not use adequate anticonception as judged by the investigator).