 FEV1 will be assessed by using a MasterScreen Pneumo spirometer Jaeger GmbH, Würzburg, Germany with filter and according to ATS recommendations. The best of three values FEV1 repeatable to within 100ml will be recorded and the percentage of predicted values will be calculated. Mannitol challenge tests will be carried out using the protocol described by Anderson et al. Mannitol will be administered as a dry powder in capsule form, inhaled from a RS01 device Pharmaxis Ltd. Frenchs Forrest, NSW, Australia Trimedal AG, Brüttisellen, Switzerland. An empty capsule will be used as a control at baseline. The test will be started with 5mg and increased doubling the doses up to 160mg. In case of no response at the 160mg dose, this dose will be repeated up to a maximum cumulative dose of 635mg. FEV1 will be measured 60 seconds after delivery of each dose. The challenge will be stopped if FEV1 fell by 15 or more, or when the maximum dose will be administered. The dose causing a 15 fall in FEV1 PD15 FEV1 will be read by interpolation on the plotted dose-response curve. Methacholine testing will be done according to the protocol of the SAPALDIA Study which is identical with the protocol of European Community Respiratory Health Survey ECRHS method 2 short-protocol. The provocation test will start with inhalation of saline diluent, and the maximum post-diluent FEV1 will be recorded two minutes later as the control value. All solutions of methacholine will be prepared by the Pharmacy of University Hospital Bern. Methacholine will be delivered using a Mefar MB3 dosimeter Mefar, Bovezzo, Italy set to deliver the aerosol over a period of one second. FEV1 will be recorded 2 minutes later and in the absence of a 20 fall in FEV1 from baseline the next dose will be given. Methacholine will b e inhaled with quadrupling doses until a fall in FEV1 greater than 20 from the control value is observed or the maximum cumulative dose of 2.0 mg is reached. The dose causing a 20 fall in FEV1 PD20 FEV1 will be read by interpolation on the plotted dose-response curve. 