Multinational, multicentre, non-pharmacological intervention, cross-sectional and longitudinal study.

Large non pharmacological studies on Small Airways Disease

Asthmatic patient inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65 years, who have signed an Informed Consent form

2. Clinical diagnosis of asthma f

   1. Positive response to methacholine challenge test
   2. Positive response to a reversibility test or
   3. Peak Flow variability (i.e. highest - lowest PEF over the day/mean value of the two, × 100) > 20% or
   4. Documented response (defined as ΔFEV1 ≥ 12% and ≥ 200 mL) after a cycle (e.g., 4 weeks) of regular maintenance anti-asthma treatment.

3. Patients with stable asthma.

4. Current smoker, ex-smoker or lifelong non-smoker Healthy subject inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65 years 2. No clinical history of asthma or COPD 3. Current smoker, ex-smoker or lifelong non-smokers 4. Normal spirometry 5. Normal airways responsiveness Asthmatic patient exclusion criteria

1. Cigarette smoking > 10 packyears
2. diagnosis of COPD
3. Asthma exacerbation in the 8 weeks prior to baseline visit
4. Clinical or functional uncontrolled respiratory, haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might compromise the results or interpretation of the study.
5. Pregnant or lactating women
6. Participation in an interventional clinical trial <12 weeks preceding baseline visit
7. Inability to comply with study procedures.
8. Alcohol or drug abuse. Healthy subject exclusion criteria

1. Cigarette smoking history > 10 packyears 2. Diagnosed upper and/or lower respiratory disease(s). 3. Clinical or functional uncontrolled haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that mightp compromise the results or interpretation of the study.

4. Pregnant or lactating women 5. Participation in an interventional clinical trial <12 weeks preceding baseline visit 6. Inability to comply with study procedures. 7. Alcohol or drug abuse.

900 subjects divided into 800 asthmatic patients and 100 healthy controls will be included. Recruitment will be balanced, at the extent possible, in order to achieve at least > 150 patients each for steps 1 - 4 and > 50 patients for step 5 as indicated in the international guidelines (GINA 2012) on the basis of their previous therapy. The 150 healthy controls will be recruited on the basis of absence of respiratory symptoms, airway obstruction and hyper responsiveness.