Nitric Oxyde Concentration in Chronic Obstructive Pulmonary Disease Patients - SANOB Study

Bronchial inflammation in COPD represents one of the main causes of not fully reversible obstruction and airflow limitation. The main inflammatory cells involved are represented by the neutrophils, while some inflammatory mediators like Interleukin-6 (IL6), Interleukin-8 (IL8), Interleukin-1 alpha (IL1alpha), Interleukin-1 beta (IL1beta), Tumor Necrosis Factor alfa (TNFalfa), Reactive Oxygen Species (ROS), Leukotriene B4 (LTB4) and Nitric Oxide (NO) provoke the disruption of the elastic alveolar bonds that support the small airways, thus invalidating their physical and mechanical characteristics. During tidal volume respiration, in such patients, the chronically obstructed small airways are subjected, the investigators suppose, to one of the following effects: * a total closure of the smaller bronchioli causing atelectasis * a cyclic opening and closure of the airways thus provoking friction and strain stress and an inflammatory response of mechanical origin. The Fraction of Exhaled Nitric Oxyde (FeNO) concentration is largely used in clinical practice as a marker to monitor the lung inflammatory status. Formoterol and Salmeterol are two of the most used Long Acting Beta 2 Agonists (LABA) for inhaled therapy of COPD, representing the basis of the bronchodilator therapy in this disease. The purpose of the study is to evaluate the possible mechanical origin of the bronchial inflammation and then the capacity of inhaled LABA in acute conditions to modify the trend of production of NO by reducing stretching and strain forces. Thus the possible decline of exhaled NO concentration will be used as an index of the small airways inflammatory state occurring after inhaled therapy. To do this the investigators will measure the exhaled NO concentration in COPD patients with moderate to severe obstruction, that is a Forced Expiratory Volume less than 70% of predicted value (FEV1\<70%pred). The evaluation will be done in four different moments: 1. at baseline, after 72 hours of pharmacological washout conditions 2. at 30 minutes after the assumption of inhaled therapy (Salmeterol 50 mcg or Formoterol 12 mcg in double blind conditions) 3. at 60 minutes after step 2 4. at 180 minutes after step 2 Together with NO concentration, also the Respiratory Frequency and Tidal Volume will be registered during each evaluation. All the subjects will be inpatients accessing a respiratory rehabilitation unit or outpatients of the ambulatory service. After every NO measure, a functional respiratory assessment will be made (spirometry, plethysmography, Carbon Monoxide (CO) diffusion lung test, Single Breath N2 washout test), together with an arterial blood gas analysis. At every step a dyspnoea assessment will be made by Visual Analogic Scale, while Modified Medical Research Council (mMRC) scale will be assessed at the beginning of the test. Every patient will repeat the four step assessment after 72 hours, while a double blind pharmacological crossover will be performed, thus creating a controlled study in witch every patients, at the end of the study, will take Salmeterol and Formoterol in a randomized way. For the study duration all the patients will perform a pharmacological washout (living the short acting inhaled Beta 2 agonists as rescue medication)