Effect of Prolonged Decubitus on Nitric Oxide Concentration in Chronic Obstructive Pulmonary Disease

Overview

* Bronchial obstruction in Chronic Obstructive Pulmonary Disease (COPD) is caused by inflammation of peripheral airways walls. * Neutrophils and other inflammatory mediators Interleukin-6 (IL6), Interleukin-8 (IL8), Interleukin-1 alpha (IL-1 alpha),Interleukin-1beta (IL-1 beta), Tumor Necrosis Factor alfa (TNF-alfa), Reactive Oxygen Species (ROS), Leukotriene B4 (LTB4), Nitric Oxyde (NO) are implicated in the inflammation. * Exhaled NO concentration is usually used to monitor bronchial inflammation * The relationship between decubitus and small airways behaviour is not well understood. * Our hypothesis is that cyclic opening and closure of peripheral airways during decubitus can provoke an inflammatory response which can be monitored by exhaled NO. * Data about these physiopathological aspects is missing in literature.

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 (IL6, IL8, IL1alpha, IL1beta, TNFalfa, ROS, LTB4, NO) provoke the disruption of the elastic alveolar bonds that support the small airways, thus invalidating their physical and mechanical characteristics. During decubitus, in such patients, the more dependent parts of the lung are subjected to gravity force, which together with chronic inflammation may cause, we suppose, one of the following effects during tidal breathing: * a total closure of the smaller bronchioli * a cyclic opening and closure of the small airways thus provoking friction 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. The purpose of the study is to evaluate the possible mechanical origin of the bronchial inflammation in correlation with prolonged supine decubitus, and so use the NO as an index of the small airways impairment in COPD patients. To do this we 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. before the patient goes to sleep while in supine position 2. immediately after the patient wakes up in the morning, still being in supine position. 3. while sitting on the bed after point 2 4. in the morning after one hour of normal patient's activities, in seated position. 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. At the beginning and after 15 days of rehabilitation a functional respiratory assessment will be made (spirometry, plethysmography, Carbon Monoxide (CO) diffusion lung test), together with an arterial blood gas analysis and a 6 minutes walking test (WT6'). An initial and a final assessment of dyspnoea will be made by Borg and Modified Medical Research Council (mMRC) scales. For the study duration all the patients will continue their inhaled therapy as usual (an ultra long acting anticholinergic once daily plus a long acting Beta-2 agonist in combination with an inhaled corticosteroid twice daily)