br Chronic obstructive pulmonary disease COPD is characteriz

Chronic obstructive pulmonary disease (COPD) is characterized by progressive obstruction of airflow, not fully reversible, which is accompanied by a chronic inflammatory response, induced by deleterious particles or gases, in airways and lung parenchyma. The most important risk factor for COPD is cigarette smoking. COPD is a collection of conditions, which include emphysema, chronic l lysine reviews with mucus hypersecretion, bronchiolar and vascular remodeling, and sometimes the presence of fibrotic areas scattered throughout the parenchyma, in which emphysema and fibrosis may coexist. There are currently no specific COPD treatments, and smoking cessation (SC) remains the most effective therapeutic intervention in patients with COPD. However, in many cases SC may only relieve the airflow obstruction and inflammatory response., Several studies in humans and animal experiments have demonstrated that, once COPD is initiated, the pulmonary inflammatory response continues, , and the enlarged alveolar airspace cannot be reversed after SC. Thus, persistent lung inflammation associated with a progressive deterioration of respiratory function (progressive decline in forced expiratory volume in 1 second) and infections in ex-smokers are an increasingly important clinical problem whose mechanistic basis remains poorly understood. Studies on mouse models of cigarette smoke (CS) identified several mechanisms by which COPD lesions may be induced., These include the activation of the innate and adaptive immune responses, that can lead to enhanced protease/antiprotease, or oxidant/antioxidant imbalances, , in lung tissue with alveolar wall degradation. The precise relationship between smoking, immune modulation in the lung, and respiratory infections is still the object of investigation because bacterial and viral infections may be critical in the induction of acute exacerbations in later COPD stages. In general, available therapies do not adequately suppress inflammation, and even inhaled corticosteroids, although effective in asthma, reduce exacerbations only to a certain extent in COPD and do not seem to reduce disease progression. In addition, new classes of drugs, such as phosphodiesterase-4 inhibitors, can prolong the time between re-exacerbations but are not potentially able to stop the vicious cycle at the basis of persistent inflammation that characterizes and influences the various clinical stages of the disease. Much of the current knowledge on the pathogenic mechanism(s) implicated in COPD derives from studies performed on several experimental animal models and in particular on smoking mice, which are able to replicate several features of human COPD., , , It was demonstrated that genetic ablation of the formyl-peptide receptor-1 () gene in mice or treatment with specific antagonists of FPRs prevents recruitment of inflammatory cells in the lung and confers protection from smoking-induced lung emphysema. These receptors, overexpressed in patients with COPD, have been recently involved, together with mitochondrial formylated peptides, also in acute lung inflammation and injury. In this context, by using a curative experimental model of CS-induced pulmonary changes that is currently used in preclinical studies the ongoing lung inflammation and deterioration that follows SC was studied as well as the role of (FPR) signaling in the persistency of inflammation. The modulation of FPR-related signaling in mice halts chronic inflammation and prevents the deterioration of alveolar structures and the remodeling of airways that follow SC in mice. It is widely accepted that the enlargement of alveolar airspaces and the remodeling of small airways induced by CS constitute the pathologic basis of airflow obstruction in COPD patients., Materials and Methods
Results
Discussion Several studies in humans and animal experiments have demonstrated that, once COPD is initiated, the pulmonary inflammatory response continues5, 6, 7 and that the enlarged alveolar airspace cannot be reversed after SC. Available therapies do not adequately suppress inflammation and are not able to stop the vicious cycle that is at the basis of persistent inflammation.