title: Beyond corticosteroids: future prospects in the management of inflammation in COPD.
abstract: Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.
authors: Service de Pneumologie et Réanimation, Hôtel Dieu, 1 Place du Parvis Notre-Dame, Paris Cedex 4, France. nicolas.roche@htd.aphp.fr
authors: N
authors: N
authors: Roche
authors: R
authors: R
authors: Marthan
authors: P
authors: P
authors: Berger
authors: A
authors: A
authors: Chambellan
authors: P
authors: P
authors: Chanez
authors: B
authors: B
authors: Aguilaniu
authors: P-Y
authors: PY
authors: Brillet
authors: P-R
authors: PR
authors: Burgel
authors: A
authors: A
authors: Chaouat
authors: P
authors: P
authors: Devillier
authors: R
authors: R
authors: Escamilla
authors: R
authors: R
authors: Louis
authors: H
authors: H
authors: Mal
authors: J-F
authors: JF
authors: Muir
authors: T
authors: T
authors: Pérez
authors: T
authors: T
authors: Similowski
authors: B
authors: B
authors: Wallaert
authors: M
authors: M
authors: Aubier
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D010641:Phenotype; D058988:Phosphodiesterase 4 Inhibitors / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D058988:Phosphodiesterase 4 Inhibitors