RT Journal Article
SR Electronic
T1 Beyond corticosteroids: future prospects in the management of inflammation in COPD
JF European Respiratory Review
JO EUROPEAN RESPIRATORY REVIEW
FD European Respiratory Society
SP 175
OP 182
DO 10.1183/09059180.00004211
VO 20
IS 121
A1 N. Roche
A1 R. Marthan
A1 P. Berger
A1 A. Chambellan
A1 P. Chanez
A1 B. Aguilaniu
A1 P-Y Brillet
A1 P-R Burgel
A1 A. Chaouat
A1 P. Devillier
A1 R. Escamilla
A1 R. Louis
A1 H. Mal
A1 J-F Muir
A1 T. Pérez
A1 T. Similowski
A1 B. Wallaert
A1 M. Aubier
YR 2011
UL http://err.ersjournals.com/content/20/121/175.abstract
AB 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.