TY - JOUR T1 - Chronic obstructive pulmonary disease: molecular and cellularmechanisms JF - European Respiratory Journal JO - Eur Respir J SP - 672 LP - 688 DO - 10.1183/09031936.03.00040703 VL - 22 IS - 4 AU - P.J. Barnes AU - S.D. Shapiro AU - R.A. Pauwels Y1 - 2003/10/01 UR - http://erj.ersjournals.com/content/22/4/672.abstract N2 - Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T‐lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease. The meeting “COPD: the important questions” held in Malta in November 2002 was sponsored by AstraZeneca. ER -