Role of infection and cytokines in the pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality world-wide. The precise sequence of events in COPD is not completely understood. Inflammation in the airways has been unanimously seen by researchers as a pivotal factor, and cigarette smoking is, without doubt, the main cause. A large proportion of heavy smokers, however, does not suffer with COPD, suggesting a role of additional risk factors in pathogenesis. The inflammatory response to cigarette smoke and infectious agents is determined by the host's genetic composition. Cigarette smoking, by altering the surface milieu of respiratory mucosa and by causing immunosuppression, increases the susceptibility of individuals to infection with respiratory viral and bacterial pathogens. Virus infection has also been recognised as a susceptibility factor for secondary bacterial infection. An investigation into the role of individual genetic variations in inflammatory cell and cytokine production and non-host factors involved in COPD forms the basis of the development of more effective strategies to intervene in pathogenesis, progression and exacerbation of COPD. The aims of this article are to review the evidence for predisposing factors for COPD, with a particular emphasis on respiratory tract infections, and to examine those findings in relation to individual genetic variations and their interactions for induction of pro-inflammatory cytokine production in the respiratory tract.