The immune system as a victim and aggressor in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disorder defined by progressive and largely irreversible airflow limitation (1). In an individual patient, various pathological conditions contribute to the clinical presentation of COPD, including: chronic bronchitis, characterized by persistent inflammation, remodelling and mucus hypersecretion in the airways; and emphysema, characterized by small airway/parenchymal destruction and alveolar airspace enlargement (1). Notably, exposure to cigarette smoke is a well-known risk factor for the development of COPD, with over 90% of COPD deaths occurring in individuals with a history of smoking (1,2). To gain mechanistic insight into how smoking promotes COPD, numerous studies have investigated the effects of tobacco smoke on biological and, in particular, immunological processes that may contribute to disease development and progression. Here, we present a broadly-encompassing framework within which to contextualize these effects (Figure 1). We propose that the effects of cigarette smoke on immune processes that drive COPD pathogenesis fall into three categories: (I) attenuation of cellular viability and barrier functions in the pulmonary environment; (II) mediation of local danger signalling; and (III) alteration of cellular responses to secondary inflammatory stimuli. Notably, many of these effects appear to represent the misappropriation of homeostatic immunological and biological processes into responses that promote continual tissue damage in the pulmonary environment. In this manner, the immune system is both the victim of cigarette smoke exposure with regards to host defense, and an aggressor in the pathogenesis of COPD