The toxic gases and particles gener-ated in tobacco smoke come into contact with lung tissues each time a puff of smoke is inhaled, and this tissue injury recurs in a cyclic fashion as each cigarette is smoked. A 20 pack year smoking history indicates that the subject’s lungs have received 20 of these short cyclic exposures per day for a cumulative total of 7300 exposures per year and 146 000 exposures over the lifetime of their smoking habit. This complex pattern of acute upon chronic inhalation injury reduces the innate defences of the lung by interfering with mucociliary clearance, 1 diminishing the inflammatory cytokine response to other stimuli, 2 and disrupting the epithelial barrier. 3 4 The tissue damaged by the smoke becomes infiltrated with innate and adaptive inflammatory immune cells and, even though tobacco smoke exposure may suppress the immune response, 5 the lymphoid cells collect to form the follicles with germinal centres that document the presence of the adaptive immune response. 6 The antigens that drive this immune response have not been clearly identified, but both microbial antigens that accumulate as a result of colonisation and infection of the lower respiratory tract, and possibly autoantigens created within injured lung tissue, have been implicated. 6–8

The classic longitudinal study of chronic bronchitis and emphysema conducted by Fletcher and associates in the late 1950s and 1960s established that only 20–25% of smokers develop airflow limitation. 9 These investigators also observed beneficial effects from stopping smoking that have been confirmed in early stage (GOLD 1 and 2) disease by