Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death worldwide and further increases in its prevalence and mortality are expected in the coming decades.¹ Continued exposure to tobacco promotes a more rapid decline in lung function and, if exposure is stopped, the disease may still progress due to ageing and persistence of inflammation. The paper by Nagai et al² in this issue of Thorax adds to the growing body of evidence about damage from oxidative stress due to cigarette smoking. Changes can persist even after the last cigarette is extinguished. The effects are more noticeable in older smokers because of long term exposure to toxic gases and particles as they concurrently age. Oxidised glutathione associated with excessive protein carbonylation accumulates in the lungs of older smokers, raising the possibility that antioxidant defences could be overwhelmed.

The lungs are exposed continuously to oxidants generated either endogenously from phagocytes and other cell types or exogenously from air pollutants or cigarette smoke. Cigarette smoke contains 10¹⁷ oxidant molecules per puff.³ The oxidants in cigarette smoke cause lung injury by a number of mechanisms including the depletion of glutathione and other antioxidants, the initiation of redox cycling mechanisms, enhancement of the respiratory burst in neutrophils and macrophages, inactivation of protease inhibitors such as α₁-antitrypsin inhibitor, and direct damage to lipids, nucleic acids and proteins.⁴ There is considerable evidence that the oxidative burden is increased in the lungs of patients with COPD and may be involved in the pathogenetic processes in the lung and in the …