Airway Extracellular Copper Concentrations Increase with Age and Are Associated with Oxidative Stress Independent of Disease State: A Case-Control Study Including Patients with Asthma and COPD

Chronic obstructive pulmonary disease (COPD) and asthma are characterised by increased oxidative stress in the lungs. The precise contribution of this stress to COPD aetiology remains unclear, partly due to the confounding influence of physiological ageing. Previous reports of increased oxidative stress in bronchoalveolar lavage (BAL) samples from individuals with COPD may at least in part be attributable to the subjects' age. This study investigated whether increased metal concentrations at the air-lung interface would contribute to oxidative stress in the lungs. We analysed BAL samples from young and old never-smokers, young asthmatic never-smokers, older smokers without COPD and COPD patients (both current and ex-smokers). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify a range of transition metals, including iron, copper, zinc, arsenic and cadmium. BAL concentrations of copper and zinc were significantly lower in young groups compared to the older groups, irrespective of smoking status or disease (<i>p</i> < 0.001 for both). BAL copper was significantly associated with several markers of oxidative stress, all of which were elevated with age: glutathione disulphide (ρ = 0.50, <i>p</i> < 0.001), dehydroascorbate (ρ = 0.67, <i>p</i> < 0.001) and 4-Hydroxynonenal (ρ = 0.43, <i>p</i> < 0.001). These data indicate that age-related increases in respiratory tract copper concentrations contribute to elevated levels of oxidative stress at the air-lung interface independently of respiratory disease.