Lung deposition and systemic bioavailability of dose delivered to smoker compared with non‐smoker COPD subjects

Introduction Inhaled drugs are the most commonly used class of medications for COPD subjects. No studies have been performed to assess the influence of smoking on lung deposition of aerosolized medication, especially for the exacerbated COPD subject. The present study aimed to assess the influence of smoking on the lung deposition of the aerosol delivered to exacerbated COPD subjects. Methods Twenty‐four exacerbated COPD subjects using automatic continuous positive airway pressure (Auto‐CPAP), 12 smokers (six females) and 12 non‐smokers (six females) were recruited in the study. The subjects participated in the study received four salbutamol study doses; 1200 µg (12 puffs 100 µg/puff) of salbutamol emitted from pMDI canister connected to AeroChamber MV spacer; 1200 µg of salbutamol emitted from pMDI canister connected to Combihaler spacer; 1 mL of salbutamol respirable solution (5000 µg/mL) nebulized by Aerogen Solo connected to its T‐piece; and 1 mL of salbutamol respirable solution nebulized by Aerogen Solo connected to Combihaler spacer with 2 puffs salbutamol MDI (200 µg salbutamol) before nebulisation. The subjects were randomised to receive the four selected dose‐adaptor combination in a sealed envelope design on days 1, 3, 5 and 7. A washout period of 24 hours was provided between each salbutamol dosing. Auto‐CPAP was adjusted at non‐invasive ventilation mode with the integrated heated humidifier, as a source of humidity. Urine samples were provided by subjects, 30 minutes and cumulatively 24 hours post inhalation, as an index of the relative and systemic bioavailability, respectively, and aliquots were retained for salbutamol analysis using solid‐phase extraction and high‐performance liquid chromatography (HPLC). On day 2 of the study, a collecting filter was placed between the aerosol generator and the subject's mask so that the subjects would not inhale the salbutamol delivered. The same study doses and/or adapters were delivered to each subject, with filters changed with each dose‐adapter combination. Salbutamol entrained on the filter was desorbed to be analysed by the HPLC. Results Significantly higher lung deposition (30 minutes urinary salbutamol) was detected with the non‐smoker compared with smokers (P