The effect of active and passive smoking on inhaled drugs in respiratory patients

All combustion processes produce primary and secondary submicrometric aerosol particles. Primary particles are produced directly by incomplete combustion, and secondary particles are formed from gas-phase precursors. When diffused into the atmosphere, each particle is subject to different mechanisms, such as nucleation, condensation, coagulation and surface reaction, by colliding with other particulate and vapour-phase constituents, giving rise to a growth in size and reduction in the total number of particles themselves that take place simultaneously in a very short time, of the order of milliseconds [1]. Environmental tobacco smoke (ETS) is a mixture of condensate and vapour-phase pollutants (.4,000 different chemical substances), and is one of the major sources of indoor aerosol pollution [2]. The condensate phase is formed by particles whose aerodynamic profile shows a major peak in the range 0.1–0.2 mm [3]. It is acknowledged that tobacco smoke and indoor ETS pollution are a worldwide problem [4], and that a relevant percentage of people who are taking inhaled aerosol medication are current smokers (.25% of asthma and chronic obstructive pulmonary disease (COPD) patients) [5, 6]. Moreover, although inhaled corticosteroids (ICSs) are the cornerstone of asthma therapy, their efficacy is dramatically reduced in asthmatic smokers [7]. Alterations in corticosteroid metabolic pathways induced by tobacco smoke have been demonstrated at the cellular level [8]. However, no research to date has been addressed at finding a possible additional explanation for the impairment of ICS effects in smokers, i.e. the interaction between ETS and inhaled drug particles at the moment of inhaled drug actuation by the patient, resulting in a possible growth in the size distribution of the inhaled medication, which represents a critical issue regarding inhaled drug deposition and efficacy [9]. According to pharmaceutical guidelines, ICSs are studied in a clean ambient, and no concern has yet been raised about this issue [10], even though smokers take their medication in highly polluted ambient air, and resistance to ICSs has been reported as a cause of reduced asthma control in asthmatic smokers [11]. The pro-inflammatory properties of tobacco smoke and interference of smoke with glucocorticoid gene expression are considered the primary explanations [12]. However, no study to date has addressed the possible physical interactions of inhaled particles with smoke aerosol in both the airways and the environment polluted by ETS. The aims of the present study were to: 1) evaluate the possible interactions affecting the aerodynamic profile of dry-powder fluticasone in the presence of tobacco smoke in