Effects of cigarette smoke on epithelial cells of the respiratory tract.

Chronic inhalation of cigarette smoke is associated with mucus hypersecretion, mucus pooling, pulmonary connective tissue damage, and chronic airflow obstruction. Cigarette smoke has therefore been causally linked to the development of chronic obstructive pulmonary disease (either chronic bronchitis or emphysema),' increased airway responsiveness,2 exacerbations of asthma,3 impaired pulmonary immune function,4 and increased pulmonary infections.5 Cigarette smoke has also been established as an important risk factor for lung,6 laryngeal,7 and nasal neoplasia.5 Pathogenetic mechanisms related to smoke-induced respiratory perturbations, however, are not fully understood. One cell type in the lung that may play a major part in the pathogenesis of cigarette smoke-induced lesions is the airway epithelial cell. These cells line the lumen of the airways, and thus are in a unique position to interact directly with inhaled cigarette smoke. Most research involving cigarette smoke and airway epithelial cells has focused on the "target" cell responses of these cells in relation to their relatively simple roles in barrier and mucociliary clearance functions. Depending in part on the chronicity of exposure, certain functions may be altered for example, ciliary beating, mucus secretion. It has recently become apparent, however, that airway epithelial cells may also act as "effector" cells, playing pivotal roles in regulation of airway reflexes, immunological and inflammatory responses, and maintenance of bronchodilation. As part of their overall response to chronic insult these cells are capable of producing and/or releasing a number of inflammatory mediators, or undergoing alterations in expression of cell adhesion molecules processes that may initiate or perpetuate airway inflammation.9 To date the influence of cigarette smoke on effector functions of epithelial cells has yet to be investigated in detail. Much of the information presented herein is based on acute in vitro cigarette smoke exposures of epithelial cell cultures or airway explants, and on relatively acute human or laboratory animal exposures. Thus, non-neoplastic and non-emphysematous end points of respiratory disease have been emphasised. Nevertheless, early events in the response to cigarette smoke or its components may be critical, and certainly an understanding of these events may help to elucidate the pathogenetic mechanisms of many chronic respiratory diseases. Components of cigarette smoke Chemical analytical studies have identified over 3800 compounds in tobacco smoke.'" Mainstream cigarette smoke is composed of a complex mixture of gases and condensed tar particles. In experimental studies cigarette smoke is often separated into two phases by a glass fibre filter that retains nearly all particulate matter greater than 01 ptm in diameter. The retained particulate matter is commonly referred to as the "tar" phase, while the material passing through the filter is referred to as the "gas" phase. Known toxins and carcinogens have been identified in both the gaseous and particulate phases." Sidestream smoke (smoke emitted from the burning tip of the cigarette) is the major constituent of environmental tobacco smoke. The chemical composition and gas-toparticle associations of environmental tobacco smoke may be different from that of mainstream smoke, owing to prolonged time and cooling in the air.'2 Sidestream cigarette smoke emissions contain carbon monoxide, ammonia, formaldehyde, benzene, nicotine, acrolein, various gases and particles, and an assortment of potentially genotoxic and/or carcinogenic organic compounds.'3 Increased pulmonary particulate burden due to cigarette smoke may also play a part in respiratory disease.'4 Recent epidemiological findings have indicated adverse effects of particulate air pollutants at concentrations below currently permissible levels.'5 Respirable suspended particles in indoor air in homes may increase from approximately 30 jtg/ m3 to greater than 60 jg/M3 due to accumulation of environmental tobacco smoke.'6 The reported effects of "cigarette smoke" may include that of mainstream smoke, variably aged environmental tobacco smoke/sidestream and exhaled smoke, gaseous phase components only, particulate phase components only, or individual chemical compounds such as acrolein,'7 acetaldehyde,'5 or formaldehyde.'9 Some studies have used aqueous extracts of cigarette smoke obtained by bubbling the smoke through a buffer, with or without filtering to remove suspended particulates,20 while other researchers have focused on free radical production arising from chemical reactions within the cigarette smoke.2' Overall, owing to the variability in experimental methodologies (including the type of "cigarette smoke") used, interstudy comparisons may be difficult to interpret. It is well to keep this in mind when reading this review. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA J A Dye K B Adler