What is the evidence for cigarette smoke increasing susceptibility to COPD

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Among the risk factors that have been related to COPD, cigarette smoke is the best studied and is a consistent finding in numerous studies [1,52,53]. In all recent guidelines on COPD, cigarette smoking has been regarded as the best-established risk factor for the development of the disease [54,55]. In addition, passive cigarette smoking has been related to chronic cough and sputum and is also a candidate risk factor for the development of airflow limitation [53,56,57].

However, from the above epidemiological studies, it is apparent that not all smokers develop clinically significant COPD, and also that there is no direct dose-effect relationship. A passive smoker may develop the disease, whereas a heavy smoker may not. These observations have led to the hypothesis that there are smokers who are susceptible to COPD.

Longitudinal epidemiological studies have suggested that a more important factor than the dose (pack/years) is the timing of the exposure to cigarette smoke [58,59]. This is summarized in the epidemiological model of COPD risk shown in Fig. 2.2. Although COPD is a disease of middle/late adult life, events that occur during early life may play a significant role. For example, active or passive smoking during adulthood, when the lungs are fully developed, may make an individual susceptible to developing COPD (Fig. 2.2). An additional effect during maturation of the respiratory system could be maternal smoking during pregnancy (Fig. 2.2a). Finally, there is a well-known third phase in adult life, in which the susceptible smoker is characterized by a rapid decline in forced expiratory volume in 1s (FEV1) (Fig. 2.2d). The timing of exposure to cigarette smoke is thus crucial and may have different and/or additive effects. Cigarette smoke may cause changes before birth (lower initial lung volume), during growth (lower maximal attained volume), in the plateau phase (earlier start of decline) and during the late phase, with an accelerated decline [1,60,61]. However, the epidemiological model discussed above may partly explain the fact that not all smokers develop COPD.

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