Understanding the Biological Differences in Susceptibility to Chronic Obstructive Pulmonary Disease between Men and Women

Abstract

There is a worldwide epidemic of chronic obstructive pulmonary disease (COPD) in women. Some large epidemiologic studies suggest that female smokers may have increased susceptibility to COPD. The biological mechanisms to explain these observations are far from certain. However, the susceptibility to the effects of cigarette smoke in women could be due to a greater deposition of toxic substances in the lung, impaired clearance of the toxins that are deposited, and/or an exaggerated biologic response to these toxins. The latter effect could be due to an increased ability to convert certain xenobiotics to more toxic metabolites or to a decreased ability to conjugate and excrete metabolites of these toxins. Female hormones, in particular estrogen, can up-regulate certain cytochrome P450 enzymes without altering detoxifying enzymes, leading to a disturbance in the balance between metabolism and conjugation. This article reviews this and other potential mechanisms that may confer increased susceptibility of COPD to female smokers.

Physical comorbidities increase the risk of psychiatric comorbidity in multiple sclerosis

“…For example, female smokers may be at increased risk of chronic obstructive pulmonary disease than male smokers (Sin et al. 2007) due to biological factors such as hormonal effects. However, social support and access to health services may also differ between men and women (Jensen et al.…”

Hormonal Influences on Lung Function and Response to Environmental Agents: Lessons from Animal Models of Respiratory Disease

“…Ben-Zaken Cohen and coworkers (55) recently reviewed some of the evidence in support of a role for sex-dependent metabolism of components of cigarette smoke as underlying the increased susceptibility of females to COPD. Estrogens have a recognized capacity to upregulate cytochrome P450 expression and activity while not affecting conjugation (Phase 2) enzymes, thereby potentially leading to an imbalance in the formation and removal of toxic intermediates of cigarette smoke components (2,55). …”

“…While genetic and environmental factors clearly have important roles, chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis, lung cancer, and other respiratory ailments have been reported to be influenced in some way by sex (1)(2)(3). Delineating the underlying contribution of sex (and, by association, sex hormones) to these diseases is complicated by the inherent difficulties associated with identifying the roles of specific factors from epidemiologic data.…”

A hypothesis for the initiation of COPD

“…However, posttranslational inactivation of repair enzymes by free radicals may enhance the accumulation of DNA damage [14]. Interestingly, female smokers have accelerated metabolism of cigarette smoke leading to increased burden of DNA adducts and mutations, but reduced DNA repair capacity [42,43] Thus, they are more susceptible to somatic mutations, which may predispose to COPD [42,43].…”