Chronic obstructive pulmonary disease (COPD), a group of progressive, debilitating respiratory conditions that includes emphysema, chronic bronchitis, and small airway disease, which cause airflow blockage and breathing-related problems, is a major public health problem.1 In 2010, there were 10.3 million physician office visits, 1.5 million emergency department visits, and 699,000 hospital discharges for COPD.1 Although tobacco cigarette smoking contributes to about 80% of COPD deaths,2 considerable proportions of COPD occur among nonsmokers.3 The childhood social environment has been suggested as a determinant of COPD for over 50 years and may partially explain the occurrence of COPD among nonsmokers.4,5

A growing body of epidemiologic evidence indicates that exposure to household dysfunction and childhood maltreatment including physical, sexual, and emotional abuse and neglect is common6–8 and that exposure to these experiences during childhood may result in toxic stress that places people at greater risk for poor health across the life course.6 It is hypothesized that adverse childhood experiences (ACEs) may lead to chronic diseases through emotional and psychophysiological responses that include dysregulation of the hypothalamic-pituitary-adrenal axis and through behavioral responses such as smoking.9–13 Previous studies have shown that self-reported ACEs are associated with several chronic diseases such as COPD,14 depression,15 heart disease,16 cancer,17,18 diabetes,7 and stroke.7

Considering that the previous findings on ACEs and COPD came from one study of health maintenance organization members who were mostly middle class, white adults in California,14 confirming these findings in the general population is critical to better understanding the etiology of COPD and to develop prevention and intervention strategies for those at risk. It also remains unknown whether the relationship between ACEs and COPD is influenced by sex. Previous studies have found a higher prevalence of COPD among women compared to men and suggest differential susceptibility to COPD by sex.19–22 Furthermore, sex differences in the relationship between ACEs and smoking status in adulthood were identified in one previous study.13 Therefore, we examined sex-specific relationships between individual ACEs and the number of ACEs with COPD in the general population of five states in this study. We also assessed whether smoking status explained the relationship of ACEs to COPD.

The analytic sample was comprised of 26,546 women (50.8%) and 19,015 men (49.2%) from five US states. The majority of respondents were non-Hispanic white (84.8%) and about a third had at least some college education (33.9%). More than half (54.0%) of respondents were never smokers, 12.7% reported ever having asthma, and 4.4% reported having COPD. The distributions of selected characteristics are presented by sex (Table 1). Compared to men, women were significantly (P<0.05) more likely to be aged ≥75 years; to be a non-Hispanic white adult; to be unmarried; to have at least some college education; to be a homemaker/student or retired; to have health insurance coverage; to have a history of asthma; and to be a never smoker. COPD prevalence did not differ significantly by sex in these five states although the prevalence was higher among women.

The overall majority (63.1%) of respondents reported having had at least one ACE before age 18. Distributions of individual ACEs and ACEs score are presented by sex (Table 2). Compared to women, men were significantly (P<0.05) more likely to report childhood verbal abuse. In contrast, women were significantly (P<0.05) more likely to report childhood sexual abuse; living with a substance abusing household member; living with a mentally ill household member; and to report ≥5 ACEs compared to men.

We assessed the prevalence of COPD by individual ACEs and ACEs score for women and men (Table 3). The unadjusted prevalence of COPD was significantly (P<0.05) higher among women with any individual ACEs than among women without. Additionally, the unadjusted prevalence of COPD was significantly (P<0.05) higher among men with a childhood history of physical abuse, sexual abuse, and household substance abuse. However, the unadjusted prevalence of COPD increased significantly (P<0.05) with an increasing ACEs score only among women.

Because we found a statistically significant interaction (P<0.10) for sex with each ACE and the ACEs score on the likelihood of COPD, we examined sex-specific relationships. We examined the likelihood of having COPD after taking into account the confounding effects of age, asthma, and sociodemographic characteristics (Table 3). We also examined the likelihood of COPD after also adjusting for smoking status as an additional covariate. Adjustment for smoking status attenuated the relationship between most individual ACEs and ACEs score with COPD among both women and men. For women, verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce during childhood (PR =1.47, 95% CI: 1.21, 1.80) were all associated with a higher likelihood of COPD compared to women who had not reported those individual ACEs. In contrast, for men, living with an incarcerated household member during childhood (PR =0.49, 95% CI: 0.31, 0.77) was associated with a lower likelihood of COPD compared to men who had not reported that individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) was associated with a higher likelihood of COPD compared to reporting no ACEs only among women.

We assessed the prevalence of COPD by individual ACEs and ACE score for women and men who had never smoked (Table 4). As expected, the prevalence of COPD among persons who had never smoked was low. The unadjusted prevalence of COPD was significantly (P<0.05) higher among women who had never smoked but had a childhood history of physical abuse, sexual abuse, and household substance abuse. We also examined the likelihood of having COPD among women and men who were never smokers (Table 4). For women who were never smokers, there was still a higher likelihood of COPD associated with physical abuse (PR =1.81, 95% CI: 1.28, 2.58), sexual abuse (PR =2.18, 95% CI: 1.46, 3.24), and living with a substance abusing household member during childhood (PR =1.70, 95% CI: 1.18, 2.43). Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.25, 3.46) remained associated with a higher likelihood of COPD compared to reporting no ACEs among women who were never smokers.

We assessed the likelihood of having COPD among women and men who were former smokers (Table 5). For women who were former smokers, there was a higher likelihood of COPD associated with verbal abuse (PR =1.55, 95% CI: 1.17, 2.05), sexual abuse (PR =2.06, 95% CI: 1.55, 2.72), living with a substance abusing household member during childhood (PR =1.75, 95% CI: 1.38, 2.22), witnessing domestic violence (PR =1.85, 95% CI: 1.43, 2.39), and parental separation/divorce (PR =1.80, 95% CI: 1.39, 2.34). Reporting ≥5 ACEs (PR =3.04, 95% CI: 2.16, 4.29) remained associated with a higher likelihood of COPD compared to reporting no ACEs among women who were former smokers. For men who were former smokers, there was a higher likelihood of COPD associated with physical abuse (PR =1.59, 95% CI: 1.08, 2.34) and living with a substance abusing household member during childhood (PR =1.44, 95% CI: 1.01, 2.05).

We assessed the likelihood of having COPD among women and men who were current smokers (Table 6). For women who were current smokers, there was a higher likelihood of COPD associated with parental separation/divorce (PR =1.37, 95% CI: 1.03, 1.83).

We ran sensitivity analyses including depression as a potential covariate because depression might result from ACEs and potentially operate through smoking. Depression was identified among respondents who answered with an affirmative response to the question “Has a doctor, nurse, or other health professional ever told you that you have […] a depressive disorder (including depression, major depression, dysthymia, or minor depression)?” The inclusion of depression reduced the analytic sample to 26,451 women and 18,946 men with complete records. Women were significantly more likely to report depression compared to men (21.3% versus 12.8%; P<0.05). Reporting ≥5 ACEs remained associated with a higher likelihood of COPD compared to reporting no ACEs among all women (PR =1.84, 95% CI: 1.38, 2.45), women who were never smokers (PR =1.78, 95% CI: 1.06, 2.98), and women who were former smokers (PR =2.75, 95% CI: 1.94, 3.91) in the stratified multivariable log-linear regressions after also adjusting for depression.

This analysis of representative, population-based data in five states indicates that experiences of childhood maltreatment and household dysfunction are related to COPD; however, this association varies for women and men. For women, after taking into account all the covariates including smoking and other covariates, verbal abuse, sexual abuse, living with a substance abusing household member, witnessing domestic violence, parental separation/divorce, and the number of ACEs experienced before age 18 were all associated with a higher likelihood of COPD. In contrast, for men, living with an incarcerated household member was associated with a lower likelihood of COPD. Moreover, for women who were never smokers, physical abuse, sexual abuse, and living with a substance abusing household member before age 18 were also associated with a higher likelihood of COPD.

While previous epidemiologic studies have reported on the relationship between ACEs and COPD,7,11 this study is notable because it is the first to suggest that sex modifies this relationship and it is also the largest study so far. The findings from the original ACEs study of health maintenance organization members in California mostly agree with our observations for the relationships between individual ACEs and the number of ACEs with COPD among women. In that study there was a graded relationship between the ACEs score with COPD prevalence, hospitalizations for COPD, and rates of prescriptions to treat COPD and the authors also observed that these relationships were only modestly attenuated after the adjustment for smoking status.11 In another analysis of the original ACEs study, a graded relationship between the ACEs score and smoking during adolescence and adulthood was observed.11 Additionally, in a study of the 2009 BRFSS, a graded association between ACEs score and smoking status was observed.12 The growing evidence on the relationship between ACEs with COPD and smoking and the relatively high prevalence of ACEs highlight the continuing need for programs and policies that decrease exposure to dysfunction and maltreatment and increase safe, stable, nurturing relationships and environments for children and families in addition to programs and policies that prevent smoking initiation and support cessation.26

The pathways by which ACEs influence COPD cannot be determined from this study alone; other unexamined factors contribute. In particular, stressful and traumatic experiences of maltreatment and household dysfunction during childhood are hypothesized to lead to chronic diseases such as COPD in adulthood through behaviors such as smoking and also emotional and psychophysiological responses, including hyperactivity of the hypothalamic-pituitary-adrenal axis;6,9 this may help explain why the relationship between ACEs and COPD persisted among women who were never smokers and the rather modest attenuation of the relationship between ACEs and COPD even after the adjustment for smoking and depression.27 Of note, in a study of the 2010 BRFSS, depressive symptoms were shown to only partially explain some of the relationship between ACEs and smoking.28 Similarly, in our analyses, the inclusion of depression did very little to explain the relationship between ACEs and COPD. Nonetheless, a number of questions regarding this relationship remain unanswered. Future studies investigating this relationship ought to consider the following: 1) are women particularly traumatized by particular ACEs? 2) are women more likely to misreport their smoking status? 3) are there other risks (such as occupational and residential exposures) that contribute to COPD among women?

An explanation for the striking sex differences observed in this study is not readily available. Our results, however, are similar to a previous study on ACEs and smoking that found verbal abuse and sexual abuse during childhood were more strongly related to smoking among women compared to men.13 Likewise, female smokers may be more susceptible to COPD compared to male smokers.29 A previous systematic review and meta-analysis of longitudinal studies indicates that the lung function in female smokers declines faster than in male smokers.22

Our findings should be interpreted in light of several limitations. First, the self-reporting of retrospective ACEs and other variables such as smoking status and COPD was not validated and might be subject to recall and other response biases.30 Second, BRFSS data are collected via telephone survey and may not be representative of adults in households without landlines and cell phones. Third, this study only assessed cigarette smoking and not other forms of combustible tobacco use, marijuana use, or secondhand smoke exposure. Finally, as the data were collected from adults in five states, the generalizability of our findings may be limited.

In conclusion, the findings of this study suggest that experiences of childhood maltreatment and household dysfunction are more highly related to COPD in women than in men. That is, more significant associations between ACEs and COPD were found for women than for men; different associations were also apparent when results were stratified by smoking status. Insofar as programs and policies that promote safe, stable, and nurturing childhood relationships and environments reduce the burden of ACEs, they might also have the potential to minimize the health consequence of COPD for women. Additionally, programs and policies that address the underlying problems caused by experiences of childhood maltreatment and household dysfunction may prove more effective than traditional smoking prevention and cessation strategies alone. Further research examining sex differences in the relationship between ACEs and chronic diseases in adulthood is warranted.