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Abstract

The prevalence of chronic obstructive pulmonary disease (COPD) among women is increasing and differences in both the management of COPD and the results of treatment between men and women have been noted. This article investigates the reasons for this increase in prevalence and the differences in natural history and COPD management between male and female patients. The main reason for the rise in prevalence of COPD in women is increased tobacco use. An additional factor is the greater susceptibility of women to damage from smoke and air pollution. The health-related quality of life is worse in women when compared with men with the same severity of disease. In addition, nutritional status is often worse in women. The most important treatment for COPD is to stop smoking. Women appear to be more dependent on cigarettes than men, and have greater difficulties stopping smoking, especially when they live with a partner who smokes. Rehabilitation is an effective treatment for both male and female COPD patients, but the focus is different: women need more emotional support and social interaction to achieve the best results.

Keywords

chronic obstructive pulmonary disease differences gender health-related quality of life rehabilitation

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the world and is predicted to become the third leading cause of death by 2020 [1]. There has been an increasing focus on gender differences during the past years, as they are thought to be related to both biological and sociocultural factors (Table 1) [2].

Table 1.

Gender differences in chronic pulmonary disease.

	Female	Male
Prevalence	Lower but rising	Higher
Susceptibility to smoke	Higher	Lower
Presentation of symptoms	More anxiety and depressive symptoms Coughing at night	More phlegm
Quality of life	Lower; more dyspnea	Better
Lung function	Higher bronchial hyper-reactivity; smoking cessation gives better improvement of lung function	Less improvement of lung function after smoking cessation
Nutritional status	Lower BMI	More prone to reduced FEV1 in the case of obesity
Exacerbations	More	Less
Comorbidities	Chronic heart failure, osteoporosis, diabetes mellitus and depression	Ischemic heart disease and alcoholism
Hospitalization	No differences	No differences
Behavioral characteristics	More visits to the pulmonary clinic and seek medical attention earlier	Less medical consumption
Medication	More sensitive to adverse effects of β₂-adrenergics	Better results from inhalatory corticoids, better inhalation technique
Smoking cessation	Need for social support and more physical and emotional dependence	More likely to be sustained nonsmokers
Rehabilitation	Greater improvement of dyspnea	More benefit from long-term rehabilitation programs
Coping strategies	Emotion focused	Problem focused
Long-term oxygen therapy	Better survival during long-term oxygen therapy Higher risk for respiratory failure	Lower survival during long-term oxygen therapy

FEV1: Forced expiratory volume in 1 s.

Diagnosing COPD is more difficult in women owing to the different presentation of symptoms when compared with men. Women report greater anxiety, more depressive symptoms and complain more about dyspnea [3]. Both the prevalence of COPD and the mortality owing to COPD among women is rising. This is attributed to the increase in smoking prevalence and the supposed higher susceptibility to tobacco use in women. This higher susceptibility is not supported by all studies: several investigations have shown that women have a greater vulnerability of the lungs [4 –6]; however, other studies do not always substantiate this finding [7 –9]. Other sex-related differences have been noted: women report a lower quality of life compared with men, even when adjusted for lung function [10]; they have a worse nutritional status; and they have a higher exacerbation frequency [2]. Women may also react differently to drug treatment and pulmonary rehabilitation.

Based on these findings, we would expect to find differences in COPD treatment strategies between men and women.

Gender differences in COPD natural history

Prevalence

The prevalence of COPD in men is still higher than in women [11,12]. COPD was once thought of as a male disease; however, the prevalence of COPD among women is increasing and there are currently more women than men dying from COPD in industrialized countries. In the UK, during the period from January 1990 to December 1997, there was a striking increase in prevalence rates of COPD in women, which outpaced that of men [11]. Suggested causes are increased tobacco use among women, an increased susceptibility of lung function impairment caused by smoking [13], and the fact that women live longer. Nonsmokers with COPD are more often women, indicating that women are more susceptible to damage from air pollution or passive smoking [14]. Behavioral characteristics of females, for example younger age when starting to smoke and their greater difficulty with stopping smoking, may also play a role [15,16].

Better recognition of a woman's different presentation of symptoms may result in an earlier diagnosis by the physician. If two identical cases – except for gender – present with cough and dyspnea, physicians are more likely to diagnose COPD in males. This bias disappears when spirometric data are added. However, women are less likely to receive a referral for spirometry; therefore, women have a greater likelihood of being incorrectly diagnosed with asthma instead of COPD, and are consequently less likely to be adequately treated for their COPD [17,18].

Symptoms

Phlegm production has a significantly higher prevalence in men, perhaps owing to social factors. Conversely, coughing during the day or night in winter, and being woken by cough has a lower prevalence in men. The prevalence of respiratory symptoms (e.g., wheeze, waking with chest tightness, dyspnea at rest, dyspnea after activity, being woken by dyspnea, being woken by coughing) is similar in both sexes [12].

Health-related quality of life

Dyspnea is defined as a subjective experience of breathing discomfort and is related to the degree of airflow obstruction, pulmonary gas exchange abnormalities, nutritional status, inspiratory muscle strength, lung hyperinflation, respiratory central output, psychological and sociocultural factors; however, correlation coefficients are low. It is the most important complaint mentioned by COPD patients and the main determinant of their quality of life.

Katsura et al. investigated the gender-associated differences in health-related quality of life (HRQoL) in patients with COPD [19]. They found that females experience more severe dyspnea as well as lower disease-specific and general HRQoL. Women complain of greater dyspnea for the same degree of airflow obstruction. Furthermore, dyspnea in women occurs earlier in life and at earlier stages of the disease compared with men. Possible explanations are the lower inspiratory muscle strength in females and their higher rate of bronchial hyper-reactivity, which increases the sensation of dyspnea [20].

De Torres et al. also showed that HRQoL is significantly worse in female patients after adjusting for age and degree of airflow limitation. It has been reported that the prevalence of anxiety and depression is higher among women with COPD, which may explain the worse QoL [10]. Worse HRQoL and increased anxiety and depression are related to frequent emergency visits and significantly more relapses [3]. Frequent exacerbations, on the other hand, give rise to a poor HRQoL, resulting in a vicious circle.

Another study by de Torres et al., however, demonstrated that female COPD patients attending a pulmonary clinic had more exacerbations and expressed more dyspnea, but no differences in the rate of hospitalization were observed. This finding confirms the more symptomatic expression in women with COPD [2]. The poor HRQoL in women requires special consideration in the design of management strategies.

Lung function

We would expect that women who smoke have a greater reduction in lung function than their male counterparts because of their greater susceptibility to damage. Watson et al. found that women with a more severe airway obstruction (assessed by the forced expiratory volume in 1 s:forced vital capacity [FEV1:FVC] ratio), have a greater decline in FEV1 compared with those with a mild airway obstruction, after adjusting for the number of cigarettes smoked, peak years and starting age of smoking [12]. This difference was greater than found in similar studies with men.

However, Anthonisen et al. concluded that lung function loss is similar between genders in patients who continue smoking [21]. This does not support the idea of greater susceptibility of the female to exposure to smoke. This bias might be explained by the lower number of women included in most studies, as well as the inclusion of mild-to-moderate COPD patients instead of severely obstructed patients. The number of pack years reached between the ages of 15 and 35 years was a significant predictor of reduced maximal lung growth in men but not in women [22]. It is possible that the damage caused by smoking occurs early in men, preventing them from obtaining their maximum lung function, and therefore making them more prone to developing COPD.

An alternative explanation for the difference in susceptibility to the effects of smoking is a genetic predisposition [16,23]. The airways of women are smaller and therefore the concentration of cigarette smoke will be higher, resulting in a greater exposure. Hormonal factors may also play a role, but this requires further investigation. In vitro estrogens are shown to possess anti-inflammatory properties that suggest an underlying mechanism for a protective effect of estrogens on respiratory function [24]. Women have higher levels of IL-8 because of cyclic hormone activity. Smoking also gives rise to IL-8 levels, which attracts neutrophilic cells, resulting in an inflammatory response in the airway, promoting obstruction and the development of COPD [24].

The Lung Health Study showed that smoking cessation gave a 2.5-times better improvement of FEV1% predicted in women during the first year compared with men [4]. In the group of COPD patients who stopped smoking, the prevalence of airway responsiveness in women was higher than in men. The model was checked for age, gender, smoking history, height and weight. When this model was also adjusted for FEV1, as a surrogate for airway caliber, this gender difference disappeared. Therefore, the higher bronchial hyper-reactivity in women appears to be due to a smaller airway caliber [25,26].

Nutritional status

The nutritional status of patients with COPD has been shown to be of great importance. Mortality increases sharply when BMI falls below 21 [27]. The BMI, degree of airway obstruction, dyspnea and exercise capacity (BODE) index is a multidimensional evaluation of disease severity and prognosis, which has been validated in a population of predominantly male COPD patients [28]. Gender differences have been found in the BODE index. For a given BODE score, women had a lower BMI. Therefore the relative weight of BMI for a given BODE score was greater in female patients compared with their matched male controls [29]. This implies that the nutritional evaluation in women with COPD is of special importance. On the other hand, a high BMI (≥30) was associated with a lesser decline in lung function in males [12]. However, in this study, weight measurements were not assessed through time and therefore it is not possible to correlate changes in weight to changes in lung function. Obesity is generally associated with a reduced FEV1, especially in men [30,31], caused by the central fat distribution to which men are prone [12].

Exacerbations

Women are not hospitalized more often than men for COPD, except in older age groups, possibly explained by the longer life expectancy of women. Mortality in COPD patients is often attributable to comorbidities. The relative mortality from respiratory causes increases among patients who die at an older age. It may be that COPD patients who die from respiratory causes are those who did not die when younger from cardiovascular disease or cancer. There are different comorbidities in females, such as chronic heart failure, osteoporosis, diabetes mellitus and anxiety or depression, which may lead to an increased frequency of hospitalization. Men demonstrate other comorbidities, mostly ischemic heart disease and alcoholism [32]. However, women tend to have more exacerbations than men. In a surveillance study in the USA, a rise in ambulatory visits was observed among women. This increase in COPD visits may be caused by the fact that women seek medical attention earlier than men [33]. However, as mentioned earlier, women also experience more exacerbations than men. They visit the pulmonary clinic more often, at a younger age and have a shorter smoking history compared with men with the same degree of airflow limitation. It seems that COPD becomes clinically more evident in women at an earlier age [2].

Management of COPD

Medication

Medical treatment does not differ significantly between male and female patients with COPD. A number of studies have investigated the different responses to medication between male and female patients. They show that inhalatory corticosteroids may have better results in men compared with women, and women could be more sensitive to adverse effects for β₂-adrenergics (e.g., albuterol); however, further studies are necessary [34]. In addition Goodman et al. demonstrated that men are more likely to have an appropriate inhalation technique [35].

Smoking

Smoking cessation is the most important management strategy in the treatment of COPD. The Lung Health Study was designed to determine whether an intervention program for smoking cessation and prescription of an inhaled bronchodilator (e.g., ipratropium bromide) could slow down the rate of decline in FEV1 in smokers with mild-to-moderate COPD. Across the 5-year follow-up, sustained female quitters gained more in predicted FEV1% than men. This shows that smoking cessation has a greater advantage for women [4]. Bjornson et al. investigated the relationship between gender and sustained smoking cessation, 12 and 36 months after entry into the Special Intervention group of the Lung Health Study. Men were significantly more likely to be sustained nonsmokers than women [15]. Gender alone does not explain all of the differences; gender differences in baseline demographic and smoking history variables also proved to be important. Men and women with a higher education were more likely to be sustained nonsmokers. However, women with an education lower than High school were significantly less likely to quit smoking than men with similar education. If participants lived with another smoker, women were less likely to quit than men. Gender differences in the need for social support for smoking cessation have been reported by other investigators [36]. At baseline, men were heavier smokers, but women reported greater physical and emotional dependence on cigarettes. Smoking level and dependence on the first cigarette of the day are established indicators of nicotine dependence. Women in the Lung Health Study who were heavy smokers and more dependent on their first cigarette of the day were less likely to be sustained nonsmokers. Pomerleau et al. also reported gender differences in physical response to nicotine, resulting in reduced cessation rates in women [37].

Prevention is still the best method of reducing this increase in incidence, making smoking-education an important factor in this issue.

Rehabilitation

The importance of pulmonary rehabilitation in the management of COPD has been proven; however, no evidence of differences between the sexes has been conclusive. Lizak et al. found that there was no difference in outcome of pulmonary rehabilitation [38] and this was confirmed in a study by Haave et al. [39]. On the other hand, a Canadian study by Laviolette et al. demonstrated that women showed greater improvement of their dyspnea than men after rehabilitation. The improvement in functional status was similar in both sexes [40]. However, Foy et al. showed that women did not benefit from long-term rehabilitation programs as much as men. Again, a greater improvement in dyspnea was observed in women, but they did not appear to be able to enhance their overall function by exercise therapy alone. This may mean that exercise alone is an insufficient form of rehabilitation for women. When looking at coping strategies, men seek professional help for personal problems less frequently than women [41]. Women use emotion-focused strategies more often, while men use problem-focused strategies. This could be explained by findings that women generally show more anxiety than men, especially regarding dyspnea [42]. Women may benefit more from rehabilitation programs that include emotional support and social interaction [43].

Long-term oxygen therapy

Franklin et al. investigated gender-related differences in annual incidence and prevalence in patients with chronic hypoxia resulting from COPD and who were treated with long-term oxygen therapy. They also studied survival after onset of oxygen therapy. The prevalence of patients on long-term oxygen therapy increased more rapidly in women than in men. This is caused by a larger increase of women starting with oxygen and a better survival of these patients. The risk of respiratory failure and long-term oxygen therapy later in life was almost twice as high among women when compared with men, when adjusted for smoking history. An explanation can be the higher susceptibility shown by women to damage from smoking cigarettes. The survival during long-term oxygen therapy is better in women than in men [44].

Conclusion

There is a growing incidence of COPD among women. Management can only be optimal when we better understand the pitfalls in diagnosing COPD in women, the differences in natural history and the different treatment strategies necessary for men and women.

Future perspective

A better understanding of gender-related symptoms and HRQoL in COPD is required for correct diagnosis and treatment. The differences between prevalence, symptoms, decrease in lung function, nutritional status, hospitalization, exacerbation frequency and disease progression between the sexes need to be explored further. We need to learn more regarding treatment responses in order to develop optimal strategies for men and women with COPD. Finally, researchers should pay more attention to investigating the effect of gender differences in COPD patients.

Executive summary

Prevalence of chronic obstructive pulmonary disease in women is rising because of increased tobacco use and higher susceptibility of lung function impairment by smoking.

Women have a different presentation of symptoms.

Health-related quality of life is worse in women, mostly because they experience more dyspnea.

There is a greater reduction in lung function in women. Smoking cessation, on the other hand, gives better improvement of the predicted forced expiratory volume in 1 second percentage.

Nutritional evaluation in women is of special importance.

Medical treatment does not differ between the sexes.

Women are less likely to be sustained nonsmokers.

Women benefit more from rehabilitation programs that include emotional support and social interaction.

Women have a higher risk of respiratory failure and need for long-term oxygen therapy. Survival on long-term oxygen therapy is better in women.

Footnotes

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Increasing Evidence for Gender Differences in Chronic Obstructive Pulmonary Disease

Abstract

Keywords

Gender differences in COPD natural history

Prevalence

Symptoms

Health-related quality of life

Lung function

Nutritional status

Exacerbations

Management of COPD

Medication

Smoking

Rehabilitation

Long-term oxygen therapy

Conclusion

Future perspective

Footnotes

References