Women represent a rapidly growing proportion of patients with chronic obstructive pulmonary disease (COPD), as can be deduced from the increasing prevalence of female tobacco use as well as the possible greater influence of cigarette smoke on those of the female gender.1,2 Women with COPD are younger,3–5 smoke less,3–5 respond at a lesser degree to lung rehabilitation treatment,6 manifest greater reactivity of the airways2 and report more dyspnea than men for the same degree of airflow obstruction.7

Health status (HS) is an important evaluation criterion in patients with COPD and its deterioration is considerable, corresponding with the severity of the disease.8–10 Among the medical studies published, there are hardly any data that suggest women being more vulnerable to the negative effects of COPD on state of health.5,11 Nevertheless, these studies included few patients with very severe COPD who were being treated with long-term oxygen therapy (LTOT). In addition, we have not found prospective studies comparing the changes in health status between men and women with COPD after said treatment.

We hypothesize that very severe COPD patients may present different responses to LTOT, depending on their gender. Therefore, this present study was designed: 1) to report the differences between men and women with very severe COPD, regarding degree of dyspnea and specific HS of the disease and 2) to provide a prospective evaluation of the response of the health status to LTOT, according to gender.

We carried out a prospective, observational study of COPD patients, recruited from the LTOT program from a third-level university hospital (Botucatu Medical School, UNESP-São Paulo State University, Brazil). All the patients met the criteria established by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and by the Brazilian Thoracic Society (BTS) for the diagnosis of COPD (post-bronchodilator FEV1/FVC ratio <0.70) and for LTOT.12,13 The additional inclusion criteria were the following: 1) stable disease, from a clinical standpoint (with no changes in dosage of the medication or administration intervals and with no exacerbations of the disease or hospitalizations in the 6 weeks prior to evaluation) and 2) patients with persistent hypoxemia after three months of oxygen therapy (to avoid the inclusion of those who received temporary oxygen supplements). The exclusion criteria were patients with concomitant respiratory diseases, such as: associated restrictive disease, sleep apnea/hypopnea syndrome, asthma, bronchiectasis and those incapable of either understanding or completing the health status questionnaire. Fig. 1 describes the study design.

Fig. 1.

Study design and patient details.

(0.23MB).

All the patients were seen in the oxygen therapy clinic every three months in order to evaluate the compliance with LTOT, determine the incidence of exacerbations/hospitalizations and adjust the oxygen flow, if necessary. During the study period, the patients received the treatment recommended for COPD and were treated appropriately for the exacerbations.12 For those subjects who missed a follow-up visit, the data for the survival state of the patient were obtained by means of a telephone call to the family, and a new appointment was scheduled, when appropriate.

The study was approved by the research committee of the Botucatu Medical School University Hospital and all the patients gave their written informed consent.

This present study clearly demonstrates a benefit of oxygen therapy on health status in hypoxemic patients with chronic obstructive pulmonary disease. The analysis of the 80 patients who completed the study demonstrated a significant improvement in the total score obtained in the SGRQ after 6 months and a significant improvement in the symptom domain after 6 months, which continued 12 months later. In the baseline period, both genders presented a similar deterioration in the state of health. However, in the analyses stratified by gender, longitudinal differences were demonstrated between men and women. In women, a persistent improvement was observed in the symptom score and total score and, in comparison, in the men there were observed significantly poorer activity and impact scores as well as total score on the questionnaire during treatment with LTOT.

During the baseline period, we identified differences between sexes in the history of tobacco use and airflow obstruction in patients who received oxygen therapy. This is a new finding and we interpreted this observation as an indication that women with COPD develop hypoxemia with a lower degree of airflow obstruction and a significantly shorter history of smoking than men. The results of this present study also support the concept that women could be more vulnerable to the harmful effects of inhaled smoke. In previous studies, designed to compare the clinical differences between genders among patients with stable COPD, the women were younger and smoked less than the men when paired by FEV1 values as a percentage of the reference values.4,5

The interest in evaluating health status has increased in recent years, as has the interest in the influence of gender in the expression of COPD. In patients with very severe disease, we have shown a substantial deterioration in state of health. This finding coincides with the results of previous studies demonstrating that health status deterioration runs parallel to disease severity.8–11 In fact, in previous studies carried out in patients with COPD with a wide variety of airflow obstruction, a greater deterioration in quality of life was reported related with health in women.4,5,7,8,11 However, when patients were classified by the severity of the obstruction (depending on the FEV1% values), there were no differences in the health status for the group of patients with more severe disease.4,8 The baseline characteristics of the patients of the present study support these findings, suggesting that those with very severe COPD present a deterioration of such a degree in their health status when they receive LTOT that it is possible that no differences are observed between sexes.

One exclusive finding of this prospective, longitudinal, interventionist study was the difference between genders in the response to oxygen therapy in COPD patients. The findings demonstrate that the women manifested significant improvements in the symptom score and total score obtained in the questionnaire during the study period; on the other hand, the activity and impact domains did not change. Nevertheless, despite a significant improvement of the symptoms, the men presented a notably poorer score in the activity domain, impact, and total score obtained in the questionnaire at the 12-month follow-up. As far as the authors are aware, only one previous longitudinal study has been published that demonstrates differences between genders after the start of oxygen therapy.21 The study evaluated patients with chronic airflow limitation in the baseline period and after initiating oxygen therapy at 3, 6, and 12 months, using both generic and specific disease questionnaires. The results obtained with the disease-specific Chronic Respiratory Questionnaire (CRQ) showed that the women obtained a significant improvement in all the domains, while the men obtained an improvement in the CRQ fatigue domain.21 The data of this present study back these findings in COPD patients, suggesting an improvement in the quality of life during oxygen therapy in women, although with a less-convincing response than in men.

Very few longitudinal studies have examined the effect of oxygen therapy on the health status of COPD patients without an analysis stratified by gender,22,23 and the results are controversial. The findings of the present study coincide with those by Eaton et al.23 who, in patients with severe COPD that met the inclusion criteria after the introduction of oxygen therapy, demonstrated a significant improvement in the health-related quality of life with a maintained or additional response at 6 months. In comparison, using the SGRQ questionnaire during a period of 6 months, Okubadejo et al.22 did not demonstrate a change in health status; nevertheless, it was a small-scale study and consequently might not have had sufficient power.

The activity domain includes the physical activities that either induce dyspnea or are limited by it. The results of the present study demonstrate that the limitation of activity, as evaluated by the activity subscale of the SGRQ, was the health status variable that notably deteriorated in men. Compared with women of the same age group, men usually perform a greater physical effort and, in contrast with this, it is predictable that the patients receiving oxygen therapy spend more time at home and reduce their general level of exercise. For this reason, it would in part explain the differences in the activity domain of the questionnaire observed between sexes during follow-up.

Dyspnea is one of the main determinants of health status in COPD patients. A previous study found a powerful correlation between the degree of dyspnea and health status on each of the subscales (symptoms, activities, and impact) obtained from the SGRQ in an extensive series of patients with COPD.24 In a later study, it was demonstrated that in patients with more severe obstruction, baseline dyspnea offered the best explanation of the general state of health and also of the activity domain and symptoms.25 Furthermore, the sensation of dyspnea is a valid indicator of survival in the first year among patients with very severe COPD treated with oxygen therapy.26 However, the index of baseline dyspnea did not change during the study period for men and women in this present research. One possible explanation of this result is that LTOT does not improve the sensation of dyspnea.9,27 Similarly, in a previous study it was observed that the dyspnea scores (Borg scale and oxygen-cost diagram) did not change after 12 months of oxygen therapy.28 In the NOTT and MRC studies, the effects of oxygen therapy on survival seemed to depend on the daily duration of the treatment, observing the better outcome among those individuals who received oxygen therapy during a greater number of hours per day.29,30

We strongly recommended the patients of the present study to use the oxygen in compliance with the prescription, and this advice was reinforced upon each visit to the clinic. In this study, the overall compliance with the treatment was 61%, and other researchers have reported similar findings.23,28 In general, the compliance with oxygen therapy was far from ideal as the percentage of patients who used oxygen for more than 15h per day varied from 37% to 65%.23,28,31 It is worrying that the underuse of oxygen therapy limits its effectiveness, but we observed a similar compliance in patients of both genders (63% compared to 59%; P=.98); therefore, the reported differences for gender regarding health status in this present study cannot be explained by the lack of treatment compliance.

When interpreting the results of the present study, some potential limitations should be considered. In the first place, the compliance with oxygen therapy was evaluated by what was reported by each patient. Nevertheless, the methods generally used for quantifying the number of hours that the patients use oxygen, such as the number of empty oxygen tanks and the readings of the mean oxygen flow received by the patient through a self-controlled device, are also prone to error. Second of all, although the smokers were not candidates for oxygen therapy, tobacco use was not confirmed with laboratory tests. Last of all, we did not analyze other variables that may influence the health status, such as psychosocial factors, socio-economic position and marital status as well as the years studied.

The present study takes on for the first time the course of the state of health in men and women with very severe COPD, treated with oxygen therapy. In the baseline period, the patients referred deterioration similar to the health status and a similar sensation of dyspnea. After treatment, in both sexes the symptom domain of the SGRQ improved. However, after 12 months of the study, in men there were significantly worse scores for the activity domain, impact and total score, at the same time there was a clinically significant poorer activity and impact in the same period. These results demonstrate that, in patients with very severe COPD, health status differs according to gender as women show a greater longitudinal response to oxygen therapy.

The authors declare having no conflict of interests.