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Original Research: COPD |

Increased Relative Mortality in Women With Severe Oxygen-Dependent COPD FREE TO VIEW

Magnus Ekström, MD; Karl A. Franklin, MD, PhD and; Kerstin E. Ström, MD, PhD
Author and Funding Information

From the Department of Respiratory Medicine (Drs Ekström and Ström), Blekinge Hospital Karlskrona, University of Lund, Karlskrona, Sweden; and the Department of Surgery (Dr Franklin), Umeå University, Umeå, Sweden.

Correspondence to: Magnus Ekström, MD, Department of Respiratory Medicine, Blekinge Hospital, SE-37185 Karlskrona, Sweden; e-mail: magnus_ekstrom@hotmail.com


Funding/Support: The study was supported by grants from the Swedish Heart and Lung Foundation, the Swedish National Board of Health and Welfare, and the Research Council of Blekinge.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(1):31-36. doi:10.1378/chest.09-0636
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Published online

Background:  Although the incidence of COPD is rapidly increasing in women, knowledge is lacking concerning differences in relative mortality and causes of death in women compared with men. We aimed to analyze differences in relative mortality and cause-specific mortality between men and women on long-term oxygen therapy (LTOT) for COPD.

Methods:  Patients starting LTOT for COPD in Sweden between January 1, 1987, and December 31, 2004, were prospectively followed until termination of LTOT or through December 31, 2004. Causes of death according to the Swedish National Causes of Death Register were compared between the study group and the general Swedish population matched for age and sex, with the relative mortality expressed as standardized mortality rates (SMRs).

Results:  A total of 7,646 patients, 4,033 women and 3,613 men, were followed for a median of 1.7 years (range 0-18.0). No patient was lost to follow-up. A total of 5,448 patients, 2,745 women and 2,703 men, died. Women had a higher SMR than men: overall mortality, SMR 12.0 (95%, 11.6-12.5) vs 7.4 (95% CI, 7.1-7.6); for respiratory disease, SMR 127.9 (95% CI, 122.4-133.6) vs 66.0 (95% CI, 63.1-69.0); cancer, SMR 3.5 (95% CI, 3.0-3.9) vs 2.2 (95% CI, 1.9-2.5); and cardiovascular disease, SMR 3.7 (95% CI, 3.3-4.1) vs 2.5 (95% CI, 2.3-2.7), respectively.

Conclusions:  In severe COPD treated with long-term oxygen, women have higher relative mortality than men both overall and for respiratory disease, as well as for cardiovascular disease and cancer.

COPD is one of the leading causes of death worldwide.1 Smoking is the major pathogenic factor, accounting for some 80% of the cases in high-income countries.2

Long-term oxygen therapy (LTOT) doubles the survival time in patients with COPD and chronic hypoxia (Pao2 < 7.3 kPa).3,4 Despite the impact of LTOT, mortality is high in patients with COPD and LTOT.5-10 Patients with COPD have increased comorbidity, such as cancer and cardiovascular disease.11 Reporting cause-specific mortality is essential because it has been shown that up to two-thirds of patients with severe COPD who are treated with LTOT die of causes other than respiratory disease.12

Previous studies of prognosis in men and women with severe, oxygen-dependent COPD have shown contradictory results. Five previous studies report that men have shorter survival time than women after starting LTOT.5-7,9,13 In contrast, Machado et al8 report that women have shorter survival time, and Cranston et al13 reported that women lost more years of life than men as compared with the general population. Sex-related differences in cause-specific mortality have not previously been studied in patients with LTOT for COPD. Knowledge about sex differences in relation to mortality is urgently needed because women have rapidly rising rates of smoking, particularly in low- and middle-income countries, and COPD is increasingly becoming a women’s disease.14 The majority of active smokers and patients starting LTOT for COPD in Sweden today are women,9,15 and the rate of women starting LTOT is predicted to increase further.9 Women have longer life expectancies than men in the general population, which might result in sex-related differences in mortality and causes of death in LTOT for COPD.16 Most patients starting LTOT are also elderly and can be expected to have relatively high background mortality.9,10 We therefore conducted a national prospective study of patients starting LTOT for COPD with the aim of studying cause-specific standardized mortality rates (SMRs) with respect to sex.

Patients starting LTOT for chronic hypoxia due to COPD in Sweden between January 1, 1987, and December 31, 2004, were included in a National Oxygen Register administered by the Swedish Society of Respiratory Medicine.17-19 Every center prescribing LTOT in Sweden agreed on the national guidelines from the Swedish Society of Respiratory Medicine, as described elsewhere.9 Patients who started LTOT more than once were excluded. All other patients were followed prospectively, with cause of death as the primary outcome, until LTOT was withdrawn or through December 31, 2004, whichever came first. Baseline data were collected at the start of LTOT on arterial blood gas tensions when breathing air and during oxygen therapy, FVC, FEV1, smoking history, the prescribed oxygen dose, the prescribed duration of oxygen treatment per day, and treatment with oral steroids.

Causes of death were obtained from the Causes of Death Register at the Swedish National Board of Health and Welfare and coded according to the ninth (before 1996) and the 10th revisions of the International Classification of Disease (ICD).20,21 ICD codes were grouped (ICD-9, ICD-10) as respiratory diseases (276C, 277, 279, 460-519×, 786; E84, E87.2, E88.0, J00-J99, R04-R06), circulatory diseases (390-459×, 785; I00-I99, R00, R01), cancer (140-239×; C00-D48), digestive organ diseases (520-579×, 787; K00-K93), endocrine (240-272, 274, 275, 278; E00-E83, E85, E86), hematologic (273, 280-289×; D50-D89), infectious diseases (001-139W; A00-B99), urogenital diseases (580-629×, 788; N00-N99), musculoskeletal diseases (710-739; M00-M99), COPD (490-492, 496; J40-J44, J96), ischemic heart disease (410-414; I20-I25), lung cancer (162; C34), heart failure (425, 428; I42, I50, I51.7), stroke (430-438; I60-I69), aortic aneurysm (441; I71), venous thromboembolism (415.1, 451; I26, I80), tuberculosis (010-018, 137; A15-A19, B90), pneumonia (481-486; J13-J18), and colon cancer (153; C18).

All patients gave their informed consent to participate. The study was approved by all ethics committees in Sweden, the Swedish National Board of Health and Welfare, and the Data Inspection Board.

Statistical Analysis

Baseline patient characteristics were expressed as mean ± SD. Age-, sex-, and calendar year-specific person time at risk for death during LTOT were calculated for each patient from the start of LTOT to the time of death, until LTOT was withdrawn, or until the end of the observation period (December 31, 2004), whichever came first. Survival after starting LTOT was compared between men and women using Cox proportional hazards regression adjusted for age and period of starting LTOT. Mortality was studied in the form of SMRs, defined as the ratio of the observed deaths in the study population to the expected number of deaths. The expected number of deaths was calculated using national age-, sex-, and calendar year-specific mortality rates from the Causes of Death Register, presented by the Swedish National Board of Health and Welfare. The underlying cause of death was used in all analyses because this is the basis for the national mortality rates. SMRs were calculated with 95% CIs. Statistical analyses were performed with SPSS 14.0 (SPSS; Chicago, IL), and Stata 10.0 (StataCorp LP; College Station, TX).

A total of 7,646 patients, 4,033 women and 3,613 men, were included in the study after exclusion of 71 patients who had started LTOT more than once. No patient was lost to follow-up. LTOT was withdrawn in 436 (5.7%) patients as a result of improvement in oxygenation (n = 195), poor compliance (n = 36), or for other reasons (n = 205).

Patient characteristics at baseline are shown in Table 1 . Women had a slightly lower mean age at the start of LTOT and a slightly higher Paco2 both when breathing air and oxygen. The prescribed duration of oxygen treatment per day and the mean Pao2 breathing oxygen were similar between the groups. Slightly more women than men were never-smokers.

Table Graphic Jump Location
Table 1 —Patient Characteristics at Study Start

All values are presented as means ± SD or a percentage.

Overall Relative Mortality

The cohort was followed for a median of 1.79 years (range 0-17.97) for women and 1.55 years (range 0-17.65) for men and generated a total of 16,175.5 person-years with risk of mortality. A total of 5,448 patients, 2,745 women and 2,703 men, died during follow-up in the study group, compared with the expected 596, resulting in increased relative mortality, SMR 9.1 (95% CI, 8.9-9.4). Both women and men had increased relative mortality for cancer and respiratory, circulatory, infectious, digestive, and urogenital diseases, as shown in Table 2.

Table Graphic Jump Location
Table 2 —SMRs for Entity of Diagnosis of Death

Expected = number of expected deaths in the general population matched for age and sex; Observed = observed number of deaths; SMR = standardized mortality rate.

a 

Causes of death with significant sex-related differences in SMR.

Sex-Related Differences in Mortality

Women had a lower absolute risk of dying compared with men, with a hazard ratio of 0.86 (95% CI, 0.81-0.91, P < .001), using Cox proportional hazard regression adjusted for age and the period of starting LTOT. Cause-specific SMRs for women and men are shown separately in Table 2. Women had significantly higher overall relative mortality than men, SMR 12.0 (95% CI, 11.6-12.5) vs SMR 7.4 (95% CI, 7.1-7.6), respectively. Women also had significantly increased relative mortality for cancer, respiratory, and circulatory disease compared with men.

Most patients died of COPD (66%), ischemic heart disease (8.6%), lung cancer (4.4%), or heart failure (2.3%) (Table 3). Women had significantly higher relative mortality than men for all four of these main causes of death. Women also had increased relative mortality from stroke, which was not observed in men. Mortality from aortic aneurysm, venous thromboembolism, tuberculosis, and pneumonia was increased in both men and women, but with no significant sex-related differences.

Table Graphic Jump Location
Table 3 —SMRs for the 10 Most Common Diagnoses of Death

See Table 2 for expansion of abbreviations.

a 

Causes of death with significant sex-related differences in SMR.

A new finding in the present study is that women have significantly higher relative mortality than men, not only concerning all-cause mortality and mortality from respiratory disease, but also from cardiovascular disease and cancer.

Studies of differences in observed survival rates between men and women after initiation of LTOT for COPD have shown contradictory results. Most studies showed higher survival rates for women,5-7,9,13 whereas the study by Machado et al8 found a survival advantage for men. Longer age-adjusted survival for women was also shown in a previously published study of some of the patients included in this study.9 The present findings illustrate that although women have better observed survival after starting LTOT, their relative mortality compared with the general population matched for age is markedly higher. Women have higher relative mortality from cancer and respiratory and cardiovascular diseases and lose more years of life than men. The higher relative all-cause mortality for women in the present study supports the findings of the study by Cranston et al13 of relative mortality in 505 patients with LTOT for COPD, in which women lost more years of life than men, compared with the general population (16.3 years for women vs 13 years for men).

The majority of studies comparing the sex-related differences of the impact of smoking in patients with COPD have studied the rate of decline in FEV1. They come to contradictory conclusions, but most studies have found that women seem more disposed to developing COPD at an earlier age than men and with less tobacco exposure.22-27 In one study, women with COPD were found to be younger, had fewer pack-years, and fewer comorbidities,28 and in another study, women were found to be less susceptible to airway obstruction.29 When women have been found to be more susceptible, the explanations have often been differences in airway diameter and airway responsiveness.27,30 But mortality, even in COPD so severe that the patient qualifies for LTOT, is not caused only by the respiratory disease. The 215 patients included in the study by Zielinski et al12 of cause-specific mortality in patients with COPD receiving LTOT died of respiratory failure (38%), cardiovascular disease (27%), pulmonary infection (11%), pulmonary embolism (10%), lung cancer (7%), or other causes (7%). However, the mortality was not related to the expected mortality based on age and sex in the population, only a few women were included, and the study did not report any sex-related differences in mortality.

The present study shows that patients who receive LTOT for severe COPD have markedly increased relative mortality from a number of different diseases and that there is a sex-related difference: women have significantly higher relative mortality than men for cancer, respiratory and cardiovascular diseases in cases of severe COPD. However, because age-adjusted mortality from cardiovascular disease in the general population is considerably lower in women than in men, death from cardiovascular disease was still more common in men who received LTOT for COPD than in women.

The strengths of the present study are its national prospective design and that it includes a larger patient group, especially more women, than other studies in the field.5-9,13 No patient was lost to follow-up, thanks to the fact that Sweden has a complete population register of vital status and causes of death. This is, to our knowledge, the first study of sex-related differences in cause-specific mortality in patients who received LTOT for COPD. Using a relative mortality model made it possible to describe the excess cause-specific mortality among the patients compared with the matched general population, and has been shown to be superior to using Cox regression models in adjusting for the effects of age and differences in life expectancy in relation to mortality.10

Several studies have questioned the validity of cause of death registers in relation to COPD, and most have found COPD to be underestimated as an underlying cause of death.31-34 The rate of underestimation of COPD as the cause of death has been shown to decrease with increasing severity of COPD, especially for women.34 Therefore, underestimation of COPD as the cause of death is probably only a minor problem in the present study of patients with known severe COPD treated with long-term oxygen.

The increased relative mortality in women as compared with men in our study could to some extent be caused by the lower age-adjusted mortality in women than in men in the general population.16 The mechanism for this is largely unknown, but it might partly be attributable to a lower prevalence of risk factors among women, most notably smoking. Although smoking rates have increased in Sweden for women, the rates of ever-smokers and the mean number of cigarettes smoked per day are still higher in men.15

Studies have shown that women may be more sensitive to the adverse health effects of smoking and may more easily develop severe COPD with respiratory failure than men on the basis of the same smoking burden.22-25 A recent Swedish study showed that the increasing incidence of women starting LTOT for severe COPD could not be explained solely by differences in smoking rates. Women also seem more susceptible to developing severe disease than men.9 We thus find it likely that the observed higher relative mortality in women who received LTOT for COPD is caused by a combination of the lower age-adjusted mortality rate for women compared with men in the general population and the fact that women starting LTOT often have more severe diseases and comorbidities that eliminate their normal survival advantage.

The present findings stress the importance of promoting smoking cessation, especially for women, who have increasing smoking rates in many parts of the world. Because mortality in severe COPD is increased in several nonrespiratory diseases, such as cardiovascular disease, earlier diagnosis and treatment of comorbidity are important in women, as they have even more increased relative mortality than men in relation to cardiovascular disease and cancer. In conclusion, in cases of severe COPD treated with long-term oxygen, women lose more years of life and have significantly higher relative mortality than men, not only overall and for respiratory disease, but also for cardiovascular disease and cancer.

Author contributions:Dr Ekström: contributed to the design of the study and the analysis, interpretation, and presentation of data, drafted the submitted article, and provided final approval of the version to be published.

Dr Franklin: contributed to the analysis and interpretation of data, revised it critically for important scientific content, and provided final approval of the version to be published.

Dr Ström: was responsible for the Swedish Oxygen Register 1987-2007 during the collection of the data, initiated the study, participated in the design, analysis, and interpretation of the data, gave advice on the drafting of the manuscript, revised the manuscript, and provided final approval of the version to be published.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Ekström received reimbursement from Union Chimique Belge for attending the European Respiratory Society annual conference in 2008. Dr Franklin has no potential conflict with any companies/organizations whose products or services may be discussed in this article. Dr Ström received reimbursement from Pifizer for attending the American Thoracic Society conference in 2006 and from Union Chimique Belge for attending the European Respiratory Society annual conference in 2008. Dr Ström also received $1,000 for lecturing at conferences organized by Boehringer-Ingelheim in 2006 and 2009.

Other contributions: The work was performed at the Department of Respiratory Medicine, Blekinge Hospital Karlskrona, University of Lund, Sweden. We thank all the physicians and nurses who collected the data. The data analysis was performed by Philippe Wagner and Jonas Ranstam (at the Swedish Musculoskeletal Competence Centre in Lund, Sweden), who also assisted with development of the study design and participated in the preparation of the manuscript.

ICD

International Classification of Disease

LTOT

long-term oxygen therapy

SMR

standardized mortality rate

Lopez AD, Mathers CD, Ezzati M, et al. Global Burden of Disease and Risk Factors. 2006; Washington The World Bank
 
Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;1635:1256-1276. [PubMed]
 
Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980;933:391-398. [PubMed]
 
Report of the Medical Research Council Working Party Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981;18222:681-686. [PubMed]
 
Miyamoto K, Aida A, Nishimura M, Aiba M, Kira S, Kawakami Y. The Respiratory Failure Research Group in Japan Gender effect on prognosis of patients receiving long-term home oxygen therapy. Am J Respir Crit Care Med. 1995;1523:972-976. [PubMed]
 
Chailleux E, Fauroux B, Binet F, Dautzenberg B, Polu JM. Predictors of survival in patients receiving domiciliary oxygen therapy or mechanical ventilation. A 10-year analysis of ANTADIR Observatory. Chest. 1996;1093:741-749. [CrossRef] [PubMed]
 
Crockett AJ, Cranston JM, Moss JR, et al. Survival on long-term oxygen therapy in chronic airflow limitation: from evidence to outcomes in the routine clinical setting. Intern Med J. 2001;318:448-454. [CrossRef] [PubMed]
 
Machado MC, Krishnan JA, Buist SA, et al. Sex differences in survival of oxygen-dependent patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;1745:524-529. [CrossRef] [PubMed]
 
Franklin KA, Gustafson T, Ranstam J, Ström K. Survival and future need of long-term oxygen therapy for chronic obstructive pulmonary disease—gender differences. Respir Med. 2007;1017:1506-1511. [CrossRef] [PubMed]
 
Foucher P, Baudouin N, Merati M, et al. Relative survival analysis of 252 patients with COPD receiving long-term oxygen therapy. Chest. 1998;1136:1580-1587. [CrossRef] [PubMed]
 
Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;286:1245-1257. [CrossRef] [PubMed]
 
Zielinski J, MacNee W, Wedzicha JA, et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch Chest Dis. 1997;521:43-47. [PubMed]
 
Cranston JM, Nguyen AM, Crockett AJ. The relative survival of COPD patients on long-term oxygen therapy in Australia: a comparative study. Respirology. 2004;92:237-242. [CrossRef] [PubMed]
 
Varkey AB. Chronic obstructive pulmonary disease in women: exploring gender differences. Curr Opin Pulm Med. 2004;102:98-103. [CrossRef] [PubMed]
 
Statistics Sweden Living Conditions. Report No. 105. Health Related Habits of Life 1980-2002. 2004; Stockholm, Sweden Statistics Sweden
 
The National Board of Health and Welfare Causes of death.http://www.socialstyrelsen.se/Publicerat/2008/10117/2008-42-6.htmAccessed May 26, 2009.
 
Ström K, Boe J. A national register for long-term oxygen therapy in chronic hypoxia: preliminary results. Eur Respir J. 1988;110:952-958. [PubMed]
 
Ström K. Survival of patients with chronic obstructive pulmonary disease receiving long-term domiciliary oxygen therapy. Am Rev Respir Dis. 1993;1473:585-591. [PubMed]
 
Ström K.O’Donohue WJ. Experience with an oxygen registry in Sweden. Long-Term Oxygen Therapy: Scientific Basis and Clinical Application. 1995; New York, NY Marcel Dekker Publisher, Inc:331-346
 
World Health Organization Manual of the International Classification of Diseases, Injuries and Causes of Death. 9th revision. 1978;Vol 1 Geneva, Switzerland WHO
 
World Health Organization Manual of the International Statistical Classification of Diseases and Health Related Problems. 10th revision. 1992;Vol 1 Geneva, Switzerland WHO
 
Xu X, Weiss ST, Rijcken B, Schouten JP. Smoking, changes in smoking habits, and rate of decline in FEV1: new insight into gender differences. Eur Respir J. 1994;76:1056-1061. [CrossRef] [PubMed]
 
Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J. 1997;104:822-827. [PubMed]
 
Langhammer A, Johnsen R, Gulsvik A, Holmen TL, Bjermer L. Sex differences in lung vulnerability to tobacco smoking. Eur Respir J. 2003;216:1017-1023. [CrossRef] [PubMed]
 
Gan WQ, Man SF, Postma DS, Camp P, Sin DD. Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis. Respir Res. 2006;7:52. [CrossRef] [PubMed]
 
Dransfield MT, Davis JJ, Gerald LB, Bailey WC. Racial and gender differences in susceptibility to tobacco smoke among patients with chronic obstructive pulmonary disease. Respir Med. 2006;1006:1110-1116. [CrossRef] [PubMed]
 
Chapman KR. Chronic obstructive pulmonary disease: are women more susceptible than men? Clin Chest Med. 2004;252:331-341. [CrossRef] [PubMed]
 
de Torres JP, Casanova C, Hernández C, Abreu J, Aguirre-Jaime A, Celli BR. Gender and COPD in patients attending a pulmonary clinic. Chest. 2005;1284:2012-2016. [CrossRef] [PubMed]
 
de Torres JP, Campo A, Casanova C, Aguirre-Jaime A, Zulueta J. Gender and chronic obstructive pulmonary disease in high-risk smokers. Respiration. 2006;733:306-310. [CrossRef] [PubMed]
 
Martinez FJ, Curtis JL, Sciurba F, et al. National Emphysema Treatment Trial Research Group Sex differences in severe pulmonary emphysema. Am J Respir Crit Care Med. 2007;1763:243-252. [CrossRef] [PubMed]
 
Mannino DM, Brown C, Giovino GA. Obstructive lung disease deaths in the United States from 1979 through 1993. An analysis using multiple-cause mortality data. Am J Respir Crit Care Med. 1997;1563 Pt 1:814-818. [PubMed]
 
Hansell AL, Walk JA, Soriano JB. What do chronic obstructive pulmonary disease patients die from? A multiple cause coding analysis. Eur Respir J. 2003;225:809-814. [CrossRef] [PubMed]
 
Huiart L, Ernst P, Suissa S. Cardiovascular morbidity and mortality in COPD. Chest. 2005;1284:2640-2646. [CrossRef] [PubMed]
 
Jensen HH, Godtfredsen NS, Lange P, Vestbo J. Potential misclassification of causes of death from COPD. Eur Respir J. 2006;284:781-785. [CrossRef] [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1 —Patient Characteristics at Study Start

All values are presented as means ± SD or a percentage.

Table Graphic Jump Location
Table 2 —SMRs for Entity of Diagnosis of Death

Expected = number of expected deaths in the general population matched for age and sex; Observed = observed number of deaths; SMR = standardized mortality rate.

a 

Causes of death with significant sex-related differences in SMR.

Table Graphic Jump Location
Table 3 —SMRs for the 10 Most Common Diagnoses of Death

See Table 2 for expansion of abbreviations.

a 

Causes of death with significant sex-related differences in SMR.

References

Lopez AD, Mathers CD, Ezzati M, et al. Global Burden of Disease and Risk Factors. 2006; Washington The World Bank
 
Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. GOLD Scientific Committee Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;1635:1256-1276. [PubMed]
 
Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med. 1980;933:391-398. [PubMed]
 
Report of the Medical Research Council Working Party Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet. 1981;18222:681-686. [PubMed]
 
Miyamoto K, Aida A, Nishimura M, Aiba M, Kira S, Kawakami Y. The Respiratory Failure Research Group in Japan Gender effect on prognosis of patients receiving long-term home oxygen therapy. Am J Respir Crit Care Med. 1995;1523:972-976. [PubMed]
 
Chailleux E, Fauroux B, Binet F, Dautzenberg B, Polu JM. Predictors of survival in patients receiving domiciliary oxygen therapy or mechanical ventilation. A 10-year analysis of ANTADIR Observatory. Chest. 1996;1093:741-749. [CrossRef] [PubMed]
 
Crockett AJ, Cranston JM, Moss JR, et al. Survival on long-term oxygen therapy in chronic airflow limitation: from evidence to outcomes in the routine clinical setting. Intern Med J. 2001;318:448-454. [CrossRef] [PubMed]
 
Machado MC, Krishnan JA, Buist SA, et al. Sex differences in survival of oxygen-dependent patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;1745:524-529. [CrossRef] [PubMed]
 
Franklin KA, Gustafson T, Ranstam J, Ström K. Survival and future need of long-term oxygen therapy for chronic obstructive pulmonary disease—gender differences. Respir Med. 2007;1017:1506-1511. [CrossRef] [PubMed]
 
Foucher P, Baudouin N, Merati M, et al. Relative survival analysis of 252 patients with COPD receiving long-term oxygen therapy. Chest. 1998;1136:1580-1587. [CrossRef] [PubMed]
 
Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J. 2006;286:1245-1257. [CrossRef] [PubMed]
 
Zielinski J, MacNee W, Wedzicha JA, et al. Causes of death in patients with COPD and chronic respiratory failure. Monaldi Arch Chest Dis. 1997;521:43-47. [PubMed]
 
Cranston JM, Nguyen AM, Crockett AJ. The relative survival of COPD patients on long-term oxygen therapy in Australia: a comparative study. Respirology. 2004;92:237-242. [CrossRef] [PubMed]
 
Varkey AB. Chronic obstructive pulmonary disease in women: exploring gender differences. Curr Opin Pulm Med. 2004;102:98-103. [CrossRef] [PubMed]
 
Statistics Sweden Living Conditions. Report No. 105. Health Related Habits of Life 1980-2002. 2004; Stockholm, Sweden Statistics Sweden
 
The National Board of Health and Welfare Causes of death.http://www.socialstyrelsen.se/Publicerat/2008/10117/2008-42-6.htmAccessed May 26, 2009.
 
Ström K, Boe J. A national register for long-term oxygen therapy in chronic hypoxia: preliminary results. Eur Respir J. 1988;110:952-958. [PubMed]
 
Ström K. Survival of patients with chronic obstructive pulmonary disease receiving long-term domiciliary oxygen therapy. Am Rev Respir Dis. 1993;1473:585-591. [PubMed]
 
Ström K.O’Donohue WJ. Experience with an oxygen registry in Sweden. Long-Term Oxygen Therapy: Scientific Basis and Clinical Application. 1995; New York, NY Marcel Dekker Publisher, Inc:331-346
 
World Health Organization Manual of the International Classification of Diseases, Injuries and Causes of Death. 9th revision. 1978;Vol 1 Geneva, Switzerland WHO
 
World Health Organization Manual of the International Statistical Classification of Diseases and Health Related Problems. 10th revision. 1992;Vol 1 Geneva, Switzerland WHO
 
Xu X, Weiss ST, Rijcken B, Schouten JP. Smoking, changes in smoking habits, and rate of decline in FEV1: new insight into gender differences. Eur Respir J. 1994;76:1056-1061. [CrossRef] [PubMed]
 
Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J. 1997;104:822-827. [PubMed]
 
Langhammer A, Johnsen R, Gulsvik A, Holmen TL, Bjermer L. Sex differences in lung vulnerability to tobacco smoking. Eur Respir J. 2003;216:1017-1023. [CrossRef] [PubMed]
 
Gan WQ, Man SF, Postma DS, Camp P, Sin DD. Female smokers beyond the perimenopausal period are at increased risk of chronic obstructive pulmonary disease: a systematic review and meta-analysis. Respir Res. 2006;7:52. [CrossRef] [PubMed]
 
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