A nationwide structure for valid long-term oxygen therapy: 29-year prospective data in Sweden.

BACKGROUND: Long-term oxygen therapy (LTOT) improves prognosis in COPD with severe hypoxemia. However, adherence to criteria for eligibility and quality of LTOT is often insufficient and varies between countries. The aim of this study was to evaluate a national structure for prescription and management of LTOT over three decades in Sweden. METHODS: The study was a prospective, population-based study of 23,909 patients on LTOT from 1987 to 2015 in the Swedish National Register of Respiratory Failure (Swedevox). We assessed the prevalence, incidence, and structure of LTOT; completeness of registration in Swedevox; and validity of prescription and management of LTOT in Sweden according to seven published quality indicators. RESULTS: LTOT was prescribed by 48 respiratory or medicine units and managed mainly by specialized oxygen nurses. Swedevox had a stable completeness of 85% of patients starting LTOT since 1987. The national incidence of LTOT increased from 3.9 to 14.7/100,000 inhabitants over the time period. In 2015, 2,596 patients had ongoing therapeutic LTOT in the registry, a national prevalence of 31.6/100,000. Adherence to prescription recommendations and fulfillment of quality criteria was stable or improved over time. Of patients starting LTOT in 2015, 88% had severe hypoxemia (partial pressure of arterial oxygen [PaO2] <7.4 kPa) and 97% had any degree of hypoxemia (PaO2 <8.0 kPa); 98% were prescribed oxygen ≥15 hours/day or more; 76% had both stationary and mobile oxygen equipment; 75% had a mean PaO2 >8.0 kPa breathing oxygen; and 98% were non-smokers. CONCLUSION: We present a structure for prescription, management, and follow-up of LTOT. The national registry effectively monitored adherence to prescription recommendations and most likely contributed to improved quality of care.

Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease.

RATIONALE: Cardiovascular drugs may improve survival in chronic obstructive pulmonary disease (COPD). However, previous studies did not account for major sources of bias, and drug effects have not been evaluated in severe COPD. OBJECTIVES: To estimate the time-dependent effects of cardiovascular drugs on survival in oxygen-dependent COPD, accounting for immortal and immeasurable time bias. METHODS: Prospective national study of patients starting long-term oxygen therapy for COPD in Sweden between 1 October 2005 and 30 June 2009. Effects on mortality were estimated using extended Cox regression adjusted for age, sex, PaO2, PaCO2, World Health Organization performance status, body mass index, comorbidity, and concomitant medications. Immortal and immeasurable time bias was addressed by analyzing all medications as time-dependent variables and accounting for hospitalized time, respectively. MEASUREMENTS AND MAIN RESULTS: Time-dependent effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, antiplatelet drugs, ß-blockers, and statins on all-cause mortality were measured. Of the 2,249 included patients, 1,129 (50%) died under observation. No patient was lost to follow-up. The adjusted time-dependent model was compatible with reduced mortality for antiplatelet drugs (hazard ratio [HR], 0.86; 95% CI, 0.75-0.99; P = 0.030) and trends for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (HR, 0.90; 95% CI, 0.79-1.04; P = 0.166) and statins (HR, 0.86; 95% CI, 0.72-1.03; P = 0.105), whereas ß-blockers increased mortality (HR, 1.19; 95% CI, 1.04-1.37; P = 0.010). CONCLUSIONS: This study supports that antiplatelet drugs improve survival and ß-blockers decrease survival in oxygen-dependent COPD.

Comorbidity and sex-related differences in mortality in oxygen-dependent chronic obstructive pulmonary disease.

BACKGROUND: It is not known why survival differs between men and women in oxygen-dependent chronic obstructive pulmonary disease (COPD). The present study evaluates differences in comorbidity between men and women, and tests the hypothesis that comorbidity contributes to sex-related differences in mortality in oxygen-dependent COPD. METHODS: National prospective study of patients aged 50 years or older, starting long-term oxygen therapy (LTOT) for COPD in Sweden between 1992 and 2008. Comorbidities were obtained from the Swedish Hospital Discharge Register. Sex-related differences in comorbidity were estimated using logistic regression, adjusting for age, smoking status and year of inclusion. The effect of comorbidity on overall mortality and the interaction between comorbidity and sex were evaluated using Cox regression, adjusting for age, sex, Pa(O2) breathing air, FEV(1), smoking history and year of inclusion. RESULTS: In total, 8,712 patients (55% women) were included and 6,729 patients died during the study period. No patient was lost to follow-up. Compared with women, men had significantly more arrhythmia, cancer, ischemic heart disease and renal failure, and less hypertension, mental disorders, osteoporosis and rheumatoid arthritis (P<0.05 for all odds ratios). Comorbidity was an independent predictor of mortality, and the effect was similar for the sexes. Women had lower mortality, which remained unchanged even after adjusting for comorbidity; hazard ratio 0.73 (95% confidence interval, 0.68-0.77; P<0.001). CONCLUSIONS: Comorbidity is different in men and women, but does not explain the sex-related difference in mortality in oxygen-dependent COPD.

Trends in cause-specific mortality in oxygen-dependent chronic obstructive pulmonary disease.

RATIONALE: Since the introduction of long-term oxygen treatment (LTOT) in chronic obstructive pulmonary disease (COPD) with chronic hypoxia, the proportion of women and the age of patients starting LTOT have increased markedly. We hypothesize that this might have led to shifts in the causes of death over time. OBJECTIVES: To test for time trends in cause-specific mortality in COPD with LTOT. METHODS: Patients starting LTOT for COPD in Sweden between January 1, 1987 and December 31, 2004 were included in a national prospective study and monitored until withdrawal of LTOT, death, or December 31, 2004. The primary end point was cause of death obtained from the Swedish Causes of Death Register. MEASUREMENTS AND MAIN RESULTS: A total of 7,628 patients (53% women) were monitored for a median of 1.7 years (range, 0-18.0 yr). No patient was lost to follow-up and 5,457 patients died during the study. The crude overall mortality increased by 1.6%/year (95% confidence interval [CI], 0.9-2.2%/yr; P < 0.001). The absolute risk of death increased for circulatory disease by 2.8%/year (95% CI, 1.3-4.3%/yr; P < 0.001) and for digestive organ disease by 7.8%/year (95% CI, 1.9-14.0%/yr; P = 0.009). The absolute risk of death decreased for respiratory disease by 2.7%/year (95% CI, 2.0- 3.3%/yr; P < 0.001) and for lung cancer by 3.4%/year (95% CI, 1.1-5.7%/yr; P = 0.004). CONCLUSIONS: In oxygen-dependent COPD, mortality has increased over time both overall and of nonrespiratory causes, including cardiovascular disease. This highlights the importance of optimized diagnostics and treatment of comorbidities to decrease morbidity and mortality.

Increased relative mortality in women with severe oxygen-dependent COPD.

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.