Standardised mortality rates in females and males with COPD and asthma.

Mortality studies of males and females with chronic obstructive pulmonary disease (COPD) and asthma have suggested that females have a poorer prognosis than males, but the results are either not unanimous or based on poorly characterised patients. The current study analysed the mortality of 279 asthma patients and 869 COPD patients, who were seeking pension due to disability, and compared mortality rates with expected rates derived from the general population. The mean follow-up period was 13.3 yrs (range 2.5-22.4 yrs) during which time 96 (34.4%) and 671 (77.2%) deaths were identified among asthma and COPD patients, respectively. The average age at study entry was 46.8 and 56.6 yrs, and the average forced expiratory volume in one second (FEV1) was 68.8 and 44.1 % predicted in the two diagnostic groups. After adjustment for predictors of survival (age, FEV1 % predicted, chronic bronchitis, body mass index, smoking status, oral prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of death was 1.21 (95% confidence interval: 0.77-1.89) and 0.98 (0.83-1.16) in females compared with males, in asthma and COPD patients, respectively. The standardised mortality rate (SMR) for males was 1.54 (1.10-2.09) and 2.7 (2.5-3.0), and for females 1.91 (1.44-2.49) and 4.8 (4.2-5.4), in asthma and COPD patients, respectively. Direct comparison of the SMR of males and females showed that females had higher mortality than males, with a rate ratio of 1.24 (0.82-1.84) and 1.8 (1.5-2.0), in asthma and COPD patients, respectively. Poisson regression analysis with control for the confounders did not change this result. Females and males with the same level of obstructive lung disease appear to have the same level of mortality. However, using standardised mortality rates, females have a higher mortality than males, suggesting that the protective effect of being female is lost in chronic obstructive pulmonary disease patients.

BMI and oral glucocorticoids as predictors of prognosis in COPD patients on long-term oxygen therapy.

AIMS: The objectives of the study were to determine whether body mass index (BMI), and oral corticosteroid use predict survival and hospitalization in hypoxaemic chronic obstructive pulmonary disease (COPD) patients. METHODS: The study was a prospective cohort study with analysis of a nationwide database (Danish Oxygen Register). We studied survival and hospitalization in 221 hypoxaemic COPD patients who were on long-term oxygen therapy (LTOT). RESULTS: Low BMI was strongly associated with high mortality (P < 0.001). Maintenance treatment with steroids was only associated with higher mortality in overweight patients (BMI > or = 25 kg/m2), RR = 3.8 (1.4-10.5), P = 0.011. Whereas BMI had no influence on risk of any hospitalization in patients using oral steroids, high BMI was independently associated with reduced risk of any hospitalization in patients without oral steroids [the RR of any hospitalization for each 1 kg/m2 increase in BMI was 0.94 (CI: 0.90-0.99), P = 0.009]. Overall, the use of oral steroids was associated with increased risk of any hospitalization, RR = 1.7 (1.2-2.4), P = 0.002. This increase was especially pronounced in the group with BMI above 25 kg/m2, where steroid treatment increased the risk of any hospitalization with RR = 3.6 (1.5-8.7), P = 0.005. CONCLUSIONS: In hypoxaemic patients on LTOT, low BMI is an independent risk factor of death and any hospitalization. Maintenance treatment with oral corticosteroids is associated with increased mortality and hospitalization in COPD patients with high BMI. Our findings suggest that loss of body weight should be avoided, and that oral corticosteroids should be used cautiously in patients on LTOT--especially those with high BMI. Further research on the role of changes in body composition as a prognostic factor is needed.

Is there any association between inhaled ipratropium and mortality in patients with COPD and asthma?

BACKGROUND: To determine whether ipratropium was associated with premature death in patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: A longitudinal cohort of 827 patients with COPD and 273 with asthma who were evaluated for compensation by two specialists in pulmonary medicine. RESULTS: By June 1999, 538 of the patients with COPD and 77 of those with asthma had died. Atthe consultation, 77% ofthe COPD patients and 8.1% of the asthmatic patients were treated with inhaled ipratropium. Ipratropium was associated with mortality risk ratio (RR) of 2.0 (95% confidence interval: 1.5-2.6) for COPD and 3.6 (1.8-7.1) for asthma patients. After adjustment for confounding factors [forced expiratory volume 1 s (FEV1), smoking habits, asthma medication, and presence of cor pulmonale] the RR for COPD was 1.6 (1.2-2.1) and for asthma 24 (1.2-5.0). CONCLUSIONS: The increased risk of premature death associated with ipratropium is of concern and necessitates further evaluation, e.g., in a randomised study.

Does long-term oxygen therapy reduce hospitalisation in hypoxaemic chronic obstructive pulmonary disease?

The aim of this study was to determine whether long-term oxygen therapy (LTOT) reduces hospitalisation in hypoxaemic patients with chronic obstructive pulmonary disease (COPD). The circumstances of initiation of LTOT (start during hospitalisation versus start as an outpatient) and compliance with oxygen were also investigated (continuous oxygen therapy (COT) > or = 15 h daily versus noncontinuous oxygen therapy (NCOT) <15 h daily). A total 246 COPD patients were studied, with each patient acting as their own control. Patients were divided into four groups: 125 patients on COT who started LTOT in conjunction with hospitalisation, 37 patients on COT who started LTOT as outpatients, 58 patients on NCOT who started LTOT in conjunction with hospitalisation and 26 patients on NCOT who started LTOT as outpatients. Admission rates, days spent in hospital and number of patients with at least one hospitalisation (ever hospitalised) were compared in two periods of 10 months before and after initiation of LTOT. Overall during the LTOT period, in comparison with the preoxygen period, the admission rates, hospital days and "ever hospitalised" were reduced by 23.8%, 43.5% and 31.2%, respectively. Among patients who started LTOT as outpatients, a tendency towards a higher effect in the compliant group was observed. This study shows that in hypoxaemic chronic obstructive pulmonary disease patients, long-term oxygen therapy is associated with a reduction in hospitalisation.

[Reliability of recorded deaths from asthma in Denmark during a 1-year period 1994-1995]. / Pålideligheden af registrerede asthmadødsfald i Danmark i en 1-års-periode 1994-1995.

INTRODUCTION: The aim of this study was to evaluate the accuracy of death certificates over a one-year period, where asthma was given as the cause of death. METHODS: All medical information available was collected on 218 patients by reviewing hospital records, records from general practitioners, and sometimes by interviewing close relatives. A panel of four pulmonologists each examined the information and independently assessed the cause of death. RESULTS: Thirty-nine were excluded, as the cause of death could not be validated. In 16 (9%) of the subjects, asthma was judged to be the definite cause of death and in 12 (7%) a possible cause. Of 151 non-asthma deaths, but registered as asthma, 109 were judged to have suffered or died from COPD and 14 from heart disease. DISCUSSION: The accuracy of Danish death certification in asthma deaths is poor, especially in the elderly, where COPD is often classified as asthma. We conclude that the true mortality from asthma in Denmark is substantially lower than that officially recorded.

Are patients on long-term oxygen therapy followed up properly? Data from the Danish Oxygen Register.

OBJECTIVES: The aim of the study was to assess the extent and quality of follow-up of patients on LTOT. SETTING: The Danish Oxygen Register. SUBJECTS: A total of 890 chronic obstructive pulmonary disease (COPD) patients who were on long-term oxygen therapy (LTOT) during the period from 1 November 1994 to 31 August 1995. MAIN OUTCOME MEASURES: The extent and quality of follow-up. RESULTS: Only 38.5% of the patients were followed up in the study period, and only 17.5% had a 'sufficient follow-up' defined as at least one follow-up visit within 10 months which included measurement of arterial blood gases or pulsoximetry with oxygen supply, verification that the patient used oxygen > or =15 h day-1 and was nonsmoker. Female gender, LTOT initiated 3-12 months ago, LTOT started by a chest physician at pulmonary department and LTOT prescribed > or =15 h day-1 were found to be significant predictors of 'sufficient follow-up' (odds ratio (OR): 1.7, 2.0, 3.7 and 1.9, respectively). CONCLUSIONS: The extent and the quality of follow-up of patients on LTOT were poor, especially if a nonpulmonary physician initiated LTOT. We recommend that more attention should be paid on proper monitoring of LTOT, and that only chest physicians should be able to prescribe and re-evaluate LTOT.

Has the perception of disability among COPD patients applying for pension changed during the last 20 years?

The aim is to examine the change in lung function, treatment and pulmonary symptoms in patients with chronic obstructive pulmonary disease (COPD) or chronic bronchitis (CB) applying for a pension during the period 1977-1996. In addition, we compared the perception of disability in males and females. From 1977 to 1996, 947 patients with COPD or CB were evaluated for obtaining economic support due to disability. In order to test the trend, the patients were divided into three periods: (1) 1977-1983, (2) 1984-1989 and (3) 1990-1996. Compared to females, males had substantial more pack-years of smoking (36 vs. 28, P<0.001), but their FEV1 was only slightly decreased (46.9% versus 49.6% predicted, P=0.047). Females reported significantly more often attacks of dyspnoea [OR: 1.5(1.00-2.2)] and any kind of dyspnoea during daytime [OR: 4.0(1.2-13.3)]. From period 1 to period 3, FEV1 increased significantly (45-53% predicted, P<0.001). Despite the increased FEV1, the use of inhaled corticosteroid had increased markedly (9-32% of the patients, P<0.001). The results did not change when patients with asthma were included. Our data suggest that both sexes, especially females, have become more aware of pulmonary symptoms and tend to react to them more actively by demanding evaluation and treatment.

Geographic variation in long-term oxygen therapy in Denmark : factors related to adherence to guidelines for long-term oxygen therapy.

STUDY OBJECTIVES: To evaluate regional differences in adherence to guidelines for long-term oxygen therapy (LTOT) in Denmark and to determine factors related to compliance with these guidelines. DESIGN: Cross-sectional study and analysis of a nationwide database (Danish Oxygen Register). SETTING: Denmark. PATIENTS: In November 1994, 1,354 COPD patients were receiving LTOT in Denmark. MEASUREMENTS AND RESULTS: Among 16 counties, the prevalence of LTOT for COPD varied from 14 to 53 per 100,000. The prevalence was highest in counties where general practitioners (GPs) were prescribing LTOT. Adherence to national guidelines for LTOT was found in 34.4% of the patients for the whole of Denmark and varied regionally from 14 to 63%. Mean compliance with guidelines was 5.3 (range, 2.9 to 9.1) times as likely if the oxygen was prescribed by a pulmonary department compared to LTOT initiated by a GP. CONCLUSIONS: Marked geographic variations in compliance with LTOT guidelines are present even in a small country as Denmark. In general, the adherence to the guidelines is poor, especially when non-chest physicians prescribe LTOT. We therefore recommend that local and national thoracic societies together with health organizations responsible for treatment should play a more forceful role in implementing the guidelines. This could be done by enhanced educational efforts, by monitoring of adherence, or even by centralizing the prescription right to departments with pulmonary physicians.

Non-continuous home oxygen therapy: utilization, symptomatic effect and prognosis, data from a national register on home oxygen therapy.

About half of all patients on home oxygen therapy receive non-continuous oxygen therapy (less than 15 h daily) (NCOT). The goal of NCOT is to improve well-being during daily activities and to improve sleep quality. The aim of this study was to evaluate the effect of NCOT on pulmonary symptoms and sleep quality, and to determine whether patients with a subjective beneficial effect differed from those without effect in terms of patients' characteristics, utilization of oxygen, hospitalization and survival. Furthermore, the relationship between the reported beneficial effect of NCOT on dyspnoea and physical activity during domestic activities was examined. During the period November 1994 to July 1995, 254 Danish patients were prescribed oxygen less than 12 h daily or 'on demand'. Of these patients, 142 (55.9%) answered a questionnaire on hours spent with oxygen and symptomatic effect of oxygen treatment. While on oxygen, 76.3% of the patients reported improved dyspnoea score (0-10) more than 0.5 points, 78.3% had improved quality of life, 59.5% improved sleep, 48.5% increased physical activity, 49.3% felt less tired and 40.0% reported improved thinking. Fifty-seven (43.2%) patients reported both improved dyspnoea and physical activity whereas seven (5.3%) patients reported that oxygen had no effect on dyspnoea but a beneficial effect on physical activity Only 11 (7.7%) patients reported no subjective improvement on oxygen. The subjective effect of NCOT was not significantly associated to hours spent with oxygen. the underlying disease, gender, hospitalization or survival. During daily activity and regardless of daily number of hours spent with oxygen, NCOT improved well-being in nearly all patients. The most pronounced improvement was reported on dyspnoea, sleep and quality of life. Very few patients sensed improved physical activity without relief in breathlessness.

[Tuberculosis in immigrants]. / Tuberkulose hos indvandrere.

Three cases of tuberculosis in immigrants are described here. The manifestations of tuberculosis in this group are often different from those seen in Danes--in casu tuberculosis of the lymph nodes, skin, bone, and intestines. Diagnosis is difficult, as Danish doctors are not familiar with the clinical picture. Language problems are common and often necessitate the presence of an interpreter. Immigrants tend to move around without notifying the responsible doctor and the resources needed to find them may not be readily available. These factors may cause a considerable delay--from months to years--in the diagnosis and treatment. Doctors examining immigrants from Africa and Asia should be aware of tuberculosis as a possible cause of disease. Secretion and biopsies from fistulae, chronic ulcerations, lymph nodes, and abscesses should always be cultured for Mycobacterium tuberculosis. The Mantoux reaction can be misleadingly negative in patients suffering from severe tuberculosis. Identification of Mycobacterium tuberculosis is not necessary for treatment--that decision is made on the clinical picture. On the other hand material for a bacteriological diagnosis should always be obtained, because of possible resistance problems.

Accuracy of recorded asthma deaths in Denmark in a 12-months period in 1994/95.

Many studies of asthma mortality rely on official registration. The aim of this study was to evaluate the accuracy of death certificates, where asthma was coded as cause of death. In a 12-month period, medical information on all subjects with asthma officially coded as the underlying cause of death in Denmark, was obtained by reviewing hospital records, contacting general practitioners and sometimes close relatives. A panel of four pulmonologists each examined the obtained information and independently assessed the cause of death. Of a total of 218 death certificates, 39 were excluded as the cause of death could not be validated. In 16 (9%) of the subjects death from asthma was judged to be the definite cause of death and in 12 (7%) death from asthma was possible. Of 151 non-asthma deaths coded as due to asthma, 109 were judged to have suffered or died from COPD and 14 from heart disease. The accuracy of Danish death certification in asthma deaths is poor, especially in the elderly, where COPD is often classified as asthma. We conclude that the true asthma mortality in Denmark is substantially lower than officially recorded.

[Long-term effect of inhaled budesonide in patients with mild to moderate chronic obstructive lung disease. The Osterbro Study]. / Langtidsvirkningen af inhaleret budesonid hos patienter med mild og moderat kronisk obstruktiv lungesygdom. Osterbro lunge studie.

We compared the effect of inhaled budesonide with placebo on decline in lung function and respiratory symptoms in a three-year study of patients with chronic obstructive pulmonary disease (COPD). We used a parallel-group, randomized, double-blind, placebo-controlled design, nested in an ongoing epidemiological survey. Patients were non-asthmatic subjects with a decreased ratio between forced expiratory volume in one second (FEV1) and vital capacity (VC); i.e., FEV1/VC < or = 0.7. All included patients had an FEV1 which was irreversible to both inhaled terbutaline and prednisolone. Two hundred and ninety patients were randomized to receive either budesonide, 1200 mcg. daily for six months followed by 800 mcg. daily for 30 months, or placebo for 36 months. Patients had a mean age of 59 years and their mean FEV1 was 2.37 liters or 86% of predicted. Crude FEV1 declines were 41.8 ml/year in the placebo group and 45.1 ml/year in the budesonide group. Using a regression model in the intention-to-treat population, patients in the placebo group had an FEV1 decline of 49.1 ml/year in contrast to 46.0 ml/year in the budesonide group; the estimated difference 3.1 ml/year (95% confidence interval--12.8-19.0) was statistically insignificant, p = 0.70. No effect of inhaled budesonide was seen on respiratory symptoms or number of exacerbations. These findings question the role of longterm inhaled corticosteroids in the treatment of mild-moderate COPD.

A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-antitrypsin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evening at home showed no significant difference in decline of FEV(1) between treatment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alpha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV(1) showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

Compliance with LTOT and consumption of mobile oxygen.

The aim of the study was to investigate compliance with long-term oxygen therapy (LTOT), the consumption of mobile oxygen and factors that might influence on these measures. The study included 182 patients with LTOT and 125 patients answered a questionnaire on daily activities. Information on arterial gas tension, lung function, and diagnosis was obtained from the medical file. Data on oxygen systems and the actual usage of oxygen were obtained from the oxygen suppliers. Seventy-six per cent of the patients had a concentrator and 35% had both stationary and mobile oxygen. Good compliance (use of oxygen > 15 h day-1) was seen in 65%. Of the tested factors, only mobile oxygen had an influence on the effective usage. Outdoor activity was reported in 65% of the patients. Only 48% of these patients had mobile units, while 21% of the home-bound patients had mobile units. Of the patients with mobile oxygen, only 39% used their mobile unit > 2 h week-1. Poorer usage of stationary oxygen was observed in patients with outdoor activity (2.4 hours day-1 less). Although only 16 (13%) patients reported a usage less than 15 h day-1, the actual consumption was less than 15 h day-1 in 29%. In conclusion, patients on LTOT tended to overestimate their oxygen usage. Acceptable compliance was observed in 65% of the patients. Only mobile oxygen had a significant impact on the overall compliance. As more patients had outdoor activities than expected, and as these activities had a negative impact on the usage of stationary oxygen, more attention must be paid on detecting outdoor activities. However, as fewer than half of the patients with outdoor activity and mobile oxygen used their mobile systems, there is a need for measures to improve compliance with mobile oxygen. Using lists referring to the actual usage and discussing the usage with the patients may improve the compliance and cost-benefit.

Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.

BACKGROUND: Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD. METHODS: We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0.7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat. FINDINGS: The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year, budesonide group 45.1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49.1 mL vs 46.0 mL per year; difference 3.1 mL per year [95% CI -12.8 to 19.0]; p=0.7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated. INTERPRETATION: Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.

Diagnostic and therapeutic process and prognosis in suspected lung cancer.

Survival rates of patients with lung cancer are poor in Denmark and worse than in the other Nordic countries. The study focuses on the diagnostic process, the selection for operation, prognostic factors and outcome in lung cancer. The study comprised 467 consecutive patients with cancer-suspect lesions. In 40% of cases the diagnostic delay exceeded 30 days. Fibreoptic bronchoscopy and fine-needle biopsy (FNB) were the most important diagnostic tests, with approximately 90% accuracy in central and peripheral lesions. FNB of peripheral lesions diagnosed benign histology or small cell lung cancer (SCLC) in 16 patients, and due to that procedure a thoracotomy was prevented. Surgery was performed on 83 (33%) of 252 patients with non-small cell lung cancer. Three-year survival was 37% in all surgically treated patients and 64% after radical operation; 59% of the patients with stage I tumours were alive after three years, but none with stage IV at diagnosis. Among patients operated on, preoperated forced expiratory volume (FEV1) was related to survival rate. Survival rates were higher in women than in men with or without surgery. Of 43 patients with SCLC, 32 received chemotherapy, and half of these were alive after one year. Conclusions from the study were that diagnosis should be speeded up and that diagnostic FNB of peripheral lesions is of value for preventing unnecessary operations. Standard registration of tumour, node, metastasis (TNM) classification, resection, FEV1 (% of predicted) and gender could increase the validity of international comparisons.

Fibrous pleural tumour producing 171 litres of transudate.

Localized fibrous tumours of the pleura (or localized benign mesothelioma) are rare, and in most cases, asymptomatic. This report describes a 48 yr old female with a right-sided fibrous pleural tumour, which produced 171 L of transudate before a correct diagnosis was reached. The tumour was surgically removed and the transudation stopped immediately.