Chronic Respiratory Disease

Aims: Benefits of long acting beta 2 agonists are unclear for severe chronic obstructive pulmonary disease (COPD) patients with poor response to short acting bronchodilators. We aimed to evaluate 1) effects of eformoterol in such patients using a ‘n-of-1’ double crossover study design, and 2) aggregate data as a double-blind, double crossover randomized control trial. Methods: Subjects with forced expiratory volume in one second (FEV₁) < 60% predicted, and poor response to short acting bronchodilators were studied six times over 18 weeks. During that time they were prescribed four weeks of either eformoterol or placebo, followed by the alternate, and then a second crossover. Four-weekly measures included six minute walk distance (6MWD), FEV₁, previous two weeks of symptoms, and chronic respiratory questionnaire (CRQ) including treatment goal items. Results: Of 27 original subjects (21 male, mean age of 70 years, five smokers, mean prebronchodilator FEV₁, 36% predicted), one subject had clinically significant concordant improvement in the CRQ dyspnoea domain and 6MWD (by 51 metres), but not for other outcomes. There were no concordant improvements in any other subjects. Aggregate double crossover data analysis demonstrated no improvement in any outcome measures. Conclusions: The ‘n-of-1’ study design and aggregate data analysis demonstrated lack of benefit from eformoterol in COPD patients with poor response to short acting bronchodilators.

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 > 25 kg/mi²), 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.

Background: Detailed polysomnography (PSG) and overnight continuous positive airway pressure (CPAP) titration as the basis for investigation and treatment of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) incurs high costs from inpatient stays and technician attendance, even when split night studies are employed. Responding to rapidly increasing demand, from 1996 the sleep service at Glasgow Royal Infirmary adopted limited sleep studies and daycase CPAP titration as first line management. Here we describe the outcomes of this service between 1996 and 1999. Methods: Data were collected from prospective records made at follow up by sleep technicians and by casenote review. Results: Results were available for 158 subjects (97.5%) of 162 commenced on CPAP during this period. One hundred and forty-eight (91%) were diagnosed by limited sleep studies and 80 (50%) were diagnosed at home. The median follow up was 23 months (interquartile range (IQR), 13-35). Median use of CPAP in those continuing therapy was 5.3 hours/night (IQR, 3.1 to 6.5) and 77% were still using CPAP at three years. Only initial low CPAP compliance (< 2 hours/night) significantly predicted early CPAP cessation. In those still on CPAP in 1999, the mean drop in Epworth Sleepiness Scale score was 4.6 points (95% confidence intervals, 3.2 to 6.0). Conclusion: These data from the CPAP population at Glasgow Royal Infirmary provide information on longterm outcomes using a diagnostic protocol based on limited sleep studies and daycase CPAP titration.

Background: Exercise limitation is a hallmark of chronic obstructive pulmonary disease (COPD) and is integral to the associated impaired health status of these patients. The poor exercise tolerance is multifactorial in origin, relating to airflow obstruction, disadvantageous lung mechanics, reduced oxygen delivery and skeletal muscle dysfunction. A number of interventions have been studied to determine whether they can impact on exercise performance. The most evidence-based of these is exercise training, which along with other approaches, both previously investigated and putative, are discussed in this review.

Background: Increasingly, molecular genetic techniques are being used to improve our understanding of a number of common late onset complex disorders, such as hypertension, Alzheimer's disease' and noninsulin dependent diabetes mellitus⁷. Molecular genetic approaches have the potential to yield new information about disease pathogenesis that may be of great importance for the development of future treatments. Aims: This review discusses the evidence for a genetic contribution to the development of chronic obstructive pulmonary disease (COPD) and specifically focuses on the hypothesis that asthma and COPD share some pathogenic mechanisms as originally proposed in 1960 in a theory that has since become known as the Dutch Hypothesis.³ In particular we will review the evidence from molecular genetics, both in support of and against the theory.

Background:Many deaths are now preceded by an end of life decision, particularly in the intensive care unit (ICU), but such practices vary considerably between countries, ICUs and individuals, depending on many factors including cultural and religious background, family and peer pressure and local practice. Aims:In this review, we will discuss the application of the four key ethical principles-beneficence, nonmaleficence, autonomy and distributive justice - to withdrawing/withholding decisions. Methods: Drawing data from several national and international studies, we then summarize the current situation across Europe regarding such practices before making some suggestions as to how we could facilitate the often difficult decision making process by improved communication between staff, patient and relatives.