A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention.</p> <p>Method</p> <p>The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee.</p> <p>Discussion</p> <p>Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R²of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981851">NCT00981851</a></p

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)

The Effects of Sleep Hypoxia on Coagulant Factors and Hepatic Inflammation in Emphysematous Rats

OBJECTIVES: To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver. METHODS: Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis. RESULTS: Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively. CONCLUSIONS: When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

<p>Abstract</p> <p>Background</p> <p>To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.</p> <p>Methods</p> <p>Epidemiologic, observational, and descriptive study (EPIDEPOC study). Patients ≥ 40 years of age with stable COPD attending primary care settings were included. Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected. Results were compared between patients with or without associated heart disease.</p> <p>Results</p> <p>A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males. When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease. Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease. Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases. The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05. Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.</p> <p>Conclusion</p> <p>Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease.</p

More Evidence that Depressive Symptoms Predict Mortality in COPD Patients: Is Type D Personality an Alternative Explanation?

The present study attempted to replicate our previous finding that depressive symptoms are a risk factor for mortality in stable chronic obstructive pulmonary disease (COPD), but in a different population with a different measure of depressive symptoms. We further investigated whether type D personality is associated with mortality in patients with COPD and whether it explains any relationship observed between depressive symptoms and mortality. In 122 COPD patients, mean age 60.8 +/- 10.3 years, 52% female, and mean forced expiratory volume in 1 s (FEV(1)) 41.1 +/- 17.6%pred, we assessed body mass index, post bronchodilator FEV(1), exercise capacity, depressive symptoms with the Hospital Anxiety and Depression Scale, and type D with the Type D Scale. In the 7 years follow-up, 48 (39%) deaths occurred. The median survival time was 5.3 years. Depressive symptoms (hazard ratio = 1.07, 95% confidence intervals = 1.00-1.14) were an independent risk factor for mortality. Type D was not associated with mortality. We can rule out type D as an explanation for the relationship between depressive symptoms and mortality observed in this sample. However, ambiguity remains as to the interpretation of the value of depressive symptoms in predicting death