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Concept: Chronic obstructive pulmonary disease


Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient.Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, carbon monoxide diffusion capacity and arterial blood gases. Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model.604 patients were included (mean age 61.9±9.7 years, forced expiratory volume in 1 second 37±18.1%predicted, 62.9% males); 229(37.9%) died during a median follow-up of 83 months. Median survival was 91.9(80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively. Carbon monoxide diffusion capacity %predicted quartiles [(best quartile (>51%): HR=: 0.33; 95% CI: 0.96-0. and second quartile (51-37.3%): HR=0.52, versus lowest quartile (<27.9%))], age (HR=:1.04; 95% CI:1.02-1.06) and arterial oxygen partial pressure (HR=: 0.85;95% CI:0.77-0.94) were the only parameters independently associated with mortality.Measurement of diffusion capacity provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.

Concepts: Oxygen, Pulmonology, Asthma, Lung, Respiratory physiology, Chronic obstructive pulmonary disease, Spirometry, Respiratory therapy


The presence of acute or chronic respiratory failure is often seen as a terminal phase of chronic obstructive pulmonary disease. A great variability in end-of-life practice is observed in these patients mainly because physicians are not always able to correctly predict survival. There is a need for a clear discussion about decision making earlier than when acute respiratory failure ensues. Indeed, a perceived poor quality of life does not necessarily correlate with a clear willingness to refuse invasive or noninvasive mechanical ventilation. It has been suggested to start palliative care earlier, together with curative and restorative care, when there is an increased intensity of symptoms. The patients eligible for palliative care are those complaining of breathlessness, pain, fatigue and depression, which in some studies accounted for a prevalence much higher than 50%. Among comfort measures for palliation, oxygen is frequently prescribed even when the criteria for long-term home oxygen therapy are not met; however, when compared with air, no benefits on dyspnoea have been found. The only drug with a proven effect on dyspnoea is morphine, but not when it is delivered with a nebuliser. Finally, noninvasive ventilation may be used only as a comfort measure for palliation to maximise comfort by minimising adverse effects.

Concepts: Pulmonology, Pneumonia, Mechanical ventilation, Palliative care, Chronic obstructive pulmonary disease, Palliative medicine, End-of-life care, Terminal sedation


Pre-clinical data demonstrate a pivotal role for interleukin (IL)-13 in the development and maintenance of asthma. This study assessed the effects of tralokinumab, an investigational human IL-13-neutralising immunoglobulin G4 monoclonal antibody, in adults with moderate-to-severe uncontrolled asthma despite controller therapies. 194 subjects were randomised to receive tralokinumab (150, 300 or 600 mg) or placebo subcutaneously every 2 weeks. Primary end-point was change from baseline in mean Asthma Control Questionnaire score (ACQ-6; ACQ mean of six individual item scores) at week 13 comparing placebo and combined tralokinumab dose groups. Secondary end-points included pre-bronchodilator lung function, rescue β(2)-agonist use and safety. Numerical end-points are reported as mean±sd. At week 13, change from baseline in ACQ-6 was -0.76±1.04 for tralokinumab versus -0.61±0.90 for placebo (p=0.375). Increases from baseline in forced expiratory volume in 1 s (FEV(1)) were 0.21±0.38 L versus 0.06±0.48 L (p=0.072), with a dose-response observed across the tralokinumab doses tested. β(2)-agonist use (puffs per day) was decreased for tralokinumab -0.68±1.45 versus placebo -0.10±1.49 (p=0.020). The increase in FEV(1) following tralokinumab treatment remained evident 12 weeks after the final dose. Safety profile was acceptable with no serious adverse events related to tralokinumab. No improvement in ACQ-6 was observed, although tralokinumab treatment was associated with improved lung function.

Concepts: Immune system, Pulmonology, Asthma, Lung, Respiratory physiology, Chronic obstructive pulmonary disease, Spirometry, Peak flow meter


Adoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring.

Concepts: Psychology, Osteoporosis, Medicine, Asthma, Pneumonia, Chronic obstructive pulmonary disease


BACKGROUND: Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future. Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes. We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes. METHODS: Breath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry. Subjects with COPD also underwent sputum induction. Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis. RESULTS: Comparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance. Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%. The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74. Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy. Models were constructed which classified subjects with [GREATER-THAN OR EQUAL TO]2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95. Potential biomarkers correlated to clinical variables were identified in each subgroup. CONCLUSION: The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups. If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease.

Concepts: Medicine, Asthma, Pneumonia, Multivariate statistics, Chronic obstructive pulmonary disease, Volatile organic compound, Organic compounds, Linear discriminant analysis


BACKGROUND: Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy. METHODS: We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables. RESULTS: An increase in ozone (O3) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2), CO, nitrate dioxide (NO2), and particulate matter (PM10 and PM2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association. CONCLUSIONS: Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.

Concepts: Pulmonology, Chronic obstructive pulmonary disease, Respiratory system, Pollution, Particulate, Smog, Air pollution, Acid rain


BACKGROUND: Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients' quality of life. METHODS: This study aimed to assess the efficacy of a 3-month Pulmonary Rehabilitation (PR) program with a further 9 months of maintenance (RHBM group) compared with both PR for 3 months without further maintenance (RHB group) and usual care in improving the quality of life of patients with moderate COPD.We conducted a parallel-group, randomized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups. Health outcomes were quality of life, exercise capacity, pulmonary function and exacerbations. RESULTS: We found statistically and clinically significant differences in the three groups at 3 months in the emotion dimension (0.53; 95%CI0.06-1.01) in the usual care group, (0.72; 95%CI0.26-1.18) the RHB group (0.87; 95%CI 0.44-1.30) and the RHBM group as well as in fatigue (0.47; 95%CI 0.17-0.78) in the RHBM group. After 1 year, these differences favored the long-term rehabilitation group in the domains of fatigue (0.56; 95%CI 0.22-0.91), mastery (0.79; 95%CI 0.03-1.55) and emotion (0.75; 95%CI 0.17-1.33). Between-group analysis only showed statistically and clinically significant differences between the RHB group and control group in the dyspnea dimension (0.79 95%CI 0.05-1.52). No differences were found for exacerbations, pulmonary function or exercise capacity. CONCLUSIONS: We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL, exercise tolerance, pulmonary function or exacerbation after a one-year, community based rehabilitation program. However, long-term improvements in the emotional, fatigue and mastery dimensions (within intervention groups) were identified.Trial registration: ISRCTN94514482.

Concepts: Health care, Medicine, Epidemiology, Clinical trial, Asthma, Pneumonia, Randomized controlled trial, Chronic obstructive pulmonary disease



BACKGROUND: There has been a large increase in treatment and in research on chronic obstructive pulmonary disease (COPD) from the common starting point of the original Global Initiative for Chronic Obstructive Lung Disease (GOLD) study. There is currently little evidence on the degree of similarity and difference between national programmes or on the linkage between research and policy. AIMS: To review the evidence on programme development and the effectiveness gap from the UK, France, Germany, and Finland. METHODS: Visits and literature reviews were undertaken for regional centres in Lancashire, Nord-Pas de Calais, and Finland, and Eurostat data on mortality and hospital discharges were analysed. And telephone interviews in Nord-Rhein Westphalia. RESULTS: There have been very significant differences in programme development from the original GOLD starting point. The UK has national strategies but they are without consistent local delivery. The French Affection de Longue Durée (ALD) programme limits special help to at most 10% of patients and there is little use of spirometry in primary care. Germany has a more general Disease Management Programme with COPD as a late starter. Finland has had a successful 10-year programme. The results for the effectiveness gap on hospital discharges show a major difference between Finland (40.7% fall in discharges) and others (increases of 6.0-43.7%). CONCLUSIONS: The results show the need for a simpler programme in primary care to close the effectiveness gap. Such a programme is outlined based on preventing the downward spiral for high-risk patients.

Concepts: Pulmonology, Asthma, Pneumonia, Chronic obstructive pulmonary disease, Spirometry, Obstructive lung disease, Respiratory diseases, The Downward Spiral


BACKGROUND: The severity of chronic obstructive pulmonary disease (COPD) should not be based on the level of airflow limitation alone. A multicomponent index such as the DOSE index (dyspnoea score (D), level of airflow obstruction (O), current smoking status (S), and exacerbations (E)) has the potential to predict important future outcomes in patients with COPD more effectively than the forced expiratory volume in one second. Health status deterioration should be prevented in COPD patients. AIMS: To investigate whether the DOSE index can predict which patients are at risk of a clinically relevant change in health status. METHODS: A prospective cohort study was performed using data from primary and secondary care. The DOSE score was determined at baseline and the 2-year change in the Clinical COPD Questionnaire (CCQ) score was calculated. Linear regression analysis was performed for the effect of a high DOSE score (≥4) on the change in CCQ score. RESULTS: The study population consisted of 209 patients (112 patients from primary care). Overall, a high DOSE score was a significant predictor of a change in CCQ score after 2 years (0.41, 95% CI 0.13 to 0.70), particularly in primary care patients. CONCLUSIONS: A DOSE score of ≥4 has the ability to identify COPD patients with a greater risk of future worsening in health status.

Concepts: Regression analysis, Linear regression, Epidemiology, Clinical trial, Asthma, Chronic obstructive pulmonary disease, Primary care, Forecasting