Physical activity and risk of all-cause and cardiovascular disease mortality in diabetic adults from Great Britain: pooled analysis of 10 population-based cohorts

OBJECTIVE To examine associations between specific types of physical activity and all-cause and cardiovascular disease (CVD) mortality in a large nationally representative sample of adults with diabetes from Great Britain. RESEARCH DESIGN AND METHODS There were a total of 3,038 participants (675 deaths) with diabetes in the Health Survey for England and the Scottish Health Surveys conducted between 1997 and 2008. Participants aged ‡50 years at baseline were followed up for an average of 75.2 months for all-cause and CVD mortality. Data were collected on selfreported frequency, duration, and intensity of participation in sports and exercise, walking, and domestic physical activity, from which the number of MET-hours/ week were derived. Sex-specific medians of time spent in each type of physical activity (for those physically active)were calculated, and Cox proportional hazards regression conducted to examine type-specific associations between the level of physical activity and all-cause and CVD mortality risk. RESULTS Inverse associations with all-cause and CVD mortality were observed for overall physical activity in a dose-response manner after adjusting for covariates. Compared with those who individuals were inactive, participants who reported some activity, but below the recommended amount, or who met the physical activity recommendations had a 26% (95%CI 39–11) and 35%(95% CI 47–21) lower all-cause mortality, respectively. Similar results were found for below/above median physical activity levels. Sports and exercise participation was inversely associated with all-cause (but not CVD)mortality, as were above average levels of walking. Domestic physical activity was not associated with mortality. CONCLUSIONS Moderate physical activity levels were associated with better prognosis in diabetic adults

Seasonality, risk-factors and burden of community-acquired pneumonia in COPD patients: A population database study using linked healthcare records

Community acquired pneumonia (CAP) is more common in patients with chronic obstructive pulmonary disease (COPD) than in the adult general population, with studies of hospitalised CAP consistently reporting COPD as a frequent comorbidity. However, despite an increasing recognition of its importance, large studies evaluating the incidence patterns over time, risk-factors and burden of CAP in COPD are currently lacking.A retrospective observational study using a large UK-based database of linked primary and secondary care records was conducted. Patients with a diagnosis of COPD aged ?40 years were followed for 5 years from the 1st January 2010. CAP and exacerbation episodes were identified from hospital discharge data and primary care coding records, and rates were calculated per month, adjusting for mortality, and displayed over time. In addition, baseline factors predicting future risk of CAP and hospital admission at CAP, were identified. 14513 COPD patients were identified: 13.4% (n=1938) had ?1 CAP episode, of whom 18.8% suffered from recurrent (?2) CAP. Highest rates of both CAP and exacerbations were seen in winter. A greater proportion of frequent, compared to infrequent exacerbators experienced recurrent CAP (5.1% versus 2.0% respectively, p&lt;0.001) 75.6% of CAP episodes were associated with hospital admission compared to 22.1% of exacerbations. Older age and increasing grade of airflow limitation were independently associated with increased odds of CAP and hospital admission at CAP. Other independent predictors of future CAP included lower body mass index, inhaled-corticosteroid use, prior frequent exacerbations and comorbidities including ischaemic heart disease and diabetes. CAP in COPD demonstrates clear seasonal patterns, with patient characteristics predictive of the odds of future CAP and hospital admission at CAP. Highlighting this burden of COPD-associated CAP during the winter period, informs us of the likely triggers and the need for more effective preventive strategies.<br/

Are sitting occupations associated with increased all-cause, cancer, and cardiovascular disease mortality risk? A pooled analysis of seven British population cohorts

Background: There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts. Methods: The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, nonoccupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education. Results: In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity. Conclusions: Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women

Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function.METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types.RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs.CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism.TRIAL REGISTRATION: Trial registration number NCT01701869

Physical Activity and Risk of All-Cause and Cardiovascular Disease Mortality in Diabetic Adults From Great Britain: Pooled Analysis of 10 Population-Based Cohorts

This is an Open Access Article. It is published by American Diabetes Association under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported (CC BY-NC-ND 3.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-nc-nd/3.0/OBJECTIVE To examine associations between specific types of physical activity and all-cause and cardiovascular disease (CVD) mortality in a large nationally representative sample of adults with diabetes from Great Britain. RESEARCH DESIGN AND METHODS There were a total of 3,038 participants (675 deaths) with diabetes in the Health Survey for England and the Scottish Health Surveys conducted between 1997 and 2008. Participants aged ‡50 years at baseline were followed up for an average of 75.2 months for all-cause and CVD mortality. Data were collected on selfreported frequency, duration, and intensity of participation in sports and exercise, walking, and domestic physical activity, from which the number of MET-hours/ week were derived. Sex-specific medians of time spent in each type of physical activity (for those physically active)were calculated, and Cox proportional hazards regression conducted to examine type-specific associations between the level of physical activity and all-cause and CVD mortality risk. RESULTS Inverse associations with all-cause and CVD mortality were observed for overall physical activity in a dose-response manner after adjusting for covariates. Compared with those who individuals were inactive, participants who reported some activity, but below the recommended amount, or who met the physical activity recommendations had a 26% (95%CI 39–11) and 35%(95% CI 47–21) lower all-cause mortality, respectively. Similar results were found for below/above median physical activity levels. Sports and exercise participation was inversely associated with all-cause (but not CVD)mortality, as were above average levels of walking. Domestic physical activity was not associated with mortality. CONCLUSIONS Moderate physical activity levels were associated with better prognosis in diabetic adults

Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD

BackgroundMatrix metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and drive tissue remodelling, key processes in the pathogenesis of COPD. The development of small airway disease has been identified as a critical mechanism in the early development of airflow obstruction but the contribution of MMPs in human disease is poorly characterised.ObjectivesWe investigated the role of MMPs and inflammatory cytokines in the lung by quantifying levels and determining relationships with the key pathological components of COPD in patients and healthy controls.MethodsWe analysed levels of MMPs and inflammatory cytokines in bronchoalveolar lavage from 24 COPD and 8 control subjects. Each subject underwent spirometry and high-resolution CT. Image analysis quantitatively assessed emphysema, bronchial wall thickening and small airways disease.ResultsMultiple MMPs (MMP-1, -2, -3, -8, -9 and -10) and cytokines (interleukin (IL) 6 and IL-8) were elevated in lungs of subjects with COPD. MMP-3, -7, -8, -9, -10 and -12 concentrations closely associated with CT markers of small airways disease. Emphysema severity was also associated with MMP-3, -7 and -10. However, there were no strong relationships between MMPs and bronchial wall thickness of the larger airways.ConclusionsPulmonary MMP concentrations are directly associated with the extent of gas trapping and small airways disease identified on CT scan. This study suggests that MMPs play a significant role in small airways remodelling, a key feature in the pathogenesis of COPD.Trial registration number NCT0170186

Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort

Eosinophilic inflammation in COPD predicts response to treatment especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations and its associations with clinical phenotype, exacerbations and infection.127 patients aged 40–85 with moderate-severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for one year. Blood eosinophils ≥2% was prevalent at baseline and predicted both predominantly raised stable state eosinophils across the year (AUC 0.841, 95%CI 0.755; 0.928), and increased risk of eosinophilic inflammation at exacerbation (OR 9.16 p&lt;0.001). Eosinophils≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49, p=0.049 and OR 0.25, p=0.065 respectively). Bacterial infection at exacerbation was highly seasonal (Winter vs Summer OR 4.74, p=0.011) in predominantly eosinophilic patients.Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important conditio

Impact of radiologically stratified exacerbations: insights into pneumonia aetiology in COPD

Abstract Background COPD patients have increased risk of developing pneumonia, which is associated with poor outcomes. It can be symptomatically indistinguishable from exacerbations, making diagnosis challenging. Studies of pneumonia in COPD have focused on hospitalised patients and are not representative of the ambulant COPD population. Therefore, we sought to determine the incidence and aetiology of acute exacerbation events with evidence of pneumonic radiographic infiltrates in an outpatient COPD cohort. Methods One hundred twenty-seven patients with moderate to very severe COPD aged 42–85 years underwent blood and sputum sampling over one year, at monthly stable visits and within 72 h of exacerbation symptom onset. 343 exacerbations with chest radiographs were included. Results 20.1% of exacerbations had pneumonic infiltrates. Presence of infiltrate was highly seasonal (Winter vs summer OR 3.056, p = 0.027). In paired analyses these exacerbation events had greater increases in systemic inflammation. Bacterial detection rate was higher in the pneumonic group, with Haemophilus influenzae the most common bacteria in both radiological groups. Viral detection and sputum microbiota did not differ with chest radiograph appearance. Conclusions In an outpatient COPD cohort, pneumonic infiltrates at exacerbation were common, and associated with more intense inflammation. Bacterial pathogen detection and lung microbiota were not distinct, suggesting that exacerbations and pneumonia in COPD share common infectious triggers and represent a continuum of severity rather than distinct aetiological events. Trial registration Trial registration Number: NCT01360398

Impact of radiologically stratified exacerbations: Insights into pneumonia aetiology in COPD

Background:COPD patients have increased risk of developing pneumonia, which is associated with poor outcomes. It can be symptomatically indistinguishable from exacerbations, making diagnosis challenging. Studies of pneumonia in COPD have focused on hospitalised patients and are not representative of the ambulant COPD population. Therefore, we sought to determine the incidence and aetiology of acute exacerbation events with evidence of pneumonic radiographic infiltrates in an outpatient COPD cohort.Methods:127 patients with moderate to very severe COPD aged 42-85 years underwent blood and sputum sampling over one year, at monthly stable visits and within 72 hours of exacerbation symptom onset. 343 exacerbations with chest radiographs were included.Results:20.1% of exacerbations had pneumonic infiltrates. Presence of infiltrate was highly seasonal (Winter vs summer OR 3.056, p=0.027). In paired analyses these exacerbation events had greater increases in systemic inflammation. Bacterial detection rate was higher in the pneumonic group, with Haemophilus influenzae the most common bacteria in both radiological groups. Viral detection and sputum microbiota did not differ with chest radiograph appearance.Conclusions:In an outpatient COPD cohort, pneumonic infiltrates at exacerbation were common, and associated with more intense inflammation. Bacterial pathogen detection and lung microbiota were not distinct, suggesting that exacerbations and pneumonia in COPD share common infectious triggers and represent a continuum of severity rather than distinct aetiological events.Trial Registration Number: NCT01360398<br/