Abstract-In 2004, the first American Heart Association scientific statement on "Air Pollution and Cardiovascular Disease" concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM Ͻ2.5 m in diameter (PM 2.5 ) over a few hours to weeks can trigger cardiovascular disease-related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM 2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM 2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality. (Circulation. 2010;121:2331-2378.)

Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension.The present study analysed data from 20,296 subjects aged o45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for.Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function.Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.

Rationale: The patterns and outcomes of noninvasive, positivepressure ventilation (NIPPV) use in patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) nationwide are unknown. Objectives: To determine the prevalence and trends of noninvasive ventilation for acute COPD. Methods: We used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample to assess the pattern and outcomes of NIPPV use for acute exacerbations of COPD from 1998 to 2008. Measurements and Main Results: An estimated 7,511,267 admissions for acute exacerbations occurred from 1998 to 2008. There was a 462% increase in NIPPV use (from 1.0 to 4.5% of all admissions) and a 42% decline in invasive mechanical ventilation (IMV) use (from 6.0 to 3.5% of all admissions) during these years. This was accompanied by an increase in the size of a small cohort of patients requiring transition from NIPPV to IMV. In-hospital mortality in this group appeared to be worsening over time. By 2008, these patients had a high mortality rate (29.3%), which represented 61% higher odds of death compared with patients directly placed on IMV (95% confidence interval, 24-109%) and 677% greater odds of death compared with patients treated with NIPPV alone (95% confidence interval, 475-948%). With the exception of patients transitioned from NIPPV to IMV, in-hospital outcomes were favorable and improved steadily year by year. Conclusions: The use of NIPPV has increased significantly over time among patients hospitalized for acute exacerbations of COPD, whereas the need for intubation and in-hospital mortality has declined. However, the rising mortality rate in a small but expanding group of patients requiring invasive mechanical ventilation after treatment with noninvasive ventilation needs further investigation.Keywords: COPD; positive-pressure ventilation; artificial respiration; epidemiology Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States and is projected to become the third leading cause of death by 2020 (1, 2). A large proportion of morbidity and mortality from COPD results from acute exacerbations, which lead to 1.5 million emergency room visits and 750,000 hospitalizations annually in the United States (3, 4). Therefore, to improve outcomes and reduce mortality due to COPD, we need to optimize the management of acute exacerbations (5), including the correct use of respiratory support modalities to treat patients with respiratory failure.Over the last decade, noninvasive, positive-pressure ventilation (NIPPV) has started playing an increasingly important role in the treatment of respiratory failure due to acute exacerbations (6-12). This is because clinical trials demonstrate good efficacy for NIPPV in reducing risk of intubation and mortality, health care providers are becoming increasingly confident with its use, and unlike IMV, it can be implemented outside the ICU, freeing up ICU beds. Therefore, it appears likely that NIPPV use will continue to increa...

Background Severe asthma is a complex heterogeneous disease associated with older age and obesity. The presence of eosinophilic (type 2) inflammation in some but not all patients with severe asthma predicts responsiveness to current treatments, but new treatment approaches will require better understanding of non-type 2 mechanisms of severe asthma. We considered the possibility that systemic inflammation - which occurs in subgroups of obese and older patients - modifies asthma to make it worse. Interleukin 6 (IL6) is a biomarker of systemic inflammation and metabolic dysfunction, and we aimed to explore the relationship between IL6, metabolic dysfunction, and asthma severity. Methods We generated a reference range in health for plasma IL6 in a cohort of healthy controls (n=93). We compared the clinical characteristics of asthmatics with plasma IL6 levels below and above the upper limit of normal (“IL6 low” and “IL-high” asthma) in two asthma cohorts - predominantly non-severe asthmatics recruited at the University of California San Francisco (UCSF)(n=249) and predominantly severe asthmatics recruited by the Severe Asthma Research Program (SARP)(n=387). Findings The upper 95th centile value for plasma IL6 in the healthy cohort was 3·1pg/mL, and 14% of UCSF cohort and 26% of the SARP cohort had plasma IL6 levels above this upper limit. The “IL6-high” patients in both asthma cohorts had a significantly higher body mass index and a higher prevalence of metabolic disease than the IL6-low patients (all p values < 0.01). IL6-high patients also had significantly lower lung function and more frequent asthma exacerbations than IL6-low patients (all p values < 0·01). Although 75% of IL6-high asthmatics were obese, 63% of obese patients were IL6-low. Among obese patients, the forced expired volume in one second (FEV1) was significantly lower in IL6-high than in IL6-low patients (mean FEV1 70·8 [S.D. 19·5] vs. 78·1 [19·7] % predicted, p = 0·002), and the percentage of patients reporting an asthma exacerbation in the past 1-2 years was higher in IL6-high than in IL6-low patients (66 vs. 48%, p = 0·003). Among non-obese asthmatics, FEV1% and asthma exacerbation outcomes were also significantly worse in IL6-high than in IL6-low patients (mean FEV1 66·4 [SD 23·1] vs. 83·2 [20·4] % predicted, p< 0·01; 59 vs. 34 %, p=0·008). Interpretation Systemic IL6 inflammation and clinical features of metabolic dysfunction - occurring most commonly among a subset of obese asthmatics but also in a small subset of non-obese patients - is associated with more severe asthma. IL6 inhibitors or treatments that improve metabolic dysfunction represent rational clinical trials to pursue for a subset of patients with severe asthma, and plasma IL6 is a biomarker that could guide patient stratification.

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