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Epidemiological studies have implicated lung inflammation as a risk factor for acute cardiovascular events, but the underlying mechanisms linking lung injury with cardiovascular events are largely unknown.Our objective was to develop a novel murine model of acute atheromatous plaque rupture related to lung inflammation and to investigate the role of neutrophils in this process.Lipopolysaccharide (LPS; 3 mg·kg(-1)) or saline (control) was instilled directly into the lungs of male apolipoprotein E-null C57BL/6J mice following 8 weeks of a Western-type diet. 24 h later, atheromas in the right brachiocephalic trunk were assessed for stability ex vivo using high-resolution optical projection tomography and histology. 68% of LPS-exposed mice developed vulnerable plaques, characterised by intraplaque haemorrhage and thrombus, versus 12% of saline-exposed mice (p=0.0004). Plaque instability was detectable as early as 8 h post-intratracheal LPS instillation, but not with intraperitoneal instillation. Depletion of circulating neutrophils attenuated plaque rupture.We have established a novel plaque rupture model related to lung injury induced by intratracheal exposure to LPS. In this model, neutrophils play an important role in both lung inflammation and plaque rupture. This model could be useful for screening therapeutic targets to prevent acute vascular events related to lung inflammation., (Copyright ©ERS 2016.)

The balance between inflammatory and repair processes is important in maintaining lung homeostasis in chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine whether or not an integrated index of a biomarker involved in inflammation, C-reactive protein (CRP), and another involved in wound repair, fibronectin, may be a good measure to predict clinical outcomes in COPD. Circulating blood levels of CRP and fibronectin were measured in 4,787 individuals with mild-to-moderate COPD who were prospectively followed for >7 yrs after blood collection as part of the Lung Health Study. To assess the balance between repair and inflammation, a simple ratio was calculated by dividing fibronectin levels by CRP levels and a Cox proportional hazards model was used to determine the relationship between this ratio and all-cause and disease-specific causes of mortality. The relationship between the fibronectin to CRP ratio and all-cause mortality was L-shaped. There was an exponential decay in the adjusted hazard function (i.e. the risk of mortality) as the ratio decreased until a value of 148 was reached, beyond which point the hazard function did not change significantly. Similar results were observed for the risk of coronary and cardiovascular mortality. Circulating fibronectin to CRP ratio is significantly associated with all-cause mortality of COPD patients. However, in contrast to other biomarkers, the relationship appears to be L-shaped (and not linear), suggesting a threshold at approximately 150. While promising, future studies are needed to validate this simple index as a biomarker in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the USA, and it remains one of the few diseases that continues to increase its numbers. The development and progression of COPD can vary dramatically between individuals. A low level of lung function remains the cornerstone of COPD diagnosis and is a key predictor of prognosis. Lung function, however, is not the only factor in determining morbidity and mortality related to COPD, with factors such as body mass index, exercise capability and comorbid disease being important predictors of poor outcomes. Exacerbations of COPD are additional important indicators of both quality of life and outcomes in COPD patients. Definitions of exacerbations can vary, ranging from an increase in symptoms to COPD-related hospitalisations and death. COPD exacerbations are more common in patients with lower levels of lung function and may lead to more rapid declines in lung function. Better understanding of the natural history of COPD may lead to better definitions of specific COPD phenotypes, better interventions and improved outcomes.

Recent data suggest that inhaled corticosteroids reduce the number of clinical exacerbations in chronic obstructive pulmonary disease (COPD). It remains unknown whether a dose/response relationship exists. The present study was conducted to evaluate the long-term impact of varying doses of inhaled corticosteroids on COPD mortality. Hospital discharge data were used to identify all patients aged > or = 65 yrs recently hospitalised due to COPD in Alberta, Canada (n = 6,740). The relative risk (RR) for all-cause mortality was compared across different dose categories of inhaled corticosteroids (none and low, medium and high doses) following hospital discharge. Inhaled corticosteroid therapy after discharge was associated with a 25% relative reduction in risk for all-cause mortality (RR 0.75, 95% confidence interval (CI) 0.68-0.82). Patients on medium- or high-dose therapy showed lower risks for mortality than those on low doses (RR 0.77, 95% CI 0.69-0.86 for low dose; RR 0.48, 95% CI 0.37-0.63 for medium dose; and RR 0.55, 95% CI 0.44-0.69 for high dose). Use of inhaled corticosteroids following hospital discharge for chronic obstructive pulmonary disease was associated with a significant reduction in the overall mortality rate. Low- was inferior to medium- or high-dose therapy in protecting against mortality in chronic obstructive pulmonary disease.