The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD). A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. ⋯ A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.
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Randomized Controlled Trial Multicenter Study
CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions.
The role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD) is controversial and a biomarker identifying patients who benefit from antibiotics is mandatory. We performed a randomised, controlled trial in patients with acute exacerbations of COPD, comparing C-reactive protein (CRP)-guided antibiotic treatment to patient reported symptoms in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy, in order to show a reduction in antibiotic prescription. Patients hospitalised with acute exacerbations of COPD were randomised to receive antibiotics based either on the GOLD strategy or according to the CRP strategy (CRP ≥50 mg·L-1). ⋯ Use of CRP as a biomarker to guide antibiotic treatment in severe acute exacerbations of COPD leads to a significant reduction in antibiotic treatment. In the present study, no differences in adverse events between both groups were found. Further research is needed for the generalisability of these findings.
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Many epidemiological studies have reported a positive association between prenatal exposure to paracetamol and childhood wheezing and asthma. We investigated whether the link between prenatal analgesic exposure and asthma/wheeze is specific to paracetamol, and whether it is causal or confounded. Using linked Swedish health register data we investigated the relation between various prescribed analgesics in pregnancy and the risk of childhood asthma/wheeze in a population of 492 999, and used negative paternal control and sibling comparison approaches to explore unmeasured confounding. ⋯ The results of the paternal control analysis did not suggest the presence of unmeasured confounding by genetics or shared environment. However, the sibling control analysis broadly suggested that associations between prenatal exposure to the analgesics and asthma/wheeze were confounded by specific maternal factors (e.g. for asthma/wheeze at age 4 years: adjusted OR 0.91 (95% CI 0.62-1.31), 0.50 (95% CI 0.17-1.45) and 0.80 (95% CI 0.50-1.29) for opioids, antimigraine drugs and paracetamol, respectively). We propose that analgesic use in pregnancy does not cause childhood asthma/wheeze and that the association is confounded by unmeasured factors that are intrinsic to the mother, such as chronic pain or anxiety.