The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Reversible airflow obstruction and nonspecific airway hyperresponsiveness are: 1) the two key features of asthma; 2) the primary concern for asthma patients; and 3) both directly caused by the airway smooth muscle (ASM). As such, controlling bronchoconstriction should be of primary importance. Unfortunately, all existing pharmacological asthma therapies that specifically target the ASM are based on decades old strategies. In the present study, the evolution of pharmacological asthma therapy will be briefly discussed, some explanations will be suggested as to why substantial new advances in this area have not occurred in several years and, finally, several new directions for novel asthma therapies will be proposed.
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Recent studies suggest that macrolides may have beneficial effects for patients at risk for certain infections. The current authors examined the effect of macrolide therapy on 30- and 90-day mortality for patients with severe sepsis caused by pneumonia. A retrospective cohort study was conducted at two tertiary teaching hospitals. ⋯ In the multivariable analysis, the use of macrolide was associated with decreased mortality at 30 days (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.2-0.7) and at 90 days (HR 0.3, 95% CI 0.2-0.6) in patients with severe sepsis and in patients with macrolide-resistant pathogens (HR 0.1, 95% CI 0.02-0.5). Macrolide use was associated with decreased mortality in patients with severe sepsis due to pneumonia and macrolide-resistant pathogens. Confirmatory studies are needed to determine whether macrolide therapy may be protective for patients with sepsis.
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Animal models are an essential step between "in vitro" testing and clinical studies. Different animal models have been useful for the study of pathophysiology, diagnosis and therapy in ventilator-associated pneumonia (VAP). Aspiration has been studied in dog and cat models and bacteriological diagnosis has been evaluated in baboons. ⋯ Different clinical, physiological, microbiological and pathological parameters of infection have been studied in this model. In addition, administration of antibiotics and inflammatory modulators and their consequences in microbiological eradication and local and systemic inflammation have been evaluated with interesting translational results. Although bronchial inoculation of healthy subjects does not resemble the common pathophysiological mechanisms, the experimental model of ventilator-associated pneumonia induced by the inoculation of high concentrations of microorganisms in mechanically ventilated piglets is useful for the study of the local and systemic responses of lung infection and for the determination of potential measures of prevention or therapeutic modulation.
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Controlled Clinical Trial
Screening for pulmonary arteriovenous malformations using transthoracic contrast echocardiography: a prospective study.
Pulmonary arteriovenous malformations (PAVMs) are associated with severe neurological complications in patients with hereditary haemorrhagic telangiectasia (HHT). The objective of the present study was to prospectively establish the diagnostic value of transthoracic contrast echocardiography (TTCE) as a screening technique for PAVM using chest high-resolution computed tomography (HRCT) as the gold standard for PAVMs. All consecutive adult patients referred for HHT screening underwent a chest HRCT (n = 299), TTCE (n = 281), arterial blood gas analysis (n = 291), shunt fraction measurement (n = 111) and chest radiography (n = 296). ⋯ The other diagnostic tests showed a considerable lower diagnostic value. The present prospective study shows that transthoracic contrast echocardiography has an excellent diagnostic value and can be used as an initial screening procedure for pulmonary arteriovenous malformations. The high false-positive rate of transthoracic contrast echocardiography possibly represents microscopic pulmonary arteriovenous malformations.
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CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients. ⋯ In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction. To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.