IntroductionThe effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence.MethodsWe searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model.ResultsEight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27).ConclusionsThe effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.

Rationale: Systemic inflammation has emerged as a key pathophysiological process that induces multiorgan injury and causes serious human diseases. Endothelium is critical in maintaining cellular and inflammatory homeostasis, controlling systemic inflammation, and progression of inflammatory diseases. We postulated that endothelium produces and releases endogenous soluble factors to modulate inflammatory responses and protect against systemic inflammation. Objective: To identify endothelial cell–released soluble factors that protect against endothelial barrier dysfunction and systemic inflammation. Methods and Results: We found that conditioned medium of endothelial cells inhibited cyclooxgenase-2 and interleukin-6 expression in macrophages stimulated with lipopolysaccharide. Analysis of conditioned medium extracts by liquid chromatography–mass spectrometry showed the presence of 5-methoxytryptophan (5-MTP), but not other related tryptophan metabolites. Furthermore, endothelial cell–derived 5-MTP suppressed lipopolysaccharide-induced inflammatory responses and signaling in macrophages and endotoxemic lung tissues. Lipopolysaccharide suppressed 5-MTP level in endothelial cell-conditioned medium and reduced serum 5-MTP level in the murine sepsis model. Intraperitoneal injection of 5-MTP restored serum 5-MTP accompanied by the inhibition of lipopolysaccharide-induced endothelial leakage and suppression of lipopolysaccharide- or cecal ligation and puncture–mediated proinflammatory mediators overexpression. 5-MTP administration rescued lungs from lipopolysaccharide-induced damages and prevented sepsis-related mortality. Importantly, compared with healthy subjects, serum 5-MTP level in septic patients was decreased by 65%, indicating an important clinical relevance. Conclusions: We conclude that 5-MTP belongs to a novel class of endothelium-derived protective molecules that defend against endothelial barrier dysfunction and excessive systemic inflammatory responses.

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The cuff-leak test was widely used for the prediction of post-extubation stridor, but controversial results limit its clinical application. The current study used real-time ultrasonography to evaluate the air-leak and hypothesised that the air-column width, measured by ultrasonography, may be correlated to the development of post-extubation stridor.From June 1, 2001 to March 1, 2002, a total of 51 planned extubations in 51 consecutively intubated patients were included. All of the patients received ultrasonographical examinations of their vocal cords and larynx in addition to an air-column width measurement within 24 h prior to extubation.The overall post-extubation stridor rate was 7.8%. The air-leak volume presented as median (interquartile range) were 300 (350) mL and 25 (20) mL, respectively, for the nonstridor and stridor groups. The air-column width during cuff deflation was 6.4 (2) mm and 4.5 (0.8) mm, respectively. They were found to be statistically significant.In conclusion, the authors demonstrated that laryngeal ultrasonography could be a reliable, noninvasive method, in the evaluation of vocal cords, laryngeal morphology and the ease of airflow, which passed through vocal cords or subglottic area due to laryngeal oedema. The aircolumn width during cuff deflation was a potential predictor of post-extubation stridor.

Background: Injurious mechanical ventilation can cause a pro-inflammatory reaction in the lungs. Recent evidence suggests an association of the renin-angiotensin system (RAS) with lung inflammation. A study was undertaken to investigate the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and to determine whether VILI can be attenuated by angiotensin converting enzyme (ACE) inhibition. Methods: Male Sprague-Dawley rats were mechanically ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non-ventilated rats were used as controls. Lung injury and inflammation were measured by the lung injury score, protein leakage, myeloperoxidase activity, pro-inflammatory cytokine levels and nuclear factor (NF)-kB activity. Expression of the RAS components was also assessed. Some rats were pretreated with the ACE inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during mechanical ventilation to assess possible protective effects on VILI. Results: In the high-volume group (n = 6) the lung injury score, bronchoalveolar lavage fluid protein concentration, pro-inflammatory cytokines and NF-kB activities were significantly increased compared with controls (n = 6). Lung tissue angiotensin II levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II receptors were also significantly increased in the high-volume group. Pretreatment with captopril or concomitant infusion with losartan or PD123319 in the high-volume group attenuated the lung injury and inflammation (n = 6 for each group). Conclusions: The RAS is involved in the pathogenesis of ventilator-induced lung injury. ACE inhibitor or angiotensin receptor antagonists can attenuate VILI in this rat model.

OBJECTIVES:The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment.INTRODUCTION:Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied.METHODS:A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function.RESULTS:The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment.CONCLUSIONS:After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment.

This study suggests that NTM may play a role in disease progression and deterioration of pulmonary function in COPD patients.

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