American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2014
Comparative StudyZ alpha-1 antitrypsin confers a pro-inflammatory phenotype that contributes to COPD.
Severe α1-antitrypsin deficiency caused by the Z variant (Glu342Lys; ZZ-AT) is a well-known genetic cause for emphysema. Although severe lack of antiproteinase protection is the critical etiologic factor for ZZ-AT-associated chronic obstructive pulmonary disease (COPD), some reports have suggested enhanced lung inflammation as a factor in ZZ-AT homozygotes. ⋯ We show here that aggregation of intracellular mutant Z-AT invokes a specific deleterious cellular inflammatory phenotype in COPD. Oxidant-induced intracellular polymerization of Z-AT in epithelial cells causes ER stress, and promotes excess cytokine and cellular inflammation. This pathway is likely to contribute to the development of COPD in ZZ-AT homozygotes, and therefore merits further investigation.
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Am. J. Respir. Crit. Care Med. · Apr 2014
Randomized Controlled Trial Multicenter StudyInhaled Colistin in Patients with Bronchiectasis and Chronic Pseudomonas aeruginosa Infection.
Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis. ⋯ Although the primary endpoint was not reached, this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection. Clinical trial registered with http://www.isrctn.org/ (ISRCTN49790596).
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Am. J. Respir. Crit. Care Med. · Apr 2014
ReviewHow Outcomes are Defined in Clinical Trials of Mechanically Ventilated Adults and Children.
Systematic reviews have considerable potential to provide evidence-based data to aid clinical decision-making. However, there is growing recognition that trials involving mechanical ventilation lack consistency in the definition and measurement of ventilation outcomes, creating difficulties in combining data for meta-analyses. To address the inconsistency in outcome definitions, international standards for trial registration and clinical trial protocols published recommendations, effectively setting the "gold standard" for reporting trial outcomes. ⋯ Ventilation outcomes reported in trials over the last 6 years typically fall into four domains: measures of ventilator dependence; adverse outcomes; mortality; and resource use. We highlight the need, first, for agreement on outcome definitions and, second, for a minimum core outcome set for trials involving mechanical ventilation. A minimum core outcome set would not restrict trialists from measuring additional outcomes, but would overcome problems of variability in outcome selection, measurement, and reporting, thereby enhancing comparisons across trials.