American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2019
Bronchoalveolar Lavage Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications.
Rationale: Gene expression of BAL cells, which samples the cellular milieu within the lower respiratory tract, has not been well studied in severe asthma. Objectives: To identify new biomolecular mechanisms underlying severe asthma by an unbiased, detailed interrogation of global gene expression. Methods: BAL cell expression was profiled in 154 asthma and control subjects. ⋯ Conclusions: Gene expression in BAL cells is influenced by factors seldomly considered. Notably, β-agonist exposure likely had a strong and immediate impact on cellular gene expression, which may not translate to important disease mechanisms or necessarily match protein levels. Leading severity-related genes were discovered in an unbiased, system-wide analysis, revealing new targets that map to asthma susceptibility loci.
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Am. J. Respir. Crit. Care Med. · Oct 2019
Risk Factors for Functional Decline and Impaired Quality of Life after Pediatric Respiratory Failure.
Rationale: Poor outcomes of adults surviving critical illness are well documented, but data in children are limited. Objectives: To identify factors associated with worse postdischarge function and health-related quality of life (HRQL) after pediatric acute respiratory failure. Methods: We assessed functional status at baseline, discharge, and 6 months after pediatric ICU discharge and HRQL 6 months after discharge in 2-week- to 17-year-olds mechanically ventilated for acute respiratory failure in the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) trial. ⋯ Independent predictors of impaired growth and development included methadone (OR = 2.27; 95% CI = 1.18-4.36) and inadequate pain management (OR = 2.94; 95% CI = 1.39-6.19). Impaired HRQL was associated with older age, non-white or Hispanic race, cancer, and inadequate sedation management (OR = 3.15; 95% CI = 1.74-5.72). Conclusions: Postdischarge morbidity after respiratory failure is common and associated with admission factors, exposure to critical care therapies, and pain and sedation management.
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Am. J. Respir. Crit. Care Med. · Oct 2019
YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib.
Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non-small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. ⋯ Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy.