American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2013
ReviewThe Impact of Genomic Changes on Treatment of Lung Cancer.
The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. ⋯ The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making.
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Am. J. Respir. Crit. Care Med. · Oct 2013
Respiratory and Auditory Cortical Processing in Children with Obstructive Sleep Apnea Syndrome.
Children with obstructive sleep apnea syndrome (OSAS) have impaired cortical processing of respiratory afferent stimuli, manifested by blunted sleep respiratory-related evoked potentials (RREP). However, whether this impairment is limited to respiratory stimuli, or reversible after successful treatment, is unknown. We hypothesized that, during sleep, children with OSAS have (1) abnormal RREP, (2) normal cortical processing of nonrespiratory stimuli, and (3) persistence of abnormal RREP after treatment. ⋯ Children with OSAS have persistent primary or irreversible respiratory afferent cortical processing deficits during sleep that could put them at risk of OSAS recurrence. OSAS does not seem to affect the cortical processing of nonrespiratory (auditory) afferent stimuli during sleep.
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Am. J. Respir. Crit. Care Med. · Oct 2013
Role of Lung Pericytes and Resident Fibroblasts in the Pathogenesis of Pulmonary Fibrosis.
The origin of cells that make pathologic fibrillar collagen matrix in lung disease has been controversial. Recent studies suggest mesenchymal cells may contribute directly to fibrosis. ⋯ We conclude that the lung contains an extensive population of Foxd1 progenitor-derived pericytes that are an important lung myofibroblast precursor population.