American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2020
Clinical TrialCombination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension: A Double-Blind, Placebo-Controlled Study.
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. ⋯ The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624).
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Am. J. Respir. Crit. Care Med. · Mar 2020
Comparative StudyAirway Mucus Hyperconcentration in Non-Cystic Fibrosis Bronchiectasis.
Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized. Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity. Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. ⋯ No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%. Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Genomic Underpinnings of Tumor Behavior in in situ and Early Lung Adenocarcinoma.
Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants. Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs. ⋯ Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers. Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Comparative StudyTemporal Trends in Critical Care Outcomes in United States Minority Serving Hospitals.
Rationale: Whether critical care improvements over the last 10 years extend to all hospitals has not been described. Objectives: To examine the temporal trends of critical care outcomes in minority and non-minority-serving hospitals using an inception cohort of critically ill patients. Measurements and Main Results: Using the Philips Health Care electronic ICU Research Institute Database, we identified minority-serving hospitals as those with an African American or Hispanic ICU census more than twice its regional mean. ⋯ This disparity in temporal trends was particularly noticeable among African American individuals, where each additional calendar year was associated with a 3% (95% CI, 0.96-0.97) lower adjusted critical illness mortality within a non-minority-serving hospital, but no change within minority-serving hospitals (hazard ratio, 0.99; 95% CI, 0.97-1.01). Similarly, although ICU and hospital lengths of stay decreased by 0.08 (95% CI, -0.08 to -0.07) and 0.16 (95% CI, -0.16 to -0.15) days per additional calendar year, respectively, in non-minority-serving hospitals, there was little temporal change for African American individuals in minority-serving hospitals. Conclusions: Critically ill African American individuals are disproportionately cared for in minority-serving hospitals, which have shown significantly less improvement than non-minority-serving hospitals over the last 10 years.
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Am. J. Respir. Crit. Care Med. · Mar 2020
Effect of Weight Loss on Upper Airway Anatomy and the Apnea Hypopnea Index: The Importance of Tongue Fat.
Rationale: Obesity is the primary risk factor for obstructive sleep apnea (OSA). Tongue fat is increased in obese persons with OSA, and may explain the relationship between obesity and OSA. Weight loss improves OSA, but the mechanism is unknown. ⋯ Conclusions: Weight loss reduced volumes of several upper airway soft tissues in subjects with obesity and OSA. Improved AHI with weight loss was mediated by reductions in tongue fat. New treatments that reduce tongue fat should be considered for patients with OSA.