American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jul 2014
MiR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production.
Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family. ⋯ The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.
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Am. J. Respir. Crit. Care Med. · Jul 2014
Multicenter Study Observational StudyClinical Mechanism of the CFTR Potentiator Ivacaftor in G551D-Mediated Cystic Fibrosis.
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6 and older with the G551D mutation. ⋯ Significant clinical and physiologic improvements were observed on initiation of ivacaftor in a broad patient population, including reduced infection with P. aeruginosa. Biomarker studies substantially improve the understanding of the mechanistic consequences of CFTR modulation on pulmonary and gastrointestinal physiology.
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Am. J. Respir. Crit. Care Med. · Jul 2014
Randomized Controlled TrialBosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia (BPHIT).
Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality. ⋯ This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP. Clinical trial registered with www.clinicaltrials.gov (NCT 00637065).
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Am. J. Respir. Crit. Care Med. · Jul 2014
Obstructive Sleep Apnea and Incident Diabetes: A Historical Cohort Study.
Despite emerging evidence that obstructive sleep apnea (OSA) may cause metabolic disturbances independently of other known risk factors, it remains unclear whether OSA is associated with incident diabetes. ⋯ Among people with OSA, and controlling for multiple confounders, initial OSA severity and its physiologic consequences predicted subsequent risk for incident diabetes.
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Am. J. Respir. Crit. Care Med. · Jul 2014
Untargeted Lipidomic Analysis in COPD: Uncovering Sphingolipids.
Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD. ⋯ Expression of lipids from the sphingolipid pathway is higher in smokers with COPD compared with smokers without COPD. Considering their potential biologic properties, they may play a role in the pathogenesis of COPD.