American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2020
Whole Blood RNA Profiles Associated with Pulmonary Arterial Hypertension and Clinical Outcome.
Rationale: Idiopathic and heritable pulmonary arterial hypertension (PAH) are rare but comprise a genetically heterogeneous patient group. RNA sequencing linked to the underlying genetic architecture can be used to better understand the underlying pathology by identifying key signaling pathways and stratify patients more robustly according to clinical risk. Objectives: To use a three-stage design of RNA discovery, RNA validation and model construction, and model validation to define a set of PAH-associated RNAs and a single summarizing RNA model score. ⋯ MR detected an association between SMAD5 levels and PAH disease susceptibility (odds ratio, 0.317; 95% confidence interval, 0.129-0.776; P = 0.012). Conclusions: A whole-blood RNA signature of PAH, which includes RNAs relevant to disease pathogenesis, associates with disease severity and identifies patients with poor clinical outcomes. Genetic variants associated with lower SMAD5 expression may increase susceptibility to PAH.
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Am. J. Respir. Crit. Care Med. · Aug 2020
Randomized Controlled Trial Multicenter StudyTargeted Retreatment of Incompletely Recovered COPD Exacerbations With Ciprofloxacin: A Double-blind, Randomised, Placebo-controlled, Multicentre Phase III Trial.
Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14. ⋯ Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy. Clinical trial registered with www.clinicaltrials.gov (NCT02300220).