American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2019
Identifying Novel Sepsis Subphenotypes Using Temperature Trajectories.
Rationale: Sepsis is a heterogeneous syndrome, and identifying clinically relevant subphenotypes is essential. Objectives: To identify novel subphenotypes in hospitalized patients with infection using longitudinal temperature trajectories. Methods: In the model development cohort, inpatient admissions meeting criteria for infection in the emergency department and receiving antibiotics within 24 hours of presentation were included. ⋯ The hyperthermic, fast resolvers had the lowest mortality rate (2.9%). Similar trajectory groups, patient characteristics, and outcomes were found in the validation cohort. Conclusions: We identified and validated four novel subphenotypes of patients with infection, with significant variability in inflammatory markers and outcomes.
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Am. J. Respir. Crit. Care Med. · Aug 2019
Randomized Controlled TrialLong-Term Azithromycin Reduces Haemophilus influenzae and Increases Antibiotic Resistance in Severe Asthma.
Rationale: The macrolide antibiotic azithromycin reduces exacerbations in adults with persistent symptomatic asthma. However, owing to the pleotropic properties of macrolides, unintended bacteriological consequences such as augmented pathogen colonization or dissemination of antibiotic-resistant organisms can occur, calling into question the long-term safety of azithromycin maintenance therapy. Objectives: To assess the effects of azithromycin on the airway microbiota, pathogen abundance, and carriage of antibiotic resistance genes. ⋯ Conclusions: In patients with persistent uncontrolled asthma, azithromycin reduced airway H. influenzae load compared with placebo but did not change total bacterial load. Macrolide resistance increased, reflecting previous studies. These results highlight the need for studies assessing the efficacy of nonantibiotic macrolides as a long-term therapy for patients with persistent uncontrolled asthma.
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Am. J. Respir. Crit. Care Med. · Aug 2019
Clinical TrialThe Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy: A Pilot Study.
Rationale: Augmentation therapy with intravenous AAT (alpha-1 antitrypsin) is the only specific therapy for individuals with pulmonary disease from AAT deficiency (AATD). The recommended standard dose (SD; 60 mg/kg/wk) elevates AAT trough serum levels to around 50% of normal; however, outside of slowing emphysema progression, its effects in other clinical outcomes have not been rigorously proven. Objectives: To evaluate the biological effects of normalizing AAT trough levels with double-dose (DD) therapy (120 mg/kg/wk) in subjects with AATD already receiving SD therapy. ⋯ Conclusions: Subjects with AATD on SD augmentation therapy still exhibit inflammation, protease activity, and elastin degradation that can be further improved by normalizing AAT levels. Higher AAT dosing than currently recommended may lead to enhanced clinical benefits and should be explored further. Clinical trial registered with www.clinicaltrials.gov (NCT01669421).