American Journal of Respiratory and Critical Care Medicine

RATIONALE: High-dose isoniazid is recommended in short-course regimens for multidrug-resistant TB (MDR-TB). The optimal dose of isoniazid and its individual contribution to efficacy against TB strains with inhA or katG mutations are unknown. OBJECTIVE: Define the optimal dose of isoniazid for patients with isoniazid-resistant TB mediated by inhA mutations. METHODS: AIDS Clinical Trials Group A5312 is a Phase 2A, open-label trial in which individuals with smear-positive pulmonary TB with isoniazid resistance mediated by an inhA mutation were randomized to receive isoniazid 5, 10 or 15 mg/kg daily for 7 days (inhA group), and controls with drug-sensitive TB received standard dose (5 mg/kg/day)...

RATIONALE: Admissions to intensive care units (ICUs) are common during terminal hospitalizations, but little is known about how ICU care affects the end-of-life experience for patients dying in hospitals and their families. OBJECTIVES: We measured the association between ICU care during terminal hospitalization and family ratings of end-of-life care for patients who died in 106 Veterans Affairs hospitals from 2010 to 2016. METHODS: Patients were divided into four categories: no ICU care, ICU-only care, mixed care (died outside ICU), and mixed care (died in ICU)...

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RATIONALE: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia. OBJECTIVE: To assess the relationship between the presence of chronic bacterial infection (CBI), reduced number of circulating eosinophils, ICS treatment and the risk of pneumonia in COPD patients. METHODS AND MEASUREMENTS: Post-hoc long-term observational study of an historical cohort of 201 COPD patients (GOLD II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months...

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RATIONALE: Obesity is the primary risk factor for 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. OBJECTIVES: To determine the effect of weight loss on UA anatomy in persons with obesity and OSA. We hypothesized that weight loss would decrease soft tissue volumes and tongue fat and these changes would correlate with reductions in apnea-hypopnea index (AHI)...

RATIONALE: Acute exacerbation during the course of idiopathic pulmonary fibrosis causes a poor prognosis. Coagulation abnormalities and endothelial damage are involved in its pathogenesis. Thrombomodulin alfa, a recombinant human soluble thrombomodulin, has anticoagulant and anti-inflammatory effects. Several clinical studies have shown that thrombomodulin alfa may improve survival of acute exacerbation. OBJECTIVES: To determine the efficacy and safety of thrombomodulin alfa compared with placebo in acute exacerbation of idiopathic pulmonary fibrosis...

RATIONALE: Vascular remodeling, including smooth muscle cell hypertrophy and proliferation, is the key pathological feature of pulmonary arterial hypertension (PAH). Prostaglandin (PG) I2 analogs (baraprost, iloprost, and treprostinil) are effective in the treatment of PAH. Of note, the clinically favorable effects of treprostinil in severe PAH may be attributable to concomitant activation of PGD2 receptor subtype 1 (DP1). OBJECTIVES: To study the role of DP1 in the progression of PAH and its underlying mechanism...

BACKGROUND: Excessive daytime sleepiness is a common disabling symptom in obstructive sleep apnea syndrome. We aimed to evaluate the efficacy and safety of pitolisant, a selective histamine H3-receptor antagonist with wake-promoting effects, for treatment of daytime sleepiness in patients with moderate to severe obstructive sleep apnea refusing continuous positive airway pressure treatment. METHODS: In an international multicenter, double-blind, randomized (3:1), placebo-controlled, parallel-design trial, pitolisant was individually titrated at up to 20 mg/day over 12 weeks...

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RATIONALE: Acute kidney injury (AKI), a common complication of sepsis, is associated with substantial morbidity and mortality and lacks definitive disease-modifying therapy. Early, reliable identification of at risk patients is important for targeted implementation of renal protective measures. PERSEVERE-II is a validated, multi-biomarker prognostic enrichment strategy to estimate baseline mortality risk in pediatric septic shock. OBJECTIVES: To assess the association between PERSEVERE-II mortality probability and the development of severe, sepsis-associated AKI on day 3 (D3 SA-AKI) in pediatric septic shock...

RATIONALE: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH). OBJECTIVES: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH. METHODS: Group 1 PAH patients were included from two national registries with genome-wide data and two local cohorts and further incorporated in a global meta-analysis. Hazard ratios (HRs) were calculated for transplant-free all-cause mortality in Hispanics with Non-Hispanic whites (NHWs) as the reference group...