American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2021
Letter Randomized Controlled TrialPulmonary Arterial Hypertension Caused by AhR Signal Activation Protecting Against Colitis.
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Am. J. Respir. Crit. Care Med. · Feb 2021
Sustained Coinfections with Staphylococcus aureus and Pseudomonas aeruginosa in Cystic Fibrosis.
Rationale: Staphylococcus aureus and Pseudomonas aeruginosa often infect the airways in cystic fibrosis (CF). Because registry studies show higher prevalence of P. aeruginosa versus S. aureus in older patients with CF, a common assumption is that P. aeruginosa replaces S. aureus over time. In vitro, P. aeruginosa can outgrow and kill S. aureus. ⋯ Contrary to common assumption, we found no pattern of replacement of S. aureus by P. aeruginosa. Many patients with CF have durable long-term coinfection with these organisms. New strategies are needed to prevent and treat these infections.
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Am. J. Respir. Crit. Care Med. · Feb 2021
Randomized Controlled TrialA Phase 2a, Double-Blind, Placebo-Controlled Randomized Trial of Inhaled TLR9 Agonist AZD1419 in Asthma.
Rationale: To examine the potential of TLR9 (Toll-like receptor 9) activation to modulate the type 2 immune response in asthma. Objectives: To evaluate efficacy and safety of AZD1419, an inhaled TLR9 agonist, in a phase 2a, randomized, double-blind trial. Methods: Adult patients with asthma with a history of elevated eosinophils (>250 cells/μl) were randomized 1:1 to receive 13 once-weekly doses of inhaled AZD1419 (1, 4, or 8 mg; n = 40) or placebo (n = 41). ⋯ Adverse events were balanced across groups, with no deaths or serious adverse events judged as causally related to AZD1419. Conclusions: AZD1419 was safe and well tolerated but did not lead to improved asthma control, despite reducing markers of type 2 inflammation. Results suggest that a novel accelerated step-down approach based on FeNO is possible for patients with well-controlled asthma.