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https://www.selleckchem.com/products/bsj-03-123.html 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 11 to receive 13 once-weekly doses of inhaled AZD1419 (1, 4, or 8 mg; n = 40) or placebo (n = 41). Inhaled corticosteroids and long-acting β2-agonist were tapered down and then discontinued. The last four doses of AZD1419 were given without maintenance medication, followed by a 40-week observation period. Primary endpoint was time to loss of asthma control (LOC).Measurements and Main Results AZD1419 induced a T-helper cell type 1-type IFN response with a sustained reduction in markers of type 2 inflammation. However, there were no statistically significant differences between AZD1419 and placebo for time to LOC, proportion of patients with LOC, changes in Asthma Control Questionnaire-five-item version, exacerbations, reliever use, FEV1, peak expiratory flow, or fractional exhaled nitric oxide (FeNO). LOC was predicted by an early rise in FeNO in 63% of patients. Despite withdrawal of maintenance treatment, 24 patients completed the study without LOC; AZD1419 n = 11, placebo n = 13. 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.Rationale Reverse triggering is an underexplored form of dyssynchrony with important clinical implications in patients with acute respiratory distress syndrome.Objectives This retrospective study iden

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