Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A (15-epi-LXA), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and single Ig IL-1R-related molecule (SIGIRR). Of interest, 15-epi-LXA induced and in an lipoxin A receptor/formyl peptide receptor 2 (ALX/FPR2) receptor-dependent manner in epithelial cells and in murine pneumonia. This SPM regulated NF-κB-induced cytokines to decrease pathogen-mediated inflammation. In addition to dampening lung inflammation, surprisingly, 15-epi-LXA also enhanced pathogen clearance with increased antimicrobial peptide expression. Taken together, to our knowledge these results are the first to identify endogenous agonists for A20 and SIGIRR expression to regulate NF-κB activity and to establish mechanisms for NF-κB regulation by SPMs for pneumonia resolution.

Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS and represent potential vascular biomarkers of ARDS risk. Clinical trial registered with www.clinicaltrials.gov (NCT01504867).

13The National Heart Lung and Blood Institute's Severe Asthma Research Program-3 investigators are detailed in the supplemental acknowledgments. BACKGROUND.In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. METHODS. ALX expression and levels of proresolving ligands (lipoxin

13The National Heart Lung and Blood Institute's Severe Asthma Research Program-3 investigators are detailed in the supplemental acknowledgments. BACKGROUND.In health, inflammation resolution is an active process governed by specialized proresolving mediators and receptors. ALX/FPR2 receptors (ALX) are targeted by both proresolving and proinflammatory ligands for opposing signaling events, suggesting pivotal roles for ALX in the fate of inflammatory responses. Here, we determined if ALX expression and ligands were linked to severe asthma (SA). CONCLUSIONS. Together, these findings have established an association between select ALX receptor ligands and asthma severity that define a potentially new biochemical endotype for asthma and support a pivotal functional role for ALX signaling in the fate of lung inflammation. METHODS. ALX expression and levels of proresolving ligands (lipoxin

Children with chronic medical conditions, including heart disease, have increased susceptibility to behavioral health concerns. We sought to evaluate the feasibility and parental opinion of anxiety screening in pediatric cardiology clinic. The PROMIS Pediatric Anxiety v2.0 Short Form 8a (PA2-S8) questionnaire was administered to 48 patients presenting to pediatric cardiology clinic for follow-up care. Parents/caregivers were asked their opinion on anxiety screening in cardiology clinic. The survey was completed by 47 out of 48 participants (median age 13, range 9-17). Fourteen (30%) participants had scores suggestive of increased anxiety symptomatology. No trends were identified between PA2-S8 score and age at diagnosis ( P = .13), age at survey administration ( P = .28), number of lifetime procedures ( P = .89), number of noncardiac specialists ( P = .13), or underlying cardiac diagnoses ( P = .55). Most families (76%) were in favor of the screening effort. This study suggests that anxiety screening in cardiology clinic is both feasible and well-received by families.