BACKGROUND:Wheezing lower respiratory tract illnesses are a major health concern in preschool children. We report the results of the ORBEX trial which evaluated the safety and efficacy of the bacterial lysate, OM-85, in the primary prevention of wheezing lower respiratory tract illness. METHODS:ORBEX is a parallel-arm, double-blind, placebo-controlled trial for the primary prevention of wheezing lower respiratory tract illness in young children at increased risk for asthma due to atopic dermatitis, parental asthma, or asthma in a blood sibling aged 4 years or older. Children aged 6-18 months were centrally randomly assigned (1:1) at 11 academic clinical sites with experience in recruiting young children in the USA to receive OM-85 3·5 mg or placebo orally for 10 days each month for 24 months and then followed for an additional 36 months to evaluate outcomes while they were off the study drug. Identical openable capsules were used for active drug and placebo, and staff, investigators, and participants were masked to treatment assignment. Participants received usual treatment for wheezing illness as per US guidelines. Randomisation was stratified by sex, age group, family history of asthma, and clinical site. The primary outcome was the time to first wheezing lower respiratory tract illness during the 36-month observation period off the study drug analysed in the intention-to-treat population, which included all randomly assigned participants. The trial is registered with clinicaltrials.gov, NCT02148796, and is completed. FINDINGS:Between Jan 3, 2017, and Nov 30, 2020, 984 children were screened for eligibility, 162 were excluded, and 822 were randomly assigned (411 to the OM-85 intervention group and 411 to the placebo group). 492 participants were male (59·9%) and 330 (40·1%) were female and the mean age of participants was 11·8 months (SD 3·8). 681 children completed the 24-month treatment period, and 596 children completed the 36-month observation period. 132 children experienced at least one wheezing lower respiratory tract illness during the observation period; 71 (21%) of 342 in the OM-85 group and 61 (18%) of 339 in the placebo group. There was no significant difference between OM-85 and placebo with respect to the time to first wheezing lower respiratory tract illness (log-rank test p value 0·35; hazard ratio 1·16 [95% CI 0·82-1·64]). The most frequent adverse events, fevers, coughs, and colds, did not differ between groups. INTERPRETATION:Oral administration of OM-85 in early life did not decrease the incidence of wheezing lower respiratory tract illness in this high-risk population. Bacterial lysates are not efficacious for the primary prevention of asthma-like symptoms during the preschool years. FUNDING:National Heart, Lung, and Blood Institute and OM Pharma with supplemental funding and provision of study drug and placebo from OM Pharma.

While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. To identify multiple distinct molecular mechanisms implicated in asthma exacerbations by characterizing respiratory illnesses among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab vs placebo. This is a secondary analysis of the Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (MUPPITS-2) double-blind, placebo-controlled, parallel-group, randomized clinical trial comparing treatment with mepolizumab vs placebo among children with exacerbation-prone asthma in low-income urban centers in 9 US cities. Data analysis was performed from September 2022 to April 2025. Participants were randomized to receive either mepolizumab (aged 6-11 years: 40 mg; aged 12-17 years: 100 mg) or matching placebo by subcutaneous injection once every 4 weeks for 52 weeks. The primary measurement was a transcriptomic modular analysis by RNA sequencing of nasal samples obtained during acute respiratory illnesses. Associations among upper airway transcriptional signatures, the clinical outcome of respiratory illnesses, and pulmonary functions were investigated. Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants (median [IQR] age, 10.0 [9.0-13.0] years; 48 [44%] female) were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module associated with T2 inflammation (log2 fold change [FC] estimate, −0.60; false discovery rate [FDR] < .05) but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo (log2 FC estimates, 0.22-0.85; FDR < .05). Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to nonexacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus, while macrophage pathways contributed specifically to viral exacerbations. Three distinct, semiorthogonal inflammatory axes were shown to underlie the majority of the heterogeneity among exacerbations in the 2 groups. The study’s findings implicate multiple alternative inflammatory pathways associated with the epithelium and macrophages, as well as mucus hypersecretion, as mechanisms of residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes can independently contribute to asthma exacerbations. ClinicalTrials.gov Identifier: NCT03292588

Rationale: Systemic corticosteroids are standard-of-care treatment for asthma exacerbations; however, little is known about whether corticosteroid effects on airway inflammatory pathways differ when added to biologic therapies targeting type 2 inflammation. Methods: 290 urban children (6-17 years) with exacerbation-prone eosinophilic asthma were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected at baseline (before treatment), post-exacerbation (5-10 days after starting systemic corticosteroids), and on treatment for RNA-sequencing. Differentially expressed genes (DEGs) were assessed using mixed effects modeling (significance threshold FDR<0.05). Results: 98 participants were evaluated following 170 exacerbation events (placebo:105, mepolizumab:65). In the placebo group, there were no significant differentially expressed genes comparing on treatment to before treatment timepoints. In the placebo group, there were 6363 significant DEGs (2734 increased, 3629 decreased) comparing post-exacerbation to on treatment. In the mepolizumab group, there were 1404 significant DEGs (664 increased, 740 decreased) comparing on treatment to before treatment (Fig1A: x-axis). In the mepolizumab group, there were 1111 significant DEGs (413 increased, 698 decreased) comparing post-exacerbation to on treatment (Figure 1A: y-axis). In the post-exacerbation versus on treatment contrasts, there were 885 overlapping significant DEGs (348 increased, 537 decreased) between the placebo and mepolizumab participants. Mepolizumab reduced expression of eosinophil-associated genes (CCL23, GATA1, CLC, PRSS33, PTGDR2, ADORA3, THBS4) on treatment, with a larger decrease post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab did not significantly alter expression of mast cell/T2 cytokine-related genes (HDC, CPA3, GATA2, TPSAB2, IL5, IL13, IL1RL1, ALOX15) on treatment; however, expression of these genes significantly decreased post-corticosteroid (more reduced than placebo) (FDR<0.05) (Fig1B). Mepolizumab increased expression of genes associated with epithelial and airway inflammation (CFTR, ERBB2, BMP3, TRPV4) on treatment; however, expression of these genes returned to baseline levels post-corticosteroid (FDR<0.05) (Fig1B). Conclusions: By comparing differential gene expression across treatment groups and time points, we identified overlapping DEGs related to systemic corticosteroid effects, DEGs related only to mepolizumab treatment, and clusters of functionally related genes with additive effects of mepolizumab plus systemic corticosteroids. Mepolizumab enhances the actions of oral corticosteroids on eosinophil related pathways in relation to exacerbations. Oral corticosteroids provide the added benefit of down-regulating mast cell and T2 cytokine pathways. Finally, oral corticosteroids reverse the up-regulation of epithelial inflammatory pathways that occurred during mepolizumab treatment.

Multiple early life environmental exposures are thought to influence childhood asthma incidence. The coronavirus disease 2019 (COVID-19) pandemic resulted in changes in air pollution levels and a marked disruption in the circulation of childhood respiratory viruses. Both air pollution and respiratory viruses have been implicated in the development of asthma and early childhood wheeze. Human behavior and daily routine practices, including family gatherings and daycare attendance, were impacted profoundly by the COVID-19 pandemic and the associated mitigation measures. The changes to human behavior and social interactions that occurred during the pandemic have and will likely continue to impact chronic diseases, including the development of asthma. This rostrum explores how childhood asthma incidence might be affected by the COVID-19 pandemic and its associated public health mitigation measures. Recently completed and ongoing clinical trials being conducted in the infant and toddler population and assessing allergic outcomes may be well positioned to examine the impact of the pandemic on asthma incidence and time to asthma onset.

Background: While biologic therapies targeting type 2 (T2) inflammation reduce acute exacerbation rates in children with asthma and T2 inflammation, exacerbations still occur, and the underlying molecular mechanisms are poorly defined. We aimed to identify the multiple distinct molecular mechanisms implicated in asthma exacerbations in children by contrasting exacerbations among urban children with eosinophilic asthma enrolled in a clinical trial comparing treatment with mepolizumab versus placebo.Methods: We performed transcriptomic modular analysis of nasal samples obtained during acute respiratory illnesses from urban children with exacerbation-prone eosinophilic asthma enrolled in the MUPPITS-2 clinical trial, which compared treatment with mepolizumab versus placebo. We investigated associations among upper airway transcriptional signatures, respiratory illnesses that resulted in exacerbations, pulmonary function, and biomarkers of T2 inflammation.Findings: Of the 290 participants enrolled in the MUPPITS-2 trial, 108 participants were sampled during 176 acute respiratory illness events. During illness events resulting in asthma exacerbations, children receiving mepolizumab demonstrated decreased expression of an eosinophil-associated module related to T2 inflammation but increased expression of gene modules associated with epithelial and macrophage inflammatory pathways relative to children receiving placebo. Both groups showed higher expression of mucus secretion and cellular stress response pathways during exacerbations relative to non-exacerbation illnesses. The mepolizumab group demonstrated upregulation of epithelial inflammatory pathways in exacerbations irrespective of a respiratory virus while macrophage pathways occurred specifically in viral exacerbations.Interpretation: Our findings implicate multiple alternative inflammatory pathways related to the epithelium and macrophages, as well as mucus hypersecretion, as probable mechanisms responsible for residual acute exacerbations in children receiving mepolizumab. Further, they indicate that multiple distinct inflammatory axes contribute to asthma exacerbations.Funding: The research reported in this publication was supported by NIH-NIAID award numbers 5UM1AI114271, UM1AI160040, and UM2AI117870, with additional support provided through award numbers UL1TRG01422, UL1RR025741, UL1TR000150, UL1TR001422, UL1 TR002535, UL1TR001876, and 5UL1TR001425–03. Additional support was also provided through an unrestricted grant from GlaxoSmithKline.Declaration of Interest: All authors except A. Togias and P. Becker report grants from NIH/NIAID during the conduct of study. W. Busse reports consulting fees from Novartis, GlaxoSmithKline, Genentech, Sanofi, AstraZeneca and Regeneron, royalties from Elsevier outside the submitted work. M. Gill reports an honorarium for and support for travel to the 2017 AAAAI meeting during the conduct of study and monetary compensation from the American Academy of Pediatrics for her work teaching the biannual Pediatrics board review course, PREP The Course. K. Hershey reports grants from Adare, during the conduct of the study. D. Jackson reports personal fees from Novartis, Pfizer, Regeneron, AstraZeneca, Sanofi and Vifor Pharma, grants and personal fees from GlaxoSmithKline and grants from NIH/NHLBI, outside the submitted work. M. Kattan reports personal fees from Regeneron, outside the submitted work. R. Gruchalla reports government employment from Center for Biologics Evaluation and Research as well as personal fees from Consulting Massachusetts Medical Society, outside the submitted work. A. Liu reports personal fees from Phadia ThermoFisher as consulting honoraria, grants and non-financial support from ResMed/Propeller Health, non-financial support from Revenio, grants and personal fees from Avillion and personal fees from Labcorp, outside the submitted work. L. Bacharier reports book royalties from Elsevier, consulting fees from Sanofi, Regeneron, Genentech, GlaxoSmithKline, DBV technologies, Teva, Medscape, Kinaset, OM Pharma and AstraZeneca, honoraria from Sanofi, Regeneron and GlaxoSmithKline, participation in advisory board for DBV Technologies, AstraZeneca and Vertex, leadership role in American Academy of Allergy Asthma & Immunology and American Board of Allergy and Immunology and medical writing services for Sanofi/Regeneron. J. Gern reports consulting fees from AstraZeneca and Meissa Vaccines, two patents related to the methods to enhance the production of rhinoviruses and stock options with Meissa Vaccines. S. Teach reports grants from NIH–NHLBI, payment from Medscape and personal fees from Uptodate. S. Lynch reports personal fees from Siolta Therapeutics, personal fees from Sanofi, a patent Reductive prodrug cancer chemothera (Stan449-PRV) issued, a patent Combination antibiotic and antibody therapy for the treatment of Pseudomonas aeruginosa infection; WO 2010091189 A1 with royalties paid to KaloBios Inc., a patent Therapeutic microbial consortium for induction of immune tolerance licensed to Siolta Therapeutics, a patent Systems and methods for detecting antibiotic resistance (WO 2012027302 A3) issued, a patent Nitroreductase enzymes. US 7687474 B2 issued, a patent Sinusitis diagnostics and treatments WO 2013155370 A1 issued, a patent Methods and systems for phylogenetic analysis US 20120264637 A1 issued, and a patent methods and compositions relating to epoxide hydrolase genes issued to Siolta Therapeutics and reports that she is a co-founder of Siolta Therapeutics, a start up company that is developing a mixed-species microbial oral therapeutic for induction of immune tolerance. All other authors declare no competing interests.Ethical Approval: The protocol was approved by a central IRB. The legal guardians of all study participants provided written informed consent and children provided assent.

This article provides an overview of the findings obtained from the Vitamin D Antenatal Asthma Reduction Trial (VDAART) spanning a period of 15 years. The review covers various aspects, including the trial's rationale, study design, and initial intent-to-treat analyses, as well as an explanation of why those analyses did not achieve statistical significance. Additionally, the article delves into the post hoc results obtained from stratified intent-to-treat analyses based on maternal vitamin D baseline levels and genotype-stratified analyses. These results demonstrate a statistically significant reduction in asthma among offspring aged 3 and 6 years when comparing vitamin D supplementation (4400 IU/d) to the standard prenatal multivitamin with vitamin D (400 IU/d). Furthermore, these post hoc analyses found that vitamin D supplementation led to a decrease in total serum IgE levels and improved lung function in children compared to those whose mothers received a placebo alongside the standard prenatal multivitamin with vitamin D. Last, the article concludes with recommendations regarding the optimal dosing of vitamin D for pregnant women to prevent childhood asthma as well as suggestions for future trials in this field.

BackgroundCockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children.ObjectiveTo determine if nasal allergen challenge (NAC) responses to cockroach allergen would improve following one year of SCIT.MethodsUrban children with asthma, that were cockroach-sensitized and reactive on NAC, participated in a yearlong randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean total nasal symptoms scores (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test (SPT) wheal size, serum allergen-specific antibody production and T-cell responses to cockroach allergen were assessed.ResultsChanges in mean NAC TNSS did not differ between SCIT-assigned (n=28) versus placebo-assigned (n=29) participants (p=0.63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum specific IgE (sIgE) decreased to a similar extent in both groups, while decreased cockroach SPT wheal size was greater among SCIT participants (p=0.04). A 200-fold increase in cockroach sIgG4 was observed among subjects receiving SCIT (p<0.001) but was unchanged in the placebo group. T-cell interleukin-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (p=0.002), while no effect was observed for interleukin-10 or interferon-gamma.ConclusionA year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum sIgG4 production and down-modulation of allergen stimulated T-cell responses.

Ratings migration are most often modeled as a time homogeneous first-order Markov chain. A novel nonlinear inversion procedure is presented for recovering a ratings migration matrix that is indirectly linked to economic factors through a single moment consistency equation. The procedure is comparable to the approach suggested by Belkin et al. (CreditMetrics Monitor 1(2):46–56, 1998) but represents an important nonparametric alternative that may be easier to implement in practice. In addition to having merit for portfolio stress testing, the empirical application of the procedure is demonstrated for the credit quality dynamics portion of CECL methodology.

PurposeThe aim of this study is to report on a simple derivation that results in what the authors refer to as the lending cap rate. The lending cap rate is a unique cap rate resulting in a property valuation that perfectly aligns the maximum loan amount for the financing of commercial real estate.Design/methodology/approachThe derivation is the result of simple algebra relating the two most common underwriting ratios: debt service coverage and loan-to-value with the formula for the present value of an annuity. Numerical examples are presented to demonstrate the calculation of the lending cap rate, property valuation and maximum loan amount. The authors also present comparative statics results.FindingsThe main finding of this research is that once a lender knows the debt service coverage ratio, loan-to-value ratio and lending terms for a specific property financing request, a simple calculation reveals the lending cap rate and the property valuation that aligns the maximum loan amount implied by the two underwriting ratios.Practical implicationsOne practical implication of the research is that a simple calculation reveals the lending cap rate which facilitates timely property evaluations for lending purposes. The methods demonstrated also offer real estate finance educators a practical means of connecting the loan underwriting process with property appraisal thereby facilitating conceptual understanding.Originality/valueThe key finding is original, and the importance of the finding is that the determination of the lending cap rate is simple and has the ability to make commercial real estate lending faster and cheaper, especially in lending situations where an evaluation rather than an appraisal is appropriate.

Mepolizumab (anti-IL5) reduces asthma exacerbations in urban children. We previously utilized nasal transcriptomics to identify inflammatory pathways (gene co-expression modules) associated with exacerbations despite this therapy. To understand mepolizumab's precise impact on these pathways, we assess gene co-expression and loss of correlation, "decoherence," using differential co-expression network analyses. 290 urban children (6-17 years) with exacerbation-prone asthma and blood eosinophils ≥150/microliter were randomized (1:1) to q4 week placebo or mepolizumab injections added to guideline-based care for 52 weeks. Nasal lavage samples were collected before and during treatment for RNA-sequencing. Differential co-expression of gene networks was evaluated to assess interactions and regulatory aspects of type-2 and eosinophilic airway inflammation. Mepolizumab, but not placebo, significantly reduced the overall expression of an established type-2 inflammation gene co-expression module (fold change=0.77, p=0.002) enriched for eosinophil, mast cell, and epithelial IL-13 response genes (242 genes). Mepolizumab uncoupled co-expression of genes in this pathway. During mepolizumab, but not placebo treatment, there was significant loss of correlation among eosinophil-specific genes including RNASE2 (EDN), RNASE3 (ECP), CLC, SIGLEC8, and IL5RA contrasting a reciprocal increase in correlation among mast cell-specific genes (TPSAB1, CPA3, FCER1A), T2 cytokines (IL4, IL5, and IL13), and POSTN. These results suggest mepolizumab disrupts the regulatory interactions of gene co-expression among airway eosinophils, mast cells and epithelium by interrupting transcription regulation in eosinophils with enhancement in mast cell and epithelial inflammation. This paradoxical effect may contribute to an incomplete reduction of asthma exacerbations and demonstrates how differential co-expression network analyses can identify targets for more precise therapies.

Identification of airway inflammatory pathways in asthma has proven essential to understanding mechanisms of disease and has led to effective personalized treatment with biologic therapies. However, relatively little is known about patterns of airway inflammation at the time of respiratory illnesses and how such patterns relate to responsiveness to biologic therapies. The MUPPITS-1 (n=106) and MUPPITS-2 (n=290) studies investigated asthma exacerbations in urban children with exacerbation-prone asthma and ≥150/microliter blood eosinophils. Children in both studies received guidelines-based asthma care; in MUPPITS-2, participants were additionally randomized (1:1) to placebo or mepolizumab. Nasal lavage samples were collected during respiratory illnesses for RNA-sequencing and analyzed by modular analysis to assess genome-wide expression patterns associated with exacerbation illnesses. Among 284 illnesses, exacerbations that occurred in the absence of mepolizumab therapy showed significantly higher upregulation of eosinophil associated inflammatory pathways (fold change values [FC]=1.27-1.43, p-values<0.05), including a Type-2 inflammation module composed of eosinophil, mast cell, and IL-13 response genes. In contrast, exacerbations that occurred while on mepolizumab therapy showed significantly higher upregulation of several epithelial inflammatory pathways (FC=1.36-1.64, p-values<0.05) including TGF-β/Smad3 signaling, extracellular matrix production, and epidermal growth factor receptor signaling. These results indicate that novel inflammatory pathways, likely originating from the airway epithelium and distinct from Type-2 or eosinophilic inflammation, drive residual exacerbations that occur in children treated with mepolizumab therapy added to guideline-based care. These findings identify likely mechanisms of persistent disease expression in these children despite significant depletion of eosinophils and can identify novel treatment targets for future studies.

The Nebraska Farm Real Estate Market Highlights 2021-2022 report represents the 44th edition of the annual series. These reports provide an important insight on agricultural land market dynamics for stakeholders across Nebraska. In today’s market, where market transactions exceeding $1 million dollars are the norm, objective market information and analysis is more critical than ever. The focus of the report continues to be on providing unbiased information for agricultural land values and rental rates so industry participants can make educated and informed decisions.

Background Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. Methods This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as >= two exacerbations in the previous year) and blood eosinophils of at least 150 cells per mu L were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. Findings Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0.96 (95% CI 0.78-1.17) with mepolizumab and 1.30 (1.08-1.57) with placebo (rate ratio 0.73; 0.56-0.96; p=0.027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. Interpretation Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

Wheezing is common in childhood, although only a small percentage of these children develop asthma. The child's wheezing phenotype and asthma predictive indices help predict the likelihood of a future asthma diagnosis. Viral infections are common in childhood with most wheezing episodes due to respiratory syncytial virus and rhinovirus . Many treatment options exist for wheezing children including both those who wheeze persistently and those who wheeze intermittently due to viral infections.

Identification of specific airway inflammatory pathways can lead to effective personalized treatment with biologics in asthma and insights to mechanisms of action.

Analytic models are developed to value farm real estate and a seller’s (buyer’s) real option to delay its sale (purchase). The model clearly shows the economic and financial fundamentals making up the capitalization rate for farmland, as well as the linkage between two asset classes: farm real estate and traded equity. Further, the most significant driver of farm real estate cap rates appears to be the risk-free rate of interest (analytically) and the yield on 10-year Treasury securities (empirically). Application of the model suggests that observed farm real estate values tend to be closer to the buyer’s rather than the seller’s real option threshold value.

Asthma exacerbations are common in urban children and have significant short- and long-term consequences. Elevated peripheral blood and airway eosinophils have been identified as risk factors for exacerbations, and therapies targeting these biomarkers reduce exacerbations in adults; however, data on anti-eosinophil treatment in children and adolescents are limited. The primary objective of this study is to determine if phenotype-directed use of mepolizumab reduces the rate of asthma exacerbations in urban children.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-a response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.

Objective: To summarize the recent evidence in the treatment of viral-induced wheezing in the infant and preschool aged child. Data Sources: Published literature obtained through PubMed database searches. Study Selections: Studies relevant to phenotypes and treatment of wheezing illnesses in infants and preschool children were included. Results: Recurrent wheezing in preschool children is common and is frequently triggered by viral respiratory tract infections. Certain phenotypes may respond to treatments differently, depending on the risk factors identified. Inhaled corticosteroids, administered continuously or intermittently, reduce the risk of virus-induced wheezing episodes. The use of leukotriene modifying agents may have a role in wheezing episodes in a select group of preschool children. Early administration of azithromycin reduces the risk of severe lower respiratory tract illnesses in children. The effect of oral corticosteroids on wheezing episodes in young children varies by degree of episode severity. Conclusion: Recurrent viral-induced wheezing illnesses has been the focus of many clinical trials, which now provide an increasingly robust evidence base for management. Additional research is needed to define optimal strategies, to best match therapies to specific phenotypes and endotypes, and will eventually begin to include therapies directed specifically at the viral triggers. (C) 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Nebraska Farm Real Estate Market Highlights 2018-2019 report represents the 41st edition to the annual series. These reports provide an important insight on agricultural land market dynamics for stakeholders across Nebraska. In today’s market, where market transactions exceeding a million dollars are the norm, objective market information and analysis is more critical than ever. The focus of the report continues to provide unbiased information on agricultural land values and rental rates so industry participants can make educated and informed decisions.