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Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet’s approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.

BACKGROUND Identifying clinical features associated with difficult-to-control asthma will help address overall control and more-effective asthma management. OBJECTIVE To evaluate our clinical observation that the proportion of patients who are overweight or obese is significantly higher in patients with difficult-to-control asthma than in patients with well-controlled asthma. METHODS This was a retrospective chart review of 400 patients, ages 5 to 18 years. Cases (n = 200) were identified as 100 subjects with difficult-to-control asthma and an inhaled corticosteroid dose of ≥1000 μg/day and 100 subjects with well-controlled asthma and an inhaled corticosteroid dose of ≤500 μg/day. The control group included 200 subjects without asthma. Multivariable logistic regression models were used to assess the relationships between asthma status and weight status, age, race, and sex. RESULTS The mean body mass index percentile (± standard deviation at 95% confidence interval) was significantly higher in the difficult-to-control asthma group versus the well-controlled asthma group versus the control group (74.66 ± 28.19 versus 54.25 ± 29.92 versus 55.19 ± 32.54; p < 0.001). Thirty-six percent of the difficult-to-control patients with asthma were obese (versus 6% of the patients with well-controlled asthma [p < 0.001] versus 13% of patients without asthma [p = 0.002]), and 47% normal weight (versus 79% of the patients with well-controlled asthma versus 75% of patients without asthma; p < 0.001). The mean age and the proportion of African Americans in the difficult-to-control asthma group were significantly higher than in the well-controlled asthma group and in the control group (p < 0.001). CONCLUSION The results of this study demonstrated a significant association between severe persistent difficult-to-control asthma and obesity, age, and race. Patients who are obese and have difficult-to-control asthma need treatment approaches that address both asthma control and weight management.

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene,SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carryingSATB1variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression and a severe phenotype. Contrastingly, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay and encode truncated proteins, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.