Allergen Content and Protease Activity in Milk Feeds from Mothers of Preterm Infants.

Rationale: There is little information regarding the allergen content of milk feeds in the preterm population. Previous studies have not performed a broad analysis of the allergenic peptide content and protease activity of milk feeds in this population. Methods: To evaluate feasibility, we initially performed mass spectrometry on 4 human milk (HM) samples (2 term and 2 preterm) from the Mommy's Milk Human Milk Biorepository (HMB) and analyzed the results against the University of Nebraska FASTA database and UniProt for a total of 2,211 protein sequences. We then further analyzed five samples from the Microbiome, Atopy, and Prematurity (MAP) study including peptidomic and protease activity analysis. Results: Each HMB sample had between 806 and 1,007 proteins, with 37-44 nonhuman proteins/sample encompassing 26 plant and animal species. In the preterm MAP samples, 784 digested nonhuman proteins were identified, 30 were nonbovine in origin. Proteins from 23 different species including aeroallergens, food, and contact allergens were identified. Protease activity was highest in HM samples without human milk fortifier and lowest in preterm formula. Conclusions: These findings represent the first preterm milk feed mass spectrometry and protease analysis with identification of known allergenic proteins to food, contact, and aeroallergens. These results raise questions of whether the composition of milk feeds in the neonatal intensive care unit impact the development of atopic disease in the preterm population and whether the complex interaction between allergens, proteases, and other HM components can serve to induce sensitization or tolerance to allergens in infants. Clinical Trial Registration Number: NCT04835935.

Dose-dependent association between inhaled corticosteroid use and risk of obesity and metabolic syndrome in asthma.

Background: Inhaled corticosteroids (ICS) are widely prescribed medications. Some studies have reported that ICS may suppress the hypothalamic-pituitary-adrenal axis and induce systemic effects. Objective: To explore the possibility of a dose-dependent association between the long-term use of ICS and the risk of obesity and other markers of metabolic syndrome. Methods: A 5-year retrospective two-arm cohort study explored patients on asthma and not on ICS relative to patients with asthma who were on varying doses of ICS (low, medium, and high) and attributes such as body mass index (BMI) trajectory and prescription of antihypertensive, antidiabetic, and cholesterol-lowering medications. Results: A total of 229 subjects with asthma were in the control cohort, and 215 subjects with asthma were in the ICS cohort. The ICS cohort was subdivided into individuals on low- (n = 88), medium- (n = 107), or high- (n = 20) dose ICS throughout the 5-year study period. For every 1-year increase in time, the BMI in the high-dose ICS group increased at a rate of 0.25 kg/m² when compared with the subjects in the control group after controlling for age and gender. Also, for every 1-year increase in time, the BMI of those on medium-dose ICS increased by 0.06 kg/m² compared with those in the control group after controlling for age and gender. The subjects on ICS also had a statistically increased risk of being prescribed antihypertensive, antidiabetic, and cholesterol-lowering medications. Conclusion: ICS use in the subjects with asthma was associated with a dose-dependent risk of increasing BMI trajectories over time and an increased requirement for antidiabetic and cholesterol-lowering medications. One possible conclusion from this study is that long-term medium- and high-dose ICS have the potential to induce systemic effects.

Correlation of skin prick testing to environmental allergens.

BACKGROUND: To diagnose and adequately treat allergies, identification of sensitizing allergens is crucial. Skin prick or serum immunoglobulin E testing determines sensitization to potential allergens. Consensus varies regarding degree of cross-reactivity between aeroallergens. OBJECTIVE: To quantify correlations between aeroallergen skin prick test results. METHODS: A total of 11,832 patients' quantitative skin prick test results and basic characteristics were obtained from a tertiary academic center's electronic medical record and deidentified. Data were analyzed using Spearman's rank correlation coefficients to detect nonlinear associations between wheal sizes of skin prick test results. RESULTS: The highest correlation among grasses was 0.903 (fescue and red top). Of note, 13 more grass pairs had correlation more than 0.8, and 19 had correlation between 0.7 and 0.8. The Northern grass comparative results are from a satellite clinic that tested more grasses than the main clinic, in which only Kentucky blue and Bermuda were tested (correlation 0.768; n = 9348). Highest correlation among weeds was 0.74 (lambs quarter and pigweed). In addition, 6 more weed pairs had correlation more than 0.7. Highest correlation among trees was 0.724 (palm and alder) and 6 more tree pairs had correlation more than 0.7. Highest correlation among molds was 0.711 (Helminthosporium and Epicoccum). Dust mite correlation between Dermatophagoides farinae and Dermatophagoides pteronyssinus was 0.848 (n = 10,022). CONCLUSION: This study confirmed the expected high degrees of correlation not only between skin prick test results of related environmental allergens but also between less closely related Northern grasses and Bermuda grass. This has implications for simplification of testing and immunotherapy protocols in the future.