Validation of inducible basophil biomarkers: Time, temperature and transportation.

BACKGROUND: The short stability window of several hours from blood collection to measuring basophil activation has limited the use of flow cytometry-based basophil activation assays in clinical settings. We examine if it is possible to extend this window to 1 day allowing for shipment of samples between laboratories. Several options exist for reporting the results including reporting all the measured values directly, calculating ratios and reporting a single value covering all measured results. Each of these options have different stability and value to the physician. METHODS: Whole blood samples from peanut allergic patients were stimulated with four different peanut concentrations at Day 0, Day 1, and Day 2. Samples were stored under temperature-controlled conditions. Flow cytometry was used to analyze the samples. The basophil activation and degranulation were measured as percentage of positive CD63 basophils and CD203c MFI fold change. Shipped samples were transported under ambient conditions. RESULTS: The results show that CD63 is a stable marker at Day 1. The CD203c ratio decreases significantly at Day 1. Calculating the CD63/IgE ratio proves to be more stable than CD63 alone. The most stable readouts are the semi-quantitative results and the trajectory of the dose response curve. Finally, we confirmed that the stability can be extended to samples shipped overnight to the laboratory. CONCLUSIONS: It is possible to extend the stability of the basophil activation assay to 1 day for samples stored at 18-25°C as well as samples shipped under ambient conditions as long as the temperature is within the 2-37°C range.

Association Between Changes in Timing of Spring Onset and Asthma Hospitalization in Maryland.

Importance: Ongoing climate change is affecting the health of communities across the globe. While direct consequences, including morbidity and mortality tied to increases in the frequency of extreme weather events, have received significant attention, indirect health effects, particularly those associated with climate change-driven disruptions in ecosystems, are less understood. Objective: To investigate how ongoing changes in the timing of spring onset related to climate change are associated with rates of asthma hospitalization in Maryland. Design, Setting, and Participants: This cross-sectional study of 29 257 patients with asthma used general additive (quasi Poisson) and mixed-effect (negative binomial) models to investigate the association between changes in the timing of spring onset, detected using satellite observations, and the risk of asthma hospitalization in Maryland from 2001 to 2012. Data analysis was conducted from January 2016 to March 2019. Exposures: Phenology data, derived from the National Aeronautics and Space Administration's Moderate Resolution Imaging Spectroradiometer, were used to calculate location-specific median dates for start of season from 2001 to 2012. How the start of season for a given year and location deviated from the long-term average was calculated and categorized as very early, early, normal, or late. Main Outcomes and Measures: Daily asthma hospitalization in Maryland during the spring season (ie, March to May). Results: There were 108 358 total asthma hospitalizations during the study period, of which 29 257 (27.0%; 14 379 [49.1%] non-Hispanic black patients; 17 877 [61.1%] women) took place during springtime. In the unadjusted model, very early (incident rate ratio [IRR], 1.17; 95% CI, 1.07-1.28) and late (IRR, 1.07; 95% CI, 1.00-1.15) onset of spring were associated with increased risk of asthma hospitalization. When the analysis was adjusted for extreme heat events and concentrations of particulate matter with an aerodynamic diameter less than 2.5 µm, the risk remained significant for very early spring onset (IRR, 1.10; 95% CI, 1.02-1.20) but not for late spring onset (IRR, 1.03; 95% CI, 0.97-1.11). Conclusions and Relevance: These results suggest that ongoing changes in the timing of spring onset, which are related to climate variability and change, are associated with asthma hospitalization. Given the high burden of allergic diseases and the number of individuals sensitized to tree pollen, these findings serve as a wake-up call to public health and medical communities regarding the need to anticipate and adapt to the ongoing changes in the timing and severity of the spring allergy season.

A comparison of fluticasone propionate nasal spray and cetirizine in ragweed fall seasonal allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are generally considered the most effective medication class for controlling allergic rhinitis. Previous comparative studies with oral antihistamines have been only partially informative due to a variety of variables encountered during their execution. OBJECTIVE: To compare fluticasone propionate nasal spray (FPNS) with the second-generation antihistamine cetirizine (oral tablet) and with placebo in a head-to-head study in a 2-week treatment study during fall ragweed season. METHODS: A total of 978 subjects were screened for this study. Six hundred and eighty-two subjects were randomized into the study (170 subjects, FPNS 200 mcg once daily; 170, cetirizine 10 mg once daily; 171, FPNS placebo; 171, cetirizine placebo) and comprised the intent-to-treat population. A 1-week placebo run-in was followed by a 2-week active treatment period during which time a total nasal symptom score (TNSS), total ocular symptom score, and the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire were collected. RESULTS: The primary efficacy end point was the mean change from baseline over the entire treatment period in A.M. reflective TNSS. The TNSS was the sum of the four individual nasal congestion, nasal itching, rhinorrhea, and sneezing scores, in which each symptom was scored on a scale of 0 to 3. Both FPNS and cetirizine improved the primary end point when compared with placebo during the active treatment period. Although there was a trend that favored FPNS with regard to the primary and secondary end points, there was not a statistical difference between the two treatments. CONCLUSION: FPNS and cetirizine were equally effective in treating fall seasonal allergic rhinitis during a 2-week head-to-head treatment investigation. Clinical trial NCT01916226, www.clinicaltrials.gov.

Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma.

RATIONALE: Exercise is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma, including protection from decrements in lung function caused by exercise. The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by standardized exercise challenge in pediatric and adolescent patients with persistent asthma. METHODS: Multicenter, randomized, double-blind, parallel group trial of 248 subjects with persistent asthma (age 4-17 years) randomized to receive fluticasone propionate/salmeterol (100/50 mcg twice daily) or fluticasone propionate alone (100 mcg twice daily) via Diskus for 4 weeks. Exercise challenge tests were performed during screening and approximately 8 hr after administration of the blinded study medication on Treatment Day 28. RESULTS: After 4 weeks of therapy both treatments provided protection following exercise challenge. The protection estimated by the maximal fall in FEV(1) was significantly better for fluticasone propionate/salmeterol (9.5 +/- 0.8% [mean +/- SE]) compared with fluticasone propionate alone (12.7 +/- 1.1%, P = 0.021). Statistically significant differences were not observed for asthma rescue-free days and asthma symptom-free days. CONCLUSION: Chronic dosing with fluticasone propionate/salmeterol in a single device provides superior protection compared with an inhaled corticosteroid alone in protecting against exercise-induced asthma in children with persistent asthma.

Asthma exacerbations in African Americans treated for 1 year with combination fluticasone propionate and salmeterol or fluticasone propionate alone.

OBJECTIVE: This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone. RESEARCH AND DESIGN METHODS: This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects >/=12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period (FP/salmeterol [FSC] 100/50 mcg [n=239] or FP 100 mcg [n=236] BID), and a 4-week FP 250 mcg BID run-out period. Annualized exacerbation rate was the primary outcome for comparing the two treatments. Other measures of asthma control included peak expiratory flow, asthma symptoms, and albuterol use. Safety was assessed through adverse events. RESULTS: Exacerbation rates were not significantly different in those treated with FSC 100/50 mcg (0.449 per year) compared with FP 100 mcg (0.529 per year, p=0.169). When the per-protocol analysis was applied, the rates were 0.465 and 0.769 per year for FSC 100/50 mcg and FP 100 mcg, respectively. Treatment with FSC 100/50 mcg provided statistically greater improvements in lung function measures and nighttime awakenings (p