Background We examined data from a Phase 2 trial {NCT00457821 } of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity. Methods Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing, and analysis was employed for the first time.. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity. Results Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal. Conclusions Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.

Background A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on two prior NIAID Inner City Asthma Consortium trials. Objective We sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. Methods The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the PROSE (Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations) study. We characterized those inner-city children with and without asthma exacerbations in the fall periods treated with guidelines based therapy (GBT) in the absence and presence of omalizumab. Results A higher saEPI was associated with an exacerbation in both the GBT alone (p<0.001, AUC 0.76) and the GBT + omalizumab group (p<0.01, AUC 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percent and number, and higher treatment step were associated with those who had an exacerbation compared to those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. Conclusions An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.

Pediatric asthma is a common chronic condition with wide-ranging implications for children's health, their families, and the health care system. The diagnosis may be relatively straightforward for the child with characteristic symptoms, triggers, and response to therapy, but there are other less common presentations that can make the diagnosis challenging. Diagnosing asthma in a toddler with recurrent wheezing can be particularly difficult. Treating asthma in a step-wise fashion usually reduces symptom frequency and improves asthma control. Asthma exacerbations and poor outcomes from acute exacerbations remain an area in which we have room for improvement. This article provides an overview of the diagnosis and management of childhood asthma for the primary care provider. [ Pediatr Ann. 2019;48(3):e103–e109.]

Background All 50 United States implemented newborn screening (NBS) for cystic fibrosis (CF) by 2010. The purpose of this study was to evaluate trends over the decade when NBS became universal to determine current rates of malnutrition, stunting, and infection rates in U.S. infants with CF. Methods Annual data were obtained on infants with CF up to 24 months of age diagnosed between 2001 and 2010 in the CF Foundation Patient Registry (CFFPR), in both the years of and after diagnosis, including method of diagnosis, demographics, and growth parameters and microbiology. Results Data were obtained on 8178 infants diagnosed with CF. The percentage of infants diagnosed by NBS increased from 15% in 2001‐83% in 2012 (P < 0.001). Mean weight, length, and weight‐for‐length z‐scores in the year of diagnosis increased from 2001 to 2012 (Wt z‐score 2001: −1.32 (SD 1.41), 2012: −0.72 (SD 1.12); Ht z‐score 2001: −1.32 (SD 1.57), 2012 −0.60 (SD 1.21); Wt/Ht Z score 2001: −0.54 (SD 1.18), 2012: 0.06 (SD 1.05); P < 0.001 for each). The proportion of infants on pancreatic enzymes decreased from 94% in 2001‐83% in 2012 (P < 0.0001). Pseudomonas aeruginosa culture positivity in the diagnosis year decreased significantly (27% in 2001, 15% in 2012, P < 0.001). Conclusions Nationwide implementation of CF NBS is temporally associated with significant improvements in growth outcomes and reductions in P. aeruginosa infections. Current rates of malnutrition, stunting, and airway infection present a target for early intervention and quality improvement efforts.

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Daily controller therapy is a mainstay of asthma treatment(1), however adherence to asthma medications is problematic(2). Traditional methods of measuring adherence do not provide day-to-day objective data. Adherence monitoring sensors that are placed directly on inhaled asthma medications attempt to address this problem(3); however it is unknown how feasible it is to integrate such devices among high-risk, asthmatic children and more evidence is needed on how to integrate these types of devices into real-life clinical practice(4).Our primary objective was to evaluate the feasibility of using a commercially available adherence device in children in a real-life clinical setting. We hypothesized that patients, parents and providers would find the devices easy to use and would continue using them if given the opportunity. MethodsThis study was approved by the Colorado Multiple Institutional Review Board (15-0211) prior to patient recruitment, and is listed on www.clinicaltrials.gov (NCT02617420). Study PopulationTwenty-five children aged 6-17 years old with asthma and at least one hospitalization or 2 emergency room visits for asthma in the last year were recruited. Written consent was obtained. Adherence was monitored for 3 months for each patient. Providers were asked to participate if they had a patient that chose to enroll.

It is recognized that asthma places a significant economic burden on the United States, with a total cost of $81.9 billion total costs including costs incurred by absenteeism and mortality. Severe asthma places a large burden of morbidity on children and their caregivers, including severe exacerbations, medication side effects, increased missed school days leading to impaired school performance, and lower caregiver quality of life. Therefore, we need to take a careful look at how we can make asthma care more efficient and cost effective, especially for those children with severe asthma. The 2019 American Thoracic Society symposium reported in this theme issue presented four aspects of managing severe asthma in children that merit attention including patient variables that affect severe asthma, understanding patient behaviors around medications, the appropriate use of bronchoscopy in diagnosis and management of severe asthma, and also the rational use of biologic therapy. This editorial will summarize key points in each of these reviews and prompt a more careful reading of each contribution.

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