Efficacy of bronchial thermoplasty in a patient panel with uncontrolled severe persistent asthma.

BACKGROUND: Bronchial thermoplasty (BT) is an approved procedure to manage uncontrolled severe persistent asthma. Many insurance providers are reluctant to pay for BT without proven benefit among their specific patient panel. OBJECTIVE: Determine if BT is effective in a panel patient panel with uncontrolled severe persistent asthma. STUDY DESIGN AND METHODS: This was an unblinded prospective study of adult subjects with uncontrolled severe persistent asthma who underwent BT. Outcomes were assessed at baseline and then 3-, 6-, 12-, 18- and 24-months post-BT. The primary metric was an improved Asthma Quality of Life Questionnaire (AQLQ) score. Other metrics included improved Asthma Control Test (ACT), peak expiratory flow rates (PEFR), spirometry, fractional excretion of nitric oxide (FeNO), number of unscheduled medical visits, and lost days of work/activity. Respiratory adverse events were assessed during the BT treatment period and at each post-BT visit. RESULTS: Twenty-nine subjects completed the study; the median interquartile range (IQR) age was 47 (42-61), and the majority were female (69%), white (93%), and non-Hispanic (90%). After BT, mean (±std) AQLQ scores improved by 1.6(±1.1) at 3 months (p < 0.0001), 1.6(±1.2) at 6 months (p < 0.0001), 1.4(±1.0) at 12 months (p < 0.0001), 1.8(±1.1) at 18 months (p < 0.0001), and 1.6 (±1.5) at 24 months (p < 0.0001). There were significant improvements in ACT, PEFR, unscheduled medical visits and lost days of work and activity. Spirometry and FeNO metrics were unchanged. The average cost for subjects completing all 3 BT procedures was approximately $15,000. CONCLUSION: BT is an effective adjunctive therapeutic modality in subjects with uncontrolled severe persistent asthma.

Building research infrastructure and multisite studies in merged health care settings: A framework for nurse scientists and health care leaders.

BACKGROUND: Merged healthcare settings, particularly those with Magnet designated sites, present distinct opportunities for PhD nurse scientists developing nursing research infrastructure. PURPOSE: This article aims to assist nurse scientists and healthcare leaders in defining nurse scientist roles, and in developing research infrastructure for conducting multi-site research in merged settings. METHOD: Practical strategies and a framework are provided to assist in building and navigating nurse scientist roles and research infrastructure development. DISCUSSION: Emphasizing the necessity of organizational support, the article underscores the importance of clear role delineation and leadership support. CONCLUSION: To optimize the contributions of nurse scientists in merged healthcare settings, especially in Magnet organizations, clear role definitions, robust research infrastructure, and strong organizational support are imperative.

Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level.

BACKGROUND: In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS: In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS: A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P = 0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P = 0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). CONCLUSIONS: The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, NCT02066298.).

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

BACKGROUND: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients. METHODS: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry. RESULTS: When quintupling the dose of fluticasone (to 250 µg twice a day) was compared with adding salmeterol (50 µg twice a day) and doubling the fluticasone (to 100 µg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age. CONCLUSIONS: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Asthma prevalence and control among schoolchildren residing near outdoor air pollution sites.

INTRODUCTION: Outdoor air pollution (OAP) contributes to poor asthma outcomes and remains a public health concern in Pittsburgh. The purpose of this study was to determine the prevalence of childhood asthma and its rate of control among Pittsburgh schoolchildren residing near OAP sites. METHODS: Participants were recruited from schools near OAP sites. Asthma prevalence and control were assessed using a validated survey. Demographics and socioeconomic status were collected by survey, BMI was calculated, secondhand smoke (SHS) exposure was assessed by salivary cotinine levels, and OAP was assessed by mobile platform monitoring. Multivariate analysis adjusted for confounders. RESULTS: In 1202 Pittsburgh elementary school students surveyed, 50.9% were female, average age was 8.5 years (SD = 1.9), 52.2% were African American and 60.6% had public health insurance. SHS exposure was relatively high at 33.9%, 17.1% of students were obese, and 70% had exposure to particulate matter (PM2.5) greater than the World Health Organization standard of 10 µg/m3. Overall prevalence of asthma was 22.5% with PM2.5, nitric oxide (NOx), sulfur (S), and zinc (Zn) significantly related to odds of asthma. Among the 270 children previously diagnosed with asthma, 59.3% were not well controlled with PM2.5, black carbon, and silicon (Si) significantly related to odds of uncontrolled asthma. CONCLUSIONS: These results demonstrate that asthma prevalence and poor disease control are significantly elevated in Pittsburgh schoolchildren exposed to high levels of OAP. Future efforts need to focus on primary prevention of asthma by reducing exposure to OAP in at risk populations.

Improved asthma outcomes among at-risk children in a pharmacist-led, interdisciplinary school-based health clinic: A pilot study of the CAReS program.

BACKGROUND: Disparities in access to care and outcomes have been identified among children with asthma living in underserved communities. The Caring for Asthma in our Region's Schoolchildren program was established to reduce disparities by providing school-based, comprehensive asthma care by a pharmacist-led, interdisciplinary team to high-risk pediatric populations in the Greater Pittsburgh area. OBJECTIVE: To investigate program impact on follow-up appointment attendance, delivery of guideline-based care, asthma control, asthma morbidity (emergency department [ED] visits, oral corticosteroid [OCS] requirement), and asthma-related knowledge and quality of life. METHODS: The study enrolled 50 children with asthma from 6 elementary schools (September 2014-December 2017). Children completed 5 visits over a 3-month period. McNemar's test assessed improvement in guideline-based controller therapy use and reduced morbidity (ED visits or OCS requirement). Generalized estimating equation analyses determined the significance of monthly improvements in asthma control, asthma knowledge, and quality of life. RESULTS: A 100% show rate was achieved in nearly all participants (92.0%). Most of the patients were African-American (56%). In children with persistent disease, only 21.4% were prescribed controller therapy at baseline, which improved to 78.5% upon enrollment (P < 0.05). Asthma control statistically significantly improved (P < 0.05), and a reduction in percentage of patients who required an ED visit or an OCS burst pre-to postintervention was also statistically significant (31.3% vs. 14.6%, P < 0.05). The goal of 100% treatment plan knowledge was achieved in 67% of caregivers within 1 month and increased from 6% to 60% in children over 3 months (P < 0.05). Asthma-related quality of life also improved statistically significantly pre-to postintervention (P < 0.05). CONCLUSIONS: Disparities in asthma outcomes owing to inadequate access to health care can be addressed. Improved asthma control, asthma medication knowledge, quality of life, and reduced morbidity in high-risk pediatric patients are achievable as demonstrated by our study. Our findings support the feasibility and value of a pharmacist-led, interdisciplinary school-based health care delivery model in providing comprehensive asthma care to at-risk pediatric populations.

Cross-Sectional Study of Influences on Maternal Decisions Regarding Feeding Premature and Ill Neonates.

This cross-sectional study investigated the influences on feeding decisions made by mothers of infants admitted to neonatal intensive care units. The primary aims were to describe discrete influences on maternal behavior and to test Fishbein and Azjen's Theory of Planned Behavior in the neonatal intensive care unit (NICU) setting. The study included a convenience sample of 445 mothers in North Texas and Wisconsin. An investigator-designed tool was administered to subjects by research team members in the study units. Significant differences between minority and dominant racial groups emerged, which highlight known disparities in perinatal outcomes. Results supported the Theory of Planned Behavior and demonstrated predictors of exclusive breastfeeding at discharge including intention, race/ethnicity, length of stay in the NICU, and beliefs that the following factors influenced feeding decisions: having help with chores or childcare at home, talking with mothers in the NICU, having the NICU nurse help with feeding, and space for breastfeeding in the NICU. Incidental findings included the observation that mothers in the only NICU with private rooms were significantly more likely to report fatigue and to perceive that unit busyness, space, and privacy affected their feeding decisions, although there was no difference in breastfeeding at discharge between this NICU and others.

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

BACKGROUND: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. METHODS: We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 µg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 µg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. RESULTS: The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). CONCLUSIONS: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Theory-Driven Evaluation of a Multisite Nursing Professional Practice Model.

Evaluation of the professional practice model is an expectation in Magnet-designated facilities. Few evaluations of practice models are theory driven. A multisite, theory-driven model evaluation was conducted that included input from a variety of sources resulting in a comprehensive revision of the model.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

BACKGROUND: Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. METHODS: In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. RESULTS: Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. CONCLUSIONS: Among young children with mild persistent asthma, as-needed use of acetaminophen was not shown to be associated with a higher incidence of asthma exacerbations or worse asthma control than was as-needed use of ibuprofen. (Funded by the National Institutes of Health; AVICA ClinicalTrials.gov number, NCT01606319.).

A randomized pilot trial of a school-based psychoeducational intervention for children with asthma.

BACKGROUND: Asthma is a common childhood illness with high morbidity and mortality among minority and socio-economically disadvantaged children. Disparities are not fully accounted for by differences in asthma prevalence, highlighting a need for interventions targeting factors associated with poorer asthma control. One such factor is psychological stress. OBJECTIVE: Here, we examine the feasibility and acceptability of "I Can Cope (ICC)," a school-based stress management and coping intervention for children with asthma. METHODS: A parallel randomized pilot trial was conducted. One hundred and four low-income children (mean age 10 years; 54% male; 70% African American) with persistent asthma were recruited from 12 urban schools and randomized to the following: (a) ICC or one of two control conditions: (b) "Open Airways for Schools (OAS)"-an asthma education intervention or (c) no treatment. RESULTS: Seventy one percentage of eligible children participated in the study, with a dropout rate of 12%. ICC was rated as highly acceptable by participating children and parents. Preliminary efficacy data suggest that when compared with no treatment, ICC resulted in decreased symptoms of depression, perceived stress and child-reported symptoms of asthma, and improvements in sleep quality and child-reported asthma control. There were no intervention-related changes in objective measures of asthma morbidity. The magnitude of intervention effects on psychological function did not differ between the ICC and OAS groups. CONCLUSIONS: Results support the feasibility and acceptability of utilizing school-based interventions to access hard to reach children with asthma. Preliminary findings offer support for future, large-scale efficacy studies of school-based interventions designed to target multiple factors that contribute to asthma disparities.

Validating the Functional Pain Scale for Hospitalized Adults.

BACKGROUND: Enhancing pain patient's ability to function and cope is important, but assessing only intensity ignores those aspects of pain. The Functional Pain Scale (FPS), addresses these dimensions but lacked validation in hospitalized adults with chronic pain. AIMS: This research was conducted to establish the FPS psychometric properties in hospitalized adults. DESIGN: A prospective pilot study examined the reliability and validity of the FPS in two acute care hospitals. SETTINGS: Adult inpatients from medical/surgical units at two hospitals. PARTICIPANTS/SUBJECTS: A convenience sample of 93 subjects from an Academic Medical Center and 51 from a tertiary care hospital who were 21-81 years old and primarily Caucasian. METHODS: Hospitalized adults with chronic pain at two facilities provided pain scores from the FPS, Numeric Rating Scale, Pain, Enjoyment of Life, and General Activities Scale, and Quality of Pain Care Scale. Test-retest reliability and construct validity were evaluated using standard correlation methods. RESULTS: Hospitalized adults aged 21-88 years with chronic pain (N = 144) were evaluated. Data supported test-retest reliability of the FPS (r = .84; p < .001), which had strong, statistically significant correlations with the Numeric Rating Scale at different study sites (r = 0.75 and r = 0.45, respectively), indicating acceptable construct validity. Significant weak correlations between the FPS and other measures of mood and functioning failed to support discriminant validity. CONCLUSIONS: Although statistically significant, the reliability and validity of FPS were not as strong in hospitalized chronic pain patients as reported for older adults in other settings.

Individualized therapy for persistent asthma in young children.

BACKGROUND: Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications. METHODS: The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response. RESULTS: Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a daily ICS and was predicted by aeroallergen sensitization but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophil counts of 300/µL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments. CONCLUSIONS: In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.

The Future of Sublingual Immunotherapy in the United States.

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

Pharmacist-led screening program for an inner-city pediatric population.

OBJECTIVES: To identify the prevalence of asthma, obesity, hypertension, and environmental tobacco smoke (ETS) exposure among youth and provide recommendations for follow-up care. METHODS: This cross-sectional study consisted of 12 health screenings for children between 5 and 17 years of age in various inner city, lower socioeconomic, and predominantly black communities throughout the city of Pittsburgh, PA. The screenings were conducted by pharmacists and student pharmacists from April 2010 to April 2012. Asthma, obesity, hypertension, and ETS screenings were offered at each event. RESULTS: A total of 144 children (50% girls, 89% black, non-Hispanic) were enrolled. Sixteen percent of the study population had a previous diagnosis of asthma; 4% were poorly controlled, and 18% were identified as having potential, undiagnosed asthma. Fifty-three percent were at an unhealthy weight (0.7% underweight, 24.3% overweight, 28.5% obese), 24% had abnormal blood pressure (12.8% prehypertension, 8.5% stage 1 hypertension, 2.8% stage 2 hypertension), and 26% had ETS exposure equivalent to that of smokers (0.7% light smokers, 17.5% smokers, and 7.7% heavy smokers). Overall, 177 specific referrals were made. The incidence of hypertension (P <0.001) and the proportion of ETS equivalent to heavy smokers increased (P = 0.019) with increased weight classification. CONCLUSION: Within this self-selected inner city, predominantly black pediatric population, there were high rates of positive screens for potential asthma, obesity, hypertension, and smoking. Additionally, the risk for high ETS exposure and hypertension increased with increasing weight. This study highlights the importance of pharmacists in disease screening and the need for alternative prevention and management strategies in disparate pediatric populations.

Randomized, double-blind, placebo-controlled trial of standardized ragweed sublingual-liquid immunotherapy for allergic rhinoconjunctivitis.

BACKGROUND: Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis (ARC), but a lack of robust evidence has deterred its use in North America. OBJECTIVE: To determine the efficacy and tolerability of standardized glycerinated short ragweed sublingual allergen immunotherapy liquid (RW-SAIL) extract in subjects with ragweed-related ARC. METHODS: This phase 3, randomized, placebo-controlled trial was conducted in North America. Subjects (age range, 18-55 years) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed. Subjects self-administered the maximum tolerated dose of RW-SAIL (n = 218) or placebo (n = 211) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season. The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores (TCS). RESULTS: During the entire season, there was a 43% decrease in TCS in subjects treated with RW-SAIL compared with placebo. Similar decreases were observed in TCS between the 2 groups during peak season (42%) and in daily symptom scores during the entire (42%) and peak (41%) seasons. The occurrence of adverse events was similar between the treatment groups; most were mild in severity. Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited. No anaphylaxis occurred. CONCLUSIONS: This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual standardized ragweed allergen immunotherapy liquid extract for the treatment of ARC.

Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial.

IMPORTANCE: Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE: To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION: Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n = 307) or matching placebo (n = 300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS: A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P = .04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. CONCLUSIONS AND RELEVANCE: Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01272635.

An asthma sports camp series to identify children with possible asthma and cardiovascular risk factors.

BACKGROUND: The prevalence of asthma and obesity in children has increased over the past several years, with obesity being associated with higher rates of asthma. In response to known disparities in asthma prevalence and morbidity, along with barriers to diagnosis, assessment and education, a comprehensive asthma sports camp series was developed and implemented. OBJECTIVE: The primary objective was to evaluate the effectiveness of utilizing a sports camp model to identify children with undiagnosed and uncontrolled asthma, and to provide recommendations for follow-up care. The secondary objectives were to identify the presence of and associations between related co-morbidities and risk factors for asthma morbidity such as obesity, hypertension and exposure to tobacco smoke; and to assess asthma medication use. METHODS: Six daylong camps at an inner-city university were offered to children 5-17 years of age over a period of two years. Asthma, body mass index, blood pressure (BP) and carbon monoxide screenings were conducted at each camp. RESULTS: In this sample, 43.7% of children had previously diagnosed asthma, and 12.6% were classified as having potential, undiagnosed asthma. Of the children with previously diagnosed asthma, 76% were considered uncontrolled. Thirty-eight percent were determined to be overweight or obese and 17% had elevated BP. CONCLUSIONS: An interdisciplinary sports camp model can be used to identify children with undiagnosed and uncontrolled asthma and cardiovascular risk factors; and to provide recommendations for follow-up care.

Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.

IMPORTANCE: In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency. OBJECTIVE: To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels. DESIGN, SETTING, AND PARTICIPANTS: The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized. INTERVENTIONS: Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained. MAIN OUTCOMES AND MEASURES: The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of ß-agonists, systemic corticosteroids, and health care). RESULTS: Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]). CONCLUSIONS AND RELEVANCE: Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248065.