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The use of a single inhaler containing the combination of an inhaled corticosteroid (ICS) and formoterol, a specific long-acting bronchodilator, for both maintenance and quick relief therapy (single maintenance and reliever therapy [SMART or MART]) is recommended by both the Global Initiative for Asthma and the National Asthma Education and Prevention Program Coordinating Committee in steps 3 and 4 of asthma management. This article provides practical advice about implementing SMART in clinical practice based on evidence and clinical experience. Fundamental to SMART is that ICS-formoterol provides quick relief of asthma symptoms similar to that of short-acting β 2 -agonists such as albuterol, while reducing the risk for severe asthma exacerbations and at an overall lower ICS exposure. Most SMART clinical trials were in adults and adolescents (aged ≥12 years), using budesonide-formoterol 160/4.5 μg (delivered dose), one inhalation once or twice daily (step 3) and two inhalations twice daily (step 4). For both steps 3 and 4, patients take additional inhalations of budesonide-formoterol 160/4.5 μg, one inhalation whenever needed for symptom relief, up to a maximum for adults and adolescents of 12 total inhalations in any single day (delivering 54 μg formoterol). The efficacy and safety of SMART with budesonide-formoterol and beclometasone-formoterol have been confirmed, but other ICS-long-acting bronchodilator combinations have not been studied. The SMART regimen should be introduced with a careful explanation of its role in self-management, preferably with a customized written asthma action plan. The cost to patients and the availability of SMART treatment will depend on the prescribed dose and national or local payer agreements., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Cloutier reports a family member who is employed by Regeneron. Dr Teach reports research funding from the NIH NHLBI, the NIH National Institute of Allergy and Infectious Diseases, the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, and EJF Philanthropies and royalty payments from UpToDate. Dr Lemanske has received personal fees from Siolta Therapeutics for a microbiome intervention and from the Food Allergy Research and Education Network. Dr Blake reports research funding from the NIH NHLBI, the NIH National Human Genome Research Institute, and Propeller Health. All authors were members of the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group.

Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups.To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (SNP) in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents.In the meta-analysis of GWAS, an SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34-1.79, p=6.3×10 -9 ). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10 -7 ).SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents ( KCNJ2-AS1 )., Competing Interests: Conflict of interest: Q. Yan reports grants from National Institutes of Health (K01HL138098), during the conduct of the study. Conflict of interest: E. Forno has nothing to disclose. Conflict of interest: E. Herrera-Luis reports grants from the Spanish Ministry of Science, Innovation and Universities (PRE2018-083837), during the conduct of the study. Conflict of interest: M. Pino-Yanes reports grants from Spanish Ministry of Economy, Industry and Competitiveness, the State Research Agency and the European Regional Development Funds from the European Union (MINECO/AEI/FEDER, UE, SAF2017-83417R), and grants from Spanish Ministry of Economy, Industry and Competitiveness (Ramón y Cajal grant RYC-2015-17205), during the conduct of the study. Conflict of interest: C. Qi has nothing to disclose. Conflict of interest: R. Rios has nothing to disclose. Conflict of interest: Y-Y. Han has nothing to disclose. Conflict of interest: S. Kim has nothing to disclose. Conflict of interest: S. Oh has nothing to disclose. Conflict of interest: E. Acosta-Pérez has nothing to disclose. Conflict of interest: R. Zhang has nothing to disclose. Conflict of interest: D. Hu has nothing to disclose. Conflict of interest: C. Eng has nothing to disclose. Conflict of interest: S. Huntsman has nothing to disclose. Conflict of interest: L. Avila has nothing to disclose. Conflict of interest: N. Boutaoui has nothing to disclose. Conflict of interest: M.M. Cloutier has nothing to disclose. Conflict of interest: M.E. Soto-Quiros has nothing to disclose. Conflict of interest: C-J. Xu has nothing to disclose. Conflict of interest: S.T. Weiss has nothing to disclose. Conflict of interest: J. Lasky-Su has nothing to disclose. Conflict of interest: M.R. Kiedrowski has nothing to disclose. Conflict of interest: C. Figueiredo has nothing to disclose. Conflict of interest: J. Bomberger has nothing to disclose. Conflict of interest: M.L. Barreto has nothing to disclose. Conflict of interest: G. Canino has nothing to disclose. Conflict of interest: W. Chen has nothing to disclose. Conflict of interest: G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, during the conduct of the study; grants from Ubbo Emmius Foundation, TETRI Foundation, GSK, Vertex, TEVA, the Lung Foundation of the Netherlands and the European Union H2020 Program, outside the submitted work; and has served on advisory boards to GSK and PURE IMS (fees paid to institution). Conflict of interest: E.G. Burchard reports grants from National Heart, Lung, and Blood Institute, National Institute of Health, General Medical Sciences, National Institute on Minority Health and Health Disparities, Tobacco-Related Disease Research Program, Food and Drug Administration, and the Sandler Family Foundation, during the conduct of the study. Conflict of interest: J.C. Celedón has received research materials from GSK and Merck (inhaled steroids) and Pharmavite (vitamin D and placebo capsules), in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work., (Copyright ©ERS 2021.)

Background: Little is known about the genetic determinants of severe asthma exacerbations., Objectives: We aimed to identify genetic variants associated with asthma hospitalizations., Methods: We conducted a genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, 1,658 of whom had at least 1 asthma-related hospitalization. This analysis was conducted by using logistic regression under an additive genetic model with adjustment for age, sex, body mass index, smoking status, and the first 5 principal components derived from genotypic data. We then analyzed data from 2 cohorts of Latino children and adolescents for replication and conducted quantitative trait locus and functional annotation analyses., Results: At the chromosome 6p21.3 locus, the single-nucleotide polymorphism (SNP) rs56151658 (8 kb from the promoter of HLA-DQB1) was most significantly associated with asthma hospitalizations (for test allele A, odds ratio = 1.36 [95% CI = 1.22-1.52]; P = 3.11 × 10 -8 ); 21 additional SNPs in this locus were associated with asthma hospitalizations at a P value less than 1 × 10 -6 . In the replication cohorts, multiple SNPs in strong linkage disequilibrium with rs56151658 were associated with severe asthma exacerbations at a P value of .01 or less in the same direction of association as in the discovery cohort. Three HLA genes (HLA-DQA2, HLA-DRB6, and HLA-DOB) were also shown to mediate the estimated effects of the SNPs associated with asthma hospitalizations through effects on gene expression in lung tissue., Conclusions: We identified strong candidate genes for asthma hospitalizations in adults in the region for class II HLA genes through genomic, quantitative trait locus, and summary data-based mendelian randomization analyses., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: Asthma is a major public health problem worldwide and is associated with excess morbidity, mortality, and economic costs associated with lost productivity. The National Asthma Education and Prevention Program has released the 2020 Asthma Guideline Update with updated evidence-based recommendations for treatment of patients with asthma., Objective: To report updated recommendations for 6 topics for clinical management of adolescents and adults with asthma: (1) intermittent inhaled corticosteroids (ICSs); (2) add-on long-acting muscarinic antagonists; (3) fractional exhaled nitric oxide; (4) indoor allergen mitigation; (5) immunotherapy; and (6) bronchial thermoplasty., Evidence Review: The National Heart, Lung, and Blood Advisory Council chose 6 topics to update the 2007 asthma guidelines based on results from a 2014 needs assessment. The Agency for Healthcare Research and Quality conducted systematic reviews of these 6 topics based on literature searches up to March-April 2017. Reviews were updated through October 2018 and used by an expert panel (n = 19) that included asthma content experts, primary care clinicians, dissemination and implementation experts, and health policy experts to develop 19 new recommendations using the GRADE method. The 17 recommendations for individuals aged 12 years or older are reported in this Special Communication., Findings: From 20 572 identified references, 475 were included in the 6 systematic reviews to form the evidence basis for these recommendations. Compared with the 2007 guideline, there was no recommended change in step 1 (intermittent asthma) therapy (as-needed short-acting β2-agonists [SABAs] for rescue therapy). In step 2 (mild persistent asthma), either daily low-dose ICS plus as-needed SABA therapy or as-needed concomitant ICS and SABA therapy are recommended. Formoterol in combination with an ICS in a single inhaler (single maintenance and reliever therapy) is recommended as the preferred therapy for moderate persistent asthma in step 3 (low-dose ICS-formoterol therapy) and step 4 (medium-dose ICS-formoterol therapy) for both daily and as-needed therapy. A short-term increase in the ICS dose alone for worsening of asthma symptoms is not recommended. Add-on long-acting muscarinic antagonists are recommended in individuals whose asthma is not controlled by ICS-formoterol therapy for step 5 (moderate-severe persistent asthma). Fractional exhaled nitric oxide testing is recommended to assist in diagnosis and monitoring of symptoms, but not alone to diagnose or monitor asthma. Allergen mitigation is recommended only in individuals with exposure and relevant sensitivity or symptoms. When used, allergen mitigation should be allergen specific and include multiple allergen-specific mitigation strategies. Subcutaneous immunotherapy is recommended as an adjunct to standard pharmacotherapy for individuals with symptoms and sensitization to specific allergens. Sublingual immunotherapy is not recommended specifically for asthma. Bronchial thermoplasty is not recommended as part of standard care; if used, it should be part of an ongoing research effort., Conclusions and Relevance: Asthma is a common disease with substantial human and economic costs globally. Although there is no cure or established means of prevention, effective treatment is available. Use of the recommendations in the 2020 Asthma Guideline Update should improve the health of individuals with asthma.

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders:A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality's (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format., (Published by Elsevier Inc.)

Background: Little is known about specialist-specific variations in guideline agreement and adoption., Objective: To assess similarities and differences between allergists and pulmonologists in adherence to cornerstone components of the National Asthma Education and Prevention Program's Third Expert Panel Report., Methods: Self-reported guideline agreement, self-efficacy, and adherence were assessed in allergists (n = 134) and pulmonologists (n = 99) in the 2012 National Asthma Survey of Physicians. Multivariate models were used to assess if physician and practice characteristics explained bivariate associations between specialty and "almost always" adhering to recommendations (ie, ≥75% of the time)., Results: Allergists and pulmonologists reported high guideline self-efficacy and moderate guideline agreement. Both groups "almost always" assessed asthma control (66.2%, standard error [SE] 4.3), assessed school/work asthma triggers (71.3%, SE, 3.9), and endorsed inhaled corticosteroids use (95.5%, SE 2.0). Repeated assessment of the inhaler technique, use of asthma action/treatment plans, and spirometry were lower (39.7%, SE 4.0; 30.6%, SE 3.6; 44.7%, SE 4.1, respectively). Compared with pulmonologists, more allergists almost always performed spirometry (56.6% vs 38.6%, P = .06), asked about nighttime awakening (91.9% vs 76.5%, P = .03) and emergency department visits (92.2% vs 76.5%, P = .03), assessed home triggers (70.5% vs 52.6%, P = .06), and performed allergy testing (61.8% vs 21.3%, P < .001). In multivariate analyses, practice-specific characteristics explained differences except for allergy testing., Conclusions: Overall, allergists and pulmonologists adhere to the asthma guidelines with notable exceptions, including asthma action plan use and inhaler technique assessment. Recommendations with low implementation offer opportunities for further exploration and could serve as targets for increasing guideline uptake., (Published by Elsevier Inc.)

Asthma imposes tremendous burden on children, families, and society. Successful management requires coordinated care among children, families, health providers, and schools. Building Bridges for Asthma Care Program, a school-centered program to coordinate care for successful asthma management, was developed, implemented, and evaluated. The program consists of five steps: (1) identify students with asthma; (2) assess asthma risk/control; (3) engage the family and student at risk; (4) provide case management and care coordination, including engagement of health-care providers; and (5) prepare for next school year. Implementation occurred in 28 schools from two large urban school districts in Colorado and Connecticut. Significant improvements were noted in the proportions of students with completed School Asthma Care Plans, a quick-relief inhaler at school, Home Asthma Action/Treatment Plans and inhaler technique ( p < .01 for all variables). Building Bridges for Asthma Care was successfully implemented extending asthma care to at-risk children with asthma through engagement of schools, health providers, and families.

Background and objectives Although primary care clinicians provide >60% of U.S. asthma care, no nationally representative study has examined variation in adherence among primary care groups to four cornerstone domains of the Expert Panel Report-3 asthma guidelines: assessment/monitoring, patient education, environmental assessment, and medications. We used the 2012 National Asthma Survey of Physicians: National Ambulatory Medical Care Survey to compare adherence by family/general medicine practitioners (FM/GM), internists, pediatricians and Community Health Center mid-level clinicians (CHC). : Although primary care clinicians provide >60% of U.S. asthma care, no nationally representative study has examined variation in adherence among primary care groups to four cornerstone domains of the Expert Panel Report-3 asthma guidelines: assessment/monitoring, patient education, environmental assessment, and medications. We used the 2012 National Asthma Survey of Physicians: National Ambulatory Medical Care Survey to compare adherence by family/general medicine practitioners (FM/GM), internists, pediatricians and Community Health Center mid-level clinicians (CHC). Methods: Adherence was self-reported ( n  = 1355 clinicians). Adjusted odds of almost always adhering to each recommendation (≥75% of the time) were estimated controlling for clinician/practice characteristics, and agreement and self-efficacy with guideline recommendations. Results: A higher percentage of pediatricians adhered to most assessment/monitoring recommendations compared to FM/GM and other groups (e.g. 71.6% [SE 4.0] almost always assessed daytime symptoms versus 50.6% [SE 5.1]-51.1% [SE 5.8], t  < 0.05) but low percentages from all groups almost always performed spirometry (6.8% [SE 2.0]-16.8% [SE 4.7]). Pediatricians were more likely to provide asthma action/treatment plans than FM/GM and internists. Internists were more likely to assess school/work triggers than pediatricians and CHC (environmental assessment). All groups prescribed inhaled corticosteroids for daily control (84.0% [SE 3.7]-90.7% [SE 2.5]) (medications). In adjusted analyses, pediatric specialty, high self-efficacy and frequent specialist referral were associated with high adherence. p  < 0.05) but low percentages from all groups almost always performed spirometry (6.8% [SE 2.0]-16.8% [SE 4.7]). Pediatricians were more likely to provide asthma action/treatment plans than FM/GM and internists. Internists were more likely to assess school/work triggers than pediatricians and CHC (environmental assessment). All groups prescribed inhaled corticosteroids for daily control (84.0% [SE 3.7]-90.7% [SE 2.5]) (medications). In adjusted analyses, pediatric specialty, high self-efficacy and frequent specialist referral were associated with high adherence. Conclusions: Pediatricians were more likely to report high adherence than other clinicians. Self- efficacy and frequent referral were also associated with adherence. Adherence was higher for history-taking recommendations and lower for recommendations involving patient education, equipment and expertise.

Objective: Effective asthma management at school can help students with asthma stay healthy, learn better and participate fully during their school day. This study sought to understand school-based asthma care from the perspective of parents and school personnel to improve asthma care at school. Methods: A cross-sectional study was conducted in Hartford, CT. School personnel from 59 schools and 322 parents/guardians were invited to participate. Four cross-sectional surveys using Likert-type scales assessed parental and school personnel satisfaction, confidence in managing asthma, policy awareness, management of asthma during physical activity, and perceived gaps surrounding school-based asthma care. Results: 263/322 (82%) eligible parents of children with asthma (mean age 8.5 ± 4.3, 56% Hispanic, 30% African American) completed surveys. Thirty six school nurses (62%), 131 teachers (8%), 14 coaches (14%), and 17 school principals (29%) participated. 90% of parents were satisfied with asthma management in school. School nurses were more aware of asthma policies than teachers (74% vs. 24%, p  < 0.001). 34% of school nurses, 30% of teachers and 36% of coaches were unaware of asthma-related absences. 14% of physical education teachers/coaches reported no asthma training. Conclusion: In this convenience sample of parents and school personnel, parents reported overall satisfaction regarding the asthma care their children receive at school, yet a number of gaps pertaining to school-based asthma care were identified. Increased asthma training and enhanced communication among school personnel is needed to address these gaps. National guidelines and resources are readily available to improve asthma care at school.

Objective: To evaluate whether school nurses can assist pediatricians in providing asthma care and reduce school absenteeism through a program called Easy Breathing for Schools (EzBfS), a 5-element school nurse-led asthma management program and the effectiveness in reducing school absenteeism., Methods: Fifteen public school nurses in an urban community implemented EzBfS during the 2015-16 and 2016-17 school years. Program elements included assessment of asthma risk and asthma control, asthma education, medication review, and a pediatrician communication tool. School absence for any reason was the primary outcome; absentee rates for students with asthma enrolled in the program were compared to students with asthma in the entire school population using negative binomial regression., Results: School nurses enrolled 251/2,126 students with physician-confirmed asthma (2015-16: n = 114 and 2016-17: n = 137). Sixty eight percent of participants were Latino and 25% were Black with a mean age of 8.7 ± 2.2 years. Absentee rates were higher in children with asthma compared to children without asthma (8.3% vs 7.0% absent, respectively P < .001). Students enrolled in the program experienced a 25% decrease in absentee rate after adjusting for age, sex, race/ethnicity, and school year (rate ratio = 0.75, 95% confidence interval, 0.67, 0.85) as compared to students with asthma not enrolled in the program. Participants also demonstrated improvement in inhaler technique score (P < .001). Ninety two percent of the nurses were satisfied with the program., Conclusion: EzBfS, a pragmatic, nurse-led asthma management program, was successfully implemented by school nurses and significantly decreased school absences among a sample of students with asthma., (Copyright © 2019 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma., Methods: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician's diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes., Results: A genome-wide significant association was identified between baseline FEV 1 /FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10 -8 in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10 -6 ). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV 1 (P = 3.3 × 10 -3 ), postbronchodilator (PB) FEV 1 (7.3 × 10 -3 ), and PB FEV 1 /FVC ratio (P = 2.7 × 10 -3 ). The identified baseline FEV 1 /FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR., Conclusions: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Pediatric asthma, the most common chronic disease of childhood, remains a significant burden to the health care system. Although there are guidelines for the management of pediatric asthma, there remain several controversies about how best to manage asthma in the primary care setting, and how to prevent asthma exacerbations and subsequent emergency department visits and hospitalizations. In this article, we address four of these controversies: use of written asthma treatment plans, the role of long-acting beta-agonists, spirometry and peak flow measurements in disease management, and engagement of school nurses in the health care team. We provide suggestions and guidance related to these topics for the pediatric primary care provider. [Pediatr Ann. 2019;48(3):e128-e134.]., (Copyright 2019, SLACK Incorporated.)

Background: Children with asthma are at increased risk for experiencing health and educational disparities because of increased school absence. School nurses are well positioned to support asthma management and improve school attendance., Objective: We sought to implement and assess the effect of the Building Bridges for Asthma Care Program on improving school attendance and measures of asthma control., Methods: Children with asthma (age, 5-14 years) in the Denver Public School System (n = 240) and the Hartford Public School System (n = 223) were enrolled in the Building Bridges Program during the 2013-2014 and 2014-2015 school years and followed until the end of the second school year. The primary outcome was school absence, with secondary outcomes, including asthma control, measured based on Childhood Asthma Control Test or the Asthma Control Test scores and rescue inhaler use., Results: Participants experienced a 22% absolute decrease in school absenteeism, the number of children with an Asthma Control Test/Childhood Asthma Control Test score of less than the control threshold of 20 decreased from 42.7% to 28.8%, and bronchodilator use greater than 2 times per week decreased from 35.8% to 22.9% (all changes were significant, P < .01)., Conclusions: Children enrolled in the Building Bridges for Asthma Care Program experienced reduced school absence and improved asthma control., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The 2007 Guidelines for the Diagnosis and Management of Asthma provide evidence-based recommendations to improve asthma care. Limited national-level data are available about clinician agreement and adherence to these guidelines., Objective: To assess clinician-reported adherence with specific guideline recommendations, as well as agreement with and self-efficacy to implement guidelines., Methods: We analyzed 2012 National Asthma Survey of Physicians data for 1412 primary care clinicians and 233 asthma specialists about 4 cornerstone guideline domains: asthma control, patient education, environmental control, and pharmacologic treatment. Agreement and self-efficacy were measured using Likert scales; 2 overall indices of agreement and self-efficacy were compiled. Adherence was compared between primary care clinicians and asthma specialists. Logistic regression models assessed the association of agreement and self-efficacy indices with adherence., Results: Asthma specialists expressed stronger agreement, higher self-efficacy, and greater adherence with guideline recommendations than did primary care clinicians. Adherence was low among both groups for specific core recommendations, including written asthma action plan (30.6% and 16.4%, respectively; P < .001); home peak flow monitoring, (12.8% and 11.2%; P = .34); spirometry testing (44.7% and 10.8%; P < .001); and repeated assessment of inhaler technique (39.7% and 16.8%; P < .001). Among primary care clinicians, greater self-efficacy was associated with greater adherence. For specialists, self-efficacy was associated only with increased odds of spirometry testing. Guideline agreement was generally not associated with adherence., Conclusions: Agreement with and adherence to asthma guidelines was higher for specialists than for primary care clinicians, but was low in both groups for several key recommendations. Self-efficacy was a good predictor of guideline adherence among primary care clinicians but not among specialists., (Published by Elsevier Inc.)

Background: Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes., Objective: We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure., Methods: A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study., Results: Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV 1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10 -8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10 -9 for all cohorts). Rs117902240 was positively associated with FEV 1 in children exposed to low dust mite allergen levels, but negatively associated with FEV 1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV 1 /forced vital capacity replicated in the independent cohorts., Conclusions: Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV 1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.

Objectives: Mobile technology for childhood asthma can provide real-time data to enhance care. What real-time adherence information clinicians want, how they may use it, and if the data meet their clinical needs have not been fully explored. Our goal was to determine whether pediatric primary care and pulmonary clinicians believe if a sensor-based mobile intervention is useful in caring for patients with asthma., Methods: We recruited participants from 3 urban, primary care and 1 pulmonary practice from July to September 2015 in Hartford, CT. Forty-one participated in four focus groups, which included a demonstration of the technology. Participants were probed with open-ended questions on the type, frequency, and format of inter-visit patient information they found useful., Results: 41 participants (mean age 49 (±13.7) years) were board-certified clinicians (41% MDs and 20% mid-level practitioners), practiced medicine on an average of 19 (±14) years, were primarily white (59%) and women (78%). Clinicians wanted 1) adherence to prescribed inhaler therapy and 2) data on inhaler technique. Clinicians wanted it at the time of a scheduled clinic visit but also wanted inter-visit alerts for excessive use of rescue therapy. Pulmonologists liked the mobile spirometer's provision of inter-visit lung function data; pediatricians did not share this view. Concerns with data accuracy were raised due to families who shared inhalers, access to smartphones, and protection of health information., Conclusions: Overall, clinicians view an asthma mobile health technology as enhancing the patient-centered medical home. Pediatric primary care clinicians and pulmonologists want different information from a mobile app.

Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium., Materials & Methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire., Results: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed., Conclusion: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population.

Puerto Ricans are disproportionately affected with asthma in the USA. In this study, we aim to identify genetic variants that confer susceptibility to asthma in Puerto Ricans.We conducted a meta-analysis of genome-wide association studies (GWAS) of asthma in Puerto Ricans, including participants from: the Genetics of Asthma in Latino Americans (GALA) I-II, the Hartford-Puerto Rico Study and the Hispanic Community Health Study. Moreover, we examined whether susceptibility loci identified in previous meta-analyses of GWAS are associated with asthma in Puerto Ricans.The only locus to achieve genome-wide significance was chromosome 17q21, as evidenced by our top single nucleotide polymorphism (SNP), rs907092 (OR 0.71, p=1.2×10 -12 ) at IKZF3 Similar to results in non-Puerto Ricans, SNPs in genes in the same linkage disequilibrium block as IKZF3 ( e.g. ZPBP2 , ORMDL3 and GSDMB ) were significantly associated with asthma in Puerto Ricans. With regard to results from a meta-analysis in Europeans, we replicated findings for rs2305480 at GSDMB , but not for SNPs in any other genes. On the other hand, we replicated results from a meta-analysis of North American populations for SNPs at IL1RL1 , TSLP and GSDMB but not for IL33 Our findings suggest that common variants on chromosome 17q21 have the greatest effects on asthma in Puerto Ricans., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Objective: To determine whether secondhand smoke (SHS) exposure is associated with greater asthma severity in children with physician-diagnosed asthma living in CT, and to examine whether area of residence, race/ethnicity or poverty moderate the association., Methods: A large childhood asthma database in CT (Easy Breathing) was linked by participant zip code to census data to classify participants by area of residence. Multinomial logistic regression models, adjusted for enrollment date, sex, age, race/ethnicity, area of residence, insurance type, family history of asthma, eczema, and exposure to dogs, cats, gas stove, rodents and cockroaches were used to examine the association between self-reported exposure to SHS and clinician-determined asthma severity (mild, moderate, and severe persistent vs. intermittent asthma)., Results: Of the 30,163 children with asthma enrolled in Easy Breathing, between 6 months and 18 years old, living in 161 different towns in CT, exposure to SHS was associated with greater asthma severity (adjusted relative risk ratio (aRRR): 1.07 [1.00, 1.15] and aRRR: 1.11 [1.02, 1.22] for mild and moderate persistent asthma, respectively). The odds of Black and Puerto Rican/Hispanic children with asthma being exposed to SHS were twice that of Caucasian children. Though the odds of SHS exposure for publicly insured children with asthma were three times greater than the odds for privately insured children (OR: 3.02 [2.84,3,21]), SHS exposure was associated with persistent asthma only among privately insured children (adjusted odds ratio (aOR): 1.23 [1.11,1.37])., Conclusion: This is the first large-scale pragmatic study to demonstrate that children exposed to SHS in Connecticut have greater asthma severity, clinically determined using a systematic approach, and varies by insurance status.

Rationale: For unclear reasons, obese children with asthma have higher morbidity and reduced response to inhaled corticosteroids., Objectives: To assess whether childhood obesity is associated with airway dysanapsis (an incongruence between the growth of the lungs and the airways) and whether dysanapsis is associated with asthma morbidity., Methods: We examined the relationship between obesity and dysanapsis in six cohorts of children with and without asthma, as well as the relationship between dysanapsis and clinical outcomes in children with asthma. Adjusted odds ratios (ORs) were calculated for each cohort and in a combined analysis of all cohorts; longitudinal analyses were also performed for cohorts with available data. Hazard ratios (HRs) for clinical outcomes were calculated for children with asthma in the Childhood Asthma Management Program., Measurements and Main Results: Being overweight or obese was associated with dysanapsis in both the cross-sectional (OR, 1.95; 95% confidence interval [CI], 1.62-2.35 [for overweight/obese compared with normal weight children]) and the longitudinal (OR, 4.31; 95% CI, 2.99-6.22 [for children who were overweight/obese at all visits compared with normal weight children]) analyses. Dysanapsis was associated with greater lung volumes (FVC, vital capacity, and total lung capacity) and lesser flows (FEV 1 and forced expiratory flow, midexpiratory phase), and with indicators of ventilation inhomogeneity and anisotropic lung and airway growth. Among overweight/obese children with asthma, dysanapsis was associated with severe disease exacerbations (HR, 1.95; 95% CI, 1.38-2.75) and use of systemic steroids (HR, 3.22; 95% CI, 2.02-5.14)., Conclusions: Obesity is associated with airway dysanapsis in children. Dysanapsis is associated with increased morbidity among obese children with asthma and may partly explain their reduced response to inhaled corticosteroids.

Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP-treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti-inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Clinicians who care for children with asthma have an obligation to coordinate asthma care with the schools. Aside from routine clinical care of asthmatic children, providers must educate the family and child about the need for an asthma treatment plan in school and support the school nurse meeting the needs of the student requiring school-based asthma care. The following article was developed by multiple stakeholders to address this need. It describes the 4 components of the School-based Asthma Management Program (SAMPRO™). SAMPRO™ details elements necessary for the education of children, families, clinicians, and school-based personnel based on a "circle of support" that would enhance multidirectional communication and promote better care for children with asthma within the school setting., Competing Interests: of potential conflict of interest: R. F. Lemanske has received travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI); is employed by the University of Wisconsin; has received grants from the National Heart, Lung, and Blood Institute (NHLBI) and Pharmaxis; has received royalties from Elsevier and UpToDate; and has received speaker honoraria from the Kuwait Allergy Society, Lurie Children’s Hospital, Boston Children’s Hospital, Health Star Communications, LA Children’s Hospital, Northwestern University, the Asthma and Allergy Foundation of America–Alaska Chapter, and the Egyptian Allergy Society. S. Kakumano has received royalties from UpToDate. K. Shanovich has received travel support, payment for writing or reviewing the manuscript, and employment from the AAAAI. N. Antos received travel support from the AAAAI School Based Management of Asthma Summit. M. M. Cloutier has received travel support from the AAAAI; has consultant arrangements with ProHealth Physicians; has received grants from the National Institutes of Health, the NHLBI, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and has received payment for lectures from Nationwide. S. Szefler has consultant arrangements with Roche, AstraZeneca, Aerocrine, Daiichi Sankyo, Boehringer Ingelheim, Genentech, and Novartis and has received grants from GlaxoSmithKline. P. Williams has received travel support from the AAAAI and is employed by Northwest Asthma & Allergy Center. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to gun violence and African ancestry have been separately associated with increased risk of asthma in Puerto Rican children., Objective: The objective of this study was to examine whether African ancestry and gun violence interact on asthma and total IgE in school-aged Puerto Rican children., Methods: This is a case-control study of 747 Puerto Rican children aged 9 to 14 years living in San Juan, Puerto Rico (n = 472), and Hartford, Connecticut (n = 275). Exposure to gun violence was defined as the child's report of hearing gunshots more than once, and the percentage of African ancestry was estimated using genome-wide genotypic data. Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. Serum total IgE (IU/mL) was measured in study participants. Multivariate logistic and linear regressions were used for the analysis of asthma and total IgE, respectively., Results: In multivariate analyses, there was a significant interaction between exposure to gun violence and African ancestry on asthma (P = .001) and serum total IgE (P = .04). Among children exposed to gun violence, each quartile increase in the percentage of African ancestry was associated with approximately 45% higher odds of asthma (95% CI, 1.15-1.84; P = .002) and an approximately 19% increment in total IgE (95% , 0.60-40.65, P = .04). In contrast, there was no significant association between African ancestry and asthma or total IgE in children not exposed to gun violence., Conclusions: Our results suggest that exposure to gun violence modifies the estimated effect of African ancestry on asthma and atopy in Puerto Rican children., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This article reviews new approaches, facilitators, barriers, and opportunities to increasing guideline-adherent care for children with asthma by primary care clinicians., Recent Findings: Primary care clinicians are challenged by the volume of guidelines and want transparent guidelines that are easy to use and that can be used in complex patients with multiple comorbidities. Programs that use decision support tools and electronic technologies and provide support from individuals new to the medical home such as panel management assistants, community health workers, patient advocates, practice facilitators, school nurses, and pharmacists may enhance use of guidelines by primary care clinicians and reduce asthma morbidity. Primary care clinician burnout and difficulty incorporating electronic asthma decision tools into current workflow are recently recognized barriers to guideline integration and improved asthma outcomes. In addition, many of these interventions are labor intensive, costly and may not be capable of being widely disseminated., Summary: Programs that simplify guidelines, provide decision support tools and use electronic technologies and an expanded medical team may improve the quality of asthma care provided by the primary care community to children and their families with asthma.

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma.

Asthma is the most common chronic disease among children. It cannot be prevented but can be controlled. Industrialized countries experience high lifetime asthma prevalence that has increased over recent decades. Asthma has a complex interplay of genetic and environmental triggers. Studies have revealed complex interactions of lung structure and function genes with environmental exposures such as environmental tobacco smoke and vitamin D. Home environmental strategies can reduce asthma morbidity in children but should be tailored to specific allergens. Coupled with education and severity-specific asthma therapy, tailored interventions may be the most effective strategy to manage childhood asthma., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rationale: Little is known about breastfeeding and asthma in Puerto Ricans, the ethnic group most affected by this disease in the US. We examined the relation between the currently recommended duration of breastfeeding and asthma in school-aged Puerto Rican children., Methods: Case-control study of 1,127 Puerto Rican children aged 6-14 years living in Hartford, Connecticut (n = 449) and San Juan, Puerto Rico (n = 678). Parental recall of breastfeeding was categorized based on duration and according to current guidelines (i.e., none, 0-6 months, and >6 months). Asthma was defined as parental report of physician-diagnosed asthma and wheeze in the previous year. We used logistic regression for the multivariate analysis, which was conducted separately for each study site and for the combined cohort. All multivariate models were adjusted for age, gender, household income, atopy, maternal asthma, body mass index, early-life exposure to environmental tobacco smoke, and (for the combined cohort) study site., Results: After adjustment for covariates, children who were breastfed for up to 6 months had 30% lower odds of asthma (95% CI = 0.5-1.0, P = 0.04) than those who were not breastfed. In this analysis, breastfeeding for longer than 6 months was not significantly associated with asthma (OR = 1.5, 95% CI = 1.0-2.4, P = 0.06)., Conclusions: Our results suggest that breastfeeding for up to 6 months (as assessed by parental recall) is associated with decreased odds of asthma in Puerto Rican children, and that there is no additional beneficial effect of breastfeeding for over 6 months. These results support current recommendations on the duration of breastfeeding in an ethnic group at risk for asthma., (© 2014 Wiley Periodicals, Inc.)

Despite significant advances in the treatment of asthma and the development of evidence-based and evidence-informed guidelines, childhood asthma morbidity remains high. One measure of asthma-associated morbidity is school absenteeism. In this rostrum we summarize key themes from 3 articles in this special issue on school-centered asthma programs. All 3 articles in this series describe several common themes that are essential for successful school-based interventions. These themes include the importance of trust and building strong partnerships, the importance of interaction and communication between multiple key stakeholders (ecological framework), the central and often overlooked role of the primary care clinician, the need for sustainable resources, and the importance of context and public policy. We then discuss how to apply the framework of implementation research to inform and evaluate school-based interventions. Finally, we make a series of recommendations for future work., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the concordance between spirometry and asthma symptoms in assessing asthma severity and beginning therapy by the general pediatrician., Study Design: Between 2008 and 2012, spirometry testing was satisfactorily performed in 894 children (ages 5-19 years) whose asthma severity had been determined by their pediatrician using asthma guideline-based clinical criteria. Spirometry-determined asthma severity using national asthma guidelines and clinician-determined asthma severity were compared for concordance using weighted Kappa coefficients., Results: Thirty percent of participants had clinically determined intermittent asthma; 32%, 33%, and 5% had mild, moderate, and severe, persistent asthma, respectively. Increasing disease severity was associated with decreases in the forced expiratory volume in 1 second/forced vital capacity (FVC) ratio (P < .001), the forced expiratory volume in 1 second/FVC% predicted (P < .0001), and the FVC% predicted (P < .01). In 319 children (36%), clinically determined asthma severity was lower than spirometry-determined severity. Concordance was 0.16 (95% CI 0.10, 0.23), and when adjusted for bias and prevalence, was 0.20 (95% CI 0.17, 0.23). When accounting for age, sex, exposure to smoke, and insurance type, only spirometry-determined asthma severity was a significant predictor of agreement (P < .0001), with worse agreement as spirometry-determined severity increased., Conclusions: Concordance between spirometry and asthma symptoms in determining asthma severity is low even when guideline-based clinical assessment tools are used. Because appropriate therapy reduces asthma morbidity and is guided by disease severity, results from spirometry testing could better guide pediatricians in determining appropriate therapy for their patients with asthma., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Because of concerns about the safety of long-acting β(2)-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS)., Objective: To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA., Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted., Study Selection: Randomized controlled trials of discontinuation of LABA therapy in patients with asthma controlled with a combination of ICS and LABA., Data Extraction: Two reviewers independently screened each title and abstract in the initial searches and then the full text of each nominated article to extract data for analyses., Results: Of 1492 screened articles, only 5 trials involving patients aged 15 years or older fulfilled a priori–specified inclusion criteria. Results did not favor the LABA step-off approach compared with no change in treatment. The LABA step-off regimen increased asthma impairment, with worse Asthma Quality of Life Questionnaire score (mean difference [95% CI], 0.32 [0.14-0.51] points lower); worse Asthma Control Questionnaire score (0.24 [0.13-0.35] points higher); fewer symptom-free days (9.15% [1.62%-16.69%] less); and greater risk of withdrawal from study resulting from lack of efficacy or loss of asthma control (risk ratio, 3.27 [2.16-4.96]). Risk of exacerbations and deaths after LABA step-off were not evaluable because of the small number of events and short duration of follow-up., Conclusions: Evidence suggests that discontinuing LABA therapy in adults and older children with asthma controlled with a combination of ICSs and LABAs results in increased asthma-associated impairment. Additional trials measuring all long-term patient-important outcomes are needed.

Vitamin D deficiency is becoming more apparent in many populations. Genetic factors may play a role in the maintenance of vitamin D levels. The objective of this study was to perform a genome-wide analysis (GWAS) of vitamin D levels, including replication of prior GWAS results. We measured 25-hydroxyvitamin D (25(OH)D) levels in serum collected at the time of enrollment and at year 4 in 572 Caucasian children with asthma, who were part of a multi-center clinical trial, the Childhood Asthma Management Program. Replication was performed in a second cohort of 592 asthmatics from Costa Rica and a third cohort of 516 Puerto Rican asthmatics. In addition, we attempted replication of three SNPs that were previously identified in a large GWAS of Caucasian individuals. The setting included data from a clinical trial of childhood asthmatics and two cohorts of asthmatics recruited for genetic studies of asthma. The main outcome measure was circulating 25(OH)D levels. The 25(OH)D levels at the two time-points were only modestly correlated with each other (intraclass correlation coefficient = 0.33) in the CAMP population. We identified SNPs that were nominally associated with 25(OH)D levels at two time-points in CAMP, and replicated four SNPs in the Costa Rican cohort: rs11002969, rs163221, rs1678849, and rs4864976. However, these SNPs were not significantly associated with 25(OH)D levels in a third population of Puerto Rican asthmatics. We were able to replicate the SNP with the strongest effect, previously reported in a large GWAS: rs2282679 (GC), and we were able to replicate another SNP, rs10741657 (CYP2R1), to a lesser degree. We were able to replicate two of three prior significant findings in a GWAS of 25(OH)D levels. Other SNPs may be additionally associated with 25(OH)D levels in certain populations.

Objective: The purpose of this study was to show the association between changes in clinician self-efficacy and readiness to change and implementation of an asthma management program (Easy Breathing)., Methods: A 36 month randomized, controlled trial was conducted involving 24 pediatric practices (88 clinicians). Randomized clinicians received interventions designed to enhance clinician self-efficacy and readiness to change which were measured at baseline and 3 years. Interventions consisted of an educational toolbox, seminars, teleconferences, mini-fellowships, opinion leader visits, clinician-specific feedback, and pay for performance. The primary outcome was program utilization (number of children enrolled in Easy Breathing/year); secondary outcomes included development of a written treatment plan and severity-appropriate therapy., Results: At baseline, clinicians enrolled 149 ± 147 (mean ± SD) children/clinician/year; 84% of children had a written treatment plan and 77% of plans used severity-appropriate therapy. At baseline, higher self-efficacy scores were associated with greater program utilization (relative rate [RR], 1.34; 95% confidence interval [CI], 1.04-1.72; P = .04) but not treatment plan development (RR, 0.63; 95% CI, 0.29-1.35; P = .23) or anti-inflammatory use (RR, 1.76; 95% CI, 0.92-3.35; P = .09). Intervention clinicians participated in 17 interventions over 36 months. At study end, self-efficacy scores increased in intervention clinicians compared to control clinicians (P = .01) and more clinicians were in an action stage of change (P = .001) but these changes were not associated with changes in primary or secondary outcomes., Conclusions: Self-efficacy scores correlated with program use at baseline and increased in the intervention arm, but these increases were not associated with greater program-related activities. Self-efficacy may be necessary but not sufficient for behavior change., (Copyright © 2012 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Puerto Rican and African American subjects share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults., Objective: We sought to examine whether a greater proportion of African ancestry is associated with lower FEV(1) and forced vital capacity (FVC) in Puerto Rican children independently of socioeconomic status, health care access, or key environmental/lifestyle factors., Methods: We performed a cross-sectional case-control study of 943 Puerto Rican children aged 6 to 14 years with (n= 520) and without (n= 423) asthma (defined as physician-diagnosed asthma and wheeze in the prior year) living in Hartford, Connecticut (n= 383), and San Juan, Puerto Rico (n= 560). We estimated the percentage of African racial ancestry in study participants using genome-wide genotypic data. We tested whether African ancestry is associated with FEV(1) and FVC using linear regression. Multivariate models were adjusted for indicators of socioeconomic status and health care and selected environmental/lifestyle exposures., Results: After adjustment for household income and other covariates, each 20% increment in African ancestry was significantly associated with lower prebronchodilator FEV(1) (-105 mL; 95% CI, -159 to -51 mL; P< .001) and FVC (-133 mL; 95% CI, -197 to -69 mL; P< .001) and postbronchodilator FEV(1) (-152 mL; 95% CI, -210 to -94 mL; P< .001) and FVC (-145 mL; 95% CI, -211 to -79 mL; P< .001) in children with asthma. Similar but weaker associations were found for prebronchodilator and postbronchodilator FEV(1) (change for each 20% increment in African ancestry, -78 mL; 95% CI, -131 to -25 mL; P= .004) and for postbronchodilator FVC among children without asthma., Conclusions: Genetic factors, environmental/lifestyle factors, or both correlated with African ancestry might influence childhood lung function in Puerto Rican subjects., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Current asthma guidelines recommend assessing the level of a patient's asthma control. Consequently, there is increasing use of asthma control as an outcome measure in clinical research studies. Several composite assessment instruments have been developed to measure asthma control., Objective: National Institutes of Health institutes and federal agencies convened an expert group to propose the most appropriate standardized composite score of asthma control instruments to be used in future asthma studies., Methods: We conducted a comprehensive search of PubMed using both the National Library of Medicine's Medical Subject Headings and key terms to identify studies that attempted to develop and/or test composite score instruments for asthma control. We classified instruments as core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop convened in March 2010 and finalized in September 2011., Results: We identified 17 composite score instruments with published validation information; all had comparable content. Eight instruments demonstrated responsiveness over time; 3 demonstrated responsiveness to treatment. A minimal clinically important difference has been established for 3 instruments. The instruments have demographic limitations; some are proprietary, and their use could be limited by cost., Conclusion: Two asthma composite score instruments are sufficiently validated for use in adult populations, but additional research is necessary to validate their use in nonwhite populations. Gaps also exist in validating instruments for pediatric populations., (Published by Mosby, Inc.)

Objective: To examine the relation between mouse allergen exposure and asthma in Puerto Rican children., Methods: Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV(1) and FEV(1)/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures., Results: Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1) in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1) (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01)., Conclusions: Mouse allergen is associated with a higher FEV(1) and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.

Background: Sensitivity to mold has been associated with asthma incidence, persistence, and severity., Objective: To examine the relationship between skin test reactivity (STR) to molds and specifically to Alternaria and asthma severity in a group of ethnically diverse children in Connecticut., Methods: Demographics and STR to 14 local allergens, including Alternaria, Penicillium, and mold mix, were obtained for 914 Puerto Rican, African American, and non-Hispanic white children., Results: A total of 126 children (14%) had a positive skin test result to mold, and 58 (6%) demonstrated STR to Alternaria. Compared with non-Hispanic white children, there was no difference in the likelihood of being sensitized to Alternaria for Puerto Rican and African American children (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.3-1.5; and OR, 0.9; 95% CI, 0.4-2.2; respectively). In an adjusted analysis, Alternaria STR was associated with severe, persistent asthma (OR, 3.4; 95% CI, 1.2-8.6) but did not predict increasing asthma severity. STR to cat (OR, 2.5; 95% CI, 1.3-4.9) and dog (OR, 2.9; 95% CI, 1.3-6.0) was also associated with severe persistent asthma. Alternaria STR was associated with severe persistent asthma independent of the total number of positive skin test results., Conclusions: Mold and Alternaria STR were uncommon among children in Connecticut. Alternaria STR was not associated with increasing asthma severity but was associated with severe, persistent asthma independent of the total number of positive skin test results. There was no association between ethnicity and Alternaria STR., (Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: We assessed whether a successful asthma-management program could be translated into pediatrician's offices, improve care, and reduce medical services use., Methods: Pediatrician's offices from 6 communities in Connecticut were trained, and all children aged 6 months or older were eligible for enrollment. Quality measures included enrollment numbers, appropriate use of anti-inflammatory therapy, and distribution of a written treatment plan. Medical services utilization data for Medicaid-insured children were expressed as relative rates (RRs) (95% confidence intervals [CIs]) before and after enrollment, and we used historical and contemporaneous comparisons and generalized estimating equations., Results: A total of 51 practices and 297 clinicians enrolled 32 680 children from 2002 to 2007; 10 467 had asthma, of whom 4354 were insured with Medicaid. Children with persistent asthma experienced decreases in the number of hospitalizations (RR: 0.51 [95% CI: 0.39-0.65]) and emergency-department visits (RR: 0.70 [95% CI: 0.68-0.84]), and there was no change in number of outpatient visits (RR: 0.99 [95% CI: 0.9-1.10]). Inhaled corticosteroid use doubled, appropriate use of anti-inflammatory therapy increased to 96%, and 94% of the children were given a written treatment plan., Conclusions: General pediatricians can successfully implement an asthma-management program that is effective in improving care for large numbers of children.

Objectives: To examine costs associated with an asthma management program that reduces asthma-related health services utilization and to calculate potential return on investment (ROI) from the Medicaid managed care plan perspective., Study Design: Cross-sectional., Methods: Clinical and economic data were obtained for 3298 ethnically diverse children with asthma (48% with persistent asthma) who resided in a poor urban community (Hartford, Connecticut) and were enrolled in Easy Breathing, an asthma management program for pediatricians. We calculated the cost per participating child with asthma during the first 3 years (July 1998 to June 2001) relative to the difference in costs for participating and nonparticipating children calculated by applying Medicaid reimbursement rates to data on services., Results: Start-up costs were $28.95 per child with asthma in year 1, and operating costs averaged $10.28 in years 2 and 3. The mean reduction in costs was $36.72 per child per year in years 2 and 3. If Medicaid managed care plans had been charged an amount equal to program operating costs after year 1 ($10.28 per child with asthma per year), at-risk health plans could have incurred cost savings of approximately $26.44 per child with asthma per year. The potential ROI for years 2 and 3 was $3.58 per US dollar spent., Conclusions: Easy Breathing reduced overall costs of care for urban children with asthma of varying severities. If managed care plans held at risk by Medicaid had reimbursed program operating costs for participants in Easy Breathing, they would have experienced a positive ROI.

Objective: To assess the contribution of organizational factors to implementation of 3 asthma quality measures: enrollment in a disease management program, development of a written treatment plan, and prescription of severity-appropriate anti-inflammatory therapy., Study Design: A total of 138 pediatric clinicians and 247 office staff in 13 urban clinics and 23 nonurban private practices completed questionnaires about their practice's organizational characteristics (eg, leadership, communication, perceived effectiveness, job satisfaction)., Results: 94% of the clinicians and 92% of the office staff completed questionnaires. When adjusted for confounders, greater practice activity and perceived effectiveness in meeting family needs were associated with higher rates of enrollment in the Easy Breathing program, whereas higher scores for 3 organizational characteristics--communication timeliness, decision authority, and job satisfaction--were associated with both higher enrollment and a greater number of written treatment plans. None of the organizational characteristics was associated with greater use of anti-inflammatory therapy., Conclusions: Three organizational characteristics predicted 2 quality asthma measures: use of a disease management program and creation of a written asthma treatment plan. If these organizational characteristics were amenable to change, then our findings could help focus interventions in areas of effective and acceptable organizational change.

Objective: To examine differences in the effectiveness of a program to reduce use of health care services in urban-dwelling black and Hispanic children as a way to understand the origins of disparities., Methods: We examined hospitalization rates, emergency department (ED) visits, outpatient visits (OPVs), and bronchodilator and inhaled corticosteroid (ICS) prescriptions in 2,362 children receiving Medicaid who were enrolled in an asthma management program (Easy Breathing) from June 1, 1998, through May 31, 2001. We used generalized estimating equations to fit multivariate marginal Poisson regression models, controlling for sex, ethnicity, asthma severity, and secular trends., Results: Hospitalization rates were high and decreased 53% for black children and 33% for Hispanic children after the intervention. The ED visits decreased for Hispanic children, and OPVs decreased for both black and Hispanic children after Easy Breathing. The ICS prescription rates increased, with a decrease in the bronchodilator to ICS ratio from 5.81 to 2.16 in black children and from 4.74 to 2.17 in Hispanic children. Hispanic children filled more prescriptions for bronchodilators and ICSs (odds ratio, 1.29; 95% confidence interval, 1.05-1.59; P = .01; and odds ratio, 1.55; 95% confidence interval, 1.14-2.11; P = .005; respectively) 3 and 12 months after Easy Breathing. Black children were more likely than Hispanic children not to fill any asthma prescription. A total of 12% of children filled no asthma prescriptions., Conclusions: Hispanic children seek more medical services than black children, whereas black children fill fewer prescriptions for bronchodilators and ICSs than Hispanic children. Easy Breathing reduces overall hospitalizations and OPVs in black and Hispanic children and asthma-specific ED visits in Hispanic children; the benefits of Easy Breathing are different in Hispanic and black children.

The purpose of this study was to examine the challenges of integrating an asthma disease management (DM) program into a primary care setting from the perspective of primary care practitioners. A second goal was to examine whether barriers differed between urban-based and nonurban-based practices. Using a qualitative design, data were gathered using focus groups in primary care pediatric practices. A purposeful sample included an equal number of urban and nonurban practices. Participants represented all levels in the practice setting. Important themes that emerged from the data were coded and categorized. A total of 151 individuals, including physicians, advanced practice clinicians, registered nurses, other medical staff, and nonmedical staff participated in 16 focus groups that included 8 urban and 8 nonurban practices. Content analyses identified 4 primary factors influencing the implementation of a DM program in a primary care setting. They were related to providers, the organization, patients, and characteristics of the DM program. This study illustrates the complexity of the primary care environment and the challenge of changing practice in these settings. The results of this study identified areas in a primary care setting that influence the adoption of a DM program. These findings can assist in identifying effective strategies to change clinical behavior in primary care practices.

Objective: The purpose of this study is to evaluate the relationship between primary care provider visits and emergency department (ED) asthma visits for urban, minority children., Design: This is a retrospective review of eligibility files and Medicaid claims for children with asthma from 1999 to 2001., Participants: Children 24 months through 17 years of age with Medicaid or state health insurance, who resided in Hartford, Connecticut, and had persistent asthma, were included., Outcome Measures: The primary outcome was the number of ICD-9 asthma-related primary care visits in the 12-month period before asthma ED visits. Secondary outcomes included the number of filled prescriptions for controller medications 3 and 12 months before emergency asthma visits., Results: One thousand four hundred seventy-four children met study criteria. Children with a greater number of asthma-related primary care visits during the previous 12 months were less likely to have asthma-related ED visits in 2000 and 2001 (both years P < 0.001). Children with an asthma-related ED visit had fewer primary care visits (for any reason) in 2000 but not in 2001 (P < 0.01). In 2000, the odds that children with 3 or more asthma-related primary care visits and a filled inhaled corticosteroid (ICS) had an asthma ED visit were 1/5 those of children with fewer asthma-related PCP visits or no filled ICS (OR = 0.20, 95% CI (0.06, 0.65)). Fewer than 17% of all children with asthma-related ED visits filled any prescription for controller medications in the 3 months before these visits., Conclusion: Asthma-related primary care visits are associated with fewer asthma-related ED visits in urban children., ((c) 2007 Wiley-Liss, Inc.)

National guidelines recommend the use of clinical history and spirometry to determine asthma severity. We examined the usefulness of the six guideline-recommended clinical questions in determining asthma severity and then compared guideline-determined severity to clinician-reported and spirometry-determined severity in a cross-sectional study of 201 children with asthma who were not receiving controller therapy. Four guideline-recommended questions (daytime and nocturnal symptoms, school absenteeism, and exercise impairment) determined asthma severity. Concordance between clinician-reported and spirometry-determined asthma severity was poor (kappa = 0.02). Clinical history alone underestimated spirometry-determined disease severity in 27% of children while spirometry results alone underestimated clinician-determined severity in 40% of children.

Objective: We sought to examine whether pediatric clinicians in private, non-health maintenance organization practices could implement the national asthma guidelines and whether, when implemented, these guidelines would decrease medical services utilization and improve asthma care for children., Methods: A trial of a disease management program (Easy Breathing II) involving 20 private pediatric practices in the greater Hartford, Connecticut area was conducted between January 1, 2001, and December 31, 2003. Demographic data on participating practitioners and patients were obtained from questionnaires. Medical services utilization data from claims were obtained from ConnectiCare, a regional managed care organization., Results: Of the 16750 children enrolled in Easy Breathing II, 2458 were enrolled in ConnectiCare and 490 had asthma. Inhaled corticosteroid use increased in the community overall during the study period. After enrollment in Easy Breathing II, with adjustment for age, gender, ethnicity, asthma severity, season, and calendar year, children with persistent asthma experienced an additional 47% increase in inhaled corticosteroid use, a 56% reduction in outpatient visits, and a 91% decrease in emergency department visits for treatment of asthma. Adherence to national asthma guidelines for prescribing inhaled corticosteroids was 95%. Seventeen of the 20 practices are still using Easy Breathing, 5 years after program implementation., Conclusions: Pediatric primary care clinicians in private practice settings can implement an asthma management program patterned after the national asthma guidelines. When implemented, this program is successful in reducing medical services utilization for children with asthma. Just as differences in patterns of medical services utilization exist in private practices, compared with urban clinics, the impact of disease management on medical services utilization differs in private practices, compared with urban clinics.

Our objective was to validate the Council of State and Territorial Epidemiologists (CSTE) definition of "probable" asthma and the Health Plan Employer Data and Information Set (HEDIS) definition of persistent asthma for diagnosis of pediatric asthma, and examine modifications that improve case recognition. CSTE and HEDIS criteria were applied to a cross-sectional study of 3,905 Medicaid children with physician-confirmed diagnosis of asthma/no asthma using a validated survey instrument based upon National Asthma Education and Prevention Program (NAEPP) Guidelines. Modified criteria were applied to another group of 1,458 non-Medicaid children from a managed care organization (MCO). Of 1,852 Medicaid children with physician-confirmed asthma, 906 had persistent asthma. CSTE identified 61% of children with "probable" asthma; HEDIS identified 44% of children with persistent asthma. Correct identification increased with greater disease severity. A modified CSTE increased sensitivity from 0.61 to 0.90, while maintaining high specificity. Three new HEDIS algorithms increased sensitivity from 0.44 to >0.84, with specificity >0.89. When applied prospectively to MCO children, these new algorithms demonstrated improved sensitivity. In conclusion, studies using current CSTE or HEDIS algorithms for case recognition underestimate asthma prevalence and overestimate asthma severity in children. Modified algorithms improve the identification of "probable" and persistent asthma., ((c) 2006 Wiley-Liss, Inc.)