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Academic medical centers are generating an increasing amount of biomedical data and there is an increasing demand for biomedical data for research purposes by research projects, research consortia, companies, and other third parties. At the same time, as the number of patients grows and the amount of data per patient grows, there is an increasing possibility that some information about some patients may become available if the data is shared with third parties and the third parties have a data breach or violate the terms of the data use agreement. Balancing the importance of research that may result in improved patient outcomes with the importance of protecting patient data is challenging. The article discusses the principles, considerations about risks and mitigating risks, and guidelines used at the University of Chicago used for making decisions about sharing biomedical data with third parties., Comment: 6 pages

Additional file 12. Summaries of GWAS for bronchial responsiveness in the Hutterites. Q-Q plot of GWAS results for bronchical responsiveness index (BRI) in the Hutterites (N=964) and Manhattan plot of GWAS results for bronchical responsiveness index (BRI) in the Hutterites (N=964).

Additional file 10. Methylation levels among cases at baseline (vehicle) look more like controls following IL-13+IL-17 stimulation. Comparison of methylation levels at the 260 DMPs in controls following IL-13+IL-17 exposure to methylation levels among cases and controls at baseline (vehicle treated).

Additional file 9. Volcano plots illustrating methylation responses to IL-13 and/or IL-17 in ASMCs. Methylation responses following 24 hours of exposure to IL-13, IL-17A, or IL-13+IL-17A compared to vehicle.

Additional file 1. Supplementary Methods. Additional details regarding cell culture conditions, data processing, and analysis.

Additional file 18. List of QTLs idenfitied in this study that are also BRI GWAS SNPs. eQTLs (lfsr

Additional file 11. Contractile measurements do not significantly differ between cases and controls or among treatment groups. Comparison of contractile measurements in IL-13 and/or IL-17A-exposed cells.

Additional file 7. A comparison of differentially expressed genes among individuals with and without asthma. Information regarding numbers of DEGs (FDR

Additional file 2. Overview of study design. An overview of the study design across two sites: Chicago and Boston.

Additional file 5. Comparison of transcriptional responses to IL-17 from another study. Genes reported by Dragon et al. to be up-regulated in response to IL-17 exposure.

Additional file 3. Volcano plots of transcriptional response to cytokines. Magnitude of transcriptional responses following 24 hours of exposure to cytokines.

Additional file 17. Overlaps of QTLs and GWAS SNPs identified in this study. Venn diagram illustrating overlaps of molecular QTLs (e- and meQTLs; lfsr

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 the addition of salmeterol than to an increase in the 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, .)

BackgroundLoss of bronchoprotection (LOBP) with a regularly used long-acting β2-adrenergic receptor agonist (LABA) is well documented. LOBP has been attributed to β2-adrenergic receptor (B2AR) downregulation, a process requiring farnesylation, which is inhibited by alendronate.ObjectiveWe sought to determine whether alendronate can reduce LABA-associated LOBP in inhaled corticosteroid (ICS)-treated patients.MethodsWe conducted a randomized, double-blind, placebo-controlled, parallel-design, proof-of-concept trial. Seventy-eight participants with persistent asthma receiving 250μg of fluticasone twice daily for 2weeks were randomized to receive alendronate or placebo while initiating salmeterol for 8weeks. Salmeterol-protected methacholine challenges (SPMChs) and PBMC B2AR numbers (radioligand binding assay) and signaling (cyclic AMP ELISA) were assessed before randomization and after 8weeks of ICS plus LABA treatment. LOBP was defined as a more than 1 doubling dose reduction in SPMCh PC20 value.ResultsThe mean doubling dose reduction in SPMCh PC20 value was 0.50 and 0.27 with alendronate and placebo, respectively (P=.62). Thirty-eight percent of participants receiving alendronate and 33% receiving placebo had LOBP (P=.81). The after/before ICS plus LABA treatment ratio of B2AR number was 1.0 for alendronate (P=.86) and 0.8 for placebo (P=.15; P=.31 for difference between treatments). The B2AR signaling ratio was 0.89 for alendronate (P=.43) and 1.02 for placebo (P=.84; P=.44 for difference). Changes in lung function and B2AR number and signaling were similar between those who did and did not experience LOBP.ConclusionThis study did not find evidence that alendronate reduces LABA-associated LOBP, which relates to the occurrence of LOBP in only one third of participants. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients. B2AR downregulation measured in PBMCs does not appear to reflect LOBP.

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 D 3 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 D 3 (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 β-agonists, systemic corticosteroids, and health care). Results Treatment with vitamin D 3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D 3 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 D 3 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 D 3 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 D 3 supplementation in patients with symptomatic asthma. Trial Registration clinicaltrials.gov Identifier:NCT01248065