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1.  Statin Exposure Is Associated with Decreased Asthma-related Emergency Department Visits and Oral Corticosteroid Use 
Rationale: Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects.
Objectives: To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort.
Methods: Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non–statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression.
Measurements and Main Results: Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95% CI, 0.81–0.99; P = 0.04). There were no differences in asthma-related hospitalizations (OR, 0.91; 95% CI, 0.66–1.24; P = 0.52).
Conclusions: Among statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings.
doi:10.1164/rccm.201306-1017OC
PMCID: PMC3863744  PMID: 24093599
HMG-CoA reductase inhibitors; asthma therapy; exacerbations
2.  Diagnostic accuracy of the bronchodilator response in children 
Background
The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood.
Objectives
We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts.
Methods
Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program.
Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs.
Results
A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%).
Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%).
Conclusions
Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.
doi:10.1016/j.jaci.2013.03.031
PMCID: PMC3759549  PMID: 23683464
Asthma; bronchodilator response; diagnosis
3.  Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D 
Background
The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD).
Objective
To determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time.
Methods
Children aged 5–12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled and oral corticosteroids (OCS) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial and serial DEXA scans of the lumbar spine were performed. Annual BMA rates were defined as: [(BMD at 4 years follow-up − BMD at baseline)/4 years].
Results
BMA was calculated for 780 subjects. In boys, baseline vitamin D levels significantly modified the relationship between OCS and BMA (vitamin D x OCS interaction, p=0.023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCS in vitamin D insufficient boys only (p<0.001). Compared to vitamin D sufficient boys, vitamin D insufficient boys exposed to more than 2 courses of oral corticosteroids per year had twice the decrease in BMA rate (relative to boys who were OCS-unexposed).
Conclusions
Vitamin D levels significantly modified the effect of oral corticosteroids on bone mineral accretion in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma may confer benefits to bone health.
doi:10.1016/j.jaci.2012.04.005
PMCID: PMC3387323  PMID: 22608570
Asthma; vitamin D; bone mineral density; corticosteroids
4.  The Pharmacogenetics and Pharmacogenomics of Asthma Therapy 
The Pharmacogenomics Journal  2011;11(6):383-392.
Despite the availability of several classes of asthma medications and their overall effectiveness, a significant portion of patients fail to respond to these therapeutic agents. Evidence suggests that genetic factors may partly mediate the heterogeneity in asthma treatment response. This review discusses important findings in asthma pharmacogenetics and pharmacogenomics studies conducted to date, examines limitations of these studies and finally, proposes future research directions in this field. The focus will be on the three major classes of asthma medications: β-adrenergic receptor agonists, inhaled corticosteroids and leukotriene modifiers. Although many studies are limited by small sample sizes and replication of the findings is needed, several candidate genes have been identified. High-throughput technologies is also allowing for large-scale genetic investigations. Thus, the future is promising for a personalized treatment of asthma, which will improve therapeutic outcomes, minimize side effects and lead to a more cost-effective care.
doi:10.1038/tpj.2011.46
PMCID: PMC3298891  PMID: 21987090
asthma; pharmacogenetics; pharmacogenomics
5.  Genetic and histological evidence for autophagy in asthma pathogenesis 
doi:10.1016/j.jaci.2011.09.035
PMCID: PMC3268897  PMID: 22040902
asthma pathogenesis; autophagy; lung function; polymorphism; SNP; ATG5; autophagosome
6.  Previously Suicidal Adolescents: Predictors of Six-Month Outcome 
Objective
To determine the baseline variables, including borderline personality disorder (BPD), associated with the six-month outcome of previously suicidal adolescents (n=263) presenting to an emergency department and treated predominantly as out-patients.
Methods
Multivariate logistic regression was used to analyze the associations between baseline variables and suicidality at six-month follow-up.
Results
BPD, previous suicide attempt(s), drug use and female gender were associated with subsequent suicidality.
Conclusions
These findings corroborate previously reported risk factors for recurring suicidality among adolescents and broaden their generalizability to those presenting to an emergency department, many diagnosed with BPD.
PMCID: PMC2583916  PMID: 19018322
adolescence; borderline personality disorder; suicide; predictors; prospective; adolescence; trouble de personnalité borderline; suicide; prédicteurs; probabilité
7.  Construct Validity of the Adolescent Borderline Personality Disorder: A Review 
Introduction
Although the term borderline personality disorder (BPD) is used to describe adolescents in clinical settings, there is confusion as to what it comprises. To further elucidate that diagnosis, this article reviews its construct validity.
Method
Relevant publications appearing in PsychInfo (1872 to present) were reviewed for the purposes of this article.
Results
Thirty-six of the approximately sixty-five publications selected for consideration were included in this review.
Conclusion
The construct validity of adolescent BPD is supported by internal consistency (comparable to that of adults), group differences (ie this diagnosis segregates BPD from non-BPD adolescents), convergent validity (ie multiple measures of this disorder measure the same pathology) and concurrent validity, whereby these youth manifest functional impairment and distress. By contrast, the adolescent BPD criteria manifest less construct validity than the adult diagnosis in that its criteria did not uniformly predict the overall diagnosis, and showed more criterion overlap with other personality disorders and a broader pattern of axis II comorbidity. Further diminishing its construct validity, factor analysis suggested that adolescent BPD was not a single entity, and its low predictive validity was demonstrated by little diagnostic stability through adolescence into adulthood.
PMCID: PMC2538734  PMID: 19030500
adolescent; review; borderline personality disorder; validity; construct; Adolescent; revu; personnalité borderline; validité; construit

Results 1-7 (7)