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Impact of Study Design on the Evaluation of Inhaled and Intranasal Corticosteroids' Effect on Hypothalamic-Pituitary-Adrenal Axis Function, Part I: General Overview of HPA Axis Study Design.

J Pharm Sci. 2013 Aug 5;

Authors: Fan Y, Ma L, Pippins J, Limb S, Xu Y, Sahajwalla CG

Abstract
Inhaled and intranasal corticosteroids (ICS and INS) are among the mainstays of the treatment for asthma and allergic rhinitis, respectively, and also carry the potential to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Several important factors affect the interpretability of trials investigating the impact of ICS and INS on the HPA axis. This paper reviews 106 published clinical trials, peer-reviewed articles, and New Drug Application reviews of approved ICS and INS, using MEDLINE and Drugs@FDA database. The trials included in this review evaluated the potential impact on HPA axis function of eight approved single-ingredient ICS and INS (beclomethasone dipropionate, budesonide, ciclesonide, flunisolide, fluticasone furoate, flucticasone propionate, mometasone furoate, and triamcinolone acetonide) and combination products containing these ingredients. The most commonly utilized design was blinded, placebo controlled, and short term (<6 weeks) for adult trials and blinded, placebo controlled, and long term (≥6 weeks) for pediatric trials. Factors potentially affecting trial results include the choice of dose, dosing duration, assay sensitivity, statistical methodology, and the study population evaluated (patients or healthy volunteers). All of these factors have the potential to affect the level of adrenal suppression detected. In conclusion, to be informative, a HPA axis study should be well designed and carefully implemented to minimize variability in results and improve the overall interpretability of data obtained. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

PMID: 23918409 [PubMed - as supplied by publisher]

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Which Biomarkers Are Effective for Identifying Th2-Driven Inflammation in Asthma?

Curr Allergy Asthma Rep. 2013 Aug 7;

Authors: Diamant Z, Tufvesson E, Bjermer L

Abstract
Recognition of asthma as a heterogeneous disease revealed different potential molecular targets and urged the development of targeted, customized treatment modalities. Evidence was provided for different inflammatory subsets of asthma and more recently, further refined to T helper (Th)2-high and Th2-low subphenotypes with different responsiveness to standard and targeted pharmacotherapy. Given these differences in immunology and pathophysiology, proof of concept studies of novel treatment modalities for asthma should be performed in adequate, well-defined phenotypes. In this review, we describe both existing and novel biomarkers of Th2-inflammation in asthma that can be applied to classify asthma subphenotypes in clinical studies and for treatment monitoring.

PMID: 23918590 [PubMed - as supplied by publisher]

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Asthma During Pregnancy and Clinical Outcomes in Offspring: A National Cohort Study.

Pediatrics. 2013 Aug 5;

Authors: Tegethoff M, Olsen J, Schaffner E, Meinlschmidt G

Abstract
BACKGROUND AND OBJECTIVEMaternal asthma is a common pregnancy complication, with adverse short-term effects for the offspring. The objective was to determine whether asthma during pregnancy is a risk factor of offspring diseases.METHODS:We studied pregnant women from the Danish National Birth Cohort (births: 1996-2002; prospective data) giving birth to live singletons (n = 66 712 mother-child pairs), with 4145 (6.2%) women suffering from asthma during pregnancy. We estimated the associations between asthma during pregnancy and offspring diseases (International Classification of Diseases, 10th Revision diagnoses from national registries), controlling for potential confounders and validating findings by secondary analyses.RESULTS:Offspring median age at end of follow-up was 6.2 (3.6-8.9) years. Asthma was associated with an increased offspring risk of infectious and parasitic diseases (hazard ratio [HR] 1.34; 95% confidence interval [CI] 1.23-1.46), diseases of the nervous system (HR 1.43; CI 1.18-1.73), ear (HR 1.33; CI 1.19-1.48), respiratory system (HR 1.43; CI 1.34-1.52), and skin (HR 1.39; CI 1.20-1.60), and potentially (not confirmed in secondary analyses) of endocrine and metabolic disorders (HR 1.26; CI 1.02-1.55), diseases of the digestive system (HR 1.17; CI 1.04-1.32), and malformations (odds ratio 1.13; CI 1.01-1.26), but not of neoplasms, mental disorders, or diseases of the blood and immune system, circulatory system, musculoskeletal system, and genitourinary system.CONCLUSIONS:To the best of our knowledge, this is the first comprehensive study of the associations between asthma during pregnancy and a wide spectrum of offspring diseases. In line with previous data on selected outcomes, asthma during pregnancy may be a risk factor for numerous offspring diseases, suggesting that careful monitoring of women with asthma during pregnancy and their offspring is important.

PMID: 23918893 [PubMed - as supplied by publisher]

Onset and persistence of respiratory/allergic symptoms in preschoolers: new insights from the PARIS birth cohort.

Allergy. 2013 Aug 6;

Authors: Rancière F, Nikasinovic L, Bousquet J, Momas I

Abstract
BACKGROUND: The natural course of childhood asthma and allergy is complex and not fully understood. We aimed to identify phenotypes based upon the time course of respiratory/allergic symptoms throughout preschool years.
METHODS: As part of the PARIS cohort, symptoms of wheezing, dry night cough, rhinitis and dermatitis were collected annually from birth to age 4 years. K-means clustering was used to group into phenotypes children with similar symptoms trajectories over the study period. Associations of phenotypes with IgE sensitization and risk factors were studied using multinomial logistic regression.
RESULTS: Besides a group with low prevalence of symptoms considered as reference (n = 1236, 49.0%), four distinct respiratory/allergic phenotypes were identified: two transient [transient rhinitis phenotype (n = 295, 11.7%), transient wheeze phenotype (n = 399, 15.8%)], without any relation with IgE sensitization, and two persistent [cough/rhinitis phenotype (n = 284, 11.3%), dermatitis phenotype (n = 308, 12.2%)], associated with IgE sensitization. Transient rhinitis phenotype was only associated with tobacco smoke exposure, which could irritate the airways. Transient wheeze phenotype was related to male sex and contact with other children (older siblings, day care attendance). Lastly, risk factors for both IgE-associated phenotypes encompassed parental history of allergy, potential exposure to allergens and stress, known to be associated with the development of allergic diseases.
CONCLUSION: This study provides evidence for the existence of different respiratory/allergic phenotypes before school age. The fact that they differ in terms of sensitization and risk factors reinforces the plausibility of distinct phenotypes, potentially linked to irritation and infections for the transient phenotypes and to allergy for the persistent phenotypes.

PMID: 23919292 [PubMed - as supplied by publisher]