Screening for hypothalamic–pituitary–adrenal axis suppression in asthmatic children remains problematic

BMJ Open 2013;3:e002935 doi:10.1136/bmjopen-2013-002935

• Epidemiology

Screening for hypothalamic–pituitary–adrenal axis suppression in asthmatic children remains problematic: a cross-sectional study

1. Ekkehard Werner Zöllner1,2, 
2. Carl J Lombard3, 
3. Ushma Galal3, 
4. Stephen Hough4,
5. Elvis M Irusen5, 
6. Eugene Weinberg6

+Author Affiliations

1. ¹Paediatric Endocrine Unit, Department of Paediatrics, Stellenbosch University, Tygerberg Children's Hospital, Cape Town, South Africa
2. ²Endocrine Unit, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa
3. ³Biostatistics Unit, Medical Research Council, Cape Town, South Africa
4. ⁴Division of Endocrinology, Department of Medicine, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
5. ⁵Pulmonology Division, Department of Medicine, Tygerberg Hospital, Stellenbosch University, Cape Town, South Africa
6. ⁶Allergy Unit, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa

1. Corresponding toDr Ekkehard Werner Zöllner; zollner@sun.ac.za

• Received 22 March 2013
• Revised 28 June 2013
• Accepted 3 July 2013
• Published 1 August 2013

Abstract

Objective To determine which parameter is the most useful screening test for hypothalamic–pituitary–adrenal suppression in asthmatic children.

Design Cross-sectional study.

Setting Paediatric allergy clinics in Cape Town, South Africa.

Participants 143 asthmatic children of mostly mixed ancestry, aged 5–12 years.

Outcome measures Primary outcome measures included Spearman correlation coefficients (r) calculated between the postmetyrapone (PMTP) serum adrenocorticotropic hormone (ACTH), 11-deoxycortisol (11DOC), 11DOC+ cortisol (C) and height, weight, height velocity, weight velocity, change in systolic blood pressure from supine to standing, early morning urinary free cortisol (UFC), morning C, ACTH and dehydroepiandrosterone sulfate (DHEAS). Secondary outcome measures were the receiver operating characteristics (ROC) curve and the diagnostic statistics for the most promising test.

Results All screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m²) were statistically significant—DHEAS for PMTP ACTH and 11DOC (r=0.20, p=0.025 and r=0.21, p=0.017); UFC (nmol/m²) for PMTP 11DOC and 11DOC+C (r=0.19, p=0.033 and r=0.20, p=0.022). The area under ROC curve for DHEAS in the 5-year to 9-year age group was 0.69 (95% CI 0.47 to 0.92). At DHEAS cut-off of 0.2 µmol/L: sensitivity=0.88 (CI 0.47 to 1.00), specificity=0.61 (CI 0.42 to 0.78), positive predictive value=0.37 (CI 0.16 to 0.62), negative predictive value=0.95 (CI 0.75 to 1.00), accuracy=0.67 (CI 0.50 to 0.81), positive likelihood ratio=2.26 (CI 1.35 to 3.78), negative likelihood ratio=0.20 (CI 0.03 to 1.30).

Conclusions No parameter is useful as a universal screening test. DHEAS may be suitable to exclude HPAS before adrenarche. Further research is needed to confirm these findings and identify factors, for example, genetic that may predict or protect against HPAS.

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RESEARCH ARTICLE

Study Design and Quality of Reporting of Randomized Controlled Trials of Chronic Idiopathic or Autoimmune Urticaria: Review

• Elodie Le Fourn mail,
 
• Bruno Giraudeau,
 
• Olivier Chosidow,
 
• Marie-Sylvie Doutre,
 
• Gérard Lorette

Abstract

Background

The recommended first-line therapy of chronic urticaria is second-generation antihistamines, but the modalities of treatment remains unclear. Numerous recommendations with heterogeneous conclusions have been published. We wondered whether such heterogeneous conclusions were linked to the quality of published studies and their reporting.

Objective

To review the study design and quality of reporting of randomized control trials investigating pharmacological treatment of autoimmune or idiopathic chronic urticaria.

Methodology/Principal Findings

MEDLINE and EMBASE were searched for pharmacological randomized controlled trials involving patients with chronic autoimmune or idiopathic urticaria, with the main outcome being treatment efficacy. Data were collected on general characteristics of the studies, internal validity, studied treatments, design of the trial, outcome measures and “spin” strategy in interpreting results. Spin was defined as use of specific reporting strategies to highlight that the experimental treatment is beneficial, despite statistically nonsignificant results. We evaluated 52 articles that met our criteria. Patients were reported as blinded in 42 articles (81%) and the outcome assessor was blinded in 37 (71%). A placebo was the only comparator in 13 (25%) studies. The study duration was <8 10="" 12="" 15="" 31.="" 33="" 37="" 39="" 4="" a="" after="" and="" articles="" assessor="" because="" blinding="" centralized.="" clear="" computed="" described="" different="" discontinuation="" double-dummy="" effects="" follow-up="" for="" had="" identical="" in="" major="" no="" nonsignificant="" not="" of="" or="" outcome.="" outcome="" p="" primary="" randomization="" recognizable="" score="" scores="" secondary="" specified="" spin="" strategy="" studies="" the="" they="" total="" treatment="" used.="" used="" was="" weeks="" were="" with="">

Conclusion

For establishing guidelines in treatment of chronic urticaria, studies should focus on choosing clinically relevant and reproducible primary outcomes, long-term follow-up, limited use of placebo and avoiding spin strategies.

Citation: Le Fourn E, Giraudeau B, Chosidow O, Doutre M-S, Lorette G (2013) Study Design and Quality of Reporting of Randomized Controlled Trials of Chronic Idiopathic or Autoimmune Urticaria: Review. PLoS ONE 8(8): e70717. doi:10.1371/journal.pone.0070717

Editor: H. Peter Soyer, The University of Queensland, Australia

Received: November 30, 2012; Accepted: June 26, 2013; Published: August 5, 2013

Copyright: © 2013 Le Fourn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was supported by a grant from Association Recommandations en Dermatologie, France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

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• References

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Predicting survival after acute exacerbation chronic obstructive pulmonary disease (ACOPD)

 

International Journal of Chronic Obstructive Pulmonary Disease

Predicting survival after acute exacerbation chronic obstructive pulmonary disease (ACOPD): is long-term application of noninvasive ventilation the last life guard?

Letter

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Authors: Esquinas AM, Matsuoka Y, Stieglitz S

Published Date August 2013 Volume 2013:8 Pages 379 - 381

DOI: http://dx.doi.org/10.2147/COPD.S49455

Received:	04 June 2013
Accepted:	11 June 2013
Published:	07 August 2013

Antonio M Esquinas,¹ Yoshinori Matsuoka,² Sven Stieglitz^3
1Intensive Care Unit, Hospital Morales Meseguer, Murcia, Spain; ²Saga Medical School Hospital, Department of Anesthesiology and Intensive Care Medicine, Saga, Japan; ³Clinic for Pneumology and Allergology, Centre for Sleep and Ventilation Medicine, Solingen, Germany

Patients with acute chronic obstructive pulmonary disease (ACOPD) admitted to an intensive care unit (ICU) still show substantial high hospital mortality (24%).¹ After ICU discharge, long-term application noninvasive ventilation (NIV) may be a reasonable and effective indication.² However, hospital mortality shows higher mortality rates for patients with COPD surviving their first episode after 2 and 5 years.^2,3 

View original paper by Titlestad and colleagues.

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Peripherally induced Tregs – role in immune homeostasis and autoimmunity

Mahesh Yadav^†, Stephen Stephan and Jeffrey A. Bluestone*

• Diabetes Center, University of California San Francisco, San Francisco, CA, USA
• Front. Immunol., 07 August 2013 | doi: 10.3389/fimmu.2013.00232

Thymically derived Foxp3⁺ regulatory T cells (tTregs) constitute a unique T cell lineage that is essential for maintaining immune tolerance to self and immune homeostasis. However, Foxp3 can also be turned on in conventional T cells as a consequence of antigen exposure in the periphery, under both non-inflammatory and inflammatory conditions. These so-called peripheral Tregs (pTregs) participate in the control of immunity at sites of inflammation, especially at the mucosal surfaces. Although numerous studies have assessed in vitro generated Tregs (termed induced or iTregs), these cells most often do not recapitulate the functional or phenotypic characteristics of in vivo generated pTregs. Thus, there are still many unanswered questions regarding the T cell receptor (TCR) repertoire and function of pTregs as well as conditions under which they are generated in vivo, and the degree to which these characteristics identify specialized features of pTregs versus features that are shared with tTregs. In this review, we summarize the current state of our understanding of pTregs and their relationship to the tTreg subset. We describe the recent discovery of unique cell surface markers and transcription factors (including Neuropilin-1 and Helios) that can be used to distinguish tTreg and pTreg subsets in vivo. Additionally, we discuss how the improved ability to distinguish these subsets provided new insights into the biology of tTregs versus pTregs and suggested differences in their function and TCR repertoire, consistent with a unique role of pTregs in certain inflammatory settings. Finally, these recent advances will be used to speculate on the role of individual Treg subsets in both tolerance and autoimmunity.

Keywords: regulatory T cell, immune tolerance, autoimmunity, neuropilin-1, Helios

Citation: Yadav M, Stephan S and Bluestone JA (2013) Peripherally induced Tregs – role in immune homeostasis and autoimmunity. Front. Immunol. 4:232. doi: 10.3389/fimmu.2013.00232

Received: 31 May 2013; Paper pending published: 16 June 2013;
Accepted: 22 July 2013; Published online: 07 August 2013.

Edited by:

Eyad Elkord, United Arab Emirates University, UAE; University of Salford, UK; University of Manchester, UK

Reviewed by:

Paul Anthony Gleeson, University of Melbourne, Australia
Johan Verhagen, University of Bristol, UK

Copyright: © 2013 Yadav, Stephan and Bluestone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jeffrey A. Bluestone, Diabetes Center, University of California San Francisco, Box 0400, 513 Parnassus Avenue, San Francisco, CA 94143-0400, USA e-mail: jeff.bluestone@ucsf.edu

^†Present address: Mahesh Yadav, Genentech, South San Francisco, CA, USA

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Research

Electronic health record-based assessment of oral corticosteroid use in a population of primary care patients with asthma: an observational study

Felicia C Allen-Ramey, Linda M Nelsen, Joseph B Leader, Dione Mercer, Henry Lester Kirchner and James B Jones

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Allergy, Asthma & Clinical Immunology 2013, 9:27 doi:10.1186/1710-1492-9-27

Published: 7 August 2013

Abstract (provisional)

Background

Oral corticosteroid prescriptions are often used in clinical studies as an indicator of asthma exacerbations. However, there is rarely the ability to link a prescription to its associated diagnosis. The objective of this study was to characterize patterns of oral corticosteroid prescription orders for asthma patients using an electronic health record database, which links each prescription order to the diagnosis assigned at the time the order was placed.

Methods

This was a retrospective cohort study of the electronic health records of asthma patients enrolled in the Geisinger Health System from January 1, 2001 to August 23, 2010. Eligible patients were 12--85 years old, had a primary care physician in the Geisinger Health System, and had asthma. Each oral corticosteroid order was classified as being prescribed for an asthma-related or non-asthma-related condition based on the associated diagnosis. Asthma-related oral corticosteroid use was classified as either chronic or acute. In patient-level analyses, we determined the number of asthma patients with asthma-related and non-asthma-related prescription orders and the number of patients with acute versus chronic use. Prescription-level analyses ascertained the percentages of oral corticosteroid prescription orders that were for asthma-related and non-asthma-related conditions.

Results

Among the 21,199 asthma patients identified in the electronic health record database, 15,017 (70.8%) had an oral corticosteroid prescription order. Many patients (N = 6,827; 45.5%) had prescription orders for both asthma-related and non-asthma-related conditions, but some had prescription orders exclusively for asthma-related (N = 3,450; 23.0%) or non-asthma-related conditions (N = 4,740; 31.6%). Among the patients receiving a prescription order, most (87.5%) could be classified as acute users. A total of 60,355 oral corticosteroid prescription orders were placed for the asthma patients in this study---31,397 (52.0%) for non-asthma-related conditions, 24,487 (40.6%) for asthma-related conditions, and 4,471 (7.4%) for both asthma-related and non-asthma-related conditions.

Conclusions

Oral corticosteroid prescriptions for asthma patients are frequently ordered for conditions unrelated to asthma. A prescription for oral corticosteroids may be an unreliable marker of asthma exacerbations in retrospective studies utilizing administrative claims data. Investigators should consider co-morbid conditions for which oral corticosteroid use may also be indicated and/or different criteria for assessing oral corticosteroid use for asthma.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.