June 21, 2013

Diagnostic approach in cases with suspected work-related asthma

Review

Diagnostic approach in cases with suspected work-related asthma

Tor B Aasen, P Sherwood Burge, Paul K Henneberger, Vivi Schlünssen and Xaver Baur

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Journal of Occupational Medicine and Toxicology 2013, 8:17 doi:10.1186/1745-6673-8-17

Published: 14 June 2013

Abstract (provisional)

Background

Work-related asthma (WRA) is a major cause of respiratory disease in modern societies. The diagnosis and consequently an opportunity for prevention are often missed in practice.

Methods

Based on recent studies and systematic reviews of the literature methods for detection of WRA and identification of specific causes of allergic WRA are discussed.

Results and conclusions

All workers should be asked whether symptoms improve on days away from work or on holidays. Positive answers should lead to further investigation. Spirometry and non-specific bronchial responsiveness should be measured, but carefully performed and validly analysed serial peak expiratory flow or forced expiratory volume in one second (FEV1) measurements are more specific and confirm occupational asthma in about 82% of those still exposed to the causative agent. Skin prick testing or specific immunoglobulin E assays are useful to document allergy to high molecular weight allergens. Specific inhalational challenge tests come closest to a gold standard test, but lack standardisation, availability and sensitivity. Supervised workplace challenges can be used when specific challenges are unavailable or the results non-diagnostic, but methodology lacks standardisation. Finally, if the diagnosis remains unclear a follow-up with serial measurements of FEV1 and non-specific bronchial hyperresponsiveness should detect those likely to develop permanent impairment from their occupational exposures.

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

Ca2+-dependent structural changes in the B-cell receptor CD23 increase its affinity for human Immunoglobulin E

Ca²⁺-dependent structural changes in the B-cell receptor CD23 increase its affinity for human Immunoglobulin E

+Author Affiliations

¹ King's College London, United Kingdom;
² University of Oxford, United Kingdom

↵* Corresponding author; email: brian.sutton@kcl.ac.uk

Capsule

Background: Immunoglobulin E (IgE) plays a central role in allergic disease. The B-cell receptor CD23 is pivotal in regulating IgE synthesis.

Results: Ca2+-dependent structural changes in CD23 enable additional interactions with IgE.

Conclusion: Mechanism for Ca2+-induced increase in affinity revealed.

Significance: Ca2+ binding brings an extra degree of modulation to CD23 function.

Abstract

Immunoglobulin E (IgE) antibodies play a fundamental role in allergic disease and are a target for therapeutic intervention. IgE functions principally through two receptors, FcεRI and CD23 (FcεRII). Minute amounts of allergen trigger mast cell or basophil degranulation by cross-linking IgE-bound FcεRI, leading to an inflammatory response. The interaction between IgE and CD23 on B-cells regulates IgE synthesis. CD23 is unique amongst Ig receptors in that it belongs to the C-type (calcium- dependent) lectin-like superfamily. While the interaction of CD23 with IgE is carbohydrate-independent, calcium has been reported to increase the affinity for IgE, but the structural basis for this activity has hitherto been unknown. We have determined the crystal structures of the human lectin-like head domain of CD23 in its Ca2+-free and Ca2+-bound forms, as well as the crystal structure of the Ca2+-bound head domain of CD23 in complex with a sub-fragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). Together with site-directed mutagenesis, the crystal structures of four Ca2+ ligand mutants, ITC, SPR and stopped-flow analysis, we demonstrate that Ca2+ binds at the principal, evolutionarily conserved binding site in CD23. Ca2+ binding drives Pro250, at the base of an IgE-binding loop (loop 4), from the trans to the cis configuration with a concomitant conformational change and ordering of residues in the loop. These Ca2+-induced structural changes in CD23 lead to additional interactions with IgE, a more entropically favorable interaction, and a thirty-fold increase in affinity of a single head domain of CD23 for IgE. Taken together, these results suggest that binding of Ca2+ brings an extra degree of modulation to CD23 function.

This Article

First Published on June 17, 2013, doi:10.1074/jbc.M113.480657jbc.M113.480657.

Extrafine inhaled corticosteroid therapy in the control of asthma

Review

(833) Total Article Views

Authors: Ivancsó I, Böcskei R, Müller V, Tamási L

Published Date June 2013 Volume 2013:6 Pages 69 - 80
DOI: http://dx.doi.org/10.2147/JAA.S25415

Received:	07 December 2012
Accepted:	30 April 2013
Published:	06 June 2013

István Ivancsó, Renáta Böcskei, Veronika Müller, Lilla Tamási

Department of Pulmonology, Semmelweis University, Budapest, Hungary

Abstract: Small airways disease plays an important role in the pathogenesis of asthma, but assessment of small airways impairment is not easy in everyday clinical practice. The small airways can be examined by several invasive and noninvasive methods, most of which can at present be used only in the experimental setting. Inhalers providing extrafine inhaled corticosteroid particle sizes may achieve sufficient deposition in the peripheral airways. Many studies have reported the beneficial effects of extrafine inhaled corticosteroids on inflammation, ie, on dysfunction in both the central and distal airways in asthmatics, and there are some data on asthma phenotypes in which the small airways seem to be affected more than in other phenotypes, including nocturnal asthma, severe steroid-dependent or difficult-to-treat asthma, asthma complicated by smoking, elderly asthmatic patients and/or patients with fixed airflow obstruction, and asthmatic children. The relevant randomized controlled clinical trials indicate that the efficacy of extrafine and nonextrafine inhaled corticosteroid formulations is similar in terms of primary endpoints, but there are certain clinically important endpoints for which the extrafine formulations show additional benefits.

Keywords: small airways, inflammation, dysfunction, noninvasive evaluation methods, peripheral deposition

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Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 125643, 11 pages
http://dx.doi.org/10.1155/2013/125643

Research Article

Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

Der-Yuan Chen,^1,2,3 Pei-Shan Song,¹ Jau-Shyong Hong,⁴ Ching-Liang Chu,⁵ I-Horng Pan,⁶ Yi-Ming Chen,^3,7 Ching-Hsiung Lin,^8,9,10 Sheng-Hao Lin,^1,8 and Chi-Chen Lin^1,11

¹Institute of Biomedical Science, National Chung-Hsing University, Taichung 402, Taiwan
²Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan
³Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 407, Taiwan
⁴Laboratory of Toxicology and Pharmacology, National Institutes of Environmental, Health Sciences, Research Triangle Park, NC 27709, USA
⁵Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
⁶Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 300, Taiwan
⁷Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
⁸Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
⁹Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan
¹⁰School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
¹¹Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung 407, Taiwan

Received 1 February 2013; Accepted 25 March 2013

Academic Editor: Beatrice Gaugler

Copyright © 2013 Der-Yuan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

June 19, 2013

Respiratory-Related Hospitalizations following Prophylaxis in the Canadian Registry for Palivizumab (2005–2012) Compared to Other International Registries

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 917068, 15 pages
http://dx.doi.org/10.1155/2013/917068

Research Article

Respiratory-Related Hospitalizations following Prophylaxis in the Canadian Registry for Palivizumab (2005–2012) Compared to Other International Registries

Bosco Paes,^1,2 Ian Mitchell,³ Abby Li,⁴ Tetsuhiro Harimoto,⁴ and Krista L. Lanctôt⁴

¹Department of Pediatrics, McMaster University, Hamilton, ON, L8S 4K1, Canada
²McMaster Children’s Hospital, 1280 Main Street West, Room HSC-3A, Hamilton, ON, L8S 4K1, Canada
³Department of Pediatrics, University of Calgary, Calgary, AB, T3B 6A8, Canada
⁴Medical Outcomes and Research in Economics (MORE) Research Group, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada

Received 25 February 2013; Accepted 17 April 2013

Academic Editor: Roberto Burioni

Copyright © 2013 Bosco Paes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Respiratory syncytial virus (RSV) infection occurs commonly in infants aged ≤2 years, and severe infection results in hospitalization with accompanying morbidity and mortality. Palivizumab has been available for prophylaxis for the past 15 years. Prospective data on patients who received palivizumab from 2005 to 2012 has been assembled in the Canadian registry (CARESS) to document utilization, compliance, and health outcomes in both hospital and community settings. Long-term data is necessary to evaluate the impact of palivizumab on the incidence of RSV infections, minimize healthcare resources, and identify which infant subpopulations are receiving prophylaxis. A database search was also conducted for similar information from published registries, and hospitalization rates were compared to results from randomized clinical trials (RCTs).Overall hospitalization rates (percent; range) for respiratory-related illnesses and RSV-specific infection in infants who meet standard indications for prophylaxis were 6.6 (3.3–7.7) and 1.55 (0.3–2.06), respectively, in CARESS, which closely aligns with registry data from 4 other countries, despite the former comprising the largest cohort of complex patients internationally. Overall RSV-related hospitalization rates were lower across registries compared to equivalent patients in RCTs. Registry data provides valuable information regarding real-world experience with palivizumab, while facilitating the genesis of new research themes.

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea

Research

Nocturnal CPAP improves walking capacity in COPD patients with obstructive sleep apnoea

Tsai-Yu Wang, Yu-Lun Lo, Kang-Yun Lee, Wen-Te Liu, Shu-Min Lin, Ting-Yu Lin, Yung-Lun Ni, Chao-Yung Wang, Shu-Chuan Ho and Han-Pin Kuo

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Respiratory Research 2013, 14:66 doi:10.1186/1465-9921-14-66

Published: 19 June 2013