Review

The value of FeNO measurement in childhood asthma: uncertainties and perspectives

Giuliana Ferrante, Velia Malizia, Roberta Antona, Giovanni Corsello and Stefania La Grutta

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Multidisciplinary Respiratory Medicine 2013, 8:50 doi:10.1186/2049-6958-8-50

Published: 31 July 2013

Abstract (provisional)

Asthma is considered an heterogeneous disease, requiring multiple biomarkers for diagnosis and management. Fractional exhaled nitric oxide in exhaled breath (FeNO) was the first useful non-invasive marker of airway inflammation in asthma and still is the most widely used. The non-invasive nature and the relatively easy use of FeNO technique make it an interesting tool to monitor airway inflammation and rationalize corticosteroid therapy in asthmatic patients, together with the traditional clinical tools (history, physical examination and lung function tests), even if some controversies have been published regarding the use of FeNO to support the management of asthma in children. The problem of multiple confounding factors and overlap between healthy and asthmatic populations preclude the routine application of FeNO reference values in clinical practice and suggest that it would be better to consider an individual "best", taking into account the context in which the measurement is obtained and the clinical history of the patient. Besides, there is still disagreement about the role of FeNO as a marker of asthma control, due to the complexity of balance among the different items involved in its determination and the lack of homogeneity in the population groups studied in the few studies conducted so far. Heterogeneity of problematic severe asthma greatly limits utility of FeNO alone as a biomarker of inflammation to optimize the disease management on an individual basis. None of the studies conducted so far demonstrated that the use of FeNO was better than current asthma guidelines in controlling asthma exacerbations. In summary, there is a large variation in FeNO levels between individuals, which may reflect the natural heterogeneity in baseline epithelial nitric oxide synthase activity and/or the contribution of other noneosinophilic factors to epithelial nitric oxide synthase activity. FeNO is a promising biomarker, but at present some limits are highlighted. We would recommend that further research can be carried out by organizing studies aimed to obtain reliable reference values of FeNO and in order to better interpret FeNO measurements in clinical settings, taking also into account the influence of genetic and environmental factors.

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Review Article

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About the role and underlying mechanisms of cofactors in anaphylaxis

Allergy

Early View (Online Version of Record published before inclusion in an issue)

1. F. Wölbing, 
2. J. Fischer, 
3. M. Köberle, 
4. S. Kaesler, 
5. T. Biedermann^*

Article first published online: 2 AUG 2013

DOI: 10.1111/all.12193

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

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Keywords:

• anaphylaxis;
• augmentation factor;
• cofactor;
• infection;
• mast cell

Abstract

Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co- or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as ‘wheat-dependent exercise-induced anaphylaxis’ (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.

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Research

Development of children's hymenoptera venom allergy quality of life scale (CHVAQoLS)

Ewa Cichocka-Jarosz, Piotr Brzyski, Beata Tobiasz-Adamczyk, Grzegorz Lis and Jacek J Pietrzyk

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Clinical and Translational Allergy 2013, 3:25 doi:10.1186/2045-7022-3-25

Published: 1 August 2013

Abstract (provisional)

Background

Venom allergy is a rare but life-threatening disease and may have a considerable impact on the health-related quality of life (HRQoL) of patients, especially children. This paper presents development of the HRQoL scale for children and adolescents with Hymenoptera venom allergy (HVA).

Methods

The study sample consisted of 71 children, born between 1992 and 2000, who presented with a history of insect sting reaction when referred for consultation in the allergy center of Polish-American Children's Hospital, Krakow, Poland, during the period from 2000 to 2010. The initial pool of 60 items - divided into 6 domains - was prepared. The items with intercorrelations higher than 0.7 were removed from each domain and then principal component analysis was conducted for each domain separately, to provide a one-dimensional subscale for each domain. Reliability of the subscales was assessed using Cronbach alpha coefficient in terms of Classical Test Theory and with rho coefficient in terms of Item Response Theory. The multidimensionality of the scale was tested using multi-trait scaling.

Results

Three to four items from each domain were subsequently selected to constitute six subscales. Rho coefficients for all the subscales reached 0.8, similar results were achieved with the Cronbach alpha coefficients. Multi-trait method showed that the majority of the items indicated stronger correlations with their own subscales than with other subscales, which proves that our constructed subscales measure different dimensions of HRQoL.

Conclusions

The presented scale comprises high validity and reliability subscales measuring six dimensions of HRQoL related to Hymenoptera venom allergy in children and adolescents. Such information may be useful in everyday clinical practice.

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MINI REVIEW ARTICLE

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Front. Immunol., 01 August 2013 | doi: 10.3389/fimmu.2013.00226

Dietary inhibitors of histone deacetylases in intestinal immunity and homeostasis

R. Schilderink, C. Verseijden and W. J. de Jonge*

• Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

Intestinal epithelial cells (IECs) are integral players in homeostasis of immunity and host defense in the gut and are under influence of the intestinal microbiome. Microbial metabolites and dietary components, including short chain fatty acids (acetate, propionate, and butyrate, SCFAs), have an impact on the physiology of IECs at multiple levels, including the inhibition of deacetylases affecting chromatin remodeling and global changes in transcriptional activity. The number and diversity of butyrate-producing bacteria is subject to factors related to age, disease, and to diet. At physiological levels, SCFAs are inhibitors of histone deacetylases (HDACs) which may explain the transcriptional effects of SCFAs on epithelial cells, although many effects of SCFAs on colonic mucosa can be ascribed to mechanisms beyond HDAC inhibition. Interference with this type of post-translational modification has great potential in cancer and different inflammatory diseases, because HDAC inhibition has anti-proliferative and anti-inflammatory effects in vitro, and in in vivo models of intestinal inflammation. Hence, the influence of dietary modulators on HDAC activity in epithelia is likely to be an important determinant of its responses to inflammatory and microbial challenges.

Keywords: HDAC, intestinal epithelium, inflammatory bowel diseases, short chain fatty acids, butyrate

Citation: Schilderink R, Verseijden C and de Jonge WJ (2013) Dietary inhibitors of histone deacetylases in intestinal immunity and homeostasis. Front. Immunol. 4:226. doi: 10.3389/fimmu.2013.00226

Received: 12 May 2013; Accepted: 18 July 2013;
Published online: 01 August 2013.

Edited by:

Cecil Czerkinsky, Göteborg University, Sweden

Reviewed by:

Emma Slack, ETH Zürich, Switzerland
J. Rodrigo Mora, Massachusetts General Hospital, USA

Copyright: © 2013 Schilderink, Verseijden and de Jonge. 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: W. J. de Jonge, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 69-71, 1105BK Amsterdam, Netherlands e-mail: w.j.dejonge@amc.uva.nl

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International Journal of Chronic Obstructive Pulmonary Disease

Should chest examination be reinstated in the early diagnosis of chronic obstructive pulmonary disease?

Original Research

(36) Total Article Views

Authors: Oshaug K, Halvorsen PA, Melbye H

Published Date July 2013 Volume 2013:8 Pages 369 - 377

DOI: http://dx.doi.org/10.2147/COPD.S47992

Received:	11 May 2013
Accepted:	18 June 2013
Published:	31 July 2013

Katja Oshaug, Peder A Halvorsen, Hasse Melbye

General Practice Research Unit, University of Tromsø, Tromsø, Norway

Background: Although proven to be associated with bronchial obstruction, chest signs are not listed among cues that should prompt spirometry in the early diagnosis of chronic obstructive pulmonary disease (COPD) in established guidelines.
Aims: We aimed to explore how chest findings add to respiratory symptoms and a history of smoking in the diagnosis of COPD.
Methods: In a cross-sectional study, patients aged 40 years or older, previously diagnosed with either asthma or COPD in primary care, answered questionnaires and underwent physical chest examination and spirometry.
Results: Among the 375 patients included, 39.7% had forced expiratory volume in 1 second/forced vital capacity -0.7. Hyperresonance to percussion was the strongest predictor of COPD, with a sensitivity of 20.8, a specificity of 97.8, and likelihood ratio of 9.5. In multivariate logistic regression, where pack-years, shortness of breath, and chest findings were among the explanatory variables, three physical chest findings were independent predictors of COPD. Hyperresonance to percussion yielded the highest odds ratio (OR = 6.7), followed by diminished breath sounds (OR = 5.0), and thirdly wheezes (OR = 2.3). These three chest signs also gave significant diagnostic information when added to shortness of breath and pack-years in receiver operating-characteristic curve analysis.
Conclusion: We found that chest signs may add to respiratory symptoms and a history of smoking in the diagnosis of COPD, and we conclude that chest signs should be reinstated as cues to early diagnosis of COPD in patients 40 years or older.

Keywords: diagnosis, COPD, physical chest examination, spirometry



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