June 26, 2013

The Asthma Phenotype in the Obese: Distinct or Otherwise? 

Journal of Allergy
Volume 2013 (2013), Article ID 602908, 8 pages
http://dx.doi.org/10.1155/2013/602908
Review Article

The Asthma Phenotype in the Obese: Distinct or Otherwise?

Sherry Farzan
North Shore-Long Island Jewish Health System, Division of Allergy and Immunology, 865 Northern Bouelvard Suite 101, Great Neck, NY 11021, USA
Received 12 February 2013; Accepted 9 May 2013
Academic Editor: Anurag Agrawal
Copyright © 2013 Sherry Farzan. 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

Asthma is a heterogenous disorder that can be classified into several different phenotypes. Recent cluster analyses have identified an “obese-asthma” phenotype which is characterized by late onset, female predominance and lack of atopy. In addition, obesity among early-onset asthmatics clearly exists and heightens the clinical presentation. Observational studies have demonstrated that asthma among the obese has a clinical presentation that is more severe, harder to control, and is not as responsive to standard controller therapies. While weight loss studies have demonstrated improvement in asthma outcomes, further studies need to be performed. The current knowledge of the existence of two obesity-asthma phenotypes (early- versus late-onset asthma) should encourage investigators to study these entities separately since just as they have distinct presentations, their course, response to therapies, and weight loss strategies may be different as well.
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Tolerance to alternative cyclooxygenase-2 inhibitors in nonsteroidal anti-inflammatory drug hypersensitive patients

Open Access
Research

Tolerance to alternative cyclooxygenase-2 inhibitors in nonsteroidal anti-inflammatory drug hypersensitive patients

Wendy SJ Malskat, André C Knulst, Carla AFM Bruijnzeel-Koomen and Heike Röckmann
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Clinical and Translational Allergy 2013, 3:20 doi:10.1186/2045-7022-3-20
Published: 24 June 2013

Abstract (provisional)

Background

Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in case of COX-2 inhibitor hypersensitivity. We aimed to investigate the tolerance to COX-2 inhibitors in patients with non-selective NSAID hypersensitivity. Furthermore, in COX-2 hypersensitive patients tolerance of a second COX-2 inhibitor was investigated.

Methods

We retrospectively analyzed 91 patients with proven non-selective NSAID hypersensitivity that underwent oral challenges with a COX-2 inhibitor. Patients with intolerance to the first challenged COX-2 inhibitor received a second challenge with a different COX-2 inhibitor.

Results

19 out of 91 (21% ) patients had a positive reaction to the first oral challenge with a COX-2 inhibitor. 14 of them underwent a second challenge with a different COX-2 inhibitor and 12 (86% ) did not react.

Conclusions

A relatively high percentage (21% ) of the non-selective NSAID hypersensitive patients did not tolerate a COX-2 inhibitor and oral challenge is advised prior to prescription of a COX-2 inhibitor. For the majority of patients reacting to a COX-2 inhibitor an alternative can be found.

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

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Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses 

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 521231, 12 pages
http://dx.doi.org/10.1155/2013/521231
Review Article

Peptide-Based Vaccinology: Experimental and Computational Approaches to Target Hypervariable Viruses through the Fine Characterization of Protective Epitopes Recognized by Monoclonal Antibodies and the Identification of T-Cell-Activating Peptides

Matteo Castelli,1 Francesca Cappelletti,1 Roberta Antonia Diotti,1 Giuseppe Sautto,1 Elena Criscuolo,1Matteo Dal Peraro,2 and Nicola Clementi1
1Microbiology and Virology Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy
2Laboratory for Biomolecular Modeling, Institute of Bioingeneering, School of Life Sciences, Ecole Polytechnique Fédérale, 1015 Lausanne, Switzerland
Received 8 May 2013; Accepted 6 June 2013
Academic Editor: Roberto Burioni
Copyright © 2013 Matteo Castelli 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

Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.
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Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis 

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 403121, 9 pages
http://dx.doi.org/10.1155/2013/403121
Review Article

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Francesca Bugli, Margherita Cacaci, Cecilia Martini, Riccardo Torelli,Brunella Posteraro, Maurizio Sanguinetti, and Francesco Paroni Sterbini
Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy
Received 14 May 2013; Accepted 13 June 2013
Academic Editor: Roberto Burioni
Copyright © 2013 Francesca Bugli 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

Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum of Candida species. Furthermore, recent studies have established an important role for Hsp90 in mediating Candidaresistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model.
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June 25, 2013

The Observed Association between Maternal Anxiety and Adolescent Asthma: Children of Twin Design Suggest Familial Effects

Logo of plosone
PLoS One. 2013; 8(6): e66040.
Published online 2013 June 12. doi:  10.1371/journal.pone.0066040
PMCID: PMC3680455

The Observed Association between Maternal Anxiety and Adolescent Asthma: Children of Twin Design Suggest Familial Effects

Ida Havland,1 Cecilia Lundholm,1 Paul Lichtenstein,1 Jenae M. Neiderhiser,2 Jody M. Ganiban,3 Erica L. Spotts,4Hasse Walum,1 David Reiss,5 and Catarina Almqvist1,6,*
Susanne Krauss-Etschmann, Editor
Author information ► Article notes ► Copyright and License information ►

Abstract

Background

Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear.

Objective

To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors).

Method

From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association.

Results

Maternal BAI anxiety (OR 2.02, CI 1.15–3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04–2.91) and psychic anxiety (OR 1.74, CI 1.05–2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding.

Conclusions

We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.

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Acceptable alternatives for forced vital capacity in the spirometric diagnosis of bronchial asthma

Int J Appl Basic Med Res. 2011 Jan-Jun; 1(1): 20–23.
PMCID: PMC3657951

Acceptable alternatives for forced vital capacity in the spirometric diagnosis of bronchial asthma

Mohamed Faisal Lutfi
Author information ► Copyright and License information ►
This article has been corrected. See Int J Appl Basic Med Res. 2012; 2(1): 62.

Abstract

Background:

In patients with advanced obstructive ventilatory disorders, expiration may last for a relatively long time until the end-of-test standards for forced vital capacity (FVC) are satisfied. This may be difficult for both the patient and the technician. The Forced expiratory volume in 3 seconds (FEV3) and Forced expiratory volume in 6 seconds (FEV6) maneuvers are simple, undemanding and easier to perform when compared with FVC; however, their reliability to be used as alternatives for FVC is controversial.

Aim:

To judge whether FEV3 and FEV6 can be used instead of FVC in detecting airway obstruction in asthmatic patients.

Settings and Design:

This study was a cross-sectional case–control laboratory-based study.

Materials and Methods:

The study involved 40 known asthmatic patients and 40 apparently healthy, gender- and age-matched controls. Spirometery was used for assessing pulmonary function according to the American Thoracic Society and European Respiratory Society criteria.

Statistical Analysis:

A significant difference in the means between the groups was performed using Student's t-test. The receiver operating characteristic (ROC) curves were used to compare efficiency of the studied spirometric measurements on asthma diagnosis.

Results:

The mean of FEV3 was not significantly different when compared with the mean of FVC (P = 0.352 for asthmatic patients and P = 0.957 for control group). This was also true when the mean of FEV6 was compared with the mean of FVC (P = 0.805 for asthmatic patients and P = 0.957 for control group). The area under the ROC curves of FEV1/FVC%, FEV1/FEV3% and FEV1/FEV6% were also comparable.

Conclusion:

FEV3 and FEV6 are accurate and reliable alternatives for FVC in assessing airway obstruction of asthmatic patients.
Keywords: Asthma, end-of-test, FVC, FEV3, FEV6, lung function tests

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Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity

Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity



Original Research

(29) Total Article Views


Authors: Wang ZY, Sundy JS, Foss CM, Barnhart HX, Palmer SM, Allgood SD, Trudeau E, Alexander KM, Levesque MC

Published Date June 2013 Volume 2013:6 Pages 81 - 92
DOI: http://dx.doi.org/10.2147/JAA.S42695

Received:12 January 2013
Accepted:08 April 2013
Published:25 June 2013
ZongYao Wang,1 John S Sundy,1 Catherine M Foss,1 Huiman X Barnhart,2 Scott M Palmer,1 Sallie D Allgood,3 Evan Trudeau,1 Katie M Alexander,3 Marc C Levesque3
1Division of Pulmonary, Allergy and Critical Care Medicine, 2Duke Clinical Research Institute,3Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USA

Background: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects.
Methods: A total of 291 participants, 18–40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects.
Results: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans.
Conclusion: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.

Keywords: total serum immunoglobulin E, IgE, skin prick test, SPT, CD14-159T, single nucleotide polymorphism, SNP, lipopolysaccharide, LPS, endotoxin



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Increased Risk of RSV Infection in Children with Down's Syndrome: Clinical Implementation of Prophylaxis in the European Union 

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 801581, 6 pages
http://dx.doi.org/10.1155/2013/801581
Research Article

Increased Risk of RSV Infection in Children with Down's Syndrome: Clinical Implementation of Prophylaxis in the European Union

Dianne van Beek,1 Bosco Paes,2 and Louis Bont1,3
1Department of Immunology, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands
2Department of Pediatrics (Neonatal Division), McMaster University, Hamilton, ON, L8S 4L8, Canada
3Division of Infectious Diseases, Department of Pediatrics, University Medical Centre Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
Received 26 March 2013; Accepted 13 June 2013
Academic Editor: Roberto Burioni
Copyright © 2013 Dianne van Beek 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

Prospective cohort studies show that Down’s syndrome (DS) is an independent risk factor for hospitalization for RSV bronchiolitis. It is unknown whether this observation has been translated into specific management for DS children. The primary goal was to assess the knowledge of healthcare providers in the European Union about RSV infection in DS children and to determine whether it influenced the implementation of prophylaxis. DS caregivers were surveyed using a standardized questionnaire, and country-specific guidelines were obtained. Fifty-three caregivers participated. Thirty-nine (86.7%) had knowledge of the increased risk of severe RSV infection in DS children, and 30 (71.4%) graded that it was important to have a statement on the use of RSV prophylaxis in existing guidelines. Twenty-eight participants had a local DS guideline; hard copies of twelve unique guidelines were obtained. Only one (8.3%) contained a statement on RSV prophylaxis for DS, and five considered such a statement for the next version. Conclusion. Most pediatricians had knowledge that DS children have an increased risk of severe RSV infection. Despite the lack of a specific RSV prophylaxis trial in DS, they felt that a statement on RSV prophylaxis in DS guidelines was important, but this was rarely present in current guidelines.
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