2764 articles - 10.09.10
1: Arerugi. 2010 Aug;59(8):965-73.
[Article in Japanese]
Kanemitsu Y, Kita H, Fuseya Y, Tanimura K, Katayama Y, Nisihara Y.
Department of Respiratory Medicine, Takatsuki Red Cross Hospital.
Background: Therapeutic effect of omalizumab was studied in Japanese patients with severe asthma. Methods: Omalizumab was administered to 10 patients with bronchial asthma diagnosed as severe or very severe persistent asthma according to Asthma Prevention Management Guideline 2009, Japan (JGL 2009). Therapeutic efficacy was assessed 16 weeks after starting the treatment using Asthma Control Test (ACT), pulmonary function tests, and the peripheral eosinophil counts. In addition, number of acute exacerbation in 16-week period after starting the treatment was compared with that in 16-week period before the treatment and the previous year respectively. The questionnaire whether or not to continue omalizumab was conducted 16 weeks after starting the treatment. Results: The total ACT score rose from 14.8 to 19.1 and peripheral eosinophil count decreased from 355.2 /mul to 209.8 /mul after starting the treatment. Peak expiratory flow and forced expiratory volume in one second also increased, though differences were insignificant. Number of acute exacerbation decreased from 3.0 times before the treatment and 2.4 times the same time last year to 1.3 times after starting the treatment. The result of the questionnaire revealed that patients wanted to discontinue because of financial burden, ambulant burden, and side effect, but no one responded to be ineffective. In fact, only the one discontinued omalizumab. Conclusion: Omalizumab produced improvement in subject symptoms and reduced acute exacerbation in patients with severe or very severe persistent asthma. The future challenge is to reduce financial and ambulant burden on patients.
Publication Types: English Abstract
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PMID: 20820138 [PubMed - in process]2: J Allergy Clin Immunol. 2010 Sep;126(3):466-76.
Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schunemann HJ.
Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada.
BACKGROUND: Allergic rhinitis represents a global health problem affecting 10% to 20% of the population. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines have been widely used to treat the approximately 500 million affected patients globally. OBJECTIVE: To develop explicit, unambiguous, and transparent clinical recommendations systematically for treatment of allergic rhinitis on the basis of current best evidence. METHODS: The authors updated ARIA clinical recommendations in collaboration with Global Allergy and Asthma European Network following the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: This article presents recommendations about the prevention of allergic diseases, the use of oral and topical medications, allergen specific immunotherapy, and complementary treatments in patients with allergic rhinitis as well as patients with both allergic rhinitis and asthma. The guideline panel developed evidence profiles for each recommendation and considered health benefits and harms, burden, patient preferences, and resource use, when appropriate, to formulate recommendations for patients, clinicians, and other health care professionals. CONCLUSION: These are the most recent and currently the most systematically and transparently developed recommendations about the treatment of allergic rhinitis in adults and children. Patients, clinicians, and policy makers are encouraged to use these recommendations in their daily practice and to support their decisions. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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PMID: 20816182 [PubMed - in process]3: Allergy. 2010 Aug 17; [Epub ahead of print]
Singh AK, Stock P, Akbari O.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
To cite this article: Singh AK, Stock P, Akbari O. Role of PD-L1 and PD-L2 in allergic diseases and asthma. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02458.x. Abstract Asthma is the result of chronic airway inflammation associated predominantly with CD4+ cells, eosinophils, mast cells, and basophils. Several T-cells subsets, including NKT cells, play a critical role in orchestrating the inflammation in the airways predominantly, by secreting interleukin-4 and interleukin-13. Recently, programmed death-1 (PD-1) with its ligands, programmed death ligand B7H1 (PD-L1) and B7DC (PD-L2), was shown to regulate T-cell activation and tolerance. PD-1 has been characterized as a negative regulator of conventional CD4+T cells. In addition, the relative roles of PD-L1 and PD-L2 in regulating the activation and function of T cells have recently been characterized. Recent studies have demonstrated that PD-L1 and PD-L2 have important but opposing roles in modulating and polarizing T-cell functions in airway hyperreactivity. Whereas the severity of asthma is greatly enhanced in absence of PD-L2, PD-L1 deficiency resulted in reduced airway hyperresponsiveness and only minimal inflammation. This observation is partially because of the polarization of NKT cells in PD-L1- and PD-L2-deficient mice. This review will discuss the recent literature regarding the role of PD-L1 and PD-L2 in allergic disease and asthma. Current understanding of the role of PD ligands in allergic asthma gives impetus to the development of novel therapeutic approaches.
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PMID: 20722638 [PubMed - as supplied by publisher]4: Allergy. 2010 Aug 17; [Epub ahead of print]
Schmitt J, Buske-Kirschbaum A, Roessner V.
Department of Dermatology, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr, Dresden, Germany.
To cite this article: Schmitt J, Buske-Kirschbaum A, Roessner V. Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02449.x. Abstract The increase in prevalence and burden of atopic diseases, i.e. eczema, rhinitis, and asthma over the past decades was paralleled by a worldwide increase in attention-deficit/hyperactivity disorder (ADHD) diagnoses. We systematically reviewed epidemiologic studies investigating the relationship between atopic diseases and ADHD. Electronic literature search in PubMed and PsycINFO (until 02/2010) supplemented by handsearch yielded 20 relevant studies totaling 170 175 individuals. Relevant data were abstracted independently by two reviewers. Six studies consistently reported a positive association between eczema and ADHD with one study suggesting effect modification by sleeping problems. Twelve studies consistently found a positive association between asthma and ADHD, which, however, appeared to be at least partly explained (confounded) by concurrent or previous eczema. Rhinitis and serum-IgE level were not related to ADHD symptomatology. We conclude that not atopic disease in general, but rather that eczema appears to be independently related to ADHD. Conclusions about temporality and whether the observed association constitutes a causal relationship are impossible, as most studies were cross-sectional (n = 14; 70%) or case-control studies without incident exposure measurement (n = 5; 25%). Another methodological concern is that the criteria to define atopic disease and ADHD were inadequate in most studies. A failure to adjust for confounders in the majority of studies was an additional limitation so that meta-analysis was not indicated. Future interdisciplinary high-quality prospective research is needed to better understand the mechanisms underlying the relationship between eczema and ADHD and to eventually establish targeted preventive and treatment strategies.
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PMID: 20716320 [PubMed - as supplied by publisher]5: J Allergy Clin Immunol. 2010 Sep;126(3):558-66. Epub 2010 Aug 1.
Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di Lorenzo G.
Dipartimento di Biopatologia e Metodologie Biomediche, Universita degli Studi di Palermo, Palermo, Italy; Unita Operativa di Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliera Universitaria Policlinico di Palermo, Palermo, Italy.
BACKGROUND: The benefit of sublingual immunotherapy (SLIT) with grass allergens for seasonal allergic rhinitis has been extensively studied, but data on efficacy are still equivocal. OBJECTIVE: To assess the effectiveness of SLIT with grass allergens in the reduction of symptoms and medication in patients with seasonal allergic rhinitis to grass pollen. METHODS: Computerized bibliographic searches of MEDLINE (1995-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials (RCTs) comparing SLIT to placebo and if they included patients with history of allergy to grass pollen treated with natural grass pollen extracts. Nineteen RCTs with 2971 patients were analyzed. The outcomes assessed were symptom and medication scores. RESULTS: Using a random-effects model, SLIT with grass allergens significantly reduces both symptoms (standardized mean difference, -0.32; 95% CI, -0.44 to -0.21) and medication use (standardized mean difference, -0.33; 95% CI, -0.50 to -0.16) compared with placebo. The treatment is more efficacious in adults than in children. Prolonging duration of preseasonal treatment for more than 12 weeks improves the treatment efficacy. CONCLUSION: This meta-analysis found that SLIT with grass allergens is effective in patients with seasonal allergic rhinitis compared with placebo. The benefit is clinically modest, and criteria are needed to identify patients most likely to benefit from SLIT. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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PMID: 20674964 [PubMed - in process]6: Clin Exp Allergy. 2010 Aug;40(8):1116-29.
Clark AT, Skypala I, Leech SC, Ewan PW, Dugue P, Brathwaite N, Huber PA, Nasser SM.
Allergy Department, Cambridge University NHS Foundation Trust, Cambridge, UK.
This guideline advises on the management of patients with egg allergy. Most commonly, egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history and the detection of egg white-specific IgE (by skin prick test or serum assay) will confirm the diagnosis in most cases. Egg avoidance advice is the cornerstone of management. Egg allergy often resolves and re-introduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive measles, mumps and rubella (MMR) vaccination. Influenza and yellow fever vaccines should only be considered in egg-allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence-based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co-morbid associations.
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PMID: 20649608 [PubMed - in process]7: Allergy. 2010 Jul 19; [Epub ahead of print]
Pfaar O, Robinson DS, Sager A, Emuzyte R.
Center for Rhinology and Allergology Wiesbaden, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Germany.
To cite this article: Pfaar O, Robinson DS, Sager A, Emuzyte R. Immunotherapy with depigmented-polymerized mixed tree pollen extract: a clinical trial and responder analysis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02413.x. Abstract Background: Rhinoconjunctivitis because of tree pollen sensitization is common in Northern Europe. Specific subcutaneous immunotherapy (SCIT) is the only disease-modifying treatment, but unmodified allergen extracts carry a risk of allergic side-effects. Our objective was to examine efficacy and safety of a depigmented-polymerized mixed tree pollen extract. Methods: A double-blind, placebo-controlled trial of 184 tree pollen allergic adults was performed. SCIT consisted of four increasing doses at 7-day intervals, then maintenance injections every 6 weeks for 18 months. Primary outcome was combined symptom and medication score during the 2008 season. Secondary outcomes included analysis at different levels of pollen exposure and a responder analysis. Adverse events were classified using the EAACI scale. Birch pollen-specific IgE and IgG(4) were measured before and after treatment. Results: The combined symptom and medication score of actively treated patients was significantly lower than those on placebo (P < 0.04). Increased efficacy was seen at high pollen exposure (median score 2.1 for active [IQR 0.7-3.4] vs 4.2 [IQR 2.4-5.3] for placebo for days with 500 or more pollen grains per m(3), a 50% reduction, P < 0.01). A modified responder analysis revealed 64% responders in the active and 32% in the placebo group (P < 0.01). There were 17 systemic reactions. All were mild (grade 1 or 2) and required no treatment. Serum birch-specific IgG(4) increased in the SCIT group (P < 0.01). Conclusions: SCIT with depigmented- polymerized tree pollen extract was clinically effective and well tolerated. Responder analysis suggested that one-third of patients treated with immunotherapy may not respond.
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PMID: 20645937 [PubMed - as supplied by publisher]8: J Allergy Clin Immunol. 2010 Aug;126(2):267-73, 273.e1. Epub 2010 Jul 10.
Liu AH, Zeiger RS, Sorkness CA, Ostrom NK, Chipps BE, Rosa K, Watson ME, Kaplan MS, Meurer JR, Mahr TA, Blaiss MS, Piault-Louis E, McDonald J.
National Jewish Health and University of Colorado School of Medicine, Pediatrics/Allergy & Immunology, Denver, CO 80206-2762, USA. LiuA@NJHealth.org
BACKGROUND: The Childhood Asthma Control Test (C-ACT) has demonstrated validity in classifying children aged 4 to 11 years as having either "well-controlled" or "not well-controlled" asthma. However, new asthma management guidelines distinguish 3 levels of asthma control. OBJECTIVE: We sought to determine a second cut point on the C-ACT to identify children with "very poorly controlled" asthma. METHODS: Binomial logistic regression was performed on data from 671 children. The specialist's rating of control was the criterion measure. Specialists' severity ratings, specialists' assessment of therapy, and FEV(1) percent predicted were used to assess the clinical validity of the cut point. RESULTS: A cut point of 12 was selected because it correctly classified the highest percentage of participants (66.3%) as having "very poorly controlled" (vs "not well controlled") asthma and demonstrated high specificity (89.8%) and moderate positive predictive value (69.1%). Children scoring 12 or less versus 13 to 19 had lower mean FEV(1) percent predicted (79.8% vs 92.6%, P = .0002) and were more frequently stepped up in therapy (72.9% vs 53.6%, P = .0131) and rated as having severe asthma (13.6% vs 4.5%, P = .0005). One month later, significant differences in C-ACT scores and lung function between these 2 groups persisted. The mean C-ACT score of participants classified as "very poorly controlled" was significantly lower than that of participants classified as "not well-controlled" (17.2 vs 20.3, respectively; P = .0001). CONCLUSION: A second cut point of 12 or less on the C-ACT identifies children with the lowest level of control, who are at risk for poorer outcomes, and is conceptually consistent with the classification of "very poorly controlled" asthma adopted by asthma management guidelines. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial Multicenter Study Research Support, Non-U.S. Gov't
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PMID: 20624640 [PubMed - indexed for MEDLINE]9: J Allergy Clin Immunol. 2010 Aug;126(2):256-62. Epub 2010 Jul 10.
Simoes EA, Carbonell-Estrany X, Rieger CH, Mitchell I, Fredrick L, Groothuis JR; Palivizumab Long-Term Respiratory Outcomes Study Group.
Department of Pediatric Infectious Diseases, University of Colorado School of Medicine, and The Children's Hospital, Aurora, Colo, USA. eric.simoes@ucdenver.edu
BACKGROUND: Although respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) in early life are followed by later airway hyperreactivity, it is unclear whether there is a causal relationship between this and an atopic diathesis. OBJECTIVES: To separate the effects of RSV LRTI and an atopic diathesis on subsequent recurrent wheezing, we examined the protective effect of previous palivizumab administration against subsequent recurrent wheeze in infants with and without a family history of atopy. METHODS: A prospective multicenter, matched, double cohort study was conducted in 27 centers in Europe and Canada. The rates of physician-diagnosed recurrent wheezing in premature infants <36 weeks gestation who had received palivizumab in the first year of life were compared to those of gestational age-matched controls. RESULTS: The relative protective effect of palivizumab on physician-diagnosed recurrent wheezing through the ages of 2 to 5 years was 68% in those with no family history of asthma (odds ratio, 0.32; (95% CI, 0.14-0.75; N = 146 palivizumab-treated, 171 untreated) and 80% in those with no family history of atopy or food allergies (odds ratio, 0.20; 95% CI, 0.07-0.59; N = 101 palivizumab-treated, 100 untreated). In contrast, there was no effect of palivizumab on subsequent recurrent wheezing in the 90 children with a family history of atopy or food allergies compared to 130 untreated infants with atopic families. CONCLUSION: Respiratory syncytial virus prophylaxis in nonatopic children decreases by 80% the relative risk of recurrent wheezing but does not have any effect in infants with an atopic family history. This suggests that RSV predisposes to recurrent wheezing in an atopy-independent mechanism. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial Comparative Study Multicenter Study Research Support, Non-U.S. Gov't
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PMID: 20624638 [PubMed - indexed for MEDLINE]10: Allergy. 2010 Jul 1; [Epub ahead of print]
Godicke V, Hundt F.
Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
To cite this article: Godicke V, Hundt F. Registration trials for specific immunotherapy in Europe: advanced guidance from the new European Medical Agency guideline. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02436.x. Abstract Marketing authorization of medicinal products is granted based on results of registration trials. The European Medical Agency (EMA) has issued general and disease state-specific guidelines for the conduct of such trials. In the area of allergic diseases, there are basically two general therapeutic approaches: Drugs that mitigate the symptoms and an approach that is targeted to the root cause of the disease, the allergen-specific immunotherapy (SIT). While the 'Guideline on the Clinical Development of Medicinal Products for the Treatment of Allergic Rhino-Conjunctivitis' (CHMP/EWP/2455/02) and the 'Note for Guidance on the Clinical Investigation of Medicinal Products in the Treatment of Asthma' (CPMP/EWP/2922/01) focuses exclusively on the development of medicinal products to treat allergic symptoms, there was no guideline for SIT in the past. In consequence, the conduct of clinical trials for SIT was widely lacking a standardized approach. This created difficulties when comparing drugs and outcomes and also uncertainty to predict marketing authorization. In 2009, the EMA has issued a new guideline on the clinical development of products for SIT. Despite some white spots in some areas, the new guideline constitutes a breakthrough with regard to guidance, harmonization and transparency in the conduct of clinical trials in SIT.
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PMID: 20608914 [PubMed - as supplied by publisher]11: J Allergy Clin Immunol. 2010 Aug;126(2):250-5, 255.e1-4. Epub 2010 Jun 26.
Lange NE, Rifas-Shiman SL, Camargo CA Jr, Gold DR, Gillman MW, Litonjua AA.
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. nlange@partners.org
BACKGROUND: The rise in asthma prevalence over the last few decades may be a result of changes in prenatal or early-life environment, including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern. OBJECTIVE: To determine whether overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children. METHODS: A total of 1376 mother-infant pairs from Project Viva, a longitudinal prebirth cohort, who had responses for food frequency questionnaires in the first and second trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined by using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets. RESULTS: None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or the multivariable model (multivariable model, odds ratio per 1-point increase in Mediterranean diet, 0.98 [95% CI, 0.89-1.08]; AHEI-P, 1.07 [0.87-1.30]; Prudent, 1.02 [0.83-1.26]; Western, 0.98 [0.81-1.19]). CONCLUSION: Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants of offspring wheeze-associated illness than is dietary pattern. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial Comparative Study Research Support, N.I.H., Extramural
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PMID: 20584543 [PubMed - indexed for MEDLINE]12: Allergy. 2010 Jun 24; [Epub ahead of print]
Choo KJ, Simons E, Sheikh A.
Allergy & Respiratory Research Group, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK.
To cite this article: Choo KJL, Simons E, Sheikh A. Glucocorticoids for the treatment of anaphylaxis: Cochrane systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02424.x. Abstract Background: Anaphylaxis is a serious hypersensitivity reaction that is rapid in onset and may result in death. A number of guidelines recommend glucocorticoids for the treatment of people experiencing anaphylaxis. Objectives: We sought to assess the benefits and harms of glucocorticoid treatment during episodes of anaphylaxis. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 3), MEDLINE (Ovid) (1966 to September 2009), EMBASE (Ovid) (1988 to September 2009), CINAHL (EBSCOhost) (to September 2009) and The Science Citation Index Expanded (SCI-EXPANDED) (1945 to September 2009). We also searched the UK National Research Register and websites listing ongoing trials and contacted international experts in anaphylaxis in an attempt to locate unpublished material. We sought to include randomized and quasi-randomized controlled trials comparing glucocorticoids with any control (either placebo, adrenaline (epinephrine), an antihistamine, or any combination of these). Two authors independently assessed articles for inclusion. Results: None of the 2496 reports identified satisfied the inclusion criteria. Conclusions: We conclude that there is no evidence from high-quality studies for the use of steroids in the emergency management of anaphylaxis. Therefore, we can neither support nor refute the use of these drugs for this purpose.
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PMID: 20584003 [PubMed - as supplied by publisher]13: J Allergy Clin Immunol. 2010 Aug;126(2):317-23. Epub 2010 Jun 25.
Gagnon R, Primeau MN, Des Roches A, Lemire C, Kagan R, Carr S, Ouakki M, Benoit M, De Serres G; PHAC-CIHR Influenza Research Network.
Centre hospitalier universitaire de Quebec, Laval University, Quebec City, Quebec, Canada.
BACKGROUND: Because influenza vaccine contains some residual egg protein, there is a theoretic risk of anaphylaxis when vaccinating patients with egg allergy. The objective of this study was to estimate the risk of anaphylaxis in children with egg allergy administered an adjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccine (Arepanrix; GlaxoSmithKline, Mississauga, Ontario, Canada). METHODS: Patients with confirmed egg allergy with a history of respiratory or cardiovascular reactions after egg ingestion were vaccinated in 2 divided doses (10% and 90%) administered at a 30-minute interval, whereas children with other types of egg-induced allergic reactions were vaccinated with a single dose. All patients remained under observation for 60 minutes after vaccination. A 24-hour follow-up telephone call was made to detect any delayed reaction. The main outcome was the occurrence of an anaphylactic reaction according to criteria specified by the Brighton Collaboration. RESULTS: Among the 830 patients with confirmed egg allergy, only 9% required the vaccine to be administered in divided doses. No patient had an anaphylactic reaction. Nine patients had minor allergic symptoms treated with an antihistamine (1 in the 60 minutes after vaccination and 8 in the following 23 hours), and 3 others received salbutamol (1 in the first 60 minutes after vaccination). Further vaccination of more than 3600 other children with reported egg allergy caused no anaphylaxis based on the criteria of the Brighton Collaboration, although 2 patients received epinephrine for symptoms compatible with allergy. CONCLUSION: Although anaphylaxis after influenza immunization is a theoretic risk, vaccination of patients with egg allergy with an adjuvanted monovalent pH1N1 influenza vaccine resulted in no cases of anaphylaxis and on that basis appears safe. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial Multicenter Study Research Support, Non-U.S. Gov't
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PMID: 20579720 [PubMed - indexed for MEDLINE]14: J Allergy Clin Immunol. 2010 Aug;126(2):274-9, 279.e1-5. Epub 2010 Jun 25.
Wegienka G, Johnson CC, Havstad S, Ownby DR, Zoratti EM.
Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, Mich, USA.
BACKGROUND: Early-life exposure to household pets has been shown to be protective against allergic sensitization in childhood. OBJECTIVE: We sought to evaluate the association between early-life pet exposure and allergic sensitization at age 18 years. METHODS: Teenagers who had been enrolled in the Detroit Childhood Allergy Study birth cohort in 1987-1989 were contacted at age 18 years. Serum total and allergen-specific IgE levels to 7 common allergens (dust mite, cat, dog, ragweed, Timothy grass, Alternaria species, and peanut; atopy was defined as any specific IgE level > or =0.35 kU/L) were measured at age 18 years. Annual interview data from childhood were used to determine indoor dog and cat (> or =50% of their time in the home) exposure during early life. Exposure was considered in various ways: first year, cumulative lifetime, and age groups, as well as multiple pets. RESULTS: Dog or cat exposure in the first year of life was not associated with atopy (relative risk, 0.97; 95% CI, 0.83-1.12). Those living with pets in the first year and atopic at 18 years had lower total IgE levels. Neither cumulative exposure nor exposure at a particular age was strongly and consistently associated with either outcome. Although not statistically significant, there was a pattern of decreased odds of sensitization among those with 2 or more pets versus no pets in the first year of life. CONCLUSIONS: Early-life pet exposure can be associated with lower total IgE levels among atopic subjects but is not strongly associated with decreased likelihood of sensitization to common allergens at age 18 years. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
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PMID: 20579718 [PubMed - indexed for MEDLINE]15: Arerugi. 2010 Jun;59(6):706-15.
[Article in Japanese]
Kobayashi S, Hayashi K, Koyama S, Tsubaki H, Itano T, Momomura M, Koyama T, Yanagawa Y.
Department of Pediatrics, School of Medicine, Teikyo University. shige@med.teikyo-u.ac.jp
BACKGROUND: Good sleep is essential for the growth and the development of children. However, sleep is often impaired in patients with atopic dermatitis (AD). It is important to assess the sleep quality in pediatric AD patients. For that purpose, we utilized actigraphy as an objective method for the assessment of sleep quality. METHODS: Childhood patients with AD (16 cases) and 8 non-allergic volunteers were recruited. Actiwatch (AW-64) was attached to each subject's wrist for 11 days at maximum. Sleep parameters were calculated with Actiware and compared among various patient groups. RESULTS: Results demonstrate that sleep was significantly compromised in patients with AD, according to the severity. Subjective scoring of the sleep quality by parents showed limited correlation with actigraphy. CONCLUSION: Actigraphy is an objective and unobtrusive method to measure the sleep quality in childhood AD patients and can provide useful outcome in clinical trial.
Publication Types: English Abstract
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PMID: 20574147 [PubMed - indexed for MEDLINE]16: J Allergy Clin Immunol. 2010 Jul;126(1):52-8.e5. Epub 2010 Jun 9.
Brehm JM, Schuemann B, Fuhlbrigge AL, Hollis BW, Strunk RC, Zeiger RS, Weiss ST, Litonjua AA; Childhood Asthma Management Program Research Group.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Mass, USA.
BACKGROUND: Asthma exacerbations, most often caused by respiratory tract infections, are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs. Vitamin D status might play a role in preventing asthma exacerbations. OBJECTIVES: We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations. METHODS: We measured 25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children randomized to receive budesonide, nedocromil, or placebo (as-needed beta-agonists): the Childhood Asthma Management Program. Using multivariable modeling, we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial. RESULTS: Thirty-five percent of all subjects were vitamin D insufficient, as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects. After adjusting for age, sex, body mass index, income, and treatment group, insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit (odds ratio, 1.5; 95% CI, 1.1-1.9; P = .01). CONCLUSION: Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20538327&dopt=ExternalLink
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PMID: 20538327 [PubMed - indexed for MEDLINE]17: J Allergy Clin Immunol. 2010 Jun;125(6):1237-1244.e2.
Busse WW, Katial R, Gossage D, Sari S, Wang B, Kolbeck R, Coyle AJ, Koike M, Spitalny GL, Kiener PA, Geba GP, Molfino NA.
University of Wisconsin School of Medicine and Public Health, Madison, Wis., USA.
BACKGROUND: Increased eosinophil levels have been linked to airway inflammation and asthma exacerbations. IL-5 is responsible for eosinophil differentiation, proliferation, and activation; IL-5 receptors are expressed on eosinophils and their progenitors, and targeting such receptors induces eosinophil apoptosis. OBJECTIVE: To evaluate the safety profile, pharmacokinetics, and pharmacodynamics of MEDI-563, a humanized mAb targeting the IL-5 receptor alpha chain. METHODS: Single, escalating, intravenous doses (0.0003-3 mg/kg) of MEDI-563 were administered to subjects with mild atopic asthma (n = 44) over approximately 3 to 30 minutes in this open-label study. Pulmonary function, symptom scores, adverse events, MEDI-563 pharmacokinetics, and levels of C-reactive protein (CRP), IL-6, eosinophil cationic protein (ECP), and eosinophils were evaluated. RESULTS: Mean peripheral blood (PB) eosinophil levels decreased in a dose-dependent fashion (baseline +/- SD, 0.27 +/- 0.2 x 10(3)/microL; 24 hours postdose, 0.01 +/- 0.0 x 10(3)/microL); 94.0% of subjects receiving >or=0.03 mg/kg exhibited levels between 0.00 x 10(3)/microL and 0.01 x 10(3)/microL. Eosinopenia lasted at least 8 or 12 weeks with doses of 0.03 to 0.1 and 0.3 to 3 mg/kg, respectively. ECP levels were reduced from 21.4 +/- 17.2 microg/L (baseline) to 10.3 +/- 7.0 microg/L (24 hours postdose). The most frequently reported adverse events were reduced white blood cell counts (34.1%), nasopharyngitis (27.3%), and increased blood creatine phosphokinase (25.0%). Mean C-reactive protein levels increased approximately 5.5-fold at 24 hours postdose but returned to baseline by study end; mean IL-6 levels increased approximately 3.9-fold to 4.7-fold at 6 to 12 hours postdose, respectively. Pharmacokinetic activity was dose proportional at doses of 0.03 to 3 mg/kg. CONCLUSION: Single escalating doses of MEDI-563 had an acceptable safety profile and resulted in marked reduction of PB eosinophil counts within 24 hours after dosing. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Publication Types: Clinical Trial, Phase I Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20513521&dopt=ExternalLink
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PMID: 20513521 [PubMed - indexed for MEDLINE]18: J Immunol. 2010 Jun 15;184(12):7229-37. Epub 2010 May 7.
Tsai YG, Yang KD, Niu DM, Chien JW, Lin CY.
Department of Pediatrics, Changhua Christian Hospital and Institute of Clinical Medicine, National Ynag-Ming University, Taipei, Taiwan, Republic of China.
Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.
Publication Types: Clinical Trial Research Support, Non-U.S. Gov't
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20483759&dopt=ExternalLink
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PMID: 20483759 [PubMed - indexed for MEDLINE]19: Clin Exp Allergy. 2010 Jul;40(7):1025-35. Epub 2010 Apr 13.
Campbell JD, Buchmann P, Kesting S, Cunningham CR, Coffman RL, Hessel EM.
Dynavax Technologies, Berkeley, CA 94710, USA. DCampbell@dynavax.com
BACKGROUND: A sensitive measurement of low numbers of intracellular cytokine-expressing antigen-specific T cells from peripheral blood mononuclear cells (PBMC) is possible using CD154 as a marker of recently activated T cells. This technique may have potential for monitoring peripheral blood T cell responses to immunotherapy. OBJECTIVE: To evaluate the applicability of this method for measuring changes in cytokine production by allergen-specific T cells in a clinical trial setting. METHODS: Ex vivo ragweed-specific CD154 and intracellular cytokine expression were evaluated using a subset of subjects in an environmental chamber study of allergic rhinitis immunotherapy. PBMC were collected and cryopreserved from Amb a 1-immunostimulatory oligodeoxynucleotide conjugate (AIC)-treated (n=17) and placebo-treated (n=15) ragweed-allergic subjects both after pre- and post-treatment ragweed exposures. In vitro allergen-stimulated CD3(+)CD4(+)CD154(+) T cell intracellular IL-4, IL-5, IL-13, and IFN-gamma expression were evaluated by flow cytometry. RESULTS: Compared with the T helper type 2 (Th2) cytokine expression measured after pre-treatment ragweed exposures, placebo-treated subjects demonstrated a significantly elevated ragweed- and Amb a 1-specific T cell IL-4 and IL-13 co-expression (P=0.005 and P=0.022, respectively) and a significantly elevated ragweed-specific IL-5 expression (P<0.001) following post-treatment ragweed exposures. In contrast, AIC-treated subjects demonstrated no increases in allergen-specific Th2 cytokine expression following post-treatment ragweed exposures. IFN-gamma expression remained low and un-changed in both groups. Subject reported total nasal symptom scores demonstrated modest but significant correlations with Amb a 1- and ragweed-stimulated intracellular Th2 cytokine responses. CONCLUSION: Combined CD154 and intracellular cytokine staining in PBMC can be used to sensitively monitor changes in antigen-specific T cell subset frequencies in clinical studies. Antigen-specific cytokine expression moderately correlated with the reported levels of allergic symptoms.
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20412135&dopt=ExternalLink
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PMID: 20412135 [PubMed - in process]20: J Allergy Clin Immunol. 2010 Mar;125(3):563-8.
Chinen J, Shearer WT.
Department of Pediatrics, Allergy and Immunology Section, Baylor College of Medicine, Houston, Tex 77030, USA. jxchinen@texaschildrenshospital.org
In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1 esterase inhibitor concentrate in patients with hereditary angioedema demonstrated the safety of its use and its efficacy to reduce the duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports, establishing the significant role of Toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced more than 15 new genetic defects related to the immune response, including of dedicator of cytokinesis 8 (DOCK8) mutations, which are responsible for the autosomal recessive form of the hyper-IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia, and myelokathexis syndrome or the occurrence of mucormycosis and Serratia species infections in patients with chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in patients with humoral immunodeficiencies was recognized, and recommendations for management were reviewed. Clinical research focused on severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when the diagnosis is made early before opportunistic infections occur.
Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Links http://www.ncbi.nlm.nih.gov/entrez/queryd.fcgi?cmd=Retrieve&db=PubMed&list_uids=20226292&dopt=ExternalLink
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PMID: 20226292 [PubMed - indexed for MEDLINE]