Nikolaos G. Papadopoulos

Rhinoviruses Infect the Lower Airways

Rhinoviruses are the major cause of the common cold and a trigger of acute asthma exacerbations. Whether these exacerbations result from direct infection of the lower airway or from indirect mechanisms consequent on infection of the upper airway alone is currently unknown. Lower respiratory infection was investigated in vitro by exposing primary human bronchial epithelial cells to rhinoviruses and in vivo after experimental upper respiratory infection of human volunteers. Bronchial infection was confirmed by both approaches. Furthermore, rhinoviruses induced production of interleukin-6, -8, and -16 and RANTES and were cytotoxic to cultured respiratory epithelium. This evidence strongly supports a direct lower respiratory epithelial reaction as the initial event in the induction of rhinovirus-mediated asthma exacerbations. The frequency of infection and the nature of the inflammatory response observed are similar to those of the upper respiratory tract, suggesting that rhinovirus infections may be one of the most important causes of lower in addition to upper respiratory disease.

Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report

Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative ** , which is endorsed by both academies.

EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy

Food allergy can result in considerable morbidity, impact negatively on quality of life, and prove costly in terms of medical care. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Guidelines for Food Allergy and Anaphylaxis Group, building on previous EAACI position papers on adverse reaction to foods and three recent systematic reviews on the epidemiology, diagnosis, and management of food allergy, and provide evidence‐based recommendations for the diagnosis and management of food allergy. While the primary audience is allergists, this document is relevant for all other healthcare professionals, including primary care physicians, and pediatric and adult specialists, dieticians, pharmacists and paramedics. Our current understanding of the manifestations of food allergy, the role of diagnostic tests, and the effective management of patients of all ages with food allergy is presented. The acute management of non‐life‐threatening reactions is covered in these guidelines, but for guidance on the emergency management of anaphylaxis, readers are referred to the related EAACI Anaphylaxis Guidelines.

Allergic Rhinitis and its Impact on Asthma (ARIA) 2008

J. Bousquet, N. Khaltaev, A. A. Cruz, J. Denburg, W. J. Fokkens, A. Togias, T. Zuberbier, C. E. Baena-Cagnani, G. W. Canonica, C. van Weel, I. Agache, N. A t-Khaled, C. Bachert, M. S. Blaiss, S. Bonini, L.-P. Boulet, P.-J. Bousquet, P. Camargos, K.-H. Carlsen, Y. Chen, A. Custovic, R. Dahl, P. Demoly, H. Douagui, S. R. Durham, R. Gerth van Wijk, O. Kalayci, M. A. Kaliner, Y.-Y. Kim, M. L. Kowalski, P. Kuna, L. T. T. Le, C. Lemiere, J. Li, R. F. Lockey, S. Mavale-Manuel , E. O. Meltzer, Y. Mohammad, J. Mullol, R. Naclerio, R. E. O Hehir, K. Ohta, S. Ouedraogo, S. Palkonen, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. A. Popov, K. F. Rabe, J. Rosado-Pinto, G. K. Scadding, F. E. R. Simons, E. Toskala, E. Valovirta, P. van Cauwenberge, D.-Y. Wang, M. Wickman, B. P. Yawn, A. Yorgancioglu, O. M. Yusuf, H. Zar Review Group: I. Annesi-Maesano, E. D. Bateman, A. Ben Kheder, D. A. Boakye, J. Bouchard, P. Burney, W. W. Busse, M. Chan-Yeung, N. H. Chavannes, A. Chuchalin, W. K. Dolen, R. Emuzyte, L. Grouse, M. Humbert, C. Jackson, S. L. Johnston, P. K. Keith, J. P. Kemp, J.-M. Klossek, D. Larenas-Linnemann, B. Lipworth, J.-L. Malo, G. D. Marshall, C. Naspitz, K. Nekam, B. Niggemann, E. Nizankowska-Mogilnicka, Y. Okamoto, M. P. Orru, P. Potter, D. Price, S. W. Stoloff, O. Vandenplas, G. Viegi, D. Williams

Practical guide to skin prick tests in allergy to aeroallergens

To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi‐Maesano I, Baena‐Cagnani CE, Bergmann KC, Bindslev‐Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth‐van‐Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova‐Baranova L, O’Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid‐Grendelmeier P, Todo‐Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2012; 67: 18–24.

An improved fluorescence assay for the determination of lymphocyte-mediated cytotoxicity using flow cytometry

The use of the chromium-release assay to determine cytotoxicity of effector against target cells has various limitations mostly due to the inherent properties of the radioactive substance. We have developed an improved flow cytometric method that is able to measure cytotoxicity, based on two fluorescent dyes. Calcein-AM, a non-fluorescent substance which is intracellularly converted to the green fluorescent calcein by esterase activity in viable cells, is initially used to stain target cells. After incubating targets with effectors for 2 h, ethidium homodimer-1, a red DNA stain non-permeable to viable cells, is added. Dead target cells are distinguished by their double (green-red) staining. Data analysis is performed by gating the regions of living target, dead target and living effector cells, based on appropriate controls. Non-specific events are subtracted from the dead target region and the ratio of specific dead target events to total target events is expressed as percent cytotoxicity. The method is used to quantify natural killer (NK) and lymphokine-activated killer (LAK) activities against the human K562 and Daudi cell lines and the murine YAC-1 and L1210 cell lines respectively, as well as cell-mediated lympholysis (CML) exerted by tumor-infiltrating lymphocytes (TIL) against autologous and allogeneic human breast cancer tumor cells. The method is fast, reliable and correlates well with the standard 51Cr-release assay.

A defective type 1 response to rhinovirus in atopic asthma

Background: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma. Methods: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)γ and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays. Results: Exposure of PBMC to RVs induced the production of IFNγ, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFNγ and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFNγ/IL-4 ratio was more than three times lower in the asthmatic group. Conclusions: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma.

IL-33–Dependent Type 2 Inflammation during Rhinovirus-induced Asthma Exacerbations In Vivo

RATIONALE Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. OBJECTIVES To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. METHODS We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirus-infected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. MEASUREMENTS AND MAIN RESULTS IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. CONCLUSIONS IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33-responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbations.

EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy

Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunologys (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence‐based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review.

International consensus on (ICON) pediatric asthma

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re‐evaluate and fine‐tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype‐specific treatment choices; however, this goal has not yet been achieved.