Publications by Year: 2009

2009
Xepapadaki P, Manios Y, Liarigkovinos T, Grammatikaki E, Douladiris N, Kortsalioudaki C, Papadopoulos NG. Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children. Pediatr Allergy Immunol [Internet]. 2009;20:423-9. WebsiteAbstract
Environmental tobacco smoke (ETS) is a significant risk factor for the presence and increased severity of asthma- and allergy-related symptoms in children. Smoking during pregnancy has detrimental effects on asthma-associated outcomes in childhood. Whether passive exposure of pregnant women to ETS may also lead to asthma in their offspring, is not known. The aim of this study was to investigate the association of passive exposure of pregnant women to ETS and asthma- and/or allergy-related symptoms in Preschool children. Cross-sectional data were collected with questionnaires from 2374 Preschool children, recruited from public and private nurseries and day-care centers. Parental smoking was significantly associated with wheezing symptoms in their children. Mother's active smoking during pregnancy significantly increased the risk for occurrence of asthma symptoms and/or medically diagnosed asthma in Preschool children in a dose-dependent manner. Passive exposure to ETS, mainly during the third trimester of pregnancy, was significantly associated with asthma- and allergy-related symptoms after adjusting for several confounders in a multivariate analysis (current wheeze: OR = 1.42, 95% CI = 1.06-1.91, pruritic rash ever: OR= 1.45, 95% CI = 1.01-2.08). Passive exposure of pregnant women to ETS during the third trimester is positively associated with asthma- and allergy-related symptoms in their Preschool age children. Public health policies should be oriented not only towards smoking cessation, but also reinforce elimination of ETS exposure of pregnant women.
Skevaki CL, Christodoulou I, Spyridaki IS, Tiniakou I, Georgiou V, Xepapadaki P, Kafetzis DA, Papadopoulos NG. Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus. Clin Exp Allergy [Internet]. 2009;39:1700-10. WebsiteAbstract
Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro-inflammatory and remodelling-associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus-induced inflammation and remodelling are less known.|We investigated whether BUD and FORM synergize in suppressing RV-induced inflammation and remodelling in the airways.|In vitro models of RV infection of BEAS-2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post-infection, at a clinically relevant concentration range (10(-6)-10(-10) m), on the production of CCL5, CXCL10, CXCL8, IL-6 and the remodelling-associated VEGF and bFGF, using ELISA and RT-PCR.|BUD effectively suppressed RV-mediated induction of all mediators studied, in a concentration-dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration-dependent, additive or synergistic effects in the suppression of RV-induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV-induced IL-6, and CCL5 at the mRNA level as compared with BUD or FORM alone.|BUD and FORM suppress RV-induced chemokines and growth factors in bronchial epithelial cells in a concentration-dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.
Spyridaki IS, Christodoulou I, de Beer L, Hovland V, Kurowski M, Olszewska-Ziaber A, Carlsen KH, Lødrup-Carlsen K, van Drunen CM, Kowalski ML, et al. Comparison of four nasal sampling methods for the detection of viral pathogens by RT-PCR-A GA(2)LEN project. J Virol Methods [Internet]. 2009;156:102-6. WebsiteAbstract
The aim of this study was to compare the efficacy and patient discomfort between four techniques for obtaining nasal secretions. Nasal secretions from 58 patients with symptoms of a common cold, from three clinical centers (Amsterdam, Lodz, Oslo), were obtained by four different methods: swab, aspirate, brush, and wash. In each patient all four sampling procedures were performed and patient discomfort was evaluated by a visual discomfort scale (scale 1-5) after each procedure. Single pathogen RT-PCRs for Rhinovirus (RV), Influenza virus and Adenovirus, and multiplex real-time PCR for RV, Enterovirus, Influenza virus, Adenovirus, Respiratory Syncytial Virus (RSV), Parainfluenza virus, Coronavirus, Metapneumovirus, Bocavirus and Parechovirus were performed in all samples. A specific viral cause of respiratory tract infection was determined in 48 patients (83%). In these, the detection rate for any virus was 88% (wash), 79% (aspirate), 77% (swab) and 74% (brush). The degree of discomfort reported was 2.54 for swabs, 2.63 for washes, 2.68 for aspirates and 3.61 for brushings. Nasal washes yielded the highest rate of viral detection without excessive patient discomfort. In contrast, nasal brushes produced the lowest detection rates and demonstrated the highest level of discomfort.
Papadopoulos NG, Philip G, Giezek H, Watkins M, Smugar SS, Polos PG. The efficacy of montelukast during the allergy season in pediatric patients with persistent asthma and seasonal aeroallergen sensitivity. J Asthma [Internet]. 2009;46:413-20. WebsiteAbstract
To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity.|This 3-week double-blind, placebo-controlled, parallel-group multicenter study compared daily montelukast 5 mg chewable tablets and placebo in patients 6-14 years of age with forced expiratory volume in 1 second (FEV(1)) > or = 60 and < or = 85% predicted, persistent asthma that is also active during allergy season, and documented sensitivity to seasonal allergens. Concomitant inhaled corticosteroid use was permitted in up to 40% of enrolled patients. The primary endpoint was the percentage change from baseline in FEV(1) over 3 weeks of treatment. Additional endpoints included the percentage change from baseline in beta-agonist use, average changes in daytime and nighttime symptom score, AM and PM peak expiratory flow rate (PEFR), investigator's global asthma evaluation, and parent/guardian global asthma evaluation at the end of the treatment period. Adverse experiences (AEs) were collected to assess safety and tolerability.|A total of 421 patients were randomized to montelukast (N = 203) or placebo (N = 218). For the primary endpoint, the percentage change from baseline FEV(1), montelukast was not significantly different from placebo (least squares mean 9.53% vs. 9.15%, respectively; p = 0.810). Compared with placebo, montelukast was associated with significantly lower (better) investigator's global asthma evaluation (LS mean 2.71 vs. 2.98; p < 0.05) and parent/guardian global asthma evaluation (LS mean: 2.63 vs. 2.90; p < 0.05) scores. There were no significant differences between treatment groups for the other efficacy evaluations. Both treatments were well tolerated, with no significant differences observed in AE rates.|Montelukast did not significantly improve FEV(1) compared with placebo over three weeks of treatment during the allergy season in pediatric patients with seasonal allergen sensitivity. (ClinicalTrials.gov identifier: NCT00289874).
Maggina P, Christodoulou I, Papaevangelou V, Tsolia M, Papadopoulos NG. Dendritic cells in viral bronchiolitis. Expert Rev Clin Immunol [Internet]. 2009;5:271-82. WebsiteAbstract
Dendritic cells (DCs) are major antigen-presenting cells that constitute a link between innate and adaptive immune responses, and are critical in the processes of control and elimination of viral infections. On the other hand, there is a large body of data strongly implicating respiratory viruses in morbidity during infancy through the induction of lower respiratory tract infections, such as bronchiolitis, and later on in childhood and adult life, mainly due to their association with asthma exacerbations. Little is known, however, about the precise role of DCs in human respiratory tract infections. This review focuses on current data, both from in vivo and in vitro studies, that highlight the interplay between DCs and the viral causes of bronchiolitis.
Heinzerling LM, Burbach GJ, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet J, Bousquet-Rouanet L, Bousquet PJ, Bresciani M, et al. GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe. Allergy [Internet]. 2009;64:1498-506. WebsiteAbstract
Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe.|The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel.|The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres.|The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe.|The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.
Bousquet PJ, Burbach G, Heinzerling LM, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet-Rouanet L, Demoly P, Bresciani M, et al. GA2LEN skin test study III: minimum battery of test inhalent allergens needed in epidemiological studies in patients. Allergy [Internet]. 2009;64:1656-62. WebsiteAbstract
The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies.|To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA(2)LEN skin prick test study.|In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection.|Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects.|Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.
Burbach GJ, Heinzerling LM, Edenharter G, Bachert C, Bindslev-Jensen C, Bonini S, Bousquet J, Bousquet-Rouanet L, Bousquet PJ, Bresciani M, et al. GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe. Allergy [Internet]. 2009;64:1507-15. WebsiteAbstract
Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease.|Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis.|While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated.|This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.
Bousquet P-J, Demoly P, Romano A, Aber W, Birchler A, Toress MJ, Terrehorst I, Arnoux B, Atanaskovic-Marcovic M, Barbaud A, et al. Pharmacovigilance of drug allergy and hypersensitivity using the ENDA–DAHD database and the GA2LEN platform. The Galenda project. Allergy. 2009;64:194–203.
Bousquet J, Burney PG, Zuberbier T, Cauwenberge P, Akdis CA, Bindslev-Jensen C, Bonini S, Fokkens WJ, Kauffmann F, Kowalski ML, et al. GA2LEN Addresses the allergy and asthma ‘epidemic’:  a GA2LEN paper. Allergy. 2009;64:969–977.
Bousquet PJ, Brozek J, Bachert C, Bieber T, Bonini S, Burney P, Calderon M, Canonica GW, e Compalati, Daures JP, et al. The CONSORT statement checklist in allergen‐specific immunotherapy: a GA2LEN paper. Allergy. 2009;64:1737-1745.