Publications by Year: 2013

2013
Swoboda I, Balic N, Klug C, Focke M, Weber M, Spitzauer S, Neubauer A, Quirce S, Douladiris N, Papadopoulos NG, et al. A general strategy for the generation of hypoallergenic molecules for the immunotherapy of fish allergy. J Allergy Clin Immunol [Internet]. 2013;132:979-81.e1. Website
Tsilochristou OA, Douladiris N, Makris M, Papadopoulos NG. Pediatric Allergic Rhinitis and Asthma: Can the March be Halted?. Paediatr Drugs [Internet]. 2013. WebsiteAbstract
The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.
Roberts G, Xatzipsalti M, Borrego LM, Custovic A, Halken S, Hellings PW, Papadopoulos NG, Rotiroti G, Scadding G, Timmermans F, et al. Paediatric rhinitis: position paper of the European Academy of Allergy and Clinical Immunology. Allergy [Internet]. 2013;68:1102-16. WebsiteAbstract
Rhinitis is a common problem in childhood and adolescence and impacts negatively on physical, social and psychological well-being. This position paper, prepared by the European Academy of Allergy and Clinical Immunology Taskforce on Rhinitis in Children, aims to provide evidence-based recommendations for the diagnosis and therapy of paediatric rhinitis. Rhinitis is characterized by at least two nasal symptoms: rhinorrhoea, blockage, sneezing or itching. It is classified as allergic rhinitis, infectious rhinitis and nonallergic, noninfectious rhinitis. Similar symptoms may occur with other conditions such as adenoidal hypertrophy, septal deviation and nasal polyps. Examination by anterior rhinoscopy and allergy tests may help to substantiate a diagnosis of allergic rhinitis. Avoidance of relevant allergens may be helpful for allergic rhinitis (AR). Oral and intranasal antihistamines and nasal corticosteroids are both appropriate for first-line AR treatment although the latter are more effective. Once-daily forms of corticosteroids are preferred given their improved safety profile. Potentially useful add-on therapies for AR include oral leukotriene receptor antagonists, short bursts of a nasal decongestant, saline douches and nasal anticholinergics. Allergen-specific immunotherapy is helpful in IgE-mediated AR and may prevent the progression of allergic disease. There are still a number of areas that need to be clarified in the management of rhinitis in children and adolescents.
Papadopoulos NG, Savvatianos S. The vital need for allergy training: removing the doubts. Prim Care Respir J [Internet]. 2013;22:5-6. Website
Pahr S, Constantin C, Papadopoulos NG, Giavi S, Mäkelä M, Pelkonen A, Ebner C, Mari A, Scheiblhofer S, Thalhamer J, et al. α-Purothionin, a new wheat allergen associated with severe allergy. J Allergy Clin Immunol [Internet]. 2013;132:1000-3.e1-4. Website
Moreira A, Bonini M, Garcia-Larsen V, Bonini S, Del Giacco SR, Agache I, Fonseca J, Papadopoulos NG, Carlsen KH, Delgado L, et al. Weight loss interventions in asthma: EAACI evidence-based clinical practice guideline (part I). Allergy [Internet]. 2013;68:425-39. WebsiteAbstract
Asthma and obesity are chronic multifactorial conditions that are associated with gene-environment interaction and immune function. Although the data are not fully consistent, it seems that obesity increases the risk of asthma and compromises asthma control.|To investigate the impact that weight changes have on asthma.|We carried out a systematic review of three large biomedical databases. Studies were scrutinized and critically appraised according to agreed exclusion and inclusion criteria. Quality assessment of eligible papers was conducted using the GRADE method. Meta-analyses of comparable studies were carried out.|Thirty studies met the eligibility criteria of the review. Interventions were limited to dietary manipulation in three studies, one of which also used anti-obesity drugs, and bariatric surgery in four. All the other studies reported observational data. Becoming obese increased the odds for incident asthma by 1.82 (95% CI 1.47, 2.25) in adults and 1.98 (95% CI 0.71, 5.52) in children. Weight loss was associated with significant improvement in mean scores for symptoms, rescue medication score, and asthma exacerbations in the only randomized controlled trial. Similarly, evidence gathered from observational studies, with follow-up ranging between 8 weeks to 1 year, and from changes 1 year after bariatric surgery showed improvements in all asthma control-related outcomes. Changes in lung function were reported in one randomized controlled and eight observational studies of asthmatic subjects, with conflicting results. Either improvement after weight loss, decline with weight gain, or no effects at all were reported. Changes in airway inflammation and responsiveness were reported only by observational studies.|Weight increases above the obesity threshold significantly increase the risk of asthma. The available studies show weak evidence of benefits from weight reduction on asthma outcomes.
Konstantinou GN, Xepapadaki P, Manousakis E, Makrinioti H, Kouloufakou-Gratsia K, Saxoni-Papageorgiou P, Papadopoulos NG. Assessment of airflow limitation, airway inflammation, and symptoms during virus-induced wheezing episodes in 4- to 6-year-old children. J Allergy Clin Immunol [Internet]. 2013;131:87-93.e1-5. WebsiteAbstract
It is disputed whether recurrent episodes of wheeze in preschool-aged children comprise a distinct asthma phenotype.|We sought to prospectively assess airflow limitation and airway inflammation in children 4 to 6 years old with episodic virus-induced wheeze.|Ninety-three children 4 to 6 years old with a history of mild, virus-induced episodes of wheeze who were able to perform acceptable fraction of exhaled nitric oxide (Feno) maneuvers and spirometry (with forced expiratory time ≥0.5 seconds) were followed prospectively. Lung function and Feno values were measured every 6 weeks (baseline) within the first 48 hours of an acute wheezing episode (day 0) and 10 and 30 days later. Symptom scores and peak flow measurement were recorded daily.|Forty-three children experienced a wheezing episode. At day 0, Feno values were significantly increased, whereas forced expiratory volume at 0.5 seconds (FEV(0.5)) significantly decreased compared with baseline (16 ppb [interquartile range {IQR}, 13-20 ppb] vs 9 ppb IQR, 7-11 ppb] and 0.84 L [IQR, 0.75-0.99 L] vs 0.99 L [IQR, 0.9-1.07 L], respectively; both P < .001). Airflow limitation at day 0 was reversible after bronchodilation. FEV(0.5) and Feno values were significantly associated with each other and with lower and upper respiratory tract symptoms when assessed longitudinally but not cross-sectionally at all time points independently of atopy. Feno and FEV(0.5) values returned to baseline levels within 10 days.|Mild episodes of wheeze in preschoolers are characterized by enhanced airway inflammation, reversible airflow limitation, and asthma-related symptoms. Feno values increase significantly during the first 48 hours and return to personal baseline within 10 days from the initiation of the episode. Longitudinal follow-up suggests that symptoms, inflammation, and lung function correlate well in this phenotype of asthma.
Le TM, Bublin M, Breiteneder H, Fernández-Rivas M, Asero R, Ballmer-Weber B, Barreales L, Bures P, Belohlavkova S, De Blay F, et al. Kiwifruit allergy across Europe: clinical manifestation and IgE recognition patterns to kiwifruit allergens. J Allergy Clin Immunol [Internet]. 2013;131:164-71. WebsiteAbstract
Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions.|We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated.|This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP.|Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract.|Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.
Hellings PW, Fokkens WJ, Akdis C, Bachert C, Cingi C, Dietz de Loos D, Gevaert P, Hox V, Kalogjera L, Lund V, et al. Uncontrolled allergic rhinitis and chronic rhinosinusitis: where do we stand today?. Allergy [Internet]. 2013;68:1-7. WebsiteAbstract
State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain.
Guibas GV, Makris M, Papadopoulos NG. Key regulators of sensitization and tolerance: GM-CSF, IL-10, TGF-β and the Notch signaling pathway in adjuvant-free experimental models of respiratory allergy. Int Rev Immunol [Internet]. 2013;32:307-23. WebsiteAbstract
Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-β was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.
Guibas GV, Manios Y, Xepapadaki P, Moschonis G, Douladiris N, Mavrogianni C, Papadopoulos NG. The obesity-asthma link in different ages and the role of Body Mass Index in its investigation: findings from the Genesis and Healthy Growth Studies. Allergy [Internet]. 2013;68:1298-305. WebsiteAbstract
To date, an obesity/asthma link is well defined in adults; however, the nature of such a link is obscure in children, partly due to Body Mass Index (BMI) limitations as a surrogate fat mass marker in childhood. We thus opted to investigate the association of adiposity with asthma in children of different ages, using several indices to assess fat mass.|Wheeze ever/in the last 12 months (current) and physician-diagnosed asthma were retrospectively reported via questionnaire by the parents of 3641 children, participating in two cross-sectional studies: 1626 children aged 2-5 (the Genesis Study) and 2015 children aged 9-13 (the Healthy Growth Study). Perinatal data were recorded from the children's medical records or reported by parents. Anthropometric measurements (i.e., BMI, waist/hip circumference, biceps/triceps/subscapular/suprailiac skinfold thickness) were conducted in both cohorts; bioelectric impedance analysis (BIA) was conducted only in preadolescent children.|In children aged 2-5, asthma was positively correlated with conicity index, waist/hip circumference, waist-to-height ratio, skinfold thickness, and skinfold-derived percentage fat mass (P < 0.05) but not BMI or BMI-defined overweight/obesity, after adjusting for several confounders. In children aged 9-13, asthma was positively associated with conicity index, waist circumference, waist-to-height ratio, skinfold thickness, skinfold-derived percentage fat mass, BIA-derived percentage fat mass, BMI, and BMI-defined overweight/obesity, following adjustment (P < 0.05). Current/ever wheeze was not consistently associated with fat mass in either population.|Fat mass is positively linked to asthma in both 2-5 and 9-13 age spans. However, the failure of BMI to correlate with preschool asthma suggests its potential inefficiency in asthma studies at this age range.
Guibas GV, Moschonis G, Xepapadaki P, Roumpedaki E, Androutsos O, Manios Y, Papadopoulos NG. Conception via in vitro fertilization and delivery by Caesarean section are associated with paediatric asthma incidence. Clin Exp Allergy [Internet]. 2013;43:1058-66. WebsiteAbstract
The association between perinatal factors and asthma inception is under rigorous investigation. Nevertheless, evidence of a correlation between asthma, conception via in vitro fertilization (IVF) and delivery through Caesarean section (C-section) is inconclusive.|We aimed to assess the relation of asthma incidence with IVF and C-section, after controlling for several potential confounding factors.|Parent-reported wheeze in the last 12 months (current), wheeze ever, physician-diagnosed asthma, method of conception, and type of delivery were recorded from questionnaires filled in by the parents of 2016 Greek children aged 9-13, (the Healthy Growth Study population). Some perinatal data were recorded from children's medical records and others were reported by parents; anthropometric measurements were also conducted in children.|IVF was correlated with physician-diagnosed asthma (OR = 2.25; 95% CI = 1.11-4.56), but not with current/ever wheeze after adjustment for potential confounding factors. After adjustment, C-section was also associated with asthma (OR = 1.39; 95% CI = 1.04-1.87), but not with current/ever wheeze. When the association of both IVF and C-section with asthma was examined in the same multivariate logistic regression model, it was weakened to borderline significance (OR = 2.04; 95% CI = 1-4.15 and OR = 1.34; 95% CI = 1-1.81 respectively).|Conception via IVF and delivery by C-section may predispose children to future asthma development. Either variable could also exert a confounding effect on the link of the other to asthma; this may partially be accountable for inconsistencies in the findings of pertinent studies.
de Monchy JG, Demoly P, Akdis CA, Cardona V, Papadopoulos NG, Schmid-Grendelmeier P, Gayraud J. Allergology in Europe, the blueprint. Allergy [Internet]. 2013;68:1211-8. WebsiteAbstract
The number of patients with allergic diseases in Europe, and thus relevant demand for health care, is continuously increasing. In this EAACI-UEMS position paper, a rationale is given for the medical specialty of allergology. General practitioners and general paediatricians usually cannot elucidate and address all causative factors. Throughout Europe, therefore, the expertise of allergologists (allergists) is required. In collaboration with other medical professionals, they take care of allergic patients, in private practices or in specialized public centres. A well-structured collaboration between allergists and allergy centres offers the possibility of rapid signalling of new trends developing in the population of allergic patients (e.g. in food and drug allergy). Allergy centres also can perform clinical (and basic) research, teach medical students, future allergists and provide postgraduate training. To prevent that the quality of care in one or several countries within Europe lags behind developments in other countries, the UEMS Section and Board on Allergology together with the European Academy of Allergy and Clinical Immunology advocates the status of a full specialty of allergology in each European country, with a further intention to align their activities (blueprint, curriculum and centre visitation) with the UEMS Section of Paediatrics.
Douladiris N, Savvatianos S, Roumpedaki I, Skevaki C, Mitsias D, Papadopoulos NG. A molecular diagnostic algorithm to guide pollen immunotherapy in southern europe: towards component-resolved management of allergic diseases. Int Arch Allergy Immunol [Internet]. 2013;162:163-72. WebsiteAbstract
Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a 'Component-Resolved Allergy Management'.
Eigenmann PA, Atanaskovic-Markovic M, O'B Hourihane J, Lack G, Lau S, Matricardi PM, Muraro A, Namazova Baranova L, Nieto A, Papadopoulos NG, et al. Testing children for allergies: why, how, who and when: an updated statement of the European Academy of Allergy and Clinical Immunology (EAACI) Section on Pediatrics and the EAACI-Clemens von Pirquet Foundation. Pediatr Allergy Immunol [Internet]. 2013;24:195-209. WebsiteAbstract
Allergic diseases are common in childhood and can cause a significant morbidity and impaired quality-of-life of the children and their families. Adequate allergy testing is the prerequisite for optimal care, including allergen avoidance, pharmacotherapy and immunotherapy. Children with persisting or recurrent or severe symptoms suggestive for allergy should undergo an appropriate diagnostic work-up, irrespective of their age. Adequate allergy testing may also allow defining allergic trigger in common symptoms. We provide here evidence-based guidance on when and how to test for allergy in children based on common presenting symptoms suggestive of allergic diseases.
de Lauzon-Guillain B, Jones L, Oliveira A, Moschonis G, Betoko A, Lopes C, Moreira P, Manios Y, Papadopoulos NG, Emmett P, et al. The influence of early feeding practices on fruit and vegetable intake among preschool children in 4 European birth cohorts. Am J Clin Nutr [Internet]. 2013;98:804-12. WebsiteAbstract
Fruit and vegetable intake in children remains below recommendations in many countries. The long-term effects of early parental feeding practices on fruit and vegetable intake are not clearly established.|The purpose of the current study was to examine whether early feeding practices influence later fruit and vegetable intake in preschool children.|The study used data from 4 European cohorts: the British Avon Longitudinal Study of Parents and Children (ALSPAC), the French Etude des Déterminants pre et postnatals de la santé et du développement de l'Enfant study, the Portuguese Generation XXI Birth Cohort, and the Greek EuroPrevall study. Fruit and vegetable intake was assessed in each cohort by food-frequency questionnaire. Associations between early feeding practices, such as breastfeeding and timing of complementary feeding, and fruit and/or vegetable intake in 2-4-y-old children were tested by using logistic regressions, separately in each cohort, after adjustment for infant's age and sex and maternal age, educational level, smoking during pregnancy, and maternal fruit and vegetable intake.|Large differences in early feeding practices were highlighted across the 4 European cohorts with longer breastfeeding duration in the Generation XXI Birth Cohort and earlier introduction to complementary foods in ALSPAC. Longer breastfeeding duration was consistently related to higher fruit and vegetable intake in young children, whereas the associations with age of introduction to fruit and vegetable intake were weaker and less consistent across the cohorts. Mothers' fruit and vegetable intake (available in 3 of the cohorts) did not substantially attenuate the relation with breastfeeding duration.|The concordant positive association between breastfeeding duration and fruit and vegetable intake in different cultural contexts favors an independent specific effect.
Bousquet J, Tanasescu CC, Camuzat T, Anto JM, Blasi F, Neou A, Palkonen S, Papadopoulos NG, Antunes JP, Samolinski B, et al. Impact of early diagnosis and control of chronic respiratory diseases on active and healthy ageing. A debate at the European Union Parliament. Allergy [Internet]. 2013;68:555-61. WebsiteAbstract
A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc-Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy (PAPA). The third project is the GA(2)LEN sentinel network.
Bonini M, Bachert C, Baena-Cagnani CE, Bedbrook A, Brozek JL, Canonica GW, Cruz AA, Fokkens WJ, Gerth van Wijk R, Grouse L, et al. What we should learn from the London Olympics. Curr Opin Allergy Clin Immunol [Internet]. 2013;13:1-3. Website
Custovic A, Johnston SL, Pavord I, Gaga M, Fabbri L, Bel EH, Souëf LP, Lötvall J, Demoly P, Akdis CA, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy. 2013;68:1520-1531.
Fox M, Mugford Μ, Voordouw J, Cornelisse-Vermaat J, Antonides C, de la Caballer BH, Cerecedo I, Zamora J, Rokicka E, Jewczak M, et al. Health sector costs of self-reported food allergy in Europe: a patient-based cost of illness study. The European Journal of Public Health . 2013:1-6.
George GV, Xepapadaki P, Moschonis G, N D, Filippou A, Tsirigoti L, Manios Y, Papadopoulos NG. Breastfeeding and wheeze prevalence in pre‐schoolers and pre‐adolescents: the Genesis and Healthy Growth studies. Pediatric Allergy and Immunology . 2013;24:772-81.
Janse JJ, Wong WKG, Potts J, Ogorodova LM, Fedorova OS, Mahesh PA, Sakellariou A, Papadopoulos NG, Knulst AC, Versteeg SA, et al. Foodborne and orofecal pathogens and allergic sensitization: EuroPrevall‐International Cooperation study. Pediatric Allergy and Immunology. 2013.
Kupczyk M, Haque S, Sterk PJ, Niżankowska-Mogilnicka E, A P, Bel EH, Chanez P, Dahlén B, Gaga M, Gjomarkaj M, et al. Detection of exacerbations in asthma based on electronic diary data: results from the 1-year prospective BIOAIR study. Thorax. 2013;68:611-618.
Baar A, Pahr S, Constantin C, Giavi S, Manoussaki A, Papadopoulos NG, Ebner C, Mari A, Vrtala S, R V. Specific IgE reactivity to Tri a 36 in children with wheat food allergy. Allergy and Clinical Immunology. 2013.