T Haahtela

Publications of T Haahtela

• Asthma guidelines implementation: a guide to the translation of GINA guidelines into improved care.

  Authors: L-P Boulet, J M Fitzgerald, M L Levy, A A Cruz, S Pedersen, T Haahtela, E D Bateman

  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 01/2012;

  In 1995 the Global Initiative on Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure thatIn 1995 the Global Initiative on Asthma (GINA) published an evidence-based workshop report as a guide to clinicians managing asthma patients, and has updated it annually to ensure that recommendations remain current. Although the report has been widely disseminated and influenced clinical practice and research, its major objective, of forming the basis for local and country initiatives to improve services for asthma patients, remains to be achieved. Over recent years, the science of guideline implementation has progressed, and encouraging examples of successful asthma programmes published. This report is intended to draw on this experience and assist with the translation of asthma guideline recommendations into quality programmes for patients with asthma using current knowledge translation principles. It also provides examples of successful initiatives in various socio-economic settings.

• Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis.

  Authors: E M Savilahti, A K Kukkonen, T Haahtela, T Tuure, M Kuitunen, E Savilahti

  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 11/2011; 42(3):405-11.

  Intestinal flora and innate immunity, and their interactions impact adaptive immunity. To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence ofIntestinal flora and innate immunity, and their interactions impact adaptive immunity. To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence of atopy. The randomly selected group of 102 infants belonged to a randomized, double-blind placebo-controlled trial where 1223 infants in high risk for allergy received, from birth to 6 months, a mixture of synbiotics, or placebo. Clinical trials registration number for the clinical trial is NCT00298337. In the subgroup, 45 received active treatment and 56 received placebo treatment. Follow-up for the emergence of sensitization and allergic diseases lasted 5 years. At the age of 3 (n = 96) and 6 (n = 87) months, we measured fecal levels of human neutrophil peptide (HNP) 1-3 and of β-defensin 2 (HBD2) using enzyme linked immunosorbent assays and concentrations of lactic acid bacteria on MRS agar. We used multifactorial regression in data analysis. Fecal levels of HNP1-3 and HBD2 decreased from the age of 3-6 months (P < 0.0001). HBD2 levels decreased less in the synbiotics group compared with placebo (P < 0.02). High fecal HBD2 levels at 6 months were associated with an increased risk for sensitization by the age of 5 years (OR 2.5, 95% confidence interval 1.1-5.8, P < 0.03). High fecal HNP1-3 levels at 6 months were associated with a decreased risk for atopic dermatitis (OR 0.4, 95% CI 0.1-1.0, P < 0.05). Samples with very low or high HBD2 levels at 6 months had low concentrations of lactic acid bacteria (P < 0.02). Early innate immunity responses in the gut are associated with the emergence of sensitization and atopic dermatitis later in childhood.

• Practical guide to skin prick tests in allergy to aeroallergens.

  Authors: J Bousquet, L Heinzerling, C Bachert, N G Papadopoulos, P J Bousquet, P G Burney, G W Canonica, K H Carlsen, L Cox, T Haahtela [......] B Rogala, A Romano, D Ryan, P Schmid-Grendelmeier, A Todo-Bom, R Valenta, S Woehrl, O M Yusuf, T Zuberbier, P Demoly

  Allergy. 11/2011; 67(1):18-24.

  This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim ofThis pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

• Ovalbumin-specific immunoglobulins A and G levels at age 2 years are associated with the occurrence of atopic disorders.

  Authors: A K Kukkonen, E M Savilahti, T Haahtela, E Savilahti, M Kuitunen

  Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 07/2011; 41(10):1414-21.

  Humoral responses to food antigens may reflect the propensity of a child's immune system to develop tolerance to innocuous antigens. Early nutrition as well as probiotics may influence theseHumoral responses to food antigens may reflect the propensity of a child's immune system to develop tolerance to innocuous antigens. Early nutrition as well as probiotics may influence these immunological responses. To study the association of humoral responses to early food antigens with the administration of prebiotics and probiotics, with the occurrence of allergy, and with the length of exclusive breastfeeding. In a randomized double-blind allergy prevention trial in high-risk children, 1018 mothers took probiotics or placebo from the 36th week of gestation, and their newborn infants received probiotics and prebiotics or placebo during 6 months. At 2 and 5 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, rhinitis) and sensitization (skin prick test ≥3 mm or serum antigen-specific IgE>0.7 kU/L). In 688 infants at age 2, we measured in sera-specific IgA, IgG, IgG1, and IgG4 antibody levels to cow's milk (CM), α-casein (CAS), β-lactoglobulin (BLG), and ovalbumin (OVA) with ELISA, and specific IgE levels to CM and hen's egg with UniCap. Probiotic treatment (n=342) compared with placebo (n=346) showed no effect on serum food-specific IgA, IgG, IgG1, or IgG4 concentrations at age 2. Atopic children had higher OVA-IgA (P<0.001), OVA-IgG (P=0.001), OVA-IgG1 (P<0.001), and egg-IgE but lower OVA-IgG4/egg-IgE ratio (P<0.001) than non-atopic children. Longer duration of exclusive breastfeeding (≥4 vs. <4 months) was associated with reduced CM- and CAS-specific serum IgA (P<0.001) and IgG levels (P<0.001; P=0.003). Allergy was associated with more intense IgA and IgG responses to OVA. Breastfeeding depressed humoral responses, whereas prebiotics and probiotics supplementation showed no immunomodulatory effect. The effect of probiotics on allergies is not mediated through food-specific antibody responses. Furthermore, OVA-specific IgA and IgG antibodies may help in assessing the risk for atopy.

• IgE response to Ascaris lumbricoides in Russian children indicates IgE responses to common environmental allergens.

  Authors: J-P Koskinen, T Laatikainen, L von Hertzen, E Vartiainen, T Haahtela

  Allergy. 03/2011; 66(8):1122-3.

• Use of a common food frequency questionnaire (FFQ) to assess dietary patterns and their relation to allergy and asthma in Europe: pilot study of the GA2LEN FFQ.

  Authors: V Garcia-Larsen, M Luczynska, M L Kowalski, H Voutilainen, M Ahlström, T Haahtela, E Toskala, A Bockelbrink, H-H Lee, E Vassilopoulou, N G Papadopoulos, R Ramalho, A Moreira, L Delgado, M G Castel-Branco, P C Calder, C E Childs, I Bakolis, R Hooper, P G Burney

  European journal of clinical nutrition. 03/2011; 65(6):750-6.

  Comparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy andComparable international data on food and nutrient intake is often hindered by the lack of a common instrument to assess food intake. The objective of this study was within the Global Allergy and Asthma European Network of Excellence (GA(2)LEN), we developed and piloted a food frequency questionnaire (FFQ) to assess its validity in Europe. Five countries participating in GA(2)LEN took part in the pilot study. A total of 200 adults aged 31-75 years were invited to complete a FFQ in two occasions and to give a blood sample. The intra-class correlation coefficient (ICC) was used to assess repeatability of the FFQ. Plasma phospholipid fatty acids (FAs) were analysed by gas chromatography. Pearson correlation was used to analyse the correlation between estimated dietary FA intake and plasma phospholipid FA levels. A total of 177 participants (89%) had complete data on FFQ(1) and plasma phospholipid FAs. In all, 152 participants (76%) completed both FFQs. ICCs between macronutrients ranged from 0.70 (saturated FAs) to 0.78 (proteins) and between 0.70 (retinol) and 0.81 (vitamin D) for micronutrients. Dietary n-3 FAs showed a good correlation with total plasma phospholipid n-3 FAs and with docosahexaenoic acid in the whole sample (0.40) and in individual countries. Poor correlations were observed for other FAs. The GA(2)LEN FFQ is an appropriate tool to estimate dietary intake for a range of nutrients across Europe regardless of cultural and linguistic differences. The FFQ seems to be useful to estimate the intake of n-3 FAs but not other FAs.

• Unaffected peak inspiratory flow through Turbuhaler during histamine inhalation challenge.

  Authors: K Nikander, M Turpeinen, A S Pelkonen, O Selroos, T Haahtela

  Allergy. 02/2011; 66(2):302-3.

• True adherence with the Turbuhaler in young children with asthma.

  Authors: K Nikander, M Turpeinen, A S Pelkonen, T Bengtsson, O Selroos, T Haahtela

  Archives of disease in childhood. 02/2011; 96(2):168-73.

  To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence,To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence, that is correct use of the inhaler. In an 18-month study, children aged 5-10 years with asthma received twice daily budesonide via a TBH. Parents and children were trained in the correct use of the inhaler before the study started. For each inhalation, peak inspiratory flow through the TBH (PIF(TBH)) was recorded with an electronic pneumotachograph. The PIF(TBH) recordings were used to calculate true adherence for the first and last 45-day periods in the study by multiplying adherence in using the device (percentage of days with PIF(TBH) recordings) with inhaler competence (correct use of inhaler defined as PIF(TBH) values >40 l/min). True adherence, adherence, inhaler competence and PIF(TBH). 115 children were treated. The mean (morning and evening) true adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true adherence was due to the decline in adherence. The largest decline in true adherence occurred in older children. True adherence with budesonide TBH treatment decreased significantly during the 18-month study due to a decrease in adherence. Inhaler competence with the correct use of the budesonide TBH was high and unchanged over the study period.

• MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine.

  Authors: J Bousquet, J Anto, C Auffray, M Akdis, A Cambon-Thomsen, T Keil, T Haahtela, B N Lambrecht, D S Postma, J Sunyer [......] E Toskala, P van Cauwenberge, A J M van Oosterhout, R Varraso, L von Hertzen, M Wickman, C Wijmenga, M Worm, J Wright, T Zuberbier

  Allergy. 01/2011; 66(5):596-604.

  The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novelThe origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.

• Practical guide to skin prick tests in allergy to aeroallergens

  Authors: J. Bousquet, L. Heinzerling, C. Bachert, N. G. Papadopoulos, P. J. Bousquet, P. G. Burney, G. W. Canonica, K. H. Carlsen, L. Cox, T. Haahtela [......] B. Rogala, A. Romano, D. Ryan, P. Schmid-Grendelmeier, A. Todo-Bom, R. Valenta, S. Woehrl, O. M. Yusuf, T. Zuberbier, P. Demoly

  Allergy. 01/2011;

  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,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 2011; DOI: 10.1111/j.1398-9995.2011.02728.x Abstract This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA2LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis–conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including ‘practicing allergists’, general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA2LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

• Allergy gap between Finnish and Russian Karelia on increase.

  Authors: Tiina Laatikainen, L von Hertzen, J-P Koskinen, M J Mäkelä, P Jousilahti, T U Kosunen, T Vlasoff, M Ahlström, E Vartiainen, T Haahtela

  Allergy. 01/2011; 66(7):886-92.

  Multinational time-trend analyses of atopic disease have shown that the East-West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy andMultinational time-trend analyses of atopic disease have shown that the East-West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy and atopic diseases in Finnish and Russian Karelia during the past 10 years have diminished and how the prevalence of atopy has evolved with successive years of birth. Two surveys with identical methodology were performed in 1997/1998 and 2007. The study population comprised randomly selected adults, aged 25-54 years, from Finnish and Russian Karelia. Serum samples were collected for total and specific IgE measurements. Clinical data were obtained by questionnaires. Sensitization rates to birch pollen increased from 7.8% to 14.8% (P < 0.001) and to cat from 6.1% to 10.8% (P < 0.001) in Finland. In Russia, no significant increase was found. Contrary to this, total IgE remained stable in Finland but decreased significantly (P < 0.001) in Russia. Analyses based on years of birth revealed that the prevalence of sensitization to allergens increased with successive birth years in Finland, but remained stable in Russia. Over the 10 years, self-reported physician-diagnosed asthma increased from 5.5% to 8.1% (P = 0.05) and hay fever from 8.1% to 13.2% (P < 0.001) in Finland. Disparities in the prevalence of atopy and atopic disease between Finnish and Russian Karelia have further grown. The 'allergy epidemic' continues in Finland and is mainly attributable to the years of birth effect shown in atopy prevalence. In Russia, no signs of the epidemic are discernible, although the decrease in total IgE may indicate a change in environmental exposure.

• Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review.

  Authors: N G Papadopoulos, I Christodoulou, G Rohde, I Agache, C Almqvist, A Bruno, S Bonini, L Bont, A Bossios, J Bousquet [......] M Rukhadze, A Stipic-Markovic, A Todo Bom, E Toskala, P van Cauwenberge, C van Drunen, J B Watelet, M Xatzipsalti, P Xepapadaki, T Zuberbier

  Allergy. 11/2010; 66(4):458-68.

  A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria areA major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

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• Exhaled nitric oxide in contrasting population samples of Finnish and Russian Karelia.

  Authors: L P Malmberg, T Laatikainen, L von Hertzen, M J Mäkelä, E Vartiainen, T Haahtela

  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 06/2010; 35(6):1416-8.

• Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults.

  Authors: S Sistonen, P Malmberg, K Malmström, T Haahtela, S Sarna, R J Rintala, M P Pakarinen

  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 03/2010; 36(5):1106-12.

  Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchialAlthough after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.

• Allergy is rare where butterflies flourish in a biodiverse environment.

  Authors: T Haahtela

  Allergy. 12/2009; 64(12):1799-803.

• GALEN skin test study III: Minimum battery of test inhalent allergens needed in epidemiological studies in patients.

  Authors: P J Bousquet, G Burbach, L M Heinzerling, G Edenharter, C Bachert, C Bindslev-Jensen, S Bonini, L Bousquet-Rouanet, P Demoly, M Bresciani [......] G Muraközi, M Orosz, C Röhnelt, G Stingl, A Todo-Bom, E von Mutius, A Wiesner, S Wöhrl, J Bousquet, T Zuberbier

  Allergy. 11/2009; 64(11):1656-62.

  Background: 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. Objective: ToBackground: 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. Objective: 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. Method: 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. Result: 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. Conclusion: 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.

• GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe.

  Authors: G J Burbach, L M Heinzerling, G Edenharter, C Bachert, C Bindslev-Jensen, S Bonini, J Bousquet, L Bousquet-Rouanet, P J Bousquet, M Bresciani [......] G Muraközi, M Orosz, N G Papadopoulos, C Röhnelt, G Stingl, A Todo-Bom, E von Mutius, A Wiesner, S Wöhrl, T Zuberbier

  Allergy. 10/2009; 64(10):1507-15.

  BACKGROUND: 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 fromBACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

• GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe.

  Authors: L M Heinzerling, G J Burbach, G Edenharter, C Bachert, C Bindslev-Jensen, S Bonini, J Bousquet, L Bousquet-Rouanet, P J Bousquet, M Bresciani [......] G Muraközi, M Orosz, N G Papadopoulos, C Röhnelt, G Stingl, A Todo-Bom, E von Mutius, A Wiesner, S Wöhrl, T Zuberbier

  Allergy. 10/2009; 64(10):1498-506.

  BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergyBACKGROUND: 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. AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

• Effects of Inhaled Corticosteroids on Metalloproteinase-8 and Tissue Inhibitor of Metalloproteinase-1 in the Airways of Asthmatic Children.

  Authors: Y Obase, P Rytilä, T Metso, A S Pelkonen, T Tervahartiala, M Turpeinen, M Mäkelä, U Saarialho-Kere, O Selroos, T Sorsa, T Haahtela

  International archives of allergy and immunology. 09/2009; 151(3):247-254.

  Background: The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue areBackground: The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo. Methods: We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide. Results: At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms. Conclusions: Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.

• Real-world clinical data identifies gender-related profiles in chronic obstructive pulmonary disease.

  Authors: T Laitinen, U Hodgson, H Kupiainen, L Tammilehto, T Haahtela, M Kilpeläinen, A Lindqvist, V L Kinnula

  COPD. 08/2009; 6(4):256-62.

  This study aims to compare diagnostic and clinical outcomes of Chronic Obstructive Pulmonary Disease (COPD) from the gender perspective using retrospective health care data and patient reportedThis study aims to compare diagnostic and clinical outcomes of Chronic Obstructive Pulmonary Disease (COPD) from the gender perspective using retrospective health care data and patient reported outcomes in a real-world setting. An electronic database was constructed from complete medical records of 844 COPD patients who were recruited in Helsinki and Turku University Central Hospitals during the years 2005-07. The patients were identified from the hospital discharge registries by ICD10 code J44.8 in the age group of 18-75 years of age. The medical history was obtained from all healthcare providers who had treated these patients during the previous 5-10 years; the study intends to continue their follow-up annually for the next 10 years. Thirty-six percent (N = 266) of the participants were women. The COPD diagnosis had been made at the same age for both genders. Women, however, reported significantly less pack-years than men. Compared to the men, the women displayed less advanced airway obstruction, but more severe gas transfer impairment. Parenchymal damage when evaluated by diffusion capacity correlated significantly stronger with FEV(1) (% of predicted) in women than men. The BMI index of the women was lower than that of the men. Cardiovascular diseases, diabetes and alcoholism were significantly more common in men, but women suffered more psychiatric conditions, especially depression. This cohort showed several significant gender dependent differences in the clinical presentation that need to taken under consideration in the assessment of COPD progression and the disease management.