Search

Background: It has been observed that mice lacking the sulfatase modifying factor (Sumf1) developed an emphysema-like phenotype. However, it is unknown if SUMF1 may play a role in Chronic Obstructive Pulmonary Disease (COPD) in humans. The aim was to investigate if the expression and genetic regulation of SUMF1 differs between smokers with and without COPD.Methods: SUMF1 mRNA was investigated in sputum cells and whole blood from controls and COPD patients (all current or former smokers). Expression quantitative trait loci (eQTL) analysis was used to investigate if single nucleotide polymorphisms (SNPs) in SUMF1 were significantly associated with SUMF1 expression. The association of SUMF1 SNPs with COPD was examined in a population based cohort, Lifelines. SUMF1 mRNA from sputum cells, lung tissue, and lung fibroblasts, as well as lung function parameters, were investigated in relation to genotype.Results: Certain splice variants of SUMF1 showed a relatively high expression in lung tissue compared to many other tissues. SUMF1 Splice variant 2 and 3 showed lower levels in sputum cells from COPD patients as compared to controls. Twelve SNPs were found significant by eQTL analysis and overlapped with the array used for genotyping of Lifelines. We found alterations in mRNA expression in sputum cells and lung fibroblasts associated with SNP rs11915920 (top hit in eQTL), which validated the results of the lung tissue eQTL analysis. Of the twelve SNPs, two SNPs, rs793391 and rs308739, were found to be associated with COPD in Lifelines. The SNP rs793391 was also confirmed to be associated with lung function changes.Conclusions: We show that SUMF1 expression is affected in COPD patients compared to controls, and that SNPs in SUMF1 are associated with an increased risk of COPD. Certain COPD-associated SNPs have effects on either SUMF1 gene expression or on lung function. Collectively, this study shows that SUMF1 is associated with an increased risk of developing COPD. [ABSTRACT FROM AUTHOR]

Background: To investigate if age, gender and smoking are associated with airway wall thickness (AWT) measured by high resolution computed tomography (HRCT) and if higher AWT is associated with lower levels of pulmonary function in healthy current- and never-smokers with a wide age range.Methods: HRCT scans were performed in 99 subjects (48 never- and 51 current-smokers, median age 39 years [IQR 22 - 54], 57% males). The AWT at an internal perimeter of 10 mm (AWT Pi10) was calculated as an overall measurement of AWT, based on all measurements throughout the lungs. Extensive pulmonary function testing was performed in all subjects.Results: Higher age was associated with a lower AWT Pi10 (b = -0.003, p < 0.001). Current-smokers had a higher AWT Pi10 than never-smokers (mean 0.49 mm versus 0.44 mm, p = 0.022). In multivariate analysis, age and current-smoking were independently associated with AWT Pi10 (age b = -0.002, p < 0.001, current-smoking b = 0.041, p = 0.021), whereas gender was not (b = 0.011, p = 0.552). Higher AWT Pi10 was associated with a lower FEV1, FEV1/FVC, FEF25-75 and higher R5, R20 and X5.Conclusions: AWT decreases with higher age, possibly reflecting structural changes of the airways. Additionally, current-smokers have a higher AWT, possibly due to remodeling or inflammation. Finally, higher AWT is associated with a lower level of pulmonary function, even in this population of healthy subjects.Trial Registration: This Study was registered at www.clinicaltrials.gov with number NCT00848406 on 19 February 2009. [ABSTRACT FROM AUTHOR]

Background: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD. Methods: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking. Cases and controls were selected from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Results: In total, 37 genetic variants showed association with COPD (p < 0.05, uncorrected). Several variants previously discovered to be associated with COPD from genetic genome-wide analysis studies were replicated using our sample. Two high-risk variants were followed-up for functional characterization in a large eQTL mapping study of 1,111 human lung specimens. The C allele of a synonymous variant, rs8040868, predicting a p.(S45=) in the gene for cholinergic receptor nicotinic alpha 3 (CHRNA3) was associated with COPD (p = 8.8 x 10-3). This association remained (p = 0.003 and OR = 1.4, 95 % CI 1.1-1.7) when analysing all available cases and controls in OLIN (n = 1,534). The rs8040868 variant is in linkage disequilibrium with rs16969968 previously associated with COPD and altered expression of the CHRNA5 gene. A follow-up analysis for detection of expression quantitative trait loci revealed that rs8040868-C was found to be significantly associated with a decreased expression of the nearby gene cholinergic receptor, nicotinic, alpha 5 (CHRNA5) in lung tissue. Conclusion: Our data replicate previous result suggesting CHRNA5 as a candidate gene for COPD and rs8040868 as a risk variant for the development of COPD in the Swedish population. [ABSTRACT FROM AUTHOR]

Background: Most randomised clinical trials typically exclude a significant proportion of asthma patients, including those at higher risk of adverse events, with comorbidities, obesity, poor inhaler technique and adherence, or smokers. However, these patients might differentially benefit from extrafine-particle inhaled corticosteroids (ICS). This matched cohort, database study, compared the effectiveness of extrafine-particle with fine-particle ICS in a real-life population initiating ICS therapy in the Netherlands.Methods: Data were from the Pharmo Database Network, comprising pharmacy and hospital discharge records, representative of 20 % of the Dutch population. The study population included patients aged 12 - 60, with a General Practice-recorded diagnosis for asthma (International Classification of Primary Care code R96), when available, ≥2 prescriptions for asthma therapy at any time in their recorded history, and receiving first prescription of ICS therapy as either extrafine-particle (ciclesonide or hydrofluoroalkane beclomethasone dipropionate [BDP]) or fine-particle ICS (fluticasone propionate or non-extrafine-particle-BDP). Patients were matched (1:1) on relevant demographic and clinical characteristics over 1-year baseline. Primary outcomes were severe exacerbation rates, risk domain asthma control and overall asthma control during the year following first ICS prescription. Secondary outcomes, treatment stability and being prescribed higher versus lower category of short-acting β2 agonists (SABA) dose, were compared over a 1-year outcome period using conditional logistic regression models.Results: Following matching, 1399 patients were selected in each treatment cohort (median age: 43 years; males: 34 %). Median (interquartile range) initial ICS doses (fluticasone-equivalents in μg) were 160 (160 - 320) for extrafine-particle versus 500 (250 - 500) for fine-particle ICS (p < 0.001). Following adjustment for residual confounders, matched patients prescribed extrafine-particle ICS had significantly lower rates of exacerbations (adjusted rate ratio [95 % CI], 0.59 [0.47-0.73]), and significantly higher odds of achieving asthma control and treatment stability in the year following initiation than those prescribed fine-particle ICS, and this occurred at lower prescribed doses. Patients prescribed extrafine-particle ICS had lower odds of being prescribed higher doses of SABA (0.50 [0.44-0.57]).Conclusion: In this historical, matched study, extrafine-particle ICS was associated with better odds of asthma control than fine-particle ICS in patients prescribed their first ICS therapy in the Netherlands. Of importance, this was reached at significantly lower prescribed dose. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke. Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE). This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.Methods: Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included. Autofluorescence (SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.Results: COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates). Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001). One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.Conclusion: In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies. The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD. [ABSTRACT FROM AUTHOR]

Background: Debate exists regarding which endpoints most sensitively reflect day-to-day variation in chronic obstructive pulmonary disease (COPD) symptoms and are most useful in clinical practice to predict COPD exacerbations. We hypothesized that short-acting β2-agonist (SABA) reliever use would predict short- and long-term exacerbation risk in COPD patients. Methods: We performed a retrospective analysis of data from a study (ClinicalTrials.gov registration: NCT00419744) comparing budesonide/formoterol 320/9 μg with formoterol 9 μg (both twice daily) in patients with moderate-to-verysevere COPD; reliever salbutamol 90 μg was provided. First occurrence of reliever use >4 (low), >10 (medium), and >20 (high) inhalations/day was assessed as a predictor of short-term (3-week) exacerbation risk. Mean daily reliever use in the week preceding the 2-month visit was investigated as a predictor of the long-term (10-month) exacerbation risk, using intervals of 2-5, 6-9, and ≥10 inhalations/day. Results: Overall, 810 patients were included (61 % male; mean age 63.2 years; post-bronchodilator forced expiratory volume in 1 s 37.7 % of predicted). First occurrence of low, medium, or high reliever use was predictive of an exacerbation within the following 3 weeks; exacerbation risk increased significantly with increasing reliever use. Mean reliever use over 1 week was predictive of long-term exacerbation risk. Patients with mean use of 2-5, 6-9, and ≥10 inhalations/day exhibited 21 %, 67 %, and 135 % higher exacerbation rates, respectively, in the following 10 months, compared with <2 inhalations/day. Budesonide/formoterol was associated with lower short- and long-term exacerbation risk than formoterol in all reliever-use groups. Conclusions: SABA reliever use is a predictor of short- and long-term exacerbation risk in moderate-to-very-severe COPD patients with a history of exacerbations receiving budesonide/formoterol or formoterol.- [ABSTRACT FROM AUTHOR]

Background: Small airways dysfunction (SAD) contributes to the clinical expression of asthma. The identification of patients who suffer from SAD is important from a clinical perspective, as targeted therapy may improve patients’ well-being and treatment efficacy. Aims: We aimed to realize the first step in the development of a simple small airways dysfunction tool (SADT) that may help to identify asthma patients having SAD. Methods: Asthma patients with and without SAD were interviewed. Patients were selected to participate in this study based on FEF50% and R5-R20 values from spirometry and impulse oscillometry respectively. Results: Ten in depth interviews and two focus groups revealed that patients with and without SAD perceived differences in symptoms and signs, habits and health related issues. For example, patients with SAD reported to wheeze easily, were unable to breathe in deeply, mentioned more symptoms related to bronchial hyperresponsiveness, experienced more pronounced exercise-induced symptoms and more frequently had allergic respiratory symptoms after exposure to cats and birds. Based on these differences, 63 items were retained to be further explored for the SADT. Conclusions: The first step of the development of the SADT tool shows that there are relevant differences in signs and respiratory symptoms between asthma patients with and without SAD. The next step is to test and validate all items in order to retain the most relevant items to create a short and simple tool, which should be useful to identify asthma patients with SAD in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age. Methods: All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis. Results: Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients. Conclusions: We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD. [ABSTRACT FROM AUTHOR]

Background Co-morbidities are common in chronic obstructive pulmonary disease (COPD). We assessed the contribution of common co-morbidities on health related quality of life (HRQoL) among COPD patients. Methods Using both generic (15D) and respiratory-specific (AQ20) instruments, HRQoL was assessed in a hospital based COPD population (N = 739, 64% males, mean age 64 years, SD 7 years) in this observational study with inferential analysis. The prevalence of their co-morbidities was compared with those of 5000 population controls. The patients represented all severity stages of COPD and the patterns of common concomitant disorders differed between patients. Results Co-morbidities such as psychiatric conditions, alcohol abuse, cardiovascular diseases, and diabetes were more common among COPD patients than in age and gender matched controls. Psychiatric conditions and alcohol abuse were the strongest determinants of HRQoL in COPD and could be detected by both 15D (Odds Ratio 4.7 and 2.3 respectively) and AQ20 (OR 2.0 and 3.0) instruments. Compared to respiratory specific AQ20, generic 15D was more sensitive to the effects of comorbidities while AQ20 was slightly more sensitive for the low FEV1. FEV1 was a strong determinant of HRQoL only at more severe stages of disease (FEV1 < 40% of predicted). Poor HRQoL also predicted death during the next five years. Conclusions The results suggest that co-morbidities may impair HRQoL at an early stage of the disease, while bronchial obstruction becomes a significant determinant of HRQoL only in severe COPD. [ABSTRACT FROM AUTHOR]

Table of contents WORKSHOP 4: Challenging clinical scenarios (CS01–CS06) CS01 Bullous lesions in two children: solitary mastocytoma S. Tolga Yavuz, Ozan Koc, Ali Gungor, Faysal Gok CS02 Multi-System Allergy (MSA) of cystic fibrosis: our institutional experience Jessica Hawley, Christopher O’Brien, Matthew Thomas, Malcolm Brodlie, Louise Michaelis CS03 Cold urticaria in pediatric age: an invisible cause for severe reactions Inês Mota, Ângela Gaspar, Susana Piedade, Graça Sampaio, José Geraldo Dias, Miguel Paiva, Mário Morais-Almeida CS04 Angioedema with C1 inhibitor deficiency in a girl: a challenge diagnosis Cristina Madureira, Tânia Lopes, Susana Lopes, Filipa Almeida, Alexandra Sequeira, Fernanda Carvalho, José Oliveira CS05 A child with unusual multiple organ allergy disease: what is the primer? Fabienne Gay-Crosier CS06 A case of uncontrolled asthma in a 6-year-old patient Ioana-Valentina Nenciu, Andreia Florina Nita, Alexandru Ulmeanu, Dumitru Oraseanu, Carmen Zapucioiu ORAL ABSTRACT SESSION 1: Food allergy (OP01–OP06) OP01 Food protein-induced enterocolitis syndrome: oral food challenge outcomes for tolerance evaluation in a Pediatric Hospital Adrianna Machinena, Olga Domínguez Sánchez, Montserrat Alvaro Lozano, Rosa Jimenez Feijoo, Jaime Lozano Blasco, Mònica Piquer Gibert, Mª Teresa Giner Muñoz, Marcia Dias da Costa, Ana Maria Plaza Martín OP02 Characteristics of infants with food protein-induced enterocolitis syndrome and allergic proctocolitis Ebru Arik Yilmaz, Özlem Cavkaytar, Betul Buyuktiryaki, Ozge Soyer, Cansin Sackesen OP03 The clinical and immunological outcomes after consumption of baked egg by 1–5 year old egg allergic children: results of a randomised controlled trial MerrynNetting, Adaweyah El-Merhibi, Michael Gold, PatrickQuinn, IrmeliPenttila, Maria Makrides OP04 Oral immunotherapy for treatment of egg allergy using low allergenic, hydrolysed egg Stavroula Giavi, Antonella Muraro, Roger Lauener, Annick Mercenier, Eugen Bersuch, Isabella M. Montagner, Maria Passioti, Nicolò Celegato, Selina Summermatter, Sophie Nutten, Tristan Bourdeau, Yvonne M. Vissers, Nikolaos G. Papadopoulos OP05 Chemical modification of a peanut extract results in an increased safety profile while maintaining efficacy Hanneke van der Kleij, Hans Warmenhoven, Ronald van Ree, Raymond Pieters, Dirk Jan Opstelten, Hans van Schijndel, Joost Smit OP06 Administration of the yellow fever vaccine in egg allergic children Roisin Fitzsimons, Victoria Timms, George Du Toit ORAL ABSTRACT SESSION 2: Asthma (OP07–OP12) OP07 Previous exacerbation is the most important risk factor for future exacerbations in school-age children with asthma S. Tolga Yavuz, Guven Kaya, Mustafa Gulec, Mehmet Saldir, Osman Sener, Faysal Gok OP08 Comparative study of degree of severity and laboratory changes between asthmatic children using different acupuncture modalities Nagwa Hassan, Hala Shaaban, Hazem El-Hariri, Ahmed Kamel Inas E. Mahfouz OP09 The concentration of exhaled carbon monoxide in asthmatic children with different controlled stadium Papp Gabor, Biro Gabor, Kovacs Csaba OP10 Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomised clinical trial Bo Chawes, Klaus Bønnelykke, Jakob Stokholm, Lene Heickendorff, Susanne Brix, Morten Rasmussen, Hans Bisgaard OP11 Lung function development in childhood Henrik Wegener Hallas, Bo Chawes, Lambang Arianto, Hans Bisgaard OP12 Is the effect of maternal and paternal asthma different in female and male children before puberty? Maike Pincus, Thomas Keil, Andreas Reich, Ulrich Wahn, Susanne Lau, Linus Grabenhenrich ORAL ABSTRACT SESSION 3: Epidemiology—genetics (OP13–OP18) OP13 Lifestyle is associated with incidence and category of allergen sensitisation: the ALADDIN birth cohort Sara Fagerstedt, Helena Marell Hesla, Emelie Johansson, Helen Rosenlund, Axel Mie, Annika Scheynius, Johan Alm OP15 Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance Jorge Esparza-Gordillo, Anja Matanovic, Ingo Marenholz, Anja Bauerfeind, Klaus Rohde, Katja Nemat, Min-Ae Lee-Kirsch, Magnus Nordenskjöld, Marten C. G. Winge, Thomas Keil, Renate Krüger, Susanne Lau, Kirsten Beyer, Birgit Kalb, Bodo Niggemann, Norbert Hübner, Heather J. Cordell, Maria Bradley, Young-Ae Lee OP16 Allergic multimorbidity of asthma, rhinitis and eczema in the first 2 decades of the German MAS birth cohort Thomas Keil, Hannah Gough, Linus Grabenhenrich, Dirk Schramm, Andreas Reich, John Beschorner, Antje Schuster, Carl-Peter Bauer, Johannes Forster, Fred Zepp, Young-Ae Lee, Renate Bergmann, Karl Bergmann, Ulrich Wahn, Susanne Lau OP17 Childhood anaphylaxis: a growing concern Filipe Benito Garcia, Inês Mota, Susana Piedade, Ângela Gaspar, Natacha Santos, Helena Pité, Mário Morais-Almeida OP18 Indoor exposure to molds and dampness in infancy and its association to persistent atopic dermatitis in school age. Results from the Greek ISAAC II study Athina Papadopoulou, Despina Mermiri, Elpida Xatziagorou, Ioannis Tsanakas, Stavroula Lampidi, Kostas Priftis ORAL ABSTRACT SESSION 4: Pediatric rhinitis—immunotherapy (OP19–OP24) OP19 Associations between residential greenness and childhood allergic rhinitis and aeroallergen sensitisation in seven birth cohorts Elaine Fuertes, Iana Markevych, Gayan Bowatte, Olena Gruzieva, Ulrike Gehring, Allan Becker, Dietrich Berdel, Michael Brauer, Chris Carlsten, Barbara Hoffmann, Anita Kozyrskyj, Caroline Lodge, Göran Pershagen, Alet Wijga, Heinrich Joachim OP20 Full symptom control in pediatric patients with allergic rhinitis and asthma: results of a 2-year sublingual allergen immunotherapy study Zorica Zivkovic, Ivana Djuric-Filipovic, Jasmina Jocić-Stevanovic, Snežana Zivanovic OP21 Nasal epithelium of different ages of atopic subjects present increased levels of oxidative stress and increased cell cytotoxicity upon rhinovirus infection Styliani Taka, Dimitra Kokkinou, Aliki Papakonstantinou, Panagiota Stefanopoulou, Anastasia Georgountzou, Paraskevi Maggina, Sofia Stamataki, Vassiliki Papaevanggelou, Evangelos Andreakos, Nikolaos G. Papadopoulos OP22 Cluster subcutaneous immunotherapy schedule: tolerability profile in children Monica Piquer Gibert, Montserrat Alvaro Lozano, Jaime Lozano Blasco, Olga Domínguez Sánchez, Rosa Jiménez Feijoo, Marcia Dias da Costa, Mª Teresa Giner Muñoz, Adriana Machinena Spera, Ana Maria Plaza Martín OP23 Rhinitis as a risk factor for asthma severity in 11-year old children: population-based cohort study Matea Deliu, Danielle Belgrave, Angela Simpson, Adnan Custovic OP24 The Global Lung Function Initiative equations in airway obstruction evaluation of asthmatic children João Gaspar Marques, Pedro Carreiro-Martins, Joana Belo, Sara Serranho, Isabel Peralta, Nuno Neuparth, Paula Leiria-Pinto POSTER DISCUSSION SESSION 1: Food allergy (PD01–PD05) PD01 Allergen-specific humoral and cellular responses in children who fail egg oral immunotherapy due to allergic reactions Marta Vazquez-Ortiz, Mariona Pascal, Ana Maria Plaza, Manel Juan PD02 FoxP3 epigenetic features in children with cow milk allergy Lorella Paparo, Rita Nocerino, Rosita Aitoro, Ilaria Langella, Antonio Amoroso, Alessia Amoroso, Carmen Di Scala, Roberto Berni Canani PD04 Combined milk and egg allergy in early childhood: let them eat cake? Santanu Maity, Giuseppina Rotiroti, Minal Gandhi PD05 Introduction of complementary foods in relation to allergy and gut microbiota in farm and non-farm children Karin Jonsson, Annika Ljung, Bill Hesselmar, Ingegerd Adlerbert, Hilde Brekke, Susanne Johansen, Agnes Wold, Ann-Sofie Sandberg POSTER DISCUSSION SESSION 2: Asthma and wheeze (PD06–PD16) PD06 The association between asthma and exhaled nitric oxide is influenced by genetics and sensitisation Björn Nordlund, Cecilia Lundholm, Villhelmina Ullemar, Marianne van Hage, Anne Örtqvist, Catarina Almqvist PD09 Prevalence patterns of infant wheeze across Europe Anna Selby, Kate Grimshaw, Thomas Keil, Linus Grabenhenrich, Michael Clausen, Ruta Dubakiene, Alessandro Fiocchi, Marek Kowalski, Nikos Papadopoulos, Marta Reche, Sigurveig Sigurdardottir, Aline Sprikkleman, Paraskevi Xepapadaki, Clare Mills, Kirsten Beyer, Graham Roberts PD10 Epidemiologic changes in recurrent wheezing infants Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Carolina Dela Bianca, Carolina Aranda, Nelson Augusto Rosário, Dirceu Solé, Javier Mallol, Luis García Marcos PD13 A single nucleotide polymorphism in the GLCCI1 gene is associated with response to asthma treatment in children IvanaBanic, Matija Rijavec, Davor Plavec, Peter Korosec, Mirjana Turkalj PD14 Pollen induced asthma: Could small molecules in pollen exacerbate the protein-mediated allergic response? Alen Bozicevic, Maria De Mieri, Matthias Hamburger PD15 A qualitative study to understand how we can empower teenagers to better self-manage their asthma Simone Holley, Ruth Morris, Frances Mitchell, Rebecca Knibb, Susan Latter, Christina Liossi, Graham Roberts PD16 Polymorphism of endothelial nitric oxide synthase (eNOS) gene among Egyptian children with bronchial asthma Mostafa M. M. Hassan POSTER DISCUSSION SESSION 3: Mechanisms—Epidemiology (PD17–PD21) PD17 Pregnancy outcomes in relation to development of allergy in a Swedish birth cohort Malin Barman, Anna Sandin, Agnes Wold, Ann-Sofie Sandberg PD18 Evolution of the IgE response to house dust mite molecules in childhood Daniela Posa, Serena Perna, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, Ulrich Wahn, Thomas Keil, Susanne Lau, Kuan-Wei Chen, Yvonne Resch, Susanne Vrtala, Rudolf Valenta, Paolo Maria Matricardi PD19 Antibody recognition of nsLTP-molecules as antigens but not as allergens in the German-MAS birth cohort Olympia Tsilochristou, Alexander Rohrbach, Antonio Cappella, Stephanie Hofmaier, Laura Hatzler, Carl-Peter Bauer, Ute Hoffmann, Johannes Forster, Fred Zepp, Antje Schuster, RaffaeleD’Amelio, Ulrich Wahn, Thomas Keil, Susanne Lau, Paolo Maria Matricardi PD20 Early life colonization with Lactobacilli and Staphylococcus aureus oppositely associates with the maturation and activation of FOXP3+ CD4 T-cells Sophia Björkander, Maria A. Johansson, Gintare Lasaviciute, Eva Sverremark-Ekström PD21 Genome-wide meta-analysis identifies 7 susceptibility loci involved in the atopic march Ingo Marenholz, Jorge Esparza-Gordillo, Franz Rüschendorf, Anja Bauerfeind, David P. Strachan, Ben D. Spycher, Hansjörg Baurecht, Patricia Margaritte-Jeannin, Annika Sääf, Marjan Kerkhof, Markus Ege, Svetlana Baltic, Melanie C Matheson, Jin Li, Sven Michel, Wei Q. Ang, Wendy McArdle, Andreas Arnold, Georg Homuth, Florence Demenais, Emmanuelle Bouzigon, Cilla Söderhäll, Göran Pershagen, Johan C. de Jongste, Dirkje S Postma, Charlotte Braun-Fahrländer, Elisabeth Horak, Ludmila M. Ogorodova, Valery P. Puzyrev, Elena Yu Bragina, Thomas J Hudson, Charles Morin, David L Duffy, Guy B Marks, Colin F Robertson, Grant W Montgomery, Bill Musk, Philip J Thompson, Nicholas G. Martin, Alan James, Patrick Sleiman, Elina Toskala, Elke Rodriguez, Regina Fölster-Holst, Andre Franke, Wolfgang Lieb, Christian Gieger, Andrea Heinzmann, Ernst Rietschel, Thomas Keil, Sven Cichon, Markus M Nöthen, Craig E Pennell, Peter D Sly, Carsten O Schmidt, Anja Matanovic, Valentin Schneider, Matthias Heinig, Norbert Hübner, Patrick G. Holt, Susanne Lau, Michael Kabesch, Stefan Weidinger, Hakon Hakonarson, Manuel AR Ferreira, Catherine Laprise, Maxim B. Freidin, Jon Genuneit, Gerard H Koppelman, Erik Melén, Marie-Hélène Dizier, A. John Henderson, Young Ae Lee POSTER DISCUSSION SESSION 4: Food allergy—Anaphylaxis (PD22–PD26) PD22 Atopy patch test in food protein induced enterocolitis caused by solid food Purificacion González-Delgado, Esther Caparrós, Fernando Clemente, Begoña Cueva, Victoria M. Moreno, Jose Luis Carretero, Javier Fernández PD23 Watermelon allergy: a novel presentation Kate Swan, George Du Toit PD24 A pilot study evaluating the usefulness of a guideline template for managing milk allergy in primary care Mudiyur Gopi, Tim Smith, Edara Ramesh, Arun Sadasivam PD26 Efficacy and safety of cow’s milk oral immunotherapy protocol Inês Mota, Filipe Benito Garcia, Susana Piedade, Angela Gaspar, Graça Sampaio, Cristina Arêde, Luís Miguel Borrego, Graça Pires, Cristina Santa-Marta, Mário Morais-Almeida POSTER DISCUSSION SESSION 5: Prevention and treatment—Allergy (PD27–PD36) PD27 Allergy-protection by the lactic acid bacterium Lactococcus lactis G121: mode-of-action as revealed in a murine model of experimental allergy Stephanie Brand, Karina Stein, Holger Heine, Marion Kauth PD29 The relationship between quality of life and morning salivary cortisol after acute bronchiolitis in infancy Leif Bjarte Rolfsjord, Egil Bakkeheim, Johan Alm, Håvard Ove Skjerven, Kai-Håkon Carlsen, Jon Olav Hunderi, Teresa Løvold Berents, Petter Mowinckel, Karin C. Lødrup Carlsen PD30 Randomised trial of the efficacy of MP29-02* compared with fluticasone propionate nasal spray in children aged ≥6 years to <12 years with allergic rhinitis Ulrich Wahn, Ullrich Munzel, William Berger PD31 10 mg of oral bilastine in 2 to 11 years old children has similar exposure to the adult therapeutic dose (20 mg) Ulrich Wahn, Román Valiente, Valvanera Vozmediano, John C. Lukas, Mónica Rodríguez PD33 Daily symptoms, nocturnal symptoms, activity limitations and reliever therapies during the three steps of IOEASMA programme: a comparison Sebastiano Guarnaccia, Luigi Vitale, Ada Pluda, Emanuele D’Agata, Denise Colombo, Stefano Felici, Valeria Gretter, Susanna Facchetti, Gaia Pecorelli, Cristina Quecchia PD34 Sensitisation to an inert aeroallergen in weaning rats and longstanding disease, in a sensitisation-tolerant and easily tolerisable rodent strain George Guibas, Evangelia Spandou, Spyridon Megremis, Peter West, Nikolaos Papadopoulos PD35 Bacterial and fungi exposure in school and allergic sensitisation in children João Cavaleiro Rufo, Joana Madureira, Inês Paciência, Lívia Aguiar, Patrícia Padrão, Mariana Pinto, Luís Delgado, Pedro Moreira, João Paulo Teixeira, Eduardo Oliveira Fernandes, André Moreira PD36 Comparative study of allergy rhinitis between two populations: children vs. adults Adriana Izquierdo Dominguez, Antonio Valero, Joaquim Mullol, Alfonso Del Cuvillo, Javier Montoro, Ignacio Jauregui, Joan Bartra, Ignacio Davila, Marta Ferrer, Joaquin Sastre POSTER VIEWING SESSION 1: Inflammation—Genetics—Immunology—Dermatology (PP01–PP09) PP01 Immune profile in late pregnancy: immunological markers in atopic asthmaticwomen as risk factors for atopy in the progeny Catarina Martins, Jorge Lima, Maria José Leandro, Glória Nunes, Jorge Cunha Branco, Hélder Trindade, Luis Miguel Borrego PP02 The impact of neonatal sepsis on development of allergic diseases Secil Conkar, Mehtap Kilic, Canan Aygun, Recep Sancak PP03 Clinical overview of selective IgE deficiency in childhood Athina Papadopoulou, Eleni Tagalaki, Lambros Banos, Anna Vlachou, Fotini Giannoula, Despina Mermiri PP04 Inverse relationship between serum 25(ΟΗ) vitamin D3 and total IgE in children and adolescence Athina Papadopoulou, Stavroula Lampidi, Marina Pavlakou, Maria Kryoni, Kostas Makris PP05 PP06 PP07 Asthma control questionnaire and specific IgE in children Snezhina Lazova, Guergana Petrova, Dimitrinka Miteva, Penka Perenovska PP08 Features of chronic urticaria of adolescents Aliya Klyucharova, Olesya Skorohodkina PP09 Cutaneous mastocytosis in children: a clinical analysis of 8 cases in Greece Dimitra Koumaki, Alkisti Manousaki, Maria Agrapidi, Lida Iatridou, Omima Eruk, Konstantinos Myridakis, Emmanouil Manousakis, Vasiliki Koumaki POSTER VIEWING SESSION 2: Food allergy—Anaphylaxis (PP10–PP47) PP10 Prognostic factors in egg allergy Maria Dimou, Maria Ingemansson, Gunilla Hedlin PP11 Evaluation of the efficacy of an amino acid-based formula in infants who are intolerant to extensively hydrolysed protein formula Nitida Pastor, Delphine de Boissieu, Jon Vanderhoof, Nancy Moore, Kaitlin Maditz PP12 Anaphylaxis and epinephrine auto-injector use: a survey of pediatric trainees Adeli Mehdi, Shaza Elhassan, Carolin Beck, Ahmed Al-Hammadi PP13 Anaphylaxis in children: acute management in the Emergency Department Ioana Maris, Ronan O’Sullivan, Jonathan Hourihane, PP14 Understanding Cumbrian schools preparedness in managing children at risk of anaphylaxis in order to provide training and support which will create healthy and safe environments for children with allergies George Raptis, Louise Michaelis PP15 A new valid and reliable parent and child questionnaire to measure the impact of food protein enterocolitis syndrome on children: the FPIES Quality of Life Questionnaire (FPIESQL), Parent and Child Short Form Audrey DunnGalvin, Matthew Greenhawt, Carina Venter, Jonathan Hourihane PP16 An in-depth case study investigation of the experiences of teenagers and young adults in growing up and living with food allergy with emphasis on coping, management and risk, support, and social and self-identity Evelyn O’Regan, Duncan Cronin, Jonathan Hourihane, Anna O’Reilly, Audrey DunnGalvin PP17 Cow’s milk protein allergy in Constantine. A retrospective study of 62 cases between 1996 and 2013 Foued Abdelaziz, Dounia Khelifi-Touhami, Nihad Selim, Tahar Khelifi-Touhami PP18 PP19 Cow’s milk and egg oral immunotherapy in children older than 5 years Pablo Merida, Ana Mª Plaza, Juan Heber Castellanos, Adrianna Machinena, Montserrat Alvaro Lozano, Jaime Lozano, Olga Dominguez, Monica Piquer, Rosa Jimenez, Mª Teresa Giner PP20 Professionals’ awareness of management of Cow’s Milk Protein Allergy (CMPA) in North Wales Hospitals Konstantinos Kakleas, Manohar Joishy, Wendmu Maskele, Huw R. Jenkins PP21 PP22 Anaphylaxis: the great unknown for teachers. Presentation of a protocol for schools Mercedes Escarrer, Agustín Madroñero, Maria Teresa Guerra, Juan Carlos Julia, Juan Carlos Cerda, Javier Contreras, Eulalia Tauler, Maria Jesus Vidorreta, Ana Rojo, Silvia Del Valle PP23 Challenges facing children with food allergies and their parents in out of school activity sectors Niamh Flynn PP24 A review of food challenges at a Regional Irish Centre Gary Foley, Carol Harmon, John Fitzsimons PP25 The use of epinephrine in infants with anaphylaxis Krasimira Baynova, Ávila Maria Del Robledo, Labella Marina PP26 PP27 PP28 Mother’s psychological state predicts the expression of symptoms in food allergic children Aaron Cortes, Alicia Sciaraffia, Angela Castillo PP29 The correlation between sIgE towards tree nuts and birch pollen in a Danish Pediatric Allergy Clinic Nanna Juel-Berg, Kirsten Skamstrup Hansen, Lars Kærgaard Poulsen PP30 Food allergy in children: evaluation of parents’ use of online social media Andreia Florina Nita, Ioana Valentina Nenciu, Adina Lazar, Dumitru Oraseanu PP31 The impact of food allergy on quality of life: FAQLQ questionnaire Rita Aguiar, Anabela Lopes, Maria J. Paes, Amélia S. Santos, M. A. Pereira-Barbosa PP32 An unexpected cause of anaphylaxis: potato Hatice Eke Gungor, Salih Uytun, Umit Murat Sahiner, Yasemin Altuner Torun PP33 Is it clinical phenotype of allergic diseases determined by sensitisation to food? Mirjana Zivanovic, Marina Atanasković-Marković PP34 PP35 Prescribing adrenaline auto-injectors in children in 2014: the data from regional pediatricians Tina Vesel, Mihaela Nahtigal, Andreja Obermayer-Temlin, Eva Šoster Križnik, Mirjana Maslar, Ruben Bizjak, Marjeta Tomšič-Matic, Sonja Posega-Devetak, Maja Skerbinjek-Kavalar, Mateja Predalič, Tadej Avčin PP36 Who should have an adrenaline autoinjector? Adherence to the European and French guidelines among 121 allergists from the Allergy Vigilance Network Guillaume Pouessel, Etienne Beaudouin, Anne M. Moneret-Vautrin, Antoine Deschildre, Allergy Vigilance Network PP37 Anaphylaxis by Anacardium Occidentale Marta Viñas, Bartolomé Borja, Nora Hernández, Mª José Castillo, Adriana Izquierdo, Marcel Ibero PP38 Anaphylaxis with honey in a child S. Tolga Yavuz, Ali Gungor, Betul Buyuktiryaki, Ozan Koc, Can Naci Kocabas, Faysal Gok PP39 Evaluation of courses adopted to children on prevention, recognition and management of anaphylaxis Tina Vesel, Mihaela Nahtigal PP40 Symptomatic dust mites and shrimp allergy: three pediatric case reports Filipa Almeida, Susana Lopes, Cristina Madureira, Tânia Lopes, Fernanda Carvalho PP41 Poor identification rates of nuts by high risk individuals: a call for improved education and support for families Camille Heming, Emily Garrett, Adam Blackstock, Santanu Maity, Rahul Chodhari PP42 DAFALL: database of food allergies in the Czech Republic Simona Belohlavkova, Eliska Kopelentova, Petr Visek, Ivana Setinova, Ivana Svarcova PP43 Serological cross-reactivity between grass and wheat is not only caused by profilins and CCDs Sigrid Sjölander, Nora Nilsson, Malin Berthold, Helena Ekoff, Gunilla Hedlin, Magnus Borres, Caroline Nilsson PP44 Oil body associated proteins in children with nuts allergy. Allergens to consider in IgE-mediated nuts allergy Loreto González Domínguez, Cristina Muñoz Archidona, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire PP45 PP46 Protective effect of helicobacter pylori infection against food allergy in children Olga Vrani, Antigone Mavroudi, Maria Fotoulaki, Maria Emporiadou, Kleomenis Spiroglou, Ioannis Xinias PP47 Anaphylaxis pathway: A road tryp-tase to success? Helyeh A. Sadreddini, Mia Warnes, Donna Traves POSTER VIEWING SESSION 3: Miscellaneous (PP48–PP58) PP48 Surveillance study on safety of SLIT in pediatric population Ivana Djuric-Filipovic, Zorica Zivkovic, Snežana Zivanovic, Gordana Kostić, Đorđe Filipovic PP49 Efficacy and safety of mixed mite subcutaneous immunotherapy among allergic rhinitis patients in the Northeastern Thailand Sawapon Sittisomwong, Siripong Sittisomwong PP50 Effect of inhaled beclomethasone or placebo on brain stem activity in a patient chronically treated with steroids: preliminary report Zygmunt Podolec, Marcin Hartel, Daria Panek, Magdalena Podolec-Rubiś, Tomasz Banasik PP51 Sensitisation to aeroallergens in patients with allergic rhinitis, asthma and atopic dermatitis in Shiraz, Southwestern Iran Elham Abbasi, Mozhgan Moghtaderi PP52 Referring a child for allergy test: how appropriate are we? Phani Sanneerappa, Alina Deliu, Moosa Kutty, Nagabathula Ramesh PP53 EBV lymphoproliferative disease and cardiac lymphoma in a STK4 deficient patient Roya Sherkat, Mohammad Reza Sabri, Bahar Dehghan, Hamid Bigdelian, Nahid Raeesi, Mino Afshar, Hamid Rahimi, Christoph Klein PP54 A case study: the effect of massive honeybees attack on various body parameters atopic girl including allergy Mohemid Al-Jebouri PP55 The role of TLR9, NLRP3 and proIL-1β in activation of antiviral innate immunity Oxana A. Svitich, Daria O. Zubacheva, Dmitrii A. Potemkin, Ludmila V. Gankovskaya, Vitalii V. Zverev PP56 Overnight pulse oximetry, as a screening tool to diagnose obstructive sleep apnoea. How effective is it? Phani Sanneerappa, Elaine OB Doyle, Paul Gallagher, Nagabathula Ramesh PP57 The presentation and management of acute urticaria and allergic reactions in children in a multi-ethnic, inner city Emergency Department (ED) Sherine Dewlett, Kin Man, Minal Gandhi, James Pocock, Anna Gerrardhughes PP58 Food allergens responsible for delayed-type sensitisation in atopy patch test in children diagnosed with autism spectrum disorder Jolanta Wasilewska, Maciej Kaczmarski, Dariusz Lebensztejn POSTER VIEWING SESSION 4: Asthma—Rhinitis (PP59–PP87) PP59 Systematic review of incense as a trigger factor for asthma Chandramani Thuraisingham, Davendralingam Sinniah PP60 Increased risks of mood and anxiety disorders in children with asthma Yue Chen, Xiaomei Mei PP61 PP62 Asthma Control Test (ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) association in children Sebnem Ozdogan, Pinar Karadeniz, Durdugul Ayyildiz-Emecen, Ummuhan Oncul PP63 Seasonal and gender variations in vitamin D levels in children with asthma and its association with pulmonary function tests Sebnem Ozdogan, Gizem Sari, Sabanur Cavdar PP64 Defining treatment response in childhood asthma: rationale and design of the Pharmacogenomics in the Childhood Asthma (PiCA) consortium Niloufar Farzan, Susanne J. Vijverberg, Colin J. Palmer, Kelan G. Tantisira, Anke-Hilseon Maitland-van der Zee behalf of the PiCA consortium PP65 Prevalence of asthma and allergic disease in patients with inflammatory disease compared to celiac disease Fatma Yavuzyilmaz, Sebnem Ozdogan, Nafiye Urganci, Merve Usta PP66 A severe case with cystic fibrosis (CF) asthma Mehmet Hoxha, Maksim Basho PP67 Severe asthma exacerbation complicated with pneumothorax in a child with uncontrolled asthma due to poor treatment compliance Ioana Valentina Nenciu, Andreia Florina Nita, Adina Lazar, Alexandru Ulmeanu, Carmen Zapucioiu, Dumitru Oraseanu PP68 Evaluation of the Pediatric Quality of Life inventory (PedsQL) asthma module among low income asthmatic children and adolescents in Sao Paolo, Brazil Gustavo F. Wandalsen, Fernanda Monteiro, Dirceu Solé PP69 Early initiation of specific immunotherapy in asthma patients leads to higher benefits Blerta Lame, Eris Mesonjesi, Arjeta Sherri PP70 Treatment resistant asthma and rhinosinusitis with recurrent pulmonary infections. Is it primary ciliary dyskinesia? Alkerta Ibranji, Laert Gjati, Gjustina Loloci, Ardii Bardhi PP71 The comparison of sensitisation to animal allergens in children- and adult- onset patients with asthma Behnam Moghtaderi, Shirin Farjadian, Dorna Eghtedari PP72 Characterisation of children less than five years with wheezing episodes in Cali, Colombia Manuela Olaya, Laura Del Mar Vasquez, Luis Fernando Ramirez, Carlos Daniel Serrano PP73 Evaluation of the patients with recurrent croup Belgin Usta Guc, Suna Asilsoy, Fulya Ozer PP74 Obesity in adolescence compromising the asthma control Guergana Petrova, Sylvia Shopova, Vera Papochieva, Snezhina Lazova, Dimitrinka Miteva, Penka Perenovska PP75 Sleep behavior in children with persistent allergic rhinitis Gustavo F. Wandalsen, Jessica Loekmanwidjaja, Márcia Mallozi, Dirceu Solé PP76 Randomised trial of the safety of MP29-02* compared with fluticasone propionate nasal spray in children aged ≥4 years to <12 years with allergic rhinitis William Berger, Ulrich Wahn, Paul Ratner, Daniel Soteres PP77 Safety and tolerability evaluation of bilastine 10 mg in children from 2 to 11 years of age with allergic rhinoconjunctivitis or urticaria Zoltán Novák, Anahí Yáñez, Kiss Ildikó, Piotr Kuna, Miguel Tortajada, Román Valiente, the Bilastine Pediatric Safety Study Group PP78 Sensitisation to Alternaria alternata: Is it a risk factor for severe rhinitis? Susana Lopes, Filipa Almeida, Tânia Lopes, Cristina Madureira, José Oliveira, Fernanda Carvalho PP79 Validation of the Patient Benefit Index (PBI) for the assessment of patient-related outcomes in allergic rhinitis in children Julia Feuerhahn, Christine Blome, Meike Hadler, Efstrathios Karagiannis, Anna Langenbruch, Matthias Augustin PP80 Efficacy of sublingual tablet of house dust mite allergen extracts in adolescents with house dust mite-associated allergic rhinitis Michel Roux, Shinji Kakudo, Efstrathios Karagiannis, Robert K. Zeldin PP81 Lung function improvement in a child treated with omalizumab for bronchial asthma Anna Sokolova, Tiago Milheiro Silva PP82 How to treat a child suffering from asthma, allergic rhinitis, allergy to peanuts and diabetes at the same time? Snezana S. Zivanovic, Vesna Cvetkovic, Ivana Nikolic, Sonja J. Zivanovic PP83 Nitric oxide in exhaled air in the relationship of the degree of sensitisation to aeroallergens Snezana S. Zivanovic, Ljiljana Saranac, Ivana Nikolic, Sonja J. Zivanovic, Zorica Zivkovic PP84 Clinical basis of diagnostic errors in pediatric asthma Zoia Nesterenko PP85 PP86 Childhood asthma control in Serbia and organised Asthma Educational Intervention (AEI) Snezana Radic, Branislava Milenkovic, Spomenka Smiljanic, Milka Micic-Stanijevic, Olivera Calovic PP87 Experience from a group of adolescents with severe allergic asthma treated with Omalizumab Anne Marie Bro Hofbauer, Lone Agertoft THEMATIC POSTER SESSION 1: Prevention and Treatment—Epidemiology (TP01–TP18) TP01 A cost effective primary school asthma education program: pilot study from inner London schools Lucy Everson, Jessica Kearney, Jonny Coppel, Simon Braithwaite, Rahul Chodhari TP02 The prevalence of allergic diseases among 14–15 years old adolescents in two Danish birth cohorts 14 years apart Elisabeth S. Christiansen, Henrik Fomsgaard Kjaer, Esben Eller, Charlotte G. Mørtz, Susanne Halken TP03 Does pattern of sensitisation to phleum pratense change with age? Is it different in children with allergic rhinitis or asthma? Cristina Román India, Ana Moreira Jorge, Loreto González Domínguez, Cristina Muñoz Archidona, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Juana Jiménez Jiménez, Luis Echeverría Zudaire TP04 Practicalities of prevention of peanut allergy: modelling a national response to LEAP Cathal O’Connor, Jonathan Hourihane TP05 Comparison of the influence of sunflower seed oil and skin care lotion on the skin barrier function of newborns: a randomised controlled trial Varvara Kanti, Lena Lünnemann, Günther Malise, Laine Ludriksone, Andrea Stroux, Wolfgang Henrich, Michael Abu-Dakn, Ulrike Blume-Peytavi, Natalie Garcia Bartels TP06 The effect of daily skin care on skin barrier properties in infants with dry skin and risk for atopic dermatitis Varvara Kanti, Lena Lünnemann, Laine Ludriksone, Marianne Schario, Andrea Stroux, Ulrike Blume-Peytavi, Natalie Garcia Bartels TP07 Change in sum total aeroallergen skin prick test wheal diameters at 6 months predicts which children will respond to subcutaneous immunotherapy by three years Thorsten Stanley, Nicolien Brandenbarg TP08 Are mobile apps regarding adrenaline auto-injectors accessed by adolescents for support and education in the community? Alia Boardman, Gary McGreevy, Emily Rodger, Katherine Knight, Victoria Timms, Trisha Taylor, Gemma Scanlan, Roisin Fitzsimons TP09 TP10 Prevention of early atopic dermatitis among low-atopy-risk infants by immunoactive prebiotics is not sustained after the first year of life Grüber Christoph, Ulrich Wahn, Margriet van Stuivenberg, Fabio Mosca, Guido Moro, Gaetano Chirico, Christian P. Braegger, Joseph Riedler, Yalcin Yavuz, Günther Boehm TP11 TP12 TP13 Treatment with Omalizumab in a 16-year-old Caucasian girl with refractory solar urticaria Stefania Arasi, Giuseppe Crisafulli, Lucia Caminiti, Federica Porcaro, Giovanni Battista Pajno TP14 Ultra-pure soft water ameliorates skin conditions of adult and child patients with atopic dermatitis Akane Tanaka, Yaei Togawa, Kumiko Oida, Naotomo Kambe, Peter Arkwright, Yosuke Amagai, Naoki Shimojo, Yasunori Sato, Hiroyuki Mochizuki, Hyosun Jang, Saori Ishizaka, Hiroshi Matsuda TP15 Potential adjuvant effect of immunomodulator to improve specific immunotherapy in asthmatic child Wisnu Barlianto, Ery Olivianto, H. M. S. Chandra Kusuma TP16 How can Component Resolved Diagnosis (CRD) influence in Specific Immunotherapy (SIT) prescription, in a Spanish children population Ana Moreira Jorge, Cristina Román India, Loreto González Domínguez, Cristina Muñoz Archidona, Juana Jiménez Jiménez, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Luis Echeverría Zudaire TP17 Mitochondrial dysfunction in food allergy: effects of L. rhamnosus GG in a mice model of peanut allergy Rosita Aitoro, Mariapia Mollica, Roberto Berni Canani, Giovanna Trinchese, Elena Alfano, Antonio Amoroso, Lorella Paparo, Francesco Amato, Claudio Pirozzi, Antonio Calignano, Rosaria Meli TP18 Prediction of atopic diseases in childhood: elevated blood eosinophils in infancy in a high risk birth cohort Siri Rossberg, Kerstin Gerhold, Kurt Zimmermann, Mohammad Zaino, Thomas Geske, Eckard Hamelmann, Susanne Lau THEMATIC POSTER SESSION 2: Food allergy—Anaphylaxis (TP19–TP38) TP19 TP20 TP21 Double-blind provocation tests in non-IgE mediated cow’s milk allergy and the occurrence of placebo reactions Sarah Bogovic, Jochem van den Berg, Chantal Janssen TP22 Gradual introduction of baked egg (BE) in egg allergic patients under 2 years old Angela Claver TP23 Randomised controlled trial of SOTI with raw hen’s egg in children with persistent egg allergy I: safety and efficacy of daily vs. weekly protocols of induction Mª Flor Martin-Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria TP24 Randomised controlled trial of SOTI with raw hen’s egg in children with persistent egg allergy II: a randomised controlled trial to study a safer, more effective and easy to perform maintenance (daily vs. every two days) pattern of egg SOTI Mª Flor Martin-Muñoz, C. Martorell, M. T. Belver, E. Alonso Lebrero, L. Zapatero, V. Fuentes, M. Piqué, A. Plaza, C. Muñoz, A. Martorell, Cristina Blasco, B. Villa, C. Gómez, S. Nevot, J. M. García, L. Echeverria TP25 Determining the safety of baked egg home reintroduction for children with mild egg allergy Brenda DeWitt, Judith Holloway, Donald Hodge TP26 Demographics, investigations and patterns of sensitisation in children with oral allergy syndrome in a London Teaching Hospital Sian Ludman, Merhdad Jafari-Mamaghani, Rosemary Ebling, Adam T. Fox, Gideon Lack, George Du Toit TP27 Airborne peanut challenge in children: allergic reactions are rare Sofia Lovén Björkman, Caroline Nilsson, Natalia Ballardini TP28 The nutty question on Pediatric Wards: to be or “nut” to be? Supriyo Basu, Jenny Hallet, Jyothi Srinivas TP29 TP30 TP31 Allergy education in nursery schools Hazel Stringer, Nicola Jay TP32 Food allergy in the first year of life Tânia Lopes, Cristina Madureira, Filipa Almeida, Susana Lopes, Paula Fonseca, Clara Vieira, Fernanda Carvalho TP33 Prevalence and geographic distribution of oral allergy syndrome in Italian children: a multicenter study Carla Mastrorilli, Carlo Caffarelli, Riccardo Asero, Salvatore Tripodi, Arianna Dondi, Gianpaolo Ricci, Carlotta Povesi Dascola, Elisabetta Calamelli, Francesca Cipriani, Andrea Di Rienzo Businco, Annamaria Bianchi, Paolo Candelotti, Tullio Frediani, Carmen Verga, Paolo Maria Matricardi TP34 Are common standardised allergen extracts used in skin test enough in the diagnosis of nuts allergy? Cristina Muñoz Archidona, Loreto González Domínguez, Ana Moreira Jorge, Sergio Quevedo Teruel, Teresa Bracamonte Bermejo, Miriam Castillo Fernández, Fernando Pineda de la Losa, Luis Ángel Echeverría Zudaire TP35 Evaluation of IgE sensitisation in children with allergic proctocolitis and its relationship to atopic dermatitis Despina Mermiri, Paraskevi Korovessi, Skevi Tiliakou, Evaggelia Tavoulari, Kalliopi-Maria Moraiti, Fotini Giannoula, Athina Papadopoulou TP36 Food allergy in children: are we managing them appropriately in the Emergency Department? Wan Jean Tee, Samir Deiratany, Raymond Seedhoo, Roisin McNamara, Ike Okafor TP37 Importance of oil body associated allergenic proteins in nuts suspected allergy children Loreto González Domínguez, Ana Moreira Jorge, Cristina Muñoz Archidona, Teresa Bracamonte Bermejo, Sergio Quevedo Teruel, Fernando Pineda de la Losa, Miriam Castillo Fernández, Luis Ángel Echeverría Zudaire TP38 Practical application of basophil activation test in children with food allergy Ekaterina Khaleva, Gennady Novic, Natalia Bychkova THEMATIC POSTER SESSION 3: Asthma (TP39–TP57) TP39 Effect of corticosteroid therapy upon serum magnesium level in chronic asthmatic children Amany Abd Al-Aziz, Amany Fatouh, Ayat Motawie, Eman El Bostany, Amr Ibrahim TP40 ADAM33 in Bulgarian children with asthma Guergana Petrova, Dimitrinka Miteva, Snezhina Lazova, Penka Perenovska, Sylvia Andonova, Alexey Savov TP41 TP42 The impact of vitamin D serum levels in asthma and allergic rhinitis Maria Zoto, Marialena Kyriakakou, Paraskevi Xepapadaki, Nikolaos G. Papadopoulos TP43 Life-threatening, first reported, paradoxical bronchospasm after nebulised Salbutamol in a 10 year old child Paraskevi Korovessi, Mariza Vassilopoulou, Athina Balaska, Lambros Banos, Stavroula Kostaridou, Despina Mermiri TP44 TP45 Asthma symptoms in children with treatment for allergic rhinoconjunctivitis Jorien Wartna, Arthur M. Bohnen, Gijs Elshout, David H. J. Pols, Patrick J. E. Bindels Erasmus MC, Rotterdam, The Netherlands TP46 Atopy increased the risk of developing exercise-induced bronchoconstriction in young athletes Sven F. Seys; Ellen Dilissen, Sarah Van der Eycken, An-Sofie Schelpe, Gudrun Marijsse, Thierry Troosters, Vincent Vanbelle, Sven Aertgeerts, Jan L. Ceuppens, Lieven J. Dupont, Koen Peers, Dominique M. Bullens TP47 The effect of higher BMI on risk for asthma and treatment outcome in overweight and obese children Ivana Banic, Sandra Bulat Lokas, Jelena Zivkovic, Boro Nogalo, Iva Mrkic Kobal, Davor Plavec, Mirjana Turkalj TP48 TP49 TP50 TP51 TP52 The impact of a multidisciplinary project intended to change the culture of nebulisers towards pressurised metered dose inhalers Georgeta Oliveira, Katharine Pike, Alda Melo, Tomás Amélia, José Carlos Cidrais Rodrigues, Cristina Serrano, José Manuel Lopes dos Santos, Carla Lopes TP53 TP54 TP55 TP56 Increased asthma control in patients with severe persistent allergic asthma after 12 month of nightly temperature controlled laminar airflow (TLA) Eckard Hamelmann, Uwe Schauer, Karl-Christian Bergmann TP57 THEMATIC POSTER SESSION 4: Drug allergy—Dermatology (TP58–TP77) TP58 Should we proceed directly to provocation challenges to diagnose drug allergy? Our experience says yes Luis Moral, Teresa Toral, Nuria Marco, Beléns García Avilés, Mª Jesús Fuentes, Jesús Garde, Cristina Montahud, Javier Perona, Mª José Forniés TP59 Anaphylaxis to 13-valent pneumococcal vaccine Esozia Arroabarren, Marta Anda, Maria Luisa Sanz, Maria Teresa Lizaso, Candida Arregui TP60 Intrapartum antibiotic exposure for treatment of group B streptococcus was not associated with the development of penicillin allergy in children Sara May, Martha Hartz, Avni Joshi, Miguel A. Park TP61 Evaluation of suspected drug hypersensitivity reactions in 169 children referred to the General Hospital Sonja Posega Devetak, Tina Vesel, Anja Koren Jeverica, Tadej Avčin TP62 Drug provocation testing: experience of a tertiary hospital Leonor Castro, Carolina Gouveia, Ana Carvalho Marques, Antonio Jorge Cabral TP63 Perioperative anaphylaxis: a growing concern in pediatric population Luis Amaral, Fabrícia Carolino, Eunice Castro, Madalena Passos, Josefina R. Cernadas TP64 Raising awareness of hypersensitivity to non-steroidal anti-inflammatory drugs in the pediatric age Fabrícia Carolino, Luís Amaral, Eunice Dias de Castro, Josefina R. Cernadas TP65 Perioperative anaphylaxis in young children: how to confirm the suspicion Josefina R. Cernadas, Fabrícia Carolino, Luís Amaral, Fernando Pineda, Armanda Gomes TP66 A case study of a child suspected to be penicillin allergic-digging deeper Katherine Knight, Roisin Fitzsimons, Helen Brough TP67 Prevalence, characteristics and risk factors of hypersensitivity reactions to antibiotics in patients with cystic fibrosis Jobst Röhmel, Carsten Schwarz, Anne Mehl, Philippe Stock, Doris Staab TP68 Antibiotic drug hypersensitivity in cystic fibrosis: A pilot study using cellular allergy tests for diagnostics Jobst Röhmel, Carsten Schwarz, Christine Seib, Doris Staab, Philippe Stock TP69 Oral antibiotics challenges in children Anita Critchlow, Alyson Barber, Nicola Jay TP70 Hypersensitivity reaction to vancomycin: a new successful desensitization protocol Belen Delavalle, Teresa Garriga, Blanca Vilá, Cristina Blasco TP71 TP72 Clinical phenotypes according to FLG gene loss of function mutations in children with atopic dermatitis Francesca Cipriani, Annalisa Astolfi, Costanza Di Chiara, Elisabetta Calamelli, Iria Neri, Annalisa Patrizi, Gianpaolo Ricci TP73 TP74 Urticaria in children: clinical and epidemiological features Katerina Neskorodova, Asya Kudryavtseva TP75 TP76 Acute urticaria at the Pediatrics Emergency Department: is it allergy? Esozia Arroabarren, Jorge Alvarez, Marta Anda, Miriam Palacios, Marta Martinez-Merino, Ibone Vaquero TP77

Background: Inflammation is a key factor in the pathogenesis of respiratory diseases. Early life exposure to microbial agents may have an effect on the development of the immune system and on respiratory health later in life.In the present work we aimed to evaluate the associations between early life microbial exposures, and fractional exhaled nitric oxide (FeNO) at school age.Methods: Endotoxin, extracellular polysaccharides (EPS) and β(1,3)-D-glucan were measured in living room dust collected at 2-3 months of age in homes of participants of three prospective European birth cohorts (LISA, n = 182; PIAMA, n = 244; and INMA, n = 355). Home dampness and pet ownership were periodically reported by the parents through questionnaires. FeNO was measured at age 8 for PIAMA and at age 10/11 for LISA and INMA. Cohort-specific associations between the indoor microbial exposures and FeNO were evaluated using multivariable regression analyses. Estimates were combined using random-effects meta-analyses.Results: FeNO at school age was lower in children exposed to endotoxin at age 2-3 months (β -0.05, 95% confidence interval (CI) -0.10;-0.01) and in children with reported dog ownership during the first two years of life (GM ratio 0.82, CI 0.70-0.96). FeNO was not significantly associated with early life exposure to EPS, β(1,3)-D-glucan, indoor dampness and cat ownership.Conclusion: Early life exposure to bacterial endotoxin and early life dog ownership are associated with lower FeNO at school age. Further studies are needed to confirm our results and to unravel the underlying mechanisms and possible clinical relevance of this finding. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that smoking asthmatics benefit less from corticosteroid treatment than neversmoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment. Methods: We analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a selfmanagement plan (n=64). Results: A total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year. Conclusions: Ex- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response. [ABSTRACT FROM AUTHOR]

Background: Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity. Methods: A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects. Results: The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1. Conclusions: Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings. [ABSTRACT FROM AUTHOR]

Background: Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega genes have been associated with the level of lung function. This study aimed to assess if GSTO SNPs interact with ETS exposure in utero and during adulthood on the level of lung function during adulthood. Methods: We used cross-sectional data of 8,128 genotyped participants from the LifeLines cohort study. Linear regression models (adjusted for age, sex, height, weight, current smoking, ex-smoking and packyears smoked) were used to analyze the associations between in utero, daily and workplace ETS exposure, GSTO SNPs, the interaction between ETS and GSTOs, and level of lung function (FEV1, FEV1/FVC). Since the interactions between ETS and GSTOs may be modified by active tobacco smoking we additionally assessed associations in never and ever smokers separately. A second sample of 5,308 genotyped LifeLines participants was used to verify our initial findings. Results: Daily and workplace ETS exposure was associated with significantly lower FEV1 levels. GSTO SNPs (recessive model) interacted with in utero ETS and were associated with higher levels of FEV1, whereas the interactions with daily and workplace ETS exposure were associated with lower levels of FEV1, effects being more pronounced in never smokers. The interaction of GSTO2 SNP rs156697 with in utero ETS associated with a higher level of FEV1 was significantly replicated in the second sample. Overall, the directions of the interactions of in utero and workplace ETS exposure with the SNPs found in the second (verification) sample were in line with the first sample. Conclusions: GSTO genotypes interact with in utero and adulthood ETS exposure on adult lung function level, but in opposite directions. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of childhood asthma covers a broad spectrum of pathological mechanisms that can lead to similarly presenting clinical symptoms, but may nonetheless require different treatment approaches. Distinct underlying inflammatory patterns are thought to influence responsiveness to standard asthma medication. Methods/design: The purpose of the PACMAN2 study is to identify inflammatory phenotypes that can discriminate uncontrolled childhood asthma from controlled childhood asthma by measures in peripheral blood and exhaled air. PACMAN2 is a nested, case-control follow-up study to the ongoing pharmacy-based "Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects" (PACMAN) study. The original PACMAN cohort consists of children aged 4-12 years with reported use of asthma medication. The PACMAN2 study will be conducted within the larger PACMAN cohort, and will focus on detailed phenotyping of a subset of the PACMAN children. The selected participants will be invited to a follow-up visit in a clinical setting at least six months after their baseline visit based on their adherence to usage of inhaled corticosteroids, their asthma symptoms in the past year, and their age (= 8 years). During the follow-up visit, current and long-term asthma symptoms, medication use, environmental factors, medication adherence and levels of exhaled nitric oxide will be reassessed. The following measures will also be examined: pulmonary function, exhaled volatile organic compounds, as well as inflammatory markers in peripheral blood and blood plasma. Comparative analysis and cluster-analyses will be used to identify markers that differentiate children with uncontrolled asthma despite their use of inhaled corticosteroids (ICS) (cases) from children whose asthma is controlled by the use of ICS (controls). Discussion: Asthmatic children with distinct inflammatory phenotypes may respond differently to antiinflammatory therapy. Therefore, by identifying inflammatory phenotypes in children with the PACMAN2 study, we may greatly impact future personalised treatment strategies, uncover new leads for therapeutic targets and improve the design of future clinical studies in the assessment of the efficacy of novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. Methods: 3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ⩾5, ⩾1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ⩾5 group was used as reference. Results: Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 - 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted '>5 years' showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001). Conclusion: Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline. [ABSTRACT FROM AUTHOR]

Background: Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms. Methods: AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry. Results: Median AWT in airways with an internal diameter of 3.5 mm (AWT3.5) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (p<0.001). In the multivariate analysis only AWT3.5 and emphysema independently explained 31.1%and 9.5%of the variance in FEV1%predicted, respectively, after adjustment for smoking behavior. Conclusions: Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated. Methods: Factors related to the presence of atopy (positive phadiatop) in 1277 mild-to-moderate COPD patients participating in EUROSCOP were analysed using regression analysis. Incidence and remission of respiratory symptoms during 3-year follow-up were analysed using generalised estimating equations models, and association of atopy with lung function decline using linear mixed effects models. Results: Independent predisposing factors associated with the presence of atopy were: male gender (OR: 2.21; 95% CI: 1.47-3.34), overweight/obese (OR: 1.41; 95% CI: 1.04-1.92) and lower age (OR: 0.98; 95% CI: 0.96-0.99). Atopy was associated with a higher prevalence of cough (OR: 1.71; 95% CI: 1.26-2.34) and phlegm (OR: 1.50; 95% CI: 1.10-2.03), but not with lung function levels or FEV1 decline. Atopic COPD patients not treated with budesonide had an increased incidence of cough over time (OR: 1.79, 95% CI: 1.03-3.08, p = 0.038), while those treated with budesonide had increased remission of cough (OR: 1.93, 95% CI: 1.11-3.37, p = 0.02) compared to non-atopic COPD patients. Conclusions: Atopic COPD patients are more likely male, have overweight/obesity and are younger as compared with non-atopic COPD patients. Atopy in COPD is associated with an increased incidence and prevalence of respiratory symptoms. If atopic COPD patients are treated with budesonide, they more often show remission of symptoms compared to non-atopic COPD patients who are treated with budesonide. We recommend including atopy in the diagnostic work-up and management of COPD. [ABSTRACT FROM AUTHOR]

Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by varying degrees of emphysematous lung destruction and small airway disease, each with distinct effects on clinical outcomes. There is little known about how microRNAs contribute specifically to the emphysema phenotype. We examined how genome-wide microRNA expression is altered with regional emphysema severity and how these microRNAs regulate disease-associated gene expression networks. Methods We profiled microRNAs in different regions of the lung with varying degrees of emphysema from 6 smokers with COPD and 2 controls (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified by mean linear intercept. Whole genome microRNA and gene expression data was integrated in the same samples to build co-expression networks. Candidate microRNA were perturbed in human lung fibroblasts in order to validate these networks. Results The expression levels of 63 microRNAs (p < 0.05) were altered with regional emphysema. A subset, including miR-638, miR-30c, and miR-181d, had expression levels that were associated with those of their predicted mRNA targets. Genes correlated with these microRNAs were enriched in pathways associated with emphysema pathophysiology (e.g. oxidative stress and accelerated aging). Inhibition of miR-638 expression in lung fibroblasts led to modulation of these same emphysema-related pathways. Gene targets of miR-638 in these pathways were amongst those negatively correlated with miR-638 expression in emphysema. Conclusions Our findings demonstrate that microRNAs are altered with regional emphysema severity and modulate disease-associated gene expression networks. Furthermore, miR-638 may regulate gene expression pathways related to the oxidative stress response and aging in emphysematous lung tissue and lung fibroblasts. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease consisting of emphysema, small airway obstruction, and/or chronic bronchitis that results in significant loss of lung function over time. Methods: In order to gain insights into the molecular pathways underlying progression of emphysema and explore computational strategies for identifying COPD therapeutics, we profiled gene expression in lung tissue samples obtained from regions within the same lung with varying amounts of emphysematous destruction from smokers with COPD (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified in each tissue sample using the mean linear intercept (Lm) between alveolar walls from micro-CT scans. Results: We identified 127 genes whose expression levels were significantly associated with regional emphysema severity while controlling for gene expression differences between individuals. Genes increasing in expression with increasing emphysematous destruction included those involved in inflammation, such as the B-cell receptor signaling pathway, while genes decreasing in expression were enriched in tissue repair processes, including the transforming growth factor beta (TGFβ) pathway, actin organization, and integrin signaling. We found concordant differential expression of these emphysema severity-associated genes in four cross-sectional studies of COPD. Using the Connectivity Map, we identified GHK as a compound that can reverse the gene-expression signature associated with emphysematous destruction and induce expression patterns consistent with TGFβ pathway activation. Treatment of human fibroblasts with GHK recapitulated TGFβ-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin β1. Furthermore, addition of GHK or TGFβ restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without COPD. Conclusions: These results demonstrate that gene-expression changes associated with regional emphysema severity within an individual's lung can provide insights into emphysema pathogenesis and identify novel therapeutic opportunities for this deadly disease. They also suggest the need for additional studies to examine the mechanisms by which TGFβ and GHK each reverse the gene-expression signature of emphysematous destruction and the effects of this reversal on disease progression. [ABSTRACT FROM AUTHOR]

Background: Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD. Methods: In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations. Results: There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70. Conclusions: Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke, the major risk factor for COPD, is known to activate matrix metalloproteinases in airway epithelium. We investigated whether metalloproteinases, particularly A Disintegrin and Metalloproteinase (ADAM)17, contribute to increased pro-inflammatory epithelial responses with respect to the release of IL-8 and TGF-α, cytokines implicated in COPD pathogenesis.Methods: We studied the effects of cigarette smoke extract (CSE) and metalloproteinase inhibitors on TGF-α and IL-8 release in primary bronchial epithelial cells (PBECs) from COPD patients, healthy smokers and non-smokers.Results: We observed that TGF-α was mainly shed by ADAM17 in PBECs from all groups. Interestingly, IL-8 production occurred independently from ADAM17 and TGF-α shedding, but was significantly inhibited by broad-spectrum metalloproteinase inhibitor TAPI-2. CSE did not induce ADAM17-dependent TGF-α shedding, while it slightly augmented the production of IL-8. This was accompanied by reduced endogenous inhibitor of metalloproteinase (TIMP)-3 levels, suggesting that CSE does not directly but rather indirectly alter activity of ADAM17 through the regulation of its endogenous inhibitor. Furthermore, whereas baseline TGF-α shedding was lower in COPD PBECs, the early release of IL-8 (likely due to its shedding) was higher in PBECs from COPD than healthy smokers. Importantly, this was accompanied by lower TIMP-2 levels in COPD PBECs, while baseline TIMP-3 levels were similar between groups.Conclusions: Our data indicate that IL-8 secretion is regulated independently from ADAM17 activity and TGF-α shedding and that particularly its early release is differentially regulated in PBECs from COPD and healthy smokers. Since TIMP-2-sensitive metalloproteinases could potentially contribute to IL-8 release, these may be interesting targets to further investigate novel therapeutic strategies in COPD. [ABSTRACT FROM AUTHOR]

Background: Macrophages have been implicated in the pathogenesis of COPD. M1 and M2 macrophages constitute subpopulations displaying pro- and anti-inflammatory properties. We hypothesized that smoking cessation affects macrophage heterogeneity in the lung of patients with COPD. Our aim was to study macrophage heterogeneity using the M2-marker CD163 and selected pro- and anti-inflammatory mediators in bronchoalveolar lavage (BAL) fluid and induced sputum from current smokers and ex-smokers with COPD. Methods: 114 COPD patients (72 current smokers; 42 ex-smokers, median smoking cessation 3.5 years) were studied cross-sectionally and underwent sputum induction (M/F 99/15, age 62 ± 8 [mean ± SD] years, 42 (31-55) [median (range)] packyears, post-bronchodilator FEV1 63 ± 9% predicted, no steroids past 6 months). BAL was collected from 71 patients. CD163+; macrophages were quantified in BAL and sputum cytospins. Pro- and antiinflammatory mediators were measured in BAL and sputum supernatants. Results: Ex-smokers with COPD had a higher percentage, but lower number of CD163+; macrophages in BAL than current smokers (83.5% and 68.0%, p = 0.04; 5.6 and 20.1 ⨰104/ml, p = 0.001 respectively). The percentage CD163+; M2 macrophages was higher in BAL compared to sputum (74.0% and 30.3%, p < 0.001). BAL M-CSF levels were higher in smokers than ex-smokers (571 pg/ml and 150 pg/ml, p = 0.001) and correlated with the number of CD163+; BAL macrophages (Rs = 0.38, p = 0.003). No significant differences were found between smokers and exsmokers in the levels of pro-inflammatory (IL-6 and IL-8), and anti-inflammatory (elafin, and Secretory Leukocyte Protease Inhibitor [SLPI]) mediators in BAL and sputum. Conclusions: Our data suggest that smoking cessation partially changes the macrophage polarization in vivo in the periphery of the lung towards an anti-inflammatory phenotype, which is not accompanied by a decrease in inflammatory parameters. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients. Methods: Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models. Results: One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies. Conclusions: This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies. [ABSTRACT FROM AUTHOR]

Background: The definition of "clinical asthma remission" is based on absence of symptoms and use of medication. However, in the majority of these subjects airway inflammation is still present when measured. In the present study we investigated whether "complete asthma remission", additionally defined by the absence of bronchial hyperresponsiveness (BHR) and the presence of a normal lung function, is associated with the absence of airway inflammation. Methods: Patients with a former diagnosis of asthma and a positive histamine provocation test were re-examined to identify subjects with complete asthma remission (no asthma symptoms or medication, PC20 histamine > 32 mg/ml, FEV1 > 90% predicted). Patients with PC20 histamine ≥ 32 mg/ml were defined as current asthmatics and were divided in two groups, i.e. asthmatics with and without BHR to adenosine 5'monophoshate (AMP). Sputum induction was performed 1 week before and 1 hour after AMP provocation. Sputum induction and AMP provocation were previously shown to be sensitive markers of airway inflammation. Results: Seven patients met criteria for complete asthma remission. Twenty-three were current asthmatics, including twelve without hyperresponsiveness to AMP. Subjects with complete asthma remission showed no AMPinduced sputum eosinophilia (median (range) 0.2 (0 - 4.6)% at baseline and 0.2 (0 - 2.6)% after AMP). After AMP, current asthmatics had a significant increase in sputum eosinophils (0.5 (0 - 26.0)% at baseline and 2.6 (0 - 32.0) % after AMP), as had the subgroup of current asthmatics without hyperresponsiveness to AMP (0.2 (0 - 1.8)% at baseline and 1.3 (0 - 6.3)% after AMP). Conclusions: Subjects with complete asthma remission, in contrast to subjects with current asthma, do not respond with eosinophilic inflammation in sputum after AMP provocations. These data lend support to the usefulness of the definition of complete asthma remission. [ABSTRACT FROM AUTHOR]

Background: Smoking is the major etiologic factor in COPD, yet the exact underlying pathogenetic mechanisms have not been elucidated. Since a few years, there is mounting evidence that a specific immune response, partly present as an autoimmune response, contributes to the pathogenesis of COPD. Increased levels of anti-Hep-2 epithelial cell and anti-elastin autoantibodies as well as antibodies against airway epithelial and endothelial cells have been observed in COPD patients. Whether the presence of these autoantibodies contributes to the pathogenesis of COPD is unclear. Methods: To test whether induction of autoantibodies against lung matrix proteins can augment the smokeinduced inflammatory response, we immunized mice with a mixture of the lung extracellular matrix (ECM) proteins elastin, collagen, and decorin and exposed them to cigarette smoke for 3 or 6 months. To evaluate whether the immunization was successful, the presence of specific antibodies was assessed in serum, and presence of specific antibody producing cells in spleen and lung homogenates. In addition, the presence of inflammatory cells and cytokines was assessed in lung tissue and emphysema development was evaluated by measuring the mean linear intercept. Results: We demonstrated that both ECM immunization and smoke exposure induced a humoral immune response against ECM proteins and that ECM immunization itself resulted in increased macrophage numbers in the lung. The specific immune response against ECM proteins did not augment the smoke-induced inflammatory response in our model. Conclusions: By demonstrating that smoke exposure itself can result in a specific immune response and that presence of this specific immune response is accompanied by an influx of macrophages, we provide support for the involvement of a specific immune response in the smoke-induced inflammatory response as can be seen in patients with COPD. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by defective extracellular matrix (ECM) turnover as a result of prolonged cigarette smoking. Fibroblasts have a central role in ECM turnover. The TGFβ induced Smad pathway provides intracellular signals to regulate ECM production. We address the following hypothesis: fibroblasts have abnormal expression of genes in the Smad pathway in COPD, resulting in abnormal proteoglycan modulation, the ground substance of ECM. Methods: We compared gene expression of the Smad pathway at different time points after stimulation with TGFβ, TNF or cigarette smoke extract (CSE) in pulmonary fibroblasts of GOLD stage II and IV COPD patients, and controls. Results: Without stimulation, all genes were similarly expressed in control and COPD fibroblasts. TGFβ stimulation: downregulation of Smad3 and upregulation of Smad7 occurred in COPD and control fibroblasts, indicating a negative feedback loop upon TGFβ stimulation. CSE hardly influenced gene expression of the TGFβ-Smad pathway in control fibroblasts, whereas it reduced Smad3 and enhanced Smad7 gene expression in COPD fibroblasts. Furthermore, decorin gene expression decreased by all stimulations in COPD but not in control fibroblasts. Conclusion: Fibroblasts of COPD patients and controls differ in their regulation of the Smad pathway, the contrast being most pronounced under CSE exposure. This aberrant responsiveness of COPD fibroblasts to CSE might result in an impaired tissue repair capability and is likely important with regard to the question why only a subset of smokers demonstrates an excess ECM destruction under influence of cigarette smoking. [ABSTRACT FROM AUTHOR]

Background: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction. In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown. We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function. Methods: Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase. Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined. Results: COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls. In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02). Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups. Conclusion: More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients. It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered. [ABSTRACT FROM AUTHOR]

Background: Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD. The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model. Methods: Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed. Results: Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4+CD25+ T cells and Foxp3 positive cells in the lungs. Additionally, the CD4+CD25+ T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells. Conclusion: These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation. Methods: 114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies. Results: Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001). Conclusion: Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years). Trial registration: NCT00158847 [ABSTRACT FROM AUTHOR]

Background: Tobacco smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD), though the mechanisms of its toxicity are still unclear. The ABC transporters multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (P-gp/MDR1) extrude a wide variety of toxic substances across cellular membranes and are highly expressed in bronchial epithelium. Their impaired function may contribute to COPD development by diminished detoxification of noxious compounds in cigarette smoke. Methods: We examined whether triple knock-out (TKO) mice lacking the genes for Mrp1 and Mdr1a/1b are more susceptible to develop COPD features than their wild-type (WT) littermates. TKO and WT mice (six per group) were exposed to 2 cigarettes twice daily by nose-only exposure or room air for 6 months. Inflammatory infiltrates were analyzed in lung sections, cytokines and chemokines in whole lung homogenates, emphysema by mean linear intercept. Multiple linear regression analysis with an interaction term was used to establish the statistical significances of differences. Results: TKO mice had lower levels of interleukin (IL)-7, KC (mouse IL-8), IL-12p70, IL-17, TNF-alpha, G-CSF, GM-CSF and MIP-1-alpha than WT mice independent of smoke exposure (P < 0.05). IL-1-alpha, IL-6, IL-8, IL-13, IL-17, TNF-alpha, G-CSF, GM-CSF and MCP-1 increased after smoke exposure in both groups, but the increase in IL-8 was lower in TKO than WT mice (P < 0.05) with a same trend for G-CSF (P < 0.10). Smoke-induced increase in pulmonary inflammatory cells in WT mice was almost absent in TKO mice. The mean linear intercept was not different between groups. Conclusion: Mrp1/Mdr1a/1b knock-out mice have a reduced inflammatory response to cigarette smoke. In addition, the expression levels of several cytokines and chemokines were also lower in lungs of Mrp1/ Mdr1a/1b knock-out mice independent of smoke exposure. Further studies are required to determine whether dysfunction of MRP1 and/or P-gp contribute to the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Background: Decorin, an extracellular matrix (ECM) proteoglycan, and TGF-β1 are both involved in lung ECM turnover. Decorin and TGF-β1 expression are decreased respectively increased in COPD lung tissue. Interestingly, they act as each other's feedback regulator. We investigated whether single nucleotide polymorphisms (SNPs) in decorin and TGF-β1 underlie accelerated decline in FEV1 and development of COPD in the general population. Methods: We genotyped 1390 subjects from the Vlagtwedde/Vlaardingen cohort. Lung function was measured every 3 years for a period of 25 years. We tested whether five SNPs in decorin (3'UTR and four intron SNPs) and three SNPs in TGF-β1 (3'UTR rs6957, C-509T rs1800469 and Leu10Pro rs1982073), and their haplotypes, were associated with COPD (last survey GOLD stage = II). Linear mixed effects models were used to analyze genotype associations with FEV1 decline. Results: We found a significantly higher prevalence of carriers of the minor allele of the TGF-β1 rs6957 SNP (p = 0.001) in subjects with COPD. Additionally, we found a significantly lower prevalence of the haplotype with the major allele of rs6957 and minor alleles for rs1800469 and rs1982073 SNPs in TGF-β1 in subjects with COPD (p = 0.030), indicating that this association is due to the rs6957 SNP. TGF-β1 SNPs were not associated with FEV1 decline. SNPs in decorin, and haplotypes constructed of both TGF-β1 and decorin SNPs were not associated with development of COPD or with FEV1 decline. Conclusion: Our study shows for the first time that SNPs in decorin on its own or in interaction with SNPs in TGF-β1 do not underlie the disturbed balance in expression between these genes in COPD. TGF-β1 SNPs are associated with COPD, yet not with accelerated FEV1 decline in the general population. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and airway inflammation, accompanied by decreased health status. It is still unknown which factors are responsible for the impaired health status in COPD. We postulated that airway inflammation negatively contributes to health status in COPD. Methods: In 114 COPD patients (99 male, age: 62 ± 8 yr, 41 [31-55] pack-years, no inhaled or oral corticosteroids, postbronchodilator FEV1: 63 ± 9% pred, FEV1/IVC: 48 ± 9%) we obtained induced sputum and measured health status (St. George's respiratory questionnaire (SGRQ)), postbronchodilator FEV1, hyperinflation (RV/TLC), and airway hyperresponsiveness to methacholine (PC20). Sputum was induced by hypertonic saline and differential cell counts were obtained in 102 patients. Results: Univariate analysis showed that SGRQ total and symptom score were positively associated with % sputum macrophages (r = 0.20, p = 0.05; and r = 0.20, p = 0.04, respectively). Multiple regression analysis confirmed these relationships, providing significant contributions of % sputum macrophages (B = 0.25, p = 0.021) and RV/TLC (B = 0.60, p = 0.002) to SGRQ total score. Furthermore, SGRQ symptom score was associated with % sputum macrophages (B = 0.30, p = 0.03) and RV/TLC (B = 0.48, p = 0.044), whilst SGRQ activity score was associated with % sputum macrophages (B = 0.46, p = 0.002), RV/TLC (B = 0.61, p = 0.015), and PC20 (B = -9.3, p = 0.024). Current smoking and FEV1 were not significantly associated with health status in the multiple regression analysis. Conclusion: We conclude that worse health status in COPD patients is associated with higher inflammatory cell counts in induced sputum. Our findings suggest that airway inflammation and hyperinflation independently contribute to impaired health status in COPD. This may provide a rationale for anti-inflammatory therapy in this disease. [ABSTRACT FROM AUTHOR]

Background: Recent reports indicate that over the next decade rates of chronic obstructive pulmonary disease (COPD) in women will exceed those in men in the western world, though in most jurisdictions, women continue to smoke less compared with men. Whether female adult smokers are biologically more susceptible to COPD is unknown. This study reviewed the available evidence to determine whether female adult smokers have a faster decline in forced expiratory volume in one second (FEV1) compared with male adult smokers and whether age modifies the relationship between cigarette smoke and lung function decline. Methods: A systematic review and a meta-analysis was performed of population-based cohort studies that had a follow-up period of at least 3 years, measured FEV1 on at least two different time points, and presented FEV1 data stratified by gender and smoking status in adults. Results: Of the 646 potentially relevant articles, 11 studies met these criteria and were included in the analyses (N = 55 709 participants). There was heterogeneity in gender-related results across the studies. However, on average current smokers had a faster annual decline rate in FEV1% predicted compared with never and former smokers. Female current smokers had with increasing age a significantly faster annual decline in FEV1% predicted than male current smokers (linear regression analysis, R² = 0.56; p = 0.008). Age did not materially affect the rate of decline in FEV1% predicted in male and female former and never smokers (p = 0.775 and p = 0.326, respectively). Conclusion: As female smokers age, they appear to experience an accelerated decline in FEV1% predicted compared with male smokers. Future research powered specifically on gender-related changes in lung function is needed to confirm these early findings. [ABSTRACT FROM AUTHOR]

Background: Patient-reported side effect questionnaires offer a simple method for the systematic measurement of drug-related side effects. In order to measure patients' inhaled corticosteroids (ICS) related side effect perceptions the 14-day retrospective Inhaled Corticosteroid Questionnaire (ICQ) was developed. In this research we aim to assess the construct validity and reliability of the ICQ and test its responsiveness to dose changes in adult asthma patients. Methods: In a cross-sectional study, current inhaler users with asthma completed the ICQ (27 with non ICS inhaler; 61 BDP equivalent daily ICS low dose ≤400 μg; 62 mid dose 401-800 μg; and 105 with high dose >800 μg). We generated 3 construct validity hypotheses: 1) a hierarchical dose-response pattern for scoring of the individual items on the ICQ, and statistically significant differences in the scores of each of the 15 ICQ domains by ICS dose group 2) an association between ICS dose and ICQ scoring after adjusting for appropriate confounders in multiple regression; 3) greater convergence between local side effect domains than between systemic and local domains of the scale. Test-retest reliability was assessed on a randomly selected subgroup of patients (n = 73) who also completed the ICQ a second time after 7 days. In a separate longitudinal study, 61 patients with asthma completed the ICQ at baseline and after changing their daily ICS dose, at 2- and 6- months, in order to test the ICQ's responsiveness. Results: All three construct validity hypotheses were well supported: 1) a statistically significant difference existed in scores for 14 domains, the high ICS dose group scoring highest; 2) ICS dose independently predicted ICQ scoring after adjusting for confounders; 3) greater convergence existed between local ICS domains than between local and systemic domains. The ICQ had good reproducibility: test-retest intraclass correlation coefficients were =0.69 for all but the 'Facial Oedema' domain. In the longitudinal study, ICQ scores for 'Voice Problems' changed significantly at 2- and 6-months from baseline and other ICQ domains displayed trends in scoring change accordant with dose modulation at 6-months. Conclusion: The ICQ has good dose-related discriminative properties, is valid, reliable, and shows potential responsiveness to ICS dose change. [ABSTRACT FROM AUTHOR]

Background: Chronic smoking is the main risk factor for chronic obstructive pulmonary disease. Knowledge on the response to the initial smoke exposures might enhance the understanding of changes due to chronic smoking, since repetitive acute smoke effects may cumulate and lead to irreversible lung damage. Methods: We investigated acute effects of smoking on inflammation in 16 healthy intermittent smokers in an open randomised cross-over study. We compared effects of smoking of two cigarettes on inflammatory markers in exhaled air, induced sputum, blood and urine at 0, 1, 3, 6, 12, 24, 48, 96 and 192 hours and outcomes without smoking. All sputum and blood parameters were log transformed and analysed using a linear mixed effect model. Results: Significant findings were: Smoking increased exhaled carbon monoxide between 0 and 1 hour, and induced a greater decrease in blood eosinophils and sputum lymphocytes between 0 and 3 hours compared to non-smoking. Compared to non-smoking, smoking induced a greater interleukin-8 release from stimulated blood cells between 0 and 3 hours, and a greater increase in sputum lymphocytes and neutrophils between 3 and 12 hours. Conclusion: We conclude that besides an increase in inflammation, as known from chronic smoking, there is also a suppressive effect of smoking two cigarettes on particular inflammatory parameters. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e.g. air pollutants and cigarette smoke components, will be discussed as well as the (mal)function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases. [ABSTRACT FROM AUTHOR]

Background: Inflammation in the airways and lung parenchyma underlies fixed airway obstruction in chronic obstructive pulmonary disease. The exact role of smoking as promoting factor of inflammation in chronic obstructive pulmonary disease is not clear, partly because studies often do not distinguish between current and ex-smokers. Methods: We investigated airway inflammation in sputum and bronchial biopsies of 34 smokers with chronic obstructive pulmonary disease (9 Global initiative for Chronic Obstructive Lung Disease stage 0, 9 stage I, 10 stage II and 6 stage III) and 26 asymptomatic smokers, and its relationship with past and present smoking habits and airway obstruction. Results: Neutrophil percentage, interleukin-8 and eosinophilic-cationic-protein levels in sputum were higher in chronic obstructive pulmonary disease (stage I-III) than asymptomatic smokers. Inflammatory cell numbers in bronchial biopsies were similar in both groups. Current smoking correlated positively with macrophages: in bronchial biopsies in both groups, and in sputum in chronic obstructive pulmonary disease. Pack-years smoking correlated positively with biopsy macrophages only in chronic obstructive pulmonary disease. Conclusion: Inflammatory effects of current smoking may mask the underlying ongoing inflammatory process pertinent to chronic obstructive pulmonary disease. This may have implications for future studies, which should avoid including mixed populations of smokers and ex-smokers. [ABSTRACT FROM AUTHOR]

Background: The new Global Obstructive Lung Disease (GOLD) guidelines advice to focus treatment in Chronic Obstructive Pulmonary Disease (COPD) on improvement of functional state, prevention of disease progression and minimization of symptoms. So far no validated questionnaires are available to measure symptom and functional state in daily clinical practice. The aim of this study was to develop and validate the Clinical COPD Questionnaire (CCQ). Methods: Qualitative research with patients and clinicians was performed to generate possible items to evaluate clinical COPD control. Thereafter, an item reduction questionnaire was sent to 77 international experts. Sixty-seven experts responded and the 10 most important items, divided into 3 domains (symptoms, functional and mental state) were included in the CCQ (scale: 0 = best, 6 = worst). Results: Cross-sectional data were collected from 119 subjects (57 COPD, GOLD stage I-III; 18 GOLD stage 0 and 44 (ex)smokers). Cronbach's α was high (0.91). The CCQ scores in patients (GOLD 0-III) were significantly higher than in healthy (ex)smokers. Furthermore, significant correlations were found between the CCQ total score and domains of the SF-36 (ρ = 0.48 to ρ = 0.69) and the SGRQ (ρ = 0.67 to ρ = 0.72). In patients with COPD, the correlation between the CCQ and FEV1%pred was ρ =-0.49. Test-retest reliability was determined in 20 subjects in a 2-week interval (Intra Class Coefficient = 0.94). Thirty-six smokers with and without COPD showed significant improvement in the CCQ after 2 months smoking cessation, indicating the responsiveness of the CCQ. Conclusion: The CCQ is a self-administered questionnaire specially developed to measure clinical control in patients with COPD. Data support the validity, reliability and responsiveness of this short and easy to administer questionnaire. [ABSTRACT FROM AUTHOR]

Background: Lung growth in utero and lung function loss during adulthood can be affected by exposure to environmental tobacco smoke (ETS). The underlying mechanisms have not been fully elucidated. Both ETS exposure and single nucleotide polymorphisms (SNPs) in Glutathione S-Transferase (GST) Omega genes have been associated with the level of lung function. This study aimed to assess if GSTO SNPs interact with ETS exposure in utero and during adulthood on the level of lung function during adulthood.Methods: We used cross-sectional data of 8,128 genotyped participants from the LifeLines cohort study. Linear regression models (adjusted for age, sex, height, weight, current smoking, ex-smoking and packyears smoked) were used to analyze the associations between in utero, daily and workplace ETS exposure, GSTO SNPs, the interaction between ETS and GSTOs, and level of lung function (FEV(1), FEV(1)/FVC). Since the interactions between ETS and GSTOs may be modified by active tobacco smoking we additionally assessed associations in never and ever smokers separately. A second sample of 5,308 genotyped LifeLines participants was used to verify our initial findings.Results: Daily and workplace ETS exposure was associated with significantly lower FEV(1)levels. GSTO SNPs (recessive model) interacted with in utero ETS and were associated with higher levels of FEV(1), whereas the interactions with daily and workplace ETS exposure were associated with lower levels of FEV(1), effects being more pronounced in never smokers. The interaction of GSTO2 SNP rs156697 with in utero ETS associated with a higher level of FEV(1) was significantly replicated in the second sample. Overall, the directions of the interactions of in utero and workplace ETS exposure with the SNPs found in the second (verification) sample were in line with the first sample.Conclusions: GSTO genotypes interact with in utero and adulthood ETS exposure on adult lung function level, but in opposite directions. [ABSTRACT FROM AUTHOR]

Background: Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers.Methods: 3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference.Results: Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 - 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted '>5 years' showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001).Conclusion: Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline.Trial Registration: Registered at http://www.trialregister.nl with trial number ISRCTN63545820. [ABSTRACT FROM AUTHOR]

Background: The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second (FEV1) in the general population.Methods: Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 FEV1 measurements during 3 surveys, respectively 7 FEV1 measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV1 measurements.Results: In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher FEV1 level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower FEV1 level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with FEV1 decline was observed.Conclusion: This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of FEV1 in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of FEV1 in the general population. [ABSTRACT FROM AUTHOR]