S Guerra

Publications (5)27.73 Total impact

• Article: Respiratory health and endotoxin: associations and modification by CD14/-260 genotype.

  I Bakolis, G Doekes, J Heinrich, J P Zock, D Heederik, M Kogevinas, S Guerra, D Norbäck, A Ramasamy, A Nevalainen, C Svanes, C M Chen, G Verlato, M Olivieri, F Castro-Giner, D Jarvis
  [show abstract] [hide abstract]
  ABSTRACT: Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU · mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.
  European Respiratory Journal 09/2011; 39(3):573-81. · 5.89 Impact Factor
• Article: ADRB2 Gly16Arg polymorphism, asthma control and lung function decline.

  C Rebordosa, M Kogevinas, S Guerra, F Castro-Giner, D Jarvis, L Cazzoletti, I Pin, V Siroux, M Wjst, J M Antò, R de Marco, X Estivill, A G Corsico, R Nielsen, C Janson
  [show abstract] [hide abstract]
  ABSTRACT: Arg/Arg homozygotes for the Gly16Arg polymorphism in the β₂-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β₂-agonists but no effect has been associated with long-acting β₂-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01-1.75; p = 0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was 2.73 (95% CI 1.28-5.82; p = 0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean ± se decrease in decline in forced expiratory volume in 1 s of 7.7 ± 2.5 mL·yr⁻¹ was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p = 0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β₂-adrenoreceptor desensitisation.
  European Respiratory Journal 03/2011; 38(5):1029-35. · 5.89 Impact Factor
• Source

  Available from: Reto Crameri

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

  J Bousquet, J Anto, C Auffray, M Akdis, A Cambon-Thomsen, T Keil, T Haahtela, B N Lambrecht, D S Postma, J Sunyer, [......], E Toskala, P van Cauwenberge, A J M van Oosterhout, R Varraso, L von Hertzen, M Wickman, C Wijmenga, M Worm, J Wright, T Zuberbier
  [show abstract] [hide abstract]
  ABSTRACT: The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and targets for therapy. A novel phenotype definition and an integrative translational approach are needed to understand how a network of molecular and environmental factors can lead to complex allergic diseases. A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics, functional genomics, bioinformatics, computational and systems biology. The following steps are proposed: (i) Identification of 'classical' and 'novel' phenotypes in existing birth cohorts; (ii) Building discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgE-associated allergic diseases; and (iv) Translational integration of systems biology outcomes into health care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes, thus expanding current knowledge of the genomic and environmental determinants of allergic diseases in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health of European citizens as well as increasing the competitiveness and boosting the innovative capacity of Europe, while addressing global health issues and ethical issues.
  Allergy 01/2011; 66(5):596-604. · 6.27 Impact Factor
• Article: Early life environment, neurodevelopment and the interrelation with atopy.

  J Sunyer, X Basagaña, J R González, J Júlvez, S Guerra, M Bustamante, R de Cid, J M Antó, M Torrent
  [show abstract] [hide abstract]
  ABSTRACT: Both neurological and immunological systems are vulnerable to early life exposures. Neurological disorders and atopy have been related in animals and humans. Our main objective was to assess whether multiple exposures to early life determinants remain associated with neurodevelopment after considering the potential intermediate role of atopy. A second objective was to assess whether genes associated with atopy may inform about the potential neurotoxical mechanisms. Children were members of the AMICS birth cohort in Menorca (n=418, 87% of the recruited). General cognition was measured with the McCarthy Scales at age 4 and atopy through specific IgE at age 4 and prick test at age 6; 85 single nucleotide polymorphisms (SNPs) in 16 atopy and detoxification genes were genotyped. Among the 27 risk factors assessed, lower maternal social class, maternal smoking during pregnancy, being first born, shorter breastfeeding, higher DDT levels in cord blood, and higher indoor levels of NO2 (among the non-detoxifiers by GSTP1 polymorphism) were independently associated with poorer cognition. These associations were apparently not mediated by the relation between atopy and general cognition. Among the candidate atopic genes, variants in NQ01 (a detoxification gene) and NPRS1 (related with affective disorders like anxiety and stress management) had a significant association with general cognition (p-value<0.001). However, adjustment for the corresponding SNPs did not change the association between the early life determinants and general cognition. Multiple environmental pre-natal exposures were associated with neurodevelopment independently of their role in the immunological system. Atopic genes related to neurodevelopment suggest some potential mechanisms.
  Environmental Research 10/2010; 110(7):733-8. · 3.40 Impact Factor
• Source

  Available from: proyectoinma.org

  Article: Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort.

  J Julvez, M Torrent, M Guxens, J M Antó, S Guerra, J Sunyer
  [show abstract] [hide abstract]
  ABSTRACT: Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy. To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later. A population-based birth cohort enrolled 482 children, 422 of them (87%) provided neurobehavioral data, 341 (71%) had specific IgE measured at the age of 4 years; and 395 (82%) had skin prick tests completed at the age of 6 years. Atopy was defined as IgE levels higher than 0.35 kU/l to any of the three tested allergens at the age of 4 or as a positive skin prick test to any of the six tested allergens at the age of 6. McCarthy Scales of Child Abilities and California Preschool Social Competence Scale were the psychometric instruments used. Twelve percent of children at the age of 4 and 17% at the age of 6 were atopic. Neurobehavioral scores were negatively associated with 6-year-old atopy after adjustment for socio-demographic and allergic factors, A relative risk of 3.06 (95% CI: 1.30-7.24) was associated with the lowest tertile (scorings < or =90 points) of the general cognitive scale. Similar results were found for verbal abilities, executive functions, and social competence. Asthma, wheezing, rhinitis, and eczema at the age of 6, but not at the age of 4, were associated with neurodevelopment at the age of 4. Neuropsychologic functioning and later atopy are negatively associated in preschool age children.
  Allergy 03/2009; 64(9):1279-85. · 6.27 Impact Factor