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1.  Relationship of child perceptions of maternal pain to children’s laboratory and nonlaboratory pain 
Previous research has established links between parent and child pain. However, little is known about sex-specific parent-child pain relationships in a nonclinical population. A sample of 186 children aged eight to 18 years (49% female) provided information on maternal and self bodily pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters’ bodily and laboratory pain, but not with sons’ pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys versus girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared with daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children’s perceptions of maternal pain may play a role in influencing children’s own experience of pain, and that maternal pain models may affect boys and girls differently.
PMCID: PMC2642517  PMID: 18592057
Children; Pain; Sex differences; Social learning
2.  Relationship of child perceptions of maternal pain to children's laboratory and non-laboratory pain 
Previous research has established links between parent and child pain. Yet little is known about sex-specific parent-child pain relationships in a non-clinical population. A sample of 186 children aged 8–18 years (49% female) provided information on maternal and self bodily-pain, assessed by asking children about the presence and location of bodily pain experienced. Children also completed three laboratory pain tasks and reported on cold pressor pain intensity, pressure pain intensity and heat pain intensity. The presence of child-reported maternal pain was consistently correlated with daughters’ bodily and laboratory pain, but not with sons’ pain in bivariate analyses. Multivariate analyses controlling for child age and maternal psychological distress indicated that children of mothers with bodily pain reported more total bodily pain sites as well as greater pressure and cold pain intensity, relative to children of mothers without bodily pain. For cold pain intensity, these results differed for boys vs. girls, in that daughters reporting maternal pain evidenced significantly higher cold pain intensity compared to daughters not reporting maternal pain. No such differences were found for boys. The findings suggest that children’s perceptions of maternal pain may play a role in influencing children’s own experience of pain and that maternal pain models may affect boys and girls differently.
PMCID: PMC2642517  PMID: 18592057
pain; sex differences; social learning; children
3.  Prenatal and Postnatal Maternal Stress and Wheeze in Urban Children 
Rationale: Critical periods for programming early wheeze risk may include pregnancy and infancy. Effects of timing remain poorly understood.
Objectives: Associations among prenatal and postnatal maternal stress and children’s wheeze were prospectively examined in 653 families. Effect modification by maternal sensitization was also examined.
Methods: Stress was indexed by a maternal negative life events (NLEs) score (range, 0–9) ascertained during pregnancy and between 1 and 2 years postpartum. Mothers reported child wheeze every 3 months up to age 2 years. Relationships of prenatal and postnatal maternal NLEs with repeated wheeze (≥2 episodes) were examined using logistic regression adjusting for covariates. Penalized splines were implemented to explore possible nonlinear associations. We also examined the interaction between prenatal stress and maternal sensitization indexed by allergen-specific IgE from maternal prenatal serum.
Measurements and Main Results: Adjusted models considering prenatal or postnatal NLEs alone both showed an exposure-response relationship between higher stress and child wheeze. When considering prenatal and postnatal stress concurrently, only children of mothers with high stress in both periods were significantly more likely to wheeze (adjusted odds ratio, 3.04; 95% confidence interval, 1.67–5.53) than children of mothers reporting low stress in both periods. Associations between high prenatal stress and wheeze were significant in children born to nonsensitized mothers (any IgE <0.35 kU/L) but not in the sensitized group (P for interaction = 0.03).
Conclusions: Although children have heightened sensitivity to maternal stress in utero and in early childhood, those with higher stress in both periods were particularly at risk for wheeze. The prenatal maternal immune milieu modified effects.
doi:10.1164/rccm.201201-0162OC
PMCID: PMC3406080  PMID: 22582161
negative life events; stress; pregnancy; maternal sensitization; childhood wheeze
4.  Negative life events and quality of life in adults with asthma 
Thorax  2006;62(2):139-146.
Background
The relationship between stress and quality of life in adults with asthma has not been well studied. Stress, quantified by negative life events, may be linked to quality of life in asthma through multiple pathways, including increase in disease severity and adverse effects on socioeconomic status (SES).
Methods
The responses to a self‐completed questionnaire assessing negative life events (NLEs) in the previous 12 months (from a 24‐item checklist) among 189 adults with asthma from a well‐characterised cohort were analysed. The relationship between the number of NLEs reported and asthma‐specific quality of life (AQOL) was measured with the Marks instrument. General linear modelling was used to test the conjoint effects of NLEs, SES and disease severity based on the Severity of Asthma Score, a validated acute and chronic disease measure.
Results
Those with annual family incomes <$60 000 reported significantly more NLEs than those with higher incomes (p = 0.03). The number of NLEs did not differ significantly between those with forced expiratory volume in 1 s <80% predicted and those with >80% predicted, nor among those with lower compared with higher Severity of Asthma Score. The frequency of NLEs was associated with poorer (higher numerical score) AQOL (p = 0.002). When studied together in the same model, combinations of income level and asthma severity (greater or lesser Severity of Asthma Score; p<0.001) and number of NLEs (p = 0.03) were both significantly associated with AQOL.
Conclusion
NLEs are associated with quality of life among adults with asthma, especially among those of lower SES. Clinicians should be aware of this relationship, especially in vulnerable patient subsets.
doi:10.1136/thx.2006.065730
PMCID: PMC2111249  PMID: 16928721
5.  Parent and child anxiety sensitivity: Relationship to children’s experimental pain responsivity 
Anxiety sensitivity (AS) or fear of anxiety sensations has been linked to childhood learning history for somatic symptoms, suggesting that parental AS may impact children’s responses to pain. Using structural equation modeling (SEM), we tested a conceptual model in which parent AS predicted child AS, which in turn predicted a hypothesized latent construct consisting of children’s pain intensity ratings for three laboratory pain tasks (cold pressor, thermal heat and pressure). This conceptual model was tested in 211 non-clinical parent-child pairs (104 girls, mean age = 12.4 years; 178 mothers). Our model was supported in girls only indicating that the sex of the child moderated the hypothesized relationships. Thus, parent AS was related to child laboratory pain intensity via its contribution to child AS in girls but not in boys. In girls, 42% of the effect of parent AS on laboratory pain intensity was explained via child AS. In boys, there was no clear link between parent AS and child AS, although child AS was predictive of experimental pain intensity across sex. Our results are consistent with the notion that parent AS may operate via healthy girls’ own fear of anxiety symptoms to influence their responses to laboratory pain stimuli.
Perspective-The present study highlights sex differences in the links among parent and child anxiety sensitivity (AS; fear of anxiety sensations) and children’s experimental pain responses. Among girls, childhood learning history related to somatic symptoms may be a particularly salient factor in the development of AS and pain responsivity.
doi:10.1016/j.jpain.2005.12.004
PMCID: PMC1540407  PMID: 16632321
anxiety sensitivity; laboratory pain; children; adolescents; parent; sex differences
6.  Maternal Anxiety and Children’s Laboratory Pain: The Mediating Role of Solicitousness 
Children  2016;3(2):10.
There has been limited empirical examination of how parent variables such as anxiety and solicitousness collectively impact child pain response. We sought to examine the relationships among maternal anxiety, solicitous parenting, and children’s laboratory anxiety and pain intensity in children with chronic pain. Participants included 80 children and adolescents (ages 8–18) with chronic pain and their mothers. Children completed questionnaires and lab pain tasks measuring their parents’ solicitous parenting, pressure, cold and heat pain anticipatory anxiety and pain intensity. Using bootstrapping analysis, maternal anxiety predicted child anticipatory anxiety and pain intensity in girls with chronic pain, which was mediated by the child’s report of parental solicitousness. For boys with chronic pain, maternal anxiety predicted boys’ anticipatory anxiety and pain intensity, with no support for mediation. This study adds to the growing literature demonstrating the impact of maternal anxiety on children’s pain. The study highlights the importance of considering parents in treatment designed to reduce children’s pain.
doi:10.3390/children3020010
PMCID: PMC4934565  PMID: 27417248
anxiety; children; chronic pain; parenting
7.  Sex differences in the relationship between maternal fear of pain and children’s conditioned pain modulation 
Journal of Pain Research  2013;6:231-238.
Background
Parental behaviors, emotions, and cognitions are known to influence children’s response to pain. However, prior work has not tested the association between maternal psychological factors and children’s responses to a conditioned pain modulation (CPM) task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.
Methods
The present study examined sex differences in the association between maternal anxiety about pain and children’s CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children’s anticipatory anxiety and pain-related fear of the CPM task were measured.
Results
Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition) in boys.
Conclusion
The findings indicate sex-specific relationships between maternal pain anxiety and children’s responses to a CPM task over and above that accounted for by the age of the child and the mother’s general psychological distress.
doi:10.2147/JPR.S43172
PMCID: PMC3615838  PMID: 23569396
diffuse noxious inhibitory controls; pediatric pain; mother-child relationship; cold pressor; pressure pain; laboratory pain
8.  Effects of Prenatal Social Stress and Maternal Dietary Fatty Acid Ratio on Infant Temperament: Does Race Matter? 
Epidemiology (Sunnyvale, Calif.)  2014;4(4):1000167.
Background
Infant temperament predicts a range of developmental and behavioral outcomes throughout childhood. Both maternal fatty acid intake and psychosocial stress exposures during pregnancy may influence infant temperament. Furthermore, maternal race may modify prenatal diet and stress effects. The goals of this study are to examine the joint effects of prenatal diet and stress and the modifying effects of race on infant behavior.
Methods
Analyses included N=255 mother-infant dyads, primarily minorities (21% Blacks; 42% Hispanics), enrolled in an urban pregnancy cohort. Maternal prenatal stress was indexed by a negative life events (NLEs) score on the Crisis in Family Systems-Revised survey. Prenatal total daily intakes of polyunsaturated fatty acids (PUFAs) (n3, n6) were estimated from a food frequency questionnaire; n3:n6 ratios were calculated. Mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), a measure of infant temperament, when the children were 6 months old. Three commonly used dimensions were derived: Orienting & Regulation, Extraversion, and Negative Affectivity. Associations among prenatal stress, maternal n3:n6 ratio, and race/ethnicity on infant temperament, controlling for maternal education and age and child sex, were examined.
Results
Among Blacks, prenatal stress effects on infant Orienting & Regulation scores were modified by maternal n3:n6 ratios (p=0.03): As NLEs increased, lower n3:n6 ratios predicted lower infant Orienting & Regulation scores, whereas higher n3:n6 ratios attenuated the effect of prenatal stress. There were no main or interaction effects predicting Extraversion or Negative Affectivity.
Conclusions
An optimal PUFA ratio may protect the fetus from stress effects on infant behavior, particularly among Blacks. These findings may have implications for later neurodevelopment and social functioning predicted by early temperamental characteristics.
doi:10.4172/2161-1165.1000167
PMCID: PMC4197958  PMID: 25328835
Psychosocial stress; Temperament; Fatty acids; Ethnicity; Race
9.  Pubertal status moderates the association between mother and child laboratory pain tolerance 
BACKGROUND:
There is limited information regarding the relationship between parent and child responses to laboratory pain induction in the absence of experimental manipulation.
OBJECTIVES:
To assess the association between responses to cold and pressure pain tasks in 133 nonclinical mothers and children (mean age 13.0 years; 70 girls), and the moderating effects of child sex and pubertal status on these mother-child relationships.
METHODS:
Mothers and children independently completed the cold and pressure pain tasks. Multiple linear regression analyses examined the association between mothers’ and children’s laboratory pain responses. The moderating effects of child sex and pubertal status were tested in the linear models by examining the interaction among mother laboratory pain responses, and child sex and pubertal status.
RESULTS:
Mothers’ cold pain anticipatory anxiety and pressure pain intensity were associated with children’s pressure pain anticipatory anxiety. Mothers’ pressure pain tolerance was associated with children’s pain tolerance for both the cold and pressure pain tasks. Mothers’ cold pain tolerance was associated with children’s pressure pain tolerance. Pubertal status moderated two of the three significant mother-child pain tolerance relationships, such that the associations held for early pubertal but not for late pubertal children. Sex did not moderate mother-child pain associations.
CONCLUSIONS:
The results indicate that mother-child pain relationships are centred primarily on pain avoidance behaviour, particularly among prepubertal children. These findings may inform interventions focused on pain behaviours, with a particular emphasis on mothers of prepubertal children, to reduce acute pain responses in their children.
PMCID: PMC3938339  PMID: 24367794
Adolescents; Children; Cold pressor task; Experimental pain; Parents
10.  Sex Differences in the Association Between Cortisol Concentrations and Laboratory Pain Responses in Healthy Children 
Gender medicine  2009;6(Suppl 2):193-207.
Background
Research in adult populations has highlighted sex differences in cortisol concentrations and laboratory pain responses, with men exhibiting higher cortisol concentrations and reduced pain responses compared with women. Yet, less is known about the relationship of cortisol concentrations to pain in children.
Objective
This study examined associations between sex, cortisol, and pain responses to laboratory pain tasks in children.
Methods
Salivary cortisol samples from subjects aged 8 to 18 years were obtained at baseline after entering the laboratory (SCb), after the completion of all pain tasks (SC1), and at the end of the session (SC2), 20 minutes later. Blood cortisol samples were also taken after completion of the pain tasks (BC1) and at the end of the session (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain tasks: pressure, heat, and cold pressor tasks. Pain measures included pain tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
Results
The study included 235 healthy children and adolescents (119 boys, 116 girls; mean age, 12.7 years; range, 8–18 years; 109 [46.4%] were in early puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly correlated with each other. Salivary cortisol levels for the total sample and for boys and girls declined significantly from SCb to SC1 (P < 0.01), although there were no significant changes from SC1 to SC2. No significant sex differences in salivary or blood cortisol levels were evident at any assessment point. Separate examination of the cortisol–laboratory pain response relationships by sex (controlling for age and time of day) suggested different sex-specific patterns. Higher cortisol levels were associated with lower pain reactivity (ie, increased pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r = 0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026). However, higher cortisol levels were related to higher pain response (ie, increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r = 0.237, P = 0.041]) in girls compared with boys.
Conclusions
These findings suggest important sex differences in cortisol–pain relationships in children and adolescents. Cortisol levels were positively associated with increased pain tolerance in boys and increased pain sensitivity in girls.
doi:10.1016/j.genm.2009.03.001
PMCID: PMC3486740  PMID: 19406369
pain; children; cortisol; sex differences
11.  Religiosity and resilience in persons at high risk for major depression 
Psychological medicine  2011;42(3):509-519.
Background
Few studies have examined religiosity as a protective factor using a longitudinal design to predict resilience in persons at high risk for major depressive disorder (MDD).
Method
High-risk offspring selected for having a depressed parent and control offspring of non-depressed parents were evaluated for psychiatric disorders in childhood/adolescence and at 10-year and 20-year follow-ups. Religious/spiritual importance, services attendance and negative life events (NLEs) were assessed at the 10-year follow-up. Models tested differences in relationships between religiosity/spirituality and subsequent disorders among offspring based on parent depression status, history of prior MDD and level of NLE exposure. Resilience was defined as lower odds for disorders with greater religiosity/spirituality in higher-risk versus lower-risk offspring.
Results
Increased attendance was associated with significantly reduced odds for mood disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring ; however, odds were significantly lower in offspring of non-depressed parents than in offspring of depressed parents. In analyses confined to offspring of depressed parents, those with high and those with average/low NLE exposure were compared: increased attendance was associated with significantly reduced odds for MDD, mood disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and increased importance was associated with significantly reduced odds for mood disorder (by 74%) only in offspring of depressed parents with high NLE exposure. Moreover, those associations differed significantly between offspring of depressed parents with high NLE exposure and offspring of depressed parents with average/low NLE exposure.
Conclusions
Greater religiosity may contribute to development of resilience in certain high-risk individuals.
doi:10.1017/S0033291711001516
PMCID: PMC3552391  PMID: 21849093
High-risk; longitudinal; major depression; religiosity; resilience
12.  Negative Life Events and Attempted Suicide in Rural China 
PLoS ONE  2015;10(1):e0116634.
Objective
This study aimed to examine the association between negative life events (NLEs) and attempted suicide in rural China.
Methods
Six rural counties were selected from disease surveillance points in Shandong province, China. A total of 409 suicide attempters in rural areas between October 1, 2009, and March 31, 2011, and an equal number of matched controls were interviewed. We compared negative life events experienced within 1 month, 1–3 months, 3–6months, and 6–2 months prior to attempted suicide for cases and prior to interview for controls. We used multivariate logistic regression to examine the association between NLEs and attempted suicide.
Results
Suicide attempters experienced more NLEs within the last year prior to suicide attempt than controls prior to interview (83.1% vs. 33.5%). There was a significant dose-response relationship between NLEs experienced within the last year and increased risk of attempted suicide. Timing of NLEs analysis showed that NLEs experienced in the last month and 6–12 months prior to suicide attempt were significantly associated with elevated risk of attempted suicide, even after adjusting for mental disorders and demographic factors. Of NLEs, quarrelling with spouse, quarrelling with other family members, conflicting with friends or neighbors, family financial difficulty, and serious illness were independently related to attempted suicide.
Conclusion
NLEs are significantly associated with increased risk for attempted suicide in rural China. Stress management and intervention may be important to prevent suicidal behavior in rural China.
doi:10.1371/journal.pone.0116634
PMCID: PMC4303417  PMID: 25611854
13.  Sex differences in parent and child pain ratings during an experimental child pain task 
Research in the field of pediatric pain has largely ignored the role of fathers in their children’s pain experiences. The first objective of the present study was to examine the effect of the presence of mothers versus fathers on children’s subjective ratings, facial expressions and physiological responses to acute pain. The second objective was to examine whether child and parent sex influence parents’ proxy ratings of their children’s pain. The final objective was to compare levels of agreement between mothers’ and fathers’ assessments of their children’s pain. Participants included 73 children (37 boys, 36 girls), four to 12 years of age, along with 32 fathers and 41 mothers. Children undertook the cold pressor pain task while observed by one of their parents. During the task, the children’s heart rates and facial expressions were recorded. Children provided self-reports and parents provided proxy reports of child pain intensity using the seven-point Faces Pain Scale. Neither child nor parent sex had a significant impact on children’s subjective reports, facial expressions or heart rates in response to acute pain. Fathers gave their sons higher pain ratings than their daughters, whereas mothers’ ratings of their sons’ and daughters’ pain did not differ. Kappa statistics and t tests revealed that fathers tended to be more accurate judges of their children’s pain than mothers. Overall, this research highlights the importance of examining both parent and child sex differences in pediatric pain research.
PMCID: PMC2671311  PMID: 18592059
Agreement; Assessment; Child; Cold pressor; Pain; Parent
14.  Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress 
Psychoneuroendocrinology  2014;0:151-163.
Summary
Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function. Differences in cortisol levels have been found in preterm infants exposed to substantial procedural stress during neonatal intensive care, compared to infants born full-term, but only a few studies investigated whether altered programming of the HPA axis persists past toddler age. Further, there is a dearth of knowledge of what may contribute to these changes in cortisol. This prospective cohort study examined the cortisol profiles in response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol, in children (n=129) born at varying levels of prematurity (24–32 weeks gestation) and at full-term (38–41 weeks gestation), at age 7 years. Further, we investigated the relationships among cortisol levels and neonatal procedural pain-related stress (controlling for multiple medical confounders), concurrent maternal factors (parenting stress, depressive and anxiety symptoms) and children’s behavioral problems. For each aim we investigate acute cortisol response profiles to a cognitive challenge as well as diurnal cortisol patterns at home. We hypothesized that children born very preterm will differ in their pattern of cortisol secretion from children born full-term, possibly depended on concurrent child and maternal factors, and that exposure to neonatal pain-related stress would be associated with altered cortisol secretion in children born very preterm, possibly in a sex-dependent way. Saliva samples were collected from 7-year old children three times during a laboratory visit for assessment of cognitive and executive functions (pretest, mid-test, end - study day acute stress profile) and at four times over two consecutive non-school days at home (i.e. morning, mid-morning, afternoon and bedtime - diurnal rhythm profile). We found that cortisol profiles were similar in preterm and full-term children, albeit preterms had slightly higher cortisol at bedtime compared to full-term children. Importantly, in the preterm group, greater neonatal procedural pain-related stress (adjusted for morphine) was associated with lower cortisol levels on the study day (p=0.044) and lower diurnal cortisol at home (p=0.023), with effects found primarily in boys. In addition, child attention problems were negatively, and thought problems were positively, associated with the cortisol response during cognitive assessment on the study day in preterm children. Our findings suggest that neonatal pain/stress contributes to altered HPA axis function up to school-age in children born very preterm, and that sex may be an important factor.
doi:10.1016/j.psyneuen.2014.09.018
PMCID: PMC4268136  PMID: 25313535
cortisol; preterm; stress; HPA axis; pain; internalizing behavior; child; sex; low birth weight; maternal interaction
15.  Exclusive Breastfeeding and Cognition, Executive Function, and Behavioural Disorders in Primary School-Aged Children in Rural South Africa: A Cohort Analysis 
PLoS Medicine  2016;13(6):e1002044.
Background
Exclusive breastfeeding (EBF) is associated with early child health; its longer-term benefits for child development remain inconclusive. We examine the associations between EBF, HIV exposure, and other maternal/child factors and the cognitive and emotional-behavioural development of children aged 7–11 y.
Methods and Findings
The Vertical Transmission Study (VTS) supported EBF in HIV-positive and HIV-negative women; between 2012 and 2014, HIV-negative VTS children (332 HIV exposed, 574 HIV unexposed) were assessed in terms of cognition (Kaufman Assessment Battery for Children Second Edition [KABC-II]), executive function (Developmental Neuropsychological Assessment Second Edition [NEPSY-II]), and emotional-behavioural functioning (parent-reported Child Behaviour Checklist, [CBCL]). We developed population means by combining the VTS sample with 629 same-aged HIV-negative children from the local demographic platform. For each outcome, we split the VTS sample into scores above or at/below each population mean and modelled each outcome using logistic regression analyses, overall and stratified by child sex. There was no demonstrated effect of EBF on overall cognitive functioning. EBF was associated with fewer conduct disorders overall (adjusted odds ratio [aOR] 0.44 [95% CI 0.3–0.7], p ≤ 0.01), and there was weak evidence of better cognition in boys who had been exclusively breastfed for 2–5 mo versus ≤1 mo (Learning subscale aOR 2.07 [95% CI 1.0–4.3], p = 0.05). Other factors associated with better child cognition were higher maternal cognitive ability (aOR 1.43 [95% CI 1.1–1.9], p = 0.02, Sequential; aOR 1.74 [95% CI 1.3–2.4], p < 0.001, Planning subscales) and crèche attendance (aOR 1.96 [95% CI 1.1–3.5], p = 0.02, Sequential subscale). Factors positively associated with executive function were home stimulation (aOR 1.36 [95% CI 1.0–1.8], p = 0.04, Auditory Attention; aOR 1.35 [95% CI 1.0–1.8], p = 0.05, Response Set) and crèche (aOR 1.74 [95% CI 1.0–3.0], p = 0.05, Animal Sorting). Maternal mental health problems and parenting stress were associated with increased emotional-behavioural problems on the total CBCL (aOR 2.44 [95% CI 1.3–4.6], p = 0.01; aOR 7.04 [95% CI 4.2–11.9], p < 0.001, respectively). Maternal HIV status was not associated with any outcomes in the overall cohort. Limitations include the nonrandomised study design and lack of maternal mental health assessment at the child’s birth.
Conclusions
EBF was associated with fewer than average conduct disorders and weakly associated with improved cognitive development in boys. Efforts to improve stimulation at home, reduce maternal stress, and enable crèche attendance are likely to improve executive function and emotional-behavioural development of children.
Bland and colleagues report that exclusive breastfeeding leads to a reduction in conduct disorder incidents in children but does not significantly impact on cognition.
Author Summary
Why Was This Study Done?
The benefits of exclusive breastfeeding (EBF) in early life are well established and include optimal nutrition and protection from infectious diseases.
The longer-term benefits of EBF on child development and behaviour are less clear, and studies in low-income settings have shown conflicting results depending on the design of the study and whether other factors known to influence development, such as HIV exposure, have been taken into account.
There is a dearth of evidence examining the development of HIV-uninfected children born to HIV-infected mothers and whether these children are disadvantaged compared to those born to HIV-uninfected mothers.
What Did the Researchers Do and Find?
This study was established in 2012 to investigate the development (cognitive and emotion-behaviour) of 1,536 HIV-negative children, born to HIV-infected and HIV-uninfected mothers, in rural South Africa, taking into account a range of current and early life factors known to be associated with child development.
Duration of EBF was associated with a reduction in conduct disorders in girls and boys, but there was no association with cognitive development in the overall sample, when allowing for other factors. Maternal intelligence quotient (IQ) was strongly associated with children’s later cognitive development.
Children born to HIV-infected mothers performed as well as the children born to HIV-uninfected mothers.
What Do the Findings Mean?
Promoting, protecting, and supporting EBF may result in fewer conduct disorders, in addition to the established benefits of improved nutrition and reduced morbidity and mortality.
Reducing conduct disorders is important because they may lead to aggressive or disruptive behaviours and are associated with an increase in later criminal behaviour and poor long-term mental health and academic achievement.
doi:10.1371/journal.pmed.1002044
PMCID: PMC4915617  PMID: 27328132
16.  4th Pediatric Allergy and Asthma Meeting (PAAM) 
Yavuz, S. Tolga | Koc, Ozan | Gungor, Ali | Gok, Faysal | Hawley, Jessica | O’Brien, Christopher | Thomas, Matthew | Brodlie, Malcolm | Michaelis, Louise | Mota, Inês | Gaspar, Ângela | Piedade, Susana | Sampaio, Graça | Dias, José Geraldo | Paiva, Miguel | Morais-Almeida, Mário | Madureira, Cristina | Lopes, Tânia | Lopes, Susana | Almeida, Filipa | Sequeira, Alexandra | Carvalho, Fernanda | Oliveira, José | Gay-Crosier, Fabienne | Nenciu, Ioana-Valentina | Nita, Andreia Florina | Ulmeanu, Alexandru | Oraseanu, Dumitru | Zapucioiu, Carmen | Machinena, Adrianna | Sánchez, Olga Domínguez | Lozano, Montserrat Alvaro | Feijoo, Rosa Jiménez | Blasco, Jaime Lozano | Gibert, Mònica Piquer | Muñoz, Mª Teresa Giner | da Costa, Marcia Dias | Martín, Ana Maria Plaza | Yilmaz, Ebru Arik | Cavkaytar, Özlem | Buyuktiryaki, Betul | Soyer, Ozge | Sackesen, Cansin | Netting, Merryn | El-Merhibi, Adaweyah | Gold, Michael | Quinn, Patrick | Penttila, Irmeli | Makrides, Maria | Giavi, Stavroula | Muraro, Antonella | Lauener, Roger | Mercenier, Annick | Bersuch, Eugen | Montagner, Isabella M. | Passioti, Maria | Celegato, Nicolò | Summermatter, Selina | Nutten, Sophie | Bourdeau, Tristan | Vissers, Yvonne M. | Papadopoulos, Nikolaos G. | van der Kleij, Hanneke | Warmenhoven, Hans | van Ree, Ronald | Pieters, Raymond | Opstelten, Dirk Jan | van Schijndel, Hans | Smit, Joost | Fitzsimons, Roisin | Timms, Victoria | Du Toit, George | Kaya, Guven | Gulec, Mustafa | Saldir, Mehmet | Sener, Osman | Hassan, Nagwa | Shaaban, Hala | El-Hariri, Hazem | Mahfouz, Ahmed Kamel Inas E. | Gabor, Papp | Gabor, Biro | Csaba, Kovacs | Chawes, Bo | Bønnelykke, Klaus | Stokholm, Jakob | Heickendorff, Lene | Brix, Susanne | Rasmussen, Morten | Bisgaard, Hans | Hallas, Henrik Wegener | Arianto, Lambang | Pincus, Maike | Keil, Thomas | Reich, Andreas | Wahn, Ulrich | Lau, Susanne | Grabenhenrich, Linus | Fagerstedt, Sara | Hesla, Helena Marell | Johansson, Emelie | Rosenlund, Helen | Mie, Axel | Scheynius, Annika | Alm, Johan | Esparza-Gordillo, Jorge | Matanovic, Anja | Marenholz, Ingo | Bauerfeind, Anja | Rohde, Klaus | Nemat, Katja | Lee-Kirsch, Min-Ae | Nordenskjöld, Magnus | Winge, Marten C.G. | Krüger, Renate | Beyer, Kirsten | Kalb, Birgit | Niggemann, Bodo | Hübner, Norbert | Cordell, Heather J. | Bradley, Maria | Lee, Young-Ae | Gough, Hannah | Schramm, Dirk | Beschorner, John | Schuster, Antje | Bauer, Carl-Peter | Forster, Johannes | Zepp, Fred | Bergmann, Renate | Bergmann, Karl | Garcia, Filipe Benito | Santos, Natacha | Pité, Helena | Papadopoulou, Athina | Mermiri, Despina | Xatziagorou, Elpida | Tsanakas, Ioannis | Lampidi, Stavroula | Priftis, Kostas | Fuertes, Elaine | Markevych, Iana | Bowatte, Gayan | Gruzieva, Olena | Gehring, Ulrike | Becker, Allan | Berdel, Dietrich | Brauer, Michael | Carlsten, Chris | Hoffmann, Barbara | Kozyrskyj, Anita | Lodge, Caroline | Pershagen, Göran | Wijga, Alet | Joachim, Heinrich | Zivkovic, Zorica | Djuric-Filipovic, Ivana | Jocić-Stevanovic, Jasmina | Zivanovic, Snežana | Taka, Styliani | Kokkinou, Dimitra | Papakonstantinou, Aliki | Stefanopoulou, Panagiota | Georgountzou, Anastasia | Maggina, Paraskevi | Stamataki, Sofia | Papaevanggelou, Vassiliki | Andreakos, Evangelos | Gibert, Monica Piquer | Spera, Adriana Machinena | Deliu, Matea | Belgrave, Danielle | Simpson, Angela | Custovic, Adnan | Marques, João Gaspar | Carreiro-Martins, Pedro | Belo, Joana | Serranho, Sara | Peralta, Isabel | Neuparth, Nuno | Leiria-Pinto, Paula | Vazquez-Ortiz, Marta | Pascal, Mariona | Plaza, Ana Maria | Juan, Manel | Paparo, Lorella | Nocerino, Rita | Aitoro, Rosita | Langella, Ilaria | Amoroso, Antonio | Amoroso, Alessia | Di Scala, Carmen | Berni Canani, Roberto | Maity, Santanu | Rotiroti, Giuseppina | Gandhi, Minal | Jonsson, Karin | Ljung, Annika | Hesselmar, Bill | Adlerbert, Ingegerd | Brekke, Hilde | Johansen, Susanne | Wold, Agnes | Sandberg, Ann-Sofie | Nordlund, Björn | Lundholm, Cecilia | Ullemar, Villhelmina | van Hage, Marianne | Örtqvist, Anne | Almqvist, Catarina | Selby, Anna | Grimshaw, Kate | Clausen, Michael | Dubakiene, Ruta | Fiocchi, Alessandro | Kowalski, Marek | Papadopoulos, Nikos | Reche, Marta | Sigurdardottir, Sigurveig | Sprikkleman, Aline | Xepapadaki, Paraskevi | Mills, Clare | Roberts, Graham | Neto, Herberto Jose Chong | Wandalsen, Gustavo Falbo | Bianca, Ana Carolina Dela | Aranda, Carolina | Rosário, Nelson Augusto | Solé, Dirceu | Mallol, Javier | Marcos, Luis García | Banic, Ivana | Rijavec, Matija | Plavec, Davor | Korosec, Peter | Turkalj, Mirjana | Bozicevic, Alen | De Mieri, Maria | Hamburger, Matthias | Holley, Simone | Morris, Ruth | Mitchell, Frances | Knibb, Rebecca | Latter, Susan | Liossi, Christina | Hassan, Mostafa M. M. | Barman, Malin | Sandin, Anna | Posa, Daniela | Perna, Serena | Hoffmann, Ute | Chen, Kuan-Wei | Resch, Yvonne | Vrtala, Susanne | Valenta, Rudolf | Matricardi, Paolo Maria | Tsilochristou, Olympia | Rohrbach, Alexander | Cappella, Antonio | Hofmaier, Stephanie | Hatzler, Laura | D’Amelio, Raffaele | Björkander, Sophia | Johansson, Maria A. | Lasaviciute, Gintare | Sverremark-Ekström, Eva | Rüschendorf, Franz | Strachan, David P. | Spycher, Ben D. | Baurecht, Hansjörg | Margaritte-Jeannin, Patricia | Sääf, Annika | Kerkhof, Marjan | Ege, Markus | Baltic, Svetlana | Matheson, Melanie C. | Li, Jin | Michel, Sven | Ang, Wei Q. | McArdle, Wendy | Arnold, Andreas | Homuth, Georg | Demenais, Florence | Bouzigon, Emmanuelle | Söderhäll, Cilla | de Jongste, Johan C. | Postma, Dirkje S. | Braun-Fahrländer, Charlotte | Horak, Elisabeth | Ogorodova, Ludmila M. | Puzyrev, Valery P. | Bragina, Elena Yu | Hudson, Thomas J. | Morin, Charles | Duffy, David L. | Marks, Guy B. | Robertson, Colin F. | Montgomery, Grant W. | Musk, Bill | Thompson, Philip J. | Martin, Nicholas G. | James, Alan | Sleiman, Patrick | Toskala, Elina | Rodriguez, Elke | Fölster-Holst, Regina | Franke, Andre | Lieb, Wolfgang | Gieger, Christian | Heinzmann, Andrea | Rietschel, Ernst | Cichon, Sven | Nöthen, Markus M. | Pennell, Craig E. | Sly, Peter D. | Schmidt, Carsten O. | Schneider, Valentin | Heinig, Matthias | Holt, Patrick G. | Kabesch, Michael | Weidinger, Stefan | Hakonarson, Hakon | Ferreira, Manuel AR | Laprise, Catherine | Freidin, Maxim B | Genuneit, Jon | Koppelman, Gerard H | Melén, Erik | Dizier, Marie-Hélène | John Henderson, A. | Lee, Young Ae | González-Delgado, Purificacion | Caparrós, Esther | Clemente, Fernando | Cueva, Begoña | Moreno, Victoria M. | Carretero, Jose Luis | Fernández, Javier | Swan, Kate | Gopi, Mudiyur | Smith, Tim | Ramesh, Edara | Sadasivam, Arun | Arêde, Cristina | Borrego, Luís Miguel | Pires, Graça | Santa-Marta, Cristina | Brand, Stephanie | Stein, Karina | Heine, Holger | Kauth, Marion | Rolfsjord, Leif Bjarte | Bakkeheim, Egil | Skjerven, Håvard Ove | Carlsen, Kai-Håkon | Hunderi, Jon Olav | Berents, Teresa Løvold | Mowinckel, Petter | Lødrup Carlsen, Karin C. | Munzel, Ullrich | Berger, William | Valiente, Román | Vozmediano, Valvanera | Lukas, John C. | Rodríguez, Mónica | Guarnaccia, Sebastiano | Vitale, Luigi | Pluda, Ada | D’Agata, Emanuele | Colombo, Denise | Felici, Stefano | Gretter, Valeria | Facchetti, Susanna | Pecorelli, Gaia | Quecchia, Cristina | Guibas, George | Spandou, Evangelia | Megremis, Spyridon | West, Peter | Papadopoulos, Nikolaos | Rufo, João Cavaleiro | Madureira, Joana | Paciência, Inês | Aguiar, Lívia | Padrão, Patrícia | Pinto, Mariana | Delgado, Luís | Moreira, Pedro | Teixeira, João Paulo | Fernandes, Eduardo Oliveira | Moreira, André | Dominguez, Adriana Izquierdo | Valero, Antonio | Mullol, Joaquim | Del Cuvillo, Alfonso | Montoro, Javier | Jauregui, Ignacio | Bartra, Joan | Davila, Ignacio | Ferrer, Marta | Sastre, Joaquin | Martins, Catarina | Lima, Jorge | Leandro, Maria José | Nunes, Glória | Branco, Jorge Cunha | Trindade, Hélder | Borrego, Luis Miguel | Conkar, Secil | Kilic, Mehtap | Aygun, Canan | Sancak, Recep | Tagalaki, Eleni | Banos, Lambros | Vlachou, Anna | Giannoula, Fotini | Pavlakou, Marina | Kryoni, Maria | Makris, Kostas | Lazova, Snezhina | Petrova, Guergana | Miteva, Dimitrinka | Perenovska, Penka | Klyucharova, Aliya | Skorohodkina, Olesya | Koumaki, Dimitra | Manousaki, Alkisti | Agrapidi, Maria | Iatridou, Lida | Eruk, Omima | Myridakis, Konstantinos | Manousakis, Emmanouil | Koumaki, Vasiliki | Dimou, Maria | Ingemansson, Maria | Hedlin, Gunilla | Pastor, Nitida | de Boissieu, Delphine | Vanderhoof, Jon | Moore, Nancy | Maditz, Kaitlin | Mehdi, Adeli | Elhassan, Shaza | Beck, Carolin | Al-Hammadi, Ahmed | Maris, Ioana | O’Sullivan, Ronan | Hourihane, Jonathan | Raptis, George | DunnGalvin, Audrey | Greenhawt, Matthew | Venter, Carina | O’Regan, Evelyn | Cronin, Duncan | O’Reilly, Anna | Abdelaziz, Foued | Khelifi-Touhami, Dounia | Selim, Nihad | Khelifi-Touhami, Tahar | Merida, Pablo | Plaza, Ana Mª | Castellanos, Juan Heber | Lozano, Jaime | Dominguez, Olga | Piquer, Monica | Jimenez, Rosa | Giner, Mª Teresa | Kakleas, Konstantinos | Joishy, Manohar | Maskele, Wendmu | Jenkins, Huw R. | Escarrer, Mercedes | Madroñero, Agustín | Guerra, Maria Teresa | Julia, Juan Carlos | Cerda, Juan Carlos | Contreras, Javier | Tauler, Eulalia | Vidorreta, Maria Jesus | Rojo, Ana | Del Valle, Silvia | Flynn, Niamh | Foley, Gary | Harmon, Carol | Fitzsimons, John | Baynova, Krasimira | Del Robledo, Ávila Maria | Marina, Labella | Cortes, Aaron | Sciaraffia, Alicia | Castillo, Angela | Juel-Berg, Nanna | Hansen, Kirsten Skamstrup | Poulsen, Lars Kærgaard | Lazar, Adina | Aguiar, Rita | Lopes, Anabela | Paes, Maria J. | Santos, Amélia S. | Pereira-Barbosa, M. A. | Eke Gungor, Hatice | Uytun, Salih | Sahiner, Umit Murat | Altuner Torun, Yasemin | Zivanovic, Mirjana | Atanasković-Marković, Marina | Vesel, Tina | Nahtigal, Mihaela | Obermayer-Temlin, Andreja | Križnik, Eva Šoster | Maslar, Mirjana | Bizjak, Ruben | Tomšič-Matic, Marjeta | Posega-Devetak, Sonja | Skerbinjek-Kavalar, Maja | Predalič, Mateja | Avčin, Tadej | Pouessel, Guillaume | Beaudouin, Etienne | Moneret-Vautrin, Anne M. | Deschildre, Antoine | Viñas, Marta | Borja, Bartolomé | Hernández, Nora | Castillo, Mª José | Izquierdo, Adriana | Ibero, Marcel | Kocabas, Can Naci | Heming, Camille | Garrett, Emily | Blackstock, Adam | Chodhari, Rahul | Belohlavkova, Simona | Kopelentova, Eliska | Visek, Petr | Setinova, Ivana | Svarcova, Ivana | Sjölander, Sigrid | Nilsson, Nora | Berthold, Malin | Ekoff, Helena | Borres, Magnus | Nilsson, Caroline | González Domínguez, Loreto | Muñoz Archidona, Cristina | Moreira Jorge, Ana | Quevedo Teruel, Sergio | Bracamonte Bermejo, Teresa | Castillo Fernández, Miriam | Pineda de la Losa, Fernando | Echeverría Zudaire, Luis Ángel | Vrani, Olga | Mavroudi, Antigone | Fotoulaki, Maria | Emporiadou, Maria | Spiroglou, Kleomenis | Xinias, Ioannis | Sadreddini, Helyeh A. | Warnes, Mia | Traves, Donna | Kostić, Gordana | Filipovic, Đorđe | Sittisomwong, Sawapon | Sittisomwong, Siripong | Podolec, Zygmunt | Hartel, Marcin | Panek, Daria | Podolec-Rubiś, Magdalena | Banasik, Tomasz | Abbasi, Elham | Moghtaderi, Mozhgan | Sanneerappa, Phani | Deliu, Alina | Kutty, Moosa | Ramesh, Nagabathula | Sherkat, Roya | Sabri, Mohammad Reza | Dehghan, Bahar | Bigdelian, Hamid | Raeesi, Nahid | Afshar, Mino | Rahimi, Hamid | Klein, Christoph | Al-Jebouri, Mohemid | Svitich, Oxana A. | Zubacheva, Daria O. | Potemkin, Dmitrii A. | Gankovskaya, Ludmila V. | Zverev, Vitalii V. | OB Doyle, Elaine | Gallagher, Paul | Dewlett, Sherine | Man, Kin | Pocock, James | Gerrardhughes, Anna | Wasilewska, Jolanta | Kaczmarski, Maciej | Lebensztejn, Dariusz | Thuraisingham, Chandramani | Sinniah, Davendralingam | Chen, Yue | Mei, Xiaomei | Ozdogan, Sebnem | Karadeniz, Pinar | Ayyildiz-Emecen, Durdugul | Oncul, Ummuhan | Sari, Gizem | Cavdar, Sabanur | Farzan, Niloufar | Vijverberg, Susanne J. | Palmer, Colin J. | Tantisira, Kelan G. | Maitland-van der Zee, Anke-Hilse | Yavuzyilmaz, Fatma | Urganci, Nafiye | Usta, Merve | Hoxha, Mehmet | Basho, Maksim | Wandalsen, Gustavo F. | Monteiro, Fernanda | Lame, Blerta | Mesonjesi, Eris | Sherri, Arjeta | Ibranji, Alkerta | Gjati, Laert | Loloci, Gjustina | Bardhi, Ardii | Moghtaderi, Behnam | Farjadian, Shirin | Eghtedari, Dorna | Olaya, Manuela | Del Mar Vasquez, Laura | Ramirez, Luis Fernando | Serrano, Carlos Daniel | Usta Guc, Belgin | Asilsoy, Suna | Ozer, Fulya | Shopova, Sylvia | Papochieva, Vera | Loekmanwidjaja, Jessica | Mallozi, Márcia | Ratner, Paul | Soteres, Daniel | Novák, Zoltán | Yáñez, Anahí | Ildikó, Kiss | Kuna, Piotr | Tortajada, Miguel | Valiente, Román | Feuerhahn, Julia | Blome, Christine | Hadler, Meike | Karagiannis, Efstrathios | Langenbruch, Anna | Augustin, Matthias | Roux, Michel | Kakudo, Shinji | Zeldin, Robert K. | Sokolova, Anna | Silva, Tiago Milheiro | Zivanovic, Snezana S. | Cvetkovic, Vesna | Nikolic, Ivana | Zivanovic, Sonja J. | Saranac, Ljiljana | Nesterenko, Zoia | Radic, Snezana | Milenkovic, Branislava | Smiljanic, Spomenka | Micic-Stanijevic, Milka | Calovic, Olivera | Hofbauer, Anne Marie Bro | Agertoft, Lone | Everson, Lucy | Kearney, Jessica | Coppel, Jonny | Braithwaite, Simon | Christiansen, Elisabeth S. | Kjaer, Henrik Fomsgaard | Eller, Esben | Mørtz, Charlotte G. | Halken, Susanne | Román India, Cristina | Jiménez Jiménez, Juana | Echeverría Zudaire, Luis | O’Connor, Cathal | Kanti, Varvara | Lünnemann, Lena | Malise, Günther | Ludriksone, Laine | Stroux, Andrea | Henrich, Wolfgang | Abu-Dakn, Michael | Blume-Peytavi, Ulrike | Garcia Bartels, Natalie | Schario, Marianne | Stanley, Thorsten | Brandenbarg, Nicolien | Boardman, Alia | McGreevy, Gary | Rodger, Emily | Knight, Katherine | Taylor, Trisha | Scanlan, Gemma | Christoph, Grüber | van Stuivenberg, Margriet | Mosca, Fabio | Moro, Guido | Chirico, Gaetano | Braegger, Christian P. | Riedler, Joseph | Yavuz, Yalcin | Boehm, Günther | Arasi, Stefania | Crisafulli, Giuseppe | Caminiti, Lucia | Porcaro, Federica | Pajno, Giovanni Battista | Tanaka, Akane | Togawa, Yaei | Oida, Kumiko | Kambe, Naotomo | Arkwright, Peter | Amagai, Yosuke | Shimojo, Naoki | Sato, Yasunori | Mochizuki, Hiroyuki | Jang, Hyosun | Ishizaka, Saori | Matsuda, Hiroshi | Barlianto, Wisnu | Olivianto, Ery | Chandra Kusuma, H. M. S. | Mollica, Mariapia | Trinchese, Giovanna | Alfano, Elena | Amato, Francesco | Pirozzi, Claudio | Calignano, Antonio | Meli, Rosaria | Rossberg, Siri | Gerhold, Kerstin | Zimmermann, Kurt | Zaino, Mohammad | Geske, Thomas | Hamelmann, Eckard | Bogovic, Sarah | van den Berg, Jochem | Janssen, Chantal | Claver, Angela | Martin-Muñoz, Mª Flor | Martorell, C. | Belver, M. T. | Alonso Lebrero, E. | Zapatero, L. | Fuentes, V. | Piqué, M. | Plaza, A. | Muñoz, C. | Blasco, Cristina | Villa, B. | Gómez, C. | Nevot, S. | García, J. M. | Echeverria, L. | DeWitt, Brenda | Holloway, Judith | Hodge, Donald | Ludman, Sian | Jafari-Mamaghani, Merhdad | Ebling, Rosemary | Fox, Adam T. | Lack, Gideon | Lovén Björkman, Sofia | Ballardini, Natalia | Basu, Supriyo | Hallet, Jenny | Srinivas, Jyothi | Stringer, Hazel | Jay, Nicola | Fonseca, Paula | Vieira, Clara | Mastrorilli, Carla | Caffarelli, Carlo | Asero, Riccardo | Tripodi, Salvatore | Dondi, Arianna | Ricci, Gianpaolo | Povesi Dascola, Carlotta | Calamelli, Elisabetta | Cipriani, Francesca | Di Rienzo Businco, Andrea | Bianchi, Annamaria | Candelotti, Paolo | Frediani, Tullio | Verga, Carmen | Korovessi, Paraskevi | Tiliakou, Skevi | Tavoulari, Evaggelia | Moraiti, Kalliopi-Maria | Tee, Wan Jean | Deiratany, Samir | Seedhoo, Raymond | McNamara, Roisin | Okafor, Ike | Khaleva, Ekaterina | Novic, Gennady | Bychkova, Natalia | Abd Al-Aziz, Amany | Fatouh, Amany | Motawie, Ayat | Bostany, Eman El | Ibrahim, Amr | Andonova, Sylvia | Savov, Alexey | Zoto, Maria | Kyriakakou, Marialena | Vassilopoulou, Mariza | Balaska, Athina | Kostaridou, Stavroula | Wartna, Jorien | Bohnen, Arthur M. | Elshout, Gijs | Pols, David H. J. | Bindels, Patrick J. E. | Seys, Sven F. | Dilissen, Ellen | Van der Eycken, Sarah | Schelpe, An-Sofie | Marijsse, Gudrun | Troosters, Thierry | Vanbelle, Vincent | Aertgeerts, Sven | Ceuppens, Jan L. | Dupont, Lieven J. | Peers, Koen | Bullens, Dominique M. | Lokas, Sandra Bulat | Zivkovic, Jelena | Nogalo, Boro | Kobal, Iva Mrkic | Oliveira, Georgeta | Pike, Katharine | Melo, Alda | Amélia, Tomás | Cidrais Rodrigues, José Carlos | Serrano, Cristina | Lopes dos Santos, José Manuel | Lopes, Carla | Schauer, Uwe | Bergmann, Karl-Christian | Moral, Luis | Toral, Teresa | Marco, Nuria | Avilés, Beléns García | Fuentes, Mª Jesús | Garde, Jesús | Montahud, Cristina | Perona, Javier | Forniés, Mª José | Arroabarren, Esozia | Anda, Marta | Sanz, Maria Luisa | Lizaso, Maria Teresa | Arregui, Candida | May, Sara | Hartz, Martha | Joshi, Avni | Park, Miguel A. | Posega Devetak, Sonja | Koren Jeverica, Anja | Castro, Leonor | Gouveia, Carolina | Marques, Ana Carvalho | Cabral, Antonio Jorge | Amaral, Luis | Carolino, Fabrícia | Castro, Eunice | Passos, Madalena | Cernadas, Josefina R. | Amaral, Luís | Dias de Castro, Eunice | Pineda, Fernando | Gomes, Armanda | Brough, Helen | Röhmel, Jobst | Schwarz, Carsten | Mehl, Anne | Stock, Philippe | Staab, Doris | Seib, Christine | Critchlow, Anita | Barber, Alyson | Delavalle, Belen | Garriga, Teresa | Vilá, Blanca | Astolfi, Annalisa | Di Chiara, Costanza | Neri, Iria | Patrizi, Annalisa | Neskorodova, Katerina | Kudryavtseva, Asya | Alvarez, Jorge | Palacios, Miriam | Martinez-Merino, Marta | Vaquero, Ibone
Clinical and Translational Allergy  2016;6(Suppl 1):1-60.
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
doi:10.1186/s13601-016-0117-8
PMCID: PMC5123301
17.  NleC, a Type III Secretion Protease, Compromises NF-κB Activation by Targeting p65/RelA 
PLoS Pathogens  2010;6(12):e1001231.
The NF-κB signaling pathway is central to the innate and adaptive immune responses. Upon their detection of pathogen-associated molecular patterns, Toll-like receptors on the cell surface initiate signal transduction and activate the NF-κB pathway, leading to the production of a wide array of inflammatory cytokines, in attempt to eradicate the invaders. As a countermeasure, pathogens have evolved ways to subvert and manipulate this system to their advantage. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are closely related bacteria responsible for major food-borne diseases worldwide. Via a needle-like protein complex called the type three secretion system (T3SS), these pathogens deliver virulence factors directly to host cells and modify cellular functions, including by suppressing the inflammatory response. Using gain- and loss-of-function screenings, we identified two bacterial effectors, NleC and NleE, that down-regulate the NF-κB signal upon being injected into a host cell via the T3SS. A recent report showed that NleE inhibits NF-κB activation, although an NleE-deficient pathogen was still immune-suppressive, indicating that other anti-inflammatory effectors are involved. In agreement, our present results showed that NleC was also required to inhibit inflammation. We found that NleC is a zinc protease that disrupts NF-κB activation by the direct cleavage of NF-κB's p65 subunit in the cytoplasm, thereby decreasing the available p65 and reducing the total nuclear entry of active p65. More importantly, we showed that a mutant EPEC/EHEC lacking both NleC and NleE (ΔnleC ΔnleE) caused greater inflammatory response than bacteria carrying ΔnleC or ΔnleE alone. This effect was similar to that of a T3SS-defective mutant. In conclusion, we found that NleC is an anti-inflammatory bacterial zinc protease, and that the cooperative function of NleE and NleC disrupts the NF-κB pathway and accounts for most of the immune suppression caused by EHEC/EPEC.
Author Summary
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) cause food-borne diseases, including watery diarrhea or severe bloody diarrhea and life-threatening kidney disease (hemolytic uremic syndrome). Upon ingestion, EPEC/EHEC colonize the cells of the epithelial lining in the intestinal tract. In response, the affected cells initiate an immune response by secreting cytokines that attract immune cells. To prevent their early elimination by the host, these bacteria have developed strategies to prevent the host immune response. They do this by injecting bacterial effectors into the host cells to disrupt the NF-κB pathway, an essential effector of the host cell immune response. In the current study, we report the discovery of an NF-κB suppressive effector in EPEC/EHEC called NleC, and its novel mechanism. We found that NleC is a zinc protease that can digest p65, a critical component of the NF-κB pathway, thus dampening the host inflammatory response. NleE is another recently identified anti-inflammatory effector. We show here that an EPEC/EHEC mutant deficient in both NleC and NleE loses most of its ability to suppress the host inflammatory response. Our findings show how two different bacterial effectors can function in cooperation to modify the host immune response.
doi:10.1371/journal.ppat.1001231
PMCID: PMC3002990  PMID: 21187904
18.  Associations between parent and child pain and functioning in a pediatric chronic pain sample: A mixed methods approach 
This study employed a mixed-method design to test sex-specific parent-child pain associations. Subjects were 179 chronic pain patients aged 11–19 years (mean = 14.34; 72% female) presenting for treatment at a multidisciplinary, tertiary clinic. Mothers and children completed questionnaires prior to their clinic visit, including measures of children’s pain, functioning and psychological characteristics. Mothers also reported on their own pain and psychological functioning. Interviews were conducted with a sub-sample of 34 mothers and children prior to the clinic visit and analyzed using a grounded theory approach. The quantitative data suggest stronger mother-daughter than mother-son pain relationships. The qualitative data suggest that girls’ pain and pain-related disability is related to an overly enmeshed mother-daughter relationship and the presence of maternal models of pain, while boys’ pain and disability is linked to male pain models and criticism and to maternal worry and solicitousness. Boys and girls appear to have developmentally incongruous levels of autonomy and conformity to maternal expectations. The mixed-method data suggest distinct trajectories through which mother and father involvement may be linked to chronic pain in adolescent boys and girls.
PMCID: PMC3105525  PMID: 21643522
Sex differences; parent-child relationships; chronic pain
19.  Persistent pain in a community-based sample of children and adolescents: Sex differences in psychological constructs 
The prevalence of persistent and recurrent pain among children and adolescents has important economic, social and psychological repercussions. The impact of chronic pain in children extends beyond the affected individuals – more than one-third of parents of children with pain report clinically significant levels of stress and depression. Although many pain-related psychological factors have been examined in chronic pediatric pain populations, much of that research involved clinical samples. Community-based research, however, is necessary to uncover the way pain is experienced by youth, regardless of whether treatment is sought or is available. This study aimed to ascertain the lifetime prevalence of pediatric pain in a Canadian community-based sample, and to explore age and sex differences in children who report persistent pain and those who do not with respect to several constructs believed to play important roles in the development and maintenance of persistent pain.
BACKGROUND:
Very few studies have investigated the psychological factors associated with the pain experiences of children and adolescents in community samples.
OBJECTIVES:
To examine the lifetime prevalence of, and psychological variables associated with, persistent pain in a community sample of children and adolescents, and to explore differences according to sex, age and pain history.
METHODS:
Participants completed the Childhood Anxiety Sensitivity Index (CASI), the Child Pain Anxiety Symptoms Scale (CPASS), the Multidimensional Anxiety Scale for Children-10 (MASC-10), the Pain Catastrophizing Scale for Children (PCS-C) and a pain history questionnaire that assessed chronicity and pain frequency. After research ethics board approval, informed consent/assent was obtained from 1022 individuals recruited to participate in a study conducted at the Ontario Science Centre (Toronto, Ontario).
RESULTS:
Of the 1006 participants (54% female, mean [± SD] age 11.6±2.7 years) who provided complete data, 27% reported having experienced pain that lasted for three months or longer. A 2×2×2 (pain history, age and sex) multivariate ANOVA was conducted, with the total scores on the CASI, the CPASS, the MASC-10 and the PCS-C as dependent variables. Girls with a history of persistent pain expressed higher levels of anxiety sensitivity (P<0.001) and pain catastrophizing (P<0.001) than both girls without a pain history and boys regardless of pain history. This same pattern of results was found for anxiety and pain anxiety in the older, but not the younger, age group.
CONCLUSIONS:
Boys and girls appear to differ in terms of how age and pain history relate to the expression of pain-related psychological variables. Given the prevalence of persistent pain found in the study, more research is needed regarding the developmental implications of persistent pain in childhood and adolescence.
PMCID: PMC3206778  PMID: 22059200
Children; Persistent pain; Psychosocial factors; Sex differences
20.  Child Effortful Control as a Mediator of Parenting Practices on Externalizing Behavior: Evidence for a Sex-Differentiated Pathway across the Transition from Preschool to School 
An explanatory model for children’s development of disruptive behavior across the transition from preschool to school was tested. It was hypothesized that child effortful control would mediate the effects of parenting on children’s externalizing behavior and that child sex would moderate these relations. Participants were 241 children (123 boys) and their parents and teachers. Three dimensions of parenting, warm responsiveness, induction, and corporal punishment, were assessed via maternal report when children were 3 years old. Child effortful control at age 3 was measured using laboratory tasks and a mother-report questionnaire. Mothers and teachers contributed ratings of child externalizing behavior at age 6. Results showed that the hypothesized model fit the data well and that the pattern of associations between constructs differed for boys and girls. For boys, parental warm responsiveness and corporal punishment had significant indirect effects on children’s externalizing behavior three years later, mediated by child effortful control. Such relations were not observed for girls. These findings support a sex-differentiated pathway to externalizing behavior across the transition from preschool to school.
doi:10.1007/s10802-010-9437-7
PMCID: PMC4133744  PMID: 20632205
Corporal punishment; Maternal warmth; Proactive discipline; Effortful control; Externalizing behavior problems; Temperament; Preschool; Sex differences
21.  Virulence gene profiling of enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli strains: a basis for molecular risk assessment of typical and atypical EPEC strains 
BMC Microbiology  2011;11:142.
Background
Enterohaemorrhagic E. coli (EHEC) can cause severe disease such as bloody diarrhoea and haemolytic uraemic syndrome in humans. Besides production of Shiga toxins, the presence of LEE (eae-gene) and non-LEE (nle) encoded effector genes harboured on O-islands OI-122, OI-71 and OI-57 is associated with EHEC virulence and their frequency in outbreaks. Genes encoded by the EHEC-plasmid are putative virulence markers of EHEC. EHEC-plasmids, LEE and non-LEE effector genes have also been detected in some strains of enteropathogenic E. coli (EPEC). The objective of this study was to analyze the relationship between EHEC and EPEC for virulence genes encoded by genomic O-islands and by the EHEC-plasmids.
Results
Nle genes ent/espL2, nleB and nleE (OI-122), nleA, nleF and nleH1-2 (OI-71), nleG5-2 and nleG6-2 (OI-57), espK (CP-933N) and the EHEC-plasmid encoded genes ehxA, espP, etpD and katP were searched in 73 typical and in 235 atypical enteropathogenic E. coli (EPEC) strains. Typical and atypical EPEC each fall into two clusters. Cluster 1 typical (n = 46) and atypical (n = 129) EPEC strains were characterized by the presence of OI-122 encoded genes and grouped together with 64 investigated EHEC strains. Cluster 2 typical (n = 27) and atypical (n = 106) strains grouped together with 52 LEE-negative, Shiga toxin-producing E. coli (STEC) and with 21 apathogenic E. coli strains. Typical EPEC Cluster 1 strains belonged to serotypes frequently involved in severe illness and outbreaks in children (O111:H2, O114:H2, O55:H6, O127:H6 and O142:H6). Atypical EPEC Cluster 1 strains were characterized by serotypes related to EHEC (O26:H11, O55:H7, O145:H28, O103:H2 and O103:H25).
Conclusion
The OI-122 encoded nleB gene was found to be most closely associated with Cluster 1 strains and may serve as a diagnostic tool for the identification of virulent EHEC and EPEC seropathotypes. OI-71 encoded genes nleA, nleF and nleH1-2 are less associated with Cluster 1 strains. EHEC-plasmid, OI-57 and CP-933 associated genes showed only weak similarities with virulent Cluster 1 EHEC and EPEC strains.
doi:10.1186/1471-2180-11-142
PMCID: PMC3133550  PMID: 21689465
22.  How Well Do Clinical Pain Assessment Tools Reflect Pain in Infants? 
PLoS Medicine  2008;5(6):e129.
Background
Pain in infancy is poorly understood, and medical staff often have difficulty assessing whether an infant is in pain. Current pain assessment tools rely on behavioural and physiological measures, such as change in facial expression, which may not accurately reflect pain experience. Our ability to measure cortical pain responses in young infants gives us the first opportunity to evaluate pain assessment tools with respect to the sensory input and establish whether the resultant pain scores reflect cortical pain processing.
Methods and Findings
Cortical haemodynamic activity was measured in infants, aged 25–43 wk postmenstrual, using near-infrared spectroscopy following a clinically required heel lance and compared to the magnitude of the premature infant pain profile (PIPP) score in the same infant to the same stimulus (n = 12, 33 test occasions). Overall, there was good correlation between the PIPP score and the level of cortical activity (regression coefficient = 0.72, 95% confidence interval [CI] limits 0.32–1.11, p = 0.001; correlation coefficient = 0.57). Of the different PIPP components, facial expression correlated best with cortical activity (regression coefficient = 1.26, 95% CI limits 0.84–1.67, p < 0.0001; correlation coefficient = 0.74) (n = 12, 33 test occasions). Cortical pain responses were still recorded in some infants who did not display a change in facial expression.
Conclusions
While painful stimulation generally evokes parallel cortical and behavioural responses in infants, pain may be processed at the cortical level without producing detectable behavioural changes. As a result, an infant with a low pain score based on behavioural assessment tools alone may not be pain free.
Rebeccah Slater and colleagues show that although painful stimulation generally evokes parallel cortical and behavioral responses in infants, pain may produce cortical responses without detectable behavioral changes.
Editors' Summary
Background.
Pain is a sensory and emotional experience. It is normally triggered by messages transmitted from specialized receptors (nociceptors) in the body to integrative centers in the spinal cord and brainstem and on to the brain, where it undergoes higher sensory and cognitive analysis, allowing the body to respond appropriately to the stimuli. While the experience of pain may be considered to be unpleasant, it is a useful tool in communicating to us and to others that there is something wrong with our bodies. Ultimately, these responses help restrict further damage to the body and start the process of healing.
In a clinical setting, the ability to communicate about pain allows an individual to seek strategies to ease the pain, such as taking analgesics. Being unable to effectively communicate one's experience of pain leaves the individual vulnerable to prolonged suffering. One such vulnerable group is infants.
Ignored and untreated pain in infants has been shown to have immediate and long-term effects as a result of structural and physiological changes within the nervous system. For example, the body responds to untreated pain by increased release of stress hormones, which may be associated with increased morbidity and mortality in the short term. Long-term effects of pain may include altered pain perception, chronic pain syndromes, and somatic complaints such as sleep disturbances, feeding problems, and inability to self-regulate in response to internal and external stressors. It has been proposed that attention deficit disorders, learning disorders, and behavioral problems in later childhood may be linked to repetitive pain in the preterm infant.
Why Was This Study Done?
Until as recently as the 1990s, newborns in some clinical centres underwent surgery with minimal anesthesia. Also, newborns received little or no pain management postoperatively or for painful procedures such as lumbar punctures or circumcisions. Since then, there has been growing awareness amongst clinicians that pain may be experienced from the earliest stages of postnatal life and that inadequate analgesia may lead to the type of long-term consequences mentioned above. However, gauging how much pain infants and young children are experiencing remains a substantial challenge. The researchers in this study wanted to assess the association between cortical pain responses in young infants and currently used tools for the assessment of pain in these infants. These current tools are based on behavioral and physiological measures, such as change in facial expression, and it is possible that these tools do not give an adequate measure of pain especially in infants born preterm.
What Did the Researchers Do and Find?
Twelve clinically stable infants were studied on 33 occasions when they required a heel lance to obtain a blood sample for a clinical reason. The researchers examined the relationship between brain activity and a clinical pain score, calculated using the premature infant pain profile (PIPP) in response to a painful event. Activity in the somatosensory cortex was measured noninvasively by near-infrared spectroscopy, which measures brain regional changes in oxygenated and deoxygenated hemoglobin concentration. The PIPP is a well-established pain score that ascribes a value to infant behavior such as change in facial expression.
They found that changes in brain activity in response to a painful stimulus were related to the PIPP scores. These changes were more strongly linked to the behavioral components of the PIPP, e.g., facial expression, than physiological components, e.g., heart rate. They also found that a positive brain response could occur in the absence of any facial expression.
What Do These Findings Mean?
Behaviors to communicate pain require motor responses to sensory and emotional stimuli. The maturity of this complex system in infants is not clearly understood. The results of this study raise further awareness of the ability of infants to experience pain and highlight the possibility that pain assessment based on behavioral tools alone may underestimate the pain response in infants.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050129.
Important papers on pain in human neonates are discussed in the open access Paediatric Pain Letter with links to original articles
The Institute of Child Health in London has a Web site describing a three-year international project on improving the assessment of pain in hospitalized children, with many useful links
The International Association for the Study of Pain (IASP) provides accurate and up-to-date information and links about pain mechanisms and treatment
doi:10.1371/journal.pmed.0050129
PMCID: PMC2504041  PMID: 18578562
23.  Relationships among Anxious Symptomatology, Anxiety Sensitivity and Laboratory Pain Responsivity in Children 
Cognitive behaviour therapy  2006;35(4):207-215.
Existing laboratory-based research in adult samples has suggested that anxiety sensitivity (AS) increases an individual’s propensity to experience pain-related anxiety which in turn enhances pain responsivity. Such relationships have not been examined in younger populations. Thus, the present study used structural equation modeling (SEM) to test a conceptual model in which AS would evidence an indirect relationship with pain intensity via its contribution to state-specific anticipatory anxiety in relation to a variety of laboratory pain tasks (cold pressor, thermal heat, and pressure pain) in 234 healthy children (116 girls; mean age = 12.6 years, range = 8–18 years). The model further hypothesized that existing anxious symptomatology would demonstrate a direct relationship with pain intensity. Results of the SEM supported the proposed conceptual model with the total indirect effect of AS accounting for 29% of the variance in laboratory pain intensity via its effects on pain-related anticipatory anxiety. AS did not however, evidence a direct relationship with pain intensity. Anxious symptomatology on the other hand, demonstrated a significant direct effect on pain intensity, accounting for 15% of variance. The combined effects of AS, anxiety symptoms, and anticipatory anxiety together explained 62% of the variance in pain intensity. These relationships did not differ for boys and girls indicating no moderating effect of sex in the proposed model. The present results support the potential benefit of assessing both AS and anxiety symptoms in children prior to undergoing painful stimulation.
doi:10.1080/16506070600898272
PMCID: PMC1783843  PMID: 17189238
children; adolescents; anxiety; anxiety sensitivity; laboratory pain; experimental pain; pain intensity
24.  Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis 
PLoS Medicine  2015;12(8):e1001865.
Background
Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach.
Methods and Findings
We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects.
Conclusions
Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.
Using a Mendelian randomization approach, Ge Zhang and colleagues examine the causal relationship between maternal height, birth size, and gestational age at birth.
Editors' Summary
Background
Soon after the birth of a baby, doting parents send messages to friends and relatives or post information on social media sites to let everyone know when their new baby boy or girl was born. They may also post information about how heavy he/she was at birth and his/her length. These pregnancy outcomes, together with gestational age at birth (the length of time that a baby has spent developing in its mother’s womb), affect the baby’s immediate health and survival. Importantly, however, these pregnancy outcomes are also associated with the risk of long-term adverse health outcomes such as obesity, cardiometabolic disorders (heart disease and conditions such as diabetes that affect how the body makes energy from food), and neuropsychiatric conditions (mental disorders attributable to diseases of the nervous system, such as depression). For example, some studies have shown an association between low birth weight and an increased risk of type 2 diabetes later in life.
Why Was This Study Done?
Identification of the environmental and genetic factors that causally influence gestational age, length, and weight at birth would improve our understanding of why these pregnancy outcomes are associated with disease during adulthood and could help in the design of strategies to prevent these diseases. Epidemiological studies (investigations that examine disease patterns in populations) suggest that, compared to tall mothers, short mothers tend to deliver their babies at earlier gestational ages, with lower birth weights and lengths. Epidemiological studies cannot show, however, whether variations in maternal height cause variations in pregnancy outcomes. Other characteristics shared by tall mothers might actually determine the size and gestational age of their offspring (confounding). Here, the researchers use “Mendelian randomization” to assess the causal effect of maternal height on the size and gestational age at birth of babies. Because gene variants are inherited randomly, they are not prone to confounding. So, if maternal height actually affects gestational age and size at birth, genetic variants (instruments) that affect maternal height should be associated with differences in gestational age and size at birth, provided confounding due to the transmission of parental alleles (variant forms of genes; people have two alleles of every gene, one inherited from each parent) is avoided by adjusting for the baby’s genotype.
What Did the Researchers Do and Find?
The researchers used phenotype data (observable characteristics such as maternal height and birth weight of the baby) and single nucleotide polymorphism (SNP; a type of genetic variant) data obtained from 3,486 Nordic mother/baby pairs. Analysis of the phenotype data indicated that maternal height was significantly associated with length, weight, and gestational age at birth (a significant association is unlikely to have arisen by chance). For their Mendelian randomization analysis, the researchers constructed a genetic score based on 697 SNPs known to be associated with adult height. To avoid confounding due to genetic sharing between the mother and baby, they determined which of the height-associated alleles each baby had inherited from its mother and used the nontransmitted haplotype score as a genetic instrument for maternal height (a haplotype is a set of DNA variations that are inherited together). Birth length and weight were significantly associated with both the maternal and paternal transmitted haplotype scores but not with the maternal nontransmitted haplotype score. However, gestational age was significantly but modestly associated with the maternal nontransmitted haplotype score.
What Do These Findings Mean?
The validity of the assumptions that underlie the Mendelian randomization approach and the design of the studies supplying the data for this analysis may affect the accuracy of the findings reported here. Nevertheless, these findings suggest that the observed association between maternal height and fetal growth measurements is mainly determined by the genetics of the baby. That is, differences in maternal height do not cause differences in birth weight or length. Rather, some of the gene variants that the baby inherits from its mother determine both its size and its mother’s height. These findings also provide weak evidence that the association between maternal height and gestational age is causal. Maternal height might, for example, causally influence gestational age by limiting the space available for the baby’s growth before birth. Finally, these findings introduce an extension to the Mendelian randomization approach that can be used to investigate causal associations between parental characteristics and offspring outcomes.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001865.
The March of Dimes, a not-for-profit organization for pregnancy and baby health, provides information about low birth weight and its consequences
Nemours, a not-for-profit organization for child health, provides information about the weight of newborn babies (in English and Spanish)
Wikipedia has pages on birth weight, gestational age, and Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
MedlinePlus provides information and links to additional resources about birth weight and a brief explanation of gestational age (in English and Spanish)
doi:10.1371/journal.pmed.1001865
PMCID: PMC4540580  PMID: 26284790
25.  Enteropathogenic Escherichia coli Uses NleA to Inhibit NLRP3 Inflammasome Activation 
PLoS Pathogens  2015;11(9):e1005121.
Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are related strains capable of inducing severe gastrointestinal disease. For optimal infection, these pathogens actively modulate cellular functions through the deployment of effector proteins in a type three secretion system (T3SS)-dependent manner. In response to enteric pathogen invasion, the Nod-like receptor pyrin domain containing (NLRP) inflammasome has been increasingly recognized as an important cytoplasmic sensor against microbial infection by activating caspase-1 and releasing IL-1β. EPEC and EHEC are known to elicit inflammasome activation in macrophages and epithelial cells; however, whether the pathogens actively counteract such innate immune responses is unknown. Using a series of compound effector-gene deletion strains of EPEC, we screened and identified NleA, which could subdue host IL-1β secretion. It was found that the reduction is not because of blocked NF-κB activity; instead, the reduction results from inhibited caspase-1 activation by NleA. Immunostaining of human macrophage-like cells following infection revealed limited formation of inflammasome foci with constituents of total caspase-1, ASC and NLRP3 in the presence of NleA. Pulldown of PMA-induced differentiated THP-1 lysate with purified MBP-NleA reveals that NLRP3 is a target of NleA. The interaction was verified by an immunoprecipitation assay and direct interaction assay in which purified MBP-NleA and GST-NLRP3 were used. We further showed that the effector interacts with regions of NLRP3 containing the PYD and LRR domains. Additionally, NleA was found to associate with non-ubiquitinated and ubiquitinated NLRP3 and to interrupt de-ubiquitination of NLRP3, which is a required process for inflammasome activation. Cumulatively, our findings provide the first example of EPEC-mediated suppression of inflammasome activity in which NieA plays a novel role in controlling the host immune response through targeting of NLRP3.
Author Summary
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) cause severe intestinal dysfunction, including watery diarrhea or severe bloody diarrhea, and acute kidney failure (hemolytic uremic syndrome). Transmitted through ingestion of contaminated food, these pathogens colonize and disrupt the linings of intestinal epithelial cells. EPEC and EHEC interrupt many cellular functions, including the inflammation response, to increase their chances of proliferation and survival in the intestine. Upon detection of the invasion, epithelial cells and immune cells secrete inflammatory cytokines to further boost the immune response for efficient clearance of the pathogens. IL-1β is an important inflammatory cytokine, and its secretion is regulated by a multimeric protein complex, termed the inflammasome, in host cells. In this study, we discovered that EPEC injects a bacterial effector protein, NleA, to inhibit the secretion of IL-1β. Exploring the potential mechanisms, we found that NleA does so by directly associating with NLRP3 (Nod-Like Receptor 3), one of the three basic components of the inflammasome, and that the presence of NleA interrupts the de-ubiquitination of NLRP3, which is a prerequisite for the assembly of the inflammasome. As a result, NleA reduces the formation of the NLRP3 inflammasome and negatively regulates the secretion of IL-1β.
doi:10.1371/journal.ppat.1005121
PMCID: PMC4557958  PMID: 26332984

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