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Atopy risk protective factor
Atopy risk protective factor
Atopy risk protective factor
Atopy risk protective factor
Atopy risk protective factor
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Atopy risk protective factor

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  • 1. WHAT YOU SHOULD HAVE READ BUT….2010 <ul><li>atopy risk & protective factors </li></ul>University of Verona, Italy Attilio Boner
  • 2. <ul><li>General considerations </li></ul>
  • 3. <ul><li>Prevalence and time trends </li></ul>
  • 4. Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483 <ul><li>A cross-sectional questionnaire survey of 798,685 children aged 13–14 years and 388,811 children aged 6–7 years. </li></ul>prevalence of wheeze in the past 12 months 40 – 35 – 30 – 25 – 20 – 15 – 10 – 5 – 0 0.7% 37.6% 2.4% 32.6% in the 13–14 year olds in the 6–7 year olds
  • 5. The prevalence of symptoms of severe asthma, defined as ≥ 4 attacks of wheeze or ≥ 1 night per week sleep disturbance from wheeze or wheeze affecting speech in the past 12 months. 0.1% 20% 0% 16% in the 13–14 year olds in the 6–7 year olds 30 – 20 – 10 – 0 <ul><li>A cross-sectional questionnaire survey of 798 685 children aged 13–14 years and 388 811 children aged 6–7 years. </li></ul>Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483
  • 6. Prevalence of current wheeze according to the written questionnaire in the 13–14 year age group . The symbols indicate prevalence values of <5% (blue square), 5 to <10% (green circle), 10 to <20% (yellow diamond) and >20% (red star). Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483
  • 7. Prevalence of symptoms of severe asthma according to the written questionnaire in the 13–14 year age group . The symbols indicate prevalence values of <2.5% (blue square), 2.5 to <5% (green circle), 5 to <7.5% (yellow diamond) and >7.5% (red star). Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483
  • 8. Prevalence of current wheeze in the 6–7 year age group . The symbols indicate prevalence values of <5% (blue square), 5 to <10% (green circle), 10 to <20% (yellow diamond) and >20% (red star). Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483
  • 9. Prevalence of symptoms of severe asthma in the 6–7 year age group . The symbols indicate prevalence values of <2.5% (blue square), 2.5 to <5% (green circle), 5 to <7.5% (yellow diamond) and >7.5% (red star). Global variation in the prevalence and severity of asthma symptoms: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) Lai Thorax 2009;64: 476-483
  • 10. Establishing the sequential progression of multiple allergic diagnoses in a UK birth cohort using the General Practice Research Database Punekar CEA 2009;39:1889 <ul><li>43 477 children born in 1990. </li></ul><ul><li>24 112 with complete follow-up until the age of 18 years. </li></ul>60 - 50 – 40 – 30 – 20 – 10 – 0 52% % children with at least one diagnosed allergic condition
  • 11. OR for development of 2 – 1 – 0 1.59 1.29 0.64 asthma eczema eczema eczema asthma rhinitis in children first diagnosed with Establishing the sequential progression of multiple allergic diagnoses in a UK birth cohort using the General Practice Research Database Punekar CEA 2009;39:1889
  • 12. Conclusions: Among children diagnosed with multiple allergic diseases there is likely to be a number of variants of 'the allergic march'. Of these, the diagnosis of eczema followed by asthma, which is in turn followed by rhinitis, is the most common trajectory . Some diagnoses indicate a possible strong protective effect of manifesting further likely allergic diagnoses. Establishing the sequential progression of multiple allergic diagnoses in a UK birth cohort using the General Practice Research Database Punekar CEA 2009;39:1889
  • 13. Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices. Punekar C EA 2010;39:1209 <ul><li>N ational General Practice Research Database (GPRD). </li></ul><ul><li>A retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. </li></ul>18-Year Prevalence of Clinician-Diagnosed Condition Eczema Asthma 50 – 40 – 30 – 20 – 10 – 0 36.5% 22.9% 11.4% Rhinitis
  • 14. Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices. Punekar C EA 2010;39:1209 <ul><li>N ational General Practice Research Database (GPRD). </li></ul><ul><li>A retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. </li></ul>Eczema Asthma 50 – 40 – 30 – 20 – 10 – 0 36.5% 22.9% 11.4% Rhinitis The 18-year prevalence of > 1 and all three conditions was 16.1% and 2.5%, respectively. 18-Year Prevalence of Clinician-Diagnosed Condition
  • 15. Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices. Punekar C EA 2010;39:1209 <ul><li>N ational General Practice Research Database (GPRD). </li></ul><ul><li>A retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. </li></ul>Eczema Asthma 50 – 40 – 30 – 20 – 10 – 0 36.5% 22.9% 11.4% Rhinitis A significant proportion of children experience and are diagnosed with multiple allergic conditions in early childhood. 18-Year Prevalence of Clinician-Diagnosed Condition
  • 16. Establishing the incidence and prevalence of clinician-diagnosed allergic conditions in children and adolescents using routinely collected data from general practices. Punekar C EA 2010;39:1209 <ul><li>N ational General Practice Research Database (GPRD). </li></ul><ul><li>A retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. </li></ul>Patterns of allergic disease co-morbidity in patients with complete follow-up (n=24 112)
  • 17. Time trends in the prevalence of peanut allergy: three cohorts of children from the same geographical location in the UK. Venter Allergy 2010:65:103 <ul><li>Prevalence of peanut allergy in 3 cohorts of children born in the same geographical location, Isle of Wight. </li></ul><ul><li>Reviewed between 3 and 4 years of age </li></ul>1989-1990 1.3% 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Peanut Sensitization Rate 1994-1996 2001-2002 3.3% 2.0% ns BORN p=0.03
  • 18. <ul><li>Stress </li></ul><ul><li>psiche </li></ul>
  • 19. Vacuum-assisted delivery is associated with late-onset asthma . Keski-Nisula Allergy 2009:64:1530 <ul><li>Perinatal data recorded during pregnancy and at the time of delivery. </li></ul><ul><li>5823 children born in Northern Finland in 1985–1986. </li></ul><ul><li>Self-administered questionnaires at the ages of 7 and 15–16 yrs and skin prick tests at the age of 15–16 yrs. </li></ul>LATE-ONSET ASTHMA In Children Delivered by Vacuum Extraction OR for 1.80 2.41 P<0.001 P<0.001 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 DOCTOR-DIAGNOSED ASTHMA AT ANY TIME
  • 20. Vacuum-assisted delivery is associated with late-onset asthma . Keski-Nisula Allergy 2009:64:1530 <ul><li>This was not explained by maternal demographic variables such as age or parity, or longer duration of delivery, fetal size, lower neonatal Apgar scores or neonatal need for intensive treatment after birth. </li></ul><ul><li>What could be plausible reasons behind the increased tendency towards asthma in those children who were born by vacuum delivery? </li></ul><ul><li>Children born by vacuum or forceps extraction are more often exposed to intrapartal distress . </li></ul><ul><li>The levels of umbilical cord blood cortisol have been increased in those neonates. </li></ul>
  • 21. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 Background:  Mental health has been reported to be associated with allergy, but only a few cohort studies have assessed if neurodevelopment predicts atopy. Objective: To investigate if neurobehavioral status of healthy 4-year-old children was associated with specific immunoglobulin E (IgE) at the same age and skin prick test results 2 years later.
  • 22. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 % CHILDREN WITH ATOPY 12% 17% 4 6 20 – 15 – 10 – 0 5 – 0 <ul><li>Population-based birth cohort (482 children). </li></ul><ul><li>Atopy defined as IgE levels > 0.35 kU/l. </li></ul><ul><li>McCarthy Scales of Child Abilities and California Preschool Social Competence Scale. </li></ul>AGE YEARS
  • 23. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 OR FOR ATOPY AT AGE 6 YEARS 3.06 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Lowest Tertile (Scorings ≤90 Points) of the General Cognitive Scale <ul><li>Population-based birth cohort (482 children). </li></ul><ul><li>Atopy defined as IgE levels > 0.35 kU/l. </li></ul><ul><li>McCarthy Scales of Child Abilities and California Preschool Social Competence Scale. </li></ul>
  • 24. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 OR FOR ATOPY AT AGE 6 YEARS 3.06 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Lowest Tertile (Scorings ≤90 Points) of the General Cognitive Scale <ul><li>Population-based birth cohort (482 children). </li></ul><ul><li>Atopy defined as IgE levels > 0.35 kU/l. </li></ul><ul><li>McCarthy Scales of Child Abilities and California Preschool Social Competence Scale. </li></ul>Neuropsychologic functioning and later atopy are negatively associated in preschool age children.
  • 25. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 The pathways between neurobehavior and atopy are not clearly elucidated One of the hypotheses is that atopic children are more likely to have clinical disturbances, such as symptoms of asthma or wheezing (and their corresponding treatments) that may affect behavior. These factors could modify the psychosocial environment of the child and create a vicious cycle, worsening the child neurodevelopment.
  • 26. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 The pathways between neurobehavior and atopy are not clearly elucidated One of the hypotheses is that atopic children are more likely to have clinical disturbances, such as symptoms of asthma or wheezing (and their corresponding treatments) that may affect behavior. These factors could modify the psychosocial environment of the child and create a vicious cycle, worsening the child neurodevelopment. However, our results appear to argue against this hypothesis
  • 27. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 Another hypothesis suggests that lower behavior scores might be indicators of chronic or acute stresses in the child's life that may affect atopy as well. However, we took into account many variables that indicate factors that could influence child stress or its management, such as sleeping hours, physical activity and ways of entertainment, parental social class and level of education, smoking, alcohol consumption, maternal parity, and marital status.
  • 28. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 Another hypothesis suggests that lower behavior scores might be indicators of chronic or acute stresses in the child's life that may affect atopy as well. However, we took into account many variables that indicate factors that could influence child stress or its management, such as sleeping hours, physical activity and ways of entertainment, parental social class and level of education, smoking, alcohol consumption, maternal parity, and marital status. None of these factors confounded the associations' strength.
  • 29. Neuropsychologic status at the age 4 years and atopy in a population-based birth cohort Julvez Allergy 2009:64:1279 This suggests the existence of direct physiologic pathways involved in the association between neurobehavior and atopy, maybe sharing genetic influences. Altered HPA function and allergic disorders may be part of these pathways, probably secondary to gene–environment interactions. elevated endogenous cortisol produced by HPA may affect the developing immune system with subsequent atopic responses and consequent allergic disorders
  • 30. Lower cortisol levels in children with asthma exposed to recurrent maternal distress from birth Dreger JACI 2010:125:116 <ul><li>Serum cortisol levels at age 7 to 10 years in relation to asthma status and exposure to maternal distress in children (n = 503). </li></ul><ul><li>Maternal distress was defined as a physician diagnosis of a depressive or anxiety disorder. </li></ul>
  • 31. Lower cortisol levels in children with asthma exposed to recurrent maternal distress from birth Dreger JACI 2010:125:116 <ul><li>Serum cortisol levels at age 7 to 10 years in relation to asthma status and exposure to maternal distress in children (n = 503). </li></ul><ul><li>Maternal distress was defined as a physician diagnosis of a depressive or anxiety disorder. </li></ul>Among children exposed to recurrent maternal distress, an elevation in cortisol levels occurs in response to an acute stressor ( venipuncture ) when there is no accompanying diagnosis of asthma, whereas, in comparison, children with asthma tend to exhibit lower cortisol levels.
  • 32. Neuroticism, extraversion, stressful life events and asthma: a cohort study of middle-aged adults Loerbroks Allergy 2009:64:1444 Background:  Stressful life events can trigger asthma exacerbations, but could also contribute to the development of incident asthma. However, only few studies have investigated the association between stressful life events and adult asthma prospectively. Likewise, stress-related personality traits (e.g. neuroticism and extraversion) may increase asthma risk, but this has been examined in only one prospective study. We therefore aimed to investigate the association between neuroticism, extraversion, stressful life events and incident asthma.
  • 33. Neuroticism, extraversion, stressful life events and asthma: a cohort study of middle-aged adults Loerbroks Allergy 2009:64:1444 <ul><li>Population-based sample of 5114 middle-aged adults. </li></ul><ul><li>Questionnaires between 1992 and 1995 on exposures to: - neuroticism, - extraversion and - three stressful life events (unemployment, having broken off a life partnership and death of a close person). </li></ul>HIGH VS LOW NEUROTICISM RR of Developing Asthma in 2002-2003 3.07 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Neuroticism is an enduring tendency to experience negative emotional states
  • 34. Neuroticism, extraversion, stressful life events and asthma: a cohort study of middle-aged adults Loerbroks Allergy 2009:64:1444 Having broken off a life partnership 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 2.24 Death of a close person Unemployment 1.06 1.65 <ul><li>Population-based sample of 5114 middle-aged adults. </li></ul><ul><li>Questionnaires between 1992 and 1995 on exposures to: - neuroticism, - extraversion and - three stressful life events (unemployment, having broken off a life partnership and death of a close person). </li></ul>RR of Developing Asthma in 2002-2003
  • 35. Neuroticism, extraversion, stressful life events and asthma: a cohort study of middle-aged adults Loerbroks Allergy 2009:64:1444 Having broken off a life partnership 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 2.24 Death of a close person Unemployment 1.06 1.65 <ul><li>Population-based sample of 5114 middle-aged adults. </li></ul><ul><li>Questionnaires between 1992 and 1995 on exposures to: - neuroticism, - extraversion and - three stressful life events (unemployment, having broken off a life partnership and death of a close person). </li></ul>RR of Developing Asthma in 2002-2003 Interpersonal conflicts may increase asthma risk, possibly along an immunological pathway.
  • 36. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Stress Activates the hypothalamic-pituitary-adrenal axis Impaired glucocorticoid receptor expression and/or function Promote and amplify airway inflammation in response to infections, allergen, or irritant exposure Release of endogenous glucocorticoids
  • 37. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 glucocorticoid binding to the intracellular receptor (GR) molecular rearrangement of the GR–heat shock protein 90 heterocomplex and interacting with specific DNA elements, termed glucocorticoid response elements (GREs) GR nuclear localization, homodimerization, and DNA binding GR signaling and glucocorticoid resistance in airway inflammation.
  • 38. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Mechanisms of glucocorticoid action. The activated GR homodimer binds to GREs, located within regulatory regions of glucocorticoid-responsive genes in the nucleus.
  • 39. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Positive GRE mediates transcriptional upregulation of anti-inflammatory genes such as NF-kB inhibitor a (IkB α ), the glucocorticoid-inducible leucine zipper (GILZ) , or IL 10. Mechanisms of glucocorticoid action. The activated GR homodimer binds to GREs, located within regulatory regions of glucocorticoid-responsive genes in the nucleus.
  • 40. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Negative GRE mediates transcriptional downregulation. Mechanisms of glucocorticoid action. The activated GR homodimer binds to GREs, located within regulatory regions of glucocorticoid-responsive genes in the nucleus.
  • 41. Mechanisms of glucocorticoid action. The activated GR homodimer binds to GREs, located within regulatory regions of glucocorticoid-responsive genes in the nucleus. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 In monomeric form, the activated GR may interact with other transcription factors such as NF-kB. This interaction can occur indirectly through transcriptional cofactor (HDAC) binding (C) or by RNA polymerase dephosphorylation (D).
  • 42. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Hypothesized mechanisms by which glucocorticoid resistance could occur. A , Glucocorticoid binding to the GR induces molecular rearrangement of the GR–heat shock protein 90 heterocomplex and promotes GR nuclear translocation, homodimerization, and DNA binding. B , This process can be modulated by GR/NF-kB interactions, directly by affecting transactivation (GRE-mediated) as well as transrepression of GR functions. C , Indirect inhibition of the GR function may be achieved by transcription factor ‘‘tethering.’’
  • 43. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 1) Alveolar epithelial cells, Clara cells, and cells of submucosal glands in the lung. Surfactant protein D a constitutive mediator of antigen clearance and is capable of interacting with cellular components of both the innate and adaptive immune systems on mucosal surfaces. Significantly increased SP-D levels. It is possible that the beneficial effects of glucocorticoid therapy are partially mediated by enhanced SP-D expression in the lung. 2) Corticosteroid treatment Role of the epithelial product surfactant protein D in asthmatic inflammation.
  • 44. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 1) Alveolar epithelial cells, Clara cells, and cells of submucosal glands in the lung. Surfactant protein D a constitutive mediator of antigen clearance and is capable of interacting with cellular components of both the innate and adaptive immune systems on mucosal surfaces. Significantly increased SP-D levels. It is possible that the beneficial effects of glucocorticoid therapy are partially mediated by enhanced SP-D expression in the lung. 2) Corticosteroid treatment Role of the epithelial product surfactant protein D in asthmatic inflammation. Studies on SP-D–deficient mice demonstrated enhanced susceptibility to inflammation in infectious and inflammatory models, including allergic airway sensitization, and abnormal activation of alveolar macrophages and dendritic cells.
  • 45. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Proposed mechanism of how stress-induced glucocorticoid insensitivity could affect the innate immune system during the allergic airway response.
  • 46. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Proposed mechanism of how stress-induced glucocorticoid insensitivity could affect the innate immune system during the allergic airway response. Altered corticosteroid responsiveness of airway epithelial cells may inhibit SP-D production.
  • 47. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Proposed mechanism of how stress-induced glucocorticoid insensitivity could affect the innate immune system during the allergic airway response. Stress abrogates inhibitory effects of corticosteroid on responsiveness of proinflammatory dendritic cells.
  • 48. Social stress and asthma: The role of corticosteroid Insensitivity Haczku JACI 2010;125:550 Proposed mechanism of how stress-induced glucocorticoid insensitivity could affect the innate immune system during the allergic airway response. Diminished SP-D levels will result in a failure to protect against dendritic cell and T H 2-cell activation and the consequent allergic airway response.
  • 49. <ul><li>virus and bacteria infections </li></ul>
  • 50. The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization – a birth cohort study. Kemp Pediatr Allergy Immunol 2009:20:536 <ul><li>Animal models show that viral respiratory infection in conjunction with allergen presentation can enhance sensitization. </li></ul><ul><li>This prospective study assesses the influence of an upper respiratory tract infection (URI) in the first month of life and the season of birth on the development of hay fever and ryegrass allergen sensitization in childhood. </li></ul>
  • 51. The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization – a birth cohort study. Kemp Pediatr Allergy Immunol 2009:20:536 <ul><li>Two birth cohorts: </li></ul><ul><ul><li>498 children were followed up at 8 yr. </li></ul></ul><ul><ul><li>415 children followed up at 16 yr. </li></ul></ul><ul><li>Parental report of an early upper respiratory tract infection (EURI) documented prospectively by a home interview at 1 month of age. </li></ul>% Children Born During the Ryegrass Pollen Season 9.6% 12.5% 15 – 10 – 0 5 – 0 1 st 2 nd BIRTH COHORTS
  • 52. The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization – a birth cohort study. Kemp Pediatr Allergy Immunol 2009:20:536 OR FOR RYE GRASS SENSITIZATION 5.8 BORN DURING THE POLLEN SEASON BORN OUTSIDE THE POLLEN SEASON 6 – 5 – 4 – 3 – 2 – 1 – 0 0.62 IN CHILDREN WITH Upper Respiratory Tract Infections in the 1° Month of Life
  • 53. The interaction between early life upper respiratory tract infection and birth during the pollen season on rye-sensitized hay fever and ryegrass sensitization – a birth cohort study. Kemp Pediatr Allergy Immunol 2009:20:536 OR FOR RYE GRASS SENSITIZATION 5.8 BORN DURING THE POLLEN SEASON BORN OUTSIDE THE POLLEN SEASON 6 – 5 – 4 – 3 – 2 – 1 – 0 0.62 Early life viral URI interacts with ryegrass allergen exposure in the development of rye grass allergen sensitization and rye grass sensitized hay fever symptoms. IN CHILDREN WITH Upper Respiratory Tract Infections in the 1° Month of Life
  • 54. <ul><li>Birth cohort’ 3,963 newborn children. </li></ul><ul><li>Followed prospectively for 8 years. </li></ul><ul><li>Daycare was defined as early (aged 0–2 yr), late (aged 2–4 yr), or none (no daycare before age 4 yr). </li></ul>AT AGE 8 YRS OR FOR 0.99 EARLY DAY CARE 0.86 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 ASTHMA ALLERGIC SENSITIZATION Early Daycare Is Associated with an Increase in Airway Symptoms in Early Childhood but Is No Protection against Asthma or Atopy at 8 Years Caudri AJRCCM 2009:180:491
  • 55. <ul><li>Birth cohort’ 3,963 newborn children. </li></ul><ul><li>Followed prospectively for 8 years. </li></ul><ul><li>Daycare was defined as early (aged 0–2 yr), late (aged 2–4 yr), or none (no daycare before age 4 yr). </li></ul>AT AGE 8 YRS OR FOR 0.99 EARLY DAY CARE 0.86 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 ASTHMA ALLERGIC SENSITIZATION Early Daycare Is Associated with an Increase in Airway Symptoms in Early Childhood but Is No Protection against Asthma or Atopy at 8 Years Caudri AJRCCM 2009:180:491 <ul><li>Early daycare is associated with an increase in airway symptoms until the age of 4 years. </li></ul><ul><li>We found no protection against asthma symptoms, hyperresponsiveness, or allergic sensitization at the age of 8 years. </li></ul>
  • 56. Background: Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant T H 2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma. Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology Horvat JACI 2010;125:617
  • 57. <ul><li>Neonatal, infant, or adult BALB/c mice were infected. </li></ul><ul><li>6 weeks later were sensitized and subsequently challenged with ovalbumin. </li></ul>Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology Horvat JACI 2010;125:617
  • 58. <ul><li>Neonatal, infant, or adult BALB/c mice were infected. </li></ul><ul><li>6 weeks later were sensitized and subsequently challenged with ovalbumin. </li></ul>Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology Horvat JACI 2010;125:617 Early-life respiratory chlamydial infections modulate immune responses, alter lung function and structure, and enhance the severity of allergic airways disease in later life.
  • 59. 0.34 Sensitization at both 2 and 5 years of age 1.0 – 0.5 – 0 <ul><li>219 Swedish infants followed to 5 years of age. </li></ul><ul><li>SPTs, sIgE, </li></ul><ul><li>serostatus against EBV. </li></ul>Early-life EBV infection protects against persistent IgE sensitization Saghafian-Hedengren JACI 2010;125:433 In 5-year-olds who were infected with EBV before the age of 2 years OR for
  • 60. 4.64 Late onset IgE sensitization In children with contraction of EBV after 2 years of age OR for 5 - 4 - 3 – 2 – 1 – 0 Early-life EBV infection protects against persistent IgE sensitization Saghafian-Hedengren JACI 2010;125:433 <ul><li>219 Swedish infants followed to 5 years of age. </li></ul><ul><li>SPTs, sIgE, </li></ul><ul><li>serostatus against EBV. </li></ul>
  • 61. <ul><li>paracetamol </li></ul>
  • 62. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. - 2.1 (paracetamol exposure in utero), - 1.5 to 3.2 (paracetamol use in infancy or childhood) - 2.9 (paracetamol use in adults) 1° Strength of effect: Increased asthma risk of up to: Shaheen SO, Thorax 2002;57:958-63. Shaheen SO, Clin Exp Allergy 2005;35:18-25. Rebordosa C, Int J Epidemiol2008;37:583-90. Koniman R, Pediatr Allergy Immunol 2007;18:128-34. Garcia-Marcos L, Int Arch Allergy Immunol2008;149:33-7. Persky V, Ann Alle Asthma Immunol 2008;101:271-8. Perzanowski MS, JACI 2008;121(suppl):S231. Shaheen SO, Thorax. 2000;55:266–270. Shaheen S, Eur Respir J. 2008;32:1231–1236. Davey G, J Allergy Clin Immunol. 2005;116:863–868. McKeever TM, Am J Respir Crit Care Med. 2005;171:966–971. Barr RG , Am J Respir Crit Care Med. 2004;169:836–841. Thomsen SF, J Asthma. 2008;45:675–676. Shaheen SO, Thorax 2002;57:958-63. Beasley R, Lancet 2008;372:1039-48.
  • 63. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. 2°Dose response: Present for paracetamol exposure - in utero - in childhood - in adults Shaheen SO, Thorax 2002;57:958-63. Shaheen SO, Clin Exp Allergy 2005;35:18-25. Beasley R, Lancet. 2008;372:1039–1048. Shaheen SO, Thorax. 2000;55:266–270. Davey G, J Allergy Clin Immunol. 2005;116:863–868. McKeever TM, Am J Respir Crit Care Med. 2005;171:966–971. Barr RG, Am J Respir Crit Care Med. 2004;169:836–841.
  • 64. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 3° Consistency/Coherence: - Consistency between different studies in different age groups in different populations worldwide Shaheen SO, Thorax. 2002;57:958–963. Shaheen SO, Clin Exp Allergy. 2005;35:18–25. Rebordosa C, Int J Epidemiol. 2008;37:583–590. Koniman R, Pediatr Allergy Immunol. 2007;18:128–134. Garcia-Marcos L, Int Arch Allergy Immunol. 2008;149:33–37. Persky V, Ann Allergy Asthma Immunol. 2008;101:271–278. Perzanowski MS, J Allergy Clin Immunol. 2008;121(suppl):S231. Beasley R, Lancet. 2008;372:1039–1048. Shaheen SO, 2000;55:266–270. Shaheen S, Eur Respir J. 2008;32:1231–1236. Davey G, J Allergy Clin Immunol. 2005;116:863–868. McKeever TM, Am J Respir Crit Care Med. 2005;171:966–971. Barr RG, Am J Respir Crit Care Med. 2004;169:836–841. Thomsen SF, J Asthma. 2008;45:675–676. Lesko SM, Pediatrics. 2002;109:e20. Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300.
  • 65. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 4° Exposure before response: Observed in studies of paracetamol exposure: - in the intrauterine environment - in infancy - in adult life Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. Shaheen SO, Thorax 2002;57:958-63. Shaheen SO, Clin Exp Allergy 2005;35:18-25. Rebordosa C, Int J Epidemiol2008;37:583-90. Koniman R, Pediatr Allergy Immunol 2007;18:128-34. Garcia-Marcos L, Int Arch Allergy Immunol2008;149:33-7. Persky V, Ann Alle Asthma Immunol 2008;101:271-8. Perzanowski MS, JACI 2008;121(suppl):S231. Beasley R, Lancet. 2008;372:1039–1048. Barr RG, Am J Respir Crit Care Med. 2004;169:836–841. Thomsen SF, J Asthma. 2008;45:675–676.
  • 66. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 5° Biologic plausibility: - Through increased oxidant- induced inflammation and potentially enhanced T H 2 response Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. Nuttall SL, J Clin Pharmacy Ther. 2003;28:251–257. Micheli L, Environ Health Perspect. 1994;102(suppl 9):63–64. Dimova S, Int J Biochem Cell Biol. 2005;37:1727–1737. Barnes PJ, Free Radic Biol Med. 1990;9:235–243. Peterson JD, Proc Natl Acad Sci U S A. 1998;95:3071–3076.
  • 67. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 6° Removal of exposure prevents disease: - Not yet examined Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. but..Giuseppina and Michele
  • 68. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 7° Specificity: - No increased risk of asthma associated with aspirin or other nonsteroidal anti-inflammatory drugs Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. Kurth T, Thorax. 2008;63:514–518. Barr RG, Am J Respir Crit Care Med. 2007;175:120–125.
  • 69. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 8° Temporal association: - International trends of increasing paracetamol use and increasing prevalence of asthma Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. Varner AE, Ann Allergy Asthma Immunol. 1998;81:347–351 der W, N Engl J Med. 2006;355:2226–2235. Bertolini A, CNS Drug Rev. 2006;12:250–275.
  • 70. The acetaminophen and asthma hypothesis 10 years on: A case to answer. Farquhar JACI 2009;124:649 9° Analogy: - Oxidant-induced airway inflammation in asthma (eg, ozone, other pollutants) - protective effects of antioxidant diet in asthma Summary of the evidence linking paracetamol use and asthma based on Bradford Hill criteria of causation Hill AB. Proc R Soc Med 1965;58:295-300. Shaheen SO, Am J Respir Crit Care Med. 2001;164:1823–1828. Rubin RN, Am J Respir Crit Care Med. 2004;169:393–398. McConnell R, Lancet. 2002;359:386–391.
  • 71. Acetaminophen Use and the Risk of Asthma in Children and Adults A Systematic Review and Metaanalysis Etminan CHEST 2009; 136:1316 OR FOR ASTHMA IN CHILDREN 1.63 AMONG SUBJECTS USING ACETAMINOPHEN 2.0 – 1.5 – 1.0 – 0.5 – 0 <ul><li>13 cross-sectional studies </li></ul><ul><li>4 cohort studies </li></ul><ul><li>2 case-control studies </li></ul><ul><li>425,140 subjects </li></ul>
  • 72. OR FOR ASTHMA IN CHILDREN 1.28 PRENATAL 2.0 – 1.5 – 1.0 – 0.5 – 0 1.47 1.60 DURING 1 ST YEAR OF LIFE 1 YEAR PRIOR TO THE DIAGNOSIS OF ASTHMA USE OF ACETAMINOPHEN Acetaminophen Use and the Risk of Asthma in Children and Adults A Systematic Review and Metaanalysis Etminan CHEST 2009; 136:1316
  • 73. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun C EA 2010; 40:619 11.5% Wheeze Eczema 8.6% % Children at 1 Year with 15 – 10 – 0 5 – 0 <ul><li>1065 pregnant women. </li></ul><ul><li>At 1 year of age, data on wheeze and eczema in the children. </li></ul>
  • 74. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun C EA 2010; 40:619 Maternal allergic history OR for Wheeze 3.0 Paracetamol use by the child OR for Eczema Maternal allergic history 3.68 Paracetamol use by the child 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 11 – 10 – 11.0 2.6 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0
  • 75. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun C EA 2010; 40:619 Bed Floor Grass Matting OR for Eczema 1.5 – 1.0 – 0.5 – 0 <ul><li>1065 pregnant women. </li></ul><ul><li>At 1 year of age, data on wheeze and eczema in the children. </li></ul>1.0 1.48 0.42 Child’s Sleeping Place
  • 76. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 Background: Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.
  • 77. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 <ul><li>Population-based birth cohort (n=301) </li></ul><ul><li>P rospectively assessed the use of analgesics during pregnancy </li></ul><ul><li>Genotyping for glutathione S transferase ( GST) polymorphisms. </li></ul>% mothers reporting acetaminophen use during pregnancy 34% 35 - 30 - 25 – 20 – 15 – 10 – 5 – 0
  • 78. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 % children with current wheezing at age 5 years 27% 30 - 25 – 20 – 15 – 10 – 5 – 0 <ul><li>Population-based birth cohort (n=301) </li></ul><ul><li>P rospectively assessed the use of analgesics during pregnancy </li></ul><ul><li>Genotyping for glutathione S transferase ( GST) polymorphisms. </li></ul>
  • 79. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 in children with prenatal exposure to acetaminophen OR for 1.71 P= 0.003 2 – 1 – 0 The risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). current wheeze
  • 80. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 Association between days of acetaminophen use during pregnancy and current wheeze at age 5 years stratified by common polymorphism in the GSTP1 gene. The interaction between any prenatal acetaminophen use and the presence of a G allele (AG or GG) in the GSTP1 (A105G) polymorphism on wheeze at age 5 was statistically significant ( p=0.009 ) in fully adjusted analyses.
  • 81. Association between days of acetaminophen use during pregnancy and current wheeze at age 5 years stratified by common polymorphism in the GSTP1 gene. The interaction between any prenatal acetaminophen use and the presence of a G allele (AG or GG) in the GSTP1 (A105G) polymorphism on wheeze at age 5 was statistically significant (p=0.009) in fully adjusted analyses. Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort Perzanowski Thorax 2010;65:118 Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.
  • 82. FEBRILE DAYS PER YEAR <ul><li>Data collected prospectively in child day care centers in the 1990’s by asking parents to record daily symptoms that included a temperature of > 38.0 °C and medications that included antipyretics. </li></ul><ul><li>Follow-up survey of allergic disease morbidity covered 928 adolescents. </li></ul>ASTHMATIC (n=93) 8.21 Adolescentswith asthma or atopic eczema have more febrile days in early childhood: A possible explanation for the connection between paracetamol and asthma? Tapiainen JACI 2010;125:751 5.49 6.79 ATOPIC ECZEMA (n=233) HEALTHY (n=826) 10 – 1 – 0 p=0.03 p=0.04
  • 83. FEBRILE DAYS PER YEAR <ul><li>Data collected prospectively in child day care centers in the 1990’s by asking parents to record daily symptoms that included a temperature of > 38.0 °C and medications that included antipyretics. </li></ul><ul><li>Follow-up survey of allergic disease morbidity covered 928 adolescents. </li></ul>ASTHMATIC (n=93) 8.21 Adolescentswith asthma or atopic eczema have more febrile days in early childhood: A possible explanation for the connection between paracetamol and asthma? Tapiainen JACI 2010;125:751 5.49 6.79 ATOPIC ECZEMA (n=233) HEALTHY (n=826) 10 – 1 – 0 p=0.03 p=0.04 The subjects with asthma at follow-up had 0.85 more days of paracetamol medication per person-year
  • 84. Eff ect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Prymula Lancet 2009;374:1339 <ul><li>459 healthy infants </li></ul><ul><li>3 prophylactic paracetamol doses every 6–8 h in the first 24 h (n=226) or </li></ul><ul><li>no prophylactic paracetamol (n=233) after each vaccination </li></ul>% of children with temperature ≥ 38°C 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 42% 66% Paracetamol NO Paracetamol
  • 85. Eff ect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Prymula Lancet 2009;374:1339 <ul><li>459 healthy infants </li></ul><ul><li>3 prophylactic paracetamol doses every 6–8 h in the first 24 h (n=226) or </li></ul><ul><li>no prophylactic paracetamol (n=233) after each vaccination </li></ul><ul><li>Antibody geometric mean (GMCs) concentrations were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, antidiphtheria, antitetanus. </li></ul><ul><li>After boosting, lower antibody GMCs persisted in the prophylactic paracetamol group for antitetanus, </li></ul><ul><li>and all pneumococcal serotypes apart from 19F. </li></ul>
  • 86. Eff ect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Prymula Lancet 2009;374:1339 <ul><li>459 healthy infants </li></ul><ul><li>3 prophylactic paracetamol doses every 6–8 h in the first 24 h (n=226) or </li></ul><ul><li>no prophylactic paracetamol (n=233) after each vaccination </li></ul><ul><li>Antibody geometric mean (GMCs) concentrations were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, antidiphtheria, antitetanus. </li></ul><ul><li>After boosting, lower antibody GMCs persisted in the prophylactic paracetamol group for antitetanus, </li></ul><ul><li>and all pneumococcal serotypes apart from 19F. </li></ul>prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced.
  • 87. Effetto vaccinazioni
  • 88. <ul><li>Allergens </li></ul>
  • 89. <ul><li>Lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th 2 response in mice challenged with LPS and an experimental harmless airborne antigen. </li></ul><ul><li>IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10–dependent manner. </li></ul><ul><li>Specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. </li></ul>Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice Bedoret J Clin Inv 2009;119:3723
  • 90. The association between early sensitization patterns and subsequent allergic disease. The DARC birth cohort study. Kjaer Pediatr Allergy Immunol 2009:20:726 <ul><li>Birth cohort of 562 children. </li></ul><ul><li>SPTs, and s-IgE. </li></ul><ul><li>Follow-up: 6 yrs. </li></ul>In Subjects with Development of Early (3-18 Mo) Food Sensitization OR for 4.0 4.0 ECZEMA ASTHMA 4.0 – 3.0 – 2.0 – 1.0 – 0 AT AGE 6 YRS
  • 91. The association between early sensitization patterns and subsequent allergic disease. The DARC birth cohort study. Kjaer Pediatr Allergy Immunol 2009:20:726 ATOPIC DERMATITIS 53% % SUBJECTS ALREADY SENSITISED TO FOOD AT THE AGE 6 MO. ASTHMA RHINOCONJUNCTIVITIS 60 – 50 – 40 – 30 – 20 – 10 – 0 42% 47% AT AGE 6 YRS
  • 92. High prevalence of sensitization to aeroallergens in children 4 yrs of age or younger with symptoms of allergic disease. Baatenburg de Jong Ped All Imm 2009:20:735 HOUSE DUST MITE % Subjects with sIgE >0.35 KU/L DOG CAT GRASS POLLEN 20 – 15 – 10 – 0 5 – 0 0 12% 7% 8% 9% <ul><li>2946 children 0 to 4 yr of age presenting with symptoms of allergic disease. </li></ul><ul><li>Specific IgE. </li></ul>
  • 93. High prevalence of sensitization to aeroallergens in children 4 yrs of age or younger with symptoms of allergic disease. Baatenburg de Jong Ped All Imm 2009:20:735 HOUSE DUST MITE % Subjects with sIgE >0.35 KU/L DOG CAT GRASS POLLEN 20 – 15 – 10 – 0 5 – 0 0 12% 7% 8% 9% <ul><li>2946 children 0 to 4 yr of age presenting with symptoms of allergic disease. </li></ul><ul><li>Specific IgE. </li></ul>Overall, 505 (17%) tests were positive to aeroallergens.
  • 94. High prevalence of sensitization to aeroallergens in children 4 yrs of age or younger with symptoms of allergic disease. Baatenburg de Jong Ped All Imm 2009:20:735 HOUSE DUST MITE % Subjects with sIgE >0.35 KU/L DOG CAT GRASS POLLEN 20 – 15 – 10 – 0 5 – 0 0 12% 7% 8% 9% <ul><li>2946 children 0 to 4 yr of age presenting with symptoms of allergic disease. </li></ul><ul><li>Specific IgE. </li></ul>Positive tests were more common in boys (19.2%) than in girls (14.2%, p <0.01)
  • 95. High prevalence of sensitization to aeroallergens in children 4 yrs of age or younger with symptoms of allergic disease. de Jong Pediatr Allergy Immunol 2009:20:735 Percentage of positive specific IgE tests to food allergens (white bars) and inhalant allergens (black bars) in children of different ages. <ul><li>2946 children 0 to 4 yr of age presenting with symptoms of allergic disease. </li></ul><ul><li>Specific IgE. </li></ul>
  • 96. Increased rate and greater severity of allergic reactions to insect sting among schoolchildren with atopic diseases Graif Pediatr Allergy Immunol 2009:20:757 <ul><li>13–14-yr-old schoolchildren. </li></ul><ul><li>10,021 ISAAC questionnaires. </li></ul>36.9% 24.8% AMONG CHILDREN WITH ANY OF THE ATOPIC DISEASES 40 – 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 0 NON-ATOPIC CHILDREN % Children Reporting an Allergic Reaction to Insect Sting P<0.0001
  • 97. Increased rate and greater severity of allergic reactions to insect sting among schoolchildren with atopic diseases Graif Pediatr Allergy Immunol 2009:20:757 <ul><li>13–14-yr-old schoolchildren. </li></ul><ul><li>10,021 ISAAC questionnaires. </li></ul>36.9% 24.8% AMONG CHILDREN WITH ANY OF THE ATOPIC DISEASES 40 – 35 – 30 – 25 – 20 – 15 – 10 – 0 5 – 0 0 NON-ATOPIC CHILDREN % Children Reporting an Allergic Reaction to Insect Sting P<0.0001 Children in the atopic group had a significantly higher rate of severe allergic reactions than the non-atopic children, (p <0.0001)
  • 98. Dynamic evolution of serum immunoglobulin E to airborne allergens throughout childhood: results from the Multi-Centre Allergy Study birth cohort Matricard Clinical & Experimental Allergy 2009;39:1551 <ul><li>273 children from the Multi-Centre Allergy Study. </li></ul><ul><li>IgE against airborne allergens at 2, 5, 7, and 10 years of age. </li></ul>183 1 p<0.0005 P=0.001 <ul><li>Hierarchy of sensitization prevalence (grass > birch > mites > cat > dog). </li></ul><ul><li>A mono-sensitization state was relatively short (measurable half-life = 3 years) as additional sensitizations were acquired frequently, and relatively soon after the first one. </li></ul><ul><li>Remission of weak sensitization (UNICAP classes 1-2) was also quite frequent, especially before 5 years of age. </li></ul><ul><li>By contrast, stronger IgE responses (>3.5 kU/l) were invariably persistent. </li></ul>
  • 99. Early sensitization was associated with a higher tendency for poly-sensitization at 10 years of age and allergic rhino-conjunctivitis and/or asthma at 13 years of age. Dynamic evolution of serum immunoglobulin E to airborne allergens throughout childhood: results from the Multi-Centre Allergy Study birth cohort Matricard Clinical & Experimental Allergy 2009;39:1551
  • 100. <ul><li>Allergens </li></ul><ul><li>acari </li></ul>
  • 101. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 <ul><li>Clinical and laboratory biomarkers in 2-year-olds that are predictive of the risk for persistent atopy and wheeze at age 5 years. </li></ul><ul><li>198 atopic family history– positive children followed to age 5 years. </li></ul>
  • 102. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 Age-related changes in IgE titers.
  • 103. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 Age-related changes in IgE titers. Aeroallergen-specific IgE titers cycled continuously within the low range in nonatopic subjects.
  • 104. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 Age-related changes in IgE titers. Atopic subjects displayed similar cycling in infancy but eventually locked into a stable pattern of upwardly trending antibody production.
  • 105. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 <ul><li>Clinical and laboratory biomarkers in 2-year-olds that are predictive of the risk for persistent atopy and wheeze at age 5 years. </li></ul><ul><li>198 atopic family history– positive children followed to age 5 years. </li></ul>Attaining mite-specific IgE titers of > 0.20 kU/L by age 2 years was associated with a 12.7% risk of persistent wheeze , increasing progressively to an 87.2% risk with increasing numbers of severe lower respiratory tract illnesses experienced.
  • 106. Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study Holt JACI 2010;125:653 Conclusion: The risk for development of persistent wheeze in children can be quantified by means of integration of measures related to early sensitization and early infections . Follow-up studies along similar lines in larger unselected populations to refine this approach are warranted.
  • 107. <ul><li>A novel neonatal mouse model of allergic airways disease. </li></ul><ul><li>Neonatal Balb/c mice were challenged three times weekly from Day 3 of life using intranasal house dust mite (HDM) or saline for up to 12 weeks. </li></ul><ul><li>T otal and eosinophilic inflammation was significantly increased in the lungs of HDM-exposed neonates from Week 2. </li></ul><ul><li>Goblet cells and peribronchiolar reticulin deposition were significantly increased in HDM-exposed neonates from Week 3. </li></ul><ul><li>HDM-exposed neonates had increased AHR from Week 2 onward. </li></ul>Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite–Exposed Neonatal Mice Saglani AJRCMB 2009:41:281
  • 108. <ul><li>A novel neonatal mouse model of allergic airways disease. </li></ul><ul><li>Neonatal Balb/c mice were challenged three times weekly from Day 3 of life using intranasal house dust mite (HDM) or saline for up to 12 weeks. </li></ul><ul><li>T otal and eosinophilic inflammation was significantly increased in the lungs of HDM-exposed neonates from Week 2. </li></ul><ul><li>Goblet cells and peribronchiolar reticulin deposition were significantly increased in HDM-exposed neonates from Week 3. </li></ul><ul><li>HDM-exposed neonates had increased AHR from Week 2 onward. </li></ul>Importantly, all abnormalities developed in parallel, not sequentially, between 2 and 3 weeks of age. Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite–Exposed Neonatal Mice Saglani AJRCMB 2009:41:281
  • 109. House Dust Mite–Promoted Epithelial-to-Mesenchymal Transition in Human Bronchial Epithelium Heijink AJRCMB 2010;42:69 Human bronchial epithelium (16HBE cells) Fibrogenic cytokine TGF-β and protease-containing aeroallergen house dust mite induce epithelial-to-mesenchymal transition (EMT), a key process in tissue repair and remodeling +TGF- β
  • 110. <ul><li>Allergens </li></ul><ul><li>Cane e gatto </li></ul>
  • 111. Cat sensitization according to cat window of exposure in adult asthmatics Oryszczyn Clinical & Experimental Allergy 2009;39:1515 183 1 p<0.0005 P=0.001 <ul><li>Tolerance to cat may be reflected by high IgG4 without IgE sensitization. </li></ul><ul><li>SPT response to cat, specific IgE and IgG4 to Fel d 1. </li></ul><ul><li>167 asthmatics (mean age 40 years) . </li></ul><ul><li>Childhood and/or current exposure to cat. </li></ul>
  • 112. 183 1 p<0.0005 P=0.001 Cat sensitization according to cat window of exposure in adult asthmatics Oryszczyn Clinical & Experimental Allergy 2009;39:1515 <ul><li>Tolerance to cat may be reflected by high IgG4 without IgE sensitization. </li></ul><ul><li>SPT response to cat, specific IgE and IgG4 to Fel d 1. </li></ul><ul><li>167 asthmatics (mean age 40 years) . </li></ul><ul><li>Childhood and/or current exposure to cat. </li></ul>
  • 113. 183 1 p<0.0005 P=0.001 Cat sensitization according to cat window of exposure in adult asthmatics Oryszczyn Clinical & Experimental Allergy 2009;39:1515 <ul><li>Tolerance to cat may be reflected by high IgG4 without IgE sensitization. </li></ul><ul><li>SPT response to cat, specific IgE and IgG4 to Fel d 1. </li></ul><ul><li>167 asthmatics (mean age 40 years) . </li></ul><ul><li>Childhood and/or current exposure to cat. </li></ul>Adult asthmatics exposed to cats since childhood present an immunologic pattern with high IgG4 and low IgE. Continuous exposure may maintain a state of immunological tolerance to cat.
  • 114. Associations between cat keeping, allergen exposure, allergic sensitization and atopic diseases: Results from the Children of Lübeck Allergy and Environment Study (KLAUS) Schäfer Pediatr Allergy Immunol 2009:20:353 <ul><li>606 children (5- to 6-yr old) were studied in the course of school entrance examination (Germany). </li></ul>Relationship between measured cat allergen exposure levels in households and prevalence of allergic sensitization in 606 school beginners.
  • 115. Associations between cat keeping, allergen exposure, allergic sensitization and atopic diseases: Results from the Children of Lübeck Allergy and Environment Study (KLAUS) Schäfer Pediatr Allergy Immunol 2009:20:353 <ul><li>606 children (5- to 6-yr old) were studied in the course of school entrance examination (Germany). </li></ul>Relationship between measured cat allergen exposure levels in households and prevalence of allergic sensitization in 606 school beginners. The data suggest a promoting effect of cat keeping for atopic diseases.
  • 116. Effects of pets on asthma development up to 8 years of age: the PIAMA study Kerkhof Allergy 2009:64:1202 <ul><li>2951 children, participating in the PIAMA birth cohort study. </li></ul>0.68 HOUSE DUST MITE SENSITAZION In Children with a Cat at Home at Age 3 Mo. OR for 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0
  • 117. Effects of pets on asthma development up to 8 years of age: the PIAMA study Kerkhof Allergy 2009:64:1202 0.49 POLLEN SENSITAZION 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 In Children with a Dog at Home at Age 3 Mo. OR for <ul><li>2951 children, participating in the PIAMA birth cohort study. </li></ul>
  • 118. Effects of pets on asthma development up to 8 years of age: the PIAMA study Kerkhof Allergy 2009:64:1202 0.49 POLLEN SENSITAZION 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 In Children with a Dog at Home at Age 3 Mo. OR for <ul><li>2951 children, participating in the PIAMA birth cohort study. </li></ul>A cat or dog at home did not significantly affect asthma incidence in each subsequent year.
  • 119. Effects of pets on asthma development up to 8 years of age: the PIAMA study Kerkhof Allergy 2009:64:1202 Incidence of asthma in different age-periods by the presence of a cat at home (A) or a dog at home (B) at the beginning of the period. Differences were not statistically significant.
  • 120. <ul><li>Funghi umidità </li></ul>
  • 121. Symptom days per 2 weeks at baseline Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children Pongracic JACI 2010;125:593 <ul><li>Participants 5 to 11 years old with at least 1 positive skin test response to a fungal allergen. </li></ul><ul><li>Indoor and outdoor airborne culturable fungi levels measured at baseline and throughout the 2-year study. </li></ul>6.3 YES 5.7 NO 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 SPTs for mold
  • 122. EXCESS SYMPTOM DAYS per 2 WEEKS ASSOCIATED WITH 10-FOLD INCREASE IN Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children Pongracic JACI 2010;125:593 <ul><li>Participants 5 to 11 years old with at least 1 positive skin test response to a fungal allergen. </li></ul><ul><li>Indoor and outdoor airborne culturable fungi levels measured at baseline and throughout the 2-year study. </li></ul>+43% INDOOR +39% OUTDOOR ALLERGENS 50 – 40 – 30 – 20 – 10 – 0 P<0.01 P<0.01
  • 123. EXCESS SYMPTOM DAYS per 2 WEEKS ASSOCIATED WITH 10-FOLD INCREASE IN Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children Pongracic JACI 2010;125:593 <ul><li>Participants 5 to 11 years old with at least 1 positive skin test response to a fungal allergen. </li></ul><ul><li>Indoor and outdoor airborne culturable fungi levels measured at baseline and throughout the 2-year study. </li></ul>+43% INDOOR +39% OUTDOOR ALLERGENS 50 – 40 – 30 – 20 – 10 – 0 P<0.01 P<0.01 During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits.
  • 124. EXCESS SYMPTOM DAYS per 2 WEEKS ASSOCIATED WITH 10-FOLD INCREASE IN Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children Pongracic JACI 2010;125:593 <ul><li>Participants 5 to 11 years old with at least 1 positive skin test response to a fungal allergen. </li></ul><ul><li>Indoor and outdoor airborne culturable fungi levels measured at baseline and throughout the 2-year study. </li></ul>+42% INDOOR +29% OUTDOOR PENICILLUM 50 – 40 – 30 – 20 – 10 – 0 P<0.01 P<0.01
  • 125. EXCESS SYMPTOM DAYS per 2 WEEKS ASSOCIATED WITH 10-FOLD INCREASE IN Differential effects of outdoor versus indoor fungal spores on asthma morbidity in inner-city children Pongracic JACI 2010;125:593 <ul><li>Participants 5 to 11 years old with at least 1 positive skin test response to a fungal allergen. </li></ul><ul><li>Indoor and outdoor airborne culturable fungi levels measured at baseline and throughout the 2-year study. </li></ul>+42% INDOOR +29% OUTDOOR PENICILLUM 50 – 40 – 30 – 20 – 10 – 0 P<0.01 P<0.01 During the study, increases in total fungal exposure and indoor Penicillium species exposure were associated with increases in symptom days and asthma-related unscheduled visits.
  • 126. Confirmed Moisture Damage at Home, Respiratory Symptoms and Atopy in Early Life: A Birth-Cohort Study Karvonen Pediatrics 2009;124;e329 <ul><li>Building inspection by building engineers </li></ul><ul><li>homes of </li></ul><ul><li>396 children </li></ul><ul><li>Follow-up with questionnaires from birth to the age of 18 months </li></ul>OR FOR PARENT- REPORTED WHEEZING 3.0 Molds in child bedroom Major need for moisture repair Obvious mold indoor 2.85 Moisture damage in the kitchen 2.7 6.1 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 1.9
  • 127. Confirmed Moisture Damage at Home, Respiratory Symptoms and Atopy in Early Life: A Birth-Cohort Study Karvonen Pediatrics 2009;124;e329 <ul><li>Building inspection by building engineers </li></ul><ul><li>homes of </li></ul><ul><li>396 children </li></ul><ul><li>Follow-up with questionnaires from birth to the age of 18 months </li></ul>OR FOR PARENT- REPORTED WHEEZING 3.0 Molds in child bedroom Major need for moisture repair Obvious mold indoor 2.85 Moisture damage in the kitchen 2.7 6.1 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 1.9 There was an increased risk for sensitization to cat dander linked with moisture and mold exposure.
  • 128. <ul><li>Allergens </li></ul><ul><li>Pollens </li></ul>
  • 129. <ul><li>Smoking </li></ul><ul><li>passive-active </li></ul>
  • 130. Second-hand smoke exposure in cars and respiratory health effects in children Kabir ERJ 2009:34:629 <ul><li>Exposure to second-hand smoke ( SHS ) in cars. </li></ul><ul><li>2,809 children of 13–14 yrs old. </li></ul>20 – 15 – 10 – 5 – 0 % CHILDREN EXPOSED TO SHS IN CARS 13.9% 15.4%
  • 131. OR in SHS Exposed Children for 1.35 1.30 WHEEZING HAY FEVER 1.5 – 1.0 – 0.5 – 0 Second-hand smoke exposure in cars and respiratory health effects in children Kabir ERJ 2009:34:629 <ul><li>Exposure to second-hand smoke ( SHS ) in cars. </li></ul><ul><li>2,809 children of 13–14 yrs old. </li></ul>
  • 132. OR in SHS Exposed Children for 1.35 1.30 WHEEZING HAY FEVER 1.5 – 1.0 – 0.5 – 0 Second-hand smoke exposure in cars and respiratory health effects in children Kabir ERJ 2009:34:629 <ul><li>Exposure to second-hand smoke ( SHS ) in cars. </li></ul><ul><li>2,809 children of 13–14 yrs old. </li></ul>Approximately 1 in 7 Irish schoolchildren are exposed to SHS in cars and could have adverse respiratory health effects.
  • 133. Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production Flouris Am J Respir Crit Care Med 2009;179:1029 <ul><li>16 (8 women) nonsmoking adults. </li></ul><ul><li>Baseline and at 0, 1, and 3 hours after a 1-hour secondhand smoke SHS exposure set at bar/restaurant. </li></ul>Mean ± SD of FEV 1 for men ( triangles ) and women ( squares ) in each trial.
  • 134. Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production Flouris Am J Respir Crit Care Med 2009;179:1029 <ul><li>16 (8 women) nonsmoking adults. </li></ul><ul><li>Baseline and at 0, 1, and 3 hours after a 1-hour secondhand smoke SHS exposure set at bar/restaurant. </li></ul>Mean ± SD of FEV 1 for men ( triangles ) and women ( squares ) in each trial. Values dropped 9.7% in men and 13.2% in women between T B and T 0 .a = significant ( P < 0.05)
  • 135. Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production Flouris Am J Respir Crit Care Med 2009;179:1029 <ul><li>16 (8 women) nonsmoking adults. </li></ul><ul><li>Baseline and at 0, 1, and 3 hours after a 1-hour secondhand smoke SHS exposure set at bar/restaurant. </li></ul>Mean ± SD of FEV 1 for men ( triangles ) and women ( squares ) in each trial. IL-4, IL-5, IL-6 and IFN-γ at 3 hours were higher than at baseline ( P < 0.05).
  • 136. Secondhand Smoke and Respiratory Symptoms Among Adolescent Current Smokers Lai Pediatrics 2009;124:1306 <ul><li>32 506 students aged 11 to 20 years. </li></ul><ul><li>Self-administered questionnaire. </li></ul>+50% +77% INCREASED LIKELYHOOD IN CURRENT SMOKERS ADOLESCENTS TO REPORT RESPIRATORY SYMPTOMS 1-4 5-7 IF EXPOSED TO SECOND HAND SMOKE IN THE HOUSE (DAYS/WEEK) 100- 80 - 60 – 40 – 20 – 0
  • 137. Secondhand Smoke and Respiratory Symptoms Among Adolescent Current Smokers Lai Pediatrics 2009;124:1306 <ul><li>32 506 students aged 11 to 20 years. </li></ul><ul><li>Self-administered questionnaire. </li></ul>+50% +77% INCREASED LIKELYHOOD IN CURRENT SMOKERS ADOLESCENTS TO REPORT RESPIRATORY SYMPTOMS 1-4 5-7 IF EXPOSED TO SECOND HAND SMOKE IN THE HOUSE (DAYS/WEEK) 100- 80 - 60 – 40 – 20 – 0 This is the first evidence that SHS exposure is associated with increased risks for persistent respiratory symptoms among adolescent current smokers.
  • 138. 2.0 – 1.5 – 1.0 – 0.5 – 0 1.55 In ETS exposed children Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam Suzuki, Thorax 2009 64: 484-489 <ul><li>A population-based large-scale cross-sectional survey </li></ul><ul><li>Hospital admissions for pneumonia among children aged <5 years (n=24,781) </li></ul>OR for hospital admissions for pneumonia
  • 139. 2.0 – 1.5 – 1.0 – 0.5 – 0 1.55 In ETS exposed children <ul><li>A population-based large-scale cross-sectional survey </li></ul><ul><li>Hospital admissions for pneumonia among children aged <5 years (n=24 781) </li></ul>OR for hospital admissions for pneumonia It is estimated that 28.7% of childhood pneumonia in this community is attributable to ETS. Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam Suzuki, Thorax 2009 64: 484-489
  • 140. Associations Between Secondhand Smoke Exposure and Sleep Patterns in Children Yolton Pediatrics 2010;125:261 WHAT’S KNOWN ON THIS SUBJECT : Adult and adolescent smokers report difficulties with sleep. Young children who are exposed to tobacco smoke have poorer sleep quality. Children with asthma report more sleep problems and are more sensitive to the respiratory effects of tobacco smoke. WHAT THIS STUDY ADDS : We report significant associations between second hand smoke (SHS) exposure, as measured with a biological marker (serum cotinine levels), and sleep problems in children with asthma. Reduction in SHS exposure is an area with the potential for significant impact in the pediatric population.
  • 141. Associations Between Secondhand Smoke Exposure and Sleep Patterns in Children Yolton Pediatrics 2010;125:261 <ul><li>219 children with asthma </li></ul><ul><li>Serum cotinine levels </li></ul>Exposure to SHS was associated with sleep problems, including: 1. longer sleep-onset delay (P =0.004) , 2. sleep-disordered breathing (P =0.02) , 3. parasomnias (P=0.002) , 4. daytime sleepiness (P =0.022) , and 5. overall sleep disturbance (P=0.0002) .
  • 142. Associations Between Secondhand Smoke Exposure and Sleep Patterns in Children Yolton Pediatrics 2010;125:261 <ul><li>219 children with asthma </li></ul><ul><li>Serum cotinine levels </li></ul>Exposure to SHS was associated with sleep problems, including: 1. longer sleep-onset delay (P =0.004) , 2. sleep-disordered breathing (P =0.02) , 3. parasomnias (P=0.002) , 4. daytime sleepiness (P =0.022) , and 5. overall sleep disturbance (P=0.0002) . Parasomnias are a category of sleep disorders that involve abnormal and unnatural movements, behaviors, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or arousal from sleep. Most parasomnias are dissociated sleep states which are partial arousals during the transitions between wakefulness and NREM sleep, or wakefulness and REM sleep.
  • 143. Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder Froehlich Pediatrics 2009;124:e1054 <ul><li>Participants (8 to 15 years, n°=2588). </li></ul><ul><li>Prenatal tobacco exposure during pregnancy. </li></ul><ul><li>Blood lead levels. </li></ul>% CHILDREN WHO MET CRITERIA FOR ADHD 8.7% 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0
  • 144. FUMO IN GRAVIDANZA
  • 145. Effects of nicotine on pulmonary surfactant proteins A and D in ovine lung epithelia Lazic Pediatric Pulmonology 2009;45:255 Exposure to nicotine significantly decreased (Surfactant proteins) SP-A gene expression ( P =0.01) and SP-A protein level in pre-term lambs. Nicotine exposure during the third trimester of pregnancy Pregnant ewes
  • 146. Effects of nicotine on pulmonary surfactant proteins A and D in ovine lung epithelia Lazic Pediatric Pulmonology 2009;45:255 Exposure to nicotine significantly decreased (Surfactant proteins) SP-A gene expression ( P =0.01) and SP-A protein level in pre-term lambs. Nicotine exposure during the third trimester of pregnancy Pregnant ewes SP-A and SP-D, are components of pulmonary innate immunity and have an important role in defense against inhaled pathogens.
  • 147. Rationale: Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives : To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation Breton AJRCCM 2009:180:462
  • 148. <ul><li>Methylation of DNA repetitive elements in buccal cells of 348 children. </li></ul><ul><li>Exposed children had significantly lower methylation of AluYb8 (β,–0.31; P = 0.03). </li></ul><ul><li>Two genes , AXL and PTPRO, showed significant increases in methylation of 0.37 ( P = 0.005) and 0.34 ( P = 0.02) in exposed children. </li></ul>Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation Breton AJRCCM 2009:180:462
  • 149. <ul><li>Methylation of DNA repetitive elements in buccal cells of 348 children. </li></ul><ul><li>Exposed children had significantly lower methylation of AluYb8 (β,–0.31; P = 0.03). </li></ul><ul><li>Two genes, AXL and PTPRO, showed significant increases in methylation of 0.37 ( P = 0.005) and 0.34 ( P = 0.02) in exposed children. </li></ul>Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation Breton AJRCCM 2009:180:462 Life-long effects of in utero exposures may be mediated through alterations in DNA methylation.
  • 150. <ul><li>In the September 1, 2009 issue of the Journal (pp. 462–467), Breton and colleagues provided further evidence that prenatal tobacco smoke (PTS) exposure may alter DNA methylation in humans. </li></ul><ul><li>Their study examined global and gene-specific methylation patterns in buccal cells from 348 and 272 children, respectively, in relation to PTS exposure. </li></ul><ul><li>The authors found significant hypomethylation associated with PTS exposure at one of two DNA repetitive elements that are markers of global DNA methylation, namely, the short interspersed nucleotide element AluYb8, but not the long interspersed nucleotide element (LINE1). </li></ul><ul><li>In contrast, the authors reported that PTS exposure was associated with lower LINE1 methylation in glutathione-S-transferase (GST) M1 null children but higher methylation in those with GSTM1. </li></ul>The Developmental Origins of Asthma: Does Epigenetics Hold the Key? Shaheen AJRCCM 2009:180:690
  • 151. <ul><li>The developmental origins of health and disease (DOHaD) hypothesis proposes that during critical periods of prenatal and postnatal development environmental exposures induce permanent changes in metabolism and physiology and thus affect risk of later disease. </li></ul><ul><li>Epigenetic mechanisms could underlie the DOHaD. </li></ul><ul><li>Changes in DNA methylation and histone modifications can selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis, and also determine when and where a gene is expressed during development. </li></ul>The Developmental Origins of Asthma: Does Epigenetics Hold the Key? Shaheen AJRCCM 2009:180:690
  • 152. <ul><li>The developmental origins of health and disease (DOHaD) hypothesis proposes that during critical periods of prenatal and postnatal development environmental exposures induce permanent changes in metabolism and physiology and thus affect risk of later disease. </li></ul><ul><li>Epigenetic mechanisms could underlie the DOHaD. </li></ul><ul><li>Changes in DNA methylation and histone modifications can selectively activate or inactivate genes that control cell growth, proliferation, and apoptosis, and also determine when and where a gene is expressed during development. </li></ul>The Developmental Origins of Asthma: Does Epigenetics Hold the Key? Shaheen AJRCCM 2009:180:690 Methylation of the C5 position of cytosine residues in DNA is a key epigenetic mark, and methylation of these cysteine-containing islands usually silences gene expression.
  • 153. In Utero Exposure to Smoking and Peripheral Chemoreceptor Function in Preterm Neonates Stéphan-Blanchard Pediatrics 2010;125:e592 <ul><li>Peripheral chemoreceptor activity by performing a 30-second hyperoxic test during active and quiet sleep. </li></ul><ul><li>Neonates born to nonsmoking ( n= 21) or smoking ( n= 16) mothers </li></ul>Prenatal smoking exposure: 1) did not modify baseline ventilation. 2) decreased peripheral chemoreceptor tonic activity during active sleep and 3) increased the response time during quiet sleep.
  • 154. In Utero Exposure to Smoking and Peripheral Chemoreceptor Function in Preterm Neonates Stéphan-Blanchard Pediatrics 2010;125:e592 <ul><li>Peripheral chemoreceptor activity by performing a 30-second hyperoxic test during active and quiet sleep. </li></ul><ul><li>Neonates born to nonsmoking ( n= 21) or smoking ( n= 16) mothers </li></ul>Prenatal smoking exposure: 1) did not modify baseline ventilation. 2) decreased peripheral chemoreceptor tonic activity during active sleep and 3) increased the response time during quiet sleep. These changes could explain the increase in the time spent in apnea (both with and without blood oxygen desaturation) and in the mean duration of apneic episodes with desaturation found in neonates exposed to smoking in utero.
  • 155. Maternal smoking during and after pregnancy and lung function in early adulthood: a prospective study Hayatbakhsh, Thorax 2009; 64: 810-814 <ul><li>21-year follow-up of mothers and their children recruited into prebirth cohort. </li></ul><ul><li>2409 young adults </li></ul><ul><li>In utero exposure to maternal smoking was associated with a reduction in FEV 1 and FEF 25–75 in males (regression coefficient -0.16) </li></ul><ul><li>Adverse effects of antenatal smoking on development of airway growth may persist into early adulthood. </li></ul>
  • 156. Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children. Xepapadaki Pediatr Allergy Immunol 2009:20:423 <ul><li>Passive exposure of pregnant women to ETS . </li></ul><ul><li>Questionnaires from 2374 Preschool children. </li></ul>In Children Born from Mother Passively Exposed to Tobacco Smoke During the 3° Trimester of Pregnancy OR for 1.42 CURRENT WHEEZE 1.5 – 1.0 – 0.5 – 0 PRURITIC RASH EVER 1.45
  • 157. Association of passive exposure of pregnant women to environmental tobacco smoke with asthma symptoms in children. Xepapadaki Pediatr Allergy Immunol 2009:20:423 <ul><li>Passive exposure of pregnant women to ETS. </li></ul><ul><li>Questionnaires from 2374 Preschool children. </li></ul>In Children Born from Mother Passively Exposed to Tobacco Smoke During the 3° Trimester of Pregnancy OR for 1.42 CURRENT WHEEZE 1.5 – 1.0 – 0.5 – 0 PRURITIC RASH EVER 1.45 Public health policies should be oriented not only towards smoking cessation, but also reinforce elimination of ETS exposure of pregnant women. X
  • 158. % women reported current active smoking 18% 20 – 15 – 10 – 5 – 0 The Effect of Active and Passive Household Cigarette Smoke Exposure on Pregnant Women With Asthma Newman CHEST 2010;137(3):601 <ul><li>2.210 pregnant women with mild and moderate-severe asthma </li></ul><ul><li>Questionnaire detailing smoking history and passive household smoke exposure. </li></ul>Among the newborns of active smokers, there was a greater risk of: 1) small for gestational age < 10th percentile P <.001 , and 2) a lower mean birth weight P < .001
  • 159. First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 % smoking mother 31% 40 – 30 – 20 – 10 – 0 <ul><li>1924 pregnant women </li></ul><ul><li>Fetal ultrasound measurements at 11 weeks (crown-rump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) </li></ul>
  • 160. First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 Mean differences in femur length (cm) and 95% CI between 20-week-old fetuses grouped by tertile of maternal daily cigarette consumption <ul><li>1924 pregnant women </li></ul><ul><li>Fetal ultrasound measurements at 11 weeks (crownerump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) </li></ul>P=0.03 -0.91 cm
  • 161. First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 Mean differences in femur length (cm) and 95% CI between 20-week-old fetuses grouped by tertile of maternal daily cigarette consumption <ul><li>1924 pregnant women </li></ul><ul><li>Fetal ultrasound measurements at 11 weeks (crownerump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) </li></ul>P=0.03 There was an inverse exposure-response relationship between cigarette consumption and FL (mean reduction in lowest compared with highest tertile 0.91 cm, p=0.033 ). -0.91 cm
  • 162. 1.58 In mothers who continued smoking OR for 2 years 5 years 2.18 P <0.017 First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 3 – 2 – 1 – 0 Children wheeze at age <ul><li>1924 pregnant women </li></ul><ul><li>Fetal ultrasound measurements at 11 weeks (crownerump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) </li></ul>P =0.03
  • 163. 1.58 In mothers who continued smoking OR for 2 years 5 years 2.18 P <0.017 First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 3 – 2 – 1 – 0 P =0.03 Children wheeze at age <ul><li>1924 pregnant women </li></ul><ul><li>Fetal ultrasound measurements at 11 weeks (crownerump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) </li></ul>Mean reduction in FEV 1 of 62 ml ( p=0.014 ) compared with controls.
  • 164. First trimester maternal tobacco smoking habits and fetal growth Prabhu Thorax 2010;65:235–240 Conclusions: Maternal smoking is associated with reduced fetal measurements in the second and third trimesters but not in the first trimester. Mothers who do not quit smoking during the first trimester deliver smaller infants who go on to have adverse respiratory outcomes in childhood.
  • 165. % smoking mothers 18% 20 – 15 – 10 – 5 – 0 Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185 <ul><li>232 infants with a birth weight ≤1500 g or a gestational age <32 weeks born in 2001 to 2006. </li></ul><ul><li>Magnetic resonance imaging at term age. </li></ul><ul><li>Maternal smoking during pregnancy. </li></ul>
  • 166. % smoking mothers 18% 20 – 15 – 10 – 5 – 0 <ul><li>232 infants with a birth weight ≤1500 g or a gestational age <32 weeks born in 2001 to 2006. </li></ul><ul><li>Magnetic resonance imaging at term age. </li></ul><ul><li>Maternal smoking during pregnancy. </li></ul>The frontal lobe (P = 0.01) and the cerebellar (P = 0.03) volumes were significantly smaller in the exposed than in the unexposed infants. Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185
  • 167. % smoking mothers 18% 20 – 15 – 10 – 5 – 0 <ul><li>232 infants with a birth weight ≤1500 g or a gestational age <32 weeks born in 2001 to 2006. </li></ul><ul><li>Magnetic resonance imaging at term age. </li></ul><ul><li>Maternal smoking during pregnancy. </li></ul>There was no association between prenatal smoking exposure and head growth or structural brain disease. Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185
  • 168. CEREBELLUM (mL) 23.1 24.5 EXPOSED NON-EXPOSED P=0.03 150 – 100 – 50 – 0 25 – 20 – 15 – 10 – 5 – 0 FRONTAL LOBE (mL) 118 127 EXPOSED NON-EXPOSED P=0.01 Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185 Magnetic Resonance
  • 169. CEREBELLUM (mL) 23.1 24.5 EXPOSED NON-EXPOSED P=0.03 150 – 100 – 50 – 0 25 – 20 – 15 – 10 – 5 – 0 FRONTAL LOBE (mL) 118 127 EXPOSED NON-EXPOSED P=0.01 Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185 Magnetic Resonance This is consistent with reports showing an association between prenatal smoking exposure and impairments in frontal lobe and cerebellar functions such as emotion, impulse control , and attention.
  • 170. CEREBELLUM (mL) 23.1 24.5 EXPOSED NON-EXPOSED P=0.03 150 – 100 – 50 – 0 25 – 20 – 15 – 10 – 5 – 0 FRONTAL LOBE (mL) 118 127 EXPOSED NON-EXPOSED P=0.01 Maternal Smoking during Pregnancy and Regional Brain Volumes in Preterm Infants Ekblad J Pediatr 2010;156:185 Magnetic Resonance This is consistent with reports showing an association between prenatal smoking exposure and impairments in frontal lobe and cerebellar functions such as emotion, impulse control , and attention. Mamma grazie per non aver mai fumato….. altrimenti sai che disastro ….
  • 171. Nicotine exerts direct effects on neural cell proliferation, survival, and migration. 1. Roy Neurotoxicol Teratol 1998;20:465. 2. Slotkin Toxicol Appl Pharmacol 2004;198:132. 3. Levitt Drug Alcohol Depend 1998;51:109. Experimental animal studies Clinical studies on the spectrum of smoking-related impairments in frontal lobe and cerebellar functions Deficits in emotion, impulse control, and attention. 1. Obel Paediatr Perinat Epidemiol 1998;12:37 . Magnetic Resonance Imaging Sheds Light on the Nature of Smoking-Induced Effects on Fetal Brain Heinonen J Pediatr 2010;156:175
  • 172. Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder Froehlich Pediatrics 2009;124:e1054 OR FOR ADHD 2.4 3 – 2 – 1 – 0 2.3 PRENATAL TOBACCO EXPOSURE HIGHER BLOOD LEAD CONCENTRATIONS <ul><li>Participants (8 to 15 years, n°=2588). </li></ul><ul><li>Prenatal tobacco exposure during pregnancy. </li></ul><ul><li>Blood lead levels. </li></ul>
  • 173. Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder Froehlich Pediatrics 2009;124:e1054 OR FOR ADHD 2.4 3 – 2 – 1 – 0 2.3 PRENATAL TOBACCO EXPOSURE HIGHER BLOOD LEAD CONCENTRATIONS <ul><li>Participants (8 to 15 years, n°=2588). </li></ul><ul><li>Prenatal tobacco exposure during pregnancy. </li></ul><ul><li>Blood lead levels. </li></ul>Reduction of these common toxicant exposures may be an important avenue for ADHD prevention.
  • 174. Prevalence of and Early-Life Influences on Childhood Strabismus Pathai Arch Pediatr Adolesc Med. 2010;164:250-257 % children with neurodevelopmental/neurologic disorders 5.8% <ul><li>Parental report of “isolated” strabismus and “neurodevelopmental” strabismus (ie, in the context of neurologic disorders). </li></ul><ul><li>343 children with strabismus </li></ul>8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0
  • 175. 1.9 OR for strabismus associated with neurodevelopmental/neurologic disorders Maternal age ≥ 35 yrs Smoking in pregnancy 3.1 <ul><li>Parental report of “isolated” strabismus and “neurodevelopmental” strabismus (ie, in the context of neurologic disorders). </li></ul><ul><li>343 children with strabismus </li></ul>4 – 3 – 2 – 1 – 0 Prevalence of and Early-Life Influences on Childhood Strabismus Pathai Arch Pediatr Adolesc Med. 2010;164:250-257
  • 176. <ul><li>2015 children age 3 years </li></ul><ul><li>maternal smoking during pregnancy </li></ul><ul><li>and postnatal exposure to environmental tobacco smoke (ETS) </li></ul>% children with dental caries 50 – 40 – 30 – 20 – 10 – 0 NO The Effect of Maternal Smoking during Pregnancy and Postnatal Household Smoking on Dental Caries in Young Children Keiko Tanaka , J Ped 2009;155;410 YES 19.6% 33% OR 1.43 Smoking during pregnancy
  • 177. <ul><li>2015 children age 3 years </li></ul><ul><li>maternal smoking during pregnancy </li></ul><ul><li>and postnatal exposure to environmental tobacco smoke (ETS) </li></ul>% children with dental caries The Effect of Maternal Smoking during Pregnancy and Postnatal Household Smoking on Dental Caries in Young Children Keiko Tanaka , J Ped 2009;155;410 Exposed to environmental smoke 30 – 20 – 10 – 0 17.8% 25% OR 1.25 NO YES
  • 178. <ul><li>2015 children age 3 years </li></ul><ul><li>maternal smoking during pregnancy </li></ul><ul><li>and postnatal exposure to environmental tobacco smoke (ETS) </li></ul>% children with dental caries The Effect of Maternal Smoking during Pregnancy and Postnatal Household Smoking on Dental Caries in Young Children Keiko Tanaka , J Ped 2009;155;410 Exposed to environmental smoke 30 – 20 – 10 – 0 17.8% 25% OR 1.25 NO YES Both in utero exposure to maternal smoking and postnatal exposure to ETS may be associated with an increased prevalence of dental caries in young children
  • 179. Association of Maternal Smoking Status With Breastfeeding Practices: Missouri, 2005 Weiser Pediatrics 2009;124:1603 <ul><li>1789 women </li></ul><ul><li>Light smokers (≤10 cigarettes per day), or moderate/heavy smokers (>10 cigarettes per day). </li></ul>% OF WOMEN EVER SMOKED WHILE PREGNANT 31% 60 – 40 – 20 – 0
  • 180. Association of Maternal Smoking Status With Breastfeeding Practices: Missouri, 2005 Weiser Pediatrics 2009;124:1603 Kaplan-Meier survival curve of breastfeeding according to smoking status. <ul><li>1789 women </li></ul><ul><li>Light smokers (≤10 cigarettes per day), or moderate/heavy smokers (>10 cigarettes per day). </li></ul>
  • 181. Association of Maternal Smoking Status With Breastfeeding Practices: Missouri, 2005 Weiser Pediatrics 2009;124:1603 <ul><li>1789 women </li></ul><ul><li>Light smokers (≤10 cigarettes per day), or moderate/heavy smokers (>10 cigarettes per day). </li></ul>Mothers who smoked initiated breastfeeding less often and weaned earlier than nonsmoking mothers. Kaplan-Meier survival curve of breastfeeding according to smoking status.
  • 182. FUMO E ASMA
  • 183. FUMO E RISPOSTA IMMUNE - INFEZIONI
  • 184. FUMO E FATTORI DI RISCHIO PER INIZIARE
  • 185. Individual and Social Influences on Progression to Daily Smoking During Adolecence Kim Pediatrics 2009; 124:895 <ul><li>270 adolescent smokers. </li></ul><ul><li>Daily smoking was defined as having smoked 1 cigarette per day in the past 30 days. </li></ul>
  • 186. Individual and Social Influences on Progression to Daily Smoking During Adolecence Kim Pediatrics 2009; 124:895 FACTOR ASSOCIATED WITH SMOKING PROGRESSION
  • 187. FUMO E RUOLO DEL PEDIATRA E DELLA SOCIETA’
  • 188. % Established smoking (having smoked≥100 cigarettes in one’s lifetime) at follow-up 17.2% <ul><li>School- and telephone-based surveys between September 1999 through November 1999 and February 2006 through February 2007 </li></ul><ul><li>2048 youths aged 16 to 21 years at follow-up </li></ul>INFLUENCE OF MOVIE SMOKING EXPOSURE AND TEAM SPORTS PARTICIPATION ON ESTABLISHED SMOKING Adachi-Mejia Arch Ped Adoles Med 2009;163:638 20 – 15 – 10 – 5 – 0
  • 189. INFLUENCE OF MOVIE SMOKING EXPOSURE AND TEAM SPORTS PARTICIPATION ON ESTABLISHED SMOKING Adachi-Mejia Arch Ped Adoles Med 2009;163:638 2 – 1 – 0 OR for smoking 1.63 2.01 Exposure to the highest quartile of movie smoking compared with the lowest Sports nonparticipants compared with participants Prevalence of established smokers across quartiles of movie smoking exposure stratified by team sports participation.
  • 190. Fumo e STOP SMOKING
  • 191. <ul><li>smoking-cessation program (Not on Tobacco [NOT]). </li></ul><ul><li>20 twice-weekly 25- to 30-minute sessions delivered during lunch periods. </li></ul><ul><li>407 students (mean age: 16 years) </li></ul>Evaluation of School-Based Smoking-Cessation Interventions for Self-Described Adolescent Smokers Joffe Pediatrics 2009;124;e187 OR for self-report quitting 2.07 In students enroled in the Not on Tobacco program At 1 mo 3 – 2 – 1 – 0 1.58 At 12 mo
  • 192. Smoking Cessation Chandler Chest 2010;137:428
  • 193. Smoking Cessation Chandler Chest 2010;137:428
  • 194. A New Breath-Holding Test May Noninvasively Reveal Early Lung Abnormalities Caused by Smoking and/or Obesity Inoue Chest 2009;136:545 <ul><li>38 healthy subjects </li></ul><ul><li>46 smokers </li></ul><ul><li>18 overweight nonsmokers ( BMI≥25 kg/m 2 ) </li></ul><ul><li>19 overweight smokers </li></ul><ul><li>8 ex-smokers </li></ul><ul><li>A modified pulse oximeter was employed for measuring the fall in pulse oximetric saturation caused by 20-s breath-holding ( Δ SpO 2 ) at resting end expiration in the sitting posture </li></ul>A new test that measures oxygen saturation during breath-holding reveals early lung abnormalities in subjects who either smoke or are overweight, especially if these factors are combined.
  • 195. Polygraph tracings of four sample subjects in the four group A New Breath-Holding Test May Noninvasively Reveal Early Lung Abnormalities Caused by Smoking and/or Obesity Inoue Chest 2009;136:545
  • 196. <ul><li>pollution </li></ul>
  • 197. <ul><li>materiale sintetico </li></ul><ul><li>pollution indoor </li></ul>
  • 198. Increase of inflammatory markers after indoor renovation activities: The LISA birth cohort study Herberth Pediatr Allergy Immunol 2009:20:563 Relation between renovation activities and cytokine concentrations in blood samples of 6-yr-old children. <ul><li>B irth cohort. </li></ul><ul><li>Concentration of inflammatory markers. </li></ul><ul><li>Renovation activities (painting, flooring, new furniture) </li></ul>
  • 199. Increase of inflammatory markers after indoor renovation activities: The LISA birth cohort study Herberth Pediatr Allergy Immunol 2009:20:563 Relation between renovation activities and cytokine concentrations in blood samples of 6-yr-old children. <ul><li>B irth cohort. </li></ul><ul><li>Concentration of inflammatory markers. </li></ul><ul><li>Renovation activities (painting, flooring, new furniture) </li></ul>Increased levels of IL-8 and Monocyte Chemoattractant Protein-1 ( MCP-1 ) in children's blood were related to renovation activities.
  • 200. Increase of inflammatory markers after indoor renovation activities: The LISA birth cohort study Herberth Pediatr Allergy Immunol 2009:20:563 Relation between type of floor covering materials and cytokine concentrations in blood samples of 6-yr-old children. <ul><li>B irth cohort. </li></ul><ul><li>Concentration of inflammatory markers. </li></ul><ul><li>Renovation activities (painting, flooring, new furniture) </li></ul>
  • 201. Increase of inflammatory markers after indoor renovation activities: The LISA birth cohort study Herberth Pediatr Allergy Immunol 2009:20:563 Relation between type of floor covering materials and cytokine concentrations in blood samples of 6-yr-old children. <ul><li>B irth cohort. </li></ul><ul><li>Concentration of inflammatory markers. </li></ul><ul><li>Renovation activities (painting, flooring, new furniture) </li></ul>In particular, new floor covering was associated with increased inflammatory markers.
  • 202. <ul><li>After renovation activities , the indoor environment reveals increased concentrations of certain substances like VOCs . </li></ul><ul><li>These organic chemicals are evaporated into the atmosphere at room temperature and may occur indoors at health relevant concentrations over a period of time. </li></ul>Increase of inflammatory markers after indoor renovation activities: The LISA birth cohort study Herberth Pediatr Allergy Immunol 2009:20:563
  • 203. <ul><li>swimming pool </li></ul><ul><li>pollution indoor </li></ul>
  • 204. Swimming pool attendance and risk of asthma and allergic symptoms in children Font-Ribera ERJ 2009:34:1304 <ul><li>3,223 9–12-yr-old children in Sabadell (Spain). </li></ul><ul><li>Questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis). </li></ul><ul><li>eczema </li></ul>In Children with Swimming Pool Attendance Before the Age of 2 Yrs Compared to Those Who Started Attending Swimming Pools after 4 Yrs of Age OR for 0.79 0.86 CURRENT ASTHMA RHINITIS 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0
  • 205. Swimming pool attendance and risk of asthma and allergic symptoms in children Font-Ribera ERJ 2009:34:1304 <ul><li>3,223 9–12-yr-old children in Sabadell (Spain). </li></ul><ul><li>Questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis). </li></ul><ul><li>eczema </li></ul>In Children with Swimming Pool Attendance Before the Age of 2 Yrs Compared to Those Who Started Attending Swimming Pools after 4 Yrs of Age OR for 0.79 0.86 CURRENT ASTHMA RHINITIS 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 Longitudinal studies are required to confirm these findings and avoid potential reverse causation.
  • 206. Swimming pool attendance and risk of asthma and allergic symptoms in children Font-Ribera ERJ 2009:34:1304 <ul><li>3,223 9–12-yr-old children in Sabadell (Spain). </li></ul><ul><li>Questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis). </li></ul><ul><li>eczema </li></ul>OR for eczema in those attending swimming pool >5 yrs versus 0 yrs 2 – 1 – 0 1.71
  • 207. Swimming pool attendance and risk of asthma and allergic symptoms in children Font-Ribera ERJ 2009:34:1304 <ul><li>3,223 9–12-yr-old children in Sabadell (Spain). </li></ul><ul><li>Questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis). </li></ul><ul><li>eczema </li></ul>OR for eczema in those attending swimming pool >5 yrs versus 0 yrs 2 – 1 – 0 1.71 An increased prevalence of eczema was associated with duration of lifetime pool attendance (OR 1.71, for >5 yrs versus 0 yrs).
  • 208. <ul><li>847 students, 13 to 18 years of age, who had attended outdoor or indoor chlorinated pools. </li></ul><ul><li>114 had attended mainly a copper-silver pool and served as a reference group. </li></ul>Impact of Chlorinated Swimming Pool Attendance on the Respiratory Health of Adolescents Bernard Pediatrics 2009;124;1110 OR FOR ASTHMA 1 14 – 12 - 10 – 8 – 6 – 4 – 2 – 0 5.39 7.32 12.6 100 100-500 500-1000 >1000 CHLORINATED POOL ATTENDANCE HOURS
  • 209. Domestic use of hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults Zock JACI 2009;124:731 <ul><li>3626 participants of the European Community Respiratory Health Survey II in 10 countries who did the cleaning in their homes. </li></ul><ul><li>Frequency of bleach use and information on respiratory symptoms. </li></ul>2.0 – 1.5 – 1.0 – 0.5 – 0 0.75 1.24 IN SUBJECTS USING BLEACH ≥4 DAYS/W OR for RESPIRATORY SYMPTOMS ALLERGY TO CAT
  • 210. Domestic use of hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults Zock JACI 2009;124:731 <ul><li>3626 participants of the European Community Respiratory Health Survey II in 10 countries who did the cleaning in their homes. </li></ul><ul><li>Frequency of bleach use and information on respiratory symptoms. </li></ul>2.0 – 1.5 – 1.0 – 0.5 – 0 0.75 1.24 IN SUBJECTS USING BLEACH ≥4 DAYS/W OR for RESPIRATORY SYMPTOMS ALLERGY TO CAT The use of bleach was not associated with indoor allergen concentrations.
  • 211. Domestic use of hypochlorite bleach, atopic sensitization, and respiratory symptoms in adults Zock JACI 2009;124:731 <ul><li>3626 participants of the European Community Respiratory Health Survey II in 10 countries who did the cleaning in their homes. </li></ul><ul><li>Frequency of bleach use and information on respiratory symptoms. </li></ul>2.0 – 1.5 – 1.0 – 0.5 – 0 0.75 1.24 IN SUBJECTS USING BLEACH ≥4 DAYS/W OR for RESPIRATORY SYMPTOMS ALLERGY TO CAT People who clean their homes with hypochlorite bleach are less likely to be atopic but more likely to have respiratory symptoms.
  • 212. Improved Biomass Stove Intervention in Rural Mexico Romieu Am. J. Respir. Crit. Care Med 2009;180:649 <ul><li>Households were randomized to receive the Patsari stove or keep their traditional open fire. </li></ul><ul><li>552 women were followed with monthly visits over 10 months. </li></ul>1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 0.77 0.29 RELATIVE RIGH FOR Respiratory Symptoms Wheezing In women who use a stove instead of open fire
  • 213. Improved Biomass Stove Intervention in Rural Mexico Romieu Am. J. Respir. Crit. Care Med 2009;180:649 <ul><li>Households were randomized to receive the Patsari stove or keep their traditional open fire. </li></ul><ul><li>552 women were followed with monthly visits over 10 months. </li></ul>1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 0.77 0.29 RELATIVE RIGH FOR Respiratory Symptoms Wheezing In women who use a stove instead of open fire Actual use of the Patsari stove was associated with a lower FEV 1 decline (31 ml) compared with the open fire use (62 ml) over 1 year of follow-up ( P =0.012 ) for women 20 years of age and older
  • 214. TWO REPRESENTATIVE HOUSEHOLD KITCHEN MEXICO Patsari chimney wood stove Open wood fire Improved Biomass Stove Intervention in Rural Mexico Romieu Am. J. Respir. Crit. Care Med 2009;180:649
  • 215. <ul><li>pollution outdoor </li></ul>
  • 216. Residential proximity to main roads during pregnancy and the risk of allergic disorders in Japanese infants: The Osaka Maternal and Child Health Study Miyake Pediatr Allergy Immunol 2010:21:22 <ul><li>756 mother–child pairs. </li></ul><ul><li>Distance of each subject's home during pregnancy from the center line of all main roads in Osaka. </li></ul><ul><li>From 16 to 24 months post-partum ISAAC questionnaire. </li></ul>22.1% 18.7% WHEEZE 30 – 25 – 20 – 15 – 10 – 0 5 – 0 0 ATOPIC ECZEMA % Children at the Age 16-24 Month with
  • 217. Residential proximity to main roads during pregnancy and the risk of allergic disorders in Japanese infants: The Osaka Maternal and Child Health Study Miyake Pediatr Allergy Immunol 2010:21:22 <ul><li>756 mother–child pairs. </li></ul><ul><li>Distance of each subject's home during pregnancy from the center line of all main roads in Osaka. </li></ul><ul><li>From 16 to 24 months post-partum ISAAC questionnaire. </li></ul>4.01 2.26 ASTHMA ATOPIC ECZEMA OR in Children Living During Faetal Life in Houses <50 m. vs ≥200 m. from Main Road p=0.02 p=0.03 4.5 – 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 Oxidative stress DOCTOR DIAGNOSED
  • 218. <ul><li>2107 children aged 9–14 years from 40 schools in Rome in 2000–1 </li></ul><ul><li>Parental questionnaires </li></ul><ul><li>Allergic sensitisation by skin prick tests spirometry </li></ul><ul><li>- 0.62% for FEV 1 </li></ul><ul><li>- 62 ml/s for FEF 25%-75% </li></ul><ul><li>- 85 ml/s for PEF </li></ul>There was a strong association between estimated NO 2 exposure per 10 μ g/m 3 increase and lung function, especially expiratory flows. Traffic-related air pollution in relation to respiratory symptoms, allergic sensitisation and lung function in schoolchildren Rosenlund Thorax 2009;64:573–580
  • 219. <ul><li>2107 children aged 9–14 years from 40 schools in Rome in 2000–1 </li></ul><ul><li>Parental questionnaires </li></ul><ul><li>Allergic sensitisation by skin prick tests spirometry </li></ul><ul><li>- 0.62% for FEV 1 </li></ul><ul><li>- 62 ml/s for FEF 25%-75% </li></ul><ul><li>- 85 ml/s for PEF </li></ul>There was a strong association between estimated NO 2 exposure per 10 μ g/m 3 increase and lung function, especially expiratory flows. Traffic-related air pollution in relation to respiratory symptoms, allergic sensitisation and lung function in schoolchildren Rosenlund Thorax 2009;64:573–580 Residential traffic-related air pollution exposure is associated with reduced expiratory flows in schoolchildren.
  • 220. <ul><li>Outdoor t raffic-related p articulate m atter up to 10 μ m in diameter (TPM 10 ). </li></ul><ul><li>Never-smokers without asthma at baseline aged 18–60 years in 1991. </li></ul><ul><li>Doctor-diagnosed asthma at follow up in 2002. </li></ul>Traffic-related air pollution correlates with adult-onset asthma among never-smokers Künzli Thorax 2009;64:664–670 Hazard Ratio per 1 μ g/m 3 change in traffic PM 10 1.30 Onset of asthma 2 – 1 – 0
  • 221. <ul><li>Outdoor t raffic-related p articulate m atter up to 10 μ m in diameter (TPM 10 ). </li></ul><ul><li>Never-smokers without asthma at baseline aged 18–60 years in 1991. </li></ul><ul><li>Doctor-diagnosed asthma at follow up in 2002. </li></ul>Traffic-related air pollution correlates with adult-onset asthma among never-smokers Künzli Thorax 2009;64:664–670 1.30 Onset of asthma 2 – 1 – 0 The data suggest a role for traffic-related pollution in adult-onset asthma. Hazard Ratio per 1 μ g/m 3 change in traffic PM 10
  • 222. <ul><li>maternal factors and atopic diseases </li></ul>
  • 223. Intrauterine bacterial growth at birth and risk of asthma and allergic sensitization among offspring at the age of 15 to 17 yrs Keski-Nisula JACI 2009;123:1305 <ul><li>Intrauterine bacterial culture recorded at the time of cesarean delivery. </li></ul><ul><li>460 children. </li></ul><ul><li>Follow-up 15-17 years. </li></ul>OR FOR 4.51 Pathogenic anaerobic bacteria and Streptococcus species at birth compared with the risk seen in subjects with negative microbial cultures. 7.34 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 ASTHMA EVER CURRENT ASTHMA
  • 224. <ul><li>Mothers colonized by Streptococcus had more clinically defined chorioamnionitis or “silent” intrauterine infections during delivery and therefore also more antibiotic administration before delivery. </li></ul><ul><li>Chorioamnionitis causes a strong proinflammatory response, and fetal exposure to these cytokines presented in amniotic fluid has been associated with an increased risk of chronic lung disease . </li></ul>Intrauterine bacterial growth at birth and risk of asthma and allergic sensitization among offspring at the age of 15 to 17 yrs Keski-Nisula JACI 2009;123:1305
  • 225. Background: One factor capable of modulating antenatal immune responses is diet. This prospective study examined the association between maternal intake of specific types of fatty acids, cholesterol, fish and meat during pregnancy and the risk of wheeze and eczema in the offspring. Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese 24 months: the Osaka Maternal - infants aged 16-24 months and Child Health Study Miyake Thorax 2009; 64: 815-821
  • 226. 0.52 OR for wheeze α -linolenic acid docosahexaenoic acid 0.37 <ul><li>763 </li></ul><ul><li>mother-child pairs. </li></ul><ul><li>Diet history questionnaire. </li></ul>1.0 – 0.5 – 0 during pregnancy between extreme quartiles Ω -3 Ω -3 Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese 24 months: the Osaka Maternal - infants aged 16-24 months and Child Health Study Miyake Thorax 2009; 64: 815-821
  • 227. 2.25 OR for ECZEMA linoleic acid n-6 polyunsaturated fatty acids 2.11 3 – 2 – 1 – 0 <ul><li>763 </li></ul><ul><li>mother-child pairs. </li></ul><ul><li>Diet history questionnaire. </li></ul>during pregnancy between extreme quartiles Ω -6 Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese 24 months: the Osaka Maternal - infants aged 16-24 months and Child Health Study Miyake Thorax 2009; 64: 815-821 Ω -6
  • 228. <ul><li>Linoleic acid is an unsaturated omega-6 fatty acid. </li></ul><ul><li>α-linoleic acid is an omega-3 fatty acid found in many vegetables oils. </li></ul><ul><li>DECOSAHEXAEMOIC ACID is an omega-3 fatty acid found in fish oil. </li></ul>Maternal fat consumption during pregnancy and risk of wheeze and eczema in Japanese 24 months: the Osaka Maternal - infants aged 16-24 months and Child Health Study Miyake Thorax 2009; 64: 815-821
  • 229. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 <ul><li>771 mother–child pairs. </li></ul><ul><li>Maternal dietary intake during pregnancy. </li></ul><ul><li>Questionnaire completed by mothers 3–4 months postpartum. </li></ul>8.4% % Infants With Atopic Dermatitis at 3-4 Months 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0
  • 230. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 3.53 p=0.02 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 OR for Doctor Diagnosis of Atopic Eczema in Infants HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY <ul><li>771 mother–child pairs. </li></ul><ul><li>Maternal dietary intake during pregnancy. </li></ul><ul><li>Questionnaire completed by mothers 3–4 months postpartum. </li></ul>
  • 231. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 3.53 p=0.02 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 OR for Doctor Diagnosis of Atopic Eczema in Infants HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY <ul><li>771 mother–child pairs. </li></ul><ul><li>Maternal dietary intake during pregnancy. </li></ul><ul><li>Questionnaire completed by mothers 3–4 months postpartum. </li></ul>Certain components of meat may affect foetal immune responses. Meat is a primary source of saturated fatty acids .
  • 232. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 3.53 p=0.02 4.0 – 3.5 – 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 OR for Doctor Diagnosis of Atopic Eczema in Infants HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY <ul><li>771 mother–child pairs. </li></ul><ul><li>Maternal dietary intake during pregnancy. </li></ul><ul><li>Questionnaire completed by mothers 3–4 months postpartum. </li></ul>The formation of heterocyclic amines during cooking and nitroso compounds in processed meat are indicated as plausible mechanisms.
  • 233. Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age: a prospective cohort study Nwaru Pediatr Allergy Immunol 2010:21:29 <ul><li>Population-based cohort study with 5-yr follow-up. </li></ul><ul><li>931 children. </li></ul><ul><li>Food frequency questionnaire. </li></ul>1.14 1.36 CITRUS FRUITS TOTAL FRUITS 1.5 – 1.0 – 0.5 – 0 OR for (+) sIgE to Inhalant Allergens at the Age 5 Years INCREASING MATERNAL CONSUMPTION
  • 234. Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age: a prospective cohort study Nwaru Pediatr Allergy Immunol 2010:21:29 <ul><li>Population-based cohort study with 5-yr follow-up. </li></ul><ul><li>931 children. </li></ul><ul><li>Food frequency questionnaire. </li></ul>0.56 VITAMIN D INTAKE BY THE MOTHER DURING PREGNANCY 1.0 – 0.5 – 0 OR for (+) sIgE to Food at the age 5 years
  • 235. Olive Oil During Pregnancy Is Associated With Reduced Wheezing During the First Year of Life of the Offspring Castro-Rodriguez, Ped Pul 2010;45:395 <ul><li>1,409 infants (mean age 16.6 months) attending healthy infant clinics in Spain. </li></ul><ul><li>Dietary data of mothers’ intake during pregnancy by food frequency questionnaire. </li></ul>% ch with any wheezing during the first year of life 50 – 40 – 30 – 20 – 10 – 0 42.2%
  • 236. Olive Oil During Pregnancy Is Associated With Reduced Wheezing During the First Year of Life of the Offspring Castro-Rodriguez, Ped Pul 2010;45:395 OR for wheezing 1.0 – 0.5 – 0 0.57 olive oil consumption during pregnancy P=0.002 <ul><li>1,409 infants (mean age 16.6 months) attending healthy infant clinics in Spain. </li></ul><ul><li>Dietary data of mothers’ intake during pregnancy by food frequency questionnaire. </li></ul>
  • 237. Olive Oil During Pregnancy Is Associated With Reduced Wheezing During the First Year of Life of the Offspring Castro-Rodriguez, Ped Pul 2010;45:395
  • 238. Olive Oil During Pregnancy Is Associated With Reduced Wheezing During the First Year of Life of the Offspring Castro-Rodriguez, Ped Pul 2010;45:395
  • 239. breastfeeding
  • 240. Breastfeeding, the use of docosahexaenoic acid (DHA)-fortified formulas in infancy and neuropsychological function in childhood C R Gale, Arch Dis Child 2010;95:174 <ul><li>There has been considerable interest in the role that </li></ul><ul><li>long-chain polyunsaturated fatty acids (LCPUFAs) </li></ul><ul><li>might play in neurodevelopment . </li></ul><ul><li>LCPUFAs, particularly the n-3 docosahexaenoic acid ( DHA ) and the n-6 arachidonic acid (AA), are found in high concentrations in the brain and retina , and accumulate during the spurt in brain growth that occurs between the last trimester of pregnancy and the first year of life. </li></ul><ul><li>LCPUFAs, especially DHA , are involved in cell signalling , </li></ul><ul><li>regulation of gene expression and neuronal growth . </li></ul>
  • 241. <ul><li>241 children aged 4 years followed up from birth </li></ul><ul><li>IQ, visual attention, visuomotor precision, sentence repetition and verbal fluency </li></ul>In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula Breastfeeding, the use of docosahexaenoic acid (DHA)-fortified formulas in infancy and neuropsychological function in childhood C R Gale, Arch Dis Child 2010;95:174
  • 242. <ul><li>241 children aged 4 years followed up from birth </li></ul><ul><li>IQ, visual attention, visuomotor precision, sentence repetition and verbal fluency </li></ul>After adjustment for potential confounding factors, particularly maternal IQ and educational attainment , the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 and 7.02 points higher than children fed unfortified formula Breastfeeding, the use of docosahexaenoic acid (DHA)-fortified formulas in infancy and neuropsychological function in childhood C R Gale, Arch Dis Child 2010;95:174
  • 243. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 <ul><li>143 infants with AD who younger than 6 months. </li></ul><ul><li>3 groups : - breastfed, - mixed feeding, and - formula fed. </li></ul><ul><li>All infants had never been fed egg or soy. </li></ul>BF MF FF 69 107 25 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 110 – 100 – Total IgE Ku/L Groups p=0.004 p=0.07
  • 244. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 BF MF FF 1.34 0.57 2.75 Specific IgE to Cow’s Milk Ku/L 3.0 – 2.5 – 2.0 – 1.5 – 1.0 – 0.5 – 0 <ul><li>143 infants with AD who younger than 6 months. </li></ul><ul><li>3 groups : - breastfed, - mixed feeding, and - formula fed. </li></ul><ul><li>All infants had never been fed egg or soy. </li></ul>ns ns Groups
  • 245. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 BF MF FF 7.97 0.09 sIgE to Egg withe Ku/L 8.43 <ul><li>143 infants with AD who younger than 6 months. </li></ul><ul><li>3 groups : - breastfed, - mixed feeding, and - formula fed. </li></ul><ul><li>All infants had never been fed egg or soy. </li></ul>p=0.002 p=0.0002 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Groups
  • 246. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 BF MF FF 7.97 0.09 sIgE to Egg withe Ku/L 8.43 <ul><li>143 infants with AD who younger than 6 months. </li></ul><ul><li>3 groups : - breastfed, - mixed feeding, and - formula fed. </li></ul><ul><li>All infants had never been fed egg or soy. </li></ul>Our results suggest that breastfeeding might not always be beneficial in allergy prevention in some high-risk infants. p=0.002 p=0.0002 10 – 9 – 8 – 7 – 6 – 5 – 4 – 3 – 2 – 1 – 0 Groups
  • 247. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 <ul><li>One limitation of our study is that the FF group was smaller than the other groups. </li></ul><ul><li>In the present study, the 3 groups (BF, MF, and FF) were not randomly divided but were determined according to parental preferences. </li></ul><ul><li>The number of infants in the FF group was small. </li></ul><ul><li>In conclusion, our results showed that BF patients with AD had a higher rate of sensitization to egg white during early infancy, which suggests that BF might not always be beneficial in allergy prevention in some high-risk infants (ie, maternal AD). </li></ul>
  • 248. Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II Nagel Eur Respir J 2009;33:993 <ul><li>Cross-sectional studies in 27 centres in 20 countries. </li></ul><ul><li>Data from 54,000 randomly selected school children (aged 8–12 yrs, 31,759 with skin prick testing). </li></ul>OR for not atopic wheezing 0.87 AFFLUENT COUNTRIES 0.80 NON AFFLUENT COUNTRIES 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 any breast feeding
  • 249. Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II Nagel Eur Respir J 2009;33:993 <ul><li>Cross-sectional studies in 27 centres in 20 countries. </li></ul><ul><li>Data from 54,000 randomly selected school children (aged 8–12 yrs, 31,759 with skin prick testing). </li></ul>OR for not atopic wheezing 0.87 AFFLUENT COUNTRIES 0.80 NON AFFLUENT COUNTRIES 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 any breast feeding Breastfeeding was not associated with atopic wheeze and objective measures of allergy .
  • 250. Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study Scholtens Thorax 2009;64:604–609 <ul><li>3115 Dutch children born in 1996/1997 </li></ul><ul><li>PIAMA (Prevention and Incidence of Asthma and Mite Allergy) </li></ul>35% % Children breast fed for >16 weeks 40 – 30 – 20 – 10 – 0
  • 251. 12.6% % children with asthma at age 8 years 20 – 15 – 10 – 5 - 0 Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study Scholtens Thorax 2009;64:604–609 <ul><li>3115 Dutch children born in 1996/1997 </li></ul><ul><li>PIAMA (Prevention and Incidence of Asthma and Mite Allergy) </li></ul>
  • 252. 12.6% % children with asthma at age 8 years 20 – 15 – 10 – 5 - 0 Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study Scholtens Thorax 2009;64:604–609 <ul><li>3115 Dutch children born in 1996/1997 </li></ul><ul><li>PIAMA (Prevention and Incidence of Asthma and Mite Allergy) </li></ul>Breast feeding (> 16 weeks vs no breast feeding) was significantly associated with a lower asthma prevalence from 3 to 8 years of age, in children of both non-allergic and allergic mothers.
  • 253. Adjusted associations between breast feeding (>16 weeks vs no breast feeding) and asthma at 3–8 years of age in children of non-allergic mothers (n=2238) Adjusted associations between breast feeding (>16 weeks vs no breast feeding) and asthma at 3–8 years of age in children of allergic mothers (n=877). Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study Scholtens Thorax 2009;64:604–609
  • 254. <ul><li>protective factors for atopic diseases: </li></ul><ul><li>-diet </li></ul>
  • 255. The traditional Chinese herbal formula ASHMI inhibits allergic lung inflammation in antigen-sensitized and antigen-challenged aged mice Busse Ann Allergy Asthma Immunol. 2010;104:236 –246 Herbal medicine treatment before and during intraperitoneal ovalbumin sensitization. Treatment reduces several features of asthma in aged antigen-sensitized and antigen-challenged mice. BALB/c mice 18 months old
  • 256. <ul><li>protective factors for atopic diseases: </li></ul><ul><li>- vitamins and minerals </li></ul>
  • 257. Higher serum folate levels are associated with a lower risk of atopy and wheeze Matsui JACI 2009;123:1253 <ul><li>Serum folate and total IgE levels. </li></ul><ul><li>8083 subjects 2 years of age and older. </li></ul>Distribution of serum total IgE levels across quintiles of serum folate. P < .001 for trend
  • 258. Higher serum folate levels are associated with a lower risk of atopy and wheeze Matsui JACI 2009;123:1253 <ul><li>Serum folate and total IgE levels. </li></ul><ul><li>8083 subjects 2 years of age and older. </li></ul>IgE LEVEL >100 KU/L Or in the 5°quintile of Folate vs the 1° quintile 0.70 0.69 0.60 ATOPY WHEEZE 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0
  • 259. Higher serum folate levels are associated with a lower risk of atopy and wheeze Matsui JACI 2009;123:1253 <ul><li>One particular dietary component that could directly influence the propensity for epigenetic modifications is folic acid , which serves as a source for methyl donors for DNA methylation. </li></ul><ul><li>The lower limit for a normal serum folate level is generally considered to be in the range of 3 to 4.5 ng/Ml. McDowell MA, NCHS data briefs no. 6. Selhub J, Food Nutr Bull. 2008;29 (suppl):S67–S73 </li></ul><ul><li>A level of greater than 26.5 ng/mL should be considered high. Morris MS, Am J Clin Nutr. 2007;85:193–200 </li></ul>
  • 260. Has mandatory folic acid supplementation of foods increased the risk of asthma and allergic disease? Ownby JACI 2009;123:1260 <ul><li>Folate functions as an important cofactor in the transfer and use of 1-carbon moieties, primarily methyl groups. </li></ul><ul><li>Folic acid supplementation before and during pregnancy dramatically reduced the risk of neural-tube defects in newborns (85% reduction with 5000 μg of folic acid per day) </li></ul>
  • 261. Dietary antioxidant intake, allergic sensitization and allergic diseases in young children Patel Allergy 2009:64:1766 Background:  Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause . Objective: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort.
  • 262. Dietary antioxidant intake, allergic sensitization and allergic diseases in young children Patel Allergy 2009:64:1766 <ul><li>957 children followed from birth. </li></ul><ul><li>SPTs at 5 and 8 years of age. </li></ul><ul><li>At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). </li></ul><ul><li>A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. </li></ul>
  • 263. Dietary antioxidant intake, allergic sensitization and allergic diseases in young children Patel Allergy 2009:64:1766 In Subjects with Higher β -Carotene Or for Allergic Diseases 0.80 0.81 5 YEARS 8 YEARS 1.0 – 0.5 – 0 <ul><li>957 children followed from birth. </li></ul><ul><li>SPTs at 5 and 8 years of age. </li></ul><ul><li>At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). </li></ul><ul><li>A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. </li></ul>AT AGE
  • 264. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Maarsingh ERJ 2009:34:191 Background: Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations. L-Arginine availability to iNOS is regulated by its cellular uptake, which can be inhibited by eosinophil-derived polycations and by arginase, which competes with iNOS for the common substrate.
  • 265. Allergen exposure Inducible nitric oxide synthase (iNOS) NO production + H O 2 (superoxide a…) Increased nitrotyrosine Airway inflammation & BHR L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Maarsingh ERJ 2009:34:191 Guinea Pig
  • 266. Allergen exposure Inducible nitric oxide synthase (iNOS) NO production + H O 2 (superoxide a…) Increased nitrotyrosine Airway inflammation & BHR L-arginina X L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Maarsingh ERJ 2009:34:191 Guinea Pig
  • 267. L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction Maarsingh ERJ 2009:34:191
  • 268. Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells Sohn Ann Allergy Asthma Immunol 2009;103:152 Stimulated with TNF α , IL-4, and IL-1β Expression of chemokines and adhesion molecules involved in eosinophil chemotaxis Cultured A549 human alveolar epithelial cells
  • 269. Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells Sohn Ann Allergy Asthma Immunol 2009;103:152 Stimulated with TNF α , IL-4, and IL-1β Expression of chemokines and adhesion molecules involved in eosinophil chemotaxis Cultured A549 human alveolar epithelial cells Down-regulated with V rotundifolia (-)
  • 270. Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells Sohn Ann Allergy Asthma Immunol 2009;103:152 Stimulated with TNF α , IL-4, and IL-1β Expression of chemokines and adhesion molecules involved in eosinophil chemotaxis Cultured A549 human alveolar epithelial cells Down-regulated with V rotundifolia (-) V rotundifolia may be useful in the treatment of asthma and other allergic diseases.
  • 271. Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells Sohn Ann Allergy Asthma Immunol 2009;103:152 Vitex rotundifolia is a medical plant that is widely used in China and Korea for the treatment of asthma, pain, cold, headache, migraine, sore eyes, chronic bronchitis, myalgia, and gastrointestinal infections such as bacterial dysentery and diarrhea. Vitex rotundifolia was purchased from the Sun Ten Pharmaceutical Co Ltd (Taipei, Taiwan),
  • 272. Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells Sohn Ann Allergy Asthma Immunol 2009;103:152 Inhibitory effects of Vitex rotundifolia (VRE) on eotaxin secretion from A549 cells stimulated with cytokines. Effect of Vitex rotundifolia (VRE) on eosinophil migration. NC indicates negative control (media only); PC, positive control (IL-4, IL-1β, and TNF- α -stimulated A549 cell). *** P < .001 compared with PC.
  • 273. <ul><li>protective factors for atopic diseases: </li></ul><ul><li>- solid food introduction vedi food allergy </li></ul>
  • 274. Factors associated with maternal dietary intake, feeding and weaning practices, and the development of food hypersensitivity in the infant Venter Pediatr Allergy Immunol 2009:20:320 <ul><li>969 pregnant women recruited at 12 wk pregnancy. </li></ul><ul><li>Food frequency questionnaire completed at 36 wk gestation. </li></ul><ul><li>Feeding practices and reported symptoms of atopy during the infants' first 3 yr of life . </li></ul>OR FOR FOOD HYPERSENSITIVITY AT 0.26 WEANING BEFORE 16 WKS 0.51 p=0.03 p=0.02 1.0 – 0.9 – 0.8 – 0.7 – 0.6 – 0.5 – 0.4 – 0.3 – 0.2 – 0.1 – 0 1 YEAR 3 YEARS
  • 275. Factors associated with maternal dietary intake, feeding and weaning practices, and the development of food hypersensitivity in the infant Venter Pediatr Allergy Immunol 2009:20:320 <ul><li>Maternal dietary intake during pregnancy and breast-feeding duration did not appear to influence the development of sensitization to food allergens or FHS. </li></ul><ul><li>Children weaned at or after 16 wk were more likely to develop food hypersensitivity (FHS) and sensitization to foods . </li></ul><ul><li>In contrast, the data regarding exposure to food allergens and age of weaning on to food allergens showed that children who were exposed to a certain food (egg, heath, peanut, cod, sesame) allergen before the age of 3–6 months were more likely to become sensitized or develop FHS to the particular food at age 1 and 3 yr . </li></ul>
  • 276. Factors associated with maternal dietary intake, feeding and weaning practices, and the development of food hypersensitivity in the infant Venter Pediatr Allergy Immunol 2009:20:320 <ul><li>Maternal dietary intake during pregnancy and breast-feeding duration did not appear to influence the development of sensitization to food allergens or FHS. </li></ul><ul><li>Children weaned at or after 16 wk were more likely to develop food hypersensitivity (FHS) and sensitization to foods . </li></ul><ul><li>In contrast, the data regarding exposure to food allergens and age of weaning on to food allergens showed that children who were exposed to a certain food (egg, heath, peanut, cod, sesame) allergen before the age of 3–6 months were more likely to become sensitized or develop FHS to the particular food at age 1 and 3 yr . </li></ul>This may indicate that although early weaning could lead to tolerization in general, the main allergenic food proteins may behave differently and that age of introduction to these needs special investigation.
  • 277. <ul><li>protective factors for atopic diseases: </li></ul><ul><li>-life-style </li></ul>
  • 278. <ul><li>Gastro-Intestinal flora </li></ul><ul><li>probiotics </li></ul>
  • 279. Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination . In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 Probiotics IgA
  • 280. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 <ul><li>Case–control study of 237 allergy prone infants participating in allergy-prevention trial. </li></ul><ul><li>Four probiotic strains pre-natally and during 6 months form birth. </li></ul><ul><li>Faecal IgA, α 1-antitrypsin α1, TNF- α , calprotectin the age of 3 and 6 mo. </li></ul>52.3% 60 – 50 – 40 – 30 – 20 – 10 – 0 % Children Developing Allergic Diseases or sIgE by the Age 2 Years
  • 281. In Infants with High Faecal IgA Concentration at the Age of 6 Months OR for 0.52 0.49 ANY ALLERGIC DISEASE IgE ASSOCIATION DISEASE 1.0 – 0.5 – 0 High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 <ul><li>Case–control study of 237 allergy prone infants participating in allergy-prevention trial. </li></ul><ul><li>Four probiotic strains pre-natally and during 6 months form birth . </li></ul><ul><li>Faecal IgA, α 1-antitrypsin α1, TNF- α , calprotectin the age of 3 and 6 mo. </li></ul>BEFORE THE AGE 2 YRS
  • 282. <ul><li>Case–control study of 237 infants participating in allergy-prevention trial. </li></ul><ul><li>Four probiotic strains pre-natally and during 6 months form birth. </li></ul><ul><li>Faecal IgA, α 1-antitrypsin α1, TNF- α , calprotectin the age of 3 and 6 mo. </li></ul>In Infants with High Faecal IgA Concentration at the Age of 6 Months OR for 0.52 0.49 ANY ALLERGIC DISEASE IgE ASSOCIATION DISEASE 1.0 – 0.5 – 0 All faecal inflammation markers ( α 1-AT, TNF- α , and calprotectin) correlated positively with faecal IgA (p <0.001). High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 BEFORE THE AGE 2 YRS
  • 283. <ul><li>Case–control study of 237 infants participating in allergy-prevention trial. </li></ul><ul><li>Four probiotic strains pre-natally and during 6 months form birth. </li></ul><ul><li>Faecal IgA, α 1-antitrypsin α1, TNF- α , calprotectin the age of 3 and 6 mo. </li></ul>In Infants with High Faecal IgA Concentration at the Age of 6 Months OR for 0.52 0.49 ANY ALLERGIC DISEASE IgE ASSOCIATION DISEASE 1.0 – 0.5 – 0 Probiotics tended to augment faecal IgA (p=0.085) and significantly increased faecal α 1-AT (p=0.001). High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 BEFORE THE AGE 2 YRS
  • 284. <ul><li>Case–control study of 237 infants participating in allergy-prevention trial. </li></ul><ul><li>Four probiotic strains pre-natally and during 6 months form birth. </li></ul><ul><li>Faecal IgA, α 1-antitrypsin α1, TNF- α , calprotectin the age of 3 and 6 mo. </li></ul>In Infants with High Faecal IgA Concentration at the Age of 6 Months OR for 0.52 0.49 ANY ALLERGIC DISEASE IgE ASSOCIATION DISEASE 1.0 – 0.5 – 0 High intestinal IgA is associated with minimal intestinal inflammation and with a reduced risk for IgE-associated allergic diseases. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases Kukkonen Pediatr Allergy Immunol 2010:21:67 BEFORE THE AGE 2 YRS
  • 285. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses Sjögren, CEA 2009;39:1842 <ul><li>Introduction: Among sensitized infants, those with high , as </li></ul><ul><li>compared with low levels, of salivary secretory IgA (SIgA) </li></ul><ul><li>are less likely to develop allergic symptoms . </li></ul><ul><li>Also, early colonization with certain gut microbiota, e.g. </li></ul><ul><li>Lactobacilli and Bifidobacterium species, might be associated </li></ul><ul><li>with less allergy development. </li></ul><ul><li>Objective: To assess whether early colonization with certain </li></ul><ul><li>gut microbiota species associates with mucosal and systemic </li></ul><ul><li>immune responses i.e. salivary SIgA and the spontaneous Toll- </li></ul><ul><li>like receptor (TLR) 2 and TLR4 mRNA expression and </li></ul><ul><li>lipopolysaccharide (LPS)-induced cytokine/chemokine </li></ul><ul><li>responses in peripheral blood mononuclear cells (PBMCs). </li></ul>
  • 286. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses Sjögren, CEA 2009;39:1842 <ul><li>Fecal samples were </li></ul><ul><li>collected at 1 week, </li></ul><ul><li>1 month and 2 months </li></ul><ul><li>after birth. </li></ul><ul><li>64 Swedish infants. </li></ul><ul><li>Followed up to 5 years of </li></ul><ul><li>age. </li></ul><ul><li>PBMCs, collected 12 </li></ul><ul><li>months after birth, </li></ul><ul><li>analysed for TLR2 and </li></ul><ul><li>TLR4 mRNA expression </li></ul><ul><li>with real-time PCR. </li></ul>Total salivary secretory IgA (SIgA) at 6 months is associated with a more diverse Bifidobacterium flora.
  • 287. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses Sjögren, CEA 2009;39:1842 The spontaneous expression of Toll-like receptor (TLR) 4 mRNA at 12 months is inversely correlated to the intensity of Bacteroides fragilis colonization at 1 month after birth. <ul><li>Fecal samples were </li></ul><ul><li>collected at 1 week, </li></ul><ul><li>1 month and 2 months </li></ul><ul><li>after birth. </li></ul><ul><li>64 Swedish infants. </li></ul><ul><li>Followed up to 5 years of </li></ul><ul><li>age. </li></ul><ul><li>PBMCs, collected 12 </li></ul><ul><li>months after birth, </li></ul><ul><li>analysed for TLR2 and </li></ul><ul><li>TLR4 mRNA expression </li></ul><ul><li>with real-time PCR. </li></ul>
  • 288. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses Y Sjögren, CEA 2009;39:1842 The lipopolysaccharide (LPS)-induced production of CCL4 (MIP-1b) (a) and IL-6 (b) from peripheral blood mononuclear cells (PBMCs), collected 12 months after birth, is inversely correlated to the intensity of Bacteroides fragilis colonization 1 month after birth.
  • 289. Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses Y Sjögren, CEA 2009;39:1842 The lipopolysaccharide (LPS)-induced production of CCL4 (MIP-1b) (a) and IL-6 (b) from peripheral blood mononuclear cells (PBMCs), collected 12 months after birth, is inversely correlated to the intensity of Bacteroides fragilis colonization 1 month after birth. Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
  • 290. Incidence of fever in relation to placebo 0 -20 – -40 – -60 – -80 - -53% p=0.008 <ul><li>326 eligible children (3–5 years of age) </li></ul><ul><li>placebo ( N=104), </li></ul><ul><li>Lactobacillus acidophilus NCFM (N=110), </li></ul><ul><li>L acidophilus NCFM + Bifidobacterium animalis subsp lactis Bi-07 ( N =112) </li></ul><ul><li>Twice daily for 6 months. </li></ul>Probiotic Effects on Cold and Influenza-Like Symptom Incidence and Duration in Children Leyer Pediatrics 2009;124;e172 -72.7% p=0.0009 SINGLE PROBIOTIC COMBINATIONS PROBIOTICS
  • 291. Antibiotic use incidence relative to placebo 0 -30 – -60 – -90 – -68.4% p=0.0002 Probiotic Effects on Cold and Influenza-Like Symptom Incidence and Duration in Children Leyer Pediatrics 2009;124;e172 -84.2% P<0.0001 SINGLE PROBIOTIC COMBINATIONS PROBIOTICS <ul><li>326 eligible children (3–5 years of age) </li></ul><ul><li>placebo ( N=104), </li></ul><ul><li>Lactobacillus acidophilus NCFM (N=110), </li></ul><ul><li>L acidophilus NCFM + Bifidobacterium animalis subsp lactis Bi-07 ( N =112) </li></ul><ul><li>Twice daily for 6 months. </li></ul>
  • 292. <ul><li>326 eligible children (3–5 years of age) </li></ul><ul><li>placebo ( N=104), </li></ul><ul><li>Lactobacillus acidophilus NCFM (N=110), </li></ul><ul><li>L acidophilus NCFM + Bifidobacterium animalis subsp lactis Bi-07 ( N =112) </li></ul><ul><li>Twice daily for 6 months. </li></ul>Antibiotic use incidence relative to placebo 0 -30 – -60 – -90 – -68.4% p=0.0002 Probiotic Effects on Cold and Influenza-Like Symptom Incidence and Duration in Children Leyer Pediatrics 2009;124;e172 -84.2% P<0.0001 SINGLE PROBIOTIC COMBINATIONS PROBIOTICS Subjects receiving probiotic products had significant reductions in days absent from group child care, by 31.8% (single strain; P.002) and 27.7% (strain combination; P <.001), compared with subjects receiving placebo treatment.
  • 293. <ul><li>parassites </li></ul>
  • 294. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam Flohr C EA 2010; 40:131 <ul><li>1566 schoolchildren aged 6–17. </li></ul><ul><li>Anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. </li></ul>1.31 OR for Appearance of Skin Sensitization over 12 Months Associated with anti-helminthic treatment p=0.03 1.5 – 1.0 – 0.5 – 0
  • 295. Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam Flohr C EA 2010; 40:131 <ul><li>1566 schoolchildren aged 6–17. </li></ul><ul><li>Anti-helminthic therapy or a placebo at 0, 3, 6, and 9 months. </li></ul>1.31 OR for Appearance of Skin Sensitization over 12 Months Associated with anti-helminthic treatment p=0.03 1.5 – 1.0 – 0.5 – 0 But not of clinical allergic disease.
  • 296. <ul><li>Genetic and Environment </li></ul>
  • 297. <ul><li>Pensare positivo riduce anche il rischio di diventare asmatici, </li></ul><ul><li>Evitare il contatto dei lattanti con agenti infettivi nei periodi di massima esposizione allergenica, </li></ul><ul><li>Nei bambini a rischio la sensibilizzazione si realizza già al 2° anno e, se si associa ad infezioni respiratorie frequenti, il rischio di asma è molto elevato, </li></ul><ul><li>Le reazioni alla puntura di imenotteri sono più frequenti negli allergici e più gravi negli asmatici, </li></ul><ul><li>Il paracetamolo aumenta il rischio di allergia ma se assunto assieme a sostanze anti-ossidanti forse no, </li></ul><ul><li>Particolare attenzione agli allergeni dotati di attività proteolitica, </li></ul><ul><li>Il fumo…non finisce di stupire… </li></ul><ul><li>L’inquinamento aumenta lo stress ossidativo e la comparsa di malattie allergiche…OK: acido folico, DHA, olio d’oliva…curcuma, resveratrolo, </li></ul><ul><li>I probitici stimolano la sintesi di IgA, inducono una modesta flogosi intestinale che possono ridurre il rischio di malattie allergiche. </li></ul>Take home
  • 298. Thank you for your attention FORMAT -/0/2011

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