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

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

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.

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

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.

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.

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

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

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.

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

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

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.

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.

87. Effetto vaccinazioni

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

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

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.

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.

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

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.

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.

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

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.

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

182. FUMO E ASMA

183. FUMO E RISPOSTA IMMUNE - INFEZIONI

184. FUMO E FATTORI DI RISCHIO PER INIZIARE

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’

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

192. Smoking Cessation Chandler Chest 2010;137:428

193. Smoking Cessation Chandler Chest 2010;137:428

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

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