What 2012 asthma and wheezing

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What 2012 asthma and wheezing

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2012  asthmaAttilio BonerUniversity ofVerona, Italy
  2. 2. Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010 R. de Marco, Eur Respir J 2012;39:883 Overall mean prevalence The same screening questionnaire by mail or phone. Random samples of the general population (age 20–44 yrs). (1991–1993; n=6,031) (1998–2000; n=18,873) (2007–2010; n=10,494)
  3. 3. Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010 R. de Marco, Eur Respir J 2012;39:883 Overall mean prevalence The same screening The asthma epidemic questionnaire by mail or is not over in Italy. phone. During the past 20 yrs, asthma prevalence has Random samples of the increased by 38%, general population (age 20–44 with a similar in parallel yrs). increase in asthma-like symptoms and (1991–1993; n=6,031) allergic rhinitis. (1998–2000; n=18,873) (2007–2010; n=10,494)
  4. 4. Effect of urbanisation on asthma, allergy and airways inflammation in a developing country setting Robinson Thorax 2011;66:1051 1441 adolescents Rates of lifetime wheezing 25 - aged 13-15 yrs enrolled from 2 settings: - a peri-urban shanty town 20 - 22% in Lima (n=725); - 23 rural villages 15 – in Tumbes (n=716). p<0.001 Questionnaires 10 – asthma and allergy, 10% environmental exposures. 05 – Spirometry, exhaled nitric oxide (eNO), 0 allergy skin testing. Lima Tumbes
  5. 5. Effect of urbanisation on asthma, allergy and airways inflammation in a developing country setting Robinson Thorax 2011;66:1051 1441 adolescents Boxplots of median particulate matter aged 13-15 yrs enrolled concentrations (approximate PM2.5) in from 2 settings: Lima and Tumbes - a peri-urban shanty town in Lima (n=725); - 23 rural villages in Tumbes (n=716). Questionnaires asthma and allergy, environmental exposures. Spirometry, exhaled nitric oxide (eNO), allergy skin testing.
  6. 6. Effect of urbanisation on asthma, allergy and airways inflammation in a developing country setting Robinson Thorax 2011;66:1051 Current Asthma Current Rhinitis Current Eczema25 -20 - 23%15 – p<0.001 p<0.00110 – 12% 12% 12% p<0.00105 – 3% 0.4%0 Lima Tumbes
  7. 7. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111• European Respiratory Society proposed a classification % with ≥1 episode of wheezing of wheeze into episodic viral confirmed by a physician. and multiple-trigger wheeze. 100 –• 160 full-term, steroid-free, infection-free children 080 – aged 4 to 26 months referred for investigation of recurrent 060 – 81% lower respiratory tract symptoms. 040 –• Lung function testing, dosimetric methacholine 020 – challenge test and FENO measurement. 00
  8. 8. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 Forced expiratory flow at functional % children with BHR residual capacity (V‘max,FRC) in multiple-trigger wheezers in multiple-trigger wheezers and non-wheezers. and non-wheezers.
  9. 9. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 Forced expiratory flow at functional Airway responsiveness residual capacity (V‘max,FRC) in multiple-trigger wheezers in multiple-trigger wheezers and non-wheezers. and non-wheezers. Forced expiratory flow at functional residual capacity (V‘max,FRC) in multiple-trigger wheezers was significantly lower than that seen in non-wheezers.
  10. 10. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 Forced expiratory flow at functional Increased airway residual capacity (V‘max,FRC) % children with BHR in multiple-trigger wheezers in multiple-trigger wheezers responsiveness and non-wheezers. and non-wheezers. (the provocative dose of methacholine causing a 40% decrease in V‟max,FRC [PD40 V‟max,FRC]) of 0.90 mg or less was significantly more common in multiple-trigger wheezers than in nonwheezers.
  11. 11. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 Lung function was significantly lower and increased airway Forced expiratory flow at functional Airway responsiveness responsiveness more(V‘max,FRC) residual capacity common in multiple-trigger wheezers in multiple-trigger wheezers in multiple-trigger wheezers than in non-wheezers. non-wheezers. and and non-wheezers.
  12. 12. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 However, there were no differences in any other Forced expiratory flow at functional features capacity (V‘max,FRC)2 wheezing groups with similar residual between the Airway responsiveness in multiple-trigger wheezers prevalences of atopy, in multiple-trigger wheezers exposure to environmental and non-wheezers. and non-wheezers. tobacco smoke and FENO levels.
  13. 13. Symptom-based classification of wheeze: how does it work in infants? Syrjänen, JACI 2011;128:1111 Moreover, the symptom-based Forced expiratory flow at functional classification max,FRCwheeze isAirway responsiveness residual capacity (V‘ of ) likely to change in multiple-trigger wheezers in significantly wheezers a single calendar year. multiple-trigger within and non-wheezers. and non-wheezers.
  14. 14. Comparison of childhood wheezing phenotypes in 2 birthcohorts: ALSPAC and PIAMA. Savenije JACI 2011;127:1505 Wheezing phenotypes Phenotypes identified in the the Avon Longitudinal PIAMA study (Netherlands) had Study of Parents And wheezing patterns that Children (ALSPAC) were similar (5760) and the to those previously reported Prevention and in ALSPAC (Scotland) , Incidence of Asthma adding further evidence and Mite Allergy to the existence of an (PIAMA) study intermediate-onset phenotype (2810). with onset of wheeze after 2 Reports of wheezing years of age. from 0 to 8 years.
  15. 15. Comparison of childhood wheezing phenotypes in 2 birthcohorts: ALSPAC and PIAMA. Savenije JACI 2011;127:1505 Wheezing phenotypes Phenotypes identified in the the Avon Longitudinal PIAMA study (Netherlands) had Associations with Study of Parents And wheezing patterns that Children (ALSPAC) asthma, atopy, were similar (5760) and the lung BHR, and to those previously reported Prevention and function were Incidence of Asthma in ALSPAC (Scotland) , remarkably adding further evidence and Mite Allergy to the existence of an (PIAMA) studyin the similar intermediate-onset phenotype (2810). 2 cohorts. with onset of wheeze after 2 Reports of wheezing years of age. from 0 to 8 years.
  16. 16. Comparison of childhood wheezing phenotypes in 2 birthcohorts: ALSPAC and PIAMA. Savenije JACI 2011;127:1505 Estimated prevalence of wheeze Estimated prevalence of wheeze at each time point from birth to at each time point from birth to age 8 years for each wheezing age 8 years for each wheezing phenotype in ALSPAC free 6-class phenotype in PIAMA optimal model (N = 5760). 5-class model (N = 2810).
  17. 17. Exclusive viral wheeze and allergic wheeze: evidence for discrete phenotypes Strippoli ERJ 2011;38:472 Leichestershire Cohort Studies. Children recruited in For each age , we assessed 1998 at an age associations between the of 1-4 yrs. three classes of triggers Followed up in 1999, using log-linear models: 2001, 2003 and 2006. A. exercise and allergens, Questions about B. exercise and infection; respiratory symptoms C. allergens and infection. during the previous 12 months and environmental exposures.
  18. 18. Exclusive viral wheeze and allergic wheeze: evidence for discrete phenotypes Strippoli ERJ 2011;38:472 Our findings provide support for an old concept proposing that infection and allergy can cause airway narrowing in susceptible individuals, either by acting directly (as trigger factors) or by induction of bronchial hyperresponsiveness Triggers and inducers: (as inducing factors). model of possible mechanisms. BHR: bronchial Exercise, in contrast, is merely a hyperresponsiveness, trigger, which leads to airway #: in susceptible individuals. narrowing only in the presence of bronchial hyperresponsiveness caused by other factors.
  19. 19. Different inflammatory phenotypes in adults and children with acute asthma Wang ERJ 2011;38:567 Adults with stable (n=29) or acute (=22) asthma. The asthma phenotype was predominantly Healthy adults (n=11). eosinophilic in children Children with stable with acute asthma (50%) (n=49) or acute (n=28) but neutrophilic in asthma. adults with acute Healthy children (n=9). asthma (82%). Sputum induction.
  20. 20. Different inflammatory phenotypes in adults and children with acute asthma Wang ERJ 2011;38:567 Proportion of neutrophils and eosinophils for adults and children with asthma.Neutrophils Neutrophils in adult inpopulation. paediatric group. EosinophilsEosinophils in in adult paediatricpopulation. group. AAA: adults with acute asthma, ASA: adults with stable asthma, HC: healthy controls, CAA: children with acute asthma, CSA: children with stable asthma, CHC: child health control.
  21. 21. Different inflammatory phenotypes in adults and children with acute asthma Wang ERJ 2011;38:567 Proportion of neutrophils and eosinophils for adults and children with asthma. Possible explanations for the eosinophilNeutrophils Neutrophils response seen in CAAs in adult inpopulation. allergen exposure, include paediatric less maintenance group. corticosteroid therapy or a different response EosinophilsEosinophils to triggers in in adult ofpopulation. acute asthma. paediatric group. AAA: adults with acute asthma, ASA: adults with stable asthma, HC: healthy controls, CAA: children with acute asthma, CSA: children with stable
  22. 22. Different inflammatory phenotypes in adults and children with acute asthma Wang ERJ 2011;38:567 Proportion of neutrophils and eosinophils for adults and children with asthma. The mixed eosinophil–neutrophil responses in CAAsNeutrophils Neutrophils in suggest that concurrent adult inpopulation. paediatric exposure to multiple group. triggers (e.g. allergens and virus infection) may Eosinophils an explanation be Eosinophils in in adult the inflammatory for paediatric population. response observed. group. AAA: adults with acute asthma, ASA: adults with stable asthma, HC: healthy controls, CAA: children with acute asthma, CSA: children with stable asthma, CHC: child health control.
  23. 23. Relation of early childhood growth and wheezing phenotypes to adult lung function Sherrill Pediatr Pulmonol 2011;46:956 •Weight growth (between 3 Participants in the Tucson and 6 years) was positively Childrens Respiratory associated with higher levels Study. of FVC at age 16 and Pulmonary function assessed 22 years (P  = 0.0001) among at ages 16 and 22. subjects who did not have preschool wheezing. Longitudinal models were •However, this association was used to determine completely absent among predictors of FVC and FEV1 subjects who had wheezing at ages 16 and 22 years. lower respiratory tract illnesses in the first 3 years of life.
  24. 24. Relation of early childhood growth and wheezing phenotypes to adult lung function Sherrill Pediatr Pulmonol 2011;46:956 •Weight growth (between 3 Participants in the Tucson and 6 years) was positively Childrens Respiratory associated with higher levels The rate of weight gain Study. of FVC at age 16 and between 3 and 6 yrs is significantly positively Pulmonary function assessed 22 years (P  = 0.0001) among at ages 16 and 22. FVC related to adult subjects who did not have and FEV1 and this preschool wheezing. association is modified Longitudinal models were •However, this association was by early wheezy used to determine completely absent among phenotypes. predictors of FVC and FEV1 subjects who had wheezing at ages 16 and 22 years. lower respiratory tract illnesses in the first 3 years of life.
  25. 25. • natural history
  26. 26. Factors influencing asthma remission: a longitudinal study from childhood to middle age Burgess Thorax 2011;66:508 % patients with asthma remission 80 – In 1968 the Tasmanian Longitudinal Health Study 70 – enrolled 7-year-old 65% 60 – schoolchildren (n=8583). 50 – Re-surveyed in 2004. 40 – Asthma remission, defined as 30 – no asthma attack for 2 years 20 – and no current asthma medication. 10 – 0
  27. 27. Factors influencing asthma remission: a longitudinal study from childhood to middle age Burgess Thorax 2011;66:508 OR for remission1.0 – 0.750.5 – 0.66 0.66 0.66 0.56 0.42 0.380.0 childhood passive childhood later-onset childhood later-onset maternal allergic rhinitis allergic rhinitis eczema eczema asthma chronic bronchitis smoking
  28. 28. Factors influencing asthma remission: a longitudinal study from childhood to middle age Burgess Thorax 2011;66:508 OR for remission. Childhood-onset asthma (OR=3.76)1.0 – was more likely to remit than adult-onset asthma 0.750.5 – 0.66 0.66 0.66 0.56 0.42 0.380.0 childhood passive childhood later-onset childhood later-onset maternal allergic rhinitis allergic rhinitis eczema eczema asthma chronic bronchitis smoking
  29. 29. Factors influencing asthma remission: a longitudinal study from childhood to middle age Burgess Thorax 2011;66:508ConclusionWhile inherited factors cannot be changed,the effect of allergic rhinitis or eczemaon asthma remission might be altered by early,aggressive treatment.Every effort should be made to lessenpassive exposure to tobacco smoke.
  30. 30. Pet shop workers: exposure, sensitization, and work-related symptoms. Renström A, Allergy 2011;66:1081 % subjects presenting 60 - 53% 50 – Subjects (n = 59) from 40 – 24 pet shops. Questionnaire and lung 30 – 34% function tests and skin prick tests. 20 – 22% 10 – 0 nasal eye asthma symptoms
  31. 31. Pet shop workers: exposure, sensitization, and work-related symptoms. Renström A, Allergy 2011;66:1081 % subjects presenting 60 - 53% 50 – However,only Subjects (n = 59) from 40 – 24 pet shops. (7%) 4 workers were previously 30 – 34% Questionnaire and lung diagnosed with function tests and skin asthma prick tests 20 – 22% 10 – 0 nasal eye asthma symptoms
  32. 32. Pet shop workers: exposure, sensitization, and work-related symptoms. Renström A, Allergy 2011;66:1081 % subjects sensitized to work-related allergens 30 – Subjects (n = 59) from 24 pet shops. 29% 20 – Questionnaire and lung function tests and skin prick tests 10 – 0
  33. 33. Pet shop workers: exposure, sensitization, and work-related symptoms. Renström A, Allergy 2011;66:1081 % subjects sensitized to work-related allergens The findings stress 30 – the importance of Subjects (n = 59) from 24 pet shops. the improving 29% knowledge of 20 – health risks and Questionnaire and lung allergen avoidance function tests and skin measures among prick tests 10 – pet shop staff 0
  34. 34. EAACI Position Paper: Prevention of work-relatedrespiratory allergies among pre-apprentices or apprentices and young workers Moscato G, Allergy 2011;66:1164 The physician in charge for the baseline health assessment should discuss the results with the young adult helping her/him in making the professional choice. The young adult should be educated to adopt all preventive measures to limit occupational exposure to potential allergens and respiratory irritants and to recognize and report immediately all possible symptoms suggestive of onset of work-related respiratory allergies or work-related exacerbations. Medical surveillance should be prioritized in the first 2–3 years of exposure and scheduled according to the clinical profile, exposure details, and reliability of available tests.
  35. 35. Familial aggregation of allergen-specific sensitization and asthma Kurzius-Spencer, Pediatr Allergy Immunol 2012;23:21 1151 families in the Crude estimates of Tucson Children‟s parent–offspring (P–O) Respiratory Study and and sibling correlations 435 families in the 2.26% were statistically Tucson Epidemiological significant for most Study of Airway allergens, ranging from Obstructive Disease 0.03 to 0.29 SPTs Physician-diagnosed asthma at age ≥8 yr
  36. 36. Familial aggregation of allergen-specific sensitization and asthma Kurzius-Spencer, Pediatr Allergy Immunol 2012;23:21 Sibling correlations for 1151 families in the specific response to Tucson Children‟s allergens were Respiratory Study and consistently higher than 435 families in the 2.26% parent–offspring (P–O) Tucson Epidemiological correlations, but this Study of Airway difference was significant Obstructive Disease only for dust mite and SPTs weed mix Physician-diagnosed asthma at age ≥8 yr
  37. 37. African ancestry, early life exposures and respiratory morbidity in early childhood. Kumar, Clin Exp Allergy 2012;42:265Background Racial disparities persist in early childhoodwheezing and cannot be completely explained by knownrisk factors.Objective To evaluate the associations of geneticancestry and self-identified race with early childhoodrecurrent wheezing, accounting for socio-economicstatus (SES) and early life exposures.
  38. 38. African ancestry, early life exposures and respiratory morbidity in early childhood. Kumar, Clin Exp Allergy 2012;42:265 % of children with recurrent wheezing1034 children in an urban, 10, – multi-racial, prospective 7,5 – birth cohort in USA.Genetic ancestry. 5,0 – 6.1%Recurrent wheezing. 2,5 – 0
  39. 39. African ancestry, early life exposures and respiratory morbidity in early childhood. Kumar, Clin Exp Allergy 2012;42:265 OR for recurrent wheezing 01.5 –1034 children in an urban, multi- 01.0 – 1.17 racial, prospective birth cohort in USA. 0.84 00.5 – p=0.005Genetic ancestry. p=0.004Recurrent wheezing. 00.0 African European ancestry ancestry
  40. 40. African ancestry, early life exposures and respiratory morbidity in early childhood. Kumar, Clin Exp Allergy 2012;42:265 OR for recurrent wheezing 01.5 – Genetic ancestry may be1034 children into evaluate a powerful way an urban, wheezing disparities multi-racial, prospective 01.0 – 1.17 birth cohortain USA. and proxy for differentially distributed 0.84Genetic ancestry. life 00.5 – genetic and early p=0.005 risk factors associated p=0.004Recurrent wheezing. with childhood recurrent wheezing. 00.0 African European ancestry ancestry
  41. 41. PerinatalRisk factors
  42. 42. Maternal obesity during pregnancy as a risk for early-life asthma. Lowe, JACI 2011;128:1107 Data from Swedish national registers. % of mothers 25 – All children (189783 children born 20 – to 129239 mothers). 20.1% Maternal BMI at each 15 – pregnancy at 8-10 weeks after conception. 10 – Asthma medication of ≥1 prescription 05 – 7.2% of inhaled steroids or montelukast. 00 OBESE OVERWEIGHT Hospital admission BMI ≥30 Kg/m2 BMI 25-29.9 Kg/m2 for asthma.
  43. 43. Maternal obesity during pregnancy as a risk for early-life asthma. Lowe, JACI 2011;128:1107 OR for asthma medication in children1.5 – 1.16 1.36 1.461.0 – 1.00.5 –00 18.5-24.9 25.0-29.9 30.0-34.9 ≥35 MATERNAL BMI (Kg/m2)
  44. 44. Maternal obesity during pregnancy as a risk for early-life asthma. Lowe, JACI 2011;128:1107 OR for asthma medication in children1.5 – 1.16 1.36 1.461.0 – 1.00.5 – If the association between maternal BMI and asthma risk in the child is causal in nature,00 it might explain between 11% and 13% 18.5-24.9 25.0-29.9 30.0-34.9 ≥35 of childhoodBMI (Kg/m2) MATERNAL asthma.
  45. 45. Oral contraceptive pill use before pregnancy and respiratory outcomes in early childhood Hancoc Pediat Allergy Immunol 2011;22:528 OCP use before pregnancy. •Combined pills were used much Lower respiratory tract more commonly than infections in 60,225 children progestin-only pills. followed to 6 months old. •Taking combined pills Wheezing in 42,520 children before pregnancy was followed to 18 months not associated with old, and asthma in 24,472 lower respiratory tract children followed to infections, wheezing, 36 months old. or asthma.
  46. 46. Oral contraceptive pill use before pregnancy and respiratory outcomes in early childhood Hancoc Pediat Allergy Immunol 2011;22:528 Progestin-only pill OCP use before pregnancy. •Combined pills were used much use in the year more commonly than Lower respiratory tract before pregnancy infections in 60,225 children progestin-only pills. had a slight followed to 6 months old. positive association •Taking combined pills Wheezingwheezing children with in 42,520 at before pregnancy was followed to 18 months old, not associated with 6-8 months old lower respiratory tract and asthma in 24,472 children aOR =1.19 infections, wheezing, followed to 36 months old. or asthma.
  47. 47. Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review Murk Pediatrics 2011;127:1125 OR for asthma if exposed to Studies published 3 – antibiotic in the first yr of life between 1950 and July 1, 2010, that assessed associations 2 – between antibiotic 2.04 exposure during 1.52 1.25 pregnancy or in the 1 – first year of life and asthma at ages 0 to 18 yrs. 0 all studies retrospective prospective studies studies
  48. 48. Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review Murk Pediatrics 2011;127:1125 OR for asthma if exposed to Studies published 3 – antibiotic in the first yr of life between 1950 and Risk estimate July 1, 2010, that assessed studies for associations 2 – between adjusted that antibiotic 2.04 for respiratory exposure during 1.52 1.25 pregnancy or in the infections is 1 – first year 1.16 OR of life and asthma at ages 0 to 18 yrs. 0 all studies retrospective prospective studies studies
  49. 49. Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review Murk Pediatrics 2011;127:1125 OR for asthma if exposed to Studies published to Antibiotics seem 3 – antibiotic in the first yr of life between 1950 and slightly increase July 1, 2010, that the risk of assessed associations childhood asthma. 2 – between antibiotic Reverse causality and 2.04 exposure during protopathic bias seem 1.52 1.25 pregnancy possible to be or in the 1 – first year of life confounders for and asthma at this relationship. ages 0 to 18 yrs. 0 all studies retrospective prospective studies studies
  50. 50. Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis Penders ERJ 2011;38:295 2 – OR for wheeze/asthma 18 longitudinal studies. Effect of antibiotic use on wheeze/ asthma. 1 – 1.27 0 Early antibiotic use
  51. 51. Infant antibiotic use and wheeze and asthma risk: a systematic review and meta-analysis Penders ERJ 2011;38:295 When we eliminated OR for 2 – studies with possible wheeze/asthma reverse causation 18 longitudinal studies. and respiratory tract infections leading Effect of antibiotic use to antibiotic use, on wheeze/ asthma. the pooled risk estimate 1 – 1.27 was attenuated to OR 1.12. 0 Early antibiotic use
  52. 52. First- and Second-Trimester Fetal Size and Asthma Outcomes at Age 10 Years Turner AJRCCM 2012;184:407 Rationale Greater early fetal size is associated with reduced asthma risk and improved lung function in early childhood. Objectives To test the hypothesis that associations between early fetal size, asthma symptoms, and lung function persist into later childhood.
  53. 53. First- and Second-Trimester Fetal Size and Asthma Outcomes at Age 10 Years Turner AJRCCM 2012;184:407 % reduction % increase927 children. in risk in FEV1First- and second-trimester +10 – of asthma fetal measurements. +6% ++5 –At 10 years of age: +00 – respiratory questionnaire spirometry, --5 – -6% bronchial challenge, and skin prick testing. -10 – For each millimeter increase -6% in first trimester size.
  54. 54. First- and Second-Trimester Fetal Size and Asthma Outcomes at Age 10 Years Turner AJRCCM 2012;184:407 OR for Asthma 3.0 –927 children.First- and second-trimester 2.5 – 2.8 fetal measurements. 2.0 –At 10 years of age: 1.5 – respiratory questionnaire 1.0 – spirometry, bronchial challenge, and 0.5 - skin prick testing. 0.0 Persistent low growth in I and II trimesters compared with persistent high growth.
  55. 55. First- and Second-Trimester Fetal Size and Asthma Outcomes at Age 10 Years Turner AJRCCM 2012;184:407 OR for Asthma 3.0 –927 children. Reduced fetal sizeFirst- and second-trimester 2.5 – 2.8 from the I trimester fetal measurements. 2.0 – is associated withAt 10increased risk years of age: 1.5 – respiratory questionnaire for asthma and 1.0 – spirometry, obstructed lung 0.5 - bronchial challenge, and function in childhood. skin prick testing. 0.0 Persistent low growth in I and II trimesters compared with persistent high growth.
  56. 56. Is large birth weight associated with asthma risk in early childhood? To, Arch Dis Child 2012;97:169 All single live birth Compared with (n=687194) born normal-birth-weight between 1 April 1995 and infants, 31 March 2001 large-birth-weight infants Followed until their 6th (2.3% of total) had a birthday slightly Birth weight was lower risk of developing categorized as asthma by age 6 after low (<2.5 kg), adjusting normal (2.5-4.5 kg), for confounders large (4.6-6.5 kg) and (adjusted RR = 0.90) extremely large (>6.5 kg)
  57. 57. Is large birth weight associated with asthma risk in early childhood? To, Arch Dis Child 2012;97:169 All single live birth (n=687194) born between 1 April 1995 and There was a trend 31 March 2001 towards Followed until their 6th increased risk of birthday asthma Birth weight was among extremely categorized as large-birth-weight low (<2.5 kg), infants normal (2.5-4.5 kg), (RR = 1.21) large (4.6-6.5 kg) and extremely large (>6.5 kg)
  58. 58. Is large birth weight associated with asthma risk in early childhood? To, Arch Dis Child 2012;97:169 All single live birth (n=687194) born Interventions to between 1 April 1995 and There was a trend reduce the 31 March 2001 towards incidence of increased risk of Followed untillarge 6th extreme their birthday weight birth asthma Birthmay help to weight was among extremely categorized as risk reduce the large-birth-weight of asthma low (<2.5 kg), infants normal (2.5-4.5 kg), (RR = 1.21) large (4.6-6.5 kg) and extremely large (>6.5 kg)
  59. 59. Is large birth weight associated with asthma risk in early childhood? To, Arch Dis Child 2012;97:169Adjusted RRs of incidence of asthma, asthma hospitalisation and asthma emergency departments visits Also low-birth-weight is associated with an increased risk of asthma
  60. 60. Low birth weight and respiratory hospitalizations in adolescence Walter Pediatr Pulmonol 2011;46:473 Estimated cumulative incidence of A population-based hospitalization for respiratory illness as a function of birth weight category retrospective cohort study using birth certificates from 1987 to 1994 to identify exposed (low birth weight) and unexposed (normal birth weight) subjects. Moderately-low-birth weight (1,500–2,499 g) and very- low-birth weight The cumulative incidence of hospitalization increases with decreasing birth weight (<1,500 g).
  61. 61. Low birth weight and respiratory hospitalizations in adolescence Walter Pediatr Pulmonol 2011;46:473 Adjusted Hazard Ratios for Hospitalization for Specific Respiratory Diagnoses in Adolescence as a Function of Birth Weight1Adjusted for birth year, sex, maternal age, race, income, marital status, and smoking status
  62. 62. Low birth weight and respiratory hospitalizations in adolescence Walter Pediatr Pulmonol 2011;46:473 Adjusted Hazard Ratios for Hospitalization for Specific Respiratory Diagnoses in Adolescence as a Function of Birth Weight Low birth weight was associated with an increased risk of respiratory hospitalizations in adolescence. Comorbidities explained some of this risk. However, low birth weight remained independently associated with an increased risk of hospitalization.1Adjusted for birth year, sex, maternal age, race, income, marital status, and smoking status
  63. 63. Low birth weight and respiratory hospitalizations in adolescence Walter Pediatr Pulmonol 2011;46:473 During adolescence Hazard Ratios for hospitalization for Asthma Respiratory Infections4 – 3.763 –2 – 1.99 1.18 1.041 –0 NBW MLBW VLBW NBW MLRW VLBW
  64. 64. Association of late pre-term birth with asthma in young children: practice-based study Goyal, Pediatrics 2011;128:e830 % children with a diagnosis of asthma at age 18 mo. 10 – Retrospective cohort study. 7925 born in 2007 05 – 8.3% at 34 to 42 weeks of gestation. Monitored from birth to 18 months. 00
  65. 65. Association of late pre-term birth with asthma in young children: practice-based study Goyal, Pediatrics 2011;128:e830 Proportions of asthma-related outcomes according to gestational-age category compared with the reference group at 39 to 42 weeks of gestation (p <0.05). Retrospective cohort study. 7925 born in 2007 at 34 to 42 weeks of gestation. Monitored from birth to 18 months.
  66. 66. Association of late pre-term birth with asthma in young children: practice-based study Goyal, Pediatrics 2011;128:e830 Proportions of asthma-related outcomes according to gestational-age category compared with the reference group at 39 to 42 weeks of gestation (p <0.05). Retrospective cohort Term infant study. Low-normal gestation 7925 born in 2007 at 34 to 42 weeks of Late pre-term gestation. Monitored from birth to 18 months.
  67. 67. Association of late pre-term birth with asthma in young children: practice-based study Goyal, Pediatrics 2011;128:e830 Proportions of asthma-related outcomes according to gestational-age category compared with the reference group Birth at late-preterm at 39 to 42 weeks of gestation (p <0.05). and low-normal Retrospective cohort Term infant gestational ages might study. Low-normal be an important risk gestation 7925 born in 2007 factor for the at 34 to 42 weeks of development of asthma Late pre-term gestation. increased and for Monitoredservice use health from birth to in early childhood. 18 months.
  68. 68. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring Li APAM 2011;165:945 Kaplan-Meier estimates of asthma risk by maternal magnetic field (MF) 626 children with exposure level during pregnancy asthma. 0.95 Followed up for 13 years. A meter to measure their MF levels (mobile phone, wireless connections) during pregnancy.
  69. 69. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring Li APAM 2011;165:945 Kaplan-Meier estimates of asthma risk by maternal magnetic field (MF) Every 1- milligauss 626 children with of exposure level during pregnancy (mG) increase asthma. maternal MF level 0.95 during pregnancy Followed up for 13 was associated with years. a 15% increased A meter of measure rate to asthma their MF levels in offspring during pregnancy. (adjusted hazard ratio 1.15)
  70. 70. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring Li APAM 2011;165:945 aHR for asthma 4 – 626 children with asthma. 3 – 3.52 0.95 Followed up for 13 years. 2 – A meter to measure 1 – 1.74 their MF levels (mobile 1 phone, wireless 00 ≤0.3 mG >0.3-2.0 mG >2.0 mG connections) during magnetic field exposure during pregnancy (MF level) pregnancy.
  71. 71. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring Li APAM 2011;165:945 aHR for asthma 4 – High maternal 626 children with asthma. Magnetic Fields 3 – 3.52 0.95 levels in Followed up for 13 pregnancy may years. 2 – increase the Arisk of asthma meter to measure 1 – 1.74 their MF levels in offspring. 1 (mobile phone, wireless connections) 00 ≤0.3 mG >0.3-2.0 mG >2.0 mG during pregnancy. magnetic field exposure during pregnancy (MF level)
  72. 72. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring Li APAM 2011;165:945 gene expression aHR for asthma 4 – or changes in 626 children with asthma. repair DNA 3 – 3.52 0.95 Followedresult 13 may up for by years. exposures. MF 2 – A meter to measure 1 – 1.74 their MF levels (mobile 1 phone, wireless 00 ≤0.3 mG >0.3-2.0 mG >2.0 mG connections) during magnetic field exposure during pregnancy (MF level) pregnancy.
  73. 73. A recurring question. Are there health effects of power-frequency magnetic fields? Editorial APAM 2011;165:959• An ongoing scientific and public debate has raged over the possibile health effects of power-frequency (50-60 Hz) magnetic fields (MFs).• Comprehensive scientific reviews conducted by various agencies, all have found that power-frequency MFs may play a role in childhood disorders but were unable to establish a mechanism or animal model to definitively support their findings.
  74. 74. A recurring question. Are there health effects of power-frequency magnetic fields? Editorial APAM 2011;165:959• Prolonged exposure of children to MFs higher than a threshold of about 4 milligauss is associated with an approximate 2-fold elevation in leukemia risk.• Li et al (APAM 2011;165:945) provide us with evidence of a somewhat novel and relatively understudied helath effect associated with MFs: an association with childhood asthma.
  75. 75. A recurring question. Are there health effects of power-frequency magnetic fields? Editorial APAM 2011;165:959• Prolonged exposure of children to MFs higher than a threshold of about The potentialassociatedhealth 4 milligauss is public with an approximate implications of this work are 2-fold elevation in leukemia risk. significant since MF exposures are widespread,• Li et al (APAM 2011;165:945) provide women evidence affecting about 14% of us with in of a somewhat novel and relatively understudied helath effect associated with MFs: an association withasthma asthma. the United States, and childhood is a relatively common disease.
  76. 76. PerinatalProtective factors
  77. 77. Mode and place of delivery, gastrointestinal microbiota and their influence on asthma and atopy Nimwegen, JACI 2011;128:948 In children with colonization by Birth Cohort Study. Clostridium difficile at age 1 mo OR for Birth characteristics, 3.0 – lifestyle factors. Atopic manifestations. 2.0 - Fecal samples at age 1 mo 2.06 1.43 (n= 1176) to determine microbiota composition. 1.0 – Blood samples at ages 1, 2, and 6 to 7 yrs to 00 determine specific IgE levels. Asthma at Eczema age 6-7 yrs
  78. 78. Mode and place of delivery, gastrointestinal microbiota and their influence on asthma and atopy Nimwegen, JACI 2011;128:948 In children with vaginal home Birth Cohort Study. delivery compared with vaginal hospital delivery OR for Birth characteristics, lifestyle factors. 1.0 – Atopic manifestations. Fecal samples at age 1 mo 0.84 0.59 0.61 (n= 1176) to determine 0.5 – microbiota composition. Blood samples 00 at ages 1, 2, and 6 to 7 yrs to Asthma at sIgE to Eczema determine specific IgE levels. age 6-7 yrs foods
  79. 79. Mode and place of delivery, gastrointestinal microbiota and their influence on asthma and atopy Nimwegen, JACI 2011;128:948 In children with vaginal home After stratification Birth Cohort Study. delivery compared with vaginal for parental history hospital delivery OR for Birth characteristics, of atopy, lifestyledecreased risk the factors. 1.0 – of sensitization Atopic manifestations. to food allergens 0.84 Fecal samples at age= 10.52) (adjusted odds ratio mo 0.61 (n= 1176) to determine and asthma (aOR = 0.47) 0.5 – 0.59 microbiota composition. among vaginally Blood samples infants home-born wasages 1, 2, and 6 to 7 yrs to at only found for children 00 Asthma at sIgE to Eczema with atopic parents. determine specific IgE levels. age 6-7 yrs foods
  80. 80. Mode and place of delivery, gastrointestinal microbiota and their influence on asthma and atopy Nimwegen, JACI 2011;128:948 In children with vaginal home Birth Cohort Study. delivery compared with vaginal hospital delivery OR for Birth characteristics, Mode and place lifestyle factors.affect of delivery 1.0 – the gastrointestinal Atopic manifestations. microbiota composition, 0.84 Fecal samples at age 1 mo which subsequently 0.61 (n= 1176) to determine influences the risk 0.5 – 0.59 microbiota composition. of atopic Blood manifestations. samples 00 at ages 1, 2, and 6 to 7 yrs to Asthma at sIgE to Eczema determine specific IgE levels. age 6-7 yrs foods
  81. 81. Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms Sonnenschein-van der Voort, Eur Respir J 2012;39:81 OR in children never-breastfed Prospective cohort vs those breasfed for 6 months for study of 2 – 5,368 children. Breastfeeding 1.57 duration. 1.44 1.26 1 – 1.25 Wheezing, shortness of breath, dry cough and persistent phlegm by questionnaires. 0 shortness persistent wheezing dry cough of breath phlegma
  82. 82. Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms Sonnenschein-van der Voort, Eur Respir J 2012;39:81 OR in children never-breastfed Prospective cohort vs those breasfed for 6 months for study ofstrongest The 2 – 5,368 children. associations per symptom Breastfeeding per year were 1.57 duration. observed for 1.44 1.26 wheezing at 1 – 1.25 Wheezing, 1 and 2 yrs shortness of breath, dry cough and persistent phlegm by questionnaires. 0 shortness persistent wheezing dry cough of breath phlegma
  83. 83. Duration and exclusiveness of breastfeeding and childhood asthma-related symptoms Sonnenschein-van der Voort, Eur Respir J 2012;39:81 OR in children never-breastfed Shorter duration of Prospective cohort breastfeeding were vs those breasfed for 6 months for associated with study of 2 – 5,368 children. of increased risks asthma-related Breastfeedingpreschool symptoms in children. 1.57 duration. associations 1.44 1.26 These seemed, at least 1 – 1.25 Wheezing, be explained partly, to shortness of breath, by infectious, dry but notand atopic cough by persistent phlegm mechanisms by questionnaires. 0 shortness persistent wheezing dry cough of breath phlegma
  84. 84. Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood Magdelijns Pediatrics 2011;128:e144 KOALA Birth Cohort •Maternal folic acid Study (n=2834). supplement use during Data on eczema pregnancy was not associated and wheeze at with increased risk of wheeze, 3, 7, 12, and 24 months, lung function, asthma, or 4 to 5 years, and related atopic outcomes in the 6 to 7 years. offspring. •Maternal ICF level in late Intracellular folic acid pregnancy was inversely (ICF) determined in associated with asthma risk at blood samples taken at ~35 weeks of pregnancy age 6 to 7 years in a (n=837). dose-dependent manner (p for trend =0.05).
  85. 85. Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood Magdelijns Pediatrics 2011;128:e144 KOALA Birth Cohort not Our results do •Maternal folic acid confirm the mouse model of Study (n=2834). supplement use during any meaningful association pregnancy was not associated Data between folic acid on eczema andsupplement use during wheeze at with increased risk of 3, 7, 12, and 24and atopic pregnancy wheeze, lung months, in the offspring. diseases 4 function, asthma, or related to 5 years, and Higher ICF levels atopic outcomes in the 6 toin pregnancy tended, 7 years. offspring. at most, toward a small Intracellular folic acid •Maternal ICF level in late decreased risk pregnancy was inversely (ICF) determined in for developing associated with asthma risk at blood samples taken at asthma. age 6 to 7 years in a ~35 weeks of pregnancy (n=837). dose-dependent manner
  86. 86. Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood Magdelijns Pediatrics 2011;128:e144Prevalence of wheeze (A) and eczema (B) at different ages
  87. 87. Folic Acid Use in Pregnancy and the Development of Atopy, Asthma, and Lung Function in Childhood Magdelijns Pediatrics 2011;128:e144 OR for asthma at 6-7 yrs1.0 – 1.0 p<0.005 for trend 0.730.5 – 0.46 0.41 0.310.0 1st Quintile 2nd Quintile 3rd Quintile 4th Quintile 5th Quintile (≤ 480 nmol/L) (481–643 (644–862 (863–1139 (≥ 1140 nmol/L) nmol/L) nmol/L) nmol/L) Intracellular folic acid Levels (Divided Into Quintiles)
  88. 88. Asthma and psyke
  89. 89. Maternal depression related to infant‘s wheezing Lefevre Pediat Allergy Immunol 2011;22:608 In cases vs controls OR 136 cases aged for maternal 2.0 – <36 mo suffering from wheezing and 1.5 – 1.98 matched healthy controls. 1.55 1.0 – State Trait Anxiety Inventory and the 0.5 – Beck Depression Inventory short 0 Depression Anxiety form. During pregnancy
  90. 90. Maternal depression related to infant‘s wheezing Lefevre Pediat Allergy Immunol 2011;22:608 OR for maternal depression 136 cases aged in wheezers vs controls <36 mo suffering 7.0 – from wheezing and matched healthy 6.0 – 5.0 – 6.7 controls. 4.0 – 3.0 – State Trait Anxiety Inventory and the 2.0 – 2.2 Beck Depression 1.0 – Inventory short 0.0 Mild Moderate-Severe form. Depression
  91. 91. Maternal depression related to infant‘s wheezing Lefevre Pediat Allergy Immunol 2011;22:608 OR for severe wheezing 5.0 – 136 cases aged <36 mo suffering from wheezing and 4.0 – 4.25 matched healthy 3.0 – controls. 2.0 – State Trait Anxiety Inventory and the 1.0 – Beck Depression 1 Inventory short 0.0 Mild Moderate-Severe form. Mother Depression
  92. 92. Maternal depression related to infant‘s wheezing Lefevre Pediat Allergy Immunol 2011;22:608 OR for severe wheezing 5.0 – 136 cases aged <36 mo suffering from wheezing and 4.0 – 4.25 It is important matched healthy 3.0 – controls. depressive assess symptoms in 2.0 – Statemothers of Trait Anxiety Inventory and the infants with 1.0 – Beck Depression asthma. 1 Inventory short 0.0 Mild Moderate-Severe form. Mother Depression
  93. 93. State-trait AnxietyInventory StateHow do you feel RIGHTNOW, at this moment:1, not at all; 2, somewhat;3, moderate; 4, very much.
  94. 94. State Trait Anxiety Inventory
  95. 95. BeckDepressionInventoryshort form.
  96. 96. Relationship between maternal demoralization, wheeze, and immunoglobulin E among inner-city children Reyes Ann Allergy Asthma Immunol 2011;107:42 Mean prenatal demoralization score on wheeze presentations within the first 5 years of a childs life. Women aged 18 to 35 years p<0.05 p<0.05 residing in New York City. Maternal demoralization (ie, psychological distress). Questionnaire and total and indoor allergen sIgE (at birth and ages 2, 3, and 5 years).
  97. 97. Relationship between maternal demoralization, wheeze, and immunoglobulin E among inner-city children Reyes Ann Allergy Asthma Immunol 2011;107:42Maternal DemoralizationMaternal demoralization was measured by the 27-item PERI-D scale at every visit (5repeated measures). The PERI-D is a composite of 8 domains (perceived physicalhealth, sadness, poor self-esteem, dread, anxiety, confused thinking,hopelessness/helplessness, and psychophysiological symptoms) encompassing the singleconstruct of demoralization. 21,27 Each question was rated on a 5-point Likert scale(scored 0 to 4), where a higher score indicated greater psychological distress, andqueried about symptoms within the last year. Developed for epidemiologic research incommunity samples and validated in a New York City sample, the PERI-D demonstratesadequate internal consistency in minority and Spanish-speaking immigrant populations(Cronbach α of 0.91 for African Americans, 0.93 for English-speaking MexicanAmericans, and 0.95 for Spanish-speaking Mexican Americans).22,2721. Clarke DM, Kissane DW. Demoralization: its phenomenology and importance.Aust N Z J Psychiatry. 2002;36:733–742. [PubMed]27. Dohrenwend BP, Shrout PE, Egri G, Mendelsohn FS. Nonspecific psychologicaldistress and other dimensions of psychopathology: measures for use in the generalpopulation. Arch Gen Psychiatry. 1980;37:1229–1236.
  98. 98. A model ofdemoralization.Clarke DM, KissaneDW. Demoralization:its phenomenology andimportance. Aust N ZJ Psychiatry.2002;36:733–742.
  99. 99. Clarke DM, Kissane DW. Demoralization: its phenomenologyand importance. Aust N Z J Psychiatry. 2002;36:733–742.
  100. 100. Relationship between maternal demoralization, wheeze, and immunoglobulin E among inner-city children Reyes Ann Allergy Asthma Immunol 2011;107:42 Mean prenatal demoralization score on wheeze presentations within the first 5 years of a childs life. Women aged 18 to 35 years p<0.05 p<0.05 residing this inner-city In in New York City. cohort, prenatal Maternal demoralization demoralization was (ie, psychological distress). associated with transient and Questionnaire and total and indoor allergen wheeze. IgE persistent specific (at birth and ages 2, 3, and 5 years).
  101. 101. Parental Stress Increases the Detrimental Effect of Traffic Exposure on Children‘s Lung Function Islam AJRCCM 2012;184:822RationaleEmerging evidence indicates that psychosocial stress enhancesthe effect of traffic exposure on the development of asthma.ObjectivesWe hypothesized that psychosocial stress would also modify theeffect of traffic exposure on lung function deficits.
  102. 102. Parental Stress Increases the Detrimental Effect of Traffic Exposure on Children‘s Lung Function Islam AJRCCM 2012;184:822 Pollutant effects were significantly larger in1,399 participants in the the high-stress compared with Southern California lower-stress households Children‟s Health Study. (interaction P value = 0.007 andLung function testing 0.05 for residential and (mean age, 11.2 yr). school total oxides of nitrogen (Nox), respectively).Traffic-related air pollution and stress. No significant NOx effects were observed in children from low-stress households.
  103. 103. Parental Stress Increases the Detrimental Effect of Traffic Exposure on Children‘s Lung Function Islam AJRCCM 2012;184:822 Effect of traffic related pollution on lung function measurements, stratified by parental stress level (low or high)*Definition of abbreviations: CI = confidence interval; MMEF = FEF25–75; NO = nitric oxide; NO2 = nitrogen dioxide; NOx = total oxides ofnitrogen.* Models adjusted for log height and square term for log height, body mass index and square term for body mass index, sex, age, age–sexinteraction, race, Hispanic ethnicity, respiratory illness at time of lung function, field technician, and community. Percent (%) change wasscaled to 2 SD (NOx = 21.8 ppb; NO = 16.2 ppb; and NO2 = 7.3 ppb) of the TRP difference between home and school (averaged acrossschools).
  104. 104. Psychological Stress: A Social Pollutant That MayEnhance Environmental Risk Wright AJRCCM 2012;184:752Psychological factors influence the programming of neuroendocrine, autonomic, and immune inflammatory processes implicated in respiratory development.Psychological stress is conceptualized as a social pollutant that, when “breathed” into the body, disrupts biological systems overlapping with those altered by physical pollutants and toxicants (e.g., immune and nonimmune inflammatory processes).Under stress, physiological systems may operate at higher or lower levels than in normal homeostatic conditions.Disturbed regulation of stress systems (e.g., hypothalamic-pituitary- adrenal [HPA] axis, autonomic nervous system) may modulate immune function leading to increased airway inflammation, remodeling, and altered airway reactivity.
  105. 105. Resilience in low-socioeconomic-status children with asthma: adaptations to stress. Chen, JACI 2011;128:970Background:Low socioeconomic status (SES) is a strong predictor of manyhealth problems, including asthma impairment;however, little is understood about why some patients defy this trendby exhibiting good asthma control despite living in adverseenvironments.Objective:This study sought to test whether a psychological characteristic,the shift-and-persist strategy (dealing with stressors by reframingthem more positively while at the same time persisting in optimisticthoughts about the future), protects low-SES children with asthma.
  106. 106. Resilience in low-socioeconomic-status children with asthma: adaptations to stress. Chen, JACI 2011;128:970
  107. 107. Resilience in low-socioeconomic-status children with asthma: adaptations to stress. Chen, JACI 2011;128:970 121 children aged 9 to 18 yrs with asthma. 1) „„I thought about the Shift-and-persist scores. things I was learning The tendency to shift oneself from the situation or in response to stressors about something good was measured by using the that would come from it‟‟. Cognitive Restructuring scale of the Responses to Stress questionnaire. 2) „„I always feel good about Smith, J Consult Clin Psychol 2000;68:976. my future‟‟. Higher scores indicated a higher tendency to positively reappraise stressful situations.
  108. 108. Resilience in low-socioeconomic-status children with asthma: adaptations to stress. Chen, JACI 2011;128:970 121 children aged 9 to 18 yrs with asthma. Children who came from Shift-and-persist scores. low-SES backgrounds The tendency to shift oneself but who engaged in in response to stressors shift-and-persist strategies was measured by using the displayed less asthma Cognitive Restructuring scale inflammation at baseline of the Responses to Stress questionnaire. (p <0.05) Smith, J Consult Clin Psychol 2000;68:976. as well as less asthma impairment Higher scores indicated a higher (p <0.01) tendency to positively reappraise stressful situations. at the 6-mo period.
  109. 109. Resilience in low-socioeconomic-status children with asthma: adaptations to stress. Chen, JACI 2011;128:970 121 children aged 9 to 18 yrs with asthma. Children In Shift-and-persist scores. who came from contrast, low-SES backgrounds The tendency to shift oneself but who engaged in shift-and-persist in response to stressors shift-and-persist strategies strategies was measured by using the displayed less asthma Cognitive Restructuring scale were not beneficial of the Responses to Stress inflammation at baseline among high-SES questionnaire. (p <0.05) as well as children with Smith, J Consult Clin Psychol 2000;68:976. less asthma impairment asthma. Higher scores indicated a higher (p <0.01) tendency to positively reappraise stressful situations. at the 6-mo period.
  110. 110. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335Background:Pre- and postnatal stress have been related to allergy in children,but evidence from prospective studies is limited.Several environmental factors can influencethe salivary cortisol level, which is used as a measure of activityof the hypothalamic-pituitary-adrenal axis.Objective:The aim of this study was to assess the association betweensalivary cortisol levels at 6 months of age and allergic manifestationsduring the first 2 years of life.
  111. 111. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 Geometric mean of salivary cortisol (nmol/L) 15 – Salivary samples for cortisol level at 6 mo 11.7 on 3 occasions during 1 day. 10 – 203 children. Blood samples 5.1 05 – at 6, 12, and 24 mo 2.9 for specific IgE. 0 Morning Afternoon Evening
  112. 112. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 Geometric mean of Salivary cortisol levels salivary cortisol (nmol/L) on all sampling occasions 15 – were related Salivary samples to the prevalence of for cortisol level at 6 mo 11.7 on 3 occasions and eczema 10 – sensitization during 1 day. during the first 2 yrs of 203 children.life, with increasing levels Blood samples leading to 5.1 05 – of cortisol at 6, 12, and 24 mo of higher prevalence 2.9 for specific IgE. and sensitization eczema. 0 Morning Afternoon Evening
  113. 113. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds at different time points of the same day. Salivary samples for cortisol level at 6 mo on 3 occasions during 1 day. 203 children. Blood samples at 6, 12, and 24 mo for specific IgE.
  114. 114. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds at different time points of the same day. An association Salivary samples and between pre- for postnatal stress mo cortisol level at 6 on 3 occasions during 1 day. and subsequent development of 203 children. allergic diseases Blood samples has previously been at 6, 12, and 24 mo indicated … for specific IgE.
  115. 115. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds … furthermore, at different time points of the same day. Salivary samplesshown it has been for cortisol infants 6 mo that level at predisposed on 3 occasions during 1 day. to allergic disease 203 children. levels have higher of cortisol Blood samples prior 24 mo at 6, 12, and to the foronset ofIgE. specific disease.
  116. 116. Stressful life events and the onset of asthma Lietzén ERJ 2011;37:1360 HR for new asthma Prospective, onset population-based 2 – cohort study. 16.881 males and females, aged 20-54 yrs 1.96 and free of diagnosed 1 – asthma at the beginning of the follow-up (January 1, 2004). Stressful life events 0 gathered with a postal Exposure to stressful survey. life events
  117. 117. Stressful life events and the onset of asthma Lietzén ERJ 2011;37:1360 HR for new asthma Prospective, This association onset population-based was robust 2 – cohort study. to adjustment 16.881smoking and having for males and females, aged 20-54 yrs at home a cat/dog 1.96 and free of diagnosed and it was observed asthma at the beginning 1 – of the follow-up those both among (January 1,and without with 2004). allergic rhinitis Stressful life events at baseline. gathered with a postal 0 Exposure to stressful survey. life events
  118. 118. Stressful life events and the onset of asthma Lietzén ERJ 2011;37:1360 Of the 10 most HR for new asthma Prospective, life popula stressful events: onset tion-based cohort 2 – study. illness of a family • the member, 16.881 males and females, aged 20-54 yrs • marital problems, 1.96 and free of diagnosed divorce or separation 1 – asthma at the beginning and of the follow-up • (January 1, 2004).a supervisor conflicts with were associated Stressful life events with the onset gathered with a postal 0 Exposure to stressful survey. of asthma. life events
  119. 119. Asthma and viruses
  120. 120. Children With Asthma Hospitalized With Seasonal or Pandemic Influenza, 2003–2009 Dawood Pediatrics 2011;128:e27 % children hospitalized with 2003–2009 influenza influenza who had asthma seasons. 50 – 2009 pandemic. 40 – 44% Surveillance of 5.3 32% 30 – million children aged 17 yrs or younger. 20 – Hospitalization with 10 – laboratory-confirmed influenza and 0 identified those 2003–2009 2009 with asthma. influenza seasons pandemic
  121. 121. Children With Asthma Hospitalized With Seasonal or Pandemic Influenza, 2003–2009 Dawood Pediatrics 2011;128:e27 % children hospitalized with 2003–2009 influenza influenza who had asthma seasons. Compared with 50 – asthmatic children 2009 pandemic. with seasonal influenza, 40 – 44% Surveillance of 5.3a higher proportion with 32% 30 – million children aged 2009 pandemic H1N1 17 influenza required yrs or younger. 20 – intensive care Hospitalization with (16% vs 22%; 10 – laboratory-confirmed influenzaP=0.01) and 0 identified those 2003–2009 2009 with asthma. influenza seasons pandemic
  122. 122. Children With Asthma Hospitalized With Seasonal or Pandemic Influenza, 2003–2009 Dawood Pediatrics 2011;128:e27 % asthmatic children with 2003–2009 influenza diagnoses of asthma exacerbations seasons. 60 – 2009 pandemic. 50 – Surveillance of 5.3 40 – 51% million children aged 17 yrs or younger. 30 – Hospitalization with 20 – 29% laboratory-confirmed 10 – influenza and 0 identified those influenza A influenza B with asthma. (seasonal or pandemic)
  123. 123. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 % children with virus detection during asthma exacerbations 90 – 80 – 87.5% 128 children with acute 70 – asthma (age 2-16 yrs). 60 – 50 – Presentation to an 40 – emergency department. 30 – 20 – Respiratory viruses in a nasal aspirate. 10 – 14.8% 0 human other rhinovirus respiratory viruses
  124. 124. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 % children with human rhinovirus C (HRVC) 60 – 128 children with acute asthma (age 2-16 yrs). 50 – 40 – 59.4% Presentation to an 30 – emergency department. 20 – Respiratory viruses in a 10 – nasal aspirate. 0 associated with more severe asthma
  125. 125. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 % children with human rhinovirus C (HRVC) HRCV 60 – accounts for the majority 128 children with acute of asthma attacks asthma (age 2-16 yrs). in children presenting to 50 – 40 – 59.4% hospital and causes more Presentation to an 30 – severe attacks emergency department. 20 – than previously known Respiratory viruses in a HRV groups 10 – nasal aspirate. and other viruses. 0 associated with more severe asthma
  126. 126. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 Frequency of human rhinovirus (HRV) and other common respiratory viruses identified in 128 children with asthma exacerbation. 128 children with acute asthma (age 2-16 yrs). Presentation to an emergency department. Respiratory viruses in a nasal aspirate.
  127. 127. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 Relatioship between human rhinovirus (HRV) C infection and severity of asthma exacerbation in 128 children. p=0.016 128 children with acute p=0.018 p=0.009 asthma (age 2-16 yrs). Presentation to an emergency department. Respiratory viruses in a nasal aspirate.
  128. 128. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 Relatioship between human rhinovirus (HRV) C infection and severity of The finding that asthma exacerbation in 128 children. HRVCs are more p=0.016 pathogenic 128 children with acute p=0.018 p=0.009 than other HRVs asthma (age 2-16 yrs). in acute asthma Presentation to anwith is consistent emergency department. a recent study of children hospitalised Respiratory viruses in a with symptoms nasal aspirate. of a respiratory infection
  129. 129. Association between human rhinovirus C and severityof acute asthma in children Bizzintino ERJ 2011;37:1037 Relatioship between human rhinovirus (HRV) C infection and severity of asthma exacerbation in 128 children. …those infected with p=0.016 HRVC were more likely 128 children with acute p=0.018 p=0.009 asthma (agerequire to 2-16 yrs). supplemental oxygen Presentation to an than those infected emergency department. with HRVA. Respiratory viruses in a nasal Miller J Clin Virol aspirate. 2009;46:85
  130. 130. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation Denlinger AJRCCM 2012;184:1007 Rationale Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds. Objectives To evaluate viral strain and load in a prospective asthma cohort during a natural cold.
  131. 131. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation Denlinger AJRCCM 2012;184:1007 52 persons with asthma % subjects developed and 14 control. asthma exacerbation 50 – Adults enrolled at the first sign of a cold, with 40 – 48% daily monitoring of 30 – 25/52 symptoms, medication use, and peak expiratory 20 – flow. 10 – Serial nasal lavage and induced sputum samples. 0
  132. 132. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation Denlinger AJRCCM 2012;184:1007 52 persons with asthma and 14 control. Adults enrolled at the Detection of HRVs first sign of a cold, with in the preceding 5 days daily monitoring of was the most common symptoms, medication attributable exposure use, and peak expiratory flow. related to exacerbation. Serial nasal lavage and induced sputum samples.
  133. 133. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation Denlinger AJRCCM 2012;184:1007 52 persons with asthma and 14 control. Those by Adults enrolled group a minor at the Detection of HRVs first sign of a cold, with A HRV were in the preceding 5 days daily monitoring of was the most common 4.4-fold more symptoms, medication likely to cause attributable exposure use, and peak expiratory flow. exacerbation related to exacerbation. ( p=0.038 ). Serial nasal lavage and induced sputum samples.
  134. 134. Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation Denlinger AJRCCM 2012;184:1007 Rhinovirus and sputum neutrophil burden in acute samples stratified by the presence or absence of an exacerbation.

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