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Szefler SJ, J Allergy Clin Immunol 2007;120:1043

p= 0.03. What would be the prophylactic treatment in children with mild persistent asthma younger than 8 years old? Budesonide / Montelukast. Szefler SJ, J Allergy Clin Immunol 2007;120:1043. Budesonide= 500 m g/day, nebules n= 134 Montelukast= 4-5 mg /day,tbt. n= 146.

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Szefler SJ, J Allergy Clin Immunol 2007;120:1043

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  1. p= 0.03 What would be the prophylactic treatment in children with mild persistent asthma younger than 8 years old? Budesonide / Montelukast Szefler SJ, J Allergy Clin Immunol 2007;120:1043 Budesonide= 500 mg/day, nebules n= 134 Montelukast= 4-5 mg /day,tbt. n= 146 • The only difference between the groups : Number of acute attacs • Budesonide: 1.23 • Montelukast: 1.63

  2. Primary efficacy variable: time to first asthma medication RESULT :No significant difference in asthma control Szefler SJ, J Allergy Clin Immunol 2007;120:1043

  3. Which controller should be given to children with mild-moderate asthma PACT STUDY Sorkness CA, JACI 2007;119:64 • N= 285, 6-14 year • Mild-moderate asthma • FEV1: >%80 • PC20 <12.5 mg/ml • Duration: 48 Hafta • Sponsor: NIH 1. Fluticason 200 mcg/ day (n:86) 2. Fluticason-Salmeterol (n:81) 100-50- 50 mcg/day 3. Montelukast 5 mg/day (n:83)

  4. Asthma control days

  5. Time to first prednisolon requirement

  6. FEV1

  7. eNO

  8. Which controller should be given to children with mild-moderate persistent asthma ? RESULTS: Fluticasone monotherapy was superior in controlling asthma than montelukast and combination treatment. However, maximum asthma control days : %64.2 . Sorkness CA, JACI 2007;119:64

  9. % 2 1 0 -1 -2 -3 -4 NS nonsmoker smoker NS Montelukast p=0.009 p=0.03 NS Beclamethasone Does smoking affect the response to asthma treatment ? Lazarus S, 2007; 175:783 1. 44 control, 2. 39 light smokers: 10-40/g mild asthma: FEV1 %70-90, DLCO >%80 /BDP - HFA 2X160 mcg/day / M. 10 mg/day Duration: 8 weeks Change in sputum eosinophilia

  10. p= 0.53 p=0.16 15 10 5 0 p=0.0006 p= 0.77 p=0.0019 p=0.03 p=0.08 P=0.19 p=0.23 Beclamethasone Montelukast morning PEF RESULTS :CS resistance occurs in patients with asthma who smoke. Montelukast may be more effective in such patients. smoker nonsmoker p= 0.09 0.2 0.15 0.1 0.05 0 p=.0003 p= 0.26 Beclamethasone Montelukast FEV1

  11. FEV1 (L) 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 P=0.02 P=0.05 P=0.02 yaş 12 16 22 “Tucson Children’s Respiratory Study” PFT in 22 years of age Lancet 2007;378:758 Quartiles of infant VmaxFRC (n:169) High Medium Low-medium Low

  12. FEF 25-75 (L/s) 88 86 84 82 80 78 76 74 0 p<0.0002 p<0.0002 p<0.0001 12 16 22

  13. THE RELATION BETWEEN THE WHEEZING PHENOTYPES AND MATERNAL COMPLICATION AND PROCEDURES Ruskoni F, Am J Respir Crit Care Med 2007;175:16 • n= 15.609, 6-7 year • % 9.5 transient early wheezing • % 5.4 persistent wheezing • % 6.1 late onset wheezing • no relation with: • Amniocenthesis • Chorion villus biopsy • C/S • weight gain during pregnancy

  14. HT, Pre-eclampsy Transient early wheezing(OR: 1.40) Persistent wheezing (OR: 1.59) Late onset wheezing (OR: 1.40) Urinary tract infections treated with AB Transient early wheezing (OR: 1.52) AB use at delivery Transient early wheezing (OR: 1.21) Persistent wheezing (OR: 1.39) Maternal diabetes Persistent wheezing (OR: 1.72) Am J Respir Crit Care Med 2007;175:16

  15. Some complications during pregnancy and at delivery may increase the risk of developing different wheezing phenotypes in childhood.

  16. The influence of maternal respiratory infections during pregnancy on infant lung function Van Putte-Katier N, Ped Pulmonol 2007;42:945 Questionnaire data Infant PFT: <2 mo, n= 431 “Single occlusion technique” (natural sleep) Crs, Rrs Cross-sectional study P=0.08 20 15 10 5 Compliance (ml/kPa/kg) 0.0 1.0 >2 Number of maternal infection

  17. Yes No

  18. Maternal food consumption and asthma, respiratory and atopic symptoms in 5 year old children Willers SM, Thorax 2007;62:773 APPLE Ever wheeze = OR: 0.63 (%95CI 0.42-0.95) Ever asthma = OR: 0.54 (%95 CI 0.32-0.92) Dr. confirmed asthma = OR: 0.47 (%95 CI 0.27-0.82) FISH (>1/ week) Dr.confirmed AD= OR: 0.57 (%95 CI 0.35-0.92 • n: 1.924 birth cohort • Follow-up: 5 yıl, • Neonatal Lung function ? • Fresh fruits • vegetables • Furit juice • Fish • Milk

  19. 1.Breast feeding is recommended for all infants 2. A dietary regimen is effective for prevention of cow’s milk allergy and eczema. Evidence that such avoidance affects asthma and rhinitis is lacking. In case of lack of breast milk, hypoallergenic formulas for at least 4 months may be considered. 3.There is no evidence for preventive effect of dietary restrictions during pregnancy, lactation and after the age of 4-6 months. Ped Allergy Immunol 2008; 19:1-4

  20. Respiratory symptoms in the first 7 years of life and birth weight in term The PIAMA birth cohort (n= 3.628) Caudri D, AJRCCM 2007;175:1078 25 20 15 10 5 0 wheezing 1-3 / y wheezing >4 / y 249 200 521 % of children with wheeze 127 418 407 105 97 290 68 218 179 45 138 1 2 3 4 5 6 7 year

  21. Wheezing at least once LRTI

  22. Coughing at night Doctor’s diagnosis of current asthma

  23. LBW is an important risk factor for respiratory symptoms and wheezing in young children. No effect after the age of 6. This situation in young children is not the same as asthma in atopic older children

  24. No smoking during pregnancy, with ETS ex. %45 %25 Smoking during pregnancy and ETS exp. Birth weight: 2.500 3.5 4.5 4 No smoking during pregnancy, no ETS exposure Birth weight, Pre and postnatal ETS exposure Respiratory symtoms Fark %6

  25. No smoking during pregnancy, no ETS exposure Birth weight 2.500 3.5 4.5 Birth weight, Pre and postnatal ETS exposure Wheezing No smoking during pregnancy, with ETS ex. Smoking during pregnancy and ETS exp.

  26. LBW babies : The effect of birth weight was greater in children exposed to ETS (%12). In the presence of ETS exposure a child with a BW 2.500 g has an 45% change each year of having resp. symptoms between the ages of 1-5, compared with 25% in a child with a BW of 4500 g. AJRCCM 2007;175:1078

  27. < 6.300 kg 6.3 – 7.1 kg > 7.1 kg Birth Weight, Early Growth, Adult LFT Canay D, Thorax 2007; 62:396 n=5.390, Birth weight, / early growth / LFT at 31 years 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 FEV1 (L) at 31 years N= 2262 men <3.330 g 3.330 - 3.720 g >3.730 g

  28. Each 500 gram increment of birth weight resulted in a 53.1 ml increase in FEV1 and a 52.5 ml increment in FVC. Poor growth in early life may restrict normal lung growth and development

  29. Characteristics of men at 31 years (n= 2.684) <3.330 g 3.330 – 3.720 >3730 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 FEV1 (L) at 31 years Nonsmokers Smokers High level Low level <25 >25 Smoking Physical BMI activity (kg/m2)

  30. Babies with LBW and poor infant growth may be at a higher higher risk for developing impaired adult lung function

  31. Growth rate of lung function in healthy preterm infant Friedrich L, AJRCCM 2007;176:1269 600 500 400 300 200 FVC (mL) 2 mo 2 year / Gestational age: 32.7 (32-34) no RDS, healthy preterm (n= 24) and term babies (n= 24) /Rapid thoracic compression technique Test 1 : 2 month Test 2: 2 year control preterm

  32. Absence of catch-up growth in airway function in 2 years of age compared to term babies 1.0 0.9 0.8 0.7 0.6 450 400 350 300 250 200 150 FEV 0.5 FEV 0.5/FVC 2 mo 2 year 2 mo 2 year

  33. 1000 800 600 400 200 FEF25-75 (mL/s) 2 mo 2 year RESULTS: Lung growth at the first years of life is proportional to somatic growth 1000 800 600 400 200 FEF 50 (mL/s) 2 mo 2 year

  34. Oral tolerance induction in children with very severe cow’s milk-induced reactions Longo G, JACI 2008; 121:343 Diagnosis of cow’s milk allergy: DBPC provocation test > 5 years n=60, Grup A (n= 30) oral tolerance induction Grup B (n=30) milk free diet

  35. Longo G, JACI 2008; 121:343

  36. Milk specific IgE Levels GROUP B GROUP A

  37. Group-A: Oral Tolerance Induction The results of DBPC : Failure %10 Partial tolerance (5 -150 ml/day) %54 Complete remission % 23 Maximum tolerance (150 ml/day) %13

  38. Group-B: Milk free diet The results of DBPC : %100 P<0.001

  39. Preschool-age children with wheezers “remodelling” & eosinophilic inflammation When do the pathologic features begin ? Saglani S, AJRCCM 2007;176:858 p<0.05 4 3 2 1 0 Age: 3 mo - 5 year n=16, mean: 29 mo, video n= 14, ort.17 mo, reported n=10 control, ort. 19 mo EG2+ volume density (%) Video reported control

  40. When do the pathologic features begin ? RBM (mm) RBM (mm) P<0.01 p<0.05 12.5 10.0 7.5 5.0 2.5 0.0 p<0.001 7 6 5 4 3 2 1 0 p=<0.05 Video reported control Video control difficult asthma

  41. Result: The characteristic pathologic findings start between 1-3 years old. Can the natural history be changed ? Eosinophilic inflammation BM WHEEZING CONTROL BM Saglani S, AJRCCM 2007;176:858

  42. Airway smooth muscle mass : Asthma, Cystic fibrosis, BE Regamey R, AJRCCM 2008; 177:837 0.001 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Age: 11.3 (8.5-13.8) year 0.01 0.01 Increased airway smooth muscle mass (both number and size) occurs in children with chronic inflammatory lung disease Vv(sm/subepitelial) Bronchial thermoplasty ? Asthma CF BE Control (24) (27) (16) (11)

  43. Basal Membrane: Cystic fibrosis, Ciliary Dyskinesia, Chr. Rec. Resp. Symp. Hilliard TN, Thorax 2007; 62: 1074 166 ** RBM (mm) 10 8 6 4 2 CF: 43 (0.3-16.8 year) CD : 7 Chr. Resp.Symp: 26 Control: 7 BM thickness is correlated with BAL TGFb level CF CD Chr. Resp.S Control

  44. Multiple-breath inert gas washout & spirometer: Which method is more sensitive in diagnosis of early structural changes in lung ? Gustavsson PM, Thorax 2008; 63: 129 45 CF, 5-19 (mean 12) year %48 homozygote, %43 heterozygote dF508 Spirometer, MBW (mean Lung Clerance Index (LCI), HRCT Parameters Sensitivity Specifity LCI ............................. % 85-94 ...................... % 43-65 FEV1............................ % 19-26 ...................... %89-100 FEF75........................... % 62-75 ...................... % 75-88

  45. Compared to HRCT : LCI = + 0.85 FEV1 = - 0.62 FEF75 = - 0.66 • LCI is more sensitive than FEV1 and FEF25-75 in CF • LCI is superior to HRCT in monitorization.

  46. OSA: Adenotonsillectomy results Otolaryngol Head Nec Surgery 2007;137:43 3-18 year Mild OSA %10 Adenotonsillectomy Obese OSA Moderate OSA %20 (n=33) Severe OSA %70 Mild OSA %5 Normal OSA Adenotonsillectomy moderate OSA %36 (n=39) severe OSA %70

  47. AHI: 23.4 (3.7-135.1) P<0.001 AHI: 17.1 (3.9-36.5) OSA: Adenotonsillectomy results Otolaryngol Head Nec Surgery 2007;137:43 Hafif OSA %10 Adenotonsillectomy Obese OSA Orta OSA %20 (n=33) Ağır OSA %70 Hafif OSA %5 Normal OSA Adenotonsillectomy Orta OSA %36 (n=39) Ağır OSA %70

  48. No OSA %24 mild OSA % 46 Moderate OSA %15 severe OSA %15 OSA: Adenotonsillectomy results Otolaryngol Head Nec Surgery 2007;137:43 mild OSA %10 Adenotonsillectomy Obese OSA moderate OSA %20 (n=33) severe OSA %70 No OSA %72 Mild OSA %5 Adenotonsillectomy Normal OSA mild OSA %18 Moderate OSA %36 moderate OSA %10 (n=39) severe OSA %70 severe OSA % 0

  49. AHI: 23.4 (3.7-135.1) OSA yok %24 Hafif OSA % 46 AHI: 3.1 (0-33.1) Orta OSA %15 Ağır OSA %15 P<0.001 P<0.01 AHI: 17.1 (3.9-36.5) OSA: Adenotonsillektomy results Otolaryngol Head Nec Surgery 2007;137:43 Hafif OSA %10 Adenotonsillectomy Obese OSA Orta OSA %20 (n=33) Ağır OSA %70 OSA yok %72 Hafif OSA %5 Adenotonsillectomy Normal OSA AHI: 1.9 (0.1-7.0) Hafif OSA %18 AHI: 1.9 (0.1-7.0) Orta OSA %36 Orta OSA %10 (n=39) Ağır OSA %70 Ağır OSA % 0

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