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What are the Determining Factors in Disease Continuing from Childhood to Adulthood?

What are the Determining Factors in Disease Continuing from Childhood to Adulthood?. Andrew Bush MD FRCP FRCPCH Imperial School of Medicine & Royal Brompton Hospital. Email: a.bush@rbht.nhs.uk. Importance of Early Life Events. Aspects of Lung Growth Important Diseases Wheezing Syndromes

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What are the Determining Factors in Disease Continuing from Childhood to Adulthood?

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  1. What are the Determining Factors in Disease Continuing from Childhood to Adulthood? Andrew Bush MD FRCP FRCPCH Imperial School of Medicine & Royal Brompton Hospital Email: a.bush@rbht.nhs.uk

  2. Importance of Early Life Events • Aspects of Lung Growth • Important Diseases • Wheezing Syndromes • Cystic Fibrosis • Chronic Lung Disease of Prematurity • Summary and Conclusions

  3. An adult view of childhood events Beam me down Scotty

  4. Normal Lung Development 1. The bronchial tree is developed by 16/40 • And even beyond to bronchioles 2. Alveoli largely develop after birth • But only for a very short time 3. Preacinar vessels follow airway development, intra-acinar those of alveoli • Acinus = 3 generations respiratory bronchioles (no cartilage), alveolar ducts & sacs

  5. Postnatal Alveolar Development • Alveolar numbers at birth: variously n = 0 - 5 X 106 • Completion of alveolarization variously age 2 - 20 years • Probable rapid phase in first 6 months, slow phase ending by two years

  6. Importance of Early Life Events • Aspects of Lung Growth • Important Diseases • Wheezing Syndromes • Cystic Fibrosis • Chronic Lung Disease of Prematurity • Summary and Conclusions

  7. Transient wheeze Non-atopic (viral induced) wheeze Atopic wheeze Stein RT et al Thorax 1997;52:946-52 Martinez FD Pediatrics 2002;109:362-7 Infant Wheezing Phenotypes ? ??

  8. The Tucson Study

  9. Evolution of lung function in Infant Wheezing Phenotypes

  10. Transient Wheezers (VAW, VIW) • Have abnormal lung function soon after birth • Have abnormal lung function before the 1st wheezing episode • Do not have AHR • Do not have eosinophilic inflammation • Do not respond to prophylactic inhaled steroids

  11. Virus Associated Wheeze and BAL Cytology • Blind non-FOB • BAL • Children • anaesthetised • for routine • surgery • No evidence • of airway • eosinophilia • in VAW Clin Exp Allergy 1997; 27: 1027-1035

  12. Further evolution of Lung Function

  13. Dunedin Multidisciplinary Health Study Sears, NEJM 2003

  14. Lung function Changes over time:ICS therapy rarely used!

  15. VAW – Lifelong Problem? • FU of 1964 cohort • 177 subjects, age 45-50 years • Adjust for age, height, gender, smoking, socio-economic status Chest 2003; 124: 18-24 P<0.05 P=NS Asth

  16. VAW – Lifelong Problem? • Rate of decline of FEV1 over 2 years Conclusion • VAW decline faster than normal, having attained normal lung function in adult life Chest 2003; 124: 18-24 P<0.05 P=NS Asth

  17. LCCF Studies • Five London CF centres • RBH, GOSH, Kings, Lewisham, Royal London • Infant and Preschool Lung Function Tests, Institute of Child Health • Prof J Stocks, Drs Per Gustafsson, Ranganathan, Aurora, Ljungberg • 47 CF infants, 187 controls

  18. Raised volume forced expiratory manoeuvres

  19. Full and partial flow-volume curves Raised volume F-V curve Flow (mL.s-1) Partial F-V curve V’maxFRC Volume (mL)

  20. FEV0.4 vs length in healthy infants and infants with CF: repeated measures ) mL ( 0.4 FEV Healthy CF Length (cm)

  21. LCCF Infant Studies: Conclusions • Airway obstruction at diagnosis even in those with no apparent respiratory illness • No ‘catch-up’ growth over next 6 months despite treatment Lancet 2001; 358: 1964-5; BlueJ 2002; 166: 1350-7; BlueJ (in press)

  22. BlueJ 2004; 169: 1209-16

  23. Adult Physicians 50 yr old man, 40 pack year history. Diagnosis?

  24. HRCT in adolescent survivor of preterm birth

  25. PFTs in “resolving” CLD • Patients 33 preterms, 24-31/40, BW 589-1891 gms • MethodsStudied at 43 weeks post-conception, then three monthly for one year; Vmax.FRC, mean SaO2 and SaO2 variability Arch Dis Child 1997; 76: F113-F117

  26. Change in Lung Function in the First Year of Life There is no evidence of catch up growth

  27. Lung Function in LBW aet 7 Yrs • Patients 130 children BW < 2 kg; 120 unselected schoolchildren • Methods All neonatal data saved; Flow volume loops (FEV0.75 not FEV1) • Statistical analysis Four groups: no illness, oxygen only, IPPV, oxygen dependant Arch Dis Child 1989; 64: 1284-93

  28. Lung Function age 7-9 years: effect of birth weight Arch Dis Child 1989; 64: 1284-93

  29. Lung Function in LBW aet 7 Yrs • Conclusions 1. Children with chronic lung disease had impaired lung function age 7-9 years 2. Low birth weight, maternal smoking and male sex had an adverse effect in the more mildly affected children Arch Dis Child 1989; 64: 1284-93

  30. Lung function at age 20-22 years

  31. Birth Weight in SGA, not AGA babies determines Lung function in adulthood, r2 = 0.44, p<0.001

  32. Control AGA SGA Exercise data at age 20-22 yearrs

  33. Importance of Early Life Events • Aspects of Lung Growth • Important Diseases • Wheezing Syndromes • Cystic Fibrosis • Chronic Lung Disease of Prematurity • Summary and Conclusions

  34. Overall Conclusions • Intrauterine Factors are Vital • Especially SGA, smoking, maternal atopy, maternal hypertension • The first three years of life are Pivotal • Offers a window for intervention • We need to find ethical ways of researching these difficult questions

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