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Childhood Asthma with an emphasis on disease misclassification and synthetic bedding.

Childhood Asthma with an emphasis on disease misclassification and synthetic bedding. Anne-Louise Ponsonby 1,2 Terence Dwyer 2 Jennifer Cochrane 2 Andrew Kemp 3 David Couper 4 Allan Carmichael 5. February 2003.

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Childhood Asthma with an emphasis on disease misclassification and synthetic bedding.

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  1. Childhood Asthma with an emphasis on disease misclassification and synthetic bedding. Anne-Louise Ponsonby1,2 Terence Dwyer 2 Jennifer Cochrane 2 Andrew Kemp 3 David Couper 4 Allan Carmichael 5 February 2003

  2. The dominant past clinical model for child asthma is that of a largely allergic (atopic) aetiology However, a systematic review of population based studies found mean population attributable risk for asthma due to atopy was only 38%. Pearce et al Thorax 2000

  3. Disease misclassification has been a large problem in asthma epidemiology Airway Obstruction viral- Allergen- induced induced HDM - allergen induced irritant-induce d other causes small airway- induced obstrution

  4. Misclassification can occur between: -Asthma and other respiratory diseases - Different types of asthma within the asthma spectrum - Different types of allergy within atopy (allergy)

  5. Within the spectrum of child asthma, the subgroup of children with severe disease are more likely to have asthma that is attributable to atopy With Respira tory Symptoms No. OR (95% CI) for Respiratory Symptoms Without Respiratory Symptoms, No. Respiratory Symptoms Population Attributable Fraction With Atopy, % With Atopy, % 1–3 episodes of wheeze in past 12 mo compared to no wheeze episodes 3.27 (2.15–4.97) 49% 38 66 526 119 4–12 episodes of wheeze in past 12 mo compared to no wheeze episodes 3.44 (1.75–6.75) 40 68 38 526 49% > 12 episodes ofwheeze in past 12 mo compared to no wheeze episodes 8.70 (3.07–24.55) 38 75% 25 84 526 Ponsonby et al Chest 2002

  6. In large studies focusing on allergic airway disease, an improved signal-to-noise ratio will be obtained by focusing on symptoms that indicate severe or persistent disease

  7. Atopic Disease Subgroups also occur within the broad group of ‘atopic’ or allergic children because different children are allergic to difference substances

  8. Again, this issue is important to consider in aetiological studies because the causal factors involved in different allergen-specific atopy may differ.

  9. House dust mite Ryegrass 29 34 44 9 Other 6 (Non-atopic n= 292) House dust mite Ryegrass 69 29 34 34 44 15 9 34 6 Other - specific (n=84) HDM Ryegrass specific (n=43) - Ponsonby et al PAI 2003 (in press)

  10. 69 29 44 15 9 34 Unadjusted OR for HDM-specific sensitisation Adjusted OR for HDM-specific sensitisation ( trend,p=0.80) Unadjusted OR for ryegrass-specific sensitisation Adjusted OR for ryegrass-specific sensitisation (trend,p=0.0001) Note, the difference in family size effect is significant, p=0.02 Ponsonby et al PAI 2003 (in press)

  11. Bedding analysis Aim To examine the role of infant upper bedding composition in the development of house dust mite allergen induced airway disease

  12. Justification for main selected outcome measures • Frequent wheeze (more than 12 wheeze episodes in the past 12 months – this outcome is strongly linked to HDM atopy (RR=19.6 (6.94, 55.56)). • Night wheeze – temporally related to exposure of interest (bedding). • Asthma – not used - only weakly associated with HDM atopy (RR = 1.65 (1.30-2.09)). Ponsonby et al J Clin Epi 2002

  13. The 1995 Tasmanian Asthma Survey Full 1995 cross-sectional sample N = 6,378 (92% of eligible) with parental questionnaires Methods The 1988 to 1995 Tasmanian Infant Health Survey (TIHS) 1988N = 1,111 (81% of eligible) infants participated in home interview and survived the first year. 1995 Follow-up sample N = 863*(78%), TIHS children born in 1988 with 1988 home interview Data, plus 1995 asthma data avail ble and parental consent for record linkage. Ponsonby et al Epidemiology 2003

  14. Is the report of wheeze and wheeze frequency valid? • Previous validation work has shown the report of wheeze over the past 12 months has a sensitivity of 0.81 and a specificity of 0.78 for the physician diagnosis of asthma in childhood. • Increasing wheeze frequency is associated with increasing deficits in child lung function. Jenkins et al, Int J Epidemiol 1996; Ponsonby et al, Chest 2002

  15. Statistical Methods • A generalized linear model with a log link function and binomial error structure was used. • Age at onset – discrete proportional hazard modelling. Armitage P, Berry G. Statistical Methods in Medical Research, 1994

  16. Statistical Methods cont. Etiologic fraction of wheeze attributable to synthetic bedding [P (aRR-1)/aRR] = 16% of moderate wheeze attributable* to synthetic bedding = 79% for frequent wheeze attributable* to synthetic bedding *Statistically attributable, causality not yet fully proven. Ponsonby et al Epidemiology 2003

  17. Respiratory symptom at age seven Infant synthetic pillow use and respiratory symptom Infant synthetic pillow use and subsequent child asthma symptoms at age seven, 1995 follow-up sample N 599 81 14 1.0 1.0 190 31 16 1.2 (0.9-1.6) 1.1 (0.8-1.5) 671 85 13 1.0 1.0 157 34 22 1.6 (1.2-2.3) 1.5 (1.1- 2.1) Infant synthetic pillow use and respiratory symptom* Infant synthetic pillow use N  N % ARR 95%CI RR 95%CI No wheeze in past year + Moderate wheeze (1-12 episodes in past year) Frequent wheeze (More than 12 episodes in past year) 28 2.8 (1.3-6.1) 9 32 2.5 (1.2-5.5) No night wheeze + Night wheeze Ponsonby et al Epidemiology 2003

  18. Child wheeze frequency over the past 12 months by current use of synthetic bedding , full 1995 cross-sectional sample Distribution of children by number of wheeze episodes (%) Bedding N Frequent wheeze * (more than 12 Episodes vs. none)  0 1-12 More than 12 ARR (95%CI) Neither pillow nor quilt synthetic + 450 82 18 0.6 1.00 Only pillow synthetic (1.5, 25) 3091 80 19 2.0 6.03 Only quilt synthetic 148 76 21 2.7 4.4 (1.1, 18) Both pillow and quilt synthetic 2373 73 24 2.7 6.4 (1.2, 35) Ponsonby et al Epidemiology 2003

  19. An investigation of non-causal explanations for the synthetic-bedding wheeze association • Not due to parent’s introduction of synthetic bedding as part of an allergen reduction strategy (synthetic bedding not associated with markers of active allergen avoidance, e.g. allergen-occlusive mattress covers) • No evidence parents of children with an-at-birth family history of asthma were selecting synthetic bedding. (Even among children with no family history of asthma, the consistent use of a synthetic pillow in early life was associated with night wheeze (aRR=3.2 (1.0-10.1) • No evidence that synthetic bedding was linked to under-management of wheeze. (Among children with asthma, synthetic bedding ®­ asthma medication use). Ponsonby et al Epidemiology 2003

  20. Features indicative of a causal relationship • High strength of association • Dose-response patterns • Temporality • prospective association evident • earlier use of bedding ® earlier disease onset • Ecological coherence • Between 1978 and 1991, declining use of feather pillows could account for 20% of increase in current wheeze overtime Butland Thorax 1997 • Consistency • Many cross-sectional studies. These results are consistent with one other birth co hort (feather bedding protective) Nafstad CEA 2002

  21. Causal Features • Biological plausibility • The adverse effect of synthetic bedding is more evident among atopic than non-atopic children, thus atopic mechanisms may be involved. The adverse effect of non-feather bedding is particularly evident among HDM allergic children (see next slide). • HDM and other allergens are much higher in synthetic than feather bedding • Direct allergen loading near the face • Volatile organic compounds • Lack of protective endotoxin products

  22. A cross-sectional assessment of the combined effect of HDM sensitization and feather quilt use on severe asthma symptoms and lung function Adjusteda rate ratio (95% CI) for severe symptoms over the past year HDM Sensitization P value P Value Feather quilt use Lung function FEV1/FVC ratio change (%) (95% CI)b 0.00 (reference) 1.00 (reference) C - Ö - C C 1.45 (0.45-4.65) 0.54 -0.37 (-1.80 to 1.06) 0.61 1.79 (0.97-3.27) 0.06 -0.31 (-1.33 to 0.71) Ö Ö 0.54 -0.68 (-1.24 to 0.13) 6.38 (2.51-16.23) Ö C 0.02 0.0001 Ponsonby et al J Clin Epi 2002

  23. Causal Features cont. • Experimental data from randomised controlled trials are not yet available. • An RCT on this issue is underway in Australia.

  24. Conclusions • Careful consideration of disease misclassification within the spectrum of asthma is required for all studies investigating the aetiology of asthma. • Synthetic bedding is prospectively associated with the subgroup of asthma that represents house dust mite related airway disease.

  25. Conclusions cont… • Observational studies have demonstrated several causal features with regard to the synthetic bedding-frequent child wheeze association. • Randomised trials are required, however, to fully exclude selection bias with regard to family choice of child bedding.

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