1. Canadian Asthma Primary Prevention Study (CAPPS) Chris Carlsten, MD MPH University of British Columbia Chris Carlsten University of British Columbia Genesis of Asthma and Allergy Workshop, Mar-1-09

2. Initiating PIs (early 1990’s) Allan Becker Moira Chan-Yeung Funding CIHR BC Lung Association Manitoba Medical Service Fund

3. Establishment of cohort Chris Carlsten, MD MPH University of British Columbia mothers of high-risk infants (n = 545) from Vancouver and Winnipeg were recruited during the third trimester of pregnancy high-risk was defined as having at least one first-degree relative with asthma or two first-degree relatives with IgE-mediated allergic disease families were randomized to the control (usual care) or intervention group avoidance of HDM, pet allergen, and ETS breast-feeding encouraged formula supplementation if necessary introduction of solid foods delayed

4. Establishment of cohort Chris Carlsten, MD MPH University of British Columbia Chan-Yeung Arch Ped 2000 Note: 380 (70%) returned for assessment at 7 years of age

5. Establishment of cohort Chris Carlsten, MD MPH University of British Columbia Chan-Yeung Arch Ped 2000

6. Exposures and related analytes (http://genapha.icapture.ubc.ca) Chris Carlsten, MD MPH University of British Columbia

7. Outcomes Chris Carlsten, MD MPH University of British Columbia A pediatric allergist-based diagnosis of asthma and rhinitis Questionnaire-based symptoms and medication use IgE in blood Atopy (skin prick positive to ≥1 of 13 antigen panel) URI (by report) Methacholine challenge PC20* * Another attractive discussion point; PC20≤2 best AUC for sensitivity and specificity relative to MD diagnosis; preliminary data from Helen Ward, PhD

8. ‘Strengths’ Chris Carlsten, MD MPH University of British Columbia high-risk cohort (enhanced for outcomes of interest) detailed phenotyping (including PC20) detailed early life exposure (including cord blood) LUR 7 year follow-up, with recent new funding for 14 years

9. ‘Weaknesses’ Chris Carlsten, MD MPH University of British Columbia High risk design limits generalizability Randomized intervention within study complicates the analysis of gene-environment interactions* Modest N * a great topic for discussion in this meeting

10. Selected publications Chris Carlsten, MD MPH University of British Columbia Becker A, Manfreda J, … Chan-Yeung M. Environmental tobacco smoke exposure and breast feeding. Archives Pediatr Adoles Med 1999;153:689-691 Chan-Yeung M, … Becker A. Umbilical cord blood mononuclear cell proliferative response … does not predict the development … rhinitis and asthma. JACI ‘99 Kaan A, … Chan-Yeung M. Cord blood IgE: … development of asthma and other allergic disorders at 12 months. Ann Allergy, Asthma and Immunol 2000;84:37-42. Zhu S, … Sandford A. Polymorphisms of IL-4, TNF-alpha, and FceRIb genes and the risk of allergic disorders in at-risk infants. AJRCCM 2000;161:1658-9. Chan-Yeung M, … Becker A. A randomized clinical trial … the primary prevention of asthma in high risk infants. Arch Pediatr Adolescent Med 2000; 154: 657-663. Hegele RG, … Chan-Yeung M. The association between respiratory viruses and symptoms in 2-week-old infants... J Pediatrics 2001; 138: 831-7. Chan-Yeung M, … Becker A. Effectiveness … in reducing allergen levels in a primary prevention of asthma study. Annals of AAI; 2002; 88:52-58. He J-Q, … Sandford AJ. Genetic variants of the IL13 and IL4 genes and atopic diseases in at-risk children. Genes and Immunity (2003) 4, 385–389 Becker A, … Chan-Yeung M. The Canadian Primary Prevention of Asthma study- outcomes at 2 years of age. J Allergy Clin Immunol 2004; 113:650-656. Chan-Yeung M, … Becker A. The Canadian Primary Prevention of Asthma in Childhood- outcomes at 7 years. JACI 2005; 116: 49-55 Chan-Yeung M, Becker A. Primary prevention of asthma and allergies in childhood. Cur Opinion Allergy Clin Immunol 2006;6:146-51 Lee KK, … Chan-Yeung M. Exposure to respiratory viruses and onset of asthma and atopy … outcome at 2 –years of age. Pediatrics Pulmonol 2007; 42:290-7 Begin P, … Laprise C. Association of urokinase-type plasminogen activator with asthma and atopy. Am J Respir Crit Care Med 2007;175:1109-16 Chan-Yeung M, … Becker A. Early life factors for bronchial hyperrepsonsiveness at age 7 in a high risk cohort. Am J Respir Crit Care Med 2007;175 A270 Chan-Yeung M, … Becker A. Atopy in early life and impact of a primary prevention program for asthma in a high risk cohort. J Allergy Clin Immunol 2007 Ferguson A, … Chan-Yeung M. Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 years in a high risk cohort. PAI 2009