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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. Initiating PIs (early 1990’s). Allan Becker Moira Chan-Yeung Funding CIHR
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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
Initiating PIs (early 1990’s) Allan Becker Moira Chan-Yeung Funding CIHR BC Lung Association Manitoba Medical Service Fund
Establishment of cohort • 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 Chris Carlsten, MD MPH University of British Columbia
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
Establishment of cohort Chris Carlsten, MD MPH University of British Columbia Chan-Yeung Arch Ped 2000
Exposures and related analytes(http://genapha.icapture.ubc.ca) 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 Outcomes Chris Carlsten, MD MPH University of British Columbia
‘Strengths’ • 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 Chris Carlsten, MD MPH University of British Columbia
‘Weaknesses’ • 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 Chris Carlsten, MD MPH University of British Columbia
Selected publications 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 Chris Carlsten, MD MPH University of British Columbia