Canadian Asthma Primary Prevention Study (CAPPS)

Chris Carlsten, MD MPHUniversity 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 CIHRBC Lung AssociationManitoba Medical Service Fund

Establishment of cohort

Chris Carlsten, MD MPHUniversity 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

Establishment of cohort

Chris Carlsten, MD MPHUniversity 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 MPHUniversity of British Columbia

Chan-Yeung Arch Ped 2000

Exposures and related analytes(http://genapha.icapture.ubc.ca)

Chris Carlsten, MD MPHUniversity of British Columbia

Outcomes

Chris Carlsten, MD MPHUniversity 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

‘Strengths’

Chris Carlsten, MD MPHUniversity 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

‘Weaknesses’

Chris Carlsten, MD MPHUniversity 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

Selected publications

Chris Carlsten, MD MPHUniversity 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