1 / 18

Early Life Exposures as “Causes” of Asthma/Atopic Phenotypes: Key Questions

Early Life Exposures as “Causes” of Asthma/Atopic Phenotypes: Key Questions. Anita L Kozyrskyj, PhD, Research Chair & Associate Professor Dept Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada The Genesis of Allergy and Asthma Workshop

abba
Download Presentation

Early Life Exposures as “Causes” of Asthma/Atopic Phenotypes: Key Questions

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Early Life Exposures as “Causes” of Asthma/Atopic Phenotypes: Key Questions Anita L Kozyrskyj, PhD, Research Chair & Associate Professor Dept Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada The Genesis of Allergy and Asthma Workshop Vancouver, March 2009 N % Body Weight Normal Weight 395 71.2 Overweight 160 28.8 Physician Diagnosis No Asthma 357 64.4 Asthma 198 35.6 Total = 555

  2. Objectives • List key questions/issues • Identify opportunities for investigation

  3. Key Questions/Issues in Early Life Exposure Measurement Timing of exposure • Is there a critical window: early pregnancy, late pregnancy, first year of life, first 3 years? Persistence of exposure • All or nothing phenomenon during a critical time period or first exposure followed by continued exposure? Accumulation of exposure • One key exposure or a combination of exposures? • Is there an additive risk in high risk children? Validity of exposure measurement • Are we measuring what we think we are (and does it matter)?

  4. Social and Economic Policies Institutions Neighborhoods/Communities `` Living Conditions `` Social Relationships Lifecourse Nutrition/care Genetic Factors Environment Child at birth

  5. SAGE: Maternal distress measure • postpartum time period only • one and 1-5 years (short-term) • persistent over 1-7 years of child’s life • late onset (after postpartum period) Continued exposure to maternal distress in early life is associated with an increased risk of childhood asthma. Kozyrskyj AL, Mai XM, McGrath P, HayGlass KT, Becker AB, MacNeil B. Am J Respir Crit Care Med 2008; 177:142-7.

  6. Risk of asthma following adjustment for additional confounding factors Child sex, maternal asthma, urban/rural, health care visits, number siblings, lower respiratory and non-respiratory tract infections, antibiotic use in 1st yr

  7. Maternal Distress: Phenomena in the 1st year of life or persistent exposure

  8. The Complexity of the Association between Socioeconomic Status and the Development of Childhood Asthma“as revealed by trajectory analyses” Kozyrskyj AL, Kendall GE, Jacoby P, Sly PD, Zubrick SR. Am J Pub Health 2009 in press

  9. Family Income Trajectories • Rather than pre-determined categories, maximum-likelihood longitudinal (latent class) modeling techniques classified children on the basis of their family’s movements in and out of low income over the child’s lifetime (timing, duration, sequence of family low income) • SAS ‘PROC TRAJ’ program was used to create family income trajectories from birth until child age 6 or 14 years. PROC TRAJ uses Bayes’s theorem to assign children to the income trajectory group for which they had the highest probability of belonging.

  10. The Complexity of the Association between Socioeconomic Status and the Development of Childhood Asthma“as revealed by trajectory analyses” Kozyrskyj AL, Kendall GE, Jacoby P, Sly PD, Zubrick SR. Am J Pub Health 2009 in press

  11. Odds ratio for asthma subsequent to chronic low income vs not, by age

  12. Are the results biologically plausible? Stress hypothesis • Pregnancy, early life stress and chronic family stress were independently associated with asthma at age 6 and diminished the SES association with asthma • Caregiver stress in early life has been associated with increased levels of pro-inflammatory cytokines in asthma. Infants (esp male) born into low income households are more likely to have an atopic profile at birth. • By age 14, chronic life stress was associated with a two-fold increase in asthma. • Children with asthma who experience both acute and chronic stress show a reduction in the expression of the glucocorticoid receptor, which can increase the airway inflammatory response to allergens.

  13. Are the results biologically plausible? Hygiene hypothesis • Children born to single-parents live in a SES environment that protects against asthma development. Single-parents made up 44% of households that “moved out of poverty.” Single-parent status diminished the inverse association between increasing income and asthma. When the increasing income trajectory was compared to chronic low income, asthma risk ↓’d by more than 60%. • Chen et al reported that asthma likelihood was lower in children whose families had moved up in income, than in children who continued to live in a low income family. Children living in increasing income families may experience higher rates of exposure to endotoxin and infections during early infancy, which may protect against asthma development. These exposures continue in chronic low income families and increase risk of asthma, as Celedon et al have found.

  14. SAGE: Absence of additive risk? Increased risk of childhood asthma from antibiotic use in early life. Kozyrskyj AL, Ernst P, Becker AB. Chest 2007: 131: 1-7.

  15. Key Questions/Issues in Early Life Exposure Assessment Indoor environment • Is endotoxin exposure in later life a valid exposure for early life? • What are the important questions to ask: living on a farm or exposure to farm animals? • How do you disentangle reverse causation for antibiotic use? Psychosocial environment • What is it about socioeconomic status that is associated with asthma? • What types of exposures are important, ie. depression vs anxiety? • How do you disentangle reverse causation for exposure maternal distress (“living” exposure which can change in response to the child)? Outdoor environment • Why measure outdoor environmental exposures when the infant/toddler spends most of her/his time indoors? • Do exposures during pregnancy matter and how can they be measured?

  16. Key Questions/Issues in Early Life Exposure Assessment Indoor environment Psychosocial environment

  17. Key Questions/Issues in Gene-Environment Interactions Indoor environment Psychosocial environment

More Related