1 / 20

Cluster Phenotypes - Background

This study investigates the complexity of asthma phenotypes by utilizing cluster analysis on data from the Busselton Health Survey (2005-2007), involving 1,970 adults. We aim to uncover distinct asthma subtypes, such as eosinophilic and neutrophilic, and intermediate phenotypes related to IgE and airway hyper-responsiveness. By examining how genetic variations correlate with these clusters, the research seeks to identify novel pathways and optimize treatment strategies for asthma management. We also consider the influence of environmental exposures and questionnaire data on phenotype classification.

zalika
Télécharger la présentation

Cluster Phenotypes - Background

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. Cluster Phenotypes - Background • Phenotypes such as “asthma” are difficult to define, variable over time and/or are subject to recall bias and are “syndromic”. • Subtypes of asthma are known to exist - • Eosinophilic, neutrophilic, paucigranulocytic, atopic, occupational. • There are intermediate phenotypes – • IgE, atopy, AHR, FEV1, eNO • Phenotypes do not “capture” “asthma” • Ho: Clusters will capture phenotypes that more strongly associate with genetic variation than “asthma”

  2. Cluster Phenotypes • Cluster Analysis (SAS) • Busselton Health Survey 2005-7 • All adults with: • Age, Sex, FEV1, FVC, eNO, eosinophil count, BMI, airway hyper-responsiveness (AHR), atopy (skin tests) • n = 1,970 • 7 clusters (each with n > 100)

  3. Cluster Phenotypes

  4. Cluster Phenotypes

  5. Cluster Phenotypes - Questions • How many clusters? • ? Sub-clusters • What other variables to collect? • Include exposure? • Include questionnaire data? • Include treatment? • Do clusters suggest pathways? • Best gene association strategy • GWAS, candidate (from lit. or pathways)?

  6. Cluster Phenotypes

  7. Excessive Airway Narrowing in a General Population n = 201 James et al. ARRD 1992;146:895-9

  8. Smooth muscle Outer wall area Inner wall area Basement membrane perimeter Airway Compartments Lumen area

  9. Excessive Airway Narrowing

  10. Airway smooth muscle in asthma: collaborative study James et al AJRCCM (rejected), Thorax (rejected), ERJ (submitted)

  11. Decline in lung function - the Busselton Health Study Females James et al AJRCCM 2005;171:109

  12. A Longitudinal Study of Childhood Asthma Followed to Adulthood FEV1/FVC Mean (SE) from 9-26 Yrs in Males and Females, by Pattern of Wheezing Sears M et al. N Engl J Med 2003;349:1414-1422

  13. Asthma (ever) (p <0.001)* (p <0.001)* (p <0.001)* (p <0.001)* *1981 vs 2005/07 Q. “Has a doctor ever told you that you had asthma?” Q. “Have you ever had asthma?”

  14. Current Asthma(AHR + recent wheeze)

  15. (p <0.001)* Wheeze (ever) (p <0.001)* (p <0.029)* *1981 vs 2005/07 Q. “Has your chest sounded wheezy on most days or nights?” Q. “Has your chest ever made a wheezing or whistling sound?”

  16. Wheeze <12 months Recent Wheeze

  17. Shortness of Breath

  18. Cough/Phlegm (p <0.02)* (p <0.02)* (p <0.02)* (p <0.02)* *1981 vs 2005

  19. Smoking

  20. Bronchitis Q. “Have you ever had bronchitis? Q. “Has your doctor ever told that you had bronchitis?”

More Related