TY - JOUR TI - Trajectories of childhood immune development and respiratory health relevant to asthma and allergy AU - Tang, Howard HF AU - Teo, Shu Mei AU - Belgrave, Danielle CM AU - Evans, Michael D AU - Jackson, Daniel J AU - Brozynska, Marta AU - Kusel, Merci MH AU - Johnston, Sebastian L AU - Gern, James E AU - Lemanske, Robert F AU - Simpson, Angela AU - Custovic, Adnan AU - Sly, Peter D AU - Holt, Patrick G AU - Holt, Kathryn E AU - Inouye, Michael A2 - Chakraborty, Arup K A2 - Teare, M Dawn A2 - Teare, M Dawn A2 - Megremis, Spyridon VL - 7 PY - 2018 DA - 2018/10/15 SP - e35856 C1 - eLife 2018;7:e35856 DO - 10.7554/eLife.35856 UR - https://doi.org/10.7554/eLife.35856 AB - Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk ‘atopic’ cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma. KW - immune development KW - respiratory disease KW - allergy KW - bioinformatics JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -