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Causes of variability in latent phenotypes of childhood wheeze - 04/05/19

Doi : 10.1016/j.jaci.2018.10.059 
Ceyda Oksel, PhD a, , Raquel Granell, PhD b, , Osama Mahmoud, PhD b, Adnan Custovic, MD, PhD a, , A. John Henderson, MD b,
on behalf of

the STELAR

  STELAR investigators: Professor Syed Hasan Arshad, Silvia Colicino, Professor Paul Cullinan, Dr John Curtin, Professor Graham Devereux, Professor John Holloway, Dr Clare S. Murray, Professor Graham Roberts, Professor Angela Simpson, and Professor Steve Turner.

Breathing Together investigators§

  Breathing Together investigators: Professor Andrew Bush, Dr Peter Ghazal, Professor Jonathan Grigg, Professor Clare M. Lloyd, Dr Benjamin Marsland, Dr Ultan Power, Professor Sejal Saglani, Professor Jurgen Schwarze, and Professor Mike Shields.

a Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom 
b Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom 

Corresponding author: Adnan Custovic, MD, PhD, Section of Paediatrics, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.Section of PaediatricsDepartment of MedicineImperial College LondonNorfolk PlaceLondonW2 1PGUnited Kingdom

Abstract

Background

Latent class analysis (LCA) has been used extensively to identify (latent) phenotypes of childhood wheezing. However, the number and trajectory of discovered phenotypes differed substantially between studies.

Objective

We sought to investigate sources of variability affecting the classification of phenotypes, identify key time points for data collection to understand wheeze heterogeneity, and ascertain the association of childhood wheeze phenotypes with asthma and lung function in adulthood.

Methods

We used LCA to derive wheeze phenotypes among 3167 participants in the ALSPAC cohort who had complete information on current wheeze recorded at 14 time points from birth to age 16½ years. We examined the effects of sample size and data collection age and intervals on the results and identified time points. We examined the associations of derived phenotypes with asthma and lung function at age 23 to 24 years.

Results

A relatively large sample size (>2000) underestimated the number of phenotypes under some conditions (eg, number of time points <11). Increasing the number of data points resulted in an increase in the optimal number of phenotypes, but an identical number of randomly selected follow-up points led to different solutions. A variable selection algorithm identified 8 informative time points (months 18, 42, 57, 81, 91, 140, 157, and 166). The proportion of asthmatic patients at age 23 to 24 years differed between phenotypes, whereas lung function was lower among persistent wheezers.

Conclusions

Sample size, frequency, and timing of data collection have a major influence on the number and type of wheeze phenotypes identified by using LCA in longitudinal data.

Le texte complet de cet article est disponible en PDF.

Key words : Childhood asthma, wheeze phenotypes, longitudinal analysis, latent class analysis, Avon Longitudinal Study of Parents and Children

Abbreviations used : ALSPAC, ARI, BIC, LCA, TCRS


Plan


 C.O. is funded through the Wellcome Trust Strategic Award 108818/15/Z. The UK Medical Research Council and the Wellcome Trust (grant 102215/2/13/2) and the University of Bristol provide core support for Avon Longitudinal Study of Parents and Children (ALSPAC). A comprehensive list of grants funding is available on the ALSPAC Web site (grant-acknowledgements.pdf). STELAR cohorts are funded by UK Medical Research Council (MRC) grants G0601361 and MR/K002449/1. This analysis was funded by the Wellcome Trust Strategic Award 108818/15/Z.
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflict of interests.


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Vol 143 - N° 5

P. 1783 - mai 2019 Retour au numéro
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