Evolution of Eczema, Wheeze, and Rhinitis from Infancy to Early Adulthood Four Birth Cohort Studies

STELAR/UNICORN investigators

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The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear. 


To investigate within-individual patterns of morbidity of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood. 


We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (filaggrin [FLG] mutations and 17q21 variants), increase the risk of multimorbidity. Measurements and Main 


Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema1wheeze1rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern. FLG mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (FLG by 2- to 3-fold, rs7216389 risk variant by 1.4- to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity. Conclusions: 

Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.

Original languageEnglish
Pages (from-to)950-960
Number of pages11
JournalAmerican journal of respiratory and critical care medicine
Issue number8
Publication statusPublished - 15 Oct 2022

Bibliographical note

Funding Information:
Supported by the UK Medical Research Council (MRC) Programme grant MR/S025340/1 (UNICORN consortium); MRC grants G0601361 and MR/ K002449/1 (STELAR consortium); Wellcome Trust Strategic Award 108818/15/Z (R.G.); Asthma UK grants no. 301 (1995–1998), 362 (1998–2001), 01/012 (2001–2004), and 04/014 (2004–2007) (MAAS); BMA James Trust (2005), the JP Moulton Charitable Foundation (2004–2016), The North West Lung Centre Charity (1997–current), and MRC grant MR/L012693/1 (2014–2018) (MAAS); and the Isle of Wight Health Authority, the National Asthma Campaign, UK grant no. 364, and NIH grants R01 HL082925-01, R01 AI091905, and R01 AI121226 (IOW).

Funding Information:
Author Contributions: A.C., A.S., S.H., and S.F. conceived and planned the study and wrote the manuscript. S.H., S.F., and G.H. analyzed the data. All authors contributed to the interpretation of the results. All authors provided critical feedback and helped shape the research, analysis, and manuscript. A.S. and C.S.M. are supported by the National Institute for Health Research Manchester Biomedical Research Centre.


  • asthma
  • atopic march
  • birth cohorts
  • eczema
  • wheeze


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