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. 2023 Oct;131(4):466–473.e6. doi: 10.1016/j.anai.2023.06.024

eTable 1.

Studies Using Unsupervised Data-Driven Methods to Study Wheeze Trajectories

Study Study population Wheeze data collection time points Wheeze trajectories Key findings
Oksel et al,1 2019 STELAR consortium of 5 birth cohorts • Infancy: 0.5-1 y
• Early childhood: 2-3 y
• Preschool or early school age: 4-5 y
• Middle childhood: 8-10 y
• Adolescence: 14-18 y
• Never or infrequent wheeze
• Early-onset preschool remitting wheeze
• Early-onset mid-childhood remitting wheeze
• Persistent wheeze
• Late-onset wheeze
• All trajectories were associated with higher risks of asthma development and poorer lung function
• Persistent trajectory was linked to the highest risk of asthma
Duijts et al,2 2016 ALSPAC cohort • 6, 18, 30, 42, 54, 69 and 81 mo • Never or infrequent wheeze
• Transient early wheeze
• Prolonged early wheeze
• Intermediate-onset wheeze
• Late-onset wheeze
• Persistent wheeze
• All trajectories were associated with higher risks of asthma development.
• Intermediate-onset and persistent wheeze were linked to the highest risk of asthma and poor lung function.
Henderson et al,3 2008 ALSPAC cohort • 6, 18, 30, 42, 54, 69 and 81 mo • Never or infrequent wheeze
• Transient early wheeze
• Prolonged early wheeze
• Intermediate-onset wheeze
• Late-onset wheeze
• Persistent wheeze
• Intermediate-onset, late-onset, and persistent wheeze were linked to a higher risk of any skin prick sensitivity.
• Maternal history of asthma and allergy increased the risk of developing all trajectories (highest risk for persistent wheeze).
Savenije et al,4 2011
Caudri et al,5 2013
ALSPAC and PIAMA cohorts • ALSPAC: 6, 18, 30, 42, 54, 69, 81, and 91 mo
• PIAMA: 3, 12, 24, 36, 48, 60, 72, 84, and 96 mo
ALSPAC:
• Never or infrequent wheeze
• Transient early wheeze
• Prolonged early wheeze
• Intermediate-onset wheeze
• Late-onset wheeze
• Persistent wheeze
PIAMA
• Never or infrequent
• Transient early wheeze
• Intermediate-onset wheeze
• Late-onset wheeze
• Persistent wheeze
PIAMA
• Intermediate-onset and persistent wheeze were linked to the highest risk of asthma and poorer lung function.
• Intermediate-onset wheeze was associated with the highest risk of allergic sensitization at 4 and 8 y.
• Consistent with results from ALSPAC.
• Male sex, parental allergy, young maternal age, higher maternal BMI, low gestational age, smoke exposure during pregnancy, having older siblings, and childcare attendance increased the risk of transient early wheeze.
• Male sex, parental allergy, and low breastfeeding increased the risk of persistent wheeze.
• Low birthweight increased the risk of intermediate-onset wheeze.
• Maternal allergy increased the risk of late-onset wheeze.
Yang et al,6 2018 Hospital-based birth cohort
in Tokyo
• Every year from 1 to 9 y • Never or infrequent wheeze
• Transient early wheeze
• School-age onset wheeze
• Early-childhood onset remitting wheeze
• Persistent wheeze
• Persistent wheeze had the highest proportion of children with a family history of allergy.
• Smoke exposure during infancy was linked to a higher risk of transient early and persistent wheeze.
Kotecha et al,7 2019 Millennium Cohort Study • 9 months and at 3, 5, 7, and 11 y • Never or infrequent wheeze
• Early wheeze
• Persistent wheeze
• Late wheeze
• Formal childcare was associated with early wheeze development.
• Maternal atopy increased the risk of developing all trajectories, especially for persistent wheeze.
Belgrave et al,8 2013 MAAS • 1, 3, 5, and 8 y • No wheezing
• Transient early wheeze
• Late-onset wheeze
• Persistent controlled wheeze
• Persistent troublesome wheeze
• Children with persistent troublesome wheeze were the most vulnerable to hospitalizations, poor lung functions, and airway hyperreactivity.
Cano-Garcinuño et al,9 2014 SLAM • 12 three-month periods between 0 and 36 mo • Never or infrequent wheeze
• Transient wheeze
• Persistent wheeze
• Late wheeze
• All 3 wheeze phenotypes were linked to a higher occurrence of active asthma at 6 y.
Chen et al,10 2012 CCCEH • In-person interview: 6, 12, 24, 36, 60, 84, and 108 mo
• Telephone interview: 3, 9, 15, 18, 21, 30, 48, and 72 mo
• Never or infrequent wheeze
• Early transient wheeze
• Early persistent wheeze
• Late-onset wheeze
• Maternal asthma increased the risk of all phenotypes as compared with never/infrequent.
• Male children had a higher risk of early persistent wheeze.
• Early persistent wheeze was more common during cold/flu season.
Lodge et al,11 2014 MACS (high-risk children) • Every 4 wk from birth to age 15 mo, once at age 18 mo, and yearly at age 2-7 y (23 time points) • Never or infrequent wheeze
• Early transient wheeze
• Early persistent wheeze
• Intermediate-onset wheeze
• Late-onset wheeze
• LRTI and childcare attendance in the first year of life and low breastfeeding were risk factors for early transient wheeze.
• Aeroallergen sensitization was a risk factor for early persistent wheeze.
• LRTI, eczema, aeroallergen, and food sensitization were risk factors for intermediate-onset wheeze whereas exposure to dogs and having no older siblings were protective.
• High exposure to parental smoke at birth and low breastfeeding were risk factors for late-onset wheeze.
Tse et al,12 2016 Project Viva • Yearly from 1 to 9 y • Never or infrequent wheeze
• Early transient wheeze
• Persistent wheeze
• Maternal asthma, early bronchiolitis, and eczema increased the risk of persistent wheeze.
Depner et al,13 2014 PASTURE • 2, 12, 18, 24, 36, 48, 60, and 72 mo • No or infrequent wheeze
• Transient wheeze
• Intermediate wheeze
• Late-onset wheeze
• Persistent wheeze
• Persistent wheeze was linked to asthma locus on chromosome 17q21.
• Late-onset wheeze was linked to atopic sensitization at 6 y.

Abbreviations: ALSPAC, Avon Longitudinal Study of Parents and Children; BMI, body mass index; CCCEH, Columbia Center for Children's Environmental Health birth cohort study; LRTI, Lower respiratory tract infection; MACS, Melbourne Atopy Cohort Study; MAAS, Manchester Asthma and Allergy Study; PASTURE, Protection against Allergy–Study in Rural Environments; PIAMA, Prevention and Incidence of Asthma and Mite Allergy; SLAM, Sibilancias de Lactante y Asma de Mayor; STELAR, Study Team for Early Life Asthma Research.