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Validation of novel wheeze phenotypes using longitudinal airway function and atopic sensitization data in the first 6 years of life: Evidence from the Southampton Women's survey
Author(s) -
Collins Samuel A.,
Pike Katharine C.,
Inskip Hazel M.,
Godfrey Keith M.,
Roberts Graham,
Holloway John W.,
Lucas Jane S.A.
Publication year - 2013
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.22766
Subject(s) - wheeze , medicine , phenotype , sensitization , airway , lung function , atopy , asthma , respiratory sounds , immunology , pediatrics , surgery , genetics , lung , biology , gene
Background In 1995 the Tucson Children's Respiratory Study (TCRS) identified clinically distinct phenotypes amongst early wheezers; the Avon Longitudinal Study of Parents And Children (ALSPAC) has recently re‐examined these. Objectives To validate statistically derived ALSPAC phenotypes in the Southampton Women's Survey (SWS) using infant and 6‐year lung function, and allergic sensitization at 1, 3, and 6 years, comparing these with TCRS phenotypes. Methods Complete 6‐year follow‐up data were available for 926 children, selected from 1,973 infants born to 12,579 women characterized pre‐conception. Ninety‐five children had V'maxFRC and FEV 0.4 measured age 5–14 weeks using rapid compression/raised volume techniques. At 6 years we performed spirometry (n = 791), fractional exhaled nitric oxide (FeNO, n = 589) and methacholine challenge (n = 234). Skin prick testing was performed at 12m, 3 and 6 years (n = 1,494, 1,255, 699, respectively). Using wheeze status questionnaire data at 6m, 12m, 2, 3 and 6 years we classified children into TCRS (never, transient early, persistent, late‐onset) and ALSPAC based groups (never, early, transient, intermediate‐onset, late‐onset, persistent). Results Amongst ALSPAC groups, persistent and late‐onset wheeze were associated with atopy at 3 and 6 years, whilst intermediate‐onset wheeze showed earlier atopic association at 1 year; all three were associated with FeNO at 6 years. Persistent wheezers had lower infant (V'maxFRC P < 0.05) and 6‐year lung function (FEV 1 , FEV 1 /FVC, and FEF 25–75 , P < 0.05), whilst late and intermediate‐onset wheezers showed no lung function deficits. Transient wheezers were non‐atopic but showed persistent lung function deficits (V'maxFRC in infancy, FEV 1 and FEF 25–75 at 6 years, all P < 0.05). Those who wheezed only in the first year (early phenotype) showed no lung function deficits. No associations were seen with 6 years bronchial hyper‐responsiveness or infancy FEV 0.4 . Conclusion SWS cohort data validates the statistically derived ALSPAC six‐class model. In particular, lung function and atopy successfully differentiate persistent, late‐onset and intermediate‐onset wheeze, whilst the Tucson “transient early” wheeze phenotype can be sub‐classified into groups that reflect early lung function. Since the 4‐class model fails to adequately differentiate phenotypes based on lung function and atopy, we propose that strong consideration be given to using the 6‐class paradigm for longitudinal outcome work in wheezing with onset in early life. Pediatr Pulmonol. 2013; 48:683–692. © 2013 Wiley Periodicals, Inc.