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

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 FEV0.4 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