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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.
Pediatr Pulmonol. 2013 Jul; 48(7):683-92.PP

Abstract

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 < 0.05) and 6-year lung function (FEV1, FEV1/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, FEV1 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 FEV0.4.

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.

Authors+Show Affiliations

Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

23401430

Citation

Collins, Samuel A., et al. "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." Pediatric Pulmonology, vol. 48, no. 7, 2013, pp. 683-92.
Collins SA, Pike KC, Inskip HM, et al. 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. Pediatr Pulmonol. 2013;48(7):683-92.
Collins, S. A., Pike, K. C., Inskip, H. M., Godfrey, K. M., Roberts, G., Holloway, J. W., & Lucas, J. S. (2013). 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. Pediatric Pulmonology, 48(7), 683-92. https://doi.org/10.1002/ppul.22766
Collins SA, et al. 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. Pediatr Pulmonol. 2013;48(7):683-92. PubMed PMID: 23401430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Collins,Samuel A, AU - Pike,Katharine C, AU - Inskip,Hazel M, AU - Godfrey,Keith M, AU - Roberts,Graham, AU - Holloway,John W, AU - Lucas,Jane S A, AU - ,, Y1 - 2013/02/08/ PY - 2012/08/07/received PY - 2012/11/09/revised PY - 2012/11/09/accepted PY - 2013/2/13/entrez PY - 2013/2/13/pubmed PY - 2014/2/1/medline SP - 683 EP - 92 JF - Pediatric pulmonology JO - Pediatr Pulmonol VL - 48 IS - 7 N2 - 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 < 0.05) and 6-year lung function (FEV1, FEV1/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, FEV1 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 FEV0.4. 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. SN - 1099-0496 UR - https://www.unboundmedicine.com/medline/citation/23401430/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_ L2 - https://doi.org/10.1002/ppul.22766 DB - PRIME DP - Unbound Medicine ER -