Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

NIH/NHLBI AsthmaNet

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods: Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P <.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusions: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

Original languageEnglish (US)
Pages (from-to)915-924.e7
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume7
Issue number3
DOIs
StatePublished - Mar 2019
Externally publishedYes

Fingerprint

Respiratory Sounds
Preschool Children
Adrenal Cortex Hormones
Phenotype
Eczema
Pets
Therapeutics
Smoke
Allergens
Tobacco
Demography
Clinical Trials
Morbidity
Research

Keywords

  • Asthma exacerbation
  • Asthma in children
  • Inhaled corticosteroid
  • Latent class analysis
  • Phenotype
  • Preschool child
  • Sensitization
  • Type 2 inflammation
  • Wheeze

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

@article{6d891d2c404f46f98c3fcf15cebaaa80,
title = "Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation",
abstract = "Background: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods: Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P <.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusions: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.",
keywords = "Asthma exacerbation, Asthma in children, Inhaled corticosteroid, Latent class analysis, Phenotype, Preschool child, Sensitization, Type 2 inflammation, Wheeze",
author = "{NIH/NHLBI AsthmaNet} and Fitzpatrick, {Anne M.} and Bacharier, {Leonard B.} and Guilbert, {Theresa W.} and Jackson, {Daniel J.} and Szefler, {Stanley J.} and Avraham Beigelman and Cabana, {Michael D.} and Ronina Covar and Fernando Holguin and Lemanske, {Robert F.} and Martinez, {Fernando D.} and Wayne Morgan and Wanda Phipatanakul and Pongracic, {Jacqueline A.} and Zeiger, {Robert S.} and Mauger, {David T.} and Sachin Baxi and Mindy Benson and Kathryn Blake and Susan Boehmer and Burnham, {Carey Ann} and Michael Cabana and Mario Castro and James Chmiel and Cori Daines and Michael Daines and Anne Fitzpatrick and Jonathan Gaffin and {Ann Gentile}, Deborah and Gower, {W. Adam} and Theresa Guilbert and Elliot Israel and Daniel Jackson and Kelly, {H. William} and Kumar, {Harsha Vardhan} and {Jason Lang}, Lang and Stephen Lazarus and John Lima and Robert Lemanske and Ngoc Ly and Fernando Martinez and Jyothi Marbin and David Mauger and Kelley Meade and James Moy and Ross Myers and Tod Olin and Ian Paul and Stephen Peters and Jacqueline Pongracic",
year = "2019",
month = "3",
doi = "10.1016/j.jaip.2018.09.016",
language = "English (US)",
volume = "7",
pages = "915--924.e7",
journal = "Journal of Allergy and Clinical Immunology: In Practice",
issn = "2213-2198",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Phenotypes of Recurrent Wheezing in Preschool Children

T2 - Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

AU - NIH/NHLBI AsthmaNet

AU - Fitzpatrick, Anne M.

AU - Bacharier, Leonard B.

AU - Guilbert, Theresa W.

AU - Jackson, Daniel J.

AU - Szefler, Stanley J.

AU - Beigelman, Avraham

AU - Cabana, Michael D.

AU - Covar, Ronina

AU - Holguin, Fernando

AU - Lemanske, Robert F.

AU - Martinez, Fernando D.

AU - Morgan, Wayne

AU - Phipatanakul, Wanda

AU - Pongracic, Jacqueline A.

AU - Zeiger, Robert S.

AU - Mauger, David T.

AU - Baxi, Sachin

AU - Benson, Mindy

AU - Blake, Kathryn

AU - Boehmer, Susan

AU - Burnham, Carey Ann

AU - Cabana, Michael

AU - Castro, Mario

AU - Chmiel, James

AU - Daines, Cori

AU - Daines, Michael

AU - Fitzpatrick, Anne

AU - Gaffin, Jonathan

AU - Ann Gentile, Deborah

AU - Gower, W. Adam

AU - Guilbert, Theresa

AU - Israel, Elliot

AU - Jackson, Daniel

AU - Kelly, H. William

AU - Kumar, Harsha Vardhan

AU - Jason Lang, Lang

AU - Lazarus, Stephen

AU - Lima, John

AU - Lemanske, Robert

AU - Ly, Ngoc

AU - Martinez, Fernando

AU - Marbin, Jyothi

AU - Mauger, David

AU - Meade, Kelley

AU - Moy, James

AU - Myers, Ross

AU - Olin, Tod

AU - Paul, Ian

AU - Peters, Stephen

AU - Pongracic, Jacqueline

PY - 2019/3

Y1 - 2019/3

N2 - Background: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods: Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P <.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusions: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

AB - Background: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Objective: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Methods: Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Results: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P <.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Conclusions: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

KW - Asthma exacerbation

KW - Asthma in children

KW - Inhaled corticosteroid

KW - Latent class analysis

KW - Phenotype

KW - Preschool child

KW - Sensitization

KW - Type 2 inflammation

KW - Wheeze

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U2 - 10.1016/j.jaip.2018.09.016

DO - 10.1016/j.jaip.2018.09.016

M3 - Article

C2 - 30267890

AN - SCOPUS:85055560473

VL - 7

SP - 915-924.e7

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

SN - 2213-2198

IS - 3

ER -