Novel Treatment-Refractory Preschool Wheeze Phenotypes Identified by Cluster Analysis of Lung Lavage Constituents.

Asthma / diagnosis Bronchoalveolar Lavage Child, Preschool Cluster Analysis Humans Infant Phenotype Respiratory Sounds
Asthma Asthma/cluster analysis Child/preschool Phenotypes Rhinovirus Wheeze Wheezing syndromes

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
07 2021
Historique:
received: 01 08 2020
revised: 25 02 2021
accepted: 24 03 2021
pubmed: 28 4 2021
medline: 23 7 2021
entrez: 27 4 2021
Statut: ppublish

Résumé

Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective. To apply unsupervised analysis of lung lavage (bronchoalveolar lavage [BAL]) variables to identify clusters of preschool children with treatment-refractory wheeze. A total of 155 children 6 years or younger underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis and sorted into clusters by Ward's method, and membership was confirmed by discriminant analysis. The model was repeatable in a 48-case validation sample and accurately classified 86% of cases. Cluster 1 (n = 60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n = 42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and two-third had increased BAL lipid-laden macrophages. Cluster 3 (n = 46) had mid-onset wheeze, low total IgE, and two-third had BAL viral transcripts, predominately human rhinovirus, with BAL neutrophilia. Cluster 4 (n = 7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils. Preschool children with recurrent wheeze refractory to inhaled corticosteroid treatment include 4 clusters: airway malacia, gastroesophageal reflux, indolent human rhinovirus bronchoalveolitis, and type-2

Sections du résumé

BACKGROUND
Preschool children with treatment-refractory wheeze often require unscheduled acute care. Current guidelines advise treatment of persistent wheeze with inhaled corticosteroids. Alternative treatments targeting structural abnormalities and specific inflammatory patterns could be more effective.
OBJECTIVE
To apply unsupervised analysis of lung lavage (bronchoalveolar lavage [BAL]) variables to identify clusters of preschool children with treatment-refractory wheeze.
METHODS
A total of 155 children 6 years or younger underwent bronchoscopy with BAL for evaluation of airway structure, inflammatory markers, and pathogens. Variables were screened with factor analysis and sorted into clusters by Ward's method, and membership was confirmed by discriminant analysis.
RESULTS
The model was repeatable in a 48-case validation sample and accurately classified 86% of cases. Cluster 1 (n = 60) had early-onset wheeze, 85% with structural abnormalities, mostly tracheamalacia, with low total IgE and agranulocytic BAL. Cluster 2 (n = 42) had later-onset wheeze, the highest prevalence of gastroesophageal reflux, little atopy, and two-third had increased BAL lipid-laden macrophages. Cluster 3 (n = 46) had mid-onset wheeze, low total IgE, and two-third had BAL viral transcripts, predominately human rhinovirus, with BAL neutrophilia. Cluster 4 (n = 7) was older, with high total IgE, blood eosinophilia, and mixed BAL eosinophils and neutrophils.
CONCLUSIONS
Preschool children with recurrent wheeze refractory to inhaled corticosteroid treatment include 4 clusters: airway malacia, gastroesophageal reflux, indolent human rhinovirus bronchoalveolitis, and type-2

Identifiants

DOI: 10.1016/j.jaip.2021.03.059 PMID: 33905917
pubmed: 33905917
pii: S2213-2198(21)00465-7
doi: 10.1016/j.jaip.2021.03.059
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2792-2801.e4

Subventions

Organisme : NIAID NIH HHS
ID : R21 AI151496
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI123337
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL109250
Pays : United States

Informations de copyright

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

W Gerald Teague (WG)

Child Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va. Electronic address: wgt2p@virgnia.edu.

Monica G Lawrence (MG)

Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.

Sanford Williams (S)

Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.

Andrea S Garrod (AS)

Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

Deborah Froh (D)

Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

Stephen V Early (SV)

Department of Otolaryngology, Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Va.

William Brand (W)

Department of Otolaryngology, Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Va.

Jeremy P Middleton (JP)

Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

Michael V Mendoza (MV)

Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

Kerry A Hollis (KA)

Department of Respiratory Therapy and Sleep Technology, University of Virginia Medical Center, Charlottesville, Va.

Kristin Wavell (K)

Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.

Peter W Heymann (PW)

Child Health Research Center, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va; Division of Respiratory Medicine, Allergy, Immunology, and Sleep, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Va.

John W Steinke (JW)

Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va.

Larry Borish (L)

Division of Allergy, Asthma, and Immunology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va; Department of Microbiology, University of Virginia School of Medicine, Charlottesville, Va.

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Techniques d'investigation › Irrigation thérapeutique › Lavage bronchoalvéolaire › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de regroupements › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Novel Treatment-Refractory Preschool Wheeze...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques respiratoires › Bruits respiratoires › Novel Treatment-Refractory Preschool Wheeze...