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. 2020 Sep;8(8):2617-2627.e4.
doi: 10.1016/j.jaip.2020.02.032. Epub 2020 Mar 7.

Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association with 1-Year Outcomes

Anne M Fitzpatrick  1 , Leonard B Bacharier  2 , Daniel J Jackson  3 , Stanley J Szefler  4 , Avraham Beigelman  2 , Michael Cabana  5 , Ronina Covar  6 , Theresa Guilbert  7 , Fernando Holguin  8 , Robert F Lemanske  3 , Fernando D Martinez  9 , Wayne Morgan  9 , Wanda Phipatanakul  10 , Jacqueline A Pongracic  11 , Hengameh H Raissy  12 , Robert S Zeiger  13 , David T Mauger  14
Affiliations

Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association with 1-Year Outcomes

Anne M Fitzpatrick et al. J Allergy Clin Immunol Pract. 2020 Sep.

Abstract

Background: Compared with adults, phenotypic characterization of children with asthma is still limited and it remains difficult to predict which children with asthma are at highest risk for poor outcomes.

Objective: To identify latent classes in a large population of treatment-adherent children with mild to moderate asthma enrolled in clinical trials and determine whether latent class assignment predicts future lung function abnormalities and exacerbation rate.

Methods: Latent class analysis was performed on 2593 children with mild to moderate asthma aged 5 18 years, with 19 variables encompassing demographic characteristics, medical history, symptoms, lung function, allergic sensitization, and type 2 inflammation. Outcomes included lung function and the annualized exacerbation rate at 12 months of follow-up.

Results: Five latent classes were identified with differing demographic features, asthma control, sensitization, type 2 inflammatory markers, and lung function. Exacerbation rates were 1.30 ± 0.12 for class 1 (multiple sensitization with partially reversible airflow limitation), 0.90 ± 0.05 for class 2 (multiple sensitization with reversible airflow limitation), 0.87 ± 0.08 for class 3 (lesser sensitization with reversible airflow limitation), 0.87 ± 0.05 for class 4 (multiple sensitization with normal lung function), and 0.71 ± 0.06 for class 5 (lesser sensitization with normal lung function). Lung function abnormalities persisted in class 1 at 12 months.

Conclusions: Children with mild to moderate asthma are a heterogeneous group. Allergic sensitization and lung function may be particularly useful in identifying children at the greatest risk for future exacerbation. Additional studies are needed to determine whether latent classes correspond to meaningful phenotypes for the purpose of personalized treatment.

Keywords: Aeroallergen sensitization; Asthma control; Asthma exacerbation; Asthma in children; Asthma outcomes; Latent class analysis; Lung function; Phenotype; Type 2 inflammation.

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Conflict of interest statement

Conflicts of interest: L. B. Bacharier reports personal fees from GlaxoSmithKline (GSK), Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, Sanofi/Regeneron, Vectura, Circassia, and AstraZeneca, outside the submitted work. D. J. Jackson reports personal fees from Vectura, Boehringer Ingelheim, Pfizer, Sanofi/Regeneron, AstraZeneca, Vifor, GSK, and Novartis, outside the submitted work. S. J. Szefler reports consultancy fees from Boehringer Ingelheim, Genentech, GSK, Aerocrine, Novartis, AstraZeneca, Daiichi Sankyo, Propeller Health, Roche, and Teva; and grants from GSK, outside the submitted work. M. Cabana reports personal fees from Merck, Thermo Fisher, Genentech, and Novartis, outside the submitted work. R. Covar reports grants from Roche and AstraZeneca; and nonfinancial support from GSK, outside the submitted work. T. Guilbert reports personal fees from the American Board of Pediatrics, Pediatric Pulmonary Sub-board, GSK, Regeneron Pharmaceuticals, Merck, Novartis/Regeneron, Aviragen, GSK/Regeneron, Sanofi/Regeneron, and Teva; grants from Sanofi/Regeneron, AstraZeneca, and the National Institutes of Health; and personal fees from UpToDate, outside the submitted work. R. F. Lemanske reports grants from Pharmaxis; and personal fees from Elsevier and UpToDate, outside the submitted work. F. D. Martinez reports grants from the National Institutes of Health/Office of the Director and Johnson & Johnson; and personal fees from Copeval as well as Commense, Inc, outside the submitted work. W. Morgan reports grants from the Cystic Fibrosis Foundation; and personal fees from the Cystic Fibrosis Foundation, Genentech, the American Thoracic Society, and the American College of Chest Physicians, outside the submitted work. W. Phipatanakul reports consulting fees from Regeneron, Novartis, GSK, and Genentech; and clinical trials support and medication/supplies for trial support from Genentech, Novartis, Thermo Fisher, ALK-Abelló, and Monaghan. J. A. Pongracic reports grants from Northwestern University, during the conduct of the study; and research grants from Boehringer Ingelheim, GSK, Teva, and Merck, outside the submitted work. R. S. Zeiger reports grants from Aerocrine, Genentech, MedI-mmune/AstraZeneca, Merck, GSK, and ALK Pharma; personal fees from AstraZeneca, Genentech, Novartis, Teva, GSK, Theravance BioPharma, Regeneron Pharmaceuticals, and Patara Pharma, outside the submitted work. D. T. Mauger reports nonfinancial support from Merck, Boehringer Ingelheim, GSK, Teva, and Vifor, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Distribution of studies within each latent class. BADGER, Best Add-On Therapy Giving Effective Response; BARD, Best African American Response to Asthma Drugs; CAMP, Childhood Asthma Management Research Program; CLIC, Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid; PACT, Pediatric Asthma Controller Trial; SIENA, Steroids in Eosinophil Negative Asthma; STICS, Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations; TREXA, Treating Children to Prevent Exacerbations of Asthma.
FIGURE 2.
FIGURE 2.
Participants with (A) FEV1 and (B) FEV1/FVC below the LLN at the end of follow-up, stratified by treatment assignment and latent class 1 (multiple sensitization with partially reversible airflow limitation), 2 (multiple sensitization with reversible airflow limitation), 3 (lesser sensitization with reversible airflow limitation), 4 (multiple sensitization with normal lung function), and 5 (lesser sensitization with normal lung function). *P <.05 vs placebo.
FIGURE 3.
FIGURE 3.
(A) Exacerbation frequency and (B) annualized rate of exacerbations (mean ± SEM) at the end of follow-up in latent classes 1 (multiple sensitization with partially reversible airflow limitation), 2 (multiple sensitization with reversible airflow limitation), 3 (lesser sensitization with reversible airflow limitation), 4 (multiple sensitization with normal lung function), and 5 (lesser sensitization with normal lung function).
FIGURE 4.
FIGURE 4.
(A) Exacerbation occurrence and (B) annualized exacerbation rate at the end of follow-up, stratified by treatment assignment and latent class 1 (multiple sensitization with partially reversible airflow limitation), 2 (multiple sensitization with reversible airflow limitation), 3 (lesser sensitization with reversible airflow limitation), 4 (multiple sensitization with normal lung function), and 5 (lesser sensitization with normal lung function). *P < .05 vs placebo.
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Comment in

  • "Asthma" or "Asthma Spectrum Disorder"?
    Custovic A. Custovic A. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2628-2629. doi: 10.1016/j.jaip.2020.06.005. J Allergy Clin Immunol Pract. 2020. PMID: 32888529 No abstract available.

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