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. 2024 Nov-Dec:234:107808.
doi: 10.1016/j.rmed.2024.107808. Epub 2024 Sep 14.

Real-world phenotyping and risk assessment of childhood asthma burden using national registries

Kjell Erik Julius Håkansson  1 , Nada Alabdulkarim  2 , Silvia Cabrera Guerrero  3 , Vibeke Backer  4 , Charlotte Suppli Ulrik  5 , Deepa Rastogi  6
Affiliations

Real-world phenotyping and risk assessment of childhood asthma burden using national registries

Kjell Erik Julius Håkansson et al. Respir Med. 2024 Nov-Dec.

Abstract

Background: Phenotype classification contributes to risk assessment of asthma. Previous studies have applied this concept primarily to adult populations and in the setting of research protocol assessments which may not be applicable to clinical settings.

Objective: Exploring the value of routinely collected clinical data for phenotype classification and risk assessment of childhood asthma.

Methods: Using hospital and laboratory data, 29,851 children in a Danish nationwide database aged 2-17 years with ICS-treated asthma in 2015 followed for two years (730 days) were classified to have T2 (elevated blood eosinophils (>300 cells/μL) and/or elevated total- or specific-IgE), and/or non-T2 risk factors (in utero tobacco exposure and/or severe viral infections). Logistic regression was applied to quantify associations of risk factors with asthma severity, control, and exacerbation risk.

Results: In a complete case analysis, 85.8 % children had at least one T2 risk factor and 29.3 % had mixed T2/non-T2 risk factors. Elevated blood eosinophils and total/specific IgE were associated with exacerbations (ORs 1.55 (1.38-1.73) and 1.41 (1.20-1.66) and higher asthma severity (1.42 (1.24-1.63) and 1.31 (1.08-1.60)), respectively. Dose-dependency was observed between blood eosinophil counts, total IgE levels, and risk of adverse outcomes. Furthermore, accumulation of risk factors demonstrated an increasing risk, with children with all four risk factors having a high risk of any adverse asthma-related outcome (OR 3.13 (2.03-4.82) CONCLUSION: Asthma phenotypic markers defined in research protocols can be reliably applied in real-world settings by utilizing data collected during routine clinical care and enable better classification of risk of adverse asthma outcomes.

Keywords: Eosinophils; Exacerbations; Pharmacoepidemiology; Phenotypes; Severe asthma.

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Conflict of interest statement

Declaration of competing interest KEJH has received personal fees from AstraZeneca, Chiesi, GSK, Sanofi and TEVA. NA, SCG declares no conflicts of interest. DR declares no conflicts of interest but does serve on a DSMB for the National Institute of Health. CSU has received personal fees from AstraZeneca, GSK, TEVA, Chiesi, Sanofi Genzyme, Boehringer-Ingelheim, Orion Pharma, Novartis, ALK-Abello, Mundipharma, Berlin Chemie, Pfizer, TFF Pharmaceuticals, Covis Pharma and Actelion. VB has received personal fees from AstraZeneca, GSK, TEVA, Sanofi Genzyme, MSD, Chiesi, Boehringer-Ingelheim, Novartis, ALK-Abello, Mundipharma, BIRK NPC and Pharmaxis.

Figures

Figure 1
Figure 1
Flowchart of study inclusion and cohort design in a nationwide Danish cohort of children and adults with inhaled corticosteroid-treated asthma.
Figure 2
Figure 2
A) Prevalence of specific risk factors and B) age- and sex adjusted odds ratios for adverse asthma-related outcomes in 29,851 children and adolescents with inhaled corticosteroid-treated asthma. C) Prevalence of cumulative number of risk factors and D) age- and sex-adjusted odds ratios for adverse asthma-related outcomes in a complete case analysis of 7,548 children and adolescents with inhaled corticosteroid-treated asthma.
Figure 3
Figure 3
Predicted probabilities and prediction intervals of poor control, exacerbations, and severe asthma in 29,851 children and adolescents aged 2-17 years with inhaled corticosteroid treated asthma across continuous measures of blood eosinophils and total Immunoglobulin E. Probabilities predicted for a 6-year-old boy.
Figure 4
Figure 4
Prevalence and overlap of T2 (elevated blood eosinophils or total- or specific-IgE) and non-T2 endo- and phenotypic risk factors in 7,548 children and adolescents aged 2-17 with inhaled corticosteroid-treated asthma.
See this image and copyright information in PMC

References

    1. Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007. Dec;62(12):1043–9. - PMC - PubMed
    1. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med. 2008;178(3):218–24. - PMC - PubMed
    1. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181(4):315–23. - PMC - PubMed
    1. Zoratti EM, Krouse RZ, Babineau DC, Pongracic JA, O’Connor GT, Wood RA, et al. Asthma phenotypes in inner-city children. J Allergy Clin Immunol. 2016. Oct;138(4):1016–29. - PMC - PubMed
    1. Pijnenburg MW, Frey U, De Jongste JC, Saglani S. Childhood asthma: pathogenesis and phenotypes. Eur Respir J. 2022. Jun;59(6). - PubMed

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