Abstract
Background
Childhood asthma is an inflammatory disease with heterogeneous outcomes. We sought to determine the impact of total IgE, blood eosinophil, allergen sensitization, and inhaled corticosteroid (ICS) on longitudinal outcomes and to identify characteristics for discriminating different outcomes.
Methods
We conducted a retrospective study in 383 childhood asthma patients and another 313 patients with blood eosinophil data only receiving regular program-based visits from September 1, 2004, to December 31, 2018. Peak expiratory flow (PEF) variability, PEF predicted %, asthma severity, and asthma control at each visit were assessed as clinical outcomes.
Results
Our data show that the percentage of blood eosinophils was significantly associated with increased asthma severity (OR: 1.043, 95% CI: 1.002–1.086, P = 0.0392). Mold sensitization was significantly associated with asthma severity (OR: 2.2485, 95% CI: 1.3253–3.8150, P = 0.0027). Characteristics including sensitization status plus ICS dosage had the best area under the receiver operating characteristic curve (AUC) value for predicting longitudinal PEF predicted % (0.6609), PEF variability (0.6885), asthma severity (0.5918), and asthma control (0.6441), respectively.
Conclusions
We showed that the risk for adverse clinical outcomes at follow-up differed between serum IgE, blood eosinophil, and allergen sensitization identified at baseline. Sensitization and ICS dosage were predictive characteristics of long-term clinical outcomes.
Impact
-
The unique aspects of the study are its longitudinal assessment of patients receiving guideline-based asthma management program to help characterize the stability of the clinical outcomes over time. Characteristics including allergen sensitization and ICS dosage demonstrated an improved capability for distinguishing between better and worse clinical outcomes. Through longitudinal serial assessment, this study indicates the risk for adverse clinical outcomes differed between children with serum IgE/blood eosinophil/allergen sensitization characterized at baseline.
This is a preview of subscription content, access via your institution
Access options
Subscribe to Journal
Get full journal access for 1 year
$119.00
only $9.15 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Buy article
Get time limited or full article access on ReadCube.
$32.00
All prices are NET prices.




References
Wenzel, S. E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 18, 716–725 (2012).
Woodruff, P. G. et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am. J. Respir. Crit. Care Med. 180, 388–395 (2009).
Ahlstedt, S. & Murray, C. S. In vitro diagnosis of allergy: how to interpret IgE antibody results in clinical practice. Prim. Care Respir. J. 15, 228–236 (2006).
Siroux, V. et al. Relationships of allergic sensitization, total immunoglobulin E and blood eosinophils to asthma severity in children of the EGEA study. Clin. Exp. Allergy 33, 746–751 (2003).
Kovac, K., Dodig, S., Tjesic-Drinkovic, D. & Raos, M. Correlation between asthma severity and serum IgE in asthmatic children sensitized to dermatophagoides pteronyssinus. Arch. Med. Res. 38, 99–105 (2007).
Borish, L. et al. Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma. Ann. Allergy Asthma Immunol. 95, 247–253 (2005).
Carroll, W. D. et al. Asthma severity and atopy: how clear is the relationship? Arch. Dis. Child. 91, 405–409 (2006).
Fitzpatrick, A. M. et al. Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. J. Allergy Clin. Immunol. 127, 382–389.e381-313 (2011).
Howrylak, J. A. et al. Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications. J. Allergy Clin. Immunol. 133, 1289–1300.e1281-1212 (2014).
Naqvi, M. et al. Association between IgE levels and asthma severity among African American, Mexican, and Puerto Rican Patients with Asthma. J. Allergy Clin. Immunol. 120, 137–143 (2007).
Pongracic, J. A. et al. Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents. J. Allergy Clin. Immunol. 138, 1030–1041 (2016).
Zoratti, E. M. et al. Asthma phenotypes in inner-city children. J. Allergy Clin. Immunol. 138, 1016–1029 (2016).
Kamfar, H. Z., Koshak, E. E. & Milaat, W. A. Is there a role for automated eosinophil count in asthma severity assessment? J. Asthma 36, 153–158 (1999).
Casciano, J. et al. Value of peripheral blood eosinophil markers to predict severity of asthma. BMC Pulm. Med. 16, 109 (2016).
Jatakanon, A., Lim, S. & Barnes, P. J. Changes in sputum eosinophils predict loss of asthma control. Am. J. Respir. Crit. Care Med. 161, 64–72 (2000).
Ulrik, C. S. Peripheral eosinophil counts as a marker of disease activity in intrinsic and extrinsic asthma. Clin. Exp. Allergy 25, 820–827 (1995).
An, J. et al. Serum eosinophil-derived neurotoxin better reflect asthma control status than blood eosinophil counts. J. Allergy Clin. Immunol. Pract. 8, 2681–2688.e2681 (2020).
Price, D. B. et al. Blood eosinophil count and prospective annual asthma disease burden: A UK Cohort Study. Lancet Respir. Med. 3, 849–858 (2015).
Lang, A. et al. Asthma severity in childhood, untangling clinical phenotypes. Pediatr. Allergy Immunol. 21, 945–953 (2010).
Badar, A. et al. Association between feno, total blood IgE, peripheral blood eosinophil and inflammatory cytokines in partly controlled asthma. J. Asthma Allergy 13, 533–543 (2020).
Deykin, A. et al. Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids. J. Allergy Clin. Immunol. 115, 720–727 (2005).
Demarche, S. et al. Step-down of inhaled corticosteroids in non-eosinophilic asthma: a prospective trial in real life. Clin. Exp. Allergy 48, 525–535 (2018).
Alvarez-Gutiérrez, F. J. et al. Comparison of the asthma control test (Act) with lung function, levels of exhaled nitric oxide and control according to the global initiative for asthma (Gina). Arch. Bronconeumol. 46, 370–377 (2010).
Sommanus, S., Direkwattanachai, C., Lawpoolsri, S. & Sitcharungsi, R. Accuracy of childhood asthma control test among Thai childhood asthma patients. Asian Pac. J. Allergy Immunol. 36, 152–158 (2018).
Kreißl, S. et al. Reduced exhaled breath condensate pH and severity of allergic sensitization predict school age asthma. J. Allergy Clin. Immunol. Pract. 9, 1570–1577 (2021).
Hogan, A. D. & Bernstein, J. A. Gina updated 2019: landmark changes recommended for asthma management. Ann. Allergy Asthma Immunol. 124, 311–313 (2020).
Expert Panel Report 3 (Epr-3). Guidelines for the diagnosis and management of asthma-summary report 2007. J. Allergy Clin. Immunol. 120, S94–S138 (2007).
Milner, A. D. & Ingram, D. Peak expiratory flow rates in children under 5 years of age. Arch. Dis. Child. 45, 780–782 (1970).
Liang, K.-Y. & Zeger, S. L. Longitudinal data analysis using generalized linear models. Biometrika 73, 13–22 (1986).
Siroux, V. et al. Phenotypic determinants of uncontrolled asthma. J. Allergy Clin. Immunol. 124, 681–687.e683 (2009).
Neuman, Å. et al. Infant wheeze, comorbidities and school age asthma. Pediatr. Allergy Immunol. 25, 380–386 (2014).
Yang, S. & Berdine, G. The receiver operating characteristic (Roc) curve. Southw. Respir. Crit. Care Chron. 5, 34–36 (2017).
Lugogo, N., Que, L. G., Gilstrap, D. L. & Kraft, M. Murray and Nadel’s Textbook of Respiratory Medicine 731–750.e737 (Elsevier, 2016).
Sears, M. R. Predicting asthma outcomes. J. Allergy Clin. Immunol. 136, 829–836 (2015).
Lee-Sarwar, K. A., Bacharier, L. B. & Litonjua, A. A. Strategies to alter the natural history of childhood asthma. Curr. Opin. Allergy Clin. Immunol. 17, 139–145 (2017).
Irvin, C. G. Middleton’s Allergy 700–714 (Elsevier, 2014).
Matucci, A., Vultaggio, A., Maggi, E. & Kasujee, I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir. Res. 19, 113 (2018).
Sacco, O. et al. Total and Allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites. Pediatr. Allergy Immunol. 14, 475–481 (2003).
Boudier, A. et al. Data-driven adult asthma phenotypes based on clinical characteristics are associated with asthma outcomes twenty years later. Allergy 74, 953–963 (2019).
Acknowledgements
We thank both Dr. Chin-Hao Chang, Ying-Ting Chao, Tse-Le Huang, and Yu-Han Chang from the Department of Medical Research, National Taiwan University Hospital, for invaluable assistance with statistical consultation, analysis, and model development/validation.
Author information
Authors and Affiliations
Contributions
J.-H.L. conceptualized and designed the study, drafted the initial manuscript, and critically reviewed and carefully revised the manuscript. A.-L.C., S.-Y.H., and K.-Y.C. collected data, carried out the initial interpretation, and reviewed and revised the manuscript. B.-L.C., Y.-H.Y., Y.-T.L., L.-C.W., H.-H.Y., and Y.-C.H. supervised data interpretation, and reviewed and revised the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Consent statement
This study was conducted in compliance with the protocol for good clinical practices and the principles of the Declaration of Helsinki. The informed consents were obtained from all participants and/or their legal guardians.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Lee, JH., Lin, YT., Chu, AL. et al. Predictive characteristics to discriminate the longitudinal outcomes of childhood asthma: a retrospective program-based study. Pediatr Res 92, 1357–1363 (2022). https://doi.org/10.1038/s41390-022-01956-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41390-022-01956-6