The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines
Open accessAbstract
Background The pathology of pediatric severe therapy-resistant asthma (STRA) is little understood. Objectives We hypothesized that STRA in children is characterized by airway eosinophilia and mast cell inflammation and is driven by the TH2 cytokines IL-4, IL-5, and IL-13. Methods Sixty-nine children (mean age, 11.8 years; interquartile range, 5.6-17.3 years; patients with STRA, n = 53; control subjects, n = 16) underwent fiberoptic bronchoscopy, bronchoalveolar lavage (BAL), and endobronchial biopsy. Airway inflammation, remodeling, and BAL fluid and biopsy specimen TH2 cytokines were quantified. Children with STRA also underwent symptom assessment (Asthma Control Test), spirometry, exhaled nitric oxide and induced sputum evaluation. Results Children with STRA had significantly increased BAL fluid and biopsy specimen eosinophil counts compared with those found in control subjects (BAL fluid, P < .001; biopsy specimen, P < .01); within the STRA group, there was marked between-patient variability in eosinophilia. Submucosal mast cell, neutrophil, and lymphocyte counts were similar in both groups. Reticular basement membrane thickness and airway smooth muscle were increased in patients with STRA compared with those found in control subjects (P < .0001 and P < .001, respectively). There was no increase in BAL fluid IL-4, IL-5, or IL-13 levels in patients with STRA compared with control subjects, and these cytokines were rarely detected in induced sputum. Biopsy IL-5+ and IL-13+ cell counts were also not higher in patients with STRA compared with those seen in control subjects. The subgroup (n = 15) of children with STRA with detectable BAL fluid TH2 cytokines had significantly lower lung function than those with undetectable BAL fluid TH2 cytokines. Conclusions STRA in children was characterized by remodeling and variable airway eosinophil counts. However, unlike in adults, there was no neutrophilia, and despite the wide range in eosinophil counts, the TH2 mediators that are thought to drive allergic asthma were mostly absent.
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Cites
Miller, M. R., Hankinson, J., Brusasco, V., Burgos, F., Casaburi, R., Coates, A., Crapo, R., Enright, P., van der Grinten, C. P. M., Gustafsson, P., et al. (2005) · European Respiratory Journal · doi:10.1183/09031936.05.00034805 · Cited by 15,627
Interpretative strategies for lung function tests
Pellegrino, R., Viegi, G., Brusasco, V., Crapo, R. O., Burgos, F., Casaburi, R., Coates, A., van der Grinten, C. P. M., Gustafsson, P., Hankinson, J., et al. (2005) · European Respiratory Journal · doi:10.1183/09031936.05.00035205 · Cited by 5,945
(2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200406-710st · Cited by 3,203
Development of the asthma control test
Nathan, R. A., Sorkness, C. A., Kosinski, M., Schatz, M., Li, J. T., Marcus, P., Murray, J. J., & Pendergraft, T. B. (2004) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2003.09.008 · Cited by 2,906
Schatz, M., Sorkness, C. A., Li, J. T., Marcus, P., Murray, J. J., Nathan, R. A., Kosinski, M., Pendergraft, T. B., & Jhingran, P. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.01.011 · Cited by 1,221
Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide
Fitzpatrick, A. M., Gaston, B. M., Erzurum, S. C., & Teague, W. G. (2006) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2006.08.019 · Cited by 197 · cited 1×
“Total IgE (IU/mL) 386 (115-1286) 40 (14-130)”
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International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J., Adcock, I. M., Bateman, E. D., Bel, E. H., Bleecker, E. R., et al. (2014) · European Respiratory Journal · doi:10.1183/09031936.00202013 · Cited by 3,926
Self-citationManagement of severe asthma: a European Respiratory Society/American Thoracic Society guideline
Holguin, F., Cardet, J. C., Chung, K. F., Diver, S., Ferreira, D. S., Fitzpatrick, A., Gaga, M., Kellermeyer, L., Khurana, S., Knight, S., et al. (2020) · European Respiratory Journal · doi:10.1183/13993003.00588-2019 · Cited by 629
Self-citationInternational consensus on (ICON) pediatric asthma
Papadopoulos, N. G., Arakawa, H., Carlsen, K. ‐., Custovic, A., Gern, J., Lemanske, R., Le Souef, P., Mäkelä, M., Roberts, G., Wong, G., et al. (2012) · Allergy · doi:10.1111/j.1398-9995.2012.02865.x · Cited by 455
Hough, K. P., Curtiss, M. L., Blain, T. J., Liu, R.-M., Trevor, J., Deshane, J. S., & Thannickal, V. J. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00191 · Cited by 432
Eifan, A. O., & Durham, S. R. (2016) · Clinical & Experimental Allergy · doi:10.1111/cea.12780 · Cited by 379
Metadata
- Authors
- Bossley, C. J., Fleming, L., Gupta, A., Regamey, N., Frith, J., Oates, T., Tsartsali, L., Lloyd, C. M., Bush, A., & Saglani, S.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 129
- Issue
- 4
- Pages
- 974-982.e13
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2002427641
- Cited by
- 316
- References
- 6
- FWCI
- 18.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Bossley, C. J., Fleming, L., Gupta, A., Regamey, N., Frith, J., Oates, T., Tsartsali, L., Lloyd, C. M., Bush, A., & Saglani, S. (2012). Pediatric severe asthma is characterized by eosinophilia and remodeling without TH2 cytokines. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2012.01.059
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