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Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma
- Source :
- Clinical & Experimental Allergy. 46:793-802
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- SummaryBackground In severe asthmatics with persistent airway eosinophilia, blockade of interleukin-5 has significant steroid-sparing effects and attenuates blood and sputum eosinophilia. The contribution of local maturational processes of progenitors within the airways relative to the recruitment of mature cells from the peripheral circulation to the development of airway eosinophilia is not known. We hypothesize that local eosinophilopoiesis may be the predominant process that drives persistent airway eosinophilia and corticosteroid requirement in severe asthmatics. Objectives In a cross-sectional study, the number and growth potential of eosinophil-lineage-committed progenitors (EoP) were assayed in 21 severe eosinophilic asthmatics, 19 mild asthmatics, eight COPD patients and eight normal subjects. The effect of anti-IL-5 treatment on mature eosinophils and EoP numbers was made in severe eosinophilic asthmatics who participated in a randomized clinical trial of mepolizumab (substudy of a larger GSK sponsored global phase III trial, MEA115575) where subjects received mepolizumab (100 mg, n = 9) or placebo (n = 8), as six monthly subcutaneous injections. Results Mature eosinophil and EoP numbers were significantly greater in the sputum of severe asthmatics compared with all other subject groups. In colony-forming assays, EoP from blood of severe asthmatics demonstrated a greater response to IL-5 than mild asthmatics. Treatment of severe asthmatics with mepolizumab significantly attenuated blood eosinophils and increased EoP numbers consistent with blockade of systemic eosinophilopoiesis. There was however no significant treatment effect on mature eosinophils, sputum EoP numbers or the prednisone maintenance dose. Conclusions and Clinical Relevance Patients with severe eosinophilic asthma have an exaggerated eosinophilopoeitic process in their airways. Treatment with 100 mg subcutaneous mepolizumab significantly attenuated systemic differentiation of eosinophils, but did not suppress local airway eosinophil differentiation to mature cells. Targeting IL-5-driven eosinophil differentiation locally within the lung maybe of relevance for optimal control of airway eosinophilia and asthma.
- Subjects :
- Adult
Male
Immunology
Comorbidity
Antibodies, Monoclonal, Humanized
Severity of Illness Index
Leukocyte Count
03 medical and health sciences
0302 clinical medicine
Eosinophilia
Eosinophilic
medicine
Humans
Immunology and Allergy
Granulocyte Precursor Cells
Anti-Asthmatic Agents
030212 general & internal medicine
Pulmonary Eosinophilia
Aged
Randomized Controlled Trials as Topic
Asthma
Myelopoiesis
Eosinophil differentiation
business.industry
Sputum
Middle Aged
respiratory system
Eosinophil
medicine.disease
Respiratory Function Tests
respiratory tract diseases
Eosinophils
Cross-Sectional Studies
Treatment Outcome
medicine.anatomical_structure
030228 respiratory system
Prednisone
Female
medicine.symptom
business
Mepolizumab
medicine.drug
Subjects
Details
- ISSN :
- 09547894
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Clinical & Experimental Allergy
- Accession number :
- edsair.doi.dedup.....e76134231b0516b395bc1588849c4d01