title: Distinct leucocyte redistribution after glucocorticoid treatment among difficult-to-treat asthmatic patients.
abstract: Difficult-to-treat asthma (DTA) represents a heterogeneous subgroup of asthma. Up to now, the lack of specific diagnosis not only complicates appropriate specification and control of asthma, but also makes targeted research difficult. The aim of this study is to categorize this heterogeneous group of DTA patients (n=27; referring to the GINA guidelines) based on the distinct leucocyte redistribution (LR) after glucocorticoid (GC) treatment. Furthermore, the effect of adjuvant therapies was investigated for its impact on LR. The frequency of CD3+, CD4+, CD8+, CD14+, CD19+ and NK cells was analysed in peripheral blood before and 3 h after systemic GC treatment, along with the markers of activation HLA-DR and CD25. Within 3 h of GC administration, a significant average decrease of 16% in CD3+CD4+ (P < or = 0.001) and a 12% increase in NK-cell frequency (P < or = 0.001) clearly distinguished two groups of patients: LR-responsive and LR-unresponsive patients. The CD3+CD8+ T-cell number and activation marker remained unchanged. Patients who received adjuvant therapy, such as methotrexate or interferon-alpha, because of poor clinical response to GC showed an LR similar to that showed by responsive patients. DTA patients comprise at least two immunologically distinct groups: patients showing an immediate decrease in CD3+CD4+ T cells and an increase in NK cells following GC administration and patients lacking an immediate change. Analysis of LR not only may allow the identification of immunologic steroid resistance, but also may be of value for immunologic determination of effective steroid doses.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Karagiannidis
authors.forename: B
authors.initials: B
authors.lastname: Rückert
authors.forename: G
authors.initials: G
authors.lastname: Hense
authors.forename: G
authors.initials: G
authors.lastname: Willer
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: K
authors.initials: K
authors.lastname: Blaser
authors.forename: C B
authors.initials: CB
authors.lastname: Schmidt-Weber
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D005938:Glucocorticoids; D011239:Prednisolone