Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction.
BACKGROUND
Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4-8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration.


METHODS
Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphocytes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28).


RESULTS
After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4(+)/CD8(+) T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines.


CONCLUSIONS
These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored.
Khor
Y H
YH
Respiratory Research Group, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. yhkhor@utas.edu.au
Feltis
B N
BN
Reid
D W
DW
Ward
C
C
Johns
D P
DP
Wood-Baker
R
R
Walters
E H
EH
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001992:Bronchoalveolar Lavage Fluid; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011657:Pulmonary Eosinophilia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013147:Spirometry
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; C508599:IL5 protein, human; D015848:Interleukin-5