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Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction


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Khor, YH, Feltis, BN, Reid, DW, Ward, C, Johns, DP, Wood-Baker, R and Walters, EH 2007 , 'Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reduction' , Clinical and Experimental Allergy, vol. 37, no. 8 , pp. 1189-1198 , doi: 10.1111/j.1365-2222.2007.02762.x.

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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 lymphoctyes),
bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of highdose
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 CD41/CD81 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.

Item Type: Article
Authors/Creators:Khor, YH and Feltis, BN and Reid, DW and Ward, C and Johns, DP and Wood-Baker, R and Walters, EH
Keywords: asthma, clinical deterioration, cytokines, ICS back-titration, inflammation
Journal or Publication Title: Clinical and Experimental Allergy
Publisher: Wiley-Blackwell Publishing Ltd.
ISSN: 0954-7894
DOI / ID Number: 10.1111/j.1365-2222.2007.02762.x
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