EFFECTS OF ICSs ON STRUCTURAL CHANGES
Epithelial Findings
In asthma, the bronchial epithelium is modified and appears
fragile and activated. Abnormalities include loss of the most
superficial layer of the epithelium, destruction of ciliated cells,
upregulation of growth factor release, and overexpression of
receptors such as epidermal growth factor receptors. The gross
morphology of the epithelium observed on endobronchial biopsies
has been controversial. The shedding of the epithelium reported
early by investigators looking at endobronchial biopsies
is now thought to be due at least in part to the sampling procedure
(30). Despite this potential confounding factor, the fragility
of the epithelium remains a reality.
No single study has demonstrated the ability of ICSs to restore
a complete normal epithelial layer (31). Short-term double-blind
controlled studies have investigated the effect of ICSs on various
components of epithelium in asthma. Laitinen and coworkers
were the first to report, based on a well-designed study using
electron microscopy, improvement in the epithelium in biopsies
obtained from budesonide-treated patients (32). In another
study, there was a tendency for regeneration of ciliated cells
(33). A long-term open study showed restoration of ciliated cells
when no change was observed in the epithelium integrity on
electron microscopy. Of note, there was no relationship between
cell restoration and the degree of bronchial hyperresponsiveness
(31). Immunostaining for growth factors such as granulocyte
macrophage colony-stimulating factor (GM-CSF) was signifi-
cantly decreased on epithelial cells after a 3-month treatment
with 1,000 g of beclomethasone sulfate, compared with the