Asthma diagnosis and treatment
Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: Effect of hydrofluoroalkane-flunisolide

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Background

We have shown previously that inflammation in asthma is not restricted to central airways but can also be demonstrated in peripheral airways. It is not clear whether inflammation of the peripheral airways is associated with structural changes and whether this remodeling process can be modulated by deposition of inhaled corticosteroids (ICSs).

Objectives

To compare remodeling in peripheral and central airways and to investigate the effects of hydrofluoroalkane (HFA)-ICS on remodeling at these sites.

Methods

Transbronchial and endobronchial biopsies were obtained from 12 patients with mild to moderate asthma before and after a 6-week course of HFA-ICS (flunisolide). Total collagen deposition, expression of collagen III, TGF-β, and α-smooth muscle actin were examined by using Van Gieson staining and immunocytochemistry, respectively.

Results

Total collagen occupied 37.7% of the wall area of peripheral airways, compared with 54.5% of the wall area of central airways (P = .04). There was no significant difference in central versus peripheral airways for collagen III or α-smooth muscle actin immunoreactivity and in the number of TGF-β+ cells in the submucosa. The only significant effect of HFA-flunisolide was a decrease in α-smooth muscle actin area in peripheral airways (13.4% vs 4.6%; P = .01) that correlated with the percentage increase in forced expiratory flow at 25% to 75% of vital capacity (rs = −1.00; P = .00).

Conclusion

Our data show that there is a considerable degree of airway remodeling in peripheral airways in patients with asthma and confirm the inability of ICS to modulate collagen deposition and TGF-β expression. Treatment with HFA-flunisolide is associated with a significant decrease in the expression of α-smooth muscle actin in peripheral airways, which correlated with improvement in peripheral airway function.

Section snippets

Study design

A single-center, open-label study was conducted in adult patients with asthma to evaluate the effect of inhaled small-particle corticosteroids (HFA-flunisolide) on peripheral lung inflammation and remodeling. The study was performed in full compliance with Food and Drug Administration Guidelines for Good Clinical Practice and was approved by the institutional review board. Patients who met the inclusion and exclusion criteria had a baseline bronchoscopy, during which transbronchial and

Collagen deposition in peripheral and central airways

At baseline, there was a significant deposition of total collagen and collagen III in both peripheral and central airways. The percentage of the airway wall occupied by collagen as identified by Van Gieson stain for total collagen was significantly higher in central airways than in peripheral airways (54.5% ± 5.6% vs 37.7% ± 6.9%; P = .04; Fig 1, A). However, there were no significant differences between the percentage of the airway stained for collagen III in central airways compared with

Discussion

The current study describes the extent of collagen deposition and the smooth muscle mass in asthmatic peripheral airways by using transbronchial biopsies and addresses the effect of treatment with HFA-flunisolide on them. We observed structural similarities between central and peripheral airways. Both categories of airway had comparable amounts of collagen III deposition and α-smooth muscle actin. However, total collagen deposition was significantly higher in central airways compared with

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    Supported by Canadian Institutes of Health Research, Forest Laboratories.

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