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

Bergeron, Celine; Hauber, Hans Peter; Gotfried, Mark; Newman, Kenneth; Dhanda, Rahul; Servi, Ronald J.; Ludwig, Mara S.; Hamid, Qutayba

doi:10.1016/j.jaci.2005.07.029

« Previous Next »The Journal of Allergy and Clinical Immunology
Volume 116, Issue 5 , Pages 983-989, November 2005

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

Celine Bergeron, MD, MSc
- From the Meakins-Christie Laboratories, McGill University, Montreal
Hans Peter Hauber, MD
- From the Meakins-Christie Laboratories, McGill University, Montreal
Mark Gotfried, MD
- Pulmonary Associates, Phoenix
Kenneth Newman, MD
- Forest Laboratories, New York
Rahul Dhanda, PhD
- Forest Laboratories, New York
Ronald J. Servi, DO
- Pulmonary Associates, Phoenix
Mara S. Ludwig, MD
- From the Meakins-Christie Laboratories, McGill University, Montreal
Qutayba Hamid, MD, PhD
- From the Meakins-Christie Laboratories, McGill University, Montreal
- Reprint requests: Qutayba Hamid, MD, PhD, Meakins-Christie Laboratories, McGill University, 3626 St-Urbain Street, Montreal, Quebec, Canada, H2X 2P2.

Received 4 April 2005; received in revised form 20 July 2005; accepted 25 July 2005. published online 04 October 2005.

Montreal, Quebec, Canada, Phoenix, Ariz, and New York, NY

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 (r_s = −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.

Key words: Asthma, flunisolide, hydrofluoroalkane, inhaled corticosteroids, remodeling, small airway, peripheral airways

Abbreviations used: ATS, American Thoracic Society, FEF_25-75, Forced expiratory flow at 25% to 75% of vital capacity, HFA, Hydrofluoroalkane, ICS, Inhaled corticosteroid