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


OBJECTIVE
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-beta, and alpha-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 alpha-smooth muscle actin immunoreactivity and in the number of TGF-beta(+) cells in the submucosa. The only significant effect of HFA-flunisolide was a decrease in alpha-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).


CONCLUSIONS
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-beta expression. Treatment with HFA-flunisolide is associated with a significant decrease in the expression of alpha-smooth muscle actin in peripheral airways, which correlated with improvement in peripheral airway function.
Bergeron
Celine
C
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Hauber
Hans Peter
HP
Gotfried
Mark
M
Newman
Kenneth
K
Dhanda
Rahul
R
Servi
Ronald J
RJ
Ludwig
Mara S
MS
Hamid
Qutayba
Q
D000199:Actins / Q000378:metabolism; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005446:Fluocinolone Acetonide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome
D000199:Actins; D018927:Anti-Asthmatic Agents; D004338:Drug Combinations; D016212:Transforming Growth Factor beta; D005446:Fluocinolone Acetonide; C007734:flunisolide; D003094:Collagen