A low MMP-9/TIMP-1 ratio suggested a predominant fibrogenic process over the inflammatory process, explaining the poor efficiency of corticosteroids. Duration of treatment and asthma severity seemed to modulate the effect of corticosteroids on MMP/TIMP. Finally, in COPD, high doses of ICS had no effect on sputum elastase, MMP-1, MMP-9, SLPI, or TIMP-1 levels.
Using high-magnification bronchovideoscopy, control subjects and patients with COPD had similar vessel densities, whereas these densities were significantly increased in asthmatic patients. A 5-year course of ICS did not decrease the density of subepithelial vessels. However, these observations were limited to the tracheal wall. In another study, a 6-week course of high dose of ICS was associated with a decrease in the number of vessels and in the total vascular area in bronchial biopsy specimens in patients with mild-to-moderate asthma. itat on
Overall, the influence of corticosteroids seems modest in remodeling (Table 3), although the effect seemed more marked with longer durations of administration. Montelukast, a cysteinyl leukotriene-1 receptor antagonist, decreases sputum eosinophils after allergen challenge in asthmatic patients. The cysteinyl leukotriene antagonist may play an important role in the pathogenesis of airway remodeling in addition to its antiinflammatory effects. Montelukast has been shown to significantly inhibit ovalbumin-induced airway smooth-muscle hyperplasia and subepithelial fibrosis in sensitized mice (Table 3). Studies on asthmatic subjects are needed, however, to confirm the antiremodeling effect of cysteinyl leukotriene-1 receptor antagonists. Antihistamines are used mostly to treat atopic diseases other than asthma. It is believed that antihistamines might be beneficial in asthma. An in vitro study shows an antiinflammatory role of antihistamines through a decrease in the migration and proliferation of eosinophils and an inhibition of mast-cell and basophil mediator release.
Table 3—Influence of Medications on Airway Structural Changes
|Variables||ICS||Leukotriene Antagonists||Short-Acting (^-Agonists||LABAs|
|Mucus glands hyperplasia||++?||++?||–||-?|
|Subepithelial collagen deposition||+- 1||+ –||–||–|
|Angiogenesis||+ +||+ +||-?||++|
|Increased smooth muscle||++?||+ +||-?||+?|
|Increased proteoglycan deposition||+ +||++?||-?||-?|
|Epithelial damage||+ + +||++?||-?||–|