Structural Changes in Airway Diseases: Profibrotic effect

This finding has led to the hypothesis that ICS might be effective in reducing RBM thickness when used for a long period of time and at a higher dose. In a group of patients with moderate-to-severe asthma, no significant differences were seen in types I and III collagen and TGF-^ immunoreactivity after a 2-week course of oral corticosteroids. The inability of ICS to inhibit TGF-^ expression may be responsible for the persistent fibrosis seen in this group of patients with severe asthma. The fact that doses of  ICS could have been too low and the duration of treatment could have been too short has been suggested as an explanation for the poor response.
Finally, Ward and coworkers reported that the variability in AHR can be partly explained by the RBM thickness, the number of BAL epithelial cells, and BAL eosinophils. Part of the improvement in AHR provided by ICS was related to early changes in inflammation, but a progressive and larger improvement was associated with subsequent changes in airway remodeling. Link

MMP/TIMP: As an imbalance in MMP/TIMP can lead to fibrosis, some studies addressed the effects of corticosteroids on MMP/TIMP. Decreased MMP-9 expression and increased TIMP-1 expression were observed on bronchial biopsy specimens after a 6-month ICS treatment in patients with mild asth-ma, suggesting that ICS can effect the MMP/ TIMP ratio leading to a profibrotic effect. However, ICS decreased BAL fluid TIMP-1 in a subgroup of patients with moderate-to-severe asthma treated with corticosteroids when compared with noncorticosteroid-treated patients with mild-to-moderate asthma. In another study, 4 weeks of ICS treatment did not affect MMP-9 or TIMP-1 levels in sputum and BAL fluid of patients with mild asthma patients. A correlation has been made between oral corticosteroid responsiveness and blood MMP-9/ TIMP-1 ratio in patients with moderate-to-severe asthma.

This entry was posted in Pulmonary Function and tagged airway inflammation, airway remodeling, antiasthmatic therapy, asthma, COPD, corticosteroids, cystic fibrosis.