Introduction: Airway inflammation in asthma is accompanied by reconstruction of the bronchial wall extracellular matrix that most likely occurs with a contribution of matrix metalloproteinases (MMPs). Recently we have reported that omalizumab may decrease reticular basement membrane (RBM) thickness together with fibronectin deposits in asthmatic airways, although mechanisms involved are unknown.
Objective: In the present study, we have investigated the impact of omalizumab on MMPs concentrations in bronchoalveolar lavage fluid (BAL) of asthmatic subjects in relation to airway remodeling changes in histology.
Patients and methods: The study group consisted of 13 severe allergic asthmatics treated with omalizumab for at least 12 months. In each subject, clinical and laboratory parameters, bronchoscopy with BAL, and endobronchial biopsy were evaluated before and after the biologic therapy. RBM thickness, fibronectin, and collagen deposits in bronchial mucosa specimens were analyzed in histology. The investigations also included BAL cytology and BAL concentrations of MMP-2, -3, and -9.
Results: Omalizumab was related to a decrease in all measured MMPs in BAL (p < 0.001, each), although such declines were not observed in each patient. The depletions were associated with a lower asthma exacerbation rate and better asthma control. Interestingly, patients who showed a decline in at least one MMP (n = 10, 77%) were characterized by a higher decrease in the RBM thickness (-1.61 [-2.02 to -0.6] vs. -0.06 [-0.09 to +3.3], p = 0.03). Likewise, individuals with lower concentrations of MMP-9 after omalizumab (n = 7, 58%) had a greater reduction in the RBM layer as compared to those with steady MMP-9 levels (-1.8 [-2.4 to -1.14] vs. -0.13 [-0.6 to -0.06] μm, p = 0.03). Moreover, the latter group also had unfavorable higher collagen I accumulation after biologic (42 [20 to 55] vs. 0 [-10 to 20]%, respectively, p = 0.03). Higher concentrations of MMPs in BAL at baseline were related to the lower systemic steroid dose and better omalizumab response concerning the decline in RBM thickness.
Conclusion: Our data suggest that omalizumab therapy is associated with decreased BAL MMPs concentration in the subgroup of asthma patients. The decline was linked with a reduction in the RBM thickness what might play a beneficial role in airway remodeling.
Keywords: Asthma; matrix metalloproteinases; omalizumab; remodeling.