Department of Pulmonology, University Hospital, Krakow, Poland.
Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland.
J Asthma. 2022 Jun;59(6):1087-1094. doi: 10.1080/02770903.2021.1903917. Epub 2021 Apr 19.
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.
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.
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.
Omalizumab was related to a decrease in all measured MMPs in BAL ( < 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 ( = 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], = 0.03). Likewise, individuals with lower concentrations of MMP-9 after omalizumab ( = 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, = 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, = 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.
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.
哮喘患者的气道炎症伴随着支气管壁细胞外基质的重建，而基质金属蛋白酶（MMPs）很可能在其中发挥作用。最近，我们报道奥马珠单抗可能会减少哮喘气道中的网状基底膜（RBM）厚度和纤维连接蛋白沉积，尽管其具体机制尚不清楚。
在本研究中，我们调查了奥马珠单抗对哮喘患者支气管肺泡灌洗液（BAL）中 MMPs 浓度的影响，同时还研究了其与组织学气道重塑变化的关系。
研究组包括 13 名接受奥马珠单抗治疗至少 12 个月的重度过敏性哮喘患者。在每个患者中，在接受生物治疗之前和之后，评估了临床和实验室参数、支气管镜检查和支气管内膜活检。在组织学中分析了支气管黏膜标本中的 RBM 厚度、纤维连接蛋白和胶原沉积。研究还包括 BAL 细胞学和 BAL 中 MMP-2、-3 和 -9 的浓度。
奥马珠单抗与 BAL 中所有 MMPs 的减少有关（ < 0.001，各指标），尽管并非每个患者都观察到这种下降。这种下降与哮喘恶化率降低和哮喘控制改善有关。有趣的是，显示至少有一种 MMP 下降的患者（ = 10，77%）的 RBM 厚度下降更为明显（-1.61 [-2.02 至 -0.6] vs. -0.06 [-0.09 至 +3.3]， = 0.03）。同样，奥马珠单抗后 MMP-9 浓度较低的患者（ = 7，58%）与 MMP-9 水平稳定的患者相比，RBM 层的减少幅度更大（-1.8 [-2.4 至 -1.14] vs. -0.13 [-0.6 至 -0.06] μm， = 0.03）。此外，后者组在接受生物治疗后胶原 I 也有更高的积累（42 [20 至 55]% vs. 0 [−10 至 20]%，分别， = 0.03）。BAL 中 MMPs 浓度较高的基线与较低的全身类固醇剂量和更好的奥马珠单抗反应有关，表现为 RBM 厚度下降。
我们的数据表明，奥马珠单抗治疗与哮喘患者亚组 BAL 中 MMPs 浓度的降低有关。这种下降与 RBM 厚度的减少有关，这可能在气道重塑中发挥有益作用。
