Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden.
Department Experimental Medical Science, Lund University, Lund, Sweden.
Clin Exp Allergy. 2018 Mar;48(3):266-277. doi: 10.1111/cea.13092. Epub 2018 Feb 15.
Asthma has been associated with increased collagen deposition in both conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector cells in asthma and have the ability to affect collagen synthesis. However, the link between clinical control and changes in bronchial and alveolar MC phenotypes and specific collagens in controlled and uncontrolled asthma remains unknown.
To investigate MC phenotypes in correlation with deposition of specific collagen subtypes in patients with controlled and uncontrolled asthma as well as to healthy controls.
The tissue expression of IgE , FcεRI and TGF-β MCs, as well as immunoreactivity of collagen I, III and VI, was assessed using immunohistochemistry on bronchial and transbronchial biopsies from controlled asthmatics (n = 9), uncontrolled asthmatics (n = 16) and healthy controls (n = 8).
In the alveolar parenchyma, the total number of MCs, as well as the number of FcεRI MCs and pro-fibrotic TGF-β MC was significantly increased in uncontrolled asthma compared to both controlled asthma and healthy controls. The proportion of TGF-β MC correlated positively to an increased immunoreactivity of alveolar collagen VI but not collagen I and III. Collagen VI was increased in the alveolar parenchyma of uncontrolled asthmatics compared to controlled asthmatics. Controlled asthmatics had an increased deposition of alveolar collagen I. In bronchi, the immunoreactivity of collagen I was increased in both controlled and uncontrolled asthmatics while collagen III was increased only in controlled asthmatics.
Patients with uncontrolled atopic asthma have an altered pro-fibrotic MC phenotype in the alveolar parenchyma that is associated with alveolar collagen VI. The present data thus support distal lung mast cell and matrix changes as histopathological features of asthma that may be of particular clinical relevance in patients who have remaining symptoms despite conventional inhaler therapy.
哮喘与气道和肺泡实质中的胶原沉积增加有关。肥大细胞（MCs）是哮喘的关键效应细胞，具有影响胶原合成的能力。然而，在控制和未控制的哮喘中，临床控制与支气管和肺泡 MC 表型的变化以及特定胶原之间的联系仍然未知。
研究 MC 表型与控制和未控制哮喘患者以及健康对照者支气管和经支气管活检标本中特定胶原亚型沉积的相关性。
采用免疫组织化学法检测控制型哮喘患者（n=9）、未控制型哮喘患者（n=16）和健康对照者（n=8）支气管和经支气管活检标本中 IgE、FcεRI 和 TGF-β MC 以及胶原 I、III 和 VI 的免疫反应性。
在肺泡实质中，与控制型哮喘和健康对照组相比，未控制型哮喘中 MC 总数以及 FcεRI MC 和促纤维化 TGF-β MC 的数量均显著增加。TGF-β MC 的比例与肺泡胶原 VI 的免疫反应性增加呈正相关，但与胶原 I 和 III 无关。与控制型哮喘相比，未控制型哮喘患者的肺泡胶原 VI 增加。控制型哮喘患者的肺泡胶原 I 沉积增加。在支气管中，控制型和未控制型哮喘患者的胶原 I 免疫反应性均增加，而仅在控制型哮喘患者中胶原 III 增加。
未控制的特应性哮喘患者的肺泡实质中存在促纤维化的 MC 表型改变，与肺泡胶原 VI 相关。因此，这些数据支持远端肺肥大细胞和基质变化作为哮喘的组织病理学特征，对于尽管接受常规吸入器治疗仍有残留症状的患者可能具有特殊的临床意义。
