Uncontrolled Asthmatics Have Increased FceRI and TGF-β-positive MC Mast Cells and Collagen VI in the Alveolar Parenchyma

Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: 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.