From the Guidelines
Irreversible airway remodeling in chronic asthma is characterized by distinct histologic features, including airway smooth muscle hypertrophy, angiogenesis, basement membrane thickening, epithelial cell destruction, increased submucosal vascularity, and subepithelial collagen deposition, as noted in a study published in the American Family Physician in 2004 1.
Key Histologic Features
The histologic features of irreversible airway remodeling in patients with chronic asthma can be summarized as follows:
- Airway smooth muscle hypertrophy
- Angiogenesis
- Basement membrane thickening
- Epithelial cell destruction
- Increased submucosal vascularity
- Subepithelial collagen deposition These changes are associated with chronic inflammation and can lead to fixed airway obstruction that does not fully respond to bronchodilators or anti-inflammatory medications.
Clinical Implications
The irreversible airway remodeling observed in chronic asthma can result in a progressive decline in lung function, despite optimal medical therapy, as discussed in a study published in the American Journal of Respiratory and Critical Care Medicine in 2000 1. This highlights the importance of early diagnosis and treatment of asthma to prevent long-term airway damage.
Pathological Features
The pathological features of asthma, including inflammatory cells, plasma exudation, edema, smooth muscle hypertrophy, mucus plugging, and shedding of epithelium, are also relevant to understanding the histologic features of irreversible airway remodeling, as described in a study published in Thorax in 1993 1. However, the most recent and highest-quality study, published in 2004 1, provides the most accurate and up-to-date information on this topic.
From the Research
Histologic Features of Irreversible Airway Remodeling
The histologic features of irreversible airway remodeling in patients with chronic asthma include:
- Goblet cell hyperplasia
- Subepithelial fibrosis
- Hyperplasia and hypertrophy of airway smooth muscle cells
- Increased airway wall thickness due to subepithelial fibrosis and hyperplasia and hypertrophy of airway smooth muscle cells and submucosal glands 2
- Collagen deposition to sub-epithelial basement membrane
- Thickening of airway mucosa
- Increase in vascularity 3
- Epithelial desquamation
- Mucosal and submucosal inflammation
- Prominent smooth muscle
- Collagen deposition below the basement membrane 4
- Altered extracellular matrix (ECM) deposition contributing to airway wall remodeling, including increased deposition of ECM proteins such as collagens, elastin, laminin, and proteoglycans around the smooth muscle 5
Key Changes in Airway Remodeling
Key changes in airway remodeling include:
- Reduction in reticular basement membrane thickness 6
- Increase in the percentage area of tissue positive for collagen 6
- Reduction in the curvature frequency of collagen fibers 6
- Increase in the percentage area positive for fibulin-1 and fibronectin 6
- No changes in elastin 6
- Destruction and subsequent remodeling of the normal bronchial architecture, manifested by a progressive decline in FEV1 4
Mechanisms of Airway Remodeling
The mechanisms of airway remodeling are closely related to progression of airway hyperresponsiveness and the severity of asthma, and are derived from airway inflammation 3. Fibroblasts or myofibroblasts play a critical role in the exaggerated deposition of collagen in asthmatic airways 2. Bone marrow-derived fibroblasts may also play a role in fibrotic remodeling in asthmatic airways 2. Airway remodeling is induced by cytokines and mediators produced in chronic allergic airway inflammation 2.