Small Airways (Bronchioles) Are Most Affected by Asthma
The small airways, particularly the bronchioles, are the primary site of airway obstruction and inflammation in asthma. 1 This area of the respiratory tree is most significantly impacted by the pathophysiological processes that characterize asthma.
Pathophysiology of Airway Involvement in Asthma
Small Airways as the Primary Site
- The inflammation in asthma involves multiple cells and cellular elements, including mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells 1
- Small airways (bronchioles) with an internal diameter of 2 mm or less that do not contain cartilage in their walls are the major site of obstruction in asthma 2, 3
- These small airways contribute only about 10% of total airway resistance in healthy individuals but become the predominant site of airflow limitation in asthma 3
Inflammatory and Structural Changes
- Inflammation leads to fibrosis and smooth muscle hyperplasia in the walls of bronchioles 2
- The respiratory bronchioles show fibrosis that extends into the alveolated portions of the walls and alveolar ducts 2
- This differs from smoking-related damage, which primarily involves the non-alveolated portions of the first generation of respiratory bronchioles 2
Evidence Supporting Small Airways as Primary Site
Physiological Evidence
- Small-airways dysfunction associates with:
- Worse control of asthma
- Higher numbers of exacerbations
- Presence of nocturnal asthma
- More severe bronchial hyperresponsiveness
- Exercise-induced asthma
- Late-phase allergic response 4
Pathological Evidence
- Histologically, inflammation and airway fibrosis characterize asthma-related small airway disease 2
- A major site of inflammatory mediator deposition is in the walls of membranous and respiratory bronchioles 2
- These small airway lesions are the likely anatomic basis for airflow limitation in asthmatic individuals 2
Distribution of Inflammation Throughout Airways
While small airways are the primary site affected, it's important to note that:
- Both the small and large airways are involved in inflammation and remodeling in asthma 3
- The distribution of different inflammatory cells across the airway wall varies in both large and small airways 3
- Inflammation can extend to the alveoli surrounding small airways in asthma 3
Clinical Implications
- Early recognition of small-airways dysfunction is important as it enables timely treatment targeting the small airways 4
- Inhaled treatment that targets the small airways may be more effective than treatment deposited more proximally 3
- Small-particle aerosols may provide better management by reaching the distal airways 5
Pitfalls in Assessment and Management
- Small airways dysfunction can already be present in patients with mild asthma but may be overlooked 4
- Traditional pulmonary function tests may not adequately detect small airways dysfunction since they contribute minimally to total airway resistance 3
- Noninvasively measuring the function of the small airways in isolation is difficult 3
In conclusion, while asthma affects the entire respiratory tree to varying degrees, the small airways (bronchioles) are the most significantly affected area and represent the primary site of airflow obstruction and inflammation in asthmatic patients.