From the Guidelines
Asthma is a chronic inflammatory disorder of the airways characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation, as defined by the expert panel report 3 (EPR-3) guidelines 1. The pathophysiology of asthma involves a complex interplay of multiple cells and cellular elements, including mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells, which contribute to airway inflammation and hyperresponsiveness.
- Airflow limitation is caused by various changes in the airway, including bronchoconstriction, airway hyperresponsiveness, and airway edema, all of which are influenced by airway inflammation.
- The inflammation in asthma is typically driven by type 2 immune responses involving T-helper 2 cells, mast cells, and eosinophils, which release inflammatory mediators like interleukins, leukotrienes, and histamine.
- When exposed to triggers such as allergens, respiratory infections, exercise, or irritants, these sensitized airways react excessively, causing bronchospasm, further inflammation, and mucus hypersecretion.
- The resulting airway narrowing causes the classic symptoms of wheezing, coughing, chest tightness, and shortness of breath, which can be assessed using spirometry to demonstrate obstruction and reversibility 1.
- Over time, chronic inflammation can lead to airway remodeling with structural changes, including subepithelial fibrosis, smooth muscle hypertrophy, and angiogenesis, which may result in some degree of fixed airflow obstruction.
- Recent studies have also highlighted the potential role of oral macrolide therapy in reducing airway inflammation in asthma, particularly in patients with severe asthma or those who are difficult to manage with conventional treatments 1.
From the Research
Pathophysiology of Asthma
The pathophysiology of asthma is characterized by:
- Chronic inflammation of the lower respiratory tract 2
- Airway inflammation, smooth-muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema 3, 4
- Increased numbers of activated eosinophils and mast cells in the airways, even in patients with mild disease 5
- Presence of proinflammatory cytokines, such as GM-CSF, interleukin(IL)-3 or IL-5, which promote the presence and survival of inflammatory cells 5
- Release of potent bronchoconstrictor mediators, such as cysteinyl leukotrienes, which contribute to airway narrowing in asthma 5
Key Features of Asthma
Asthma is a:
- Chronic inflammatory disorder of the airways resulting in hyperreactivity and recurrent episodes of wheezing, chest tightness, or coughing 3, 4
- Heterogenic condition that is underdiagnosed and undertreated despite available effective treatments 2
- Condition that features variable airway obstruction and bronchial hyperresponsiveness 2
- Condition that can be classified into different subtypes, including intermittent or persistent, and allergic or nonallergic 3, 4
Cellular and Molecular Mechanisms
The pathophysiology of asthma involves:
- Th2 lymphocytes, whose cytokine secretion leads to mast cell stimulation, eosinophilia, leukocytosis, and enhanced B-cell IgE production 6
- Multiple cell types and inflammatory mediators, including eosinophils, mast cells, and T-lymphocytes 6, 5
- Airway structural changes caused by persisting inflammation, such as airway epithelial damage, or altered smooth muscle function or volume 5