Pathophysiology of Asthma
Asthma is fundamentally a chronic inflammatory disease of the airways characterized by bronchoconstriction, airway edema, and increased mucus production, with distinct inflammatory patterns that differ significantly between children and adults. 1
Core Pathophysiologic Mechanisms
Airway Inflammation and Structural Changes
The primary pathologic feature is chronic airway inflammation that leads to bronchial hyperresponsiveness, variable airflow obstruction, and respiratory symptoms including wheezing, shortness of breath, chest tightness, and cough 1
The inflammatory process involves airway edema, mucus hypersecretion, and infiltration of inflammatory cells into the bronchial walls, creating the characteristic obstructive pattern 1
Airway remodeling occurs early in the disease course, even in childhood, involving structural changes to the airways that may lead to partially reversible or fixed airflow obstruction over time 2, 3
These structural changes include smooth muscle hypertrophy, subepithelial fibrosis, mucous gland hyperplasia, and alterations in the extracellular matrix that contribute to progressive airway dysfunction 2
Bronchial Hyperresponsiveness
Airway hyperresponsiveness is a fundamental characteristic where airways react excessively to various stimuli including cold air, atmospheric irritants, exercise, viral infections, allergens, and pharmacologically active chemicals 4
This hyperresponsiveness appears to be genetically determined, though the exact mechanisms remain incompletely understood 4
Two major theories explain the underlying defect: (1) abnormal beta-adrenergic receptor-adenylate cyclase function with decreased adrenergic responsiveness, and (2) increased cholinergic activity in the airways 4
Age-Specific Inflammatory Patterns
Childhood Asthma: Type 2 (T2)-High Endotype
Children predominantly exhibit T2-high asthma characterized by eosinophilic airway inflammation driven by IgE-mediated allergic responses and cytokines including IL-4, IL-5, and IL-13 1
Inflammatory involvement in children is localized more in peripheral (small) airways rather than central airways, distinguishing pediatric from adult disease 5, 2
Children with acute asthma exacerbations display a dominant eosinophilic inflammatory phenotype, contrasting sharply with the neutrophilic pattern seen in adults during acute episodes 5
Disproportionate narrowing of peripheral airways and decreased static elastic recoil predispose infants and young children to more severe airway obstruction 4
Adult Asthma: T2-Low Endotype More Common
Adults more commonly exhibit T2-low asthma featuring either neutrophilic or paucigranulocytic airway inflammation sustained by IL-8, IL-17, IL-22, and other T-cell-related cytokines 1
Adult-onset asthma is generally less quiescent than childhood-onset disease, with more frequent relapses, fewer remissions, poorer treatment response, and worse overall prognosis 1
Neutrophilic inflammation during acute exacerbations is characteristic of adult asthma, representing a fundamentally different inflammatory response than in children 5
Triggers and Risk Factors
Childhood-Specific Determinants
Viral respiratory infections are the predominant trigger for asthma symptoms and exacerbations in children, especially those under 5 years of age 1, 6
Genetic and perinatal risk factors include positive family history of asthma and atopy, genetic polymorphisms, and epigenetic markers 1
Early-life respiratory tract infections, allergic comorbidities (eczema, allergic rhinitis, food allergies), and lung function deficits are important determinants of persistent asthma from childhood into adulthood 1
Active smoking in adolescence significantly increases risk of persistent asthma symptoms 1
Adult-Onset Risk Factors
- Female gender, allergic sensitization and comorbidity, smoking, low socioeconomic status, and poor medication adherence (especially in the first years after diagnosis) are the most common risk factors for adult-onset asthma 1
Clinical Implications of Pathophysiology
Disease Heterogeneity
Asthma is a heterogeneous syndrome rather than a single disease entity, with variable clinical manifestations, therapeutic responses, and multiple triggering factors 3
The shift from phenotype to endotype classification has enabled better understanding of clinical differences and identification of targeted biological therapies for severe asthma 1
Progressive Airway Changes
In children, asthma may impair airway development and reduce maximally attained lung function, with these deficits potentially persisting into adulthood 7
Adult asthma may accelerate lung function decline and increase risk of fixed airflow obstruction, with early-onset asthma having greater impact than late-onset disease 7
Corticosteroids do not alter the natural history of the disease and may not prevent progressive decline of lung function in severe asthma, indicating that inflammation alone does not fully explain disease progression 5
Airway Obstruction Components
Airway obstruction comprises both bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucus secretion, and inflammatory cell infiltration 3
The presence of only partial reversibility in some patients indicates that structural remodeling contributes significantly to chronic airflow limitation 3