Pathophysiology of RSV Bronchiolitis
RSV bronchiolitis is characterized by acute inflammation, edema and necrosis of epithelial cells lining the small airways, increased mucus production, and bronchospasm, leading to bronchiolar obstruction through a combination of epithelial destruction, inflammatory cell infiltration, and debris accumulation. 1
Primary Pathologic Mechanisms
Epithelial Cell Damage and Necrosis
- Circumferential infection of small bronchiole epithelium occurs, with basal cells characteristically spared from infection 2
- Both type 1 and type 2 alveolar pneumocytes become infected during RSV bronchiolitis 2
- Necrosis of respiratory epithelium is a hallmark feature, with columnar cell cytopathology in the bronchioles directly impacting the development of bronchiolar obstruction 3, 4
- Epithelial cell debris contributes significantly to airway obstruction 2
Inflammatory Response
- Inflammatory infiltrates center on bronchial and pulmonary arterioles, consisting primarily of CD69+ monocytes, CD3+ double-negative T cells, CD8+ T cells, and neutrophils 2
- Submucosal cellular infiltration with lymphocytic infiltration occurs throughout the small airways 3, 5
- Most inflammatory cells concentrate submuscular to the airway, but many cells traverse the smooth muscle into the airway epithelium and lumen 2
- Neutrophil distribution is predominantly between arterioles and airways, while mononuclear cell distribution occurs in both airways and lung parenchyma 2
Airway Obstruction
- Airway obstruction results from epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema 2
- Dense plugs of debris form in the bronchioles, causing subsequent bronchiolar obstruction 3
- Excessive mucus production contributes to the obstructive process 1, 3
- Compression from hyperplastic lymphoid follicles compounds the obstruction 2
Physiologic Consequences
Respiratory Mechanics
- Functional residual capacity (FRC) increases due to air trapping 5
- Dynamic compliance falls as a result of small airway obstruction 5
- Bronchospasm contributes to airway narrowing, though failure to respond to bronchodilators suggests muscle spasm plays a relatively minor role compared to inflammatory obstruction 1, 5
Immunologic Mechanisms
- IgE-mediated reactions and release of inflammatory mediators may exacerbate acute obstruction 3
- IgE antibodies to RSV and leukotriene C4 are found more frequently in respiratory secretions of infants who wheeze during and after bronchiolitis 5
- These immunologic responses may contribute to chronic obstructive pulmonary dysfunction following acute infection 3
Clinical Manifestations of Pathophysiology
The pathophysiologic changes manifest clinically as tachypnea, wheezing, crackles, use of accessory muscles, and nasal flaring 1. The inflammatory obstruction and epithelial damage explain why affected infants become increasingly dyspneic and hypoxic for 3-4 days before spontaneous improvement occurs 5. The predominance of inflammatory debris over bronchospasm explains the limited efficacy of bronchodilator therapy in this condition 5.