Classification and etiology
Bronchial asthma is divided into two main groups and also has several specific forms:
- Exogenous (atopic). The most frequent type, usually debuting in childhood. It is based on a genetic predisposition to atopy. Environmental allergens (pollen, house dust, food factors) act as triggers. A positive family history is often traceable, and attacks are accompanied by allergic rhinitis, eczema, or urticaria.
- Endogenous (non-reaginic). An idiopathic variant triggered by viral infections or pollutants (ozone, nitrogen dioxide, sulfur dioxide). Blood IgE levels remain normal, and family history is unremarkable. It is believed that viruses damage the mucosa and lower the sensitivity threshold of vagus nerve receptors.
- Iatrogenic (aspirin-induced). Develops in predisposed individuals upon intake of aspirin and other NSAIDs. The drugs block the cyclooxygenase pathway of arachidonic acid metabolism. As a result, the process shifts to the lipoxygenase pathway, leading to massive leukotriene release and potent bronchospasm.
- Occupational. Arises upon regular contact with occupational hazards: vapors (epoxy resins), gases (toluene), or dust (cotton, wood, platinum salts). Requires prior sensitization.
Pathogenesis and Cellular Mechanisms
Classic atopic asthma is based on an IgE-mediated type I hypersensitivity reaction. T-helper 2 lymphocytes (Th2) act as the main regulators of the process. They produce key cytokines:
- IL-4 — triggers the production of immunoglobulins E (IgE).
- IL-5 — recruits and activates eosinophils.
- IL-13 — stimulates excessive mucus production.
Synthesized IgEs fixate on the surface of mast cells. Upon inhaling an allergen, cross-linking of these antibodies occurs. Mast cells instantly degranulate, releasing mediators. This leads to the opening of intercellular mucosal junctions: the antigen penetrates deep into the tissues, contacting new mast cells. The epithelium begins to secrete chemokines, enhancing the influx of leukocytes.
A special role is played by eosinophils. They release major basic protein and cationic protein, which are directly toxic to the respiratory epithelium. Eosinophil peroxidase causes oxidative stress, and the cells themselves synthesize new portions of leukotrienes, sustaining inflammation even without re-exposure to the allergen.
Clinical Presentation and Inflammatory Mediators
A typical attack lasts from an hour to several hours. The patient experiences severe expiratory dyspnea (difficult expiration) and wheezing. Air penetrates the lungs freely, but due to bronchospasm and thick mucus, cannot exit back. Progressive hyperventilation of the distal parts develops. In the interictal period, breathing is free, although spirometry may record mild abnormalities.
Symptoms are caused by the action of mediators:
- Leukotrienes ($C_4, D_4, E_4$) cause persistent bronchoconstriction, edema, and mucus secretion.
- Acetylcholine (via the vagus nerve) directly contracts smooth muscles.
- Histamine and prostaglandin $D_2$ enhance spasm and dilate blood vessels.
The response proceeds in two phases: acute (develops in minutes) and late (starts in 4–8 hours and lasts up to a day).
If the attack is not aborted by medications (bronchodilators, corticosteroids) and drags on for days or weeks, status asthmaticus (status asthmaticus) occurs. This is a dangerous complication with severe hypoxia, hypercapnia, and acidosis, which can become fatal. However, in most cases, the chronic course of the disease leads to disability rather than death.
Pathology and Remodeling
Morphological changes are best studied in patients who died from status asthmaticus. Macroscopically, the lungs are sharply hyperinflated due to accumulated air, areas of minor atelectasis are visible, and bronchi are plugged with viscous mucous plugs.
Microscopically, Curschmann spirals (twisted strands of desquamated epithelium) and Charcot-Leyden crystals (clusters of crystallized eosinophil proteins) are found in the mucus. Bronchial walls are densely infiltrated by eosinophils.
Chronic inflammation (Th2 type) inevitably leads to airway remodeling. This process may start several years before the first clinical symptoms. It is based on a genetic predisposition (e.g., expression of the ADAM33 gene by fibroblasts and smooth muscle cells).
Components of remodeling:
- Thickening of the basement membrane of the bronchial epithelium.
- Chronic edema and infiltration of the mucosa by mast cells and eosinophils.
- Hypertrophy of submucosal glands.
- Hypertrophy of smooth muscle cells and collagen deposition under the epithelium.
The abbreviation SEC helps remember the triad of microscopic findings in asthma: Spirals of Curschmann (desquamated epithelium), Eosinophils (main inflammatory cells), Charcot-Leyden crystals (eosinophil proteins).
Class and exam questions
How does obstruction in asthma fundamentally differ from COPD?
The main difference is the reversibility of the process. In bronchial asthma, obstruction is reversible (abated spontaneously or by drugs), whereas in COPD, airway narrowing is primarily irreversible.
Why does an asthma attack cause dyspnea specifically on expiration?
Air penetrates the lungs relatively easily during inhalation, but due to bronchospasm and obstruction of bronchioles by viscous mucus, it cannot exit back. This leads to expiratory dyspnea and progressive lung hyperinflation.
How can aspirin provoke an attack?
In predisposed individuals, NSAIDs block the cyclooxygenase pathway of metabolism. As a result, the entire cascade shifts to the lipoxygenase pathway, causing massive leukotriene production and, consequently, severe bronchospasm.
What else to study on this topic
- The role of interleukins (IL-4, IL-5, IL-13) in the development of the allergic response
- Mechanisms of formation of the early and late phases of the asthmatic response
- Toxic effect of eosinophil proteins on the respiratory epithelium
- Pathogenesis of the non-reaginic (non-atopic) form of the disease
- Genetic factors and the role of the ADAM33 gene in bronchial remodeling
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