Bronchial asthma

Classification and main forms

Depending on etiological factors and developmental mechanisms, two main forms of the disease are distinguished. Both lead to bronchospasm, but are triggered by different factors.

Depending on symptom severity, the disease is divided into well-controlled (no signs), partially controlled (1–2 signs), and uncontrolled (3–4 signs).

Pathogenesis of atopic asthma

Atopic bronchial asthma develops via the mechanism of type I hypersensitivity reaction (according to the Gell and Coombs classification). A crucial role here is played by genetic predisposition, which manifests as overproduction of class E immunoglobulins (IgE), high density of Fc receptors on the surface of mast cells, and increased permeability of tissue barriers.

The development of the allergic response can be divided into several stages:

1. Activation of Th2 response. Type 2 T-helper lymphocytes overreact to the antigen and begin releasing specific cytokines. IL-4 triggers IgE synthesis, IL-5 recruits and activates eosinophils, and IL-13 stimulates excessive mucus production.
2. Sensitization. The produced IgE molecules bind to mast cell membranes, preparing them for the reaction.
3. Re-exposure. Upon re-entry of the allergen into the airways, it binds to IgE molecules. Cross-linking of receptors occurs, causing massive mast cell degranulation.
4. Bronchospasm. Histamine and a complex of leukotrienes (slow-reacting substance of anaphylaxis) are released into the tissue. Their combined action leads to a powerful spasm of the bronchial smooth muscle.
5. Amplification of inflammation. Mediators widen intercellular contacts of the epithelium, allowing new portions of the antigen to penetrate deeper into the tissues. This activates epithelial cells, which secrete chemokines, attracting new eosinophils and Th2 lymphocytes.

Pathogenesis of non-atopic and special forms

In non-atopic (endogenous) asthma, inflammation is triggered by viruses and toxic pollutant gases. Viral damage to the mucous membrane leads to a lowered threshold of vagus nerve receptor sensitivity. As a result, the slightest irritation causes persistent and severe bronchospasm. An additional factor is local immunodeficiency: reduced production of interferon-gamma by the epithelium promotes cytotoxic cell death and virus dissemination. This explains the prolonged course of acute respiratory viral infections (ARVI) in children with asthma.

Special non-allergic forms of the disease are also distinguished:

• Exercise-induced asthma. Active hyperventilation during exertion causes cooling and drying of the bronchial tree mucosa. This irritates specific cold receptors, triggering reflex bronchospasm.
• «Aspirin» asthma. Intake of nonsteroidal anti-inflammatory drugs (e.g., acetylsalicylic acid) blocks the cyclooxygenase pathway of arachidonic acid metabolism. Metabolism is forcibly «shunted» to the lipoxygenase pathway. The result is a sharp overproduction of leukotriene $D_4$, which is a potent bronchoconstrictor.

Clinical and morphological picture and outcomes

Clinically, an attack is characterized by expiratory dyspnea (difficulty exhaling), suffocation, cough, and wheezing. Outside of attacks, the patient's breathing remains clear.

At the microscopic level, eosinophilic infiltrates, epithelial damage and desquamation, neoangiogenesis (formation of new vessels), as well as an imbalance in the «protease-antiprotease» system are found in the bronchial walls. The bronchial lumens are often obturated with thick mucus.

Major outcomes and complications:

• Status asthmaticus. An extremely severe, prolonged attack (lasting from several days to weeks) that is not relieved by standard medications. It leads to progressive hypoxia, hypercapnia, metabolic acidosis, and type II respiratory failure. Without emergency care, it ends in death.
• Chronic respiratory failure. Progressive bronchial remodeling leads to patient disability.
• «Atopic march».l Regular transformation of allergic diseases in a chain: atopic dermatitis $\rightarrow$ allergic rhinitis $\rightarrow$ bronchial asthma.
• Churg-Strauss syndrome. Progression of isolated airway inflammation into a severe systemic disease — eosinophilic granulomatosis with polyangiitis (leukocytoclastic vasculitis).

Class and exam questions

What else to study on this topic

• Mechanisms of Churg-Strauss syndrome development
• Imbalance of the «protease-antiprotease» system during bronchial remodeling
• The role of the vagus nerve in the pathogenesis of endogenous asthma
• Molecular and genetic foundations of the «atopic march»
• Criteria for bronchial asthma control (clinical scale)

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.