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Bronchial Asthma

*Asthma bronchiale*

For medical students2 min readUpdated 2026-10-10

Bronchial asthma is a chronic inflammatory and allergic respiratory disease. Its primary clinical hallmark is recurrent attacks of breathlessness characterized by expiratory dyspnea (difficulty exhaling). The underlying pathology is chronic inflammation of the airway walls, leading to marked bronchial hyperresponsiveness.

Reaction TypeImmediate-type hypersensitivity (Type I) mediated by IgE antibodies

Common TriggersCold air, pollen, house dust, sulfur dioxide, infections

Key CytokineInterleukin-4 (IL-4), which drives immunoglobulin E synthesis

Therapeutic BasisBronchodilators for spasm relief and anti-inflammatory agents

Disease Development and the Role of Inflammation

The pathogenesis of bronchial asthma is rooted in a chronic inflammatory process. Persistent inflammation causes damage to the airway epithelium. This results in bronchial hyperresponsiveness — an abnormally high sensitivity of the bronchi to various stimuli.

The pathological cascade in the bronchial wall includes several sequential steps:

Vasodilation and increased vascular permeability.
Marked mucosal edema.
Migration of leukocytes (predominantly eosinophils) into the bronchial tissue.
Release of specific "eosinophilic proteins" by activated eosinophils, which exert cytotoxic effects and further disrupt the epithelial layer.

Immunological Phase: Mechanisms of Sensitization

The disease develops via an immediate-type hypersensitivity mechanism. Initial antigen contact triggers a complex cellular cascade:

A macrophage phagocytoses and presents the foreign antigen.
With the participation of interleukin-1 (IL-1), T-helper cells are activated and differentiate into Th2 cells.
T-helper cells and macrophages begin secreting regulatory cytokines. IL-3 stimulates mast cell proliferation, while IL-5 increases the eosinophil population.
Interleukin-4 (IL-4) plays a pivotal role. It induces B lymphocytes to differentiate into plasma cells and synthesize IgE class antibodies.
Free IgE immunoglobulins circulate in the blood and bind to high-affinity receptors (FcεRI) on mast cell membranes. This establishes organismal sensitization.

Pathochemical Phase: Degranulation and Mediators

When the antigen re-enters the body, it binds to IgE molecules already fixed on mast cells. This triggers cellular activation and degranulation — the massive release of preformed biologically active substances into the extracellular space.

Concurrently, arachidonic acid metabolism is initiated within the mast cell. The enzyme phospholipase A2 cleaves it from cell membrane phospholipids, after which the process proceeds along two pathways:

Cyclooxygenase (COX-2) pathway: Prostaglandins are synthesized.
5-Lipoxygenase (5-LOX) pathway: Cysteinyl leukotrienes are generated.

All released mediators are divided into two groups. Bronchoconstrictor agents (histamine, platelet-activating factor, and leukotrienes forming the "slow-reacting substance of anaphylaxis") provoke acute bronchospasm. Chemotactic factors (leukotriene B4 and platelet-activating factor) recruit additional waves of eosinophils, sustaining inflammatory infiltration.

Effector Phase and Pharmacological Intervention

Airway tone directly depends on receptors located on bronchial smooth muscle cells. Stimulation of $M_3$ muscarinic receptors, adenosine $A_1$ receptors, and leukotriene receptors leads to luminal narrowing (bronchoconstriction). Conversely, stimulation of $\beta_2$-adrenergic receptors induces smooth muscle relaxation (bronchodilation).

To manage acute attacks, bronchodilators targeting these pathways are employed:

$\beta_2$-agonists: Stimulate $\beta_2$ receptors, actively dilating the bronchi.
Anticholinergics (Muscarinic antagonists): Block $M_3$ receptors, eliminating the cholinergic component of bronchospasm.
Methylxanthines (theophylline): Act as adenosine receptor antagonists and block $A_1$ receptors.

Additionally, direct-acting myotropic antispasmodics are used to influence smooth muscle tone.

Mnemonic

To easily remember the sites of action for bronchodilators, use the rule "Stimulate the relaxer, block the constrictor": drugs stimulate $\beta_2$-adrenergic receptors ($\beta_2$-agonists) and block $M_3$ muscarinic receptors (anticholinergics) alongside $A_1$ adenosine receptors (methylxanthines).

Frequently asked questions

What are the daily doses and regimens of inhaled glucocorticosteroids in severe bronchial asthma?

In severe bronchial asthma, medium or high doses of inhaled glucocorticosteroids (ICS) are used in combination with long-acting beta-agonists (LABA). This treatment corresponds to step 5 therapy.

While exact daily dosages for severe forms vary, known dosing options for fixed combinations include:

Budesonide + formoterol — 100/6 mcg (very low doses).
Budesonide + formoterol — 200/6 mcg (low doses).

Drugs can be administered via a single inhaler regimen (MART therapy), where one inhaler is used for both maintenance therapy and symptom relief.

What international treatment steps according to GINA guidelines are distinguished in the management of bronchial asthma?

According to GINA guidelines, five treatment steps are identified for managing bronchial asthma, assigned based on disease severity.

Steps 1 and 2 — Used for mild asthma (e.g., low-dose ICS and formoterol as needed).
Steps 3 and 4 — Prescribed for moderate asthma to achieve good control.
Step 5 — Required to control severe asthma (includes medium to high doses of ICS combined with long-acting beta-agonists).

What is bronchial hyperresponsiveness and why does it occur?

It is a pathologically heightened sensitivity of the airways to irritants (cold air, allergens). It develops as a consequence of chronic inflammation and damage to the bronchial epithelium by eosinophilic cytotoxic proteins.

What role does interleukin-4 (IL-4) play in pathogenesis?

IL-4 is a key mediator of sensitization. It stimulates B lymphocytes to produce class E immunoglobulins (IgE) and promotes the expression of IgE receptors on the membranes of mast cells and basophils.

How is the "slow-reacting substance of anaphylaxis" formed?

It consists of cysteinyl leukotrienes synthesized within mast cells. The process begins with the cleavage of arachidonic acid by phospholipase A2, after which the enzyme 5-lipoxygenase (5-LOX) converts it into leukotrienes.

Go deeper

Differences between high-affinity ($Fc\epsilon RI$) and low-affinity ($Fc\epsilon RII$) IgE receptors.
Detailed mechanism of action of myotropic antispasmodics.
The role of platelet-activating factor (PAF) in bronchoconstriction and chemotaxis.
Specific functions of prostaglandins ($E_2, I_2, D_2$) in the inflammatory cascade.