Asthma Overview and Severity

Asthma Overview

• Asthma is a chronic inflammatory airway disorder causing recurrent bronchospasm.
• Symptoms include wheezing, breathlessness, chest tightness, and cough, especially at night or early morning.
• Key characteristics include intermittent and reversible airway obstruction.
• Chronic inflammation with eosinophils and hyperreactivity of bronchial smooth muscle cells are also present.
• Increased mucus secretion is another key feature.

Severe Airway Hyperreactivity

• In severe cases, even trivial stimuli can trigger attacks.
• Diverse cells play a role in the inflammatory response, notably eosinophils, mast cells, macrophages, lymphocytes, neutrophils, and epithelial cells.

Asthma Incidence

• Asthma prevalence has significantly increased in affluent countries over the past few decades.
• One hypothesis for this trend is the hygiene hypothesis, proposing a lack of exposure to microbes and allergens in early childhood leads to immune system hyperreactivity later in life.
• However, no mechanistic evidence supports this hypothesis.

Asthma Pathogenesis

• Genetic predisposition to type I hypersensitivity (atopy) contributes.
• Chronic and acute inflammation of the airways plays a key role, including differing patterns (eosinophilic, neutrophilic, etc.).
• Bronchial hyperresponsiveness to various stimuli (e.g., respiratory infections, environmental factors, allergens) is crucial.
• Asthma can be classified as atopic (allergy-related) or nonatopic.

Atopic Asthma

• The most common form of asthma, typically starting in childhood.
• Often associated with a positive family history of atopy (allergy) or asthma.
• Allergens like dust, pollen, animal dander, or food, or infections can trigger attacks.
• Diagnosis relies on episodic symptoms and airflow improvement with bronchodilators; skin testing for allergens and immunoassays for IgE antibodies.

Type 2 Helper T Cells (Th2)

• Activated Th2 cells release cytokines (e.g., IL-4, IL-5, IL-13) triggering a cascade of events:
• Increased IgE production from B cells, sensitizing mast cells to allergens.
• Increased eosinophil recruitment and activation leading to mucus production.
• The process involves IgE binding to Fc receptors on mast cells resulting in inflammatory mediator release.

Early and Late Phase Reactions

• Early phase: characterized by bronchoconstriction, increased mucus and vasodilation, caused by mediators like histamine and leukotrienes.
• Late phase: inflammatory response involving Th2 cells, eosinophils and other leukocytes.
• Both phases lead to structural changes known as airway remodeling

Airway Remodeling

• Long-term inflammation can cause changes in airway structure including smooth muscle hypertrophy, mucus gland increase, vascular changes, and subepithelial fibrosis.

Nonatopic Asthma

• Patients usually lack evidence of allergen sensitization.
• Respiratory infections (e.g., viruses) and environmental triggers (e.g., air pollutants, cold air) are more common triggers.
• Similar symptoms and treatment options to atopic asthma, though less common.

Drug-Induced Asthma

• Aspirin is the most common trigger.
• A complex mechanism involving prostaglandin abnormalities is likely.
• Occupational exposure (e.g. epoxy resin, organic/chemical dusts) can trigger similar reactions.

Asthma Morphology

• Lungs are inflated.
• Thick, tenacious mucous plugs ("Curschmann spirals"), eosinophils, and crystals ("Charcot-Leyden crystals") are common findings.
• Airway thickening, increased vascularity, and mucus gland enlargment are characteristic.

Asthma Clinical Features

• Severe dyspnea (shortness of breath) and wheezing are key symptoms due to bronchoconstriction and mucus plugging.
• Episodes typically last for hours to days.
• Patient intervals between attacks may be symptom-free but show subtle impairments on pulmonary function testing.

Asthma Treatment

• Mild episodic asthma: primarily treated symptomatically with bronchodilators (e.g., beta-agonists), and glucocorticoids, sometimes with leukotriene inhibitors.
• Severe cases: Treatments may include anti-IgE therapy (blocks IgE action) or therapies targeting IL-4, IL-5, and IgE, as well as other specific immune mediators.