Asthma: Types and Characteristics

• Asthma is a chronic inflammatory disease characterized by recurrent attacks of widespread broncho-constriction, known as airway hyper-responsiveness, in response to various stimuli.
• Asthma is a reversible obstructive pulmonary disease, either spontaneously or with treatment.

Types of Asthma

• Atopic (immunological, allergic) asthma and Non-atopic (non-immunological, non-allergic) asthma are two types of asthma
• Drug-induced asthma is caused by NSAIDs, especially Aspirin, and is associated with nasal polyps and chronic bronchitis.
• Occupational asthma is associated with fumes (plastics), organic and chemical dust (wood, cotton), gases and other chemicals (formaldehyde).

Atopic Asthma

• More common, typically affects children and young individuals.
• Family history of asthma or atopic disease is usually present.
• Preceding allergic illness (atopy) is present.
• Pathogenesis involves a Type I hypersensitivity reaction.
• IgE levels in the serum are elevated.
• Common allergens include inhaled allergens such as house dust, animal dander, plant pollens, and fungi.

Non-Atopic Asthma

• Less common, can occur at any age, mainly in late adulthood.
• Family history of asthma or atopic disease is absent.
• Preceding allergic illness (atopy) is absent.
• Pathogenesis involves hyperirritability of the bronchial tree, but the exact mechanism is unclear.
• IgE levels in the serum are normal.
• Triggers include infection, exposure to cold, physical exercise, anxiety, emotions, aspirin, and inhaled irritants.

Risk Factors of Asthma

• Environmental allergens
• Exercise, hyperventilation
• Viral respiratory infections
• Exposure to cold
• Aspirin or (NSAID) hypersensitivity
• Inhaled air pollutants such as smoking
• Occupational exposure including fumes (plastics), organic and chemical dusts (wood, cotton), gases and other chemicals (formaldehyde)

Pathogenesis of Type 1 Hypersensitivity Reaction (Atopic Asthma)

• Initial allergen exposure leads to macrophages presenting allergens to CD4 T cells, which differentiate into CD4 T2 cells.
• CD4 T2 cells produce specific cytokines such as IL-4, IL-5, and IL-13.
• IL-4 stimulates B lymphocytes to mature into plasma cells.
• Plasma cells secrete IgE specific to the allergen, which binds to mast cells.
• Mast cells degranulate and release histamine and other mediators.
• Subsequent exposure to the allergen causes it to bind directly to IgE on the surface of mast cells, leading to degranulation and the release of histamine and other mediators, causing manifestations of the early phase.
• IL-13 attracts other cells and releases other mediators that cause the late phase.

Phases of Asthma

• Early phase starts within 30-60 minutes after exposure to the allergen.
• Late phase starts hours (5-6 hours) after exposure.

Mediators in Early Phase

• Histamine
• Leukotrienes
• Platelet-activating factor

Effects of Early Phase Mediators

• Vasodilation (VD)
• Edema due to increased vascular permeability
• Bronchospasm
• Increased mucous secretion

Mediators in Late Phase

• IL-4, IL-5, IL-13
• Major basic protein

Effects of Late Phase Mediators

• Attraction of eosinophils
• Attraction of mast cells
• Damage of surface epithelium caused by major basic protein secreted by eosinophils
• Exposure of vagal nerve endings
• Easy passage of inhaled allergen to mast cells in the subepithelium

Microscopic Examination

• Increased mucous leads to Luminal mucous plug
• Goblet cell hyperplasia and thickened basement membrane happens in the Surface epithelium
• Smooth muscle hypertrophy and hyperplasia, and Mucous gland hyperplasia happens in the wall.
• Abundant eosinophils and eosinophilic derived substances such as Curschman spirals and Charcot- leyden crystals
• Increased vascular permeability & Eventually fibrosis

What Causes Airflow Obstruction in Asthma?

• Acute bronchoconstriction due to IgE dependent release of mediators (early response)
• Airway edema
• Exudation of serum proteins and cellular debris with mucus plug formation
• Airway remodeling resulting from structural changes due to chronic inflammation that impacts the extent of airway obstruction reversibility

Sputum Examination

• Sputum is viscous and yellow, rich in eosinophils.

Microscopy Findings in Sputum

• Curschman spirals: Corkscrew-shaped twist of condensed mucus.
• Charcot-Leyden crystals: Mainly in atopic asthma, have the shape of a pair of long, narrow, pyramids placed base-to-base and are derived from an eosinophil lysophospholipase binding protein called galectin-10.
• Creola bodies: Compact clusters or strips of columnar epithelial cells shed from the bronchus.

Diagnosis of Asthma Includes

• Clinical presentation and history
• Pulmonary Function Tests (PFT)
• Allergy tests

Clinical Presentation and History

• Recurrent attacks of wheezing, cough, shortness of breath (dyspnea), and chest tightness (4 cardinal symptoms)
• Symptoms variable over time & intensity and are Worse at night
• Symptoms triggered by precipitating factors
• Family history of asthma
• Other allergic manifestations.
• Past history of precipitating factors (exercise, cold weather, viral infection)

Allergy Tests

• Skin Prick test and Serologic (serum IgE) testing

Skin Prick Test

• Works on the principle of activating IgE antibodies on the skin’s mast cells.
• Contraindications: children < 2 years of age, pregnant women & elderly
• Advantages: the lower cost and the shorter time to obtain results.
• Disadvantages: fewer allergens can be tested

Serologic (serum IgE) Testing

• Detecting circulating IgE antibody levels against specific allergens in blood
• Using either RAST (radioallergosorbent tests) or enzyme-linked immunosorbent assay (ELIZA)

Mimickers of Asthma (Differential Diagnosis)

• Aspiration of foreign bodies (nuts) that get trapped in the large airways, acting as a ball-valve causing hyperinflation and eventual respiratory distress.
• Cystic fibrosis (genetic disorder causing thick mucus plugs that are difficult to clear)
• Chronic obstructive pulmonary disease (COPD)
• Congestive heart failure (cardiac asthma) causes dyspnea, cough, and wheezing due to pulmonary edema; when the heart fails to pump adequately, fluid builds up in the pulmonary lymphatics and venous capillaries, causes edema of the lungs and promote wheezing

Acute Severe Asthma (Status Asthmaticus)

• Defined as an episode of progressive worsening of asthma symptoms and progressive decrease in lung function
• It is a medical emergency that can lead to acute respiratory failure and death if not recognized and managed appropriately.

Risk Factors of Acute Severe Exacerbation

• Major risk factors include: A recent history of poorly controlled asthma, severe asthma, a history of endotracheal intubation for asthma, intensive care unit admission for asthma
• Minor risk factors include Exposure to allergens, tobacco smoke, older patients, aspirin sensitivity, long duration of asthma

Asthma is a chronic inflammatory disease marked by airway hyper-responsiveness and recurrent bronchoconstriction. There are several types of asthma including atopic, non-atopic, drug-induced, and occupational asthma. Atopic asthma is more common, especially in children, and is often linked to family history and Type I hypersensitivity reactions.