Asthma is an obstructive airway disorder caused by an immune reaction. It is characterized by episodic bronchoconstriction, inflammation of the bronchial walls, and increased mucus secretion. The airway obstruction leads to symptoms such as episodic wheezing, dyspnea, a feeling of chest tightness, and a cough. Asthma can be divided into two main categories: extrinsic and intrinsic.

Extrinsic (Allergic or Atopic) Asthma

Extrinsic (or allergic or atopic) asthma is a type 1 hypersensitivity reaction that normally begins in childhood. Family history increases the risk of extrinsic asthma. Common airborne allergens that can trigger allergic asthma include feces of dust mites, cockroach allergens, and animal dander. A skin hypersensitivity test is conducted to diagnose this type of asthma. Potential allergens are injected into the skin. A positive test is the production of an immediate wheel (swelling in the skin) and flare reaction (redness of the skin due to vasodilation).

The pathophysiology of atopic asthma involves an antigen presenting cell (APC) that presents a portion of an allergen like pollen to a naïve T helper cell and also secretes IL-4 which triggers the naïve T-helper cell to differentiate into a T helper 2 cell (TH2). The TH2 cell then interacts with a B-cell and releases IL-4 that causes the B-cell to produce IgE antibodies. The Fc region of IgE antibodies bind to mast cells and become their cell surface receptors; this mediates a faster immune response upon subsequent exposure to the allergen. People with allergic asthma typically have high serum levels of IgE. TH2 cells also release IL-5, which activates eosinophils, and IL-13, which causes submucosal glands to secrete mucus (see figure below).

Created by BYU-I Student 2018

On subsequent exposure to the same allergen, there is an early and late asthmatic response:

Immediate and Late Phases of Allergic Asthmatic Reaction Images by BYU-I Student 2018

Repeated asthmatic episodes bring about more lasting changes to the airway in a process called “airway remodeling.” In this remodeling, immune cells like mast cells, macrophages, eosinophils, and neutrophils accumulate underneath a thickened basement membrane. Underlying smooth muscle cells also undergo hypertrophy and hyperplasia. Goblet cells divide and subepithelial mucous glands undergo hypertrophy, producing excess mucus that blocks the airway. Increased airway vascularity is also observed with asthma and provides nutrients for the actively dividing cells and for mucus production.

There are several causes and contributors to the development of asthma:

Intrinsic (Non-Atopic) Asthma

The pathophysiological mechanisms of intrinsic (non-atopic) asthma are not well understood. Intrinsic asthma is not caused by allergies. With this type of asthma, a positive family history is much less common and no evidence for allergen sensitization can be found because allergen skin tests are usually negative. While there is no obvious role of allergens driving the inflammatory processes, there is much similarity to allergic asthma: Blood IgE levels are elevated, the same inflammatory cytokines are released, TH2 cells dominate (less TH1 cells), and mast cell/eosinophil activation occurs in a similar fashion. Theories postulate that intrinsic asthma is due to physiological processes that involve immune cell activation by physical irritation (like air particles, flow rates and temperature). Other theories suggest possible “super antigens” that may involve non-specific T-cell activation. There is also the possibility of hapten interactions and autoimmune responses.

Some triggers for non-atopic asthma include respiratory viral infections, air pollutants (like sulfur dioxide, nitrogen dioxide, and ozone from smog), occupational exposure (like fumes from epoxy resins and plastics), organic dusts (like wood and cotton), gasses (like toluene), chemicals (like formaldehyde) and even seemingly harmless actions like exercise and cold exposure. Other triggers may be emotional trauma, changes in hormone levels, and exposure to bronchial irritants such as strong odors and smoke. Some episodes of intrinsic asthma are seasonal.

Certain drugs can also be a trigger for asthma. For example, NSAIDs can induce a classic triad of asthma symptoms including chronic rhinosinusitis, nasal polyps, and bronchial asthma. It is believed that this type of asthma is due to a decrease in the production of a prostaglandin called PGE-2. PGE-2 can inhibit enzymes like 5-lipoxygenase that are responsible for the production of leukotrienes (bronchoconstrictors and vasodilators). Treatment with NSAIDs like aspirin and ibuprofen results in less PGE-2 production and therefore less inhibition of leukotriene production. This results in an increase in leukotrienes which are responsible for the increased bronchoconstriction observed in this type of asthma.

Diagnosis and Treatment of Asthma

The cardinal symptoms of asthma include chest tightness, dyspnea or shortness of breath, coughing that may or may not produce sputum, and wheezing. Classic asthma attacks can last for several hours. Asthma symptoms seem to worsen at night.

Diagnosis is done by assessing the patient’s history and symptoms. Determining their family history as it relates to asthma is important. Skin tests can reveal allergic responses to particular allergens. Blood tests can reveal specific IgE antibodies as well as eosinophil counts. Eosinophils in the sputum can also support a diagnosis of asthma.

Pulmonary function tests are also used to diagnose asthma. It would be good to review the following tests from your previous anatomy and physiology courses: forced expired volume in 1 second (FEV1) over forced vital capacity (FVC) (FEV1/FVC) ratio and peak expiratory flow (PEF). For someone having an asthmatic attack, you can expect the FEV1/FVC ratio to be lower than the normal value of 75-80%. This is because it is very difficult for someone with an obstructive lung disease like asthma to exhale quickly because they have increased airway resistance. PEF is a measure of a person’s maximum rate of expiration after full inspiration and thus can give an indication if there is an obstruction of the airways. This measurement is obtained using a handheld peak flow meter and can be used for diagnosis or monitoring asthma. If an individual’s PEF drops 80% below their personal best, action should be taken to treat the asthma flareup.

Common pharmaceutical treatments for asthma include:

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