Asthma Medicines

A challenge test may be used by the physician to demonstrate that a patient with a normal result on pulmonary function testing may indeed have asthma. This bronchial challenge or provocation testing would only be performed if the patient’s history and physical findings suggested that the patient is asthmatic but spirometry was normal. It is not a routine part of pulmonary function testing. The substances or agents commonly used for challenge testing include histamine, methacholine, and cold air.

Histamine is stored in allergy cells such as mast cells and is released during allergic or asthmatic attacks. It is thought to be one of the mediators of asthma. For this reason it is very suitable for provoking asthma in challenge testing. Methacholine is a chemical that stimulates one part of the nervous system called the parasympathetic nervous system to fire. If inhaled into the bronchial tubes in an asthmatic subject, methacholine will trigger impulses that produce airway constriction. Cold air irritates the bronchial tubes and may also be used for challenge testing. In an asthmatic subject with hyperreactive airways, inhaling cold air will produce significant tightening of the bronchial tubes.

In the patient thought to have occupational asthma the specific offending substance may be used to confirm the direct link between the substance and the patient’s asthmatic reaction. A similar challenge test has been used in patients to confirm allergy to sulfites and aspirin. With any challenge test there is a risk of a severe asthmatic reaction and for this reason these tests are reserved for difficult diagnostic situations and are only performed under careful observation and control.

Guidelines have been developed for performing and interpreting bronchial challenge testing. It is vital to standardize this type of testing to avoid “false positive” or “false negative” results. Generally, for a provocation test to be positive, there must be at least a 15 percent fall in airflow after inhaling the challenge material.

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Although asthma may be defined by the factors noted above, its cause remains uncertain. At this time it appears several factors are involved.

Heredity

Heredity certainly plays a major role: asthma and allergy often occur in families. Geneticists have located a gene on chromosome 11 that is strongly associated with allergy and speculate that several other genes may also be involved. One study suggests that a variant gene may direct the immune system to “overreact” to allergic stimuli by allowing a protein known as Immunoglobulin E (IgE) to “lock on&” to the surface of allergy cells called mast cells. When IgE reacts with allergy substances known as allergens, the mast cell disintegrates, releasing irritating chemicals that cause inflammation. These chemicals are the asthma mediators. Further research will undoubtedly produce a more detailed explanation for the genetic basis of asthma.

The Immune System

The immune system also plays a major role in the development of asthma. The immune system has two basic branches: cellular and humoral. Cellular immunity involves white blood cells called lymphocytes that can be provoked or “sensitized.” An example of this would be the body’s rejection process against a transplanted organ. Humoral immunity involves production of substances called antibodies that circulate in the blood. An example would be how the body reacts to a vaccination by producing antibodies. An antigen (may be called an allergen) is a substance capable of provoking the immune response.

Lymphocytes, Mast Cells, and Eosinophils

In asthma, the immune system is provoked in two ways. First, the cellular elements are mobilized and activated. Microscopic studies of the lining of the bronchial tubes in asthma have revealed increased numbers of lymphocytes. These cells produce substances that result in an increase in the number of mast cells that are known to store and release many irritating chemicals involved in production of the asthmatic reaction. These chemical substances or mediators of asthma produce inflammation. Another active cell that is “recruited” by lymphocytes found in the inflamed bronchial lining is the eosinophil. Large numbers of these cells may also be found in the blood of allergic and asthmatic individuals.

Immunoglobulin E

The second major immune response in asthma is the production of antibodies known as immunoglobulins, which is stimulated by substances released by the activated lymphocytes. One type, Immunoglobulin E or IgE, may be produced by inhaling a specific foreign substance such as ragweed. When the IgE attaches to the surface of the mast cell, a process is initiated that leads to release of the “asthma chemicals” and an ensuing asthmatic reaction.

Allergy

Allergy is the leading cause of asthma. In many patients allergens, activated lymphocytes, mast cells, eosinophils, and IgE all play major roles in the immune response that produces the asthmatic reaction. However, asthma may also occur without allergy. In nonallergic patients doctors believe the immune response may be triggered by infection.

Viruses

Viral infections in susceptible individuals have been thought to be potent triggers for the development of asthma. Researchers have recently demonstrated that viruses may cause human immune system cells to produce IgE. Animal research has shown that viruses are capable of altering the nervous impulses that stimulate the bronchial tubes. The altered nerve impulses may then produce constriction in the bronchial tubes. Susceptible patients with viral bronchial infections may become “sensitized” and display all the features noted in the definition of asthma.

The Environment

Environmental irritants, such as cigarette smoker pollutants (ozone, particulates), dust, and chemicals and proteins found in the home and the workplace are also considered capable of provoking the asthmatic response. These irritants may account for large numbers of asthmatic attacks each year and may also, in part, explain an increase in the number of asthma cases.

The Nervous System

Another possible cause of asthma is a dysfunction of nerve receptors or endings in the muscle surrounding the bronchial tubes that produces constriction of the air passage. Research has shown that an imbalance may exist in the nervous system that supplies the bronchial tubes of asthmatic individuals. This inborn error may shift the balance of forces toward those nerve signals that promote narrowing of the bronchial passages.

The Future

At this time the specific causes of asthma and the signals that are involved in starting the chain reaction that produces the disease are unknown. In the last five years promising research has shown that asthma is an inflammatory disease with features similar to other illnesses such as arthritis. This breakthrough is likely to lead to a further understanding of the causes of asthma and will likely form the basis for greater advances in treatment.

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