Asthma Medicines

Beta-Agonists

Since asthma is characterized by narrowing of bronchial tubes caused by tightening of bronchial wall muscle, treatment has traditionally focused on reversing this process, which is called bronchodilatation. The medications that produce this effect are bronchodilators. At this time the most effective bronchodilators are the Bzadrenergic agonists. These drugs are all derivatives of epinephrine which has effects on both the heart (termed beta-I) and lung (beta-2). Epinephrine is an important hormone produced in the body by the adrenal gland but has been synthesized in the laboratory. The B2-adrenergic agonists have been developed to be “selective” stimulants of lung structures, avoiding unwanted effects on the heart and blood vessels such as high blood pressure and palpitations. Their effects are produced through nerve endings called receptors located within the lungs. One such B2-receptor is located in the muscle layer that surrounds the bronchial tube. With the administration of these agents and stimulation of the receptor the bronchial wall muscle relaxes, producing bronchodilatation.

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An asthmatic attack is one of the most striking medical emergencies. One of my first experiences with severe asthma was in the intensive care unit of Bellevue Hospital. I had been called to consult on a fifty-six-year-old woman who was having a severe asthmatic attack. As I entered the unit and approached the bedside, I noted several physicians already in attendance. The patient was sitting upright with labored breathing and I could hear her wheezing from several feet away. It was clear that she was not doing well despite continuous oxygen and medicated aerosol treatment. Unable to speak due to shortness of breath, her expression was one of fear and desperation. Several days later, greatly improved after vigorous treatment, I asked her to describe what she had been feeling during her attack. “It was like I was drowning.”

In the asthmatic attack there is constriction or tightening of the bronchial wall muscle, and secretion of mucus, often with “plugging” of small air tubes, as well as inflammation and swelling of the bronchial lining. The end result is blockage or obstruction of the bronchial tubes. The frequency, duration, and severity of the asthmatic attack varies markedly from patient to patient.

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Following the careful review of the patient’s history and physical examination the physician will proceed to several commonly used laboratory tests to complete the diagnostic evaluation. There is no universal”checklist” of tests for every patient since there is great variation in each case. Physicians may also have differences in their laboratory evaluations.

Blood Tests

In the laboratory evaluation of asthma it would be common to evaluate the patient’s blood count looking for “allergy cells” called eosinophils. The physician may also obtain a level of IgE, the immunoglobulin in the blood that is often elevated in allergic patients. .

X-rays

A chest x-ray is often necessary to exclude many of the entities discussed above that can mimic asthma. It does not serve to confirm the diagnosis since the features of asthma occurring within the bronchial tubes cannot be seen on a chest x-ray.

Occasionally, the chest x-ray may show that the lungs are greatly expanded and appear larger than normal or hyperinflated. This occurs in asthma because air may enter the bronchial tubes but have difficulty being exhaled, also known as “air-trapping.” This x-ray finding cannot be used as a diagnostic tool for asthma since the same finding may occur in emphysema and in some cases of bronchitis.

Often the physician will order sinus x-rays as part of the laboratory evaluation. Evidence of sinusitis or nasal polyps would identify patients as high-risk candidates for asthma. In addition, the sinusitis may be viewed as a potential aggravating factor in asthmatic attacks and thus become a focus of treatment of individual patients. There is a recent trend toward using the more detailed CAT scan for this exam because of the increased information it provides.

Sputum Exam

Examination of swabs of nasal mucus or chest phlegm (sputum) may be helpful in diagnosing asthma. Microscopic examination may identify abundant eosinophils that would be characteristic of allergy and asthma. The presence of pus cells called neutrophils would suggest an infectious process; for example, bronchitis or sinusitis. The physician may request a culture of the coughed sputum if pus cells are seen under the microscope.

Pulmonary Function Testing

Forced Expiratory Maneuver

The most important laboratory test the physician performs in the diagnosis of asthma is pulmonary function testing. Before the testing begins the patient’s age, race, sex, height, and weight are recorded. From these statistics the expected normal values are determined. These are called the predicted normals and they are determined from statistical analysis of large groups of normal subjects.

The most common test involves a device known as a spirometer, which measures the amount of air (volume) expelled by the patient as well as its speed as the air is exhaled forcefully. In this simple but extremely important maneuver the patient is asked to take a full deep breath in, then exhale fully and forcefully this is called a maximum forced expiratory maneuver. In tracing this maneuver the physician determines the maximum amount of air the patient can expel after the deepest inhalation. This amount is called the vital capacity.

As air is expelled the airflow is measured throughout the maneuver until the patient is unable to exhale further. One extremely useful measurement is of the greatest flow that can be obtained after the patient has inhaled fully and forcefully exhaled. This is termed peak expiratory flow rate or “peak flow.” This important and easily performed. Flow rates are recorded at the beginning, middle, and end of the forced exhalation maneuver and so is the amount of air expelled each second. As air is exhaled by the lungs it is the large bronchial tubes (large airways) that empty first with the smaller passages (small airways) contributing a greater share as exhalation continues and ends. In one second a certain amount of air should normally be exhaled with an expected increase as time increases. The one-second measurement is often a good reflector of the large airways and measurements toward the middle and end of the breath usually determine the condition of smaller air passages.

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To understand asthma you must first consider the normal structure of the lung. and we will define asthma.

The Normal Lung

The Bronchial Tubes

In a normal lung, two systems coexist to permit its function of enriching the blood with oxygen and excreting carbon dioxide. Oxygen is the fuel for metabolism while carbon dioxide represents the waste product.

The first system is a series of hollow connecting airways that form the bronchial tubes. Imagine that this system resembles a large branching tree with the trunk being the windpipe (trachea) that begins below the voice box (larynx). Branching of this bronchial “tree” occurs frequently to the smallest imaginable airway, a bronchiole. The inner lining of the bronchial tubes is a delicate membrane called the bronchial mucosa. Although normally pale and innocent in appearance, this membrane is capable of becoming inflamed and swollen in an asthmatic attack. Mucus glands within the layers of the bronchial lining can produce large quantities of extremely thick secretion when stimulated by infection or asthma triggers. In the wall of the bronchial tubes is a smooth muscle layer capable of contracting, producing narrowing or bronchoconstriction, and relaxing, producing widening or bronchodilatation.

The Alveoli

The second system within the lung consists of millions of tiny air sacs or alveoli. Think of these sacs surrounding the small bronchial tubes like grapes surrounding a stem. A bronchiole is surrounded by alveoli. Each of the smallest bronchioles allows air to enter and leave multiple alveoli. Within these small air sacs the vital gas exchange takes place. Within the wall of these sacs blood courses within small vessels called capillaries. This blood has been returned from all parts of the body where it has been used for metabolism. As it enters the capillaries it is low in oxygen and high in carbon dioxide. The extremely thin walls of these blood vessels allow the exchange of oxygen and carbon dioxide. The blood leaves the alveoli oxygen rich with lower carbon dioxide levels.

The Nervous System And The Lung

Besides reviewing the normal structure of the lung, it is important to understand the role of the nervous system and how it relates to bronchial asthma. The nervous system is generally divided into the centre tures of the brain and spinal cord and peripheral nerve structures distributed throughout the body.

The Autonomic Nervous System

One major subdivision of the nervous system is called the autonomic nervous system, which is responsible for the unconscious control of major body functions and is divided into a parasympathetic and a sympathetic branch. These systems extend throughout the body but are extremely important in lung function. Just think of these two systems as balancing each other. For example, stimulating the parasympathetic system causes the bronchial tubes to constrict while stimulating the sympathetic nervous system produces the opposite reaction (dilatation). In a normal lung a balance of these two systems maintains open airways. In an asthmatic lung, an imbalance occurs, favoring the parasympathetic system that produces narrowing or constriction of the air tubes.

Adrenergic Versus Cholinergic Effects

The effects produced through the nerve pathways are mediated by chemicals called neurotransmitters. These chemicals act at nerve endings or receptor sites throughout the body. In the parasympathetic nervous system the neurotransmitter is a chemical substance known as acetylcholine. Agents or medications that mimic the effects of this substance are called cholinergic agents. In the sympathetic nervous system the neurotransmitter is a substance known as epinephrine or adrenaline. Agents or medications that mimic the effects of adrenaline are called adrenergic agents.

Receptors: Alpha and Beta

It is important to familiarize yourself with the different types of receptors that exist in the nerve endings. These receptors are divided into alphas and betas based on how they respond to medication. In general, alpha receptors excite and beta receptors usually inhibit or relax. Alpha receptors seem to be less important in regulating bronchial tubes than beta receptors. Beta receptors are classified as B1, found in the heart muscle, and B2, found in the bronchial tubes and other parts of the body.

Definition of Asthma

That asthma has been defined in so many ways reflects the complexity of this illness. Several features of asthma are covered by the currently accepted definition.

Airway Obstruction: Reversible

First, the airways of the lung or bronchial tubes are narrowed. This is called “airway obstruction” since air can no longer flow smoothly through elaborate system of branching tubes. Since these tubes can dilate a asthma this obstruction is called reversible, an important aspect of definition since it may distinguish asthma from other bronchial illnesses fixed or irreversible obstruction such as bronchitis and emphysema

This narrowing within the bronchial tubes has occurred due to a tightening or constriction of the muscle that exists in the bronchial, reaction may be thought of as a muscle “spasm” that results in narrowing of the bronchial tubes, similar to any muscle cramp.

It is these narrowed or “obstructed” airways that produce one of the common features of asthma, the wheeze. As air is exhaled through these tubes, its movement is turbulent and produces this sound.

Inflammation

The second element included in defining asthma is the presence of inflammation, the red, swollen appearance of the inside of the tubes. This characteristic of asthma has received a great deal of attention recently and has become the focus of much of asthma therapy. The inflammation is present in the lining (the mucosa) of the bronch which can be examined by inserting into them a lighted scope bronchoscope. With this instrument a physician can also obtain of the bronchial lining and its secretions. Under a microscope these samples may show large numbers of cells that carry substances called mediators capable of causing inflammation. Using these techniques, the mediators released by inflammatory cells when an attack occurs can be measured and identified.

Hyperirritability

The third defining feature is increased responsiveness or hyperirritability the bronchial tubes and their tendency to”overreact” and narrow. ‘”twitchy” has also been used in this regard. This irritability is often demonstrated by the sudden, severe attacks patients can experience when exposed to substances such as pollen, animal dander, dust, and fumes. This hyperreactivity forms the basis for bronchial provocation or challenge testing that is used by physicians to diagnose asthma in patients whose illnesses do not fit easily into the other definitions.

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