Asthma

What is asthma?

Asthma is a chronic inflammation of the bronchial tubes (airways) that causes swelling and narrowing (constriction) of the airways. The result is difficulty breathing. The bronchial narrowing is usually either totally or at least partially reversible with treatments.

Bronchial tubes that are chronically inflamed may become overly sensitive to allergens (specific triggers) or irritants (nonspecific triggers). The airways may become "twitchy" and remain in a state of heightened sensitivity. This is called "bronchial hyperreactivity" (BHR). It is likely that there is a spectrum of bronchial hyperreactivity in all individuals. However, it is clear that asthmatics and allergic individuals (without apparent asthma) have a greater degree of bronchial hyperreactivity than nonasthmatic and nonallergic people. In sensitive individuals, the bronchial tubes are more likely to swell and constrict when exposed to triggers such as allergens, tobacco smoke, or exercise. Amongst asthmatics, some may have mild BHR and no symptoms while others may have severe BHR and chronic symptoms.

Asthma affects people differently. Each individual is unique in their degree of reactivity to environmental triggers. This naturally influences the type and dose of medication prescribed, which may vary from one individual to another.

From the past to the present

Physicians in ancient Greece used the word asthma to describe breathlessness or gasping. They believed that asthma was derived from internal imbalances, which could be restored by healthy diet, plant and animal remedies, or lifestyle changes.

Allergy jargon

Asthma is derived from the Greek word Panos, meaning panting.

Chinese healers understood that xiao-chiran, or "wheezy breathing," was a sign of imbalance in the life force they called qi. They restored qi by means of herbs, acupuncture, massage, diet, and exercise.

The Hindu philosophers connected the soul and breath as part of the mind, body, and spirit connection. Yoga uses control of breathing to enhance meditation. Indian physicians taught these breathing techniques to help manage asthma.

Allergy fact

Maimonides was a renowned 12th-century rabbi and physician who practiced in the court of the sultan of Egypt. He recommended to one of the Royal Princes with asthma that he eat, drink, and sleep less. He also advised that he engage in less sexual activity, avoid the polluted city environment, and eat a specific remedy...chicken soup.

The balance of the "four humors," which was derived from the Greco-Roman times, influenced European medicine until the middle of the 18th century. In a healthy person, the four humors, or bodily fluids -- blood, black bile, yellow bile, and phlegm -- were in balance. An excess of one of these humors determined what kinds of disorders were present. Asthmatics who were noted for their coughing, congestion, and excess mucus (phlegm) production were therefore regarded as "phlegmatic."

By the 1800s, aided by the invention of the stethoscope, physicians began to recognize asthma as a specific disease. However, patients still requested the traditional treatments of the day, such as bloodletting, herbs, and smoking tobacco. These methods were used for a variety of conditions, including asthma. Of the many remedies that were advertised for asthma throughout the 19th century, none were particularly helpful.

Allergy fact

As early as 1892, the famous Canadian-American physician Sir William Osler suggested that inflammation played an important role in asthma.

Bronchial dilators first appeared in the 1930s and were improved in the 1950s. Shortly thereafter, corticosteroid drugs that treated inflammation appeared and have become the mainstay of therapy used today.

The scope of the problem

Asthma is now the most common chronic illness in children, affecting one in every 15. In North America, 5% of adults are also afflicted. In all, there are about 1 million Canadians and 15 million Americans who suffer from this disease.

The number of new cases and the yearly rate of hospitalization for asthma have increased about 30% over the past 20 years. Even with advances in treatment, asthma deaths among young people have more that doubled.

Allergy fact

There are about 5,000 deaths annually from asthma in the U.S. and about 500 deaths per year in Canada.

Normal bronchial tubes

Before we can appreciate how asthma affects the bronchial airways, we should first take a quick look at the structure and function of normal bronchial tubes.

The air we breathe in through our nose and mouth passes through the vocal cords (larynx) and into the windpipe (trachea). Th

e air then enters the lungs by way of two large air passages (bronchi), one for each lung. The bronchi divide within each lung into smaller and smaller air tubes (bronchioles), just like branches of an inverted tree. Inhaled air is brought through these airways to the millions of tiny air sacs (alveoli) that are contained in the lungs. Oxygen (O₂) passes from the air sacs into the bloodstream through numerous tiny blood vessels called capillaries. Similarly, the body's waste product, carbon dioxide (CO₂), is returned to the air sacs and then eliminated upon each exhalation.

Normal bronchial tubes allow rapid passage of air in and out of the lungs to ensure that the levels of O₂ and CO₂ remain constant in the bloodstream. The outer walls of the bronchial tubes are surrounded by smooth muscles that contract and relax automatically with each breath. This allows the required amount of air to enter and exit the lungs to achieve this normal exchange of O₂ and CO₂. The contraction and relaxation of the bronchial smooth muscles are controlled by two different nervous systems that work in harmony to keep the airways open.

The inner lining of the bronchial tubes, called the bronchial mucosa, contains: (1) mucus glands that produce just enough mucus to properly lubricate the airways; and (2) a variety of so-called inflammatory cells, such as eosinophils, lymphocytes, and mast cells. These cells are designed to protect the bronchial mucosa from the microorganisms, allergens, and irritants we inhale, and which can cause the bronchial tissue to swell. Remember, however, that these inflammatory cells are also important players in the allergic reaction. Therefore, the presence of these cells in the bronchial tubes causes them to be a prime target for allergic inflammation.

How does asthma affect breathing?

Asthma causes a narrowing of the breathing airways, which interferes with the normal movement of air in and out of the lungs. Asthma involves only the bronchial tubes and does not affect the air sacs or the lung tissue. The narrowing that occurs in asthma is caused by three major factors: inflammation, bronchospasm, and hyperreactivity.

Inflammation

The first and most important factor causing narrowing of the bronchial tubes is inflammation. The bronchial tubes become red, irritated, and swollen. This inflammation increases the thickness of the wall of the bronchial tubes and thus results in a smaller passageway for air to flow through. The inflammation occurs in response to an allergen or irritant and results from the action of chemical mediators (histamine, leukotrienes, and others). The inflamed tissues produce an excess amount of "sticky" mucus into the tubes. The mucus can clump toget

her and form "plugs" that can clog the smaller airways. Specialized allergy and inflammation cells (eosinophils and white blood cells), which accumulate at the site, cause tissue damage. These damaged cells are shed into the airways, thereby contributing to the narrowing.

Bronchospasm

The muscles around the bronchial tubes tighten during an attack of asthma. This muscle constriction of the airways is called bronchospasm. Bronchospasm causes the airway to narrow further. Chemical mediators and nerves in the bronchial tubes cause the muscles to constrict. Bronchospasm can occur in all humans and can be brought on by inhaling cold or dry air.

Hyperreactivity (hypersensitivity)

In patients with asthma, the chronically inflamed and constricted airways become highly sensitive, or reactive, to triggers such as allergens, irritants, and infections. Exposure to these triggers may result in progressively more inflammation and narrowing.

The combination of these three factors results in difficulty with breathing out, or exhaling. As a result, the air needs to be forcefully exhaled to overcome the narrowing, thereby causing the typical "wheezing" sound. People with asthma also frequently "cough" in an attempt to expel the thick mucus plugs. Reducing the flow of air may result in less oxygen passing into the bloodstream, and if very severe, carbon dioxide may dangerously accumulate in the blood.

The importance of inflammation

Inflammation, or swelling, is a normal response of the body to injury or infection. The blood flow increases to the affected site and cells rush in and ward off the offending problem. The healing process has begun. Usually, when the healing is complete, the inflammation subsides. Sometimes, the healing process causes scarring. The central issue in asthma, however, is that the inflammation does not resolve completely on its own. In the short term, this results in recurrent "attacks" of asthma. In the long term, it may lead to permanent thickening of the bronchial walls, called airway "remodeling." If this occurs, the narrowing of the bronchial tubes may become irreversible and poorly responsive to medications. Therefore, the goals of asthma treatment are: (1) in the short term, to control airway inflammation in order to reduce the reactivity of the airways; and (2) in the long term, to prevent airway remodeling.

Allergy assist

The hallmark of managing asthma is the prevention and treatment of airway inflammation.

It is also likely that control of the inflammation will prevent airway remodeling and thereby prevent permanent loss of lung function.

Various triggers in susceptible individuals result in airway inflammation. Prolonged inflammation induces a state of airway hyperreactivity, which might progress to airway remodeling unless treated effectively.

Which triggers cause an asthma attack?

Asthma symptoms may be activated or aggravated by many agents. Not all asthmatics react to the same triggers. Additionally, the effect that each trigger has on the lungs varies from one individual to another. In general, the severity of your asthma depends on how many agents activate your symptoms and how sensitive your lungs are to them. Most of these triggers can also worsen nasal or eye symptoms.

Triggers fall into two categories:

• allergens ("specific") and



• nonallergens -- mostly irritants (nonspecific).

Once your bronchial tubes (nose and eyes) become inflamed from an allergic exposure, a re-exposure to the offending allergens will often activate symptoms. These "reactive" bronchial tubes might also respond to other triggers, such as exercise, infections, and other irritants. The following is a simple checklist.

Common Asthma Triggers:

Al

lergens

• "seasonal" pollens


• year-round dust mites, molds, pets, and insect parts


• foods, such as fish,egg, peanuts, nuts, cow's milk, and soy
  

• additives, such as sulfites


• work-related agents, such as latex

Allergy fact

About 80% of children and 50% of adults with asthma also have allergies.

Irritants

• respiratory infections, such as those caused by viral "colds," bronchitis, and sinusitis


• drugs, such as aspirin, other NSAIDs (nonsteroidal antiinflammatory drugs), and beta
blockers (used to treat blood pressure and other heart conditions)


• tobacco smoke


• outdoor factors, such as smog, weather changes, and diesel fumes

• indoor factors, such as paint, detergents, deodorants, chemicals, and perfumes


• nighttime


• GERD (gastroesophageal reflux disorder)

• exercise, especially under cold dry conditions


• work-related factors, such as chemicals, dusts, gases, and metals


• emotional factors, such as laughing, crying, yelling, and distress

• hormonal factors, such as in premenstrual syndrom.

The many faces of asthma

The many potential triggers of asthma largely explain the different ways in which asthma can present. In most cases, the disease starts in early childhood from 2-6 years of age. In this age group, the cause of asthma is often linked to exposure to allergens, such as dust mites, tobacco smoke, and viral respiratory infections. In very young children, less than 2 years of age, asthma can be difficult to diagnose with certainty. Wheezing at this age often follows a viral infection and might disapp

ear later, without ever leading to asthma. As

thma, however, can develop again in adulthood. Adult-onset asthma occurs more often in women, mostly middle-aged, and frequently follows a respiratory tract infection. The triggers in this group are usually nonallergic in nature.

Types: allergic (extrinsic) and nonallergic (intrinsic) as

thma

Your doctor may refer to asthma as being "extrinsic" or "intrinsic." A better understanding of the nature of asthma can help explain the differences between them. Extrinsic, or allergic asthma, is more common (90% of all cases) and typically develops in childhood. Approximately 80% of children with asthma also have documented allergies. Typicall

y, there is a family history of allergies. Additionally, other allergic conditions, such as nasal allergies or eczema, are often also present. Allergic asthma often goes into remission in early adulthood. However, in 75% of cases, the asthma reappears later.

Intrinsic asthma represents about 10% of all cases. It usually develops after the age of 30 and is not typically associated with allergies. Women are more fr

equently involved and many cases seem to follow a respiratory tract infection. The condition can be difficult to treat and symptoms are often chronic and year-round.

Typical symptoms and signs of asthma

The symptoms of asthma vary from person to person and in any individual from time to time. It is important to remember that many of these symptoms can be subtle and similar to those seen in other conditions. All of the symptoms mentioned below can be present in other respiratory, and sometimes, in heart conditions. This potential confusion makes identifying the settings in which the symptoms occur and diagnostic testing very important in recognizing this disorder.

The following are the four major recognized asthma symptoms:

• Shortness of breath, especially with exertion or at night



• Wheezing is a whistling or hissing sound when breathing out

• Coughing may be chronic, is usually worse at night and early morning, and may occur after exercise or when exposed to cold, dry air



• Chest tightness may occur with or without the above symptoms

Asthma fact

A sthma is classified according to the frequency and severity of symptoms, or "attacks," and the results of pulmonary (lung) function tests.

• 30% of affected patients have mild, intermittent (less than two episodes a week) symptoms of asthma with normal breathing tests



• 30% have mild, persistent (two or mores episodes a week) symptoms of asthma with normal or abnormal breathing tests



• 40% have moderate or severe, persistent (daily or continuous) symptoms of asthma with abnormal breathing tests

Acute asthma attack

An acute, or sudden, asthma attack is usually caused by an exposure to allergens or an upper-respiratory-tract infection. The severity of the attack depends on how well your underlying asthma is being controlled (reflecting how well the airway inflammation is being controlled). An acute attack is potentially life-threatening because it may continue despite the use of your usual quick-relief medications (inhaled bronchodilators). Asthma that is unresponsive to treatment with an inhaler should prompt you to seek medical attention at the closest hosp

ital emergency room or your asthma specialist office, depending on the circumstances and time of day. Asthma attacks do not stop on their own without treatment. If you ignore the early warning signs, you put yourself at risk of developing status asthmaticus.

Allergy fact

Prolonged attacks of asthma that do not respond to treatment with bronchodilators are a medical emergency. Physicians call these severe attacks "status asthmaticus," and they require immediate emergency care.

The symptoms of severe asthma are persistent coughing and the inability to speak full sentences or walk without shortness of breath. Your chest may feel closed, and your lips may have a bluish tint. In addition, you may feel agitation, confusion, or an inability to concentrate. You may hunch your shoulders, sit or stand up to breathe more easily, and strain your abdominal and neck muscles. These are signs of an impending respiratory system failure. At this point, it is unlikely that inhaled medications will reverse this process. A mechanical ventilator may

be needed to assist the lungs and respiratory muscles. A face mask or a breathing tube is inserted in the nose or mouth for this treatment. These breathing aids are temporary and are removed once the attack has subsided and the lungs have recovered sufficiently to resume the work of breathing on their own. A short hospital stay in an intensive-care unit may be a result of a severe

attack that has not been promptly treated. To avoid such hospitalization, it is best, at the onset of symptoms, to begin immediate early treatment at home or in your doctor's office.

What medications are used in the treatment of asthma?

Most asthma medications work by relaxing bronchospasm (bronchodilators) or reducing inflammation (corticosteroids). In the treatment of asthma, inhaled medications are generally preferred over tablet or liquid medicines, which are swallowed (oral medications). Inhaled medications act directly on the airway surface and airway muscles where the asthma problems initiate. Absorption of inhaled medications into the rest of the body is minimal. Therefore, adverse side effects are fewer as compared to oral medications. Inhaled medication

s include beta-2 agonists, anticholinergics, corticosteroids, and cromolyn sodium. Oral medications include aminophylline, leukotriene antagonists, beta-2 agonists, and corticosteroid tablets.

Historically, one of the first medications used for asthma was adrenaline (epinephrine). Adrenaline has a rapid onset of action in open

ing the airways (bronchodilation). It is still often used in emergency situations for asthma. Unfortunately, adrenaline has many side effects, including rapid heart rate, headache, nausea, vomiting, restlessness, and a sense of panic.

Medications chemically similar to adrenaline have been developed. These medications, called beta-2 agonists, have the bronchodilati

ng benefits of adrenaline without many of its unwanted side effects. Beta-2 agonists are inhaled bronchodilators which are called "agonists" because they promote the action of the beta-2 receptor of bronchial wall muscle. This receptor acts to relax the muscular wall of the airways (bronchi), resulting in bronchodilation. The bronchodilator action of beta-2 agonists starts within minute

s after inhalation and lasts for about four hours. Examples of these medications include albuterol (Ventolin HFA, Proventil HFA), levalbuterol (Xopenex), metaproterenol (Alupent), pirbuterol acetate (Maxair), and terbutaline sulfate (Brethaire). Recently, chlorofluorocarbons (CFCs) have been removed from all MDI inhalers because of the environmental effects on the ozone layer. These have been replaced by a new propellant, hydroflouroalkane (HFA). Patients may notice that the jet they feel in the back of their throat is less intense when comp

ared with the CFC inhaler. They should be instructed that they are still receiving the same amount of medication though it may feel different than their older inhaler. Another very important point that patients must be aware of is that "floating" these new inhalers does not help in determining the amount of medication left in the MDI. In the past, the CFC devices could be floated in a bowl of water. With more medicine in the inhaler, the canister would sink and gradually float as it

emptied. This is not the case with the HFA inhalers, as floating will actually clog the inhaler. The number of accuations must be counted to determine if medication is still left in the inhaler. Shaking the inhaler is not an effective method of determining how much medication is left. Often propellant (HFA) will continue to come out of the inhaler even after the medication is used up. At the present, only one albuterol inhaler comes with a counter device and this is Ventolin HFA.

A new group of long-acting beta-2 agonists has been developed with a sustained duration of effect of 12 hours. These inhalers can be taken twice a day. Salmeterol xinafoate (Serevent) and formoterol (Foradil) are examples of this group of medications. The long-acting beta-2 agonists should not used for acute attacks. Beta-2 agonists can have side effects, such as anxiety, tremor, palpitations or fast heart rate, and lowering of blood potassium. There is data to suggest that taking long-acting beta-2 agonists alone may be life-threatening. They are best taken along with inhaled corticosteroids (see below).

Just as beta-2 agonists can dilate the airways, beta blocker medications impair the relaxation of bronchial muscle by beta-2 receptors and can cause constriction of airways, aggravating asthma. Therefore, beta blockers, such as the blood pressure medications propranolol (Inderal) and atenolol (Tenormin), should be avoided by asthma patients if possible.

The anticholinergic agents act on a different type of nerves than the beta-2 agonists to achieve a similar relaxation and opening of the airway passages. These two groups of bronchodilator inhalers when used together can produce an enhanced bronchodilation effect. An example of a commonly used anticholinergic agent is ipratropium bromide (Atrovent). Ipratropium takes longer to work as compared with the beta-2 agonists, with peak effectiveness occurring two hours after intake and lasting six hours. These agents are more effective in patients with COPD.

When symptoms of asthma are difficult to control with beta-2 agonists, inhaled corticosteroids (cortisone) are often added. Corticosteroids can improve lung function and reduce airway obstruction over time. Examples of inhaled corticosteroids include beclomethasone dipropionate (Beclovent, Qvar, and Vanceril), triamcinolone acetonide (Azmacort), budesonide (Pulmocort), and flunisolide (Aerobid). The ideal dose of corticosteroids is still unknown. The side effects of inhaled corticosteroids include hoarseness, loss of voice, and oral yeast infections. Early use of inhaled corticosteroids may prevent irreversible damage to the airways.

To decrease the deposition of medications on the throat and increase the amount reaching the airways, spacers can be helpful. Spacers are tube-like chambers attached to the outlet of the MDI canister. Spacer devices can hold the released medications long enough for patients to inhale them slowly and deeply into the lungs. A spacing device placed between the mouth and the MDI can improve medication delivery and reduce the side effects on the mouth and throat. Rinsing out the mouth after use of a steroid inhaler also can decrease these side effects.

Combination inhaler therapy is now available for the treatment of asthma. These medications include Advair (fluticasone and salmeterol) and Symbicort (budesonide and formoteral). Symbicort uses the standard MDI inhaler device (a counter device will be added in the near future). Advair has a unique powdered delivery system with a built-in counter.

Cromolyn sodium (Intal) prevents the release of certain chemicals in the lungs, such as histamine, which can cause asthma. Exactly how cromolyn works to prevent asthma needs further research. Cromolyn is not a corticosteroid and is usually not associated with significant side effects. Cromolyn is useful in preventing asthma but has limited effectiveness once acute asthma starts. Cromolyn can help prevent asthma triggered by exercise, cold air, and allergic substances, such as cat dander. Cromolyn may be used in children as well as adults.

Theophylline (Theodur, Theoair, Slo-bid, Uniphyl, Theo-24) and aminophylline are examples of methylxanthines. Methylxanthines are administered orally or intravenously. Before the inhalers became popular, methylxanthines were the mainstay of treatment of asthma Caffeine that is in common coffee and soft drinks is also a methylxanthine drug! Theophylline relaxes the muscles surrounding the air passages and prevents certain cells lining the bronchi (mast cells) from releasing chemicals, such as histamine, which can cause asthma. Theophylline can also act as a mild diuretic, causing an increase in urination. For asthma that is difficult to control, methylxanthines can still play an important role. Dosage levels of theophylline or aminophylline are closely monitored. Excessive levels can lead to nausea, vomiting, heart-rhythm problems, and even seizures. In certain medical conditions, such as heart failure or cirrhosis, dosages of methylxanthines are lowered to avoid excessive blood levels. Drug interactions with other medications, such as cimetidine (Tagamet), calcium channel blockers (Procardia), quinolones (Cipro), and allopurinol (Xyloprim) can further affect drug blood levels.

Corticosteroids are given orally for severe asthma unresponsive to other medications. Unfortunately, high doses of corticosteroids over long periods can have serious side effects, including osteoporosis, bone fractures, diabetes mellitus, high blood pressure, thinning of the skin and easy bruising, insomnia, emotional changes, and weight gain.

Expectorants help thin airway mucus, making it easier to clear the mucus by coughing. Potassium iodide is not commonly used and has the potential side effects of acne, increased salivation, hives, and thyroid problems. Guaifenesin (Entex, Humibid) can increase the production of fluid in the lungs and help to decrease the apparent thickness of the mucus but can also be an airway irritant for some people.

In addition to bronchodilator medications for those patients with atopic asthma, avoiding allergens or other irritants can be very important. In patients who cannot avoid the allergens, or in those whose symptoms cannot be controlled by medications, allergy shots are considered. The benefits of allergy shots (desensitization) in the prevention of asthma has not been firmly established. Some doctors are still concerned about the risk of anaphylaxis, which occurs in one in 2 million doses given. Allergy shots most commonly benefit children allergic to house dust mites. Other benefits can be seen with pollens and animal dander.

In some asthma patients, allergy antibodies of one form known as immunoglobulin E (IgE) may play a key role. If these substances are elevated in the blood, a new form of medication may be helpful for severe asthma. An antibody to IgE, known as omalizumab (Xolair) has been developed. This must be administered by injection in a doctor's office. This is extremely expensive. However, for patients with asthma that is difficult to manage, this option may be helpful.

In some asthma patients, avoidance of aspirin, or other NSAIDs (commonly used in treating arthritis inflammation) is important. In other patients, adequate treatment of backflow of stomach acid (esophageal reflux) prevents irritation of the airways. Measures to prevent esophageal reflux include medications, weight loss, dietary changes, and stopping cigarettes, coffee, and alcohol. Examples of medications used to reduce reflux include omeprazole (Prilosec) and ranitidine (Zantac). Patients with severe reflux problems causing lung problems may need surgery to strengthen the esophageal sphincter in order to prevent acid reflux (fundoplication surgery).

Asthma At A Glance

• Asthma is a chronic inflammation of the bronchial tubes (airways) that causes swelling and narrowing (constriction) of the airways. The bronchial narrowing is usually either totally or at least partially reversible with treatments.
• Asthma is now the most common chronic illness in children, affecting one in every 15.
• Asthma involves only the bronchial tubes and usually does not affect the air sacs or the lung tissue. The narrowing that occurs in asthma is caused by three major factors: inflammation, bronchospasm, and hyperreactivity.
• Allergy can play a role in some, but not all, asthma patients.
• Many factors can precipitate asthma attacks and they are classified as either allergens or irritants.
• Symptoms of asthma include shortness of breath, wheezing, cough, and chest tightness.
• Asthma is usually diagnosed based on the presence of wheezing and confirmed with breathing tests.
• Chest X-rays are usually normal in asthma patients.
• Avoiding precipitating factors is important in the management of asthma.
• Medications can be used to reverse or prevent bronchospasm in patients with asthma.