Dr John V. Fahy University of California San Francisco
2008-07-28
Definition :
Asthma is a common disease of the lungs characterized by intermittent episodes of shortness of breath, wheezing, and feelings of chest tightness.
Introduction
Asthma is a common disease of the lungs characterized by intermittent episodes of shortness of breath, wheezing, and feelings of chest tightness. Common precipitants of wheezing episodes are exercise, cold air, exposure to allergens (for example, cat dander or house dust mite), and viral infections of the nose and lungs. Asthma usually starts in childhood, and it often occurs in people with other allergic diseases such as eczema and hay fever.
As the prevalence of allergies has increased in the past 50 years, the prevalence of asthma also has increased, and asthma now affects approximately 7% of the population. There is significant geographic variation in the prevalence of asthma with the highest prevalence occurring in countries with a western lifestyle. Within western countries asthma is more common in urban than in rural environments and more common in African Americans than in Caucasians. In children, asthma is more common in boys than in girls, but in adults it is more common in women than men. The reasons for these epidemiologic observations are not clear, but much attention has been given to the “hygiene hypothesis,” which argues that the rise of allergies and asthma in countries with a western lifestyle can be attributed to the promotion of living environments that reduce the exposure of infants and young children to bacteria and viruses. The hygiene hypothesis contends that an unintended consequence of this reduction in exposure to bacteria and viruses is the promotion of immune responses geared to respond inappropriately to harmless environmental allergens like house dust mite and cat dander. The mechanism of the gender difference in asthma in adults is not understood, but probably relates to an as-yet poorly defined role for sex hormones in promoting asthma in teen-aged females.
Although death from acute asthma attacks is relatively uncommon, it does occur, and an important warning sign is a previous bad attack of asthma. The reason why asthma is a public health concern, however, is not because of the number of deaths it causes, but because asthma is a frequent cause of emergency room visits (1.8 million per year in the U.S.) and hospitalizations (400,000 per year in the U.S). The cost of treating asthma in emergency rooms and in hospitals in the U.S. alone is $2.9 billion annually.
What causes asthma?
Asthma occurs in genetically susceptible people who encounter environmental stimuli (especially in young childhood) that promote asthma. The genetic susceptibility factors are now better understood, thanks to powerful new technologies for uncovering the gene variants that occur in patients with asthma. However, although asthma is frequently one manifestation of an allergic tendency in an individual, it is not known why only about 25% of people with nasal allergies develop asthma. It is also not known why asthma is severe in some patients, but relatively mild in most. It is thought that specific genetic susceptibility factors promote the development of asthma or severe asthma in some patients with allergies. As knowledge increases about the genetic factors that cause different types of asthma, it is hoped that asthma treatments will be tailored to an individual’s specific genetic risk(s). The environmental stimuli important for the development of asthma include allergens, viruses, bacteria, cigarette smoke, and food, but much needs to be learned about the relative importance of these different stimuli and the time windows that are important for specific environmental exposures. The role of environment as a cause of asthma is therefore the subject of much ongoing research. With the rise in obesity in children and adults, this research includes study of the link between obesity and asthma. Currently, it is thought that obesity is an independent risk factor for the development of asthma.
What part of the lungs does asthma affect?
Asthma is a disease that affects the airways. To understand asthma and its treatment it is important to have a basic understanding of the anatomy and physiology of the lung and of the abnormalities that occur in the airways of asthmatics.
Normal lung anatomy: The structure of the lung can be compared to the structure of a tree. The wind-pipe, medically known as the trachea, is equivalent to the trunk of a tree. Like a tree trunk, the trachea divides into ever-smaller branches called bronchial tubes or airways, which are tubular structures surrounded by concentric bands of muscle (Figure 1). The muscle layer surrounding the airways is not under voluntary control, and its function is unknown. Unlike muscle in the gut, which is important for the propulsive movement of food and digested food, the movement of air in the airways is not dependent on the muscle surrounding the airways but on the rhythmic negative and positive pressure cycles generated by the movement of the diaphragm.
Normal lung functions: The smallest airways open into clusters of air sacs called alveoli, which are surrounded by tiny blood vessels. The main function of the airways is to transport air into and out of the alveoli so that oxygen in inhaled air can diffuse into blood in the blood vessels surrounding the alveoli and so that waste carbon dioxide generated by the body can diffuse out of blood, into the alveolar spaces, and out of the body via the airways. The air we breathe is not sterile or free of pollutants, and the airways need a system to protect the lungs from infection or damage from inhaled toxins. The main protection system in the airways is a lining of sticky mucus. This mucus is secreted by mucus cells, including cells called goblet cells, and it is comprised of two layers - a watery liquid layer called the “sol” and an overlying gel-like mucus layer called the “gel”) (Figure 2). Tiny hair like structures called cilia on top of epithelial cells (the main lining cell type cells lining the airways) beat rhythmically and in a coordinated way in the liquid layer to propel the mucus out of the lungs toward the mouth where it is swallowed or coughed out. In this way, airway mucus traps inhaled particles like bacteria, viruses, and air pollutants. Because airway mucus is constantly being moved out of the lung by the “mucociliary escalator,” the trapped particles are moved out as well and do not get a chance to stay in the lung long enough to cause lung disease.
Figure 2: Schematic representation of how airway mucus is made up of two layers ("sol" and "gel") and how it sits on top of cilia on epithelial cells. The cilia beat is a coordinated way to move mucus from inside the lungs toward the mouth.
Figure 3: Eosinophils are prominent in the airway secretions from asthmatics: Eosinophils are a type of white blood cell, and they often occur at sites of allergic inflammation. The figure shows cells in a sputum sample from an asthmatic subject, and there are many eosinophils visible (highlighted with black arrow-heads). Eosinophils are identified by their red granules when the sputum slide is stained with a staining solution containing eosin.
The fact that airway inflammation is a prominent feature of asthma is the rationale for emphasizing treatment of asthma with anti-inflammatory drugs such as inhaled corticosteroids.
How is asthma diagnosed?
The diagnosis of asthma is based on symptoms of intermittent episodes of shortness of breath, especially with exercise, exposure to airborne allergens, or head colds. Shortness of breath and wheezing are non-specific symptoms, however, and a diagnosis of asthma requires confirmation from pulmonary function tests (breathing tests). X-rays cannot diagnose asthma, because the chest x-ray appearance is often normal in asthma, but x-rays can show evidence that air is being “trapped“ in the lungs (a finding that occurs in asthma but in some other lung diseases as well), and x-rays can identify other causes of shortness of breath and direct attention way from asthma as a diagnosis.
Spirometry: Pulmonary function tests require patients to take a deep breath and to exhale forcefully into a machine called a spirometer, which records how much air is exhaled and how fast. Results of spirometry tests from patients with asthma show that they can often exhale as much air as normal – their forced vital capacity [FVC] is normal – but it takes them longer to exhale. This prolonged exhalation time is reflected in a lower than normal forced expired volume in one second (FEV1). The FEV1 is normally 75% of the FVC, but this ratio is lower in asthmatics. The reason for the lower than normal FEV1 is excessive contraction of airway smooth muscle. This excessive smooth muscle contraction can be reversed, at least partially, by drugs such as albuterol (Ventolin, Proventil, Xopenex), which relax airway smooth muscle by stimulating beta-adrenergic receptors on the surface of the muscle cells. Albuterol, and other drugs in the beta agonist drug class, act quickly to relax airway smooth muscle, so spirometry before and after albuterol treatment can be done within the same half-hour period. If the FEV1 increases by 12% or greater following treatment with albuterol, then this result is indicative of asthma.
Peak flow meters: Asthma is an intermittent disease, and patients with asthma can have normal pulmonary function tests on days when they are free of symptoms. If the results of spirometry are normal, then measurement of daily peak flow rates using a portable peak flow meter is a test that can be used to pick up asthma. Peak flow meters are easy to use and allow measurements of lung function at home. If diary card data from twice daily measures of peak flow show low readings during periods of exercise, or low readings first thing in the morning (when many asthmatics experience wheezing), then these findings support a diagnosis of asthma.
Methacholine challenge test: Methacholine is a chemical which causes airway smooth muscle to contract. Non-asthmatic subjects need to inhale a relatively large concentration of methacholine to have a 15% decrease in their FEV1. In contrast, asthmatics are very sensitive to methacholine, and low concentrations are sufficient to cause a 15% decrease in FEV1 (Figure 4). Measuring sensitivity to inhalation of methacholine is therefore a good way to diagnose asthma in patients in whom the diagnosis is difficult or in doubt.
Figure 4: Methacholine hyper-responsiveness is a characteristic of asthma: The figure shows the relationship between the concentration of methacholine inhaled (X axis) and the % decline in FEV1 (Y axis) in four asthmatic subjects (red) and four non asthmatic subjects (blue). Note that asthmatics have larger declines in FEV1 at lower concentrations of inhaled methacholine.
Diagnosing asthma in children: The diagnosis of asthma in young children can be difficult, because symptoms of lung infections in children under the age of five mimic the symptoms of asthma, and children under the age of five years are usually unable to perform lung function tests properly. For children with a family history of asthma, a current history of allergies or eczema, and a clear history of exercise- or allergen-induced wheezing symptoms, it is possible to make a diagnosis of asthma. For children whose symptoms occur only when they have colds or chest infections, it may be necessary to wait until they are older and getting less frequent infections to be sure about a diagnosis of asthma.
What is the treatment for asthma?There is no cure for asthma, although not all children with asthma will continue to experience asthma symptoms as adults. The long-term goal for managing asthma is to minimize symptoms (including symptoms during exercise), reduce the risk of getting bad attacks of asthma, reduce the risk of loss of lung function from asthma, and minimize the side effects of asthma medications. This goal can be achieved in the vast majority of patients using several effective classes of asthma medications, avoidance of airborne allergens, and education about asthma.
Principals of asthma managementAsthma is a disease for which treatment is effective in providing good symptom relief and freedom from attacks in most patients. Treatment includes asthma medications, allergen avoidance, and disease education.
Guidelines for the treatment of asthma emphasize a partnership between the patient and the health care provider. Patients should take every opportunity to get educated about their asthma, including during visits to their doctor’s office and to the hospital. Part of education is information about the rationale for treatment with different asthma medications, the proper use of inhalers (good inhaler technique), and allergen avoidance.
Asthma that does not respond to usual medications or allergen avoidance measures may be resistant to treatment because of the coexistence of another disease that is known to make asthma worse. Examples of these other diseases include gastroesophageal reflux (“heartburn,” which may be asymptomatic), allergic rhinitis (“hay-fever”), sinusitis (which can be asymptomatic when chronic), obesity, severe allergies to aspergillus (a disease called “allergic bronchopulmonary aspergillosis”), obstructive sleep apnea, stress, and depression. Diagnosing and treating these conditions may improve asthma control.
Asthma MedicationsSeveral types of medication are used to treat asthma:
1. Short Acting Beta agonists (Albuterol [called Salbutamol in Europe], Levalbuterol, Pirbuterol).
Short Acting Beta agonists are used to quickly relieve symptoms of asthma. These drugs act on the beta-adrenergic receptors of airway smooth muscle cells and cause the muscle cells to relax. This has the effect of dilating the airway and improving airflow. Most asthmatics experience very rapid relief from symptoms of chest tightness when they inhale albuterol, and albuterol is the mainstay of treatment for acute attacks of asthma. The mildest forms of asthma can be managed by use of albuterol on an as-needed basis for symptoms of wheeze or shortness of breath.
2. Inhaled corticosteroids (Budesonide, Beclomethasone, Fluticasone, Flunisolide, Momethasone, Triamcinolone acetonide).
Inhaled corticosteroids are the main types of medicine used to control asthma, because they improve may aspects of asthma controls including symptoms, lung function, and frequency of asthma attacks. Their onset of action is not fast and they are usually not used to manage an acute attack of asthma.
The dose of inhaled corticosteroids used in inhalers is much less than the dose in steroid tablets, and the benefits of steroid inhalers outweigh the risk of steroid side effects.
3. Long acting beta agonists (Salmeterol, Formoterol)
Long acting beta agonists are used in combination with inhaled corticosteroids to improve asthma control. The mechanism of action of salmeterol and formoterol is similar to that of albuterol, but the duration of their effect is at least twice as long. Unlike albuterol, salmeterol and formoterol are not used as stand-alone medicines to relieve asthma symptoms, but rather as part of combination inhalers which combine one of these drugs with an inhaled corticosteroid.
4. Combination inhalers (Advair [salmeterol + fluticasone]; Foradil (formoterol + budesonide).
Combination inhalers include two drugs – a long acting beta agonist and an inhaled corticosteroid, and these combination inhalers are used to improve asthma control. These combination inhalers have proven to be effective in controlling asthma that is not controlled by treatment with inhaled corticosteroids alone.
5. Oral corticosteroids (prednisone, prednisolone, methylprednisolone)
Tablets which contain a corticosteroid are usually used in short bursts to treat asthma attacks, but sometimes patient with severe asthma need to take steroid tablets every day control their asthma.
6. Inhibitors of the leukotriene receptor pathway (Montelukast, Zafirlukast, Zileuton)
Drugs which inhibit the leukotriene receptor pathway are used to control asthma symptoms. Leukotrienes are chemicals in the body that can cause smooth muscle contraction, leakiness of blood vessels, and mucus secretion. Inhibiting leukotrienes improves asthma symptoms and these mediations can be used instead of inhaled corticosteroids, although they are usually not as effective.
7. Cromolyn and Nedocromil
Cromolyn and nedocromil are used to control asthma and to prevent exercise-induced asthma. These drugs prevent the release of allergic chemicals from mast cells, a cell that is involved in wheezing caused by allergies and exercise. These drugs can be effective in preventing asthma brought on by exercise and they can be a replacement for inhaled corticosteroids, although they are usually not as effective.
8. Theophylline
Theophylline is prescribed as a tablet and it is used to control asthma. It acts by inhibiting adenosine receptors and by inhibiting phosphodiesterases enzymes, effects which result in relaxation of airway smooth muscle, but which also cause troublesome side effects (fast heart rate, nausea). The dose of this drug is adjusted based on the blood levels, which vary from patient to patient.
9. Omalizumab
Omalizumab is precribed as an injection to be given every 2 or 4 weeks, and it is used to treat more severe forms of asthma. Omalizumab inhibits immunoglobulin E - a protein in the body that interacts with inhaled or ingested allergens to cause allergic reactions. Omalizumab is given as an injection every two or four weeks.
10. Ipratropium Bromide
Ipratropium Bromide is prescribed to treat acute attacks of asthma. This drug inhibits cholinergic nerve stimulation in the airways, an effect which relaxes airway smooth muscle and may decrease mucus secretion. It is most commonly used for management of patients with chronic bronchitis and emphysema, but it is also used as a nebulizer (liquid mist) treatment to manage an acute asthma attack, in which case it is used in combination with albuterol or levalbuterol.
Taking medication correctlySome patients find asthma inhalers difficult to use, so it is important to take time to learn from the health care provider how to use inhalers properly and how to recognize when they are empty. Side effects from inhaled corticosteroids, such as hoarseness or thrush, can be greatly minimized by gargling with water immediately after using steroid inhalers.
Other treatments for asthmaAllergen avoidance: Many asthmatics are allergic to house dust mites or to cat dander, and these allergies can make asthma worse. House dust mite exposures can be reduced, especially in the bedroom, by limiting carpeting or soft furnishings that can trap house dust. Wrapping mattresses and pillows in special materials can limit house dust mites in bedding. Cat exposures can be reduced by preventing cats from being in bedrooms and by washing cats.
Allergy shots: The evidence supporting the use of allergy shots for asthma is not strong, but shots may be effective in some asthmatics who have well defined allergies.
Treatment plans for asthmaPatients with asthma should monitor their symptoms or peak flow rates in order to assess their level of asthma control and to pick up on signs of worsening asthma. In patients who do not perceive symptoms well, peak flow monitoring may be particularly helpful as a way to detect worsening asthma. A peak flow meter is a plastic portable device that records peak flows when patient fill their lungs and blow quickly into it. It is a useful device for monitoring trends in lung function at home. Treatment plans work best for asthma when they are formalized as a written document between the patient and the health care provider. This document provides clear instructions for what measures to take when asthma symptoms worsen or peak flow rates decrease (e.g., how to adjust medication, and when to seek medical care).
Asthma AttacksAsthma attacks are periods of uncontrolled asthma in which the patient experiences increased symptoms of shortness of breath, chest tightness, cough, and sputum. Asthma attacks can come on quickly following a specific exposure (e.g., cat dander exposure) or during exercise. Attacks can also come on more slowly (e.g., asthmatics who get a head cold often notice that their asthma gets worse over a day or two). Asthma attacks can sometimes be controlled by taking more frequent inhalations of albuterol until the attack resolves. More severe attacks, however, require a visit to an urgent care clinic or to the emergency room. Asthma attacks need to be taken seriously because they can sometimes be severe and even life threatening. Clues to a severe attack include severe symptoms, or symptoms that are not relieved by albuterol. In addition, a history of prior attacks requiring treatment in an emergency room or in an intensive care unit should alert a patient that their asthma attack may need to be treated at the hospital.
Health care providers who assess patients with asthma will take history of asthma attacks into account in their assessment of an individual patient’s asthma severity. Thus, even if lung function is good or if daily symptoms of asthma are minimal, a history of frequent bad attacks, or attacks which require hospitalization, will be taken into account by the provider when he/she is developing a treatment plan. This is because a history of severe asthma attacks portends a risk of future severe attacks, and the provider will initiate measures to decrease this risk.
Web based resources for asthma
1. Asthma information
http://www.nhlbi.nih.gov/health/public/lung/index.htm#asthma
http://www.thoracic.org/sections/education/patient-education/patient-education-materials/patient-information-series/asthma-and-exercise-for-children-and-adults.html
http://www.lungusa.org/site/apps/nlnet/content3.aspx?c=dvLUK9O0E&b=2058817&content_id={05C5FA0A-A953-4BB6-BB74-F07C2ECCABA9}¬oc=1
http://www.lungusa.org/site/apps/nlnet/content3.aspx?c=dvLUK9O0E&b=2058817&content_id={39966A20-AE3C-4F85-B285-68E23EDC6CA8}¬oc=1
http://www.aaaai.org/patients/gallery/childhoodasthma.asp
http://www.aaaai.org/patients/gallery/adultasthma.asp
2. Asthma Treatment Guidelines
http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.htm
3. Allergen avoidance:
http://www.aaaai.org/media/resources/academy_statements/position_statements/ps36.asp
4. Using inhalers properly
http://patients.uptodate.com/topic.asp?file=al_asthm/5100