Asthma
Asthma is a predisposition to chronic inflammation of the lungs in which the airways (bronchi) are reversibly narrowed. Asthma affects 7% of the population, and 300 million worldwide. During asthma attacks (exacerbations of asthma), the smooth muscle cells in the bronchi constrict, and the airways become inflamed and swollen. Breathing becomes difficult, and asthma causes 4,000 deaths a year in the U.S. Attacks can be prevented by avoiding triggering factors and by drug treatment. Drugs are used for acute attacks, commonly inhaled beta-2 agonists. In more serious cases, drugs are used for long-term prevention, starting with inhaled corticosteroids, and then long-acting β2-agonists if necessary. Leukotriene antagonists are less effective than corticosteroids but have no side effects. Monoclonal antibodies such as mepolizumab and omalizumab are sometimes effective. Prognosis is good with treatment.
In contrast to chronic obstructive pulmonary disease and chronic bronchitis, the inflammation of asthma is reversible. In contrast to emphysema, asthma affects the bronchi, not the alveoli.
The National Heart, Lung and Blood Institute defines asthma as a common chronic disorder of the airways characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness (bronchospasm), and an underlying inflammation.
Public attention in the developed world has recently focused on asthma because of its rapidly increasing prevalence, affecting up to one in four urban children.
| Severity | Symptom frequency | Nighttime symptoms | Peak expiratory flow rate or FEV1 of predicted | Variability of peak expiratory flow rate or FEV1 |
|---|---|---|---|---|
| Intermittent | < once a week | ≤ twice per month | ≥ 80% predicted | < 20% |
| Mild persistent | > once per week but < once per day | > twice per month | ≥ 80% predicted | 20–30% |
| Moderate persistent | Daily | > once per week | 60–80% predicted | > 30% |
| Severe persistent | Daily | Frequent | < 60% predicted | > 30% |
Signs and symptoms
Because of the spectrum of severity within the asthma, some people with asthma only rarely experience symptoms, usually in response to triggers, where as other more severe cases may have marked airflow obstruction at all times.
Asthma exists in two states: the steady-state of chronic asthma, and the acute state of an acute asthma exacerbation. The symptoms are different depending on what state the patient is in.
Common symptoms of asthma in a steady-state include: nighttime coughing, shortness of breath with exertion but no dyspnea at rest, a chronic 'throat-clearing' type cough, and complaints of a tight feeling in the chest. Severity often correlates to an increase in symptoms. Symptoms can worsen gradually and rather insidiously, up to the point of an acute exacerbation of asthma. It is a common misconception that all people with asthma wheeze—some never wheeze, and their disease may be confused with another Chronic obstructive pulmonary disease such as emphysema or chronic bronchitis.
An acute exacerbation of asthma is commonly referred to as an asthma attack. The cardinal symptoms of an attack are shortness of breath (dyspnea), wheezing and chest tightness. Although the former is "often regarded as the sine qua non of asthma, some patients present primarily with coughing, and in the late stages of an attack, air motion may be so impaired that no wheezing may be heard. When present the cough may sometimes produce clear sputum. The onset may be sudden, with a sense of constriction in the chest, breathing becomes difficult, and wheezing occurs (primarily upon expiration, but can be in both respiratory phases). It is important to note inspiratory stridor without expiratory wheeze however, as an upper airway obstruction may manifest with symptoms similar to an acute exacerbation of asthma, with stridor instead of wheezing, and will remain unresponsive to bronchodilators.
| Sign/Symptom | Mild | Moderate | Severe | Imminent respiratory arrest |
|---|---|---|---|---|
| Alertness | May show agitation | Agitated | Agitated | Confused/Drowsy |
| Breathlessness | On walking | On talking | Even at rest | |
| Talks in | Sentences | Phrases | Words | |
| Wheeze | Moderate | Loud | Loud | Absent |
| Accessory muscle | Usually, not used | Used | Used | |
| Respiratory rate (/min) | Increased | Increased | Often >30 | |
| Pulse rate (/min) | 100 | 100-120 | >120 | <60 (Bradycardia) |
| PaO2 | Normal | >60 | <60, possible cyanosis | |
| PaCO2 | <45 | <45 | >45 |
Signs of an asthmatic episode include wheezing, prolonged expiration, a rapid heart rate (tachycardia), and rhonchous lung sounds (audible through a stethoscope). During a serious asthma attack, the accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck) may be used, shown as in-drawing of tissues between the ribs and above the sternum and clavicles, and there may be the presence of a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest.
During very severe attacks, an asthma sufferer can turn blue from lack of oxygen and can experience chest pain or even loss of consciousness. Just before loss of consciousness, there is a chance that the patient will feel numbness in the limbs and palms may start to sweat. The person's feet may become cold. Severe asthma attacks which are not responsive to standard treatments, called status asthmaticus, are life-threatening and may lead to respiratory arrest and death.
Though symptoms may be very severe during an acute exacerbation, between attacks a patient may show few or even no signs of the disease.
Prevention and Control
Prevention of the development of asthma is different from prevention of asthma episodes. Aggressive treatment of mild allergy with immunotherapy has been shown to reduce the likelihood of asthma development. In controlling symptoms, the crucial first step in treatment is for patient and doctor to collaborate in establishing a specific plan of action to prevent episodes of asthma by avoiding triggers and allergens, regularly testing for lung function, and using preventive medications.
Current treatment protocols recommend controller medications such as an inhaled corticosteroid, which helps to suppress inflammation and reduces the swelling of the lining of the airways, in anyone who has frequent (greater than twice a week) need of relievers or who has severe symptoms. If symptoms persist, additional controller drugs are added until almost all asthma symptoms are prevented. With the proper use of control drugs, patients with asthma can avoid the complications that result from overuse of rescue medications.
Patients with asthma sometimes stop taking their controller medication when they feel fine and have no problems breathing. This often results in further attacks after a time, and no long-term improvement.
The only preventive agent known is allergen immunotherapy. Controller medications include the following:
- Inhaled glucocorticoids are the most widely used prevention medications and normally come as inhaler devices (ciclesonide, beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone). Long-term use of corticosteroids can have many side effects including a redistribution of fat, increased appetite, blood glucose problems and weight gain. High doses of steroids may cause osteoporosis. These side effects are generally not seen with the inhaled steroids when used in conventional doses for control of asthma due to the smaller dose which is targeted to the lungs, unlike the higher doses of oral or injected preparations. Patients on the highest doses of inhaled steroids should take prophylactic treatment (usually Calcium and exercise, but sometimes Fosamax or similar) to prevent osteoporosis. Deposition of steroids in the mouth may result in oral thrush. Deposition near the vocal cords can cause hoarse voice. These may be minimised by rinsing the mouth with water after inhaler use, as well as by using a spacer. Spacers also generally increase the amount of drug that reaches the lungs. A new agent, ciclesonide, is inactive until activated in the lung. For this reason changing to ciclesonide can relieve dysphonia in some patients.
- Leukotriene modifiers (montelukast, zafirlukast, pranlukast, and zileuton) provide both anti-spasm and anti-inflammatory effects. In general they are weaker than inhaled corticosteroids, but the do not have any steroid side-effects and the benefit is additive with inhaled steroid.
- Mast cell stabilizers (cromoglicate (cromolyn), and nedocromil). These medications are believed to prevent the initiation of the allergy reaction, by stabilizing the mast cell. They are not effective once the reaction has already begun, and typically must be used 4 times a day for maximal effect. But they do truly prevent asthma symptoms and are nearly free of side-effects.
- Antimuscarinics/anticholinergics (ipratropium, oxitropium, and tiotropium). These agents both relieve spasm and reduce formation of mucous. They are more effective in patients with empysema or 'smokers lung.' They are rarely effective in asthma and are not true asthma controller medications.
- Methylxanthines (theophylline and aminophylline). These agents are bronchodilators with minimal anti-inflammatory effect. At one time they were the only effective asthma medications available. They are sometimes considered if sufficient control cannot be achieved with inhaled glucocorticoid, leukotriene modifier, and long-acting β-agonist combintaions.
- Antihistamines are often used to treat the nasal allergies which can accompany asthma. Older agents are too drying and can result in thick mucous so should be avoided. Newer antihistamines which do not have this effect can safely be used by patients with asthma.
- Allergy Desensitization, also known as allergy immunotherapy, may be recommended in some cases where allergy is the suspected cause or trigger of asthma. Allergy shots are dangerous in severe asthma and in uncontrolled asthma. However if allergy immunotherapy is started early in the disease there is a good chance that a remission of asthma can be induced (aka "asthma cure"). Typically the need for medication is reduced by about half with injection allergy immunotherapy, when done correctly. If a patient is only allergic to one or two items, oral allergy immunotherapy can be used. This is safe, much easier in young children, and is about half as effective. Unfortunately if a patient is allergic to more than 2 or 3 items then oral therapy cannot be given in a dose which is proven safe and effective.
- Omalizumab, an IgE blocker, can help patients with severe allergic asthma that is not well controlled with other drugs. It is expensive, but not compared with hospitalization(s). It requires regular injections.
- Methotrexate is occasionally used in some difficult-to-treat patients.
- If chronic acid indigestion (GERD) contributes to a patient's asthma, it should also be treated, because it may prolong the respiratory problem.
- Chronic sinus disease may be a contributing factor in difficult to control asthma, and should be evaluated.
Long-acting β2-agonists
Long-acting bronchodilators (LABD) are similar in structure to short-acting selective beta2-adrenoceptor agonists, but have much longer side chains resulting in a 12-hour effect, and are used to give a smoothed symptomatic relief (used morning and night). While patients report improved symptom control, these drugs do not replace the need for routine preventers, and their slow onset means the short-acting dilators may still be required. In November 2005, the American FDA released a health advisory alerting the public to findings that show the use of long-acting β2-agonists could lead to a worsening of symptoms, and in some cases death. In December 2008, members of the FDA's drug-safety office recommended withdrawing approval for these medications in children. Discussion is ongoing about their use in adults.
Currently available long-acting beta2-adrenoceptor agonists include salmeterol, formoterol, bambuterol, and sustained-release oral albuterol. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol (Advair in the United States, and Seretide in the United Kingdom). Another combination is budesonide/formoterol which is commercially known as Symbicort.
