Allergic Asthma: Symptoms and Treatment
Posted: May 2006
H. Henry Li, MD, PhD
Michael A. Kaliner, MD FAAAAI
The word asthma derives from the Greek word for panting, or breathlessness, and thus describes the primary symptom of this disease. Asthma can be defined clinically as recurrent airflow obstruction causing intermittent wheezing, breathlessness, chest tightness and cough, sometimes with sputum production. Our current concept of asthma revolves around three related components: symptoms are caused by intermittent or persistent reversible airflow obstruction, there is underlying airway inflammation, and the airways express increased responsiveness to a variety of stimuli (such as allergens or cold air).
Allergic asthma can be classified into four clinical phases, based upon symptoms and pulmonary function testing. This classification system allows physicians to communicate more uniformly regarding asthma severity and facilitates the creation of general guidelines for treatment. The four categories currently employed are:
Mild intermittent asthma,
Mild persistent asthma,
Moderate persistent asthma,
Severe persistent asthma.
Patients with mild intermittent asthma have symptoms less than twice weekly and the patient is otherwise asymptomatic. Pulmonary function studies are normal except during periods of disease and exacerbations are brief and easily treated.
Patients with mild persistent asthma have symptoms more than twice a week but less than daily. The symptoms are severe enough to interfere with daily activities and may interrupt sleep up to twice a month. Pulmonary function studies are normal or show mild airflow obstruction which is reversible with the inhalation of a bronchodilator.
Moderate persistent asthma indicates the stage of disease where symptoms occur daily, and the disease severity warrants regular use of medications for control. Patients are constantly aware of their disease, require medications on a daily basis, have their sleep interrupted at least weekly, and have to accommodate their life style to the disease. Pulmonary function is moderately abnormal, with the FEV1 being 60-80% of the predicted value.
Severe persistent asthma is defined as continuous symptoms despite the correct use of medications. The severity of the disease limits physical activities and is associated with frequent exacerbations and sleep interruption. Treatment requires combinations of medications on a constant basis. Pulmonary function tests are severely affected with the FEV1 being <60% of predicted.
A patient may fit into one category upon initial visit and another after treatment or during an exacerbation. For example, a patient with mild persistent disease can be exposed to allergens or develop a respiratory infection and have a severe exacerbation of asthma, changing the disease classification from mild to severe, until the exacerbation is resolved. Conversely, a patient with severe persistent symptoms can be treated effectively with resolution of symptoms and be reclassified to a mild category while on treatment.
The symptoms of asthma are caused by intermittent reversible episodes of airflow obstruction manifested clinically by cough, wheezing, chest tightness and dyspnea. When evaluating a patient with asthma, each of the following should be assessed:
- Family and personal history of atopic disease, including results of previous skin testing
- Age of onset of asthma, frequency and severity of symptoms and attacks
- Pattern (including seasons) and places of occurrence of asthmatic attacks
- Environmental conditions or factors that trigger symptoms and
- The severity of the disease. This is judged by:
- Wheezing episodes per day, week or month,
- The number of missed school or work days per year,
- Whether sleep is interrupted and how often this occurs,
- The necessity for emergency room or urgent care visits,
- The number of hospitalizations for asthma.
Other parameters to be assessed include
- Details of previous pharmacologic or immunologic therapy and its efficacy
- The presence of concomitant diseases or conditions that may influence asthma, including:
- Gastro-esophageal reflux or laryngopharyngeal reflux, and
- Bronchitis or smoking.
Early in the disease, symptoms may include a vague, heavy feeling of tightness in the chest and in the allergic patient, there may be associated rhinitis and conjunctivitis symptoms. Typical symptoms which patients experience include coughing, wheezing, chest tightness and dyspnea. Cough in asthma is usually non-productive, but it may progress to expectoration of viscous, mucoid sputum which is difficult to clear. If the sputum turns purulent or discolored, an infection may be present, as the sputum in asthma is usually clear to light yellow in color.
There is a subgroup of asthmatics whose asthma is characterized solely by cough, without overt wheezing, the "cough variant of asthma". If this syndrome is suspected, airflow should be examined by spirometry before and after bronchodilator inhalation or after methacholine inhalation challenge. The cough responds well to inhaled glucocorticosteroid medications.
Patients with allergic asthma, as suggested by seasonal exacerbations or allergen-related triggering events, may be sensitive to pollens, dust mites, animal danders, mold spores, occupational dusts, or insects. Less frequently, some children may have food allergy which provokes asthma. Atopic patients are often allergic to many allergens and may react to tiny amounts of allergens. The most sensitive way to identify potentially relevant allergens is by appropriate allergy skin testing. Because allergen avoidance is so important in asthma management, it is usually recommended that any asthmatic who wheezes more than 2 days per week be skin tested.
To complicate the identification of relevant triggers, many asthmatics also respond to non-allergic conditions, cigarette smoke, noxious fumes, upper respiratory tract infections, or weather conditions by wheezing.
In the completely asymptomatic patient, results of chest examination will be normal, although head, eye, ear, nose, and throat examination may disclose concomitant serous otitis media, allergic conjunctivitis, allergic rhinitis, nasal polyps, paranasal sinus tenderness, signs of postnasal drip, or pharyngeal mucosal lymphoid hyperplasia. Clubbing of the fingers is extremely rare in uncomplicated asthma, and this finding should direct the physician's attention toward diseases such as bronchiectasis, cystic fibrosis, pulmonary neoplasm, or cardiac disease. Many symptomatic asthmatics can be diagnosed by careful auscultation of the chest which reveals the presence of expiratory wheezing and a somewhat prolonged expiratory phase.
With an acute severe asthma exacerbation, patients may be restless, agitated, orthopneic, tachypneic, breathing through pursed lips with a prolonged expiratory phase, using accessory muscles of respiration. They may be diaphoretic, cough frequently, have audibly wheezing and be cyanotic. Cyanosis occurs only with profound arterial oxygen desaturation and is a grave sign that appears late in the course of severe asthma. Vital signs will confirm the physician's impression that the patient is tachypneic, and evaluation of the blood pressure may show that the patient has a pulsus paradoxus. The latter sign, when present, is a relatively reliable indicator of severe asthma. Although a low-grade fever is usually of viral origin, the presence of an elevated temperature should alert the physician to search for a possible bacterial infection requiring antibiotic therapy.
Examination of the chest in severe asthma will often show signs of hyperinflation, such as hyperresonance on percussion and low, immobile diaphragms. In milder stages of asthma, wheezing may be detected on forced expiration, but with increasing severity, wheezing may also be heard on inspiration. In some episodes of severe asthma, wheezing may be heard early in the course of disease, but with increasing obstruction of the airways, the wheezing may seem to "improve" as increasing difficulty in ventilation develops. This abatement of wheezing may be taken as a clinical sign of improvement and result in less-than-optimal treatment. As the patient improves, one may notice the reverse situation; namely, that wheezing may increase in intensity. Again, this finding should not be erroneously interpreted as worsening of the asthma. The major point is that in judging the severity of asthma, the physician must rely on many physical findings (such as the use of accessory muscles and the presence of paradoxical pulse) as well as the degree of wheezing. As the patient recovers, the improvement takes place most often in reverse order of the appearance of symptoms, i.e., there is a sequential loss of mental status abnormalities, cyanosis, pulsus paradoxus, use of accessory muscles, dyspnea, tachypnea, and, finally, wheezing. It is important to note, however, that when the attack appears to have ended clinically, abnormal pulmonary function is still present and may persist for days. Treatment of any severe exacerbation should be continued well past the symptomatic period and close outpatient follow-up is indicated.
About 50% of asthmatics older than 30 years of age are concomitantly allergic. Younger asthmatics have an even higher incidence of allergies. Thus, coincidental allergies are far and away the most common underlying condition associated with the development of asthma. One should suspect allergy as a contributing factor when there is a family history of allergic diseases, the clinical presentation includes seasonal exacerbations or exacerbations related to exposures to recognized allergens, and there is concomitant allergic rhinitis or other allergic disease. Other factors to support allergy include the presence of a slight-to-moderate blood total eosinophilia (300 to 1000/mm3) or eosinophilia in the sputum. Skin testing can be used to confirm IgE directed against incriminated allergens.
Because limiting exposure to allergens and allergy immunotherapy are both specifically helpful in treating allergic asthmatic subjects, a careful search for possible allergies is indicated in nearly all asthmatics, certainly all persistent asthmatics. It was once thought that allergic asthma was associated with a milder form of disease, but this contention has not been borne out. Allergic asthma is as severe as any other kind of asthma. In fact, the efficacy of omalizumab in treating moderate to severe asthma indicates that reducing IgE, and thereby reducing allergy, has a beneficial effect on even severely affected asthmatics.
In addition to allergen-induced asthma, many other factors and conditions such as exercise, infection, occupational chemical exposures, side effects to medications such as beta adrenergic blocking agents, bronchitis, and Churg-Strauss allergic granulomatosis can also cause asthma. Sinusitis, GERD, hyperthyroidism, pregnancy and infections may complicate asthma.
It is not currently possible to prevent the onset of asthma in susceptible individuals. Accumulating evidence indicates that allergen sensitization is one of the most significant factors leading to the development of asthma. It is conceivable that perinatal intervention leading to the reduction of IgE sensitization and the subsequent development of allergies might be beneficial. Approaches which modulate the Th2/Th1 responses still require further clinical investigation. For those allergic children who do not yet have asthma, there is some limited evidence that using antihistamines may reduce the chance of subsequently developing wheezing. In addition, allergen-specific immunotherapy for allergic rhinitis in children may reduce the chance of them developing asthma.
In order to avoid the respiratory infections which can exacerbate asthma, annual influenza vaccines are recommended for asthmatic patients. It must first be established if the patient is allergic to egg, and if the available vaccine has been grown on an egg-based medium it should not be prescribed. Vaccine against Streptococcus pneumoniae should also be considered.
Avoidance of exposure to the incriminated allergens should underlie all pharmacotherapy.
Over the past decade, the treatment of asthma has changed remarkably, largely because of the increased understanding of the pathophysiology of the disease, and the recognition of the importance of airway inflammation. Recognizing that the airflow obstruction in asthma is due to a combination of airway wall edema, increased mucus secretion, increased inflammation, bronchial smooth muscle contraction and increased airway irritability and not just bronchospasm, as was once thought, has led to a fundamentally altered approach to asthma therapy.
One way to summarize the basic concepts of this approach is based upon separating the treatments used in asthma into specific (long term controlling) agents and symptomatic (short term relieving) agents. "Specific agents" reduce the underlying causes of asthma and thereby reduce the symptoms of the disease and the need for symptomatic agents. "Symptomatic agents" act only by reducing the symptoms of airflow obstruction and have no effect on the underlying causes of asthma. For example, inhaled corticosteroids (ICCS) reduce airway inflammation and act specifically, while a short acting beta adrenergic agent (SABA) acts only to relax smooth muscle and reduce bronchospasm, a symptomatic action. Thus, treatments used for asthma can be separated into specific treatments and symptomatic treatments.
All patients should receive one or more specific treatments and may also receive symptomatic treatments, as needed. As a patient's symptoms warrant classification into one of the more severe categories of asthma, patients may require more medications, both specific and symptomatic. Thus, the general approach in a more severely affected patient is to treat initially with combinations of specific and symptomatic therapies in order to totally control the symptoms and then to reduce the treatments to the least amount of medications required to maintain remission.
Mild intermittent asthma only requires treatment with SABA, on an as-needed basis. At the next level, mild persistent asthma requires more chronic dosing, and the usual approach is to use a low-to-moderate dose of ICCS and/or a leukotriene modifier, plus a SABA given on an as-needed basis. Moderate asthma is usually treated with a higher dose of ICCS and/or a long acting bronchodilator (LABA) or a leukotriene antagonist. The combination of LABA and ICCS, e.g., fluticasone/salmeterol or budesonide/formoterol, is recognized as an effective treatment option in the moderate or severe asthmatic patient. Oral theophylline may be used in addition to or in place of the LABA or leukotriene antagonist. In selected moderate to severe patients, anti-IgE (omalizumab) might be added to reduce the need for ICCS.
For severe persistent asthmatic patients, the combination of higher doses of ICCS and LABA is the preferred treatment option. These patients may also require leukotriene antagonists, and, if symptoms persist, oral corticosteroids (CCS). Monoclonal anti-IgE can be given to moderate to severe persistent asthmatics to reduce exacerbations, lower CCS requirement, and reduce disease severity.
In all patients, symptomatic therapies are also given, to be used on an as needed basis. The goal in all of these patients is to tailor the medicines and their doses to control the level of the disease, always trying for optimal control with the lowest effective dose of medications.
A brief summary of the basic concepts of asthma management includes the following:
- Daily use of specific treatments (long term control treatments), often used in combination.
- Symptomatic use of bronchodilators (quick relief medications) used only on an as-needed basis.
- Step therapy:
- Use whatever dose or combination of therapies that are required to totally control symptoms and achieve a maximum, personal best, peak flow,
- Once completely controlled, step down the treatment plan to the lowest effective doses of medication while maintaining symptom control and personal best peak flow.
- Regular follow-up visits.
- Written management plan (including emergency treatment plan).
- At home monitoring with peak flow meters.
- Allergy management is superimposed upon other treatment modalities for long-term control at all levels of asthma.
Concurrent upper airway disease, eg, allergic rhinitis, sinusitis, should be treated, and the total dose of inhaled corticosteroids must be monitored.
Allergen injection immunotherapy is effective in allergic asthma as well as in allergic rhinoconjunctivitis and has been shown to lead to highly significant improvements in symptoms, reduction in rescue medication, and improvements in both allergen specific and non-specific bronchial hyperresponsiveness. Immunotherapy is particularly effective in seasonal asthma, although less effective in perennial asthma. Bronchial asthma is a risk-factor for systemic reactions to immunotherapy and should not be considered in poorly-controlled asthmatics.
Asthma is one of the most common chronic diseases worldwide. It is estimated that 150 million people around the world suffer from asthma. Mortality has reached over 180,000 annually. In Western Europe the incidence of asthma has doubled in ten years. Around 8% of the Swiss population suffers from asthma as compared with only 2%, 25-30 years ago. In the United States, there were an estimated 20.3 million asthmatics in 2001; the number of asthmatics has leapt by over 60% since the early 1980s and deaths have doubled to 5,000 a year. There are about 3 million asthmatics in Japan of whom 7% have severe asthma and 30% have moderate asthma. In Australia, one child in six under the age of 16 is affected.
Asthma is not just a public health problem for developed countries. In developing countries, the incidence of the disease varies greatly. India has an estimated 15-20 million asthmatics and rough estimates indicate a prevalence of between 10% and 15% in 5-11 year old children.
In the Western Pacific Region of WHO, the incidence varies from over 50% among children in the Caroline Islands to virtually zero in Papua, New Guinea. In Brazil, Costa Rica, Panama, Peru and Uruguay, prevalence of asthma symptoms in children varies from 20% to 30%. In Kenya, it approaches 20%.
Worldwide, the economic costs associated with asthma are estimated to exceed those of TB and HIV/AIDS combined. In the United States, for example, annual asthma care costs (direct and indirect) exceed US$6 billion.
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