Asthma Therapy:

Because of their broad anti-inflammatory effects, inhaled corticosteroids are the cornerstone of maintenance therapy in mild, moderate, or severe persistent asthma. They are the only agents clearly demonstrated to have disease-modifying properties: they reduce bronchial hyperreactivity and slow or halt progressive loss of airway function. Other benefits include reduced symptom severity, improvement in peak expiratory flow (PEF) and spirometric measures, and prevention of exacerbations.

Some patients and physicians are concerned about the long-term use of these agents.^1-3 Like most medications, corticosteroids may have side effects. However, at recommended dosages, inhaled corticosteroids do not have frequent, clinically significant, or irreversible effects on the following parameters in children: vertical growth, bone mineral density, ocular toxicity, and suppression of the adrenal/pituitary axis. Long-term use continued through adulthood may increase the relative risk of such conditions as osteoporosis, cataracts, and glaucoma.^4-6

For most patients, the benefits of inhaled corticosteroids outweigh the risks. Educating patients and their families about the use of these agents is an important step in ensuring compliance with an asthma management program.

Does your patient with asthma need inhaled corticosteroids? The answers to the 5 questions in this article can help you decide.

Does the patient have asthma?

Asthma is a complex inflammatory syndrome with many possible clin- ical presentations.^7-9 Key indicators are listed in Table 1. Not all wheezing is asthma, and not all asthma presents with wheezing. A diagnosis of asthma is based on findings from the history and physical examination that indicate an episodic pattern of respiratory symptoms and the demonstration of reversible airway obstruction on spirometry. A 12% increase in forced expiratory volume in 1 second (FEV₁) following 2 puffs of a β₂-agonist is considered diagnostic.^4,8 If the pretreatment FEV₁ is normal, the diagnosis can be made if the patient demonstrates bronchospasm (a 20% decrease in FEV₁) following a histamine, methacholine, or cold-air challenge.

Children as young as 5 years can usually be evaluated with spirometry. However, it is sometimes difficult to complete a spirometric evaluation in children younger than 7 or 8 years. Therefore, the diagnosis of asthma in these children may be based on improvement in or resolution of symptoms following inhalation or nebulizer treatment with a short-acting β₂-agonist.^8,10

In practice, the diagnosis of asthma is frequently presumptive, based on observed or patient-reported improvement in wheezing, coughing, breathing, or PEF rate following inhalation of a bronchodilator. The likelihood of an asthma diagnosis is increased by a family history of asthma; a personal history of eczema or allergic rhinitis; or episodic breathing difficulties related to exercise, exposure to irritants (including cold air, cigarette smoke, and strong odors), or allergic triggers (such as dust, animal dander, pollen, mold, or cockroaches).¹¹

In adults with symptoms of new onset, consider alternative diagnoses, such as chronic obstructive pulmonary disease (especially in smokers), gastroesophageal reflux disease, occupational exposures, pneumonia, congestive heart failure, neoplasm, vocal cord dysfunction or, rarely, pulmonary emboli.⁸ Children (especially those younger than 3 years) who present with wheezing may be reacting to an acute illness, such as respiratory syncytial viral infection, and will have only a few episodes of bronchospasm that come and go for 6 months to a year and never recur.¹² In an otherwise healthy young child who has wheezing or breathlessness of sudden onset, always consider airway obstruction from a foreign body.

If the patient has asthma, proceed to question 2. If not, plan additional evaluation as warranted by the differential diagnosis. Consider consultation with an asthma specialist if the patient's symptoms are ambiguous.

How severe is the asthma?

2Although clinical and epidemiologic information related to mild intermittent asthma is scant, as many as 40% to 50% of asthmatic patients appear to have disease of this severity.⁹ Patients with mild intermittent asthma may have only 2 or 3 short episodes each year.¹³ Persistent asthma is comparable to other chronic inflammatory conditions, with some level of underlying disease punctuated by recurrent exacerbations.

Severity classification. Although there is no evidence-based asthma severity classification, the system developed by the National Asthma Education and Prevention Program (NAEPP) appears to be a reasonable clinical tool for guiding initial asthma treatment (Table 2).^4,8 Asthma is classified as intermittent (long periods with no symptoms) or persistent (no long periods without symptoms). Persistent asthma may be mild, moderate, or severe.⁴ Severity is determined by the frequency, intensity, and duration of symptoms; level of airflow obstruction; and the extent to which asthma interferes with daily activities.

The presence of any single feature places the patient in that category. For example, a patient who has a few hours of daytime wheezing 3 or 4 times a year and normal FEV₁ but who wakes up once a week with a coughing spell would be classified as having mild persistent asthma because of the frequency of nighttime symptoms.

When trying to ascertain the severity of your patient's asthma, avoid asking general questions, such as, "How is your asthma doing?" This type of question often invites vague and irrelevant answers. Instead, ask the following:

• How many days of the week do you have symptoms?
• Do the symptoms last all day or only part of the day?
• How many nights a week or month do you have symptoms?
• Do you have long periods (weeks or months) without any symptoms?

The answers to these questions determine whether your patient is likely to require inhaled corticosteroids. Using the same questions at each visit lets the patient know what you expect and elicits specific answers. These questions can also be used to assess treatment outcomes. Reassessing severity at regularly scheduled appointments (not just following exacerbations) allows you to adjust the dosage of inhaled corticosteroids and other asthma medications.

Which patients need inhaled corticosteroids? Most patients seen in primary care have mild intermittent or mild persistent asthma. Mild intermittent asthma with few exacerbations and no intervening symptoms or activity limitations may be a different condition from chronic asthma or may represent differential disease expression based on genotype and early environmental exposures. It can be managed with as-needed therapy, such as a short-acting inhaled β₂-agonist; maintenance medication is not required.¹⁴

Patients with mild, moderate, or severe persistent symptoms have clear signs of continuous inflammation and need daily inhaled corticosteroids. Other anti-inflammatory medications, such as cromolyn, are usually inadequate to control symptoms in patients with moderate or severe persistent asthma, although they may be effective in mild persistent asthma.^4,15

Asthma severity may vary with the season. Patients with mild or even moderate persistent asthma may be eligible for step-down therapy that involves the use of inhaled corticosteroids for only a few weeks or months during and following exacerbations.^11,14 Those with moderate persistent asthma require a medium- to high-dose inhaled corticosteroid, and those with severe persistent asthma require a high-dose inhaled corticosteroid, in addition to other medications. It is important to help patients and their families understand that asthma is a chronic inflammatory process, rather than an episodic disease, and that therefore daily maintenance medication is crucial for optimal well-being.

Unrecognized symptoms. Recent studies suggest that many children classified as having mild intermittent asthma may have unrecognized and untreated persistent symptoms.^16-18Patients and their families may fail to recognize recurrent symptoms as manifestations of asthma or may dismiss them as "normal" limitations.¹⁷ Clinical experience indicates that adults also have unrecognized and untreated asthma, although few studies address this condition. Therefore, it is important to ask a patient specifically about daytime and nighttime symptoms, including coughing, wheezing, shortness of breath, chest tightness, nighttime awakenings, and exercise intolerance.

If a patient reports a few hours of symptoms 2 or 3 days a week or a few nights a month, ascertain whether he or she has other symptoms or limitations on activity. For example, if the patient is a child who prefers not to play outside or chooses only quiet activities on the playground, determine whether he has exercise-induced symptoms or poorly controlled recurrent symptoms that he has not previously reported.

Similarly, question a sedentary adult who has asthma about whether he experiences breathing problems on exertion. A 2- or 3-week trial of inhaled corticosteroidsin a sedentary person with mild intermittent asthma may provide relief. Some persons with asthma describe symptoms as "fatigue" or "activity intolerance" because they do not perceive them as asthma-related dyspnea or breathlessness.

Because the course of asthma is variable, the severity of the disease may change over time. Sometimes the reason for this is clear: a move to a new climate with a new set of allergens, pregnancy, or increased exposure to smoke or occupational irritants may increase asthma severity. Referral to an allergist may be warranted if asthma severity increases with no clear cause.

Does the patient have exacerbations?

3The NAEPP classification of asthma severity is based on clinical manifestations of disease in an untreated person. Patients with asthma at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent asthma have severe or life-threatening exacerbations separated by long periods with no symptoms or mild symptoms and normal pulmonary function.

A severe exacerbation is indicated by a PEF rate that is less than 50% of personal best or predicted value. Accessory muscle use and suprasternal retractions also suggest severe exacerbation.⁸

The NAEPP guidelines suggest that during exacerbations corticosteroid therapy may be initiated or increased as follows^4,8:

• For mild exacerbations in patients taking an inhaled corticosteroid, double the dose until PEF returns to its predicted value or personal best.
• For moderate to severe exacerbations and for mild exacerbations that persist despite an increased dose of inhaled corticosteroids, prescribe a course of oral corticosteroids.
• Continue more intensive treatment for several days, until symptoms and PEF are normal. Recovery from an exacerbation is often gradual.

Patients with a history of life-threatening exacerbations require an exhaustive history to ascertain the presence of allergies, asthma triggers, and irritants. You may wish to refer such patients to specialists who can evaluate them thoroughly for underlying problems, including unrecognized symptoms of persistent asthma.

Does the patient have asthma triggers that can be identified and controlled?

4Successful long-term management of asthma requires identification and control of environmental factors that increase asthma symptoms and/or precipitate exacerbations (see Health Guide, page 1079). Pharmacotherapy is best implemented in conjunction with environmental control measures that reduce a patient's exposure to known asthma triggers. The NAEPP lists 4 groups of environmental factors that contribute to asthma severity⁸:

• Inhalant allergens.
• Occupational exposures.
• Medical/pharmacologic factors.
• Irritants.

The principal environmental indoor irritant is cigarette smoke. The most troublesome indoor allergens are house dust mites, cockroaches, fungi (molds), and animal dander.¹¹

Ask all patients with asthma about their exposure to these substances. Assess allergen exposure in all locations where a patient spends significant amounts of time, including home, school or workplace, day care or baby-sitter's home, and friends' homes. Many children spend significant time with divorced or separated noncustodial parents or other relatives, and these locations should also be evaluated.

Provide patients with checklists of symptoms and possible exposures that can be completed in the waiting room.^4,8 Such lists are particularly helpful in identifying possible indoor allergens at home without suggesting fault or laxity in housekeeping.

Indoor allergens. House dust mites are commonly found in carpets, stuffed animals, upholstered furniture, pillows, comforters, and bedding in homes in the central and southern United States. Cockroaches are a common pest in many older apartments and houses, especially in inner cities. Discoloration on the walls and floors of showers and other areas in bathrooms or locker rooms, especially on grout, suggests mold. Furry or feathered animals that are kept indoors (especially cats or dogs that sleep in patients' bedrooms) are common sources of allergens. Food allergies may be associated with the pulmonary symptoms of anaphylaxis but are rarely considered triggers or causes of asthma.^4,8,11

Outdoor allergens. These are usually seasonal. A history of seasonal exacerbations may be the first step in identification of specific outdoor allergens. Maps that provide average peak times for specific types of allergens are available on the Internet. Sources include www.aaaai.org and www. weather.com/activities/health/ allergies. The response to seasonal allergens can vary from year to year according to the pollen load. "New" allergies may be recognized at any age. Without careful questioning, patients and families may fail to recognize the seasonal nature of symptoms.

Allergy testing. If the history provides evidence of exacerbations in response to indoor or outdoor allergens, additional testing may be indicated.¹¹ A positive test for allergen sensitivity can reinforce the need for avoidance strategies, such as:

• Use of mattress, pillow, and box spring covers.
• Removal of stuffed animals, wall-to-wall carpeting, and throw rugs from the bedroom.
• Cleaning moldy surfaces with diluted chlorinated bleach.
• Keeping pets out of the bedroom.

If the history of exposure is unclear or insufficient or if immunotherapy is being considered, further testing and referral to an allergist are indicated.

The role of inhaled corticosteroids. The allergy and inflammatory cascades are clearly linked and are now referred to as allergic inflammation in asthma.⁷ Treating asthma with daily inhaled corticosteroids may interrupt this process. In patients with predictable seasonal allergies, a good strategy is to prescribe inhaled corticosteroids for a few weeks or months beginning 2 to 3 weeks before usual symptom onset.¹¹

Concurrently removing, minimizing, or desensitizing patients to known triggers may allow improved asthma control with lower doses of inhaled or oral corticosteroids. Complete avoidance is frequently impossible, but decreasing the exposure to allergens can relieve symptoms dramatically.

Are asthma management goals being met?

5The goal of asthma management is to improve outcomes that matter to patients and their families. These include the ability to work or attend school, be physically active, have satisfying and uninterrupted sleep, and enjoy a good quality of life. Both patients and physicians want fewer unscheduled office and emergency department visits and fewer hospitalizations. Physicians want to be able to manage their patients' asthma with the most effective drug regimen, the fewest exacerbations, and the highest satisfaction.

Inhaled corticosteroids can help achieve important goals for both patients and physicians. Even in patients with mild persistent asthma, daily inhaled corticosteroid use has been shown to reduce work and school absences, decrease asthma-related nighttime awakenings, reduce hospitalizations and urgent care visits, provide more symptom-free days, and result in lower total loss of income and out-of-pocket expenditures.⁵

References:

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15. The Childhood Asthma Management Program Research Group. Long-term effects of budesonide or nedocromil in children with asthma. N Engl J Med. 2000;343:1054-1063.
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