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Asthma

Guidelines for Children and Adults

Nancy Evans, BS

Courses are approved by CECBEMS and the California Emergency Medical Services Authority. For more information about accreditation, click here. Nurse practitioners may apply these contact hours to pharmacy continuing education and prescriptive authorization.

Asthma is a chronic inflammatory disease of the airways that causes recurrent episodes of wheezing, shortness of breath, coughing, and chest tightness, particularly at night and in the early morning. These episodes are related to widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment (National Asthma Education and Prevention Program [NAEPP], 1997).

EPIDEMIOLOGY

Since 1980 asthma has reached epidemic proportions in the United States, affecting an estimated 20 million people, nearly 9 million of them children (National Heart, Lung, and Blood Institute, 2006). According to the Centers for Disease Control and Prevention (CDC), in 2004 asthma accounted for:

• More than 4000 deaths
• Nearly half a million hospitalizations
• Nearly 2 million emergency department (ED) visits

People of all ages suffer from asthma, but the disease most commonly begins in childhood. Some children experience less severe symptoms as they grow older and, in some cases, the disease may resolve altogether. However, recent research suggests that symptoms may recur in more than one-third of those with a history of childhood asthma (Taylor et al., 2003) perhaps due to a change in environmental exposure that exacerbates persistent inflammation.

Asthma is the most common chronic disease of children and the leading cause of school absenteeism, accounting for more than 12 million lost school days. It is also the leading cause of work loss for adults, accounting for an estimated 24 million lost work days each year. Asthma affects proportionately more children than adults, more women than men, and more nonwhites than whites (Mannino et al., 2002). Incidence is highest among African American children living in urban areas.

Asthma can be life-threatening. Mortality is highest among African Americans between the ages of 15 and 24. Despite the development of more effective medications for asthma, the death rate from asthma has increased in recent years. Between 1979 and 1996, the number of children dying from asthma increased more than three-fold. Fortunately, the mortality rate among children with asthma has declined since then; however, it is increasing among adults over age 75 (American Lung Association, 2006).

Asthma not only exacts a tremendous cost in suffering and loss of life but also in financial terms. According to the American Lung Association, direct healthcare costs for asthma in the United States exceed $11.5 billion, nearly half of which represents the cost of prescription drugs. The cost of lost productivity adds another $4.6 billion, for a total of more than $16 billion.

ETIOLOGY

No single cause of childhood asthma has been identified. Thus it is considered a multifactorial disease to which familial, allergenic, socioeconomic, and environmental factors may contribute. The most common predisposing factor is inherited susceptibility to allergic reactions, a condition called atopy. A child whose mother has asthma is almost three times as likely to develop asthma as the child whose mother does not have asthma. However, the rapid increase in asthma prevalence cannot be explained by genetic factors because it takes many generations for genetic changes to occur. Many people diagnosed with asthma have no family history of atopy or asthma.

Obesity

The dramatic rise in the number of overweight and obese persons over the past two decades has paralleled the rise in asthma rates. A number of recent studies suggest that the association of asthma and obesity may be causal rather than by chance (Gilliland et al., 2003; Guerra et al., 2004; Poulain, 2006). Australian scientists have identified a protein—acid-binding protein aP2—which not only causes obesity and Type 2 diabetes but also plays a role in allergic respiratory diseases such as asthma (Shum et al., 2006). Fat tissue also produces a number of inflammatory mediators such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 in the serum of obese persons, which may contribute to airway inflammation (Weiss, 2005; Bergeron et al., 2005).

Pregnancy

Pregnancy also appears to increase a woman's risk of asthma, and the risk rises with the number of births. The reason for this link is unclear but researchers suspect it may be related to hormonal changes during pregnancy (Jenkins et al, 2006).

Women who have asthma prior to become pregnant are at high risk of premature birth and having a low birthweight infant, both of which put the child at risk of developing respiratory complications. A recent study indicates that many women on Medicaid stop or reduce their use of asthma medications during pregnancy, despite the fact that national guidelines recommend continued use of these drugs (Enriquez et al., 2006).

Researchers in Detroit found that obese women with asthma have a higher incidence of preeclampsia and cesarean deliveries than women without asthma. However, they surmised that the complications are more likely related to obesity rather than to asthma (Hendler, 2006).

Environmental Factors

A number of environmental factors have been identified as triggers for asthma attacks, and some of them may even cause asthma. These include contaminants in indoor and outdoor air, as well as viral infections. Indoor-air contaminants include animal dander, dust mites, cockroach droppings, wood smoke, oil smoke, and secondhand tobacco smoke.

Secondhand tobacco smoke has many of the same ingredients as diesel exhaust, including particulate matter (PM), respiratory irritants, and thousands of toxic chemicals such as 1-3 butadiene, benzene and formaldehyde. Research suggests that prenatal exposures, including exposure to secondhand smoke, may cause immune system changes that predispose infants to early development of asthma and allergies. Maternal exposure to secondhand smoke during pregnancy can affect the respiratory health of the fetus as well as increase the risk of low birthweight and premature delivery (CDC, 2006). Mothers who smoke during pregnancy compromise their infants' pulmonary function, increasing the risk of persistent wheezing in their children at least until age 6. Breastfeeding appears to mitigate the effects of these exposures, since infants who are breastfed are less likely to develop asthma than those who are fed infant formula (Kull et al., 2005).

Reducing prenatal and early childhood exposures to potential asthma triggers can significantly reduce the prevalence of asthma. In one large prospective Canadian study, researchers found that prenatal lifestyle modifications before birth and during the first year of life reduced the prevalence of asthma in the intervention group by 56 percent at age 7 years compared with the control group. The intervention included avoidance of house dust, pets, and environmental tobacco smoke beginning before birth coupled with breastfeeding and delayed introduction of solid foods during the first 12 months of life (Chan-Yeung et al., 2005).

According to the American College of Asthma and Allergy (ACAAI) consensus document (Fiochi et al., 2006), breastfeeding and delaying the introduction of solid foods for at least the first six months of life protects children against allergies. Certain foods (eg, cow's milk) that are linked to increased risk for allergies should be avoided for the first year of life. Eggs should not be offered until age 2 and peanuts, tree nuts, fish, and other seafood should be avoided until at least age 2. ACAAI also recommends that fruits, vegetables, meats, soy, and cereal be introduced one at a time and the child's response be carefully monitored for potential allergic reaction.

Chlorinated indoor swimming pools may also increase the risk of asthma. The most recent of several studies implicating the byproducts of chlorination of water as a risk factor for asthma found a relationship between asthma prevalence and the number of indoor chlorinated swimming pools per inhabitant in 21 European countries (Marc & Bernard, 2006). The researchers reported that in the United Kingdom, for example, asthma rates rose by 2.73 percent for every chlorinated pool available to residents. A study in Sweden found that repeated exposure to chlorination byproducts in the air of indoor swimming pools increased the inflammatory response in lung tissue by impairing the anti-inflammatory function of Clara cell protein (CC16) (Lagerkvist et al., 2004). Researchers in Belgium and Australia earlier reported similar findings, linking exposure to chlorinated pools with hyperpermeability of lung tissue and asthma prevalence (Bernard et al., 2003).

Dampness and mold are also linked with asthma and asthma-related symptoms in both children and adults. A study in Finland found a significant increase in new cases of adult-onset asthma related to the presence of visible mold and/or mold odor in the workplace: More than one-third of exposed workers developed asthma; women, the young, and smokers were most vulnerable to the effects of workplace mold (Jaakkola et al., 2002). Many other studies have identified residential dampness and mold as triggers of asthma-related symptoms and asthma attacks.

Contaminants in outdoor air include pollen, herbicides, pesticides, ozone, nitrogen oxides (NOx), particulate matter (PM), and vehicle exhaust, especially diesel exhaust. The earlier in life a child is exposed to these contaminants the greater the risk of developing asthma.

Occupational Asthma

Adult-onset asthma may be caused by exposures in the workplace and/or at home, and symptoms can be exacerbated by smoking. Occupational asthma is the most common type of occupational lung disease in the developed world. According to the American Academy of Allergy, Asthma and Immunology, up to 15 percent of asthma cases in the United States may be related to workplace exposures; therefore, clinicians should consider occupational exposures in all adults known or suspected to have asthma.

Scientists expect the prevalence of occupational asthma to remain high because more than 250 industrial chemicals, referred to as chemical sensitizers, are known to cause the disease, and new chemicals are introduced into the workplace each year. Chemical agents are estimated to cause 40 percent of cases of occupational asthma (Bernstein, 2003).

Chemical sensitizers known to cause asthma and to trigger asthma attacks in pre-existing asthma include the isocyanates, acid anhydrides, methacrylates, complex amines, metalworking fluids, and several metals. Chronic exposure to latex, certain pesticides, grain dust, wood dust, and bacterial toxins, and high-level exposure to certain chemicals such as corrosive, acid, or alkaline smoke, vapor or gas, can also cause asthma. Table 1 (below) shows major causes of occupational asthma and workers at risk. Workers who smoke are at higher risk of developing asthma related to occupational exposure than nonsmokers.

Clinicians need to ask adult patients about possible work-related exposures that could cause or exacerbate asthma. Patients may need referral to an allergist/immunologist for evaluation to confirm the diagnosis of asthma, determine whether the asthma is caused or triggered by workplace exposures, and initiate appropriate avoidance therapy.

TABLE 1

OCCUPATIONAL ASTHMA AND WORKERS AT RISK

Source	Agents	Workers at risk
Animals, insects, and fungi	Animal proteins	Animal handlers, laboratory research workers, poultry workers
	Prawns, crabs	Processors of these foods
	Egg protein	Egg producers
	Fungal amylase	Bakers
Grains, flours, plants	Grain dust	Grain storage workers, farm workers
	Wheat, rye, soy flours	Bakers, millers
	Latex	Healthcare workers
	Green coffee beans, castor beans	Coffee bean baggers and handlers, coffee roasters, chemists
Drugs and enzymes	Proteases from Bacillus subtilus	Detergent industry workers
	Pancreatin, papain, pepsin	Food technologists, laboratory workers
	Methyldopa, salbutamol, dichloramine, piperazine, dihydrochloride, spiramycin, penicilllins, sulphathiazole, sulphonechloramides, chloramines-T, phosdrin, pancreatic extracts	Pharmaceutical workers
Wood dusts	Western red cedar, California redwood, cedar of Lebanon, iroko, ramin, African zebrawood	Sawmill workers, joiners, carpenters, woodworkers
	Mahogany, mansonia, oak	Sawmill workers, pattern makers
Chemicals	Di-isocyanates	Polyurethane, plastics, varnish workers, foam manufacturers printers, laminators, rubber workers, boat builders, office workers, refrigerator manufacturers, toy makers
	Acid anhydrides	Epoxy resins, alkyl resins, plastics workers
	Complex amines	Photographers, shellac workers, painters
	Azodicarbonamide	Plastics workers, rubber workers
	Reactive dyes	Textile workers
	Methyl methacrylate	Healthcare workers
Metals	Platinum salts	Platinum-refining workers
	Cobalt	Hard-metal grinders
	Chromium, nickel	Metal-plating workers
Other	Metalworking fluids	Machinists
	Aluminum pot room emissions	Aluminum-refining workers
	Colophony in solder flux	Electronics workers
Source: Canadian Centre for Occupational Health and Safety, 2005.

Occupational asthma leads to substantial disability, resulting in loss of income and quality of life. Early diagnosis, elimination of the causative exposure, and early use of inhaled steroids are key to minimizing these effects. However, prevention of new cases is equally important and requires collaboration between industry and occupational health professionals.

PATHOPHYSIOLOGY

Asthma results from complex interactions among inflammatory cells, mediators, and other cells and tissues in the airway. The inflammatory process of asthma is accompanied by bronchial hyperreactivity (hyperresponsiveness). The severity of hyperreactivity depends on the severity of the inflammation.

During an acute asthma episode (an exacerbation), the smooth muscles in the bronchi constrict, narrowing the airways and obstructing airflow. In addition, the acute inflammatory response increases mucus secretion and edema of the airway mucosa, damaging the airway epithelium. Over time, this sequence of events causes the airways to stiffen, contributing to persistent abnormalities in lung function.

Airways show the effect of asthma. Illustration courtesy of National Heart, Lung, and Blood Institute.

CLINICAL FINDINGS

Over the past decade, both broadcast and print media have spotlighted asthma, its prevalence, and the various initiatives to prevent, diagnose, and treat the disease. Comprehensive guidelines for the diagnosis and management of asthma are readily available from the National Asthma Education and Prevention Program (NAEPP) and from the Global Initiative on Asthma (GINA). Despite these efforts, asthma remains underdiagnosed and inadequately controlled. Challenges include the difficulties of early and accurate diagnosis, lack of appropriate clinician, patient, and family education, and poor compliance with prescribed therapeutic regimens.

Effective treatment of asthma begins with correct diagnosis and classification of the disease. Clinical judgment is essential to this process because signs and symptoms vary within and among individuals over time. Some patients experience only mild and infrequent symptoms, while others experience more severe and frequent symptoms.

Onset of asthma symptoms may be sudden or gradual and symptoms may resolve quickly or persist for hours or even days. Because allergies contribute to most cases of asthma, asthma triggers vary from person to person, depending on their individual allergies. Clinicians may overlook or misdiagnose asthma in adults, attributing their symptoms to cardiac, pulmonary, or bronchial conditions. This is particularly true among older adult patients.

KEY ELEMENTS IN DIAGNOSIS

To establish the diagnosis of asthma, the clinician must determine that:

• Episodic symptoms of airflow obstruction are present.
• Airflow obstruction is at least partly reversible.
• Alternative diagnoses are excluded.

This process requires a detailed medical history (Boxes 1 and 2); physical examination focusing on the upper respiratory tract, chest, and skin; and spirometry to demonstrate reversibility (NAEPP, 1997).

The medical history can help:

• Identify the symptoms likely to be due to asthma.
• Identify patterns of symptoms and/or family history of asthma or allergies.
• Assess the severity of asthma, based on symptom frequency and severity, exercise tolerance, hospitalizations, current medications.
• Identify possible precipitating factors, such as viral respiratory infections, environmental exposures at home, work, daycare or school.

Physical examination focused on the upper respiratory tract, chest, and skin can reveal findings that increase the probability of asthma, such as:

• Hyperexpansion of the thorax, especially in children; use of accessory muscles; hunched shoulders; and chest deformity.
• Sounds of wheezing during normal breathing, or a prolonged phase of forced exhalation. Wheezing during forced exhalation does not necessarily indicate airflow limitation. Wheezing may be absent in mild, intermittent asthma, or between exacerbations.
• Increased nasal secretion, mucosal swelling, and nasal polyps.
• Atopic dermatitis/eczema or other manifestation of an allergic skin condition.

Asthma is classified according to severity of symptoms and frequency of acute attacks or exacerbations: mild intermittent, mild persistent, moderate persistent, and severe persistent. Criteria for establishing these classifications are shown in Table 2 (NAEPP, 1997).

TABLE 2

CLASSIFICATION OF ASTHMA SEVERITY: CLINICAL FEATURES BEFORE TREATMENT*

Level	Symptoms**	Nighttime symptoms	Lung Function
STEP 4 severe persistent	Continual symptoms Limited physical activity Frequent exacerbations	Frequent	FEV1 or PEF ≤ 60% of predicted function
STEP 3 moderate persistent	Daily symptoms Daily use of inhaled short-acting beta2-agonist Exacerbations affect activity Exacerbations ≥ 2 times a week; may last days	>1 time a week	FEV1 or PEF >60% to <80% of predicted function
STEP 2 mild persistent	Symptoms >2 times a week but <1 time a day Exacerbations may affect activity	>2 times a month	FEV1 or PEF ≥ 80% or more of predicted function
STEP 1 mild intermittent	Symptoms ≤ 2 times a week Asymptomatic and normal PEF between exacerbations Exacerbations brief (from a few hours to a few days); intensity may vary	≤ 2 times a month	FEV1 or PEF ≥ 80% or more of predicted function
* The presence of one of the features of severity is sufficient to place a patient in that category. An individual should be assigned to the most severe grade in which any feature occurs. The characteristics noted in this table are general and may overlap because asthma is highly variable. Furthermore, an individual's classification may change over time. ** Patients at any level of severity can have mild, moderate, or severe exacerbations. Some patients with intermittent asthma experience severe and life-threatening exacerbations separated by long periods of normal lung function and no symptoms. Source: NAEPP, 2003.

SIGNS AND SYMPTOMS

Key indicators for considering a diagnosis of asthma are summarized in Box 3. These indicators include wheezing, cough that worsens at night, and/or a history of difficult breathing or chest tightness. Pulmonary function testing (spirometry) is necessary to determine whether airflow limitations are reversible.

TESTS

Pulmonary Function (Spirometry)

Spirometry measurements (FEV₁, FVC, FEV₁/FVC) before and after inhalation of a short-acting bronchodilator such as albuterol help determine the presence of airflow obstruction and whether it is reversible in the short term. Spirometry is generally useful in children ages 4 and older; However, some children cannot manage the maneuver until after age 7.

Spirometry measures the maximal volume of air forcibly exhaled from the point of maximal inhalation (forced vital capacity, FVC) and the volume of air exhaled during the first second of the FVC (forced expiratory volume in 1 second, FEV₁). Airflow obstruction is indicated by reduced FEV₁ and FEV₁/FVC values relative to reference or predicted values. Significant reversibility is indicated by an increase of >12 percent and 200 mL in FEV₁ after inhaling a short acting bronchodilator (American Thoracic Society, 2001).

Additional Tests

Depending on the patient, additional tests may be necessary to help rule out other respiratory or cardiac conditions and to identify asthma triggers, assess severity, and investigate potential complications.

Additional pulmonary function studies include lung volumes and inspiratory and expiratory flow volume loops, to confirm or rule out co-existing chronic obstructive pulmonary disease, a restrictive defect, or possible central airway obstruction. In smokers and older patients, a diffusing capacity test can help differentiate between asthma and emphysema.

Assessment of diurnal variation in peak expiratory flow (PEF) over 1 to 2 weeks is recommended in patients who have asthma symptoms but normal spirometry. The PEF is usually lowest on first awakening and highest several hours before the midpoint of the waking day (between noon and 2 p.m.). The PEF should be measured close to those two times, before taking an inhaled short-acting beta2-agonist in the morning and after taking one in the afternoon. A 20 percent difference in these two measurements suggests asthma.

Chest x-ray may be needed to rule out other diagnoses such as tumors. Allergy testing helps identify asthma triggers. The nose should be evaluated for possible polyps and the sinuses evaluated for infectious or inflammatory disease. It may be necessary to investigate for gastroesophageal reflux disease.

TREATMENT

Effective treatment of asthma requires a partnership between the clinician and the patient (or parent, in the case of young children). It is essential that patients and families understand how to manage asthma in their daily life, including ways to reduce or eliminate asthma triggers, and how to recognize signs and symptoms of an asthma attack requiring emergency treatment. NAEPP (1997) has outlined the key points in periodic assessment and monitoring of patients with asthma.

Goals of therapy include:

• Preventing chronic and troublesome symptoms (eg, coughing or breathlessness at night, in the early morning, or after exertion)
• Maintaining (near) "normal" pulmonary function
• Maintaining normal activity levels, including exercise and other physical activity
• Preventing recurrent exacerbations of asthma and minimizing the need for emergency department (ED) visits or hospitalizations
• Providing optimal drug therapy with minimal or no adverse effects
• Meeting patients' and families' expectations of, and satisfaction with, asthma care

To determine whether the goals of therapy are being met requires periodic assessment and ongoing monitoring of asthma, including measurements of the following:

• Signs and symptoms of asthma
• Pulmonary function
• Quality of life/functional status
• History of asthma exacerbations
• Drug therapy
• Patient-provider communication and patient satisfaction

The primary methods for monitoring asthma are clinician assessment and patient self-assessment. Clinician assessment involves follow-up evaluation to monitor quality of life and functional status, exacerbations, and effectiveness of therapy as well as periodic spirometry tests: (1) at the time of initial assessment, (2) after treatment is initiated and symptoms and PEF have stabilized, and (3) at least every 1 to 2 years.

To ensure effectiveness of drug therapy, ongoing monitoring should include assessment of patient adherence to the regimen, inhaler technique, level of usage of as-needed inhaled short-acting beta2-agonist, frequency of oral corticosteroid "burst" therapy, changes in dosage of inhaled anti-inflammatory or other long-term-control medications, and side effects of medications. One simple assessment tool is the Asthma Control Test (Box 4, below).

The clinician also needs to ask the patient about possible side effects of medications, such as shakiness, nervousness, bad taste, throat irritation, cough or upset stomach. With children or new patients, it's important to ask them to show how they use their inhaler. Incorrect inhaler technique impairs medication effectiveness and can lead to noncompliance because the patient thinks the medication isn't working.

Clinicians also need to routinely assess the effectiveness of patient-provider communication and patient satisfaction, by monitoring satisfaction with asthma control as well as satisfaction with quality of care (Box 5).

Patients with mild intermittent or mild persistent asthma that has been under control for at least 3 months should be seen by a clinician about every 6 months (NAEPP, 1997). Those with uncontrolled and /or severe persistent asthma and those needing additional supervision to help them adhere to their treatment plan should be seen more often.

Patient self-assessment includes following a written action plan based on signs and symptoms and/or PEF. This is particularly important for those with moderate-to-severe persistent asthma or a history of severe exacerbations.

The NAEPP (2003) recommends that clinicians provide written action plans as part of an overall effort to educate patients in self-management, particularly for patients with moderate or severe persistent asthma. The type and frequency of self-assessment should be individualized, based on asthma severity, patient's ability to perceive airflow obstruction, availability of peak flow meters, and patient preferences.

Action plans are typically based on either peak flow monitoring or symptom monitoring. A meta-analysis of studies on the effect of written action plans showed that children who keep track of their daily asthma symptoms have fewer emergency department visits than children who use plans based on peak-flow monitoring (Bhogal et al., 2006).

Each patient's action plan should include the following elements:

• Explicit, patient specific recommendations for environmental control and other preventive efforts needed to avoid or reduce the impact of exacerbations
• An algorithm of procedures describing how to use long term and rescue medications and how to adjust them when conditions change
• Steps the patient should take when medicines are ineffective or when an emergency occurs
• Contacts for seeking urgent care (NAEPP, 2003)

Patients need careful instruction in how and when to do peak flow monitoring (Box 6, below) as well as how to recognize symptom patterns that signal inadequate asthma control and the need for additional therapy.

TEACHING USE OF THE PEAK FLOW METER

Teaching patients how to use their peak flow meter is essential to effective management of asthma. Clinicians need to explain that the peak flow meter is a device that measures how well air moves out of the lungs. During an asthma episode, the airways of the lungs usually begin to narrow slowly. Using the peak flow meter give an early warning about narrowing in the airways hours, sometimes even days, before asthma symptoms occur.

By taking medications early (before symptoms), patients may be able to prevent a severe asthma episode or quickly stop an asthma episode that does occur. Peak flow meters are used to check patients' asthma in the way that blood pressure cuffs are used to check high blood pressure. Using the peak flow meter helps patients and their doctor:

• Learn what makes their asthma worse
• Decide if their treatment plan is working well
• Decide when to add or stop medicine
• Decide when to seek emergency care

A peak flow meter is most helpful for patients who must take asthma medication daily. Patients age 5 and older are usually able to use a peak flow meter. Box 6 teaches the basics about peak flow meter use.

Personal Best Peak Flow Number

Teach patients that their personal best peak flow number is the highest peak flow number achieved over a 2- to 3- week period when their asthma is under good control. Good control means feeling good and not having any asthma symptoms. Each patient's asthma is different, and one patient's best peak flow may be higher or lower than the peak flow of another patient of the same height, weight, and sex. It is important to find one's own personal best peak flow number because the treatment plan is based on it. To find the personal best peak flow number, peak flow readings should be taken:

• At least twice a day for 2 to 3 weeks
• When you wake up and between noon and 2 p.m.
• Before and after you take short-acting inhaled beta2-agonist for quick relief, if you take this medicine
• As instructed by your doctor

The Peak Flow Zone System

Once patients know their personal best peak flow number, the clinician can customize the action plan. The peak flow numbers are put into zones that are set up like a traffic light. This helps patients know what to do when peak flow numbers change. For example:

• Green Zone (more than ___ L/min [80% of your personal best number]) signals good control. No asthma symptoms are present. Take your medicines as usual.
• Yellow Zone (between ___ L/min and ___ L/min [50% to <80% of your personal best number]) signals caution. You must take a short-acting inhaled beta2-agonist right away. Also, your asthma may not be under good day-to-day control. Ask your doctor if you need to change or increase your daily medicines.
• Red Zone (below ___ L/min [50% of your personal best number]) signals a medical alert. You must take a short-acting inhaled beta2-agonist (quick-relief medicine) right away. Call your doctor or emergency department and ask what to do, or go directly to the hospital emergency room. Record your personal best peak flow number and peak flow zones in your asthma diary.

Track Your Peak Flow Daily

Teach patients to measure their peak flow when they wake up, before taking medicine, and to write down the peak flow number in the diary every day, or as you instruct them.

Actions to Take When Peak Flow Numbers Change

Patients need to know how to respond when their peak flow numbers change. Give them examples:

• If your PEF goes between 50 and 80 percent of personal best (yellow zone). Action: Take a short-acting inhaled beta2-agonist (quick-relief medicine) as prescribed by your doctor.
• If your PEF increases 20 percent or more when measured before and after taking a short-acting inhaled beta2-agonist (quick-relief medicine). Action: Ask your doctor about adding more medication to better control your asthma (for example, an anti-inflammatory medication).

Long-term daily peak flow monitoring helps patients with moderate-to-severe persistent asthma:

• Detect early changes in disease status
• Evaluate responses to changes in therapy
• Assess severity of symptoms in those with poor perception of airflow obstruction
• Gain a quantitative measure of impairment

If long-term daily peak flow monitoring is not used, a short-term (2–3 week) period of peak flow monitoring is recommended to establish the patient's personal best PEF. Long-term daily peak flow monitoring is not recommended for patients with mild intermittent or mild persistent asthma, unless the patient, family, and/or clinician find it useful in guiding therapeutic decisions. Any patient who develops severe exacerbations may benefit from peak flow monitoring.

Patients who use a bronchodilator should measure their PEF on waking from sleep in the morning before using a bronchodilator. If the morning PEF is below 80 percent of the patient's personal best, PEF should be measured more than once a day, always before using a bronchodilator. This will alert patients to any worsening of their asthma and the need for more medication. A PEF below 50 percent of personal best indicates a severe asthma exacerbation.

Patients should use the same peak flow meter over time to ensure consistency of readings. If a meter needs to be replaced, it is important to replace it with the same brand, because there is variability across brands.

REDUCING ENVIRONMENTAL EXPOSURES

Drug therapy alone cannot achieve optimal control of asthma symptoms. It is also essential to reduce or eliminate environmental exposures that increase asthma severity. Exposure to irritants or allergens (triggers) to which patients are sensitive worsens symptoms and precipitates asthma exacerbations. For (at least) those patients with persistent asthma who are on daily medications, the clinician should:

• Identify allergen exposures
• Use the patient's history to assess sensitivity to seasonal allergens
• Use skin testing or in vitro testing to assess sensitivity to perennial indoor allergens.
• Assess the significance of positive tests in the context of the patient's medical history

Factors that contribute to asthma severity can be classified into four groups: inhalant allergens, occupational exposures, nonallergic factors, and other factors. These are summarized below:

• Inhalant allergens
• Animal allergens
• Housedust mites
• Cockroach droppings
• Molds
• Outdoor allergens (pollen, grain dust)
• Occupational exposures (See Table 1, above)
• Irritants
• Tobacco smoke
• Indoor/outdoor pollution and irritants, such as chlorinated swimming pools
• Other factors
• Rhinitis/sinusitis
• Gastroesophageal reflux disease (GERD)
• Sensitivity to aspirin, other nonsteroidal anti-inflammatory drugs, and sulfites
• Topical and systemic beta-blockers
• Viral respiratory infections

Assessment of the patient's sensitivity and exposure to allergens is based on the history plus skin testing or in vitro testing. Skin testing should be limited to those allergens to which the patient reports exposure. Once specific factors that worsen asthma have been identified, the patient or caretaker can initiate appropriate control measures.

Patients with any level of asthma should avoid:

• Exposure to allergens to which they are sensitive
• Exposure to secondhand smoke
• Exertion when air pollution levels are high
• Use of beta-blockers
• Sulfite-containing food and drink (such as wines) and other foods to which they are sensitive

Adult patients with severe persistent asthma, nasal polyps, or a history of sensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) should be counseled concerning the risk of severe and even fatal exacerbations from using these drugs.

Patients should be treated for such co-existing conditions as rhinitis, sinusitis, or gastroesophageal reflux disease (GERD), if present.

Patients with persistent asthma should receive an annual influenza vaccine. Respiratory infections such as influenza can be more serious in people with asthma, and these infections can often lead to pneumonia and acute respiratory disease. Despite this, according to CDC only one-third of all asthmatic adults receive the flu vaccine annually (CDC, 2003).

PATIENT AND FAMILY EDUCATION

Successful management of asthma requires a partnership between clinician and patient (or parent/caretaker) and ongoing education of the patient and family. Patient education should begin at the time of diagnosis and be integrated into every step of clinical asthma care.

Patient education is a major factor in overcoming barriers to optimal asthma control. Less than half of children with asthma adhere to their recommended treatment. Multiple barriers to achieving optimum control are related to the treatment itself, the clinician or the patient (Table 3).

TABLE 3

BARRIERS TO ACHIEVING OPTIMUM ASTHMA CONTROL

Treatment-related barriers	Prolonged, complex, inconvenient regimens
	Cost of medication
	Adverse effects of medications
	Delayed onset of action
Clinician-related barriers	Difficulty in scheduling
	Multiple care providers disrupt continuity of care
	Perceived clinician disinterest
	Time constraints
Patient-related barriers	Poor understanding of need for treatment
	Low literacy
	Stigmatization, embarrassment
	Distrust of medical establishment
	Forgetfulness
	Co-existing psychological problems (eg, depression)
	Low motivation to change behavior
	Lack of social support
Source: Bender, 2002; Bukstein et al., 2005.

When nurses, pharmacists, respiratory therapists, and other health professionals are available to support and expand patient education, a team approach is most effective. The principal clinician should introduce the key educational messages (Box 7) and negotiate agreements with patients. Other members of the healthcare team should reinforce and expand these messages during office visits and telephone calls. All team members should document in the patient's record the key educational points, patient concerns, and actions the patient agrees to take.

Researchers in a multi-center study funded by CDC, the Inner-City Asthma Intervention (ICAI), reported difficulties in implementing evidence-based interventions in poor, disadvantaged populations. Only half the 4100 children enrolled completed the core intervention activities and only small improvements were noted in their asthma control. However, the lessons learned in this research underscore the importance of multi-disciplinary patient education. For example, researchers found that a social worker is best suited to address family living conditions, social welfare, and mental health issues as part of asthma education. Based on the lessons learned, researchers developed the Alleviate Asthma! tool kit for healthcare organizations to use in education and outreach. The kit is available publicly online at http://www.achp.org.

One critical factor in patient education that is often overlooked by doctors, nurses, and other healthcare providers is illiteracy. A recent report from the National Center for Education Statistics (NCES) estimates that 12 percent of adults in the United States have a "below basic" level of "document literacy," which is the ability to read and understand documents such as drug or food labels. More than half of those in the lowest literacy group had not finished high school. According to NCES, 27 percent of older adults had below basic document literacy (Kutner, Greenberg & Baer, 2005).

Research also shows that many adults in the United States have a low level of "health literacy," the ability to understand and use health-related information. One survey found that more than one-third of English-speaking patients and more than one-half of primarily Spanish-speaking patients at U.S. public hospitals have low health literacy (Howard et al., 2005). Although ethnic minority groups are disproportionately affected by low literacy, most adults in the United States with low literacy skills are white, native-born Americans.

Identification of patients with low literacy skills is essential to successful health outcomes in managing any chronic disease such as asthma. However, it must be done with care and sensitivity to avoid making the patient feel guilt or shame. One physician carries an empty prescription bottle in her pocket when she works in the clinic to use as a screening tool. She tells patients "This is not your medication, but if it were, tell me how you would take it" (Marcus, 2006). Collaboration with social workers and health educators can help physicians better meet the needs of patients with asthma who have low literacy skills.

Teaching asthma self-management needs to be tailored to the needs of each patient, being sensitive to cultural beliefs, practices, and ability to understand the treatment regimen. Patient education includes teaching and reinforcing at every opportunity:

• Basic facts about asthma
• Roles of medication
• Skills: inhaler/spacer/holding chamber use, self-monitoring
• Environmental control measures
• When and how to take rescue actions

Jointly develop treatment goals. Encourage an active partnership by providing all patients with a written daily self-management plan and an action plan for exacerbations. Action plans are especially important for patients with moderate-to-severe asthma and patients with a history of severe exacerbations. Provide appropriate patients with a daily asthma diary.

Encourage adherence by promoting open communication; individualizing, reviewing and adjusting plans as needed; emphasizing goals and outcomes; and encouraging family involvement (NAEPP, 1997).

Patient/family/caregiver education helps patients gain the motivation, skill, and confidence to control their asthma and communicates the importance of collaboration in asthma treatment. Research shows that asthma education can be cost-effective and can reduce morbidity for both adults and children, especially among high-risk patients.

ENVIRONMENTAL CONTROL MEASURES

Reducing exposure to indoor and outdoor allergens that may cause or exacerbate asthma is fundamental to successful asthma management. Educating patients and families about these environmental exposures helps them make changes that improve patient well-being, reduce the need for short-acting (rescue) medications, and decrease the number and severity of exacerbations. One website offers parents a virtual room-by-room tour to see what changes would reduce environmental exposures in and around the house. It is found at http://www.checnet.org/healthehouse/home/index.asp.

Patients and families can make changes at home that will reduce or eliminate the allergens to which the patient is sensitive and improve the quality of indoor air. Those changes include eliminating allergens, tobacco smoke, and other indoor and outdoor pollutants.

ALLERGENS

• Animal dander: Remove animal from house or, at a minimum, keep animal out of patient's bedroom and use a filter on air ducts that lead to bedroom.
• Housedust mites
• Encase mattress in an allergen-impermeable cover; encase pillow in an allergen-impermeable cover or wash it weekly; wash patient's sheets and blankets in hot water weekly (water temperature of 130°F is necessary for killing mites).
• Vacuum carpets once or twice a week to reduce accumulation of house dust. Patients sensitive to house dust should avoid using conventional vacuum cleaners, and stay out of rooms where a vacuum cleaner is being or has just been used. If patients must vacuum, they should wear a dust mask or use a central vacuum unit with the collecting bag outside the house or a vacuum cleaner fitted with a HEPA (high-efficiency particulate air) filter or with a double bag.
• Remove carpets from the bedroom; avoid sleeping or lying on upholstered furniture; remove carpets that are laid on concrete.
• Using a dehumidifier will further help reduce growth of dust mites in areas of the country where outside air remains humid for most of the year.
• Cockroaches: Use poison bait or traps to control. Do not leave food or garbage exposed.
• Pollens (trees, grass, weeds) and outdoor molds: To avoid exposures, adults should stay indoors with windows closed during the season in which they have problems with outdoor allergens, especially during the afternoon. If possible, use air conditioning during hot weather, which also helps control humidity sufficiently to reduce house-dust mite growth.
• Indoor mold: Fix all leaks and eliminate water sources associated with mold growth; clean moldy surfaces. If possible, reduce indoor humidity to less than 50 percent.

Indoor air-cleaning devices are no substitute for other environmental measures described above, particularly in regard to dust mites and cockroach allergens. However, air-cleaning devices with HEPA filters can reduce airborne cat dander, mold spores, and particulate tobacco smoke. Ionic ozone-generating air cleaners are not effective in removing airborne particles and may raise the indoor level of ozone above federal standards, thereby exacerbating asthma symptoms (EPA, 2006).

Professional cleaning of the air ducts of heating/ventilation/air conditioning systems can reduce levels of airborne fungi. However, the effect on dust mites or animal dander has not been studied.

Tobacco Smoke

One of the most hazardous exposures to eliminate from all indoor environments is tobacco smoke. According to the American Lung Association, an estimated 440,000 Americans die each year from diseases caused by smoking. Tobacco smoke is a major trigger for asthma exacerbations and may even cause asthma in infants and young children.

As mentioned earlier, a pregnant woman who smokes increases the risk of wheezing in her developing child. Thus it is critical that no one smoke in a home where there are infants, children, or pregnant women, or where there is a family member who has asthma. Daycare centers and workplaces should also be smoke-free zones.

There are many free or low-cost resources available to help smokers quit, including brochures, books, videos, audiotapes, online support groups, and courses. The CDC and American Lung Association websites list many resources for patients and health professionals.

Other Pollutants and Irritants

Patients and families need to reduce or eliminate exposure to the following potential asthma triggers:

• Wood-burning stoves or fireplaces
• Unvented stoves or heaters
• Other irritants (eg, perfumes and fragranced products, cleaning agents, room sprays, scented candles)

MEDICATIONS

Underdiagnosis and inappropriate therapy are major contributors to asthma morbidity and mortality. One study showed that physicians prescribed appropriate asthma medications only 60 percent of the time, and inappropriate prescribing was generally related to too much of a drug rather than too little (Twiggs et al., 2004).

One of the six goals of asthma therapy, stated earlier, is to provide optimal drug therapy with minimal to no adverse effects. The NAEPP recommends a stepwise approach to drug therapy:

• The amount and frequency of medication is dictated by asthma severity and directed toward suppression of airway inflammation.
• Initiating therapy at a higher level at the onset to establish prompt control and then stepping down.
• Continued monitoring to ensure asthma control.
• Stepping down therapy gradually and cautiously once control is achieved and sustained. If no clear benefit is seen at 4 to 6 weeks, consider alternative therapies or diagnoses.
• Step-down therapy is necessary to identify the minimum medication needed to maintain control.

The NAEPP recommendations are general guidelines for therapeutic decision making. They are not intended to be prescriptions for individual treatment. Specific therapy should be tailored to the needs and circumstances of individual patients, and accompanied at every step by patient education and measures to control factors that contribute to the severity of asthma.

The choice of medication for initial daily long-term-control therapy in patients with mild or moderate persistent asthma should consider:

• Treatment effectiveness
• Individual patient's history of previous response to therapies
• Ability of the patient and family to use the medication correctly
• Anticipated patient and family adherence to the treatment regimen

Therapeutic strategies are considered to be a clinician-patient partnership. Education of patients (and parents of children with asthma) is essential for achieving optimal asthma control.

Regular follow-up visits (at 1- to 6-month intervals) are essential to maintain asthma control and consider appropriate step-down therapy. When the benefits of therapy have been sustained for 2 to 4 months, a step down in therapy is attempted. If there are no clear benefits within 4 to 6 weeks, alternative therapies or diagnoses need to be considered.

At each step, patients (and parents/caretakers of children with asthma) are advised to avoid or control allergens, irritants, or other factors that increase asthma severity. If there are difficulties achieving or maintaining control of asthma, or if the patient requires step 4 (severe persistent) care, referral to an asthma specialist for consultation or comanagement is recommended. Referral may be considered for patients who require step 3 (moderate persistent) care. For patients younger than 3 years, referral is recommended if the patient requires step 3 or step 4 care and should be considered if the patient requires step 2 (mild persistent) care.

Until 2003 two general classes of medications were available for the management of asthma: long-term control medications used to achieve and maintain control of persistent asthma and quick-relief (rescue) medications (short-acting beta2-agonists such as albuterol) used to treat acute symptoms and exacerbations. Patients with persistent asthma require both classes of medication.

In 2003 the Food and Drug Administration (FDA) approved the first monoclonal anti-IgE antibody for the treatment of asthma, an injectable drug called omalizumab (Xolair). This antibody is intended for patients with moderate-to-severe allergic asthma that is not well-controlled by inhaled corticosteroids and long-term beta2-agonists. According to the FDA analysis of the research on omalizumab, the drug will help only about 15 percent of patients to avoid an asthma attack.

Some patients taking omalizumab were able to reduce their use of corticosteroids as well as the number of exacerbations and unscheduled outpatient visits, significantly improving their asthma-related quality of life (Walker et al., 2004). Patients who receive omalizumab for the first time have a risk of anaphylaxis, a life-threatening reaction, so the first injection must be given in a physician's office. The other major safety issue is an increase in various cancers in 0.5 percent of patients using omalizumab for less than one year compared with 0.2 percent of those given placebo (Xolair product labeling, 2004). Other adverse effects seen in clinical trials include rash, diarrhea, nausea, vomiting, epistaxis, menorrhagia, and hematoma (FDA, 2003).

There are still uncertainties about the efficacy and safety of omalizumab because studies to date are based on one year or less of treatment with the drug. The NAEPP guidelines published in 2003 made no recommendation concerning omalizumab. The cost of the drug may also limit its use: annual costs per patient range from $10,000 to $24,000, depending on the dose.

The most potent and effective long-term asthma control medications available include inhaled corticosteroids (such as budesonide, beclomethasone, fluticasone) and long-acting beta2-agonists (such as salmeterol). Inhaled corticosteroids reduce inflammation of the airways and long-acting beta2-agonists (bronchodilators) dilate airways by relaxing airway smooth muscle. Early intervention with these medications can improve asthma control and normalize lung function.

The NAEPP guidelines (2003) recommend inhaled corticosteroids (glucocorticoids) as first-line treatment for children and adults with persistent asthma. Research indicates that no other types of long-term control medications (eg, cromolyn sodium, leukotriene modifiers, methylxanthines) were as effective in controlling asthma symptoms and improving asthma outcomes.

Studies suggest that patients with inadequate symptom control who are receiving low-to-medium doses of inhaled corticosteroids may benefit by the addition of salmeterol to their regimen rather than increasing the dose of corticosteroids. The NAEPP (2003) recommends that long-acting beta2-agonists such as salmeterol should be used only with anti-inflammatory medication.

EARLY TREATMENT AND THE PROGRESSION OF ASTHMA

In deciding when to begin daily inhaled corticosteroid therapy for patients with asthma, clinicians consider the goals of controlling and preventing symptoms. Although these drugs have been shown to provide superior asthma control during treatment, they do not appear to alter the progression of the disease in children ages 5 to 12 (NAEPP, 2003).

Children whose asthma symptoms begin before 3 years of age have shown declines in lung function growth by age 6 (Castro-Rodriguez et al., 2000), whereas those whose symptoms occur after age 3 do not exhibit these deficits (CAMP, 2000). There is insufficient evidence to determine whether treatment for children before age 3 can prevent deficits in lung function. Because treatment for infants and young children has not been adequately studied, recommendations for treatment are based on extrapolations from studies in older children and adults (NAEPP, 2003).

NAEPP guidelines (2003) recommend that clinicians initiate long-term treatment in infants and young children who have had four or more episodes of wheezing in the past year if wheezing lasts more than 24 hours and if the patient has other risk factors such as a family history of asthma, atopic dermatitis, or allergic rhinitis.

Clinicians need to monitor carefully the patient's response to therapy. Once control of asthma symptoms is established and sustained, a careful step-down in therapy should be attempted. If clear benefit is not observed within 4 to 6 weeks, alternative therapies or diagnoses are considered.

Adults with asthma have also shown progressive declines in lung function, with persistent airflow limitation and lack of response to treatment. Some experts believe this may be caused by airway remodeling (changes in structure of the airways) due to chronic inflammation. Although more research is needed to resolve this issue, the possible role of chronic inflammation suggests a rationale for early intervention with anti-inflammatory therapy.

ALTERNATIVE TREATMENTS

Cromolyn sodium and nedocromil can be considered as alternatives to inhaled corticosteroids for mild persistent asthma but they are not the preferred therapies. Leukotriene modifiers, or LTRAs (montelukast [for patients ≥2 years of age], zafirlukast [for patients ≥7 years of age] or the 5-lipoxygenase inhibitor zileuton [for patients ≥12 years of age]) are alternative but not preferred therapies for mild persistent asthma. The LTRAS also may be used as combination therapy in the treatment of moderate persistent asthma (NAEPP, 2003).

ROUTES OF ADMINISTRATION

Asthma medications may be administered by either inhaled or systemic routes (orally or parenterally). Inhalation medications offer two advantages: (1) higher concentrations can be delivered more directly, quickly, and effectively to the airways; (2) systemic side effects are avoided or minimized.

Inhaled medications, also called aerosols, are available in a variety of devices, each involving different technique and quantity of drug delivered to the lung. Whatever device is selected, patients need instruction in its correct use and to have their inhalation technique monitored regularly.

Patients should also be instructed on the importance of mouth washing with water after the use of inhaled medications to prevent systemic effects such as oral candidiasis (thrush). Using a spacer or holding chamber and/or reducing dosage further reduces the risk of candidiasis. Some studies suggest that inhaled medications increase the risk of gum inflammation, so it may be advisable for patients to rinse their mouths and also brush their teeth and gums after using inhalers.

Most aerosol medications used for asthma are available as metered dose inhalers (MDIs) and use chlorofluorocarbons (CFCs) as a propellant. The CFCs account for 95 percent or more of the formulation emitted from an MDI. Any portion of the inhaled propellant that is systemically absorbed is quickly excreted, unchanged, when the patient exhales.

Chlorofluorocarbons have been found to deplete stratospheric ozone and have been banned internationally; however, a temporary medical exemption permits their use in asthma medications until 2009. Alternatives include MDIs with nonchlorinated propellants such as hydrofluoroalkane (HFA) 134a, multidose dry powder inhalers, and other hand-held devices with convenience and delivery characteristics similar to current MDIs. An MDI for albuterol with HFA 134a has been approved for use; other non-CFC products and delivery systems are expected in the future.

Until recently, patients using most MDIs did not have a reliable way of telling when their inhalers were out of medication, unless they kept a diary of how many puffs they used. However, the newer multi-dose dry powder inhalers such as Serevent and Advair have integrated dose counters. With the forthcoming phase-out of CFCs, newer HFA inhalers will be available with integrated dose counters so that patients are aware when medication is running low (Sander et al., 2006).

Safety issues concerning short-acting inhaled beta2-agonists:

• Short-acting inhaled beta2-agonists such as albuterol are the medications of choice for relieving acute bronchospasm and for preventing exercise-induced bronchospasm (EIB).
• Increasing use of short-acting beta2-agonists or use of more than one canister per month signals inadequate control of asthma and the need to initiate or intensify anti-inflammatory therapy.
• Regularly scheduled, daily use of short-acting beta2-agonists is not recommended. (NAEPP, 1997)

Prior to 1990, many clinicians prescribed regular schedules of short-acting, inhaled beta2-agonists for asthma patients, believing this regimen improved overall asthma symptom control. Since 1990, however, research has disproved those beliefs, particularly for moderate and mild asthma. In moderate asthma, regular use of fenoterol, a potent inhaled beta2-agonist, significantly reduced asthma control and objective markers of pulmonary function.

In mild asthma, regularly scheduled use of albuterol, compared to use only as-needed, showed no significant differences in outcomes. Although regularly scheduled use of short-acting beta2-agonists in mild asthma produced no harmful effects in a four-month period, it also produced no demonstrable benefits. Studies with moderate asthma resulted in similar findings; thus regularly scheduled daily use of short-acting beta2-agonists is not recommended (NAEPP, 1997).

Safety issues concerning long-acting inhaled beta2-agonists:

• Long-acting beta2-agonists such as salmeterol (Serevent) enhance the effectiveness of inhaled corticosteroid therapy, especially in controlling EIB and nighttime symptoms. Daily use of long-acting beta2-agonists generally should not exceed 84 mcg (salmeterol = four puffs).
• Salmeterol is not to be used for treatment of acute symptoms or exacerbations.
• Patient education regarding correct use of medications containing salmeterol is critical. These medications should be used only with anti-inflammatory therapies, such as inhaled corticosteroids.
• Patients should be instructed not to stop anti-inflammatory therapy while taking salmeterol even though their symptoms may significantly improve.

Note: On November 18, 2005, the Food and Drug Administration (FDA) notified manufacturers of Advair Diskus, Foradil Aerolizer, and Serevent Diskus to update their existing product labels with new warnings and a medication guide for patients to alert professionals and patients that these medicines may increase the chance of severe asthma episodes and death with these episodes occur. Even though these products decrease the frequency of asthma episodes, they may make asthma episodes more severe when they occur. Adverse effects appeared to be related to two factors: race and concurrent corticosteroid use.

The so-called black box warning on medications containing salmeterol was based on a large clinical trial in which African Americans who were taking Serevent had a significantly greater number of asthma-related adverse events, including deaths, compared with those taking a placebo (Nelson et al., 2006). Significantly more asthma-related deaths were reported in all patients, both African American and white, who were using Serevent but were not using corticosteroids. Even though the NAEPP guidelines recommend the use of inhaled corticosteroids, fewer than 50 percent of the participants were taking the medications.

Safety issues concerning inhaled corticosteroids include:

• Inhaled corticosteroids are the most effective long-term therapy available for mild, moderate, or severe persistent asthma. In general, these drugs are well tolerated and safe at the recommended dosages.
• The potential but small risk of adverse events from the use of inhaled corticosteroids is well balanced by their efficacy.

To reduce the potential for adverse effects, NAEPP recommends the following measures:

• Use of spacers/holding chambers to administer inhaled corticosteroids.
• Rinsing the mouth (and spitting) after inhalation.
• Use the lowest possible dose of inhaled corticosteroids to maintain symptom control.
• For better symptom control, especially for nocturnal symptoms, consider adding a long-acting inhaled beta2-agonist to a low-to-medium dose of inhaled corticosteroid rather than using a higher dose of inhaled corticosteroid.
• Monitor growth of child patients.
• For postmenopausal women, consider supplements of calcium (1,000–1,500 mg daily) and vitamin D (400 units daily).

Inhaled Corticosteroids and Children's Linear Growth

Reduction in growth rate in children or adolescents may result from inadequate control of chronic diseases such as asthma or from the use of corticosteroids for treatment. However, the potential but small risk delayed growth related to use of inhaled corticosteroids is well balanced by their effectiveness.

The potential for adverse effects on linear growth appears to be dose-dependent. Although low-to-medium doses of inhaled corticosteroids may have the potential to slightly slow growth during the first year of treatment, research suggest that the effect is small, not progressive, and may be reversible. Prospective studies following children for more than 10 years suggest that predicted final height is attained (NAEPP, 2003).

When high doses of inhaled corticosteroids are necessary to achieve satisfactory control of symptoms, adjunctive long-term-control therapy should be initiated so as to reduce the dose of inhaled corticosteroids and thus minimize the dose-related long-term effects on growth. High doses of inhaled corticosteroids in children with severe persistent asthma are less likely to have an adverse effect on linear growth than oral systemic corticosteroids (NAEPP, 2003).

Physicians should monitor the growth of children and adolescents who are using any corticosteroids and weigh the benefits of corticosteroid therapy and asthma control against the possibility of growth suppression or delay if the patient's growth appears slowed (NAEPP, 2003).

Rare individuals may be more susceptible to the effects of using inhaled corticosteroids even at conventional doses. At higher doses among these individuals, there appears to be a dose-dependent effect on different measures of hypothalamic-pituitary-axis (HPA) function, including reduced cortisol excretion and adrenal suppression.

Inhaled corticosteroids do not appear to have adverse effects on bone mineral density in children (CAMP, 2000), nor do low-to-medium doses of inhaled corticosteroids increase the incidence of subcapsular cataracts or glaucoma (CAMP, 2000; Jick al., 2001). High (>2000 mg) cumulative lifetime doses of inhaled corticosteroids may slightly increase the prevalence of cataracts, as suggested in two retrospective studies of adult and older patients (Cumming et al., 1997; Jick et al., 2001).

LONG-TERM MANAGEMENT

Regular follow-up visits at 1- to 6-month intervals are essential to assess control and the possibility of a step-down in therapy. During these visits, clinicians also need to review and monitor the patient's daily self-management and action plans, medications and self-management behaviors (inhaler techniques and peak flow monitoring).

Continued monitoring is essential to ensure that asthma is well-controlled. Indicators of control are PEF values showing less than 10 to 20 percent variability or consistently greater than 80 percent of the patient's personal best, minimal symptoms, minimal need for short-acting inhaled beta2-agonist, absence of nighttime awakenings, and no activity limitations. If control is not achieved with initial therapy—for example, within 1 month—the pharmacologic plan, and possibly the diagnosis, should be re-evaluated.

The NAEPP guidelines recommend referral to an asthma specialist for consultation or comanagement of the patient if:

• There are difficulties achieving or maintaining control of asthma
• Immunotherapy is being considered
• The patient requires step 4 care (step 3 or 4 for infants and young children), or
• The patient has had a life-threatening exacerbation

Referral may be considered if the patient requires step 3 care (or step 2 care for infants and young children).

IMMUNOTHERAPY

The NAEPP guidelines suggest that allergen immunotherapy may be considered for asthma patients when:

• There is clear evidence that symptoms are related to exposure to an unavoidable allergen to which the patient is sensitive,
• Symptoms occur continuously throughout the year or during a major portion of the year, and
• Pharmacologic management fails to control symptoms because the medication is ineffective, multiple medications are required, or the patient is not accepting of medication.

If allergen immunotherapy is elected, it should be administered only in a physician's office, where facilities and trained personnel are available to treat any life-threatening reaction that can, but rarely does, occur.

Research indicates that immunotherapy, usually with single allergens, can reduce asthma symptoms caused by exposure to grass, cat, housedust mites, ragweed, Cladosporium, and Alternaria. Little research is available on multiple allergen mixes, which are commonly used in clinical practice.

The course of allergen immunotherapy is typically 3 to 5 years. Reactions to immunotherapy, especially bronchoconstriction, are more frequent among patients with asthma, particularly those whose disease is poorly controlled, compared with those with allergic rhinitis. Thus, this therapy remains controversial among experts.

EXACERBATIONS

Asthma exacerbations are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness, or some combination of these symptoms (NAEPP, 1997). Exacerbations are characterized by decreases in expiratory airflow that can be documented and quantified by simply measuring lung function (spirometry or PEF). These objective measures indicate the severity of an exacerbation more reliably than the severity of symptoms.

The principal goals for treating asthma exacerbations are correction of significant hypoxemia by administering supplemental oxygen, rapid reversal of airflow obstruction, and reduction of the likelihood of recurrence of severe airflow instruction by intensifying therapy. In rare cases, alveolar hypoventilation requires mechanically assisted ventilation.

Rapid reversal of airflow reduction is best achieved by repetitive or continuous administration of an inhaled short-acting beta2-agonist and early administration of systemic corticosteroids to patients with moderate-to-severe exacerbations or to patients who fail to respond promptly and completely to a short-acting inhaled beta2-agonist. A short course of systemic corticosteroids is often useful to reduce the likelihood of recurrence of exacerbations.

Achieving these goals requires close serial monitoring of lung function to quantify the severity of airflow obstruction and its response to treatment. The improvement in FEV₁ after 30 minutes of treatment correlates significantly with a broad range of indices of the severity of asthma exacerbations.

The PEF or FEV₁ values should be used to guide treatment decisions, as well as the patient's history, current symptoms and physical findings. In using PEF expressed as a percentage of personal best, it is important to consider the impact of irreversible airflow obstruction. For a patient whose best PEF is 160 L/min, for example, a drop of 40 percent represents severe, potentially life-threatening obstruction.

Because severe exacerbations of asthma can be life-threatening, care must be prompt. Every physician's office should have the medication and equipment (a short-acting beta2-agonist and the means to administer it as an aerosol, plus a source of supplemental oxygen) available to initiate effective therapy. Key points in management of asthma exacerbations are summarized in Box 8.

According to NAEPP (2003), the available evidence suggests that antibiotic therapy offers no benefit for asthma exacerbations except as needed to treat coexisting conditions. For example, patients presenting with fever and purulent sputum, evidence of pneumonia, or suspected bacterial sinusitis should receive antibiotics in addition to standard care for exacerbations.

Severe exacerbations demand close observation for deterioration, frequent treatment, and repetitive assessment of lung function. Thus most severe exacerbations of asthma require prompt transfer to an emergency department for a complete course of therapy.

If not treated promptly and appropriately, exacerbations can be life-threatening. Patients at high risk of asthma-related death (Box 8, above) require intensive education, monitoring and care. They should be counseled to seek medical care early during an exacerbation and instructed about the availability of ambulance services. Boxes 9 and 10 present risk factors for death from asthma.

Infants also require special attention because they are at high risk for respiratory failure (Box 10).

HOME MANAGEMENT OF EXACERBATIONS

Patients or parents who recognize the signs of exacerbations and are able to begin treatment at home can prevent exacerbations from becoming severe. Taking such action also gives them a sense of control over the asthma. However, the quality of care at home depends on the patient's or parent's abilities, understanding, and experience and on ready access to emergency care.

To prepare patients for home management of asthma exacerbations the NAEPP (1997) recommends the following measures:

• Teach all patients (and parents of children with asthma) how to monitor symptoms so as to recognize early signs of deterioration and how to adjust their medications accordingly.
• Teach patients with moderate-to-severe persistent asthma and those with a history of severe exacerbations how to monitor their peak flow to assess the severity of the exacerbation and response to therapy.
• Provide a written action plan to be followed in the event of an exacerbation, especially to patients with moderate-to-severe persistent asthma and those with a history of severe exacerbations.
• Children should also receive a plan appropriate to the school setting. The plan should direct the patient to adjust medications in response to particular signs, symptoms, and peak flow measurements, and should state when to seek medical help.
• Tailor the plan to the needs of the individual patient and review the plan with the patient and family.
• Teach patients to seek medical help early if (1) an asthma exacerbation is severe, (2) therapy does not give rapid sustained improvement, or (3) there is further deterioration.
• Advise patients with moderate-to-severe persistent asthma or a history of severe exacerbations to have the medication and equipment (peak flow meter, compressor-driven nebulizer for young children) readily available for treating exacerbations at home.

The NAEPP does not recommend the following techniques because there are no studies that show them to be effective and they may delay patients from seeking medical care:

• Drinking large volumes of liquids or breathing warm, moist air, such as mist from a hot shower.
• Using over-the-counter (OTC) products such as antihistamines, cold remedies, and bronchodilators. The OTC metered-dose inhalers may provide temporary bronchodilation but their use should not delay seeking medical care.
• Pursed-lip breathing and other forms of controlled breathing may help the patient remain calm during respiratory distress but they do not improve lung function.

Posted August 11, 2006

Expires October 1, 2008

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