Outpatient Treatment Of Pediatric Asthma

Appropriate outpatient management of pediatric asthma should be of great interest to any practitioner who provides health care to children. Since asthma is generally recognized as the most common chronic pediatric illness with around 6.9% prevalence rate,¹ children with asthma are seen frequently in doctor's offices and clinics. Furthermore, asthma severity and symptom profiles vary widely among patients and even with the same patient over time; making individualized management challenging. Just the same, if sound principles of outpatient management are used, inpatient management should be an infrequent necessity. General principles of pediatric asthma management must be comprehensive and based on current scientific data, but also flexible enough to be adapted to individual patient circumstances.

One of the most significant advances in asthma treatment has been the publication of several guidelines on the diagnosis and management of this disease. The most recent of these guidelines, (published in 1997) was developed by the National Heart, Lung, and Blood Institute (NHLBI) through their National Asthma Education and Prevention Program (NAEPP) titled the Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma, (EPR2). Within these guidelines specific recommendations for pediatric asthma management are readily addressed. As a foundation for good pediatric outpatient asthma management, I would recommend that all physicians and ancillary health care providers become very familiar with that publication. It must be recognized however, that guidelines are not a "cookbook" for disease management. One should pick and choose the pieces of information that are applicable to a patient's individual circumstances.

Outpatient management of asthma can be readily divided into long-term control of persistent and/or recurrent asthma, and acute management of asthma exacerbations. In this article we will first consider long-term control, (also described as "asthma maintenance"), as applied to children and adolescents. This category of asthma management can be further divided into three aspects: 1) ongoing monitoring, 2) controlling asthma triggers, and 3) pharmacological therapy. Each of these aspects presents unique challenges in regard to the pediatric patient. Finally, we will conclude with a discussion of the management of asthma "attacks."

Correct asthma management must start with correct diagnosis. In the EPR2 guidelines a step approach has been used for both diagnosis and management. There are four levels of severity thus four levels of intervention.

It is important to have in mind the goals of therapy. Here again, the EPR2 guidelines have established 6 practical goals, which, in most cases, can be achieved (see Table 1). Meeting these goals requires ongoing monitoring of multiple areas of individual patient care.

Table 1. Goals of Therapy

The purpose of periodic assessment and ongoing monitoring is to determine whether
goals of asthma therapy are being acheived. The goals of therapy are as follows:

Prevent chronic and troublesome symptoms (e.g. coughing or breathlessness in the night, in the early morning, or after exertion);
Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits and hospitalizations;
Maintain normal activity levels (including exercise and other physical activity);
Maintain (near) "normal" pulmonary function;
Provide optimal pharmacotherapy with minimal or no adverse effects; and
Meet patient's and families' expectations of satisfaction with asthma care.

Minimizing asthma exacerbations (periods of increased severity and frequency of symptoms from baseline) is also important in determining overall success of asthma control. Some children with infrequent low-grade symptoms have frequent asthma "attacks." Exacerbations or asthma "attacks" often lead to urgent office visits, ER visits, or hospitalizations, all of which are primary contributors to the high cost of asthma management. Asthma exacerbations are almost always the precedent to asthma morbidity and mortality. For all these reasons, exacerbations should be closely monitored. Milder attacks requiring increased use of bronchodilators 2 to 3 times a month, or more severe attacks requiring treatment with oral corticosteroids 2 to 3 times a year, may suggest the need for more aggressive long-term treatment; even if symptoms are infrequent in between exacerbations. Parent's adherence to an aggressive treatment plan during exacerbations must be monitored as a critical success factor for reducing the risk of asthma mortality.

Successful asthma management means not just reducing asthma symptoms and exacerbations but doing so while allowing a normal active and happy life. With few exceptions, children with asthma can participate in activities that require exertion. Parents of asthmatic children often need to be encouraged by the physician to not hold the child back.

School attendance should be monitored to determine if days missed secondary to asthma were necessary. Frequent school absenteeism may suggest the need for more aggressive asthma therapy. Some children suffer from frequent nocturnal symptoms even when asthma is controlled by other measurements. Loss of sleep from asthma symptoms can be reduced by therapy directed specifically toward nocturnal asthma. Any chronic illness can lead to significant psychosocial problems in a child or the child's family. Specific questions must be asked about psychosocial issues, as patients or parents do not readily bring them up.

A recommendation for asthma monitoring is the use of more objective measures of lung function. This can be accomplished with spirometry and peak-flow monitoring. Spirometry is helpful in confirming asthma severity initially, and in monitoring response to treatment over time. Spirometry, however, is unreliable in patients under age five.

For home monitoring and routine monitoring in the primary care physician's office, peak expiratory flow (PEF) monitoring with a peak flow meter (PFM) works well. PEF provides a fairly accurate measure of airflow obstruction if done correctly. There are many brands of PFM's, all of which are fairly easy to use. Just the same, patient and parent education with demonstration of use is necessary for accurate measurements. The patient should always use the PFM while standing. The patient should start with maximal inspiration. There should be a complete seal of the lips around the mouthpiece. The PEF "maneuver" is performed with a maximal hard and fast single expiration. The maneuver should be performed 3 times, with the best of the three efforts recorded.

To critically interpret PEF values there must be a normative standard for comparison. A patient's personal best PEF is the highest measurement achieved over a 2 to 3 week period when the patient's asthma is under good control, (i.e., having symptoms less than 2 times a week). Initially, when treatment is just beginning and good control may not yet be achieved, predicted values can be used as an estimate of personal best.

PEF values have been divided into zones for clinical interpretation of degree of airflow obstruction and corresponding need for intervention. The "green" zone is 80% - 100% of personal best and suggests good control or no clinical air flow obstruction. The "yellow" zone is between 50% - 80% of personal best. These means airflow obstruction and asthma symptoms are usually present. Quick relief medications should be started if the patient drops into the yellow zone. Staying in the yellow zone or recurrent drops in the yellow zone over time suggests loss of long-term control and an increase in maintenance therapy may be necessary. The "red" zone is below 50% of personal best. This suggests a medical alert and the need for aggressive quick-relief therapy. The patient's physician should be contacted if PEF drops into the red zone and cannot be readily improved.

Peak flow monitoring has been shown helpful for ongoing asthma monitoring,^2,3 and can be used in several ways. Patients with moderate and severe persistent asthma may benefit from long-term daily monitoring.⁴ Short term daily monitoring may be helpful to periodically determine personal best (which increases in children as their age increases) or to assess severity of an asthma exacerbation and response to treatment. Routine PEF is best checked shortly after waking up in the morning before any asthma medications are taken. If the value is below 80% of personal best, appropriate treatment should be started and more frequent PEF measurement checked throughout the day. PEF is probably most helpful in patient's who are judged to be poor perceivers of their asthma severity.⁵ In these patients use of PFM's may encourage appropriate treatment before air flow obstruction gets critical. For many parents, PFM's remove some of the guesswork, preventing both over and under treatment of children, especially when accurate communication of symptoms cannot be expected due to age. It should always be remembered, however, that PFM's are effort dependent. They are rarely accurate below age 4. Reliability also varies with maturity and cooperation. At best, PFM's and PEF measurement is only a tool to be used along with other methods of ongoing monitoring to assess asthma severity and the achievement of management goals.

A key feature of on-going monitoring is assessing the use and effectiveness of prescribed asthma medications. Lack of adherence to medication regimes is a common cause for poor symptom control. A common cause of non-adherence to regimen is medication side effects, both real and perceived. Even concerns for potential side effects (especially in regard to inhaled or oral corticosteroids) may prevent medications from being used as prescribed. Open discussion about how each medicine works, as well as, potential side effects can avoid adherence problems up front. If side effects occur a different but comparable medicine may be considered.⁶

Many asthma medications come in the form of inhalants. These include solutions for nebulization, metered dose inhalers (MDI), and more recently dry powder inhalers (DPI's). All these delivery devices require patient and parent education for effective use. The majority of younger children (and even some older children and adolescents) cannot master good inhaler technique because of the need for coordination of device actuation and slow, steady inhalation. In these cases, spacer devices can greatly improve efficacy by increased deliver of the medication⁷. It could be argued that all patients using inhaled corticosteroids should use a spacer as this reduces the risk of local oral adverse effects such as candidiasis.⁸ MDI's with spacer can be taught to children as young as 3-4 years-of-age. DPI's (spacers not applicable) can be taught to children as young as age 5. Children under 5 can readily use nebulizers. Inhaled corticosteroids (ICS's) may be necessary for children 5 and under with moderate to severe persistent asthma but ICS's do not come as nebulization solutions in this country. There are some brands of spacers that come with masks allowing for MDI use even in infants.⁹

The second major aspect of long-term management is controlling asthma triggers. A trigger is any factor that increases asthma symptoms or decreases asthma control. There are several categories of pediatric asthma triggers including: 1) upper respiratory infections, 2) exercise, 3) irritants, 4) allergens, 5) weather changes, and 6) emotions/stress. Triggers vary for each child so education on trigger avoidance must be individualized. An in-depth history of potential triggers and possibly objective evaluations (such as allergy testing) should be under taken in all children with persistent asthma.

Viral upper respiratory infections (URI's) are probably the leading cause of prolonged asthma exacerbations in children.¹⁰ Certainly, viral respiratory infections can lead to bronchiolitis and wheezing even in children without asthma. However, after a child has had 3 or 4 episodes of "bronchiolitis" with associated wheezing within the first few years of life, a diagnosis of asthma should be strongly considered.

Another upper respiratory infection, which may contribute to asthma severity, is bacterial sinusitis. Although the cause-and-effect relationship of sinusitis and asthma is of some debate, several investigators have shown aggressively treating sinusitis when present can lead to better control of asthma symptoms.^11,12 Sinusitis should be considered when an exacerbation is not rapidly responding to appropriate treatment or long-term control cannot be established with higher doses of maintenance medications.

Most older children with any degree of asthma have exercise-induced asthma (EIA).¹³ The incidence of EIA may approach 100% given sufficient exercise intensity.¹⁴ Exercise is one trigger asthmatic children should not generally avoid as exercise is essential for overall physical and mental health. Symptoms of EIA may include a dry cough or wheezing with exertion or just the inability to keep up with other children at play. The symptoms often peak 5 to 10 minutes after exercise has stopped.

The most effective treatment of EIA is the prophylactic use of inhaled Beta agonists 20 to 30 minutes before onset of exertion.¹⁴ Cromolyn or Nedocromil sodium can be added as a second medicine if the Beta agonist does not work adequately by itself.¹⁴ A warm-up phase before exercise may also reduce the likelihood of EIA. During and shortly after asthma exacerbations, it may be necessary to temporarily avoid all but limited exertion. Notifying teachers and coaches about a child's EIA may prevent conflict and reduce the risk of attacks at school.

Irritants are some of the most readily avoidable asthma triggers. These include any strong fume, odor, or smoke. Cessation of cigarette smoking in the home should be addressed when applicable since it has been shown to be a definite asthma risk factor. ^{15,
16} Outdoor activities may need to be limited on days when pollution levels are high.

The relationship between allergic sensitization (atopy) and asthma is well recognized in the ERR2 guidelines. The ERR2 guidelines suggest that patients with persistent asthma have allergy testing performed to reliably determine sensitivity to perennial indoor allergens. Sensitivity to outdoor seasonal allergens can often be determined with a good history. Allergen avoidance has the potential for decreasing asthma symptoms and reducing the amount of medicine required to control asthma.¹⁹ Practical environmental control measures should be given to parents of children with asthma who have documented sensitivity by allergy testing (see Table 2). Motivation to perform these environmental controls will usually be higher if the child has actually been shown to be allergic.

Table 2. Summary Of Control Measures For Indoor Dust-Borne Allergens

Animal Dander: Remove animal from house or, at a minimum, keep animal out of patient's bedroom and seal or cover with a filter air ducts that lead to bedroom.

House-Dust Mites:

Essential — Encase mattress in an allergen-impermeable cover or wash it weekly; wash sheets and blankets on the patien's bed in hot water weekly (water temperature of 130�F or greater is necessary for killing mites).

Desirable _ Reduce indoor humidity to less than 50%; remove carpets from the bedroom; avoid sleeping or lying on upholstered furniture; remove carpets that are laid on concrete.

Cockroaches: Use poison bait or traps to control. Do not leave food or garbage exposed.

Pollens (from trees, grass or weeds) and Outdoor Molds: To avoid exposure, adults should stay indoors with windows closed during the season in which they have problems with outdoor allergens, especially during the afternoon.

Indoor Mold: Fix all leaks and eliminate water sources associated with mold growth; clean moldy surfaces. Consider reducing indoor humidity to less than 50%.

The final aspect of long-term-control management is pharmacologic therapy. A major impetus in the development of management guidelines was the recognition that under-treatment of asthma was a major cause for rising morbidity and mortality. Furthermore, over the past 20 years an ever-growing mountain of evidence proves asthma is a chronic inflammatory lung disease^20-21 and airway inflammation can be demonstrated even in the mild cases of asthma.^22-23 For this reason, the focus of pharmacologic therapy for long-term-control management is anti-inflammatory medications. In the EPR2 guidelines anti-inflammatory medicines are recommended in all patients with persistent asthma (severity level 2 to 4).

To gain and maintain control of asthma symptoms and air flow obstruction, a step-wise approach to pharmacologic therapy is recommended in the EPR2 guidelines (see Tables 3 and 4). The step-wise approach has been divided into recommendations for children older than age 5 and age 5 to infancy, taking into consideration the special needs of this later age group. A step-wise approach has several advantages. It provides a more standardized approach, matching the amount and frequency of medications to severity of asthma. The focus for this approach is to gain asthma control by achieving the six goals of management. The level of intervention is stepped up until control is achieved. To more promptly gain control the level of therapy should be initiated at a higher level than the child's step of severity. When appropriate and as soon as possible step down therapy is begun to determine the minimal amount of medication necessary to maintain control. The ongoing monitoring techniques discussed previously in this article are crucial in determining the need for step-up or step-down interventions. Furthermore, before step-up therapy is initiated, other factors that diminish asthma control (such as triggers or psychosocial issues) must be investigated and dealt with if present. As stated earlier, the step-wise approach is a general guideline for disease management and not a prescription for the correct treatment of all asthma patients.

There are a number of effective asthma medications alluded to in the previous discussion on long-term-control step-wise management. Special attention will now be given to each of these medications especially in regard to their use in pediatric asthma management.

Cromolyn sodium has been used for asthma treatment for more than 20 years. In 1989, nedocromil sodium, a closely related MDI product became available. Both have similar anti-inflammatory actions and are generally used for long-term-control therapy. They also have the ability to inhibit EIA if used 20 to 30 minutes before exertion but not as effectively as short-acting inhaled Beta agonist. Their appeal in pediatric asthma management is their excellent safety profile. Except for a rare incidence of acute cough at time of usage, they have no other side effects. Furthermore, cromolyn comes as a nebulization solution for easy use in small children and infants. Their disadvantage is a dosing recommendation of 4 times a day, with progressive reduction in dosing frequency leading to progressive loss of efficacy. It must also be recognized that both of these medications have only mild to moderate anti-inflammatory action. The clinical effectiveness of cromolyn and nedocromil is definitely less predictable than inhaled corticosteroids (discussed later). When either medication is started for maintenance therapy, patients and parents should be informed of the delayed onset of action. It usually takes several days for onset of action and it can take up to one month for maximum efficacy.

Inhaled corticosteroids (ICS) have been proven the most consistently effective long-term-control medication (see related article).^24-29

Sustained-release theophylline is still an effective medication for the control of asthma symptoms when used appropriately. Its main action is mild-to-moderate bronchodilation. Some studies suggest it has mild anti-inflammatory action as well.³⁰ Theophylline is usually best used as adjunct therapy with other more definitive anti-inflammatory medications. It can also be effective in the control of nocturnal asthma if given in the late evening for the 12-hour sustained-release preparations or late afternoon for the 24-hour sustained-release preparations. The occasional GI and neurological AE's, as well as the need to monitor serum levels weighs against the routine use of this long-standing asthma medication.

Long acting Beta-agonists also provide sustained bronchodilation with antagonism to airway broncho-constriction and are generally well tolerated. They come in both oral sustained-release tablets and one inhaled product (Salmeterol�). All have an action duration of about 12 hours. This class of medication should only be used as adjunct therapy added to anti-inflammatory medications and for nocturnal asthma symptoms not otherwise controlled. Long-acting Beta-agonists should never be used as quick-relief medications or as the only long-term-control med. In both cases, there is the potential for "masking" worsening acute or chronic asthma. Patients often feel better quickly with the addition of long-acting Beta-agonists to their regimen. Patient and parent education on correct use of these medications is very important, including instructions not to stop their anti-inflammatory medications while on long-acting Beta-agonists.

Leukotriene modifiers are the newest category of asthma medicines with a truly novel mechanism of action.³¹ They will be discussed in greater detail in another article in this publication titled, "New Pharmaceutical Agents in the Management of Asthma."

Immunotherapy or "allergy shots" should be considered as a supplementary treatment in children with significant allergic asthma. Numerous studies have proven it effective in reducing asthma symptoms, improving quality of life, and attenuating airway hyper-responsiveness.^32-34 Successful results with immunotherapy rely heavily on proper patient selection. A clear relationship between acute or chronic asthma symptoms and allergen exposure should be demonstrated through positive tests for specific Ig E antibodies (usually skin tests) and a plausible environmental history. Immunotherapy is not without risk, although severe reactions are rare. It should be prescribed and supervised by a qualified allergist/immunologist and administered in a physician's office where facilities and trained staff are available for treating life-threatening reactions.

Despite good effort toward long-term control management, for most patients, asthma exacerbations will occasionally occur. Emphasis is placed on early and aggressive treatment of attacks, reducing the risk of progression and shortening the length of the attack. The first step in early treatment is early recognition. Here, intense parent and patient education of both common and subtle symptoms of asthma can pay off. In older children PFM's can provide objective information on severity of acute airflow obstruction. It could be argued that pharmacologic treatment of exacerbations should be started at the beginning of a viral URI, even before asthma symptoms appear.

Pharmacologic treatment of exacerbations always starts with aggressive use of inhaled short-acting Beta agonist.³⁵ Doses of 2-4 puffs by MDI's or single nebulization treatments should relieve symptoms and reverse air flow obstruction within ten to twenty minutes. If symptoms are not readily relieved, the dose of inhaled Beta agonists should be repeated and an oral corticosteroid burst should be started at a dose of 1 to 2mg/kg per day up to a maximum of 60-80mg per day.³⁶ Incomplete response to short-acting Beta agonists also necessitates contact with a physician or designated health care provider. If there is good initial response to Beta agonist (significant symptom relief for at least 3 hours), continued use up to every 3 to 4 hours for 1 to 2 days might be necessary. Prolonged need of q 4 hour inhaled short acting Beta agonist for more than 2 days also indicates the need for an oral steroid burst.

When burst steroid therapy is started it should be continued for 3 to 5 days depending upon patient response. If treatment with oral corticosteroids goes longer than 5 to 7 days, gradual tapering of the dose should be considered to allow recovery of the suppressed hypothalamic-pituitary-adrenal (HPA) axis. Tapering of the corticosteroids may also be considered after a 3 to 5 day burst if the patient's symptoms are not back to base line. This allows continued anti-inflammatory effects while reducing the risk of short-term systemic steroid side effects. Continued use of short acting inhaled Beta agonist at a frequency of b.i.d. to q.i.d. may be appropriate for several days after an exacerbation. Reduction of airway hyper-responsiveness after an asthma attack can take weeks. The risk of another exacerbation within this period is high. The gradual reduction of these quick-relief medications post-exacerbation may reduce this risk significantly.

Aggressive strategies for management of asthma attacks must be discussed in advance with the patient and parent at the time of initial diagnosis and reiterated throughout follow-up. A written exacerbation treatment plan can minimize uncertainty during these times of anxiety. A written treatment plan should include interventions coordinated to symptom severity, as well as PFM zones (when age appropriate). It is also important to ensure patients have an adequate supply of quick-relief medications (including oral corticosteroids) and appropriate equipment (i.e., nebulizers, spacers, PFM's, etc.) at all times. Also, it should be stressed that medicines and equipment must be taken when the family travels.

The overall successful outpatient management of pediatric asthma requires significant effort and time. Ultimately, pediatric outpatient management for asthma is best accomplished as a partnership between all members of the healthcare team and the patient and patient's family.