Abstract: All children with asthma should have periodic office visits, usually every 3 to 6 months, in which asthma action plans are updated. Periodic assessment of lung function by peak expiratory flow or office spirometry can help determine the appropriate treatment strategy. Low daily doses of inhaled corticosteroids remain the first and most effective choice of therapy for persistent asthma. If this approach is inadequate, adding a second medication, such as a leukotriene modifier or a long-acting ß2-agonist, is suggested. Short-acting ß2-agonists remain the most important therapy for intermittent asthma. For most children, the best route is via a metered-dose inhaler with either a spacer or valved holding chamber. If these agents are inadequate, a short course of oral corticosteroids may be required. (J Respir Dis. 2005;26(8):348-358)
Children are referred to me on a weekly basis because of poorly controlled asthma despite appropriate medications. In about 10% to 15% of these patients, the diagnosis is wrong or incomplete. Usually, however, the reasons for poor control are more subtle and are related to a combination of minor details that doom the regimen to failure.
Many management details may be debated among asthma specialists, and we all have our own biases. We must continually dedicate ourselves to practicing evidence-based medicine. However, clinical research on the management of childhood asthma is limited, and each child is different. We often have to extrapolate from adult studies, which frequently are short-term (less than 6 months) and are designed to acquire FDA approval for certain medications. How does that help pediatricians and family physicians concerned about long-term use of medication?
Asthma is sometimes difficult to control, and the current drugs are not perfect. Adherence to therapy is a major factor, and nonadherence is not always simply the result of inadequate patient education. Who can blame parents for being suspicious about long-term side effects of medications?
While it is imperative to integrate new evidence into our practice, it is equally important never to become too dogmatic. My approach constantly changes, and this may be true for all physicians who listen to their patients and work hard to help them.
In this article, I will offer practical suggestions to help manage asthma in children.
Any review of asthma management should begin with the excellent guidelines from the National Asthma Education and Prevention Program (NAEPP)1 and the Global Initiative for Asthma (GINA). I do not believe physicians must follow these guidelines exactly, but they should know when and why to adapt them.
I recommend that all physicians review the NAEPP guidelines for the diagnosis and management of asthma, which were first published in 1992 and were revised in 1997. In June 2002, an update focused on the management of asthma in children. These documents can be accessed on the National Heart, Lung, and Blood Institute Web site1: http://www.nhlbi. nih. gov/guidelines/ asthma/ index.htm.
Pocket guides and quick-reference sheets designed for physicians, nurses, patients, and parents are available on the GINA Web site2: http://www.ginasthma.com.
The office visit for children with asthma involves a number of important steps:
Review the goals of management at every visit.
Insist on routine periodic visits just for asthma.
Decide whether preventive or intermittent therapy is indicated.
Use either a peak expiratory flow (PEF) meter or spirometry to help quantify the severity of the child's asthma.
Give each patient a written asthma action plan at every visit.
During each office visit, it is key to ask children with asthma (and their parents) whether they believe that therapy is meeting their needs. Tell them that they should not settle for inadequate control and that the regimen will be changed if it is not working.
Suggested management goals are listed in Table 1.
The most important recommendation is that all children with asthma should have periodic office visits specifically for asthma (Table 2). The details of the preceding interval can be reviewed, and parents, patients, and physicians can agree on a clear action plan for the next interval (usually 3 to 6 months) (Table 3).
Unfortunately, many children with asthma see their physicians only when they are sick or during yearly health maintenance visits. There usually is inadequate time during these visits to manage asthma properly .
Preventive versus intermittent therapy
Some parents might prefer to give medications only when needed, but this approach is not always appropriate. Many children thought to have mild intermittent asthma do not really have mild intermittent asthma.
Parents should focus on their child's asthma control during the past 6 months--whether the asthma has interfered with activities of daily living or the child has missed school, has had emergency department (ED) visits or hospital admissions, has coughed all night, or has been feeling less than well. In these cases, I believe the potential risks of taking daily medications are outweighed by the benefits.
The NAEPP guidelines suggest that each child should be classified into 1 of 4 categories, based on clinical condition before treatment or before asthma has been adequately controlled (Table 4).
Assessing lung function
Periodic quantification of lung function by PEF meter or office spirometry can help determine the appropriate treatment strategy. Most physicians are familiar with the PEF meter, but many have not yet added the spirometer to their armamentarium. I encourage every primary care provider to obtain an inexpensive office spirometer, which gives much more information than just the PEF.3,4
How can a spirometer help? One of the goals of asthma management is for patients to have normal or near-normal lung function when they are well and not taking medications. Spirometry is more sensitive and less effort-dependent than PEF measurement.
If spirometry shows significant obstruction when the patient is not taking medications, he or she may have subtle symptoms consistent with chronic bronchospasm. Often, patients appear well in the office and deny any complaints until they (or their parents) are told of their spirometric results. Then, they may describe having had low-level morning cough, difficulty in exercising, or more frequent use of their rescue inhaler.
When parents recognize and correlate these symptoms with pulmonary function, they are much more likely to insist that the child take daily medications. If the symptoms are consistent with mild intermittent asthma and the child has normal lung function when well and not taking medications, parents and physicians are more likely to agree that intermittent therapy seems most appropriate.
Obtaining reliable spirometric results is challenging, particularly for children younger than 6 years. With practice, some can perform reproducible maximal forced expiratory maneuvers as young as age 3 or 4 years. If the procedure is rushed or the expiratory maneuver is inadequate (such as inhalation not deep enough, expiration not as hard as possible, lungs not emptied completely, or best effort not made), the results can be misleading. Knowing how to distinguish between accurate and inaccurate results is a vital skill for any physician managing asthma in children.
Case scenario: Anna was a 10-year-old whose asthma appeared to be triggered only by viral infec- tions. She was not taking any routine medications, and she denied any symptoms within the past 6 months.
Physical examination findings were normal. However, spirometry revealed significant obstruction. After checking the patient's flow-volume curves, I suspected that the nurse might not have coached her to blow as hard as she could. I repeated the procedures and found no significant airway obstruction. The 2 sets of results shown in Table 5 demonstrate that these tests are effort-dependent, and the results can be very misleading if not interpreted properly.
Asthma action plan
Giving the patient a written asthma action plan at the end of every visit is important. Asthma is often poorly controlled because of confusion or miscommunication. If few exacerbations occur, parents may forget what to do. Mark the date on the action plan so that parents can follow the current plan rather than an obsolete one.
The 2002 NAEPP update1 lists the following regarding the treatment of persistent asthma:
Low daily doses of inhaled corticosteroids remain the first and most effective choice (Table 6).
While long-term inhaled corticosteroid therapy can temporarily decrease growth velocity, evidence suggests that final adult height is not affected.5
Low to medium doses of long-term inhaled corticosteroids have no effect on bone mineral density in children nor do they increase the risk of cataracts or glaucoma.6
The doses of inhaled corticosteroids can often be lowered significantly between exacerbations. Asthma can be controlled in some children with the use of once-daily doses (except during viral exacerbations), which markedly improves adherence. If low doses are inadequate, I suggest adding a second medication rather than using higher doses of inhaled corticosteroids.7 Basically, there are 2 choices: a leukotriene modifier or a long-acting ß2-agonist.
The addition of a leukotriene modifier is appealing for children who have chronic allergic rhinitis, because this medication can also help the upper respiratory tract.8,9 Literature on the use of long-acting ß2-agonists in children has been developing slowly, but these agents are very effective in adults.10 I believe that long-acting ß2-agonists are safe and effective when they are combined with inhaled corticosteroids.11 I do not recommend giving children daily long- or short-acting ß2-agonists alone. To minimize the corticosteroid dose, more children are now given all 3 medications: inhaled corticosteroids, inhaled long-acting ß2-agonists, and leukotriene modifiers.
Given parents' and physicians' concerns about corticosteroids, it is not surprising that the leukotriene modifiers, such as montelukast, have rapidly become popular therapy for mild persistent asthma, although generally, low daily doses of inhaled corticosteroids are more effective monotherapy.12
I am reluctant to give very young children (younger than 3 or 4 years) any long-term asthma medication unless there is no other choice. For instance, data from young animals suggest that corticosteroids can have a deleterious effect on lung growth.13,14 I am not aware of data that suggest this is a problem with commonly prescribed doses of inhaled corticosteroids, but I believe our approach should be conservative in young children, especially those who were born prematurely.
Only a minority of children with asthma truly have intermittent asthma. These patients do not typically have significant atopy, and their primary triggers are respiratory infections and exercise. This becomes increasingly unusual after 6 to 8 years of age.
If the patient has significant allergies to environmental triggers, such as animal dander, mold and mold spores, pollen, house dust mites, or cockroaches, he or she is likely to be exposed to some of these triggers daily (for months or all year). When these allergens are combined with exposure to irritants, such as tobacco smoke, it is not surprising that intermittent therapy often proves inadequate.
Intermittent therapy is frequently inadequate for younger children whose only trigger is viral infection, because these patients may have many infections from September to June. However, older children (aged 6 to 9 years) may have only 2 or 3 viral infections during the school year, so intermittent ther-apy can be an excellent choice for them. These children may also start to show signs of significant exercise-induced bronchospasm, which is very responsive to intermittent therapy.
In some patients, I discontinue drug therapy during summer vacation. If children cannot get through the summer without taking medications, they are unlikely to do well without medication during the school year. Parents must understand that with intermittent therapy, some coughing and chest congestion may occur a few days before the medications have a chance to work.
Many parents do not give children asthma medications because the doctor has told them the "chest is clear." However, children can have significant airflow obstruction, as documented by spirometry, without wheezing on auscultation. The key is to give medication early. If parents give the medication after the child has coughed for a few days or started to wheeze, the results will be disappointing.
Many physicians and parents spend too much time trying to determine whether coughing is associated with the upper respiratory tract or is a sign of asthma. If you are convinced a child has asthma, it is usually best to give medications as soon as coughing starts.
Short-acting ß2-agonists: Albuterol and other short-acting ß2-agonists, such as levalbuterol and pirbuterol, remain the most important therapy for intermittent asthma, and usually, they adequately control symptoms. For most children, the best route is via a metered-dose inhaler (MDI) with a spacer or valved holding chamber. Better lung deposition results from an MDI with a holding chamber and mouthpiece than with a holding chamber and mask, but the latter is usually best for children younger than 5 or 6 years who are not able to hold onto a mouthpiece properly and consistently.
Although many studies have documented that albuterol via an MDI with a holding chamber is either as effective as or better than nebulized albuterol, many parents believe the opposite.15,16 The most common reason for failure with MDIs is confusion about the appropriate dose: 2 puffs are rarely adequate. Start with 4 puffs, and use more if necessary.
Most children can use an MDI with a masked holding chamber adequately and comfortably by age 3 years or, often, younger. The most difficult ages are from 8 months to 2Z\x years, when children may not allow a mask to be held to their face securely enough to maintain an adequate seal. In this case, parents may blow nebulized mist in the child's face. Children get a small amount of medication by this method, but it works because much medication (usually 2.5 mg of albuterol) is put into the nebulizer. Nebulizers can be noisy and time-consuming, but they can be the best choice for certain patients.
Levalbuterol (available only in a nebulizer solution) is an excellent choice for children who have unacceptable side effects from albuterol. There do not appear to be clinically important differences in the efficacy or pharmacodynamics of this drug compared with standard (racemic) albuterol.17,18
Pirbuterol is a very useful short-acting ß2-agonist, particularly in the management of exercise-induced asthma (EIA) in older children. It is administered via a breath-activated device, which is helpful for children who do not want to carry a spacer.
Corticosteroids: If ß2-agonists are inadequate, the gold standard (evidence-based approach) is a short course of oral corticosteroids. No long-term side effects are associated with short-term therapy, although some children have had significant behavioral side effects after a few days.19 Some children have personality changes as a re-sult of taking high doses of inhaled corticosteroids.
Many asthma specialists use inhaled corticosteroids on an intermittent basis or increase the dose during an acute exacerbation to avoid the use of oral corticosteroids. While this approach can sometimes be successful,20 most evidence suggests that oral corticosteroids are much more effective.21 Much higher doses of inhaled corticosteroids are needed for intermittent use than for preventive therapy, and this approach appears much less successful in young children whose illnesses progress very quickly. If the dose is increased enough, inhaled corticosteroids can help the patient with acute illness; however, the risks may be the same as for children who are taking oral corticosteroids.
While other causes of exercise intolerance may be mistaken for asthma, the symptoms of EIA can be subtle and frequently missed. Exercise testing can be very helpful; however, the diagnosis usually can be made from the history taking alone or from assessing the response to a short-acting bronchodilator given before exercise.
Generally, EIA occurs in children between ages 6 and 8 years; it is particularly common during soccer. Some children have symptoms as a result of running during school recess. Children in middle and high school often have EIA during physical education classes, especially during a "mile run." If the patient's symptoms are not fairly easily prevented with appropriate treatment, a more specific diagnostic approach is required. Table 7 lists some key points on the management of EIA.
Case scenario: Billy came to my office when he was aged 16 years. He was a dedicated member of his high school's cross-country team, but recently, he had complained of difficulty in breathing during practices, usually after about 7 to 10 miles of running.
At another institution, a routine 6-minute exercise test had failed to demonstrate exercise-induced bronchospasm. The physician suggested that Billy was trying to let his parents and coach know that he did not want to continue this difficult sport. Neither the patient nor his parents believed this.
Billy performed exercise tests at our facility. I kept the treadmill at the highest speed and sharpest angle for an additional 20 minutes, until this incredibly fit boy started to huff and puff. After 4 to 5 minutes of hyperventilating, he started to wheeze. His pulmonary function tests clearly indicated asthma.
ED AND INPATIENTMANAGEMENT
Children in status asthmaticus must receive aggressive therapy as soon as they arrive in the ED. The debate about giving ß2-agonists via nebulizer (intermittent or continuous) or MDI with a holding chamber is more about hospital economics and resource use than patient outcome. Either approach is reasonable, provided that the hospital staff is well trained to work with children.
Indications for mechanical ventilation have been described.22 Avoid intubation if possible.23 If the child's mental status is healthy, be ready to intubate when necessary. Noninvasive positive pressure ventilation sometimes helps and is probably underused.
Systemic corticosteroids are the most important elements in successful hospital care of childhood asthma. Most experts prefer the intravenous route, but venous access can be a major issue in children, and oral corticosteroids can be used.24 There are no data that support dosages of methylprednisolone or prednisone of more than 2 mg/kg/d, and side effects increase dramatically with higher doses. High doses may be necessary in critically ill children, but attempts to lower the doses should be made as soon as possible.
In many EDs, intravenous magnesium sulfate (usually, 25 mg/kg to 2 g) is given and provides additional bronchodilation, especially in severe cases.25 The anticholinergic agent ipratropium is also frequently given in addition to albuterol in children admitted with asthma, and some studies suggest a modest benefit.26 Some children appear to respond to these additional medications, but often, the benefits are unimpressive. The most important step for a child hospitalized with asthma is to change the home regimen.
REFERRAL TO AN ASTHMA SPECIALIST
Many factors play a role in the decision to refer a patient to an allergist or pulmonologist. Most asthma guidelines agree that consultation should be considered if there is any question about the diagnosis or if a patient has experienced any of the following, despite appropriate management:
Moderate or severe persistent asthma.
Multiple asthma-related urgent visits within 1 year.
Multiple hospitalizations for asthma.
Frequent bursts or prolonged use of oral corticosteroids.
Life-threatening exacerbations of asthma (such as those requiring ICU admissions or intubation).
Lack of achievement of expected therapeutic goals or unacceptable side effects of therapy.
Substantial asthma-related interference with quality of life.
The most important steps in the management of asthma in children are to enlist patients and their parents in the effort, meet with them on a regular basis, continually clarify the goals of therapy, listen to their concerns, and consider more than one solution. I have not met a child for whom one regimen remained appropriate throughout childhood.
After each office visit, give the patient a written asthma action plan tailored to the interval between visits, usually 3 to 6 months. Success depends more on adherence to therapy than on the specific medications. Determine whether your patients are taking their medications and, if necessary, rearrange their regimen to make it possible. Scheduled periodic office visits specifically for asthma are critical, even when a child is well.
1. National Asthma Education and Prevention Program.
Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma (1997)
Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics 2002.
Bethesda, Md: National Heart, Lung, and Blood Institute and National Institutes of Health; 2002. NIH publication 02-5074. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/ index.htm. Accessed July 21, 2005.
2. Global Initiative for Asthma.
Pocket Guide for Asthma Management and Prevention: A Pocket Guide for Physicians and Nurses.
Updated 2003 from the National Heart, Lung, and Blood Institute/World Health Organization Workshop Report: Global Strategy for Asthma Management and Prevention, issued January 1995 and revised 2002. Bethesda, Md: National Institutes of Health; 2002. NIH publication 02-3659. Available at: http://www. ginasthma.com. Accessed July 21, 2005.
3. Bahceciler NN, Barlan IB, Nuhoglu Y, Basaran MM. Risk factors for the persistence of respiratory symptoms in childhood asthma.
Ann Allergy Asthma Immunol.
4. Blonshine SB. Pediatric pulmonary function testing.
Respir Care Clin N Am.
5. MacKenzie C. Effects of inhaled corticosteroids on growth.
J Allergy Clin Immunol.
1998;101(4 pt 2):S451-S455.
6. Cave A, Arlett P, Lee E. Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects.
7. Lipworth BJ, Jackson CM. Second-line controller therapy for persistent asthma uncontrolled on inhaled corticosteroids: the step 3 dilemma.
8. Nayak-Anjuli S, Philip G, Lu S, et al. Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall.
Ann Allergy Asthma Immunol.
9. Bisgaard H. Leukotriene modifiers in pediatric asthma management.
10. Dutta EJ, Li JT. Beta-agonists.
Med Clin North Am.
11. Skoner DP. Balancing safety and efficacy in pediatric asthma management.
2002;109 (2 suppl):381-392.
12. Ducharme FM. Inhaled glucocorticoids versus leukotriene receptor antagonists as single agent asthma treatment: systematic review of current evidence.
13. Luyet C, Burri PH, Schittny JC. Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development.
Am J Physiol Lung Cell Mol Physiol.
14. Srinivasan G, Bruce EN, Houtz PK, Bruce MC. Dexamethasone-induced changes in lung function are not prevented by concomitant treatment with retinoic acid.
Am J Physiol Lung Cell Mol Physiol.
15. Amirav I, Newhouse MT. Metered-dose inhaler accessory devices in acute asthma: efficacy and comparison with nebulizers: a literature review.
Arch Pediatr Adolesc Med.
16. Ploin D, Chapuis FR, Stamm D, et al. High-dose albuterol by metered-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: a double-blind, randomized equivalence trial.
2000; 106(2 pt 1):311-317.
17. Boulton DW, Fawcett JP. The pharmacokinetics of levosalbutamol: what are the clinical implications?
18. Ahrens RC, Weinberger M. Levalbuterol and racemic albuterol: are there therapeutic differences?
J Allergy Clin Immunol.
19. Kayani S, Shannon DC. Adverse behavioral effects of treatment for acute exacerbation of asthma in children: a comparison of two doses of oral steroids.
20. Volvovitz B, Bentur L, Finkelstein Y, et al. Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone.
J Allergy Clin Immunol.
1998;102(4 pt 1):605-609.
21. Hendeles L, Sherman J. Are inhaled corticosteroids effective for acute exacerbations of asthma in children?
22. Nair SJ, Cloutier MM. Managing severe asthma exacerbations in children.
J Respir Dis Pediatrician.
23. Werner HA. Status asthmaticus in children: a review.
24. Ratto D, Alfaro C, Sipsey J, et al. Are intravenous corticosteroids required in status asthmaticus?
25. Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial.
26. Craven D, Kercsmar CM, Myers TR, et al. Ipratropium bromide plus nebulized albuterol for the treatment of hospitalized children with acute asthma.