Management of Asthma in Children

Author: James P. Kemp, Judith A. Kemp
Date: April 1, 2001

The prevalence of asthma in children has increased 160 percent since 1980, and the disease currently affects nearly 5 million children in the United States. The National Asthma Education and Prevention Program provides guidelines for improved asthma care. The goals of this program are to limit the frequency, severity and costliness of asthma exacerbations through extensive education of physicians, children and caregivers. The four components of asthma management include regular assessment and monitoring, control of factors that contribute to or aggravate symptoms, pharmacologic therapy and education of children and their caregivers. The guidelines recommend a stepwise approach to pharmacologic treatment, starting with aggressive therapy to achieve control and followed by a "step down" to the minimal therapy that will maintain control. Quick relief of symptoms can be achieved preferentially by the use of short-acting beta2 agonists. Medications for long-term control should be considered for use in children with persistent symptoms. Inhaled corticosteroids are the most potent long-term anti-inflammatory medications. Other options include long-acting beta2 agonists, cromolyn sodium and nedocromil, antileukotriene agents and theophylline. All have advantages and disadvantages in individual situations. (Am Fam Physician 2001;63:1341-8,1353-4.)

Asthma currently affects nearly 5 million children in the United States--more than 5 percent of the population younger than 18 years.(1) In children four years or younger, the prevalence increased 160 percent from 1980 to 1994, and from 1980 to 1993, the death rate from asthma nearly doubled among persons five to 24 years.(1) Asthma is 26 percent more prevalent and results in more severe disability and more frequent hospitalizations in black children than in white children, and black children are four to six times more likely to die of asthma.(2,3) In children younger than 15 years, asthma accounts for 3 million physician visits, 570,000 emergency department visits, 164,000 hospital stays, 8.7 million prescriptions and 10 million missed school days per year.(4,5)

These statistics highlight the need to aggressively manage this disease and its symptoms. Unfortunately, anti-inflammatory agents such as inhaled corticosteroids are not yet prescribed for all patients with persistent asthma(6) and, even when these medications are prescribed, they may be underutilized because parents fear the possibility of adverse side effects or children have difficulty using metered-dose inhalers (MDIs). New therapeutic options are available and with aggressive, appropriate therapy, physicians can prescribe an asthma management regimen to ameliorate symptoms, control disease and allow normal activity even in children as young as one to two years.

Pathophysiology

Asthma is a chronic inflammatory disorder that produces airway hyper-responsiveness, airflow limitation and persistent respiratory symptoms, such as wheezing, coughing, chest tightness and shortness of breath.(7) Airflow limitation is produced by acute bronchoconstriction, airway edema, mucous plug formation and airway remodeling.(8)

Asthma has immediate and delayed inflammatory responses. During the early phase, mast cells release mediators (e.g., histamine, leukotrienes, prostaglandins and thromboxanes) that lead to vasodilation, edema and bronchoconstriction.(9) Leukotrienes, recently recognized as key culprits in asthma, are approximately 1,000 times more potent than histamines in mediating an inflammatory response. Their powerful chemotactic effect on neutrophils, monocytes and lymphocytes enhances the inflammatory response.(10)

During the late phase, cytokines are released that prolong inflammation and activate eosinophils, basophils, lymphocytes and mast cells. Chronic inflammation may result in smooth muscle hyperplasia, bronchial hyper-responsiveness and increased collagen deposition beneath the basement membrane, which further narrows the airway.(11)

Diagnosis

Fifty to 80 percent of children with asthma develop symptoms before five years of age.(12) Asthma symptoms vary widely and may mimic other childhood diseases (e.g., upper respiratory infections). When parents report episodic or persistent coughing, wheezing, shortness of breath, rapid breathing or chest tightness, and if these symptoms are worse during the evening or early morning hours, or are associated with triggers (e.g., exercise, allergen exposure), the physician should suspect asthma.

Alternative diagnoses should be excluded. Wheezing is not present in all patients with asthma and is not a sign exclusive to asthma. Wheezing may be caused by respiratory infections, rhinitis, sinusitis or vocal cord dysfunction. Before a definitive diagnosis of asthma is reached, consideration should be given to other factors, such as foreign body aspiration, or to other diseases, such as cystic fibrosis or heart disease, that may be causing the patient's symptoms.

Obtaining a medical history is essential to establishing the diagnosis of asthma. Factors associated with the onset of asthma symptoms include allergy, family history of asthma or allergy, perinatal exposure to tobacco smoke, viral respiratory infections, male gender and low birth weight.(13) Young children who develop persistent asthma are likely to have increased serum IgE levels at nine months of age, atopic dermatitis and rhinitis (unrelated to upper respiratory infection) during their first year, severe lower respiratory infections requiring hospitalization and diminished airway function by six years of age.(13)

Identification of symptom patterns, severity of symptoms and precipitating factors will support the diagnosis of asthma: "How often and when do episodes occur?" "What is their duration?" "Do symptoms occur or worsen during the night, with exercise or with an infection?" "Are they precipitated or aggravated by specific triggers?" "Do they interfere with sleep or daily activities, or require emergency department or hospital visits?" "How often are short-acting bronchodilators used?" "Are symptoms temporarily relieved by bronchodilators?"(14)

Pulmonary function tests should be, and allergy tests may be conducted to confirm the diagnosis.(15) Spirometry performed before and 15 to 20 minutes after the child inhales a short-acting bronchodilator assesses airflow obstruction and determines its reversibility. Pulmonary function results consistent with asthma include variable airflow obstruction (20 percent or more) with serial spirometry or peak expiratory flow (PEF) measurements, and an increase in forced expiratory volume in one second (FEV1) of 12 percent or more after bronchodilator therapy. Unfortunately, routine pulmonary function testing is unreliable in infants and many preschool children. These tests may be a more reliable indicator in children who are three to four years of age, but considerable variation exists because of poor technique and the use of adult-sized equipment. In most children, the primary diagnostic tool is clinical assessment.(16) However, pulmonary function tests should be performed as soon as possible.

A significant percentage of patients (75 to 85 percent) with asthma have positive immediate hypersensitivity skin tests (IgE), indicating the vital role that allergy plays in pediatric asthma. Atopy is the strongest predictor for wheezing progressing to asthma; therefore, a history of allergies is significant.(17)

Treatment

Treatment should include patient education, trigger avoidance and drug therapy regimens that enable patients to function without limitations from asthma symptoms. Table 118 summarizes the standard diagnosis and treatment parameters and provides a list of commonly used medications.

EDUCATION

Education for patients and caregivers should focus on the identification and avoidance of triggers, understanding the uses of prescribed medications and the importance of compliance and monitoring, as well as the proper use of inhalation devices.(19) Daily self-management plans provide guidance for patients in peak flow monitoring, medication usage and symptom reporting. Emergency action plans help identify an exacerbation and delineate the actions to take. These plans should be developed in consultation with caregivers and patients, and provided to them in writing. Excellent examples of these plans are provided in the asthma guidelines from the National Asthma Education and Prevention Program of the National Heart, Lung, and Blood Institute.(20) (The guidelines are available on the Web at: http://www.nhlbi support.com/asthma/index.html).

TRIGGERS AND ENVIRONMENTAL CONTROL

Cromolyn sodium (Intal) and nedocromil (Tilade) are first-line, daily anti-inflammatory inhaled agents that inhibit early- and late-phase bronchoconstriction, with virtually no serious side effects and no known drug interactions.(26) These medications are available in MDI and nebulizer formulations; however, frequent administration is required (up to four doses daily), which may discourage compliance.(24) Furthermore, these agents are less effective than corticosteroids in many patients. Nedocromil's bitter taste may discourage compliance in some children.

Antileukotriene agents were developed to inhibit the effects of leukotrienes. This class of drugs represents the first new approach to asthma therapy in 25 years. The leukotriene receptor antagonists montelukast (Singulair) and zafirlukast (Accolate), and the 5-lipoxygenase inhibitor zileuton (Zyflo) are unique in their ability to target specific components of asthmatic inflammation.(29) Montelukast is available for the treatment of children with asthma who are six to 14 years of age, at a dosage of 5 mg once daily at bedtime. A 10-mg tablet is approved for use in children older than 15 years,(30) and the FDA recently approved a 4- or 5-mg chewable tablet for children two to five years. Zafirlukast is also FDA-labeled for the treatment of children with asthma who are older than seven years, at a dosage of 10 mg twice daily.(31) Although zileuton is FDA-labeled for pediatric treatment, it is prescribed infrequently because it has a four-times daily dosing regimen and a risk of hepatotoxicity that requires monitoring.

Although the role of these drugs continues to evolve, the antileukotrienes have demonstrated efficacy against exercise- and allergen-induced bronchoconstriction, and an additive benefit in the treatment of patients with symptomatic, moderate asthma who are taking maintenance inhaled corticosteroids.(32,33) They reduce the need for rescue medication in patients with mild asthma and are appropriate as long-term therapy in patients who require more than an occasional treatment with beta2-agonist bronchodilators. Data on the safety of montelukast and zafirlukast are excellent, with an adverse event profile similar to that of placebo.(31,32) Churg-Strauss syndrome (an eosinophil-associated vasculitis) has reportedly been associated (rarely) with corticosteroid withdrawal and may represent an unmasking of a previously unrecognized condition.(34)

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(33.) Pearlman DS, Ostrom NK, Bronsky EA, Bonuccelli CM, Hanby LA. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children. J Pediatr 1999;134:273-9.

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JAMES P. KEMP, M.D., is clinical professor of pediatrics in the Division of Immunology and Allergy at the University of California School of Medicine, San Diego, and immediate past president of the American Academy of Allergy/Asthma and Immunology. Dr. Kemp earned his medical degree from the University of Virginia School of Medicine, Charlottesville, and completed a residency in pediatrics at Emory University School of Medicine, Atlanta. Dr. Kemp completed a fellowship in pediatric allergy and immunology at the University of California, San Francisco, School of Medicine.

JUDITH A. KEMP, D.O., is in private practice in San Diego. She earned her medical degree from the College of Osteopathic Medicine of the Pacific (now Western Health Sciences University), Pomona, Calif., and completed a residency in family practice at Sharp/Grossmont Hospital, San Diego.

Address correspondence to James P. Kemp, M.D., Allergy and Asthma Medical Group and Research Center, 9610 Granite Ridge Dr., Ste. B, San Diego, CA 92123 (e-mail: JPK3355@aol.com). Reprints are not available from the authors.

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