Management of Pediatric Asthma: Focus on the Expert Panel Report 3

Definition and impact of asthma 

Asthma is a chronic inflammatory disorder of the airways involving numerous cell types and mediators. Patients with asthma exhibit variable and recurring symptoms, including recurrent episodes of cough or wheeze, breathlessness, and chest tightness (National Asthma Education and Prevention Program [NAEPP], 2007). The airflow obstruction responsible for the symptoms is largely reversible and related to bronchial smooth muscle contraction (broncho-constriction), inflammation of the airway mucosal surface leading to edema and increased mucus production, and hyperresponsiveness or increased bronchial reactivity.

Diagnosis is challenging in young children who often present with transient episodes of wheezing or reactive airways disease with or without respiratory viral infections.

Asthma is unique because it has a significant direct impact on people across the continuum of life, from the young to the very old. It is a leading diagnosis among children and is associated with significant morbidity as measured in exacerbations, missed days of school, and decreased quality of life. According to national statistics, more than 20 million people in the United States have asthma, including 9 million children and adolescents (American Lung Association, 2005; Dey, Schiller, & Tai, 2004). In other surveys, nearly 12% of children report an asthma diagnosis, and the prevalence is disproportionately higher among lower socioeconomic groups (Bloom & Dey, 2006; Cloutier, Hall, Wakefield, & Bailit, 2005). Children experience 4 million asthma attacks annually, and 44% of hospitalizations for this disease occur in children (Hall & Owings, 2002). In 2002, 14.7 million days were missed from school reportedly due to asthma. Diagnosis is challenging in young children who often present with transient episodes of wheezing or reactive airways disease with or without respiratory viral infections.

Risk factors for asthma development 

Wheezing that occurs early in life is considered a risk factor for asthma development; however, young patients exhibit varying patterns of wheeze, ranging from transient wheeze that resolves, wheezing during viral infections in the absence of atopy, and persistent wheezing. In addition, many patients experience wheezing during childhood that resolves during adolescence. In these patients, the symptom may never occur again or may develop later in life.

The major risk factors associated with asthma development are the presence of atopy, recurrent respiratory viral illnesses, and early exposure to allergens (Stewart, 2008). Atopy refers to a genetic predisposition to allergic diseases, including atopic dermatitis and eczema. The Modified Asthma Predictive Index indicates major asthma risk factors as a parental history of asthma, clinician diagnosis of atopic dermatitis, and evidence of sensitization to at least one aero-allergen (Guilbert et al., 2004). Respiratory viral illnesses are both a risk factor and a trigger for asthma. Specifically, severe infection with respiratory syncytial virus is associated with asthma development later (Sigurs et al., 2005). The impact of early allergen exposure as a risk factor is less clear. Early exposure to dust mites and cockroach roach allergen is associated with higher asthma rates; however, data are conflicting about whether a pet in the home acts as a risk or protective factor (Hesselmar, Abert, Aberg, Eriksson, & Bjorksten, 1999; Litonjua, Carey, Burge, Weiss, & Gold, 2001).

Pathogenesis and pathophysiology 

Pediatric asthma is characterized by episodic wheezing and reversible airflow obstruction. The concomitant presence of allergies is more prevalent in children compared with adults. Available evidence suggests that loss of lung function occurs early in life for asthma patients, even before a pattern of recurrent or persistent wheezing is evident (Taussig et al., 2003). Some patients continue to exhibit spirometric declines despite adequate long-term control therapy.

Common triggers for asthma symptoms and exacerbations include upper respiratory viral infections, exposures to allergens or irritants, exercise, and cold air. Other conditions that are often present in children with asthma and can aggravate asthma control include gastroesophageal reflux disease, allergic rhinitis, and sinusitis. Among young children, the most frequent cause of asthma symptoms is a viral respiratory infection. For infants and children who wheeze with viral upper respiratory infections, two patterns develop: either persistence of symptoms throughout childhood, or a disappearance of symptoms in the preschool years.

Bronchoconstriction, hyperresponsiveness, and airway edema are principal features attributed to underlying inflammation of asthma. The chronic effects of inflammation include changes in airway structure, exhibited as sub-basement membrane fibrosis, mucus hypersecretion, smooth muscle hypertrophy, and damage to epithelial cells. Permanent remodeling of the airway occurs in some but not all patients.

National asthma guidelines 

Recommendations concerning asthma management are available from the NAEPP. In 2007, Guidelines for the Diagnosis and Management of Asthma's Expert Panel Report 3 was published and provides evidence-based recommendations (NAEPP, 2007). The guidelines describe three categories for management based on the patient's age: 0 to 4 years, 5 to 11 years, and 12 years and older. Each category includes a six-step approach for management, with consideration provided for age-appropriate management considerations.

Diagnostic considerations 

Data suggest that symptoms develop in more than 50% of children with asthma before age 5 years. Under-diagnosis is a frequent problem, especially in children who exhibit wheezing with respiratory infections. Although clinicians who treat children often are reluctant to make a diagnosis of asthma, recurrent episodes of cough and wheezing most often are due to asthma in both children and adults. It is prudent, however, to consider the differential diagnoses described in Box 1.

The main components of asthma diagnosis include the patient history, physical examination, and selected diagnostic testing based on the patient's age. Diagnosis can be challenging in young patients based on the absence of objective parameters. A key feature in the history is reported wheezing with respiratory infections, although wheezing in the absence of infection may predict more persistent disease. The presence of risk factors for asthma development is important to explore. These include previous respiratory infections and environmental exposures to a variety of allergens and irritants.

Based on the episodic nature of asthma, the physical examination is often relatively normal. Because of the prevalence of allergies in childhood asthma, signs of allergic rhinitis or dermatologic allergies may be present. Lung examination is often normal during asymptomatic periods, and signs and symptoms, including wheezing, coughing, decreased air movement, and accessory muscle retractions, are only present during acute episodes.

Objective data that can be obtained in older children can facilitate a diagnosis of asthma. Spirometry testing is important for asthma diagnosis and monitoring and should be considered for children as young as age 5 or 6 years, although a child's ability to perform spirometry is highly variable at this age. Evidence for airflow obstruction on spirometry is reflected in a reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity. These results basically measure the volume of air exhaled in the first second of a maximal exhalation (FEV1) and the total volume of air exhaled (forced vital capacity). A ratio of less than 75% is consistent with asthma in children. The actual FEV1 result provides evidence for asthma severity (see severity classification).

A recent American Thoracic Society workshop addressed the benefit of widespread screening for asthma in children (Gerald et al., 2007). Participants concluded that, based on current evidence, a good rationale does not exist for population-based asthma screenings. The participants suggest that clinicians should be attentive to recurrent or persistent symptoms among children followed by appropriate workup and assessment.

Other objective testing in the diagnosis of asthma include peak expiratory flow rates, post-bronchodilator testing to evaluate reversibility, bronchial challenges with methacholine or histamine, and skin testing or serologic testing for the presence of atopy and allergies.

Other objective testing in the diagnosis of asthma include peak expiratory flow rates, post-bronchodilator testing to evaluate reversibility, bronchial challenges with methacholine or histamine, and skin testing or serologic testing for the presence of atopy and allergies. These tests may be useful in selected clinical situations or when the diagnosis is difficult.

Classification: severity and control 

In the current asthma guidelines, there was a major shift in emphasis from categorizing patients based on disease severity to a new focus on asthma control. At the time of diagnosis or initial assessment, the patient can be categorized according to severity as described in Table 1, Table 2, Table 3. After therapeutic strategies are initiated, ongoing monitoring should focus on control. The categories of control are well controlled, not well controlled, and very poorly controlled, which are described in Table 4, Table 5, Table 6.

Table 1. Asthma severity classification for patients aged 0 to 4 years

	Components of severity	Intermittent	Mild persistent	Moderate persistent	Severe persistent
	Impairment
	Symptoms	≤2 days/week	≥2 days/week, but not daily	Daily	Throughout the day
	Nighttime awakenings	None	1 to 2 times/month	3 to 4 times/month	>1 time each week
	SABA rescue use	≤2 days/week	≥2 days/week, but not daily	Daily	Several times each day
	Interference with normal activity	None	Minor limitation	Some limitation	Extremely limited
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1/year	≥2 in 6 months; or ≥4 wheezing episodes in a year lasting >1 day

SABA, Short-acting inhaled β2 agonists. Lung function assessments are not practical for this age group. National Asthma Education and Prevention Program, 2007.

Table 2. Asthma severity classification for patients 5 to 11 years

	Components of severity	Intermittent	Mild persistent	Moderate persistent	Severe persistent
	Impairment
	Symptoms	≤2 days/week	≥2 days/week, but not daily	Daily	Throughout the day
	Nighttime awakenings	≤2 times/month	3 to 4 times/month	≥1 times/week, but not nightly	Often nightly
	SABA rescue use	≤2 days/week	≥2 days/week, but not daily	Daily	Several times each day
	Interference with normal activity	None	Minor limitation	Some limitation	Extremely limited
	Lung function	Normal FEV1 between exacerbations; FEV1>80%; ratio >85%	FEV1>80%; ratio >80%	FEV1 60-80%; ratio 75%-80%	FEV1<60%; ratio <75%
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1 per year	≥2 per year

FEV1, Forced expiratory volume in 1 second; SABA, Short-acting inhaled β2 agonists. National Asthma Education and Prevention Program, 2007.

Table 3. Asthma severity classification for patients ≥12 years

	Components of severity	Intermittent	Mild persistent	Moderate persistent	Severe persistent
	Impairment
	Symptoms	≤2 days/week	≥2 days/week, but not daily	Daily	Throughout the day
	Nighttime awakenings	≤2 times/month	3 to 4 times/month	≥1 times/week, but not nightly	Often nightly
	SABA rescue use	≤2 days/week	≥2 days/week, but not daily	Daily	Several times each day
	Interference with normal activity	None	Minor limitation	Some limitation	Extremely limited
	Lung function	Normal FEV1 between exacerbations;	FEV1>80%;	FEV1 60%-80%;	FEV1<60%;
		FEV1>80%; normal ratio	normal ratio	ratio reduced by 5%	ratio reduced >5%
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1 per year	≥2 per year

FEV1, Forced expiratory volume in 1 second; SABA, short-acting inhaled β2 agonists. National Asthma Education and Prevention Program, 2007.

Table 4. Asthma control classification for patients aged 0 to 4 years

	Components of control	Well controlled	Not well controlled	Very poorly controlled
	Impairment
	Symptoms	≤2 days/week	>2 days/week, or multiple times for ≤2 days/week	Throughout the day
	Nighttime awakenings	≤1 time/month	> 1 time/month	>1 time each week
	SABA rescue use	≤2 days/week	≥2 days/week	Several times each day
	Interference with normal activity	None	Some limitation	Extremely limited
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1 per year	2-3 times per year	>3 times per year
	Treatment-related adverse effects	Assess potential adverse effects based on frequency and intensity ranging from none to very troublesome and worrisome

SABA, Short-acting inhaled β2 agonists. Lung function assessments are not practical for this age group. For asthma that is not well controlled, consider one step up in therapy. For very poorly controlled asthma, consider a short course of oral corticosteroids and a step up in therapy. National Asthma Education and Prevention Program, 2007.

Table 5. Asthma control classification for patients aged 5 to 11 years

	Components of control	Well controlled	Not well controlled	Very poorly controlled
	Impairment
	Symptoms	≤2 days/week	>2 days/week, or multiple times for ≤2 days/week	Throughout the day
	Nighttime awakenings	≤1 time/month	≥2 times/month	≥2 times/week
	SABA rescue use	≤2 days/week	>2 days/week	Several times each day
	Interference with normal activity	None	Some limitation	Extremely limited
	Lung function	FEV1>80%; ratio >80%	FEV1 60%-80%; ratio 75%-80%	FEV1<60%; ratio <75%
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1 per year	≥2 per year
	Treatment-related adverse effects	Assess potential side effects based on frequency and intensity ranging from none to very troublesome and worrisome

FEV1, Forced expiratory volume in 1 second; SABA, short-acting inhaled β2 agonists. For asthma that is not well controlled, consider one step up in therapy. For very poorly controlled asthma, consider a short course of oral corticosteroids and a step up in therapy. National Asthma Education and Prevention Program, 2007.

Table 6. Asthma control classification for patients aged ≥12 years

	Components of control	Well controlled	Not well controlled	Very poorly controlled
	Impairment
	Symptoms	≤2 days/week	>2 days/week	Throughout the Day
	Nighttime awakenings	≤2 time/month	1 to 3 times/week	≥4 times/week
	SABA rescue use	≤2 days/week	>2 days/week	Several times each day
	Interference with normal activity	None	Some limitation	Extremely limited
	Lung function	FEV1 or peak flow >80%	FEV1 or peak flow 60%-80%	FEV1 or peak flow <60%
	Validated questionnaires
	ATAQ	0	1-2	3-4
	ACQ	≤0.75	≥1.5	N/A
	ACT	≥20	16-19	≤15
	Risk
	Exacerbations requiring oral corticosteroids	0 to 1 per year	≥2 per year
	Treatment-related adverse effects	Assess potential side effects based on frequency and intensity ranging from none to very troublesome and worrisome.

ACQ, asthma control questionnaire; ACT, asthma control test; ATAQ, asthma therapy assessment questionnaire; FEV1, Forced expiratory volume in 1 second; SABA, short-acting inhaled β2 agonists. For asthma that is not well controlled, consider one step up in therapy. For very poorly controlled asthma, consider a short course of oral corticosteroids and a step up in therapy. National Asthma Education and Prevention Program, 2007.

Severity and control are described in two specific domains: impairment and risk. Impairment refers to the patient's current condition and how it affects his or her life. Risk is assessed based on the potential for future problems associated with their asthma. Assessment of severity or control involves the use of similar measures: nature and frequency of symptoms, use of rescue therapies (short-acting β2 agonist [SABA]), limitations in activity because of asthma, spirometry or peak flow measurements, and exacerbation frequency. A combination of measures should be used in assessing severity or control. An emerging measure that may become more important in the near future is the use of exhaled nitric oxide measurements. Exhaled nitric oxide may be related to inflammatory activity in the airways and could become a usual monitoring parameter for asthma severity and control.

The new focus on control offers the advantage of clearly identifying patients whose asthma is not well controlled or is very poorly controlled. The clinician can use the various tools available for assessing control and, based on the results, interventions can be made to improve lung function and asthma control.

Long-term management 

The major components of asthma management are education of the patient and family, strategies to reduce or eliminate exposure to known asthma trigger, pharmacotherapy, and an appropriate self-management plan. The clinician should give ample attention to each of these areas in an effort to optimize asthma control for the benefit of the patient.

Education 

Educational strategies for patients with asthma and their families are based on numerous factors, including patient age and the family situation and dynamics. Sufficient evidence exists to support the value of educating children and their families about self-management skills in improving numerous asthma-related outcomes (Brown et al., 2002, Butz et al., 2005). The guidelines describe the educational process as a partnership between the clinician, patient, and the caregivers. The clinician should make an assessment of the child's ability and receptivity to receive educational messages, information about the home environment and usual routine for care of the child, and the family's involvement in the patient's illness. Key educational messages to be communicated are listed in Box 2. Education should be offered at multiple points of care.

One of the important components of education relates to the use of inhalation devices. Inhalation therapy is a common method of treating asthma, and proper use of inhalation devices is essential to achieve the therapeutic benefit. Inhalation devices differ significantly in their directions for use, and patients require initial instruction and observation, as well as periodic follow-up, to ensure proper use. This is true for all currently available inhalation devices.

Pharmacotherapy recommendations 

Age-specific recommendations are available for asthma management in the current asthma guidelines (NAEPP, 2007). These recommendations are based on the available evidence for the individual age groups and, for each age category, there are six steps of therapy, as described in Table 7. In some cases at the younger ages, there has not been adequate research to support recommendations for some of the available therapies. In other cases, however, the recommendations are inferred through extrapolation from other age groups. The various options are available based on the heterogeneity of asthma, which suggests that no single therapy is the optimal choice for every patient in a specific severity category.

Table 7. Stepwise approach to asthma management∗

	Age Category (y)	Step 1	Step 2†	Step 3	Step 4	Step 5	Step 6
	0-4	SABA as needed	Preferred Low-dose ICS	Medium-dose ICS	Medium-dose ICS plus either LABA or montelukast	High-dose ICS plus either LABA or montelukast	High-dose ICS plus either LABA or montelukast plus oral corticosteroids
			Alternative Cromolyn or montelukast
	5 to 11	SABA as needed	Preferred Low-dose ICS	Medium-dose ICS or low-dose ICS plus LABA, LTRA, or theophylline	Preferred Medium-dose ICS plus LABA	Preferred High-dose ICS plus LABA	Preferred High-dose ICS plus LABA plus oral corticosteroids
			Alternative Cromolyn or LTRA or nedocromil or theophylline		Alternative Medium-dose ICS plus LTRA or theophylline	Alternative High-dose ICS plus either LTRA or theophylline	Alternative High-dose ICS plus LTRA or theophylline plus oral corticosteroids
	≥12	SABA as needed	Preferred Low-dose ICS	Preferred Medium-dose ICS or low-dose ICS plus LABA	Preferred Medium-dose ICS plus LABA	High-dose ICS plus LABA and consider omalizumab for patients with allergies	High-dose ICS plus LABA plus oral corticosteroids and consider omalizumab for patients with allergies
			Alternative Cromolyn or LTRA or nedocromil or theophylline	Alternative Low-dose ICS plus LTRA or theophylline or zileuton	Alternative Medium-dose ICS plus LTRA or theophylline or zileuton

ICS, Inhaled corticosteroid; LABA, long-acting β2 agonist; LTRA, leukotriene receptor antagonist; SABA, short-acting β2 agonist.

∗ Patient education, environmental control, and management of co-morbidities should be considered at each step. † Subcutaneous allergen immunotherapy should be considered at Steps 2 through 4 for patients with allergies, ages 5 years and older. National Asthma Education and Prevention Program, 2007.

Challenges with inhalation therapies 

Pharmacological management of asthma is largely accomplished through the use of medications delivered by inhalation. This practice presents unique challenges to the management of this condition because the proper use of inhalation delivery systems is imperative in order to receive benefit from these therapies. Improper inhalation technique is another type of adherence problem. It is well established that the clinician should spend time instructing the patient initially and then periodically evaluate the patient's use of the device.

Inhalation devices vary in the recommended technique for use, which also complicates this issue. For pediatric patients, the clinician should assess the appropriateness of specific inhalation devices based on the patient's ability and willingness to use it. Despite these challenges, inhalational therapies for asthma offer significant advantages over oral agents in terms of effectiveness and safety.

Adjusting asthma therapies 

Strategies are available for stepping up or stepping down asthma therapies based on the degree of control. Step-up should be considered when the patient's asthma is not well controlled or very poorly controlled. Prior to a decision about step-up, however, the clinician should review the patient's adherence pattern, inhaler technique, and compliance with nonpharmacologic recommendations, including environmental control. Another recommendation that is sometimes overlooked in the asthma guidelines is related to stepping-down treatment regimens once the patient's asthma has been well controlled and he or she is symptom-free and without exacerbations for an extended period. Step-down should be considered after the patient's asthma has been well controlled for at least 3 months. There are obvious advantages to a step-down in therapy related to patient convenience, cost of therapy, and reducing the risk of adverse effects.

Acute exacerbations 

Despite the best efforts in management, some patients will experience exacerbations of their asthma which are unavoidable. Acute exacerbations of asthma in children should be treated promptly and aggressively to ensure the best possible outcome. The general principles of management do not differ significantly among children and adults. They include intensification of short-acting bronchodilator therapy and using adequate doses of systemic corticosteroids.

Following treatment of an acute exacerbation in the primary care provider's office, emergency department, or hospital, the patient should receive instructions concerning a discharge plan. The basic premise of this plan is to continue the treatment for the acute exacerbation and to advise the patient that he or she should notice an incremental improvement each day. If there is not improvement each day, or significant improvement over a few days, the patient and family should be instructed to return for evaluation and treatment. In most cases, patients should receive follow-up care in at least 30 days following the exacerbation.

Specific considerations for pediatric patients with asthma 

Pediatric patients with asthma have age-specific issues that should be considered in their management. Very young patients are dependent on their parents or caregivers for their management. Many decisions regarding care are outside the direct control of the patient; thus, the clinician should consider home environment and family dynamic issues when developing treatment plans. For each category of pediatric patients, key clinical activities that have been identified as being important for the various age categories are described in Table 8.

Table 8. Recommended key activities for asthma management

	Age group (y)	Key clinical activity
	0-4	Consider the use of daily long-term control therapy
		Monitor response to treatment closely and adjust as needed
	5-11	Involve child in developing a written asthma action plan
		Promote physical activity
		Monitor for disease progression and altered lung growth
	≥12	Involve youth in developing written asthma action plan
		Promote physical activity

Modified from National Asthma Education and Prevention Program, 2007.

The presence of asthma during the adolescent years presents specific challenges to the clinician. Included among these are behavioral or attitudinal issues related to the lack of acceptance of an illness, symptom denial, carelessness about inhalational exposures, adherence problems, over-exertion without adequate pretreatment, and relational problems with family and health care providers (de Benedictis & Bush, 2007). Special techniques including peer education, networking, and careful attention to relationship building are effective strategies to maintaining control during this period of rapid changes.

Summary 

Comprehensive asthma management involves patient education, including education about inhalation techniques, environmental control strategies, appropriate pharmacotherapy, and an effective plan for self-monitoring by the patient.