Michael H. Mellon, MD

Asthma is the most prevalent chronic disease in children.

 In the United States, asthma affects approximately 1.4 million children younger than 5 years

 and causes frequent activity limitations

 Unfortunately, a substantial number of children in this age-group have suboptimal asthma control, demonstrated by the higher rates of emergency department (ED) visits and hospitalizations in preschool-aged children than in older children.

In the United States, mothers of children aged 1 to 5 years with persistent weekly asthma-like symptoms (ie, cough, wheeze, breathlessness) have reported that 22% of the children had an ED visit and 11% had been hospitalized within the past 6 months.

 In 2007, approximately 851,000 children younger than 5 years had an asthma attack in the past year, which represents 61% of the children with asthma in this agegroup. 

 These findings suggest that the treatment goals of asthma are not currently being met in preschoolaged children.

The goal of asthma therapy, detailed in the 2007 National Heart, Lung, and Blood Institute and National Asthma Education and Prevention Program's Expert Panel Report 3 (EPR-3),

 is to control asthma by reducing both the impairment and risk domains. Impairment addresses the daily impact of asthma on traditional clinical indices and quality of life. Risk refers to the negative consequences of the disease or pharmacotherapy.

Impairment is reduced by preventing chronic and troublesome symptoms, minimizing short-acting β

-adrenergic agonist (SABA) use to 2 or fewer days a week, maintaining near-normal pulmonary function, maintaining normal activity levels, and meeting patients' and families' expectation of and satisfaction with asthma care. Risk is reduced by preventing recurrent exacerbations of asthma and minimizing the need for ED visits or hospitalizations, preventing reduced lung growth, and providing optimal pharmacotherapy with minimal or no adverse events. Both domains may respond differently to treatment. Treatments are selected and adjusted on the basis of the patient's level of asthma control, which is determined by assessments made by the health care provider (HCP) and caregiver.

This review provides an overview on how to assess and achieve asthma control in children younger than 5 years and presents answers based on current asthma guidelines to the following questions that arise during clinic visits:

What are the current recommendations for initial controller or step-up therapy?

What is the preferred therapy when initiating daily controller medications?

Are the child's respiratory symptoms controlled?

What is the Test for Respiratory and Asthma Control in Kids (TRACK

What are the next steps for a child with uncontrolled respiratory symptoms?

How can caregivers help children achieve asthma control?


 When a child presents with frequent or chronic respiratory symptoms (

), establishing an accurate diagnosis of asthma is the first step to achieving disease control. As many as 50% to 80% of children who have asthma have symptoms before 5 years of age.

However, there are several diagnostic challenges in this age-group of children with asthmalike symptoms. First, asthma is a heterogeneous disease with variable presentation in the frequency, type, and severity of symptoms.

 Second, spirometry is recommended for the diagnosis of asthma in children older than 5 years and adults, but is not generally feasible in preschool-aged children.

 Finally, asthma symptoms are common in childhood respiratory ailments, including recurrent URTIs.

. Matt is a 3-year-old boy who presents to the office with his mother because she completed TRACK online (

), and Matt received a TRACK score of 60. On the basis of what she read, a TRACK score lower than 80 means that Matt's breathing problems may not be under control, whereas a score of 80 or higher would suggest that his symptoms were under control. Therefore, she is worried about her child's breathing.

. The mother states that Matt was recently seen at an after-hours clinic because he has been coughing more, especially at night, which results in his awakening. He usually is sick after an upper respiratory tract infection (URTI), which almost always “goes to his chest,” she said. After these episodes, he seems to get out of breath when he “runs around too much” at the playground. However, between these episodes, he basically is in good health.

. A review of Matt's chart shows that he was first seen in the office for an acute respiratory infection with wheezing at 7 months of age. Over the past year, he has had 4 sick visits for respiratory complaints with diagnoses of recurrent pneumonia and reactive airway disease. He recently had an urgent care visit and was treated with nebulized albuterol and oral prednisolone for 4 days, which appeared to resolve the episode.

. Matt has no known allergies. He currently uses a jet nebulizer and compressor to deliver albuterol treatments as needed. Matt's mother reports that Matt uses his albuterol medication about once or twice a week, especially during the winter months.

. Matt's mother notes that she herself has had asthma since childhood and that Matt's father suffers from “sinus” allergies in the fall.

. Remarkable findings upon PE include increased nasal secretions and some mucosal swelling. The lungs are clear. 

 In preschool-aged children, the diagnosis of asthma is based largely on clinical judgment and the assessment of symptoms and PE.

 Components of the diagnostic evaluation for this age-group include a detailed medical history; an assessment of the frequency, type, and pattern of symptoms (

A patient's medical history allows the HCP to evaluate factors that indicate a likely diagnosis of asthma. Key indicators suggestive of asthma are wheezing, recurrent respiratory symptoms, a history of nighttime cough, symptoms that occur or worsen in the presence of a trigger, and responsiveness to a bronchodilator. Although no one indicator is diagnostic, the presence of multiple indicators increases the probability of an asthma diagnosis. Preschool-aged children with asthma often present with recurrent wheezing associated with a viral infection or complaints of recurrent pneumonia or bronchitis.

Some of the physical findings suggestive of asthma include hyperexpansion of the thorax, wheezing on chest auscultation, increased nasal secretions, mucosal swelling, atopic dermatitis, or other allergic manifestations. 

 During the evaluation, HCPs should also consider possible alternative diagnoses and perform appropriate tests, if indicated (

). Some possible alternative diagnoses in infants and children include allergic rhinitis, cystic fibrosis, and  gastroesophageal reflux disease. Chest radiographs, pulmonary function tests (in older children), and allergy testing are some of the additional studies that aid in the evaluation of children with recurring symptoms suggestive of asthma.

. For a child whose medical history, family history, and PE are suggestive of asthma (

 a therapeutic trial of SABA therapy (eg, albuterol), antiinflammatory therapy (eg, inhaled corticosteroid [ICS]), or both clinically helps one decide whether a child has asthma.

 Observation of symptom improvement after administration of albuterol while the child is in the office or at home during wheezing episodes also assists in establishing the diagnosis. If a SABA alone, administered by nebulizer or metered- dose inhaler (MDI) every 4 to 6 hours, does not control symptoms, the HCP should initiate a short course of an oral corticosteroid (OCS) and observe the effect of this combination on the wheezing. The role of OCSs in the future management of the child's wheezing episodes then should be decided and included in the asthma management plan.

For children with persistent asthma, as defined by the impairment or risk domains of the EPR-3, a trial of an ICS is indicated.

 Response should be monitored carefully for reduction in impairment symptoms, a reduction in the frequency and severity of exacerbations, or both. If there is no clear response to the therapeutic trial within 4 to 6 weeks, adherence to the treatment recommendation and device technique should be evaluated.

 Alternative diagnoses or adjustment of therapies should be considered if both adherence and technique are satisfactory. Marked clinical improvement during treatment with SABAs and ICSs and a return of symptoms when treatment is stopped support a diagnosis of asthma.


 The natural history of asthma in children younger than 5 years varies.

 Two general patterns of illness include the remission of symptoms during preschool years and the persistence of symptoms throughout childhood. The Tucson Children's Respiratory Study followed children from birth and found that of the group who had wheezing before age 3 years, 60% would report no wheezing episodes at 6 years of age.

 These children, who were called transient infant wheezers,

 did not have a family or personal history of atopy, had symptoms only during the first 3 years of life,

 and had diminished lung function from birth.

The remaining 40% of the children who continued to wheeze into the school-aged years consisted of persistent nonatopic wheezers and, mostly, persistent atopic wheezers.

 Children with nonatopic wheezing did not have a family or personal history of atopy, but unlike the transient wheezers, their symptoms continued beyond 6 years of age but diminished in preadolescence.

 Children with the persistent atopic wheezing phenotype had atopy and a family history of asthma. These children continued to wheeze throughout the schoolaged years, often without associated viral infections, and represented the usual phenotype of childhood asthma in the 5- to 11-year age-group.

The persistence of asthma in a given child cannot be definitively predicted.

 However, the Asthma Predictive Index (API) was developed to allow one to assess the likelihood that a child with frequent wheezing in the first 3 years of life will experience persistent asthma

 so that the child can be monitored and appropriate treatment started. Children with a positive API have a parental history of asthma or physician-diagnosed atopic dermatitis or 2 of the following: physician-diagnosed allergic rhinitis, wheezing apart from colds, or blood eosinophilia of 4% or higher.

A retrospective analysis of 1246 patients from the Tucson Children's Respiratory Study showed that the API had a specificity of 97.4%, which is the likelihood that the schoolchildren without asthma from the original cohort would, when looking back at their histories, have had a negative API in their infancy.

 The study also demonstrated a positive predictive value of 76.6%, which is the probability that infants with a positive API would have had active asthma from ages 6 to 13 years, and a negative predictive value of 68.3%, which is the probability that infants with a negative API would not have experienced asthma at school age. In other words, the API was unable to correctly predict approximately 23% of persistent wheezers and 30% of transient wheezers. 

 Nonetheless, the API is currently the only available guide to assist in predicting which infants with frequent wheezing are likely to develop persistent asthma during their school years.

 Additional ongoing research is focusing on furthering phenotype- based asthma classification and individualizing treatments.


 Once a diagnosis is made, additional information should be gathered to classify asthma severity, which is the intrinsic intensity of the disease.

 The initial classification of asthma severity is made before the child is taking long-term control medication. Severity classification is based on the domains of impairment and risk (

). Children are classified as having intermittent, mild persistent, moderate persistent, or severe persistent asthma on the basis of the assessments of both domains.

The assessment of impairment in children younger than 5 years is based on the frequency of symptoms, nighttime awakenings, and reliever use of SABAs, as well as the child's ability to engage in age-appropriate activities. The level of impairment is based on the most severe category in which any feature occurs. Recurrence of symptoms or SABA use more than 2 times a week indicates persistent asthma. Nighttime awakenings and even minor limitations in activities are also indicators of persistent disease in this age-group. Children with minimal or no impairment may have persistent disease depending on their risk domain. Therefore, it is important for HCPs who diagnose intermittent asthma in a child to periodically revaluate the child for frequency and severity of exacerbations.

The assessment of risk is based on the frequency of exacerbations.

 Generally, young children experience about 4 to 6 “colds” per year, particularly in the fall and winter months.

 In preschool- and school-aged children, hospitalizations and ED visits for asthma begin to increase every September and peak in the early fall,

 which is associated with an increase in viral respiratory tract infections. 

 For very young children, however, data to link exact frequencies of exacerbations with different levels of asthma severity are inadequate. A preschooler may have exacerbations in the absence of daily symptoms between attacks. A child who has only 1 exacerbation a year may be classified as having intermittent asthma. What is important is that children with intermittent asthma can have severe asthma exacerbations. According to the guidelines, a child with 2 or more exacerbations within 6 months requiring treatment with an OCS, even without symptoms in between, is considered to have persistent asthma. However, this recommendation is based on panel consensus judgment and clinical experience because the clinical literature addressing the subject was insufficient (Evidence level D).

WHAT ARE THE CURRENT RECOMMENDATIONS FOR INITIAL CONTROLLER OR STEP-UP THERAPY?


 Failure of over-the-counter medications to relieve a child's recurring respiratory symptoms is often the impetus for a visit to the pediatrician's office.

 Before initiating therapy, it is important for the HCP to determine what medications the child is currently taking and to establish the step of therapy the child is on, based on the 6-step treatment chart of the guidelines (

). It is also important to assess the need for these medications and whether continued treatment would be beneficial. The child already may be using an inhaled SABA as needed for quick relief of symptoms.

 The HCP should determine the frequency of inhaled SABA use to assess the need to step up therapy.


 While the original API was developed to assess the likelihood that a child would experience persistent asthma, a modified API (mAPI) was used as an inclusion criterion in the Prevention of Early Asthma in Kids (PEAK) study to examine whether long-term ICS treatment would prevent disease progression in 285 children aged 2 to 3 years at high risk for persistent asthma.

The original API was modified because allergic rhinitis is difficult to diagnose in young children and previously conducted studies have shown that early allergic sensitization to milk or eggs are predictors for developing persistent asthma. 

 Differences between the mAPI and the original API are described in 

 A positive mAPI requires the child to have at least 1 of 3 major risk factors or 2 of 3 minor risk factors. The PEAK study showed that children with the phenotype of a positive mAPI who received fluticasone propionate 88 µg twice daily had a significantly greater proportion of episode-free days (

 = .006) and reduction in exacerbations requiring systemic corticosteroids (

 < .001) compared with children who received placebo over the 2-year treatment period.

 The children were followed for 1 year after treatment was discontinued. Findings from the treatment-free year did not support a disease-altering effect after ICS discontinuation.

Nevertheless, the outcome of the PEAK trial led to the guideline recommendation that a long-term daily controller (ICS) be initiated for reducing risk and impairment in children younger than 5 years who have had 4 or more episodes of wheezing in the past year that lasted more than 1 day and affected sleep and who have risk factors for developing persistent asthma based on the mAPI.

 Many children have intermittent episodes of viral-induced wheezing, and the PEAK trial helps define which of those children with recurrent episodes will benefit from maintenance therapy. A daily long-term controller also should be considered for children with impairment (eg, persistent symptoms) or risk as outlined in 

Moreover, the guidelines recommend a stepwise treatment approach to maintain long-term asthma control (

 Daily controller therapy is recommended for persistent disease. An ICS is the preferred step 2 controller. A step up in therapy is warranted if asthma control is inadequate and a step down in therapy is recommended to achieve control with the minimal necessary amount of medication. A step down in therapy, with an ICS dose reduction of 25% to 50%, should be considered whenever the child's asthma has been well controlled for 3 or more months.

WHAT IS THE PREFERRED THERAPY WHEN INITIATING DAILY CONTROLLER MEDICATIONS?

. A low-dose daily ICS is the preferred therapy when initiating daily controller treatment.

 Many clinical trials with ICSs have enrolled patients 12 years or older. The generalizability of these results to younger children has not been clearly established. However, a recent meta-analysis of 29 studies in infants and preschoolers aged 1 month to 5 years who received an ICS showed that in 2805 children from 16 studies, those who received an ICS had significantly fewer wheezing/ asthma exacerbations (18.0%) than those who received placebo (32.1%; relative risk: 0.59; 95% confidence interval: 0.52 - 0.67; 

 Moreover, children on an ICS used significantly less albuterol and had significantly greater mean improvements from baseline in symptoms score, forced expiratory volume in 1 second, and peak expiratory flow (

Articles

Asthma is the most prevalent chronic disease in children. In the United States, asthma affects approximately 1.4 million children younger than 5 years and causes frequent activity limitations and hospitalizations.

Michael H. Mellon, MD

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A Guide to Monitoring and AchievingAsthma Control in ChildrenYounger Than 5 Years