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0–4 Years of Age: The Expert Panel recommends that essential elements in the evaluation include the history, symptoms, physical examination, and assessment of quality of life, as discussed in "Component 1: Measures of Asthma Assessment and Monitoring." A therapeutic trial with medications listed in will also aid in the diagnosis. Several studies show that as many as 50–80 percent of children who have asthma develop symptoms before their fifth birthdays. Diagnosis can be difficult in this age group and has important implications. On the one hand, asthma in early childhood is frequently underdiagnosed (receiving such inappropriate labels as chronic bronchitis, wheezy bronchitis, reactive airway disease (RAD), recurrent pneumonia, gastroesophageal reflux, and recurrent upper respiratory tract infections). Therefore, many infants and young children do not receive adequate therapy. On the other hand, not all wheeze and cough are caused by asthma, and caution is needed to avoid giving infants and young children inappropriate prolonged asthma therapy. Episodic or chronic wheeze, cough, and breathlessness also may be seen in other, less common, conditions, including cystic fibrosis, vascular ring, tracheomalacia, primary immunodeficiency, congenital heart disease, parasitic disease, and foreign-body aspiration.

Diagnosis is complicated by the difficulty in obtaining objective measurements of lung function in this age group. 5–11 Years of Age: The Expert Panel recommends that the diagnosis in children 5 years of age and older should follow the same procedures recommended in "Component 1: Measures of Asthma Assessment and Monitoring."

Although asthma clearly has been demonstrated to be associated with airway inflammation and structural changes in adult patients, the age when these changes begin in asthma has not yet been defined precisely. Elevations in both inflammatory cells and mediators have been demonstrated in bronchoalveolar lavage specimens obtained from preschool children who have recurrent wheezing (). Recently, endobronchial biopsy specimens from infants who have wheezing and documented airflow obstruction that was both reversible and nonreversible following the administration of bronchodilator were compared to four other groups of subjects: infants who had wheezing without airflow obstruction, school-aged children who had difficult-to-control asthma, and both school-aged children and adults who did not have asthma (). In the infants who had wheezing, regardless of bronchodilator reversibility or atopic status, the characteristic histopathologic features of thickening of the laminar reticularis and eosinophil inflammation were absent. Taken together, these data indicate that the airway inflammatory responses and structural changes that are characteristic of asthma develop during the preschool years and may follow, and not precede, the physiologic changes associated with asthma.

Among children 5 years of age and younger, the most common cause of asthma symptoms is viral respiratory infection. At present, the relative contributions of airway inflammation, bronchial smooth muscle abnormalities, or other structural factors in producing wheeze with acute viral upper respiratory infections are unknown. Two general patterns of illness appear in infants and children who have wheezing with acute viral upper respiratory infections: a remission of symptoms in the preschool years and persistence of asthma throughout childhood. No absolute markers are available to predict the prognosis of an individual child; however, an asthma predictive index has been developed that identifies risk factors for developing persistent asthma. Children under 3 years of age who had four or more episodes of wheezing in the past year that lasted more than 1 day and affected sleep are significantly likely to have persistent asthma after the age of 5 years if they also have either (1) one of the following: parental history of asthma, a physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens, OR (2) two of the following: evidence of sensitization to foods, ≥4 percent peripheral blood eosinophilia, or wheezing apart from colds (See section 2, "Definition and Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma.").

The Expert Panel concludes that evidence to date does not support the previously hypothesized contention that early intervention with an ICS, either continuously (; ) or intermittently (), may alter the underlying severity or progression of the disease. ICSs should be used to control asthma symptoms and to improve the child's quality of life, but their use should not be initiated or prolonged for the purpose of changing the natural history of the disease (i.e., the underlying severity or progression of asthma) (Evidence A). Although a preliminary, retrospective study suggested that appropriate control of childhood asthma may prevent more serious asthma or irreversible obstruction in later years (), these observations were not verified in a more recent long-term randomized controlled trial (RCT) in children 5–12 years of age () (Evidence A). The best available evidence does not support the assumption that children 5–12 years of age who have mild or moderate persistent asthma, on average, have a progressive decline in lung function. A followup analysis from the Childhood Asthma Management Program (CAMP) study indicates, however, that a subset of participants in both treatment and placebo groups experienced progressive reductions in lung growth compared to predicted measures (). Further studies are needed to assess this risk fully.

Observational prospective data from other large groups of children suggest that the timing of the CAMP intervention was too late, as most loss of lung function in early childhood asthma appears to occur during the first 3–5 years of life (; ). A recent study enrolled children 2–3 years of age who were at high risk of developing persistent asthma and compared ICS therapy to placebo. The study demonstrated that this intervention clearly reduced symptom burden and the frequency of exacerbations while the ICS was administered daily for 2 years, but this therapy did not prevent the reappearance of persistent symptoms in the year of followup after discontinuing therapy ().

The Expert Panel recommends that the following measures be monitored over the course of children's followup visits, especially in those children who have moderate or severe persistent asthma (require Step 3 care or higher), to assess both impairment and risk domains for the development of progressive disease: course of medications, including increasing use of SABAs and escalation of long-term control medications; episodes of severe exacerbations requiring systemic corticosteroids, urgent care visits, or hospitalizations; pulmonary function measures including prebronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC) and FEV 1 (percent predicted) and postbronchodilator FEV 1 (percent predicted) (Evidence B). If these measures so indicate, therapy should be stepped up to ensure adequate asthma control. See for a sample patient record for monitoring asthma progression in children. Although there is no indication that treatment alters the progression of asthma severity in children, asthma is highly variable over time (see sections on "Natural History" and "Pathophysiology"), and treatment may have to be adjusted accordingly.

The Expert Panel recommends that the goal of asthma therapy is to maintain long-term control of asthma with the least amount of medication and hence minimal risk for adverse effects. Control of asthma may be viewed in the context of two domains—impairment and risk—and within these domains, defined as follows (Evidence A). ▪ Reducing impairment — Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness in the daytime, in the night, or after exertion) — Require infrequent use (≤2 days a week) of SABA for quick relief of symptoms (not including prevention of EIB) — Maintain (near) normal pulmonary function — Maintain normal activity levels (including exercise and other physical activity and attendance at work or school) — Meet patients' and families' expectations of and satisfaction with asthma care ▪ Reducing risk — Prevent recurrent exacerbations of asthma and minimize the need for ED visits or hospitalizations — Prevent progressive loss of lung function; for children, prevent reduced lung growth — Provide optimal pharmacotherapy with minimal or no adverse effects The Expert Panel recommends that the stepwise approach to therapy, in which the dose and number of medications and frequency of administration are increased as necessary (Evidence B, extrapolated from studies in older children and adults) and decreased when possible (Evidence D), is used to achieve and maintain this control.

The distinction between assessing impairment and risk to make treatment decisions draws attention to the multifaceted nature of asthma and the need to consider all manifestations of the disease. Assessing both domains emphasizes the need to consider separately asthma's effects on quality of life and functional capacity on an ongoing basis (i.e., at present) and the risks asthma presents for adverse events in the future, such as exacerbations or progressive reduction in lung growth. These domains may respond differentially to treatment. For example, a large study of children who had asthma revealed that 30 percent of the low-dose ICS treatment group, whose levels of impairment (symptoms, SABA use, lung function) improved, remained at risk of exacerbations requiring oral systemic corticosteroids ().

The steps of care for managing asthma to achieve and maintain this control are presented in and . Deciding which step of care is appropriate for a patient depends on whether long-term control therapy is being initiated for the first time or whether therapy is being adjusted (i.e., stepped up to regain control or stepped down, for patients who have maintained control for a sufficient length of time, to determine the minimal amount of medication required to maintain control and/or reduce the risk of side effects). The classification of asthma severity, which considers the severity of both impairment and risk domains, provides a guide for initiating therapy for patients who are not currently taking long-term control medications. (See and for children 0–4 years of age and 5–11 years of age, respectively.) Once therapy is selected, or if the patient is already taking long-term control medication, the patient's response to therapy will guide decisions about adjusting therapy based on the level of control achieved in both the impairment and risk domains ( for children 0–4 years of age and for children 5–11 years of age).

0–4 Years of Age: Initiating Long-Term Control Therapy. The Expert Panel concludes that initiating daily long-term control therapy: ▪ Is recommended for reducing impairment and risk of exacerbations in infants and young children who had four 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: either (1) one of the following: parental history of asthma, a physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens OR (2) two of the following: evidence of sensitization to foods, ≥4 percent peripheral blood eosinophilia, or wheezing apart from colds (Evidence A). ▪ Should be considered for reducing impairment in infants and young children who consistently require symptomatic treatment more than 2 days per week for a period of more than 4 weeks (Evidence D). ▪ Should be considered for reducing risk in infants and young children who have a second asthma exacerbation requiring systemic corticosteroids within 6 months (Evidence D). Recognition of these children and treatment with daily low-dose ICS therapy can significantly reduce overall symptom burden and the frequency of exacerbations, even though such treatment will not alter the underlying severity of asthma in later childhood ().

▪ May be considered for use only during periods of previously documented risk for a child (Evidence D). If daily long-term control therapy is discontinued after the season of increased risk, written asthma action plans indicating specific signs of worsening asthma and actions to take should be reviewed with the caregivers, and a clinic contact should be scheduled 2–6 weeks after discontinuation of therapy to ascertain whether adequate control is maintained satisfactorily (Evidence D). Because of seasonal variations in exacerbations among children, such as during the seasons of increased upper respiratory infections (), it is possible, although not yet evaluated systematically, that some of the children described above may require daily therapy only during previously documented periods of increased risk of exacerbations for that individual.

5–11 Years of Age: Initiating Long-Term Control Therapy. The Expert Panel recommends daily long-term control therapy for children who have persistent asthma (Evidence A). In deciding when to initiate daily long-term control therapy, the clinician must weigh the possible long-term effects of inadequately controlled asthma versus the possible adverse effects of medications given over prolonged periods. Long-term studies in children 5–12 years of age at the time of enrollment conclude that ICSs improve health outcomes for children who have mild or moderate persistent asthma, and that the potential albeit small risk of delayed growth from the use of ICSs is well balanced by their effectiveness (Evidence A) (). Furthermore, available long-term data indicate that most children treated with recommended doses of ICSs achieve their predicted adult heights (). It is noted that the long-term prospective studies on growth involved budesonide, and retrospective analyses included studies on beclomethasone, but the results have been generalized to include all ICS preparations. Although different preparations and delivery devices may have a systemic effect at different doses, all short-term studies on numerous preparations suggest that the effect of ICSs on growth is a drug-class effect.

The Expert Panel recommends that, if a child is already taking long-term control medication, treatment decisions are based on the level of asthma control that has been achieved: therapy should be stepped up if necessary to achieve control (Evidence B—extrapolated from studies in youths and adults) (See and .). After identifying the patient's treatment step, based on the patient's or parents' report of what medications the patient is currently taking, classify the level of control by measuring impairment based on symptoms, SABA use, and lung function (in children 5–11 years of age) and risk based on previous exacerbations and potential side effects. In general, the assessment leads to the following sequence of actions. ▪ Address the impairment domain. Consider factors related to the different age groups. — 0–4 years of age: The level of impairment generally is judged on the most severe symptom. The risk domain is usually more strongly associated with asthma morbidity than the impairment domain, because children are often symptom free between exacerbations.

— 5–11 years of age: The level of impairment generally is judged on the most severe measure among symptom report, asthma control score (using validated tools if available), and pulmonary function measures. For patients at step 3 or higher care, if office spirometry is feasible and suggests poorer control than does the assessment of impairment based on other measures, consider fixed airway obstruction as the explanation and reassess the other measures of impairment. If fixed airway obstruction does not appear to be the explanation, consider a step up in therapy, because low FEV 1 is a predictor of risk for exacerbations in children. (See "Component 1: Measures of Asthma Assessment and Monitoring.") — The Expert Panel recommends the following actions if control of the impairment domain is not achieved and maintained at any step of care: ♦ Patient adherence and technique in using medications correctly should be assessed and addressed as appropriate (Evidence C). See "Component 2: Education for a Partnership in Asthma Care" for discussion on assessing adherence. Key questions to ask the child and parent include: Which medicines is your child currently taking? How often? Who is responsible for administering the child's medicine? Please show me how the child takes the medicine. How many times a week does the child miss taking the medication?

What problems have you/your child had taking the medicine (cost, time, lack of perceived need)? What concerns do you have about your asthma medicines? ♦ Other factors that diminish control of asthma impairment should be addressed as possible reasons for poor response to therapy and targets for intervention (Evidence C). These factors include the presence of a coexisting condition (e.g., sinusitis), a new or increased exposure to allergens or irritants, or psychosocial problems. In some cases, alternative diagnoses, such as vocal cord dysfunction (VCD), should be considered. ♦ If patient adherence, inhaler technique, and environmental control measures are adequate, and asthma is not well controlled, a step up in treatment may be needed (Evidence B—extrapolated). For patients who have asthma that is not well controlled, in general step up one treatment step. For patients who have very poor asthma control, consider increasing treatment by two steps, a course of oral corticosteroids, or both (Evidence D).

▪ Address the risk domain. — The Expert Panel recommends the following actions if control of the risk of exacerbations is not achieved or maintained (Evidence D): ♦ 0–4 years of age: If there is a history of one or more exacerbations, review adherence to medications and control of environmental exposures, review the patient's written asthma action plan to confirm that it includes oral prednisone for patients who have histories of severe exacerbations, and consider stepping up therapy to the next level (Evidence D). ♦ 5–11 years of age: If the history of exacerbations suggests poorer control than does the assessment of impairment, the following actions are recommended: reassess the impairment domain, review adherence to medications and control of environmental exposures, review the patient's written asthma action plan to confirm that it includes oral prednisone for patients who have a history of severe exacerbations, and consider a step up in therapy, especially for children who have reduced lung function (, ). — Address the risk domain with regard to side effects. The Expert Panel recommends consideration of alternative and/or adjunctive therapies within the step of care the patient is receiving if the patient experiences troublesome or debilitating side effects. In addition, confirm efforts to control environmental exposures (Evidence D).

▪ Consider referral to an asthma specialist. The Expert Panel recommends referral to an asthma specialist for consultation or comanagement of the patient if (Evidence D): — There are difficulties achieving or maintaining control of asthma. — A child 0–4 years of age requires step 3 care or higher (step 4 care or higher for children 5–11 years of age) to achieve and maintain control or if additional education is indicated to improve the patients' management skills or adherence. Referral may be considered if a child 0–4 years of age requires step 2 care or a child 5–11 years of age requires step 3 care. — The patient has had an exacerbation requiring hospitalization. — Immunotherapy or other immunomodulators are considered, or additional tests are indicated, to determine the role of allergy.

The Expert Panel recommends that regular followup contact is essential (Evidence B). Contact at 1- to 6-month intervals is recommended, depending on the level of control; consider a 3-month interval if a step down in therapy is anticipated (Evidence D). Clinicians need to assess whether control of asthma has been maintained and whether a step up or down in therapy is appropriate. Clinicians also need to monitor and review the written asthma action plan, which includes the medications, and the patient's self-management behaviors for daily management and handling worsening asthma (e.g., inhaler and peak flow monitoring techniques, actions to control factors that aggravate his or her asthma) (See "Component 2: Education for a Partnership in Asthma Care," figures 3–11 and 3–15 , respectively.).

The Expert Panel recommends that once well-controlled asthma is achieved and maintained for at least 3 months, a reduction in pharmacologic therapy—a step down—can be considered helpful to identify the minimum therapy for maintaining well-controlled asthma (Evidence D). The opinion of the Expert Panel is that the dose of ICS may be reduced about 25–50 percent every 3 months to the lowest dose possible required to maintain control (Evidence D). Reduction in therapy should be gradual, because asthma control can deteriorate at a highly variable rate and intensity. The patient should be instructed to contact the clinician if and when asthma worsens. Guidelines for the rate of reduction and intervals for evaluation have not been validated, and clinical judgment of the individual patient's response to therapy is important. Patients may relapse when the ICS is completely discontinued (; ; ); however, giving daily therapy only during periods of documented risk for a child (e.g., seasons of viral respiratory infections) may be considered (Evidence D).

The following recommendations for different steps of pharmacologic therapy to gain and maintain asthma control are intended to be general guidelines for making therapeutic decisions. They are not intended to be prescriptions for individual treatment. Specific therapy should be tailored to the needs and circumstances of individual patients. Pharmacologic therapy must be accompanied at every step by measures to control those environmental factors and comorbid conditions that can impede asthma control and by patient education (See section 3, "Component 2: Education for a Partnership in Asthma Care" and "Component 3: Control of Environmental Factors and Comorbid Conditions That Affect Asthma.").

The Expert Panel recommends that treatment of young children is often in the form of a therapeutic trial; therefore, it is essential to monitor the child's response to therapy. If there is no clear response within 4–6 weeks, the therapy should be discontinued and alternative therapies or alternative diagnoses considered (Evidence D). If there is a clear and positive response for at least 3 months, a step down in therapy should be undertaken to the lowest possible doses of medication required to maintain asthma control (Evidence D). Treatment for young children, especially infants, has not been studied adequately. Recommendations are based on expert opinion, limited data, and extrapolations from studies in older children and adults (; ).

The following long-term control medications are approved by the FDA for young children: ▪ ICS budesonide nebulizer solution (approved for children 1–8 years of age) ▪ ICS fluticasone DPI (approved for children 4 years of age and older) ▪ Long-acting inhaled beta 2 -agonist (LABA) salmeterol DPI and combination product (salmeterol + fluticasone) DPI (approved for children 4 years of age and older) ▪ LTRA montelukast, based on safety data rather than efficacy data, in a 4 mg chewable tablet (approved for children 2–6 years of age) and in 4 mg granules (approved down to 1 year of age) ▪ Cromolyn nebulizer (approved for children ≥2 years of age)

Several delivery devices are available for infants and young children. The dose received may vary considerably among devices and age groups. (See "Component 4: Medications," figure 3–24 , for a summary of therapeutic issues regarding aerosol delivery devices.) In general, children less than 4 years of age will have less difficulty with an MDI plus valved holding chamber (VHC) with a face mask or a nebulizer with a face mask. The child's caregivers must be instructed in the proper use of nebulizers, appropriate size of face masks, and how to use VHCs with and without face masks for medication delivery to be effective and efficient. Using the "blow by" technique, holding the mask or open tube near the infant's nose and mouth, is not appropriate. For younger children, nebulizer therapy is an option for administering budesonide and cromolyn. Children between 3 and 5 years old may begin therapy with an MDI and spacer or VHC alone, but if the desired therapeutic effects are not achieved, they may require a nebulizer or an MDI plus spacer or VHC and face mask.

presents treatment options within the stepwise approach to therapy. Selection of the step of care for a patient depends on whether long-term control therapy is being initiated for the first time or therapy is being adjusted. Classifying severity in patients not currently taking long-term control medication will guide decisions for initiating therapy (See .). Assessing the level of asthma control in patients taking long-term control medication will guide decisions for adjusting therapy (See .). , , and list usual dosages of asthma medications.

The Expert Panel recommends the following treatment for intermittent asthma: ▪ SABA taken as needed to treat symptoms is usually sufficient therapy for intermittent asthma (). If effective in relieving symptoms, intermittent use of SABA can continue on an as-needed basis. Increasing use, however, may indicate more severe or inadequately controlled asthma and thus a need to step up therapy. ▪ The Expert Panel recommends the following actions for managing exacerbations due to viral respiratory infections, which are especially common in children (). These exacerbations may be intermittent yet severe. — If the symptoms are mild, SABA (every 4–6 hours for 24 hours, longer with a physician consult) may be sufficient to control symptoms and improve lung function. If this therapy needs to be repeated more frequently than every 6 weeks, consider a step up in long-term care. — If the viral respiratory infection provokes a moderate-to-severe exacerbation, a short course of oral systemic corticosteroids should be considered (1 mg/kg/day prednisone or equivalent for 3–10 days). — For those patients who have a history of severe exacerbations with viral respiratory infections, consider initiating oral systemic corticosteroids at the first sign of the infection.

▪ The Expert Panel recommends that a detailed written asthma action plan be developed for those patients who have intermittent asthma and a history of severe exacerbations (Evidence B) (See "Component 2: Education for a Partnership in Asthma Care."). Intermittent asthma—infrequent exacerbations separated by periods of no symptoms and normal pulmonary function—is often mild. Some patients, however, who have intermittent asthma experience sudden, severe, and life-threatening exacerbations. It is essential to treat these exacerbations accordingly. The patient's written asthma action plan should include indicators of worsening asthma (specific symptoms) as well as specific recommendations for using SABAs, early administering of oral systemic corticosteroids, and seeking medical care. Furthermore, periodic monitoring (See "Component 1: Measures of Asthma Assessment and Monitoring.") of the patient is appropriate to evaluate whether the patient's asthma is indeed intermittent. The occurrence of two or more severe exacerbations within 6 months without symptoms in between them is an example of a child's having minimal or intermittent impairment, but a persistent, high risk of exacerbation. In the opinion of the Expert Panel, this child should be considered to have persistent asthma (See .). Such children can benefit from daily long-term control therapy (, ).

The Expert Panel recommends the following therapy for persistent asthma: ▪ Daily long-term control medication at step 2 or above is recommended for children who had four or more wheezing episodes in 1 year and risk factors for persistent asthma (Evidence A). Consider daily therapy for children who have a second exacerbation requiring oral systemic corticosteroids in 6 months or children who consistently require symptomatic treatment >2 days a week for > 4 weeks (Evidence D). ▪ Quick-relief medication must be available. SABA should be taken as needed to relieve symptoms (). The intensity of treatment will depend on the severity of the exacerbation (See section 5, "Managing Exacerbations of Asthma."). Use of SABA more than 2 days a week for symptom control (not prevention of EIB), or increasing use, indicates the need for additional long-term control therapy. ▪ To gain more rapid control of asthma, a course of oral systemic corticosteroids may be necessary for the patient who has an exacerbation at the time long-term control therapy is started or in patients who have moderate or severe asthma with frequent interference with sleep or normal activity ().

▪ Close monitoring of the child's response to therapy is recommended (); treatment recommendations are based on limited data in this age group, and thus treatment is often in the form of a therapeutic trial. If no clear response occurs within 4–6 weeks and medication technique and adherence are satisfactory, the treatment should be discontinued and a change in therapy or alternative diagnoses should be considered. If there is a clear and positive response for at least 3 months, a step down in therapy should be undertaken to the lowest possible doses of medication required to maintain asthma control (Evidence D). ▪ Giving daily therapy only during specific periods of previously documented risk for a child may be considered (Evidence D). Although this approach is not yet evaluated, it is possible that children who have specifically defined periods of increased risk for symptoms and exacerbations (e.g., during the seasons in which viral respiratory infections are common) may require daily long-term control therapy only during this historically documented period of risk. If long-term control therapy is discontinued, then written action plans for recognizing and handling signs of worsening asthma should be reviewed with the caregivers, and followup appointments 2–6 weeks later should be conducted to ensure that asthma control is maintained.

▪ Preferred treatment for step 2 care is daily ICS at a low dose (Evidence A based on studies of individual drug efficacy in this age group; comparator trials are not available). ▪ Alternative, but not preferred, treatments include (listed in alphabetical order) cromolyn (Evidence B—extrapolated from studies in older children) and montelukast (Evidence A). If an alternative treatment is selected and adequate asthma control is not achieved and maintained in 4–6 weeks, then discontinue that treatment and use the preferred medication before stepping up therapy. ▪ Theophylline is not recommended as alternative treatment () because of its erratic metabolism during viral infections and febrile illness in children less than 5 years of age and the need to closely monitor and control serum concentrations.