Predicting Who is Likely to Develop Persistent Asthma

Recurrent wheezing in infants and young children comprises a heterogeneous group of conditions with different risk factors and prognoses. Viral infections (respiratory syncytial virus, rhinovirus, coronavirus, human metapneumovirus, adenovirus, parainfluenza and adenovirus) are common triggers of wheezing in preschool age children, even in those who will not develop persistent asthma later on. Factors or exposures early in life such as prematurity, fetal nutrition, duration of pregnancy, viral lower respiratory tract infections in the first years of life, cigarette smoke exposure, air pollution, postnatal nutrition, breastfeeding, family size, maternal age, socioeconomic status and allergen exposure have been implicated to varying degrees. Observational studies have also demonstrated an increased risk of asthma attributed to acetaminophen exposure during prenatal periods, infancy, childhood and even adulthood. Genetics, atopy and prematurity appear to be the most important host risk factors in the development of asthma.

Several types of ‘wheezers’ in the young age group based on time of onset and outcome (transient or intermittent vs persistent) have been identified from longitudinal studies. The investigators from the Tucson Children’s Respiratory Group enrolled over 1,000 newborns served by a large health maintenance organization to evaluate factors involved in early-onset wheezing in relationship to persistent wheezing at 6 years of life. About half of the children had at least one episode of wheezing by 6 years of age. Nearly one third of the cohort had at least one episode of wheezing by 3 years of age. Only 40% of children who wheezed early had persistent wheezing at age 6 years. Of the total group, 20% had at least one episode of wheezing associated with a respiratory tract infection during the first 3 years of life but had no wheezing at 6 years (‘transient wheezers’), 14% did not wheeze during the first 3 years of life but had wheezing at 6 years (‘late-onset wheezers’), and 15% had wheezing at age 3 and 6 years (‘persistent wheezers’). The ‘transient wheezers’ were more likely to have diminished airway function and a history of maternal smoking and were less likely to be atopic. The ‘late-onset wheezers’ had a similar percentage of atopic children to ‘persistent wheezers’ and were likely to have mothers with asthma. Hence, there seems to be a similar genetic predisposition for the asthma phenotype characterizing both ‘persistent’ and ‘late-onset wheezers’. Essentially all of the current natural history studies have found that allergic disease and evidence of pro-allergic immune development are significant risk factors for persistent asthma.

An asthma predictive index (API) using a combination of clinical and easily obtainable laboratory data to help identify children age ≤3 years with a history of wheezing at risk of developing persistent asthma was developed from the Tucson cohort. Information on parental asthma diagnosis and prenatal maternal smoking status was obtained at enrollment, while the child’s history of asthma and wheezing and physician-diagnosed allergic rhinitis or eczema, along with measurements of blood eosinophil count, were obtained at the follow-up visits. Two indices were used to classify the children. The stringent index required recurrent wheezing in the first 3 years plus one major (parental history of asthma or physician-diagnosed eczema) or two of three minor (eosinophilia, wheezing without colds, allergic rhinitis) risk factors, whereas the loose index required any episode of wheezing in the first 3 years plus one major or two of three minor risk factors. Children with a positive loose index were 2.6 to 5.5 times more likely to have active asthma sometime during the school years. In contrast, risk of asthma increased to 4.3 to 9.8 times when the stringent criteria were used. In addition, at least 90% of young children with a negative ‘loose’ or ‘stringent’ index will not develop ‘active asthma’ in the school age years.

A modified version of the API (mAPI) incorporates inhalant allergen sensitization as an additional major risk factor and food allergen sensitization as an additional minor risk factor to take into account important findings from other longitudinal natural history asthma studies. In the Berlin Multicentre Allergy Study, additional risk factors for asthma and bronchial hyperreactivity at age 7 years included persistent sensitization to foods (i.e. hen’s egg, cow’s milk, wheat and/or soy) and perennial inhalant allergens (i.e. dust mite, cat), especially in early life. In a prospective, randomized, controlled study of food allergen avoidance in infancy evaluating the development of atopy at age 7 years in a high-risk cohort, egg, milk and peanut allergen sensitization were risk factors for asthma. With these additional considerations, an mAPI has been used in an early intervention study for young children with recurrent wheezing. Henceforth, it has been adapted by the NAEPP EPR3 asthma guidelines as a requirement along with a history of four wheezing episodes per year lasting more than 24 hours upon which initiation of controller therapy should be considered.

These wheezing phenotypes derived from epidemiologic and longitudinal data are more helpful for prognostication and usually have limited clinical utility when a medical provider is faced with a child with recurrent wheezing or chronic cough. Hence, other phenotypes may have greater relevance when management decisions have to be made or clinical trials are undertaken. For example, a symptom-based classification, i.e. episodic (wheeze only in discrete time periods, mostly associated with upper respiratory infection) vs multi-trigger (symptom also occurs with activity, laughing, crying or even at night outside of an acute illness), was proposed by the European Task Force in 2008. However its clinical applicability is limited as children can switch between the two categories at different times, and this classification does not consider the frequency, seasonality and severity of the episodes. A preschool child may have exercise-induced wheeze only when he/she is also having an acute episode or shortly after. During the late fall, winter and early spring in most areas in the northern hemisphere, preschool children who are in regular contact with other children can develop back to back viral respiratory illnesses that can each last up to 2 weeks or even longer. A child with a viral illness requiring a hospital admission is in the same classification as a child whose viral-induced wheezing illness is treated with a bronchodilator alone. Lastly, it is not known if there is a unique immunopathologic difference that can affect treatment between the two phenotypes. Therefore, clinical guidelines suggest starting treatment based on frequency of symptoms, severity of episodes and presence of risk factors.

Confounding Factors

The first practical consideration in approaching the wheezing child is to ensure that an alternative diagnosis is not present. In addition, infants and small children have a greater degree of bronchial hyperresponsiveness (BHR), which may predispose them to wheeze.

The differential diagnosis of wheezing in infants and young children includes conditions such as foreign body aspiration, structural airway anomalies, congenital lobar emphysema, abnormalities of the great vessels (e.g. vascular rings), congenital heart disease, cystic fibrosis, recurrent aspiration, immunodeficiency, infections, ciliary dyskinesia and mediastinal masses. Other clinical features, such as neonatal onset of symptoms, associated failure to thrive, diarrhea or vomiting, focal lung or cardiovascular findings, clubbing, constant wheezing, and hypoxemia outside of an acute illness, suggest an alternative diagnosis and require special investigations. Additional factors in addition to age at onset of symptoms that should be taken into consideration include triggers for the respiratory symptoms and aggravating conditions such as nighttime occurrences, environmental exposure, physical exertion, feeding, positioning and infections. Clearly, making the correct diagnosis is essential because the treatment for these conditions can vary substantially. For example, in children with significant gastroesophageal reflux, improvement in asthma symptoms with concomitant reduction in asthma medication use occurred after a prokinetic agent was instituted. A practical approach that can be considered for a young child in whom asthma is strongly suspected is an empiric trial of asthma controller therapy while other evaluations are still being pursued ( Figure 32-1 ).

Algorithm for suggested management of infants and young children with suspected or established asthma. GERD – gastroesophageal reflux disease.

Diagnostic Tools to Evaluate Asthma in Young Children

Preschool children present some diagnostic challenges inherent to their young age such that a confirmation of a diagnosis can be difficult to make. Infants and young children are too young to reliably perform objective measures of disease activity. Furthermore, they are unable to provide their own history so clinicians must depend on the parents’/caregivers’ report. Werk et al sought to determine the factors primary care pediatricians believe are important in establishing an initial diagnosis of asthma. Questionnaires on asthma diagnosis consisting of 20 factors obtained from the National Heart, Lung, and Blood Institute (NHLBI) National Asthma Education Prevention Program (NAEPP) Expert Panel Report 2 (EPR2) guidelines and an expert local panel of subspecialists were sent to 862 active members of the Massachusetts American Academy of Pediatrics. Over 80% of the respondents rated five factors as necessary or important in establishing the diagnosis of asthma: recurrent wheezing, symptomatic improvement following bronchodilator use, presence of recurrent cough, exclusion of other diagnoses, and suggestive peak expiratory flow rate findings. Of note, 27% of the respondents indicated that a child had to be older than 2 years; 18% indicated that fever must be absent during an exacerbation.

The diagnosis of asthma in young children is based largely on clinical judgment and an assessment of symptoms and physical findings. The following characteristics are suggestive of asthma: wheezing or recurrent or persistent nonproductive cough or difficult breathing that may be worse at night or occurring with exercise, laughing, crying or exposure to tobacco smoke in the absence of a respiratory infection; reduced activity or interest in running or playing compared to other children with easy fatigability during walks; presence of other personal allergic diseases (atopic dermatitis or allergic rhinitis) or family history of asthma in first degree relatives; and response to either therapeutic trial of a corticosteroid or a short-acting bronchodilator as needed. Because lung function measurements in infants and small children are difficult to obtain, a trial of treatment is often a practical way to make a diagnosis of asthma in young children.

At present, for adults and older children, easily performed lung function measures and noninvasive markers of airway inflammation can be used to make the diagnosis of asthma, monitor asthma control or guide therapeutic decisions. The following section will highlight available procedures and techniques with the potential to measure lung function and airway inflammation in the young child.

Management

The goals of asthma management are not different between older children and preschool aged children – to attain good symptom control and allow normal activity levels, reduce exacerbations, optimize lung function and minimize medication side-effects. Available asthma guidelines such as the National Asthma Education Prevention Program Expert Panel Report 3 (NAEPP EPR3) and the Global Initiative for Asthma (GINA) update 2014 report acknowledge the special challenges unique to the management of asthma in preschool children; hence a specific approach and treatment recommendations for preschool children with asthma are presented. Both sets of guidelines emphasize maintenance of asthma control as the goal for asthma management and use of ICS as the preferred therapy for persistent asthma. A comprehensive management is outlined in several components and/or sections and generally includes: establishment of patient/doctor partnership and provision of education to enhance the patient’s/family’s knowledge and skills for self-management (appropriate use of devices and medications); identification and management of risk and precipitating factors and co-morbid conditions that may worsen asthma; adequate assessment and monitoring of disease activity (including symptom monitoring by parent/caregiver); appropriate selection of medications to address the patient’s needs; and management of asthma exacerbations (with provision of a written asthma action plan). The details of each of these elements are discussed in Chapter 29 .

Key differences between the two clinical guidelines are apparent. The approach implemented by the NAEPP EPR3 on starting controller therapy is based on the concept of asthma severity, which is the intrinsic intensity of disease and applicable for patients not receiving controller therapy. The guidelines have a separate set of criteria for various age groups and Table 32-1 summarizes the classification of asthma severity for children 0 to 4 years old. The classification of asthma severity is contingent upon the domains of impairment and risk and the level of severity is based on the most severe impairment or risk component. Impairment includes an assessment of the child’s recent symptom frequency (daytime and nighttime), need for short-acting β ₂ -agonists for quick relief, and ability to engage in normal or desired activities. Risk refers to an evaluation of the child’s likelihood of developing asthma exacerbations. Of note, in the absence of frequent symptoms, ‘persistent’ asthma should be considered and therefore long-term controller therapy initiated for infants or children who have risk factors for asthma (i.e. using the mAPI: any of parental history of asthma, physician-diagnosed atopic dermatitis, or sensitization to aeroallergens OR two of the following: wheezing apart from colds, sensitization to foods, or peripheral eosinophilia) AND four or more episodes of wheezing over the past year that lasted longer than 1 day and affected sleep OR two or more exacerbations within 6 months requiring systemic corticosteroids.

In the most recent iteration of the GINA global strategy, much emphasis is devoted to a ‘shared-care approach’ using an effective patient-healthcare provider partnership that has been shown to improve outcomes, and the process of ‘assess, adjust treatment, and review response’. Eliciting specific goals of treatment from caregivers and providing education are key elements in this partnership. The process of assessing (diagnosis, symptom control, risk factors, inhaler technique, adherence and parent preference), adjusting treatment (medications, nonpharmacological strategies and treatment of modifiable risk factors), and reviewing response (medication effectiveness and side-effects) is recommended on an ongoing basis.

Controller Therapy for Small Children with Persistent Asthma

Based on the NAEPP EPR3 guidelines, upon establishing a diagnosis of asthma in young children, initiation of controller therapy is warranted for persistent asthma. The most important determinant of dosing is the clinician’s judgment of the patient’s presenting degree of severity. Initiation of long-term controller therapy should also be considered for infants and younger children who have risk factors for asthma (i.e. modified asthma predictive index: parental history of asthma, physician-diagnosed atopic dermatitis or sensitization to aeroallergens or two of the following: wheezing apart from colds, sensitization to foods or peripheral eosinophilia) and four or more episodes of wheezing over the past year that lasted longer than 1 day and affected sleep or two or more exacerbations in 6 months requiring systemic corticosteroids.

Medication dose adjustment is appropriate based on levels of asthma control, although dose-response relationships are not well studied. For preschool children already on a controller medication, management is tailored based on the child’s level of control. As with the classification of asthma severity, assessment of asthma control is based on both impairment and risk ( Table 32-2 ). The three levels of asthma control are ‘well controlled’, ‘not well controlled’ and ‘very poorly controlled’. Children whose asthma is not well controlled have daytime symptoms or need for rescue albuterol >2 days/week, nighttime symptoms more than once a month but not more than once a week, ‘some limitation’ with normal activity, had two to three exacerbations in the past year, and an FEV ₁ of 60–80% of predicted (or FEV ₁ /FVC ratio 75–80%) for children 5 years of age or older. Children with very poorly controlled asthma have symptoms ‘throughout the day’, nocturnal symptoms more than once weekly, need for rescue albuterol several times per day, ‘extreme limitations’ with normal activity, had ≥3 exacerbations in the past year, and for children at least aged 5 years, an FEV ₁ of <60% of predicted or FEV ₁ /FVC ratio <75%. Using a validated questionnaire to monitor quality of life for older children is recommended and perhaps the TRACK questionnaire discussed in a subsequent section may now be applied in younger children.

TABLE 32-2

Assessing Asthma Control and Adjusting Therapy in Children Aged 0 to 4 Years

Components of Control		Classification of Asthma Control (0–4 yr)
		Well Controlled	Not Well Controlled	Very Poorly Controlled
Impairment	Daytime symptoms	≤2 d/wk but not more than once on each day	>2 d/wk	Throughout the day
	Nighttime awakenings	≤1×/mo	>1×/mo	>1×/wk
	SABA use for symptoms (not EIB pretreatment)	≤2 d/wk	>2 d/wk	Several times per day
	Interference or limitations with normal activity	None	Some limitation	Extremely limited
Risk	Exacerbations requiring oral systemic corticosteroids	0–1/yr	2–3/yr	>3 yr
	Treatment-related adverse effects	Medication side-effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk
Recommended action for treatment per NAEPP guidelines		Maintain current treatment Regular follow-up every 1–6 months Consider step down if well controlled for at least 3 months	Step up (1 step) and reevaluate in 2–6 weeks If no clear benefit in 4–6 weeks, consider alternative diagnoses or adjusting therapy For side-effects, consider alternative treatment options	Consider short course of oral systemic corticosteroids Step up (1–2 steps), and reevaluate in 2 weeks If no clear benefit in 4–6 weeks, consider alternative diagnoses or adjusting therapy For side-effects, consider alternative treatment options

 

Notes:

• •
  

  The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.

  
  
• •
  

  The level of control is based on the most severe impairment or risk category. Assess impairment domain by caregiver’s recall of previous 2 to 4 weeks. Symptom assessment for longer periods should reflect a global assessment such as inquiring whether the patient’s asthma is better or worse since the last visit.

  
  
• •
  

  At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g. requiring urgent, unscheduled care, hospitalization or ICU admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma .

  
  
• •
  

  Before step-up therapy:

  
  
  
  
  • •
    

    Review adherence to medications, inhaler technique and environmental control.

    
    
  • •
    

    If alternative treatment option was used in a step, discontinue it and use preferred treatment for that step.

  
  

National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma – Summary Report 2007. Available at: http://www.nhlbi.nih.gov.easyaccess2.lib.cuhk.edu.hk/guidelines/asthma/asthgdln.htm .

The NAEPP EPR3 provides an expanded stepwise treatment approach ( Figure 32-2 ) even for young children. The choice of initial therapy is based on assessment of asthma severity. For patients who are already on controller therapy, modification of treatment is based on assessment of asthma control and responsiveness to therapy. A major objective of this approach is to identify and treat all ‘persistent’ and uncontrolled asthma with antiinflammatory controller medication. Management of intermittent asthma is short-acting inhaled β-agonist as needed for symptoms and for pre-treatment for those with exercise-induced bronchospasm (Step 1). The type(s) and amount(s) of daily controller medications to be used are determined by the asthma severity and control rating. Even for young children, the preferred treatment for ‘persistent asthma’ is daily ICS therapy, with or without an additional medication. Alternative medications for Step 2 include a leukotriene receptor antagonist (montelukast) or a nonsteroidal antiinflammatory agent (cromolyn). For young children (≤4 years of age) with moderate and severe persistent asthma, medium-dose ICS monotherapy is recommended and combination therapy of medium-dose ICS plus either a long-acting β-agonist (LABA) or montelukast is to be initiated only as a Step 4 treatment for uncontrolled asthma. Children with severe persistent asthma (Treatment Steps 5 and 6) should receive high-dose ICS, a LABA or montelukast, and an oral corticosteroid, if required. A rescue course of systemic corticosteroids may be necessary at any step.

Stepwise approach for managing asthma in children aged 0 to 4 years.

*Alphabetical order is used when more than one treatment option is listed within either preferred or alternative therapy.

Notes:

• •
  

  The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.

  
  
• •
  

  If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.

  
  
• •
  

  If clear benefit is not observed within 4 to 6 weeks and patient/family medication technique and adherence are satisfactory, consider adjusting therapy or alternative diagnosis.

  
  
• •
  

  Studies on children aged 0 to 4 years are limited. Step 2 therapy is based on Evidence A. All other recommendations are based on expert opinion and extrapolation from studies in older children. The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.

ICS – Inhaled corticosteroid; LABA – inhaled long-acting β ₂ -agonist; prn – as needed; SABA – inhaled short-acting β ₂ -agonist.

National Asthma Education and Prevention Program: Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma – Summary Report 2007. J Allergy Clin Immunol 2007;120(Suppl):S94–138. (Available at: http://www.nhlbi.nih.gov.easyaccess2.lib.cuhk.edu.hk/guidelines/asthma/asthgdln.htm .)

The ‘step-up, step-down’ approach initially introduced in the earlier versions of the NAEPP guidelines and slightly modified in the current iteration is discussed in further detail in Chapter 29 . The NAEPP guidelines emphasize initiating higher-level controller therapy at the outset to establish prompt control, with measures to ‘step down’ therapy once good asthma control is achieved. Initially, airflow limitation and the pathology of asthma may limit the delivery and efficacy of ICS such that stepping up to higher doses and/or combination therapy may be needed to gain asthma control. Asthma therapy can be stepped down after good asthma control has been achieved and ICS has had time to achieve optimal efficacy, by determining the least number or dose of daily controller medications that can maintain good control, thereby reducing the potential for medication adverse effects. If step-up therapy is being considered at any point, it is important to check delivery device technique and adherence, implement environmental control measures and identify and treat co-morbid conditions.

The GINA 2014 global strategy also now offers a stepwise approach in the long-term management of asthma in very young children. However, if control is still inadequate despite 3 months of controller therapy, the following should be addressed before any step-up treatment is offered: that any other possible alternative or confounding condition is entertained; assessment of inhaler technique; adherence is acceptable; and exposure to allergens or tobacco smoke is avoided. The criteria for ‘well controlled’, ‘partly controlled’ and ‘uncontrolled’ asthma according to the GINA global strategy are summarized in Table 32-3 , based on a 4-week recall. ‘Well-controlled’ asthma is characterized by at most daytime symptoms once a week, rescue/reliever treatment less than 2 times a week, absence of any activity limitation due to asthma, and no nocturnal cough or awakenings. ‘Partly controlled’ asthma has one to two of the following: ≥2 daytime symptoms a week, ≥2 rescue bronchodilator use, any nocturnal cough/awakenings, or limitations of activities. Lastly, ‘uncontrolled’ asthma is defined as presence of three or all features characteristic of ‘partly controlled’ asthma present in any week or exacerbation occurring once in any week.

TABLE 32-3

GINA Assessment of Asthma Control in Children 5 Years and Younger

A. Level of Symptom Control
	In the past 4 weeks, has the child had:	Yes	No
	Daytime asthma symptoms for more than a few minutes?
	Any night waking or coughing due to asthma?
	Reliever medication needed more than once a week (excludes reliever taken before exercise)?
	Any activity limitation due to asthma? (Runs/plays less than other children, tires easily during walks/playing?)
Controlled (none of the above)
Partly controlled (1–2 of these)
Uncontrolled (3–4 of these)
B. Future Risk for Poor Asthma Outcomes
Risk factors for asthma exacerbations • Uncontrolled asthma symptoms • One or more severe exacerbations in previous year • The start of the child’s usual ‘flare-up’ season (especially if autumn or fall) • Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens (e.g. house dust mite, cockroach, pets, mold), especially in combination with viral infection • Major psychological or socioeconomic problems for child or family • Poor adherence with controller medication, or incorrect inhaler technique
Risk factors for fixed airflow limitation • Severe asthma with several hospitalizations • History of bronchiolitis
Risk factors for medication side-effects • Systemic: frequent courses of oral corticosteroids; high-dose and/or potent inhaled corticosteroids • Local: moderate/high-dose or potent inhaled corticosteroids; incorrect inhaler technique; failure to protect skin or eyes when using inhaled corticosteroids by nebulizer or spacer with facemask

 

Adapted from the Global strategy for asthma management and prevention 2014. Available at: http://www.ginasthma.org .

The stepwise approach in the GINA 2014 global strategy has important differences from the NAEPP EPR3 ( Table 32-4 ). For Step 1 which recommends as needed short-acting β-agonist as the preferred controller choice for children with infrequent viral wheezing, with few or no interval symptoms, intermittent inhaled corticosteroid therapy is an alternative option if short-acting β-agonist treatment is not enough. Intermittent high-dose ICS therapy given at the onset of a respiratory illness is further demonstrated to be as beneficial as maintenance therapy with ICS in children with recurrent wheezing and with risk factors for persistent asthma. Because it has the potential to cause side-effects if given quite often during the year at higher doses, this should be considered for families who are able to use this intervention responsibly. Step 2 treatment is recommended for young children with symptom pattern consistent with asthma and not well controlled or with 3 or more exacerbations per year or with frequent wheezing episodes occurring every 6 to 8 weeks. Similar to the NAEPP EPR3 recommendation are the preferred medication using daily low-dose ICS (for at least 3 months trial) and the alternative option using a leukotriene receptor antagonist, but GINA 2014 global strategy now also includes intermittent ICS for Step 2 as an alternate option. The National Institute of Health sponsored AsthmaNet is currently undertaking a clinical trial comparing these three treatments in young children with persistent asthma. Preferred Step 3 treatment is double ‘low-dose’ ICS, indicated for children with established asthma not well controlled on low-dose ICS. The alternative option is low-dose ICS with a leukotriene receptor antagonist. The highest step (Step 4) basically proposes a referral to a specialist for expert advice. Additional options include adding a leukotriene receptor antagonist, theophylline or a low-dose oral corticosteroid (for a few weeks only) until control improves, increasing the dose or frequency of ICS delivery or adding intermittent ICS to regular daily ICS, particularly if exacerbations are the main concern. Through all these, the process of assessing, adjusting treatment and reviewing response should be actively enforced. Regular assessment of symptom control and risk of exacerbations, inhaler technique, adherence and parents’ understanding and preference should be undertaken. The need for controller therapy should be evaluated and treatment should be adjusted as symptoms in this age group may remit at certain times of the year or even over time. Once therapy is discontinued, a close follow-up within 3 to 6 weeks is ideal, and caregivers should be provided with a written asthma action plan that incorporates early warning signs of worsening asthma control and what to do or who to contact when the child’s condition deteriorates.

TABLE 32-4

Stepwise Approach to Long-Term Management of Asthma in Children 5 Years and Younger (Global Initiative for Asthma 2014)

	Step 1	Step 2	Step 3	Step 4
PREFERRED CONTROLLER CHOICE		Daily low-dose ICS	Double ‘low-dose’ ICS	Continue controller and refer for specialist assessment
Other controller options		LTRA Intermittent ICS	Low-dose ICS + LTRA	Add LTRA Increase ICS frequency Add intermittent ICS
RELIEVER	As needed short-acting β 2 -agonist
CONSIDER THIS STEP FOR CHILDREN WITH	Infrequent viral wheezing and no or few interval symptoms	Symptom pattern consistent with asthma and asthma symptoms not well controlled, or ≥3 exacerbations per year Symptom pattern not consistent with asthma but wheezing episodes occur frequently, e.g. every 6–8 weeks Give diagnostic trial for 3 months	Asthma diagnosis, and not well controlled on low-dose ICS	Not well controlled on double ICS
			First check diagnosis, inhaler skills, adherence, exposures
KEY ISSUES	ALL CHILDREN • Assess symptom control, future risk, co-morbidities • Self-management: education, inhaler skills, written asthma action plan, adherence • Regular review: assess response, adverse events, establish minimal effective treatment • (Where relevant): environmental control for smoke, allergens, indoor/outdoor air pollution

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