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Asthma in children younger than 12 years: Initial evaluation and diagnosis

Asthma in children younger than 12 years: Initial evaluation and diagnosis
Literature review current through: Jan 2024.
This topic last updated: Oct 25, 2023.

INTRODUCTION — Asthma is a significant health problem worldwide, and it is one of the most common chronic diseases of childhood in many countries [1,2]. The prevalence in different countries ranges from 1 to 18 percent. In the United States, for example, over nine million children have been ever told they had asthma, and 5.5 million still have asthma [3]. Establishing a diagnosis of asthma involves a careful process of history taking, physical examination, and diagnostic studies. The differential diagnosis of wheezing and/or cough must be carefully considered, particularly in infants and very young children, for whom testing for reversible airflow obstruction is not easy to perform and not done routinely (table 1 and table 2 and table 3 and algorithm 1).

The epidemiology, initial evaluation, and diagnosis of childhood asthma are reviewed here. The assessment of severity/control and monitoring and treatment of childhood asthma are discussed separately. (See "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control" and "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies" and "Asthma in children younger than 12 years: Quick-relief (rescue) treatment for acute symptoms".)

The pathogenesis, genetics, risk factors, and natural history of asthma are also reviewed separately. (See "Pathogenesis of asthma" and "Genetics of asthma" and "Risk factors for asthma" and "Wheezing phenotypes and prediction of asthma in young children" and "Natural history of asthma".)

EPIDEMIOLOGY — A wide global variation exists in the prevalence of asthma, with higher rates typically seen in higher-income countries [4]. Asthma is the most common chronic disease in childhood in resource-rich countries. A significant increase in the estimated prevalence of asthma was seen in resource-rich countries in the 1980s and 1990s, with slower rates of increase in the 2000s and a plateau thereafter [5]. Approximately 5.8 percent of US children had asthma in 2020, down from 7.5 percent in 2018 and 9.4 percent in 2010 [6,7]. However, asthma prevalence continues to increase in other countries such as China [8]. Possible causes that impact asthma prevalence are reviewed in detail separately. (See "Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors".)

Disparities in prevalence remain, with higher prevalence seen in children with lower access to resources and those living in the Southern US and the highest prevalence still seen in Puerto Rican and non-Hispanic Black American children, particularly for those living in urban environments [6,9,10]. Before the onset of puberty, boys have a higher current prevalence of asthma than girls (9.2 versus 7.4 percent) [3,11]. This trend reverses in adolescence, the reasons for which remain unknown. Lifetime asthma prevalence for children was 12.7 percent in 2013 and 2016. The prevalence of asthma appears to have plateaued in other countries as well [12-16].

Asthma exacerbation rates among children with current asthma in the United States decreased from a rate of 62 percent among children <18 years old in 2001 to 48 percent in 2014 but increased in 2016 to 54 percent [3,10].

HISTORY — The history in a child with suspected asthma should focus on the presence of symptoms, typical symptom patterns, precipitating factors or conditions (ie, atopy), and known asthma risk factors (table 4).

Additional history that should be obtained in a child with established asthma who presents for disease monitoring includes previous and current therapy (controller and quick-relief medication use), exposure to triggers, utilization of health care services (emergency department [ED], hospital, unscheduled clinic visits), school attendance and performance, and participation in physical activity. Review of an asthma questionnaire such as the Asthma Control Test may provide additional useful information. (See "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control", section on 'Assessment of control'.)

The evaluation of a child who presents with an acute asthma exacerbation is discussed separately. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)

Symptoms — Evaluating the presence of asthma symptoms is an important first step in establishing a proper diagnosis. Coughing and wheezing are the most common symptoms of childhood asthma. Breathlessness, chest tightness or pressure, and chest pain also are reported. Poor school performance and fatigue may indicate sleep deprivation from nocturnal symptoms.

Cough — The presence of a nocturnal cough, a cough that recurs seasonally, a cough in response to specific exposures (eg, cold air, exercise, laughing, allergen exposure, or crying), or a cough that lasts more than three weeks, especially after an acute respiratory infection (see 'Respiratory tract infections' below), should raise the suspicion for asthma [17]. Although wheezing is considered the hallmark of childhood asthma, cough is frequently the sole presenting complaint [18]. The most common cause of chronic cough in children older than three years is asthma, even if it is not accompanied by wheezing. The cough is typically dry and hacking but may be productive; when the cough is productive, clear or whitish sputum may be expectorated (which often contains eosinophils). It is not unusual for chronic cough lasting more than three weeks to be labeled "bronchitis" and to be treated with medications such as cough suppressants, decongestants, or antibiotics. However, these types of cough may be manifestations of asthma and are likely to respond to asthma therapy. (See "Approach to chronic cough in children".)

Wheeze — Wheezing is a high-pitched, musical sound produced when air is forced through narrow airways. The wheezing of asthma tends to be polyphonic (varied in pitch), reflecting the heterogeneous distribution of affected airways. When airflow obstruction becomes severe, wheezing can be heard on both inspiration and expiration. In contrast to asthma, central airway obstruction may cause a harsh expiratory monophonic wheeze, as occurs with tracheomalacia. Upper airway obstruction (eg, vocal cord dysfunction) should be suspected if an inspiratory monophonic (of single pitch) wheeze (typically called stridor) is the only audible sound episodically. (See "Assessment of stridor in children".)

A silent chest in the context of an asthma exacerbation implies airflow limitation of such severity that audible wheezes cannot be produced; this represents a medical emergency. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)

Seasonal symptoms — Symptoms that are worse in certain pollen seasons are characteristic of atopic asthma. Trees in temperate climates pollinate in early spring, grasses in summer, and weeds in the fall. Children who are sensitive to molds tend to wheeze or cough during rainy seasons or if they are exposed to flooding or indoor dampness. Other allergic symptoms, such as rhinitis, conjunctivitis, or eczema, may flare concurrently with the chest complaints. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Allergic conjunctivitis: Clinical manifestations and diagnosis" and "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis".)

Symptom patterns — Chronic asthma symptoms assume several typical patterns:

Intermittent exacerbations superimposed upon an asymptomatic baseline

Chronic symptoms punctuated by periods of worsening symptoms

Morning "dipping" (an accentuation of the physiologic cycle of pulmonary function in normal individuals, characterized by worsening of symptoms and decreased peak flow in the early morning, with improvement as the day progresses)

Precipitating factors — Wheezing or cough may occur at any time, but certain patterns and precipitating factors (table 5) are typical. Depending upon the type and intensity of the provocative agent, most acute asthma exacerbations have a slow onset over several days. Uncommonly, severe attacks may occur suddenly and with minimal warning, resulting in life-threatening exacerbations [19-23]. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management" and "Trigger control to enhance asthma management".)

Respiratory tract infections — Viral upper respiratory infections (URIs) are the most important triggering factor for patients with asthma of all ages, including infants and young children [24]. Clustering of asthma attacks between fall and spring suggests viral illness-induced phenomena [25,26]. Among children who are hospitalized for wheezing, respiratory syncytial virus, influenza virus, and rhinovirus are most common in those younger than three years (depending upon the season); rhinovirus is most common among older children [25]. (See "Role of viruses in wheezing and asthma: An overview".)

One study found that clusters of asthma hospitalizations in school-aged children in Canada occurred predictably after they returned to school following summer vacation and other breaks [27]. Specifically, there was a "September asthma epidemic" approximately 18 days after Labor Day (the first Monday of September), with a lesser increase in attacks two days later in preschool children and six days later in adults. Viral infections were the presumed cause, although a reduction in daily asthma medication use (eg, therapeutic holiday) during the summer months has also been implicated.

Chronic sinusitis (which is often bacterial) and respiratory infections due to Mycoplasma pneumoniae and Chlamydia pneumoniae may precipitate worsening of asthma [28-32]. (See "Pneumonia caused by Chlamydia pneumoniae in children" and "Mycoplasma pneumoniae infection in children", section on 'Other respiratory manifestations'.)

Exercise — Exercise-induced bronchospasm (EIB) has a high positive predictive value for presence of asthma and may be the only manifestation of asthma in children [33,34]. It occurs in up to 90 percent of children with asthma [35].

Typical symptoms are shortness of breath, chest tightness, and cough. Exercise-triggered symptoms typically develop several minutes into prolonged exercise. Symptoms usually resolve with rest over 30 to 60 minutes. Lung function changes little or may even improve somewhat during most of the actual period of exercise. Lung function may begin to deteriorate towards the end of the exercise period and can fall quite markedly in some patients. The major fall in lung function normally occurs 5 to 10 minutes after stopping the exercise. Lung function then normally returns spontaneously to baseline over 30 to 45 minutes. A late-phase reaction occurs in a small proportion of patients with asthma [36], and some patients have both an immediate and a late-phase response to exercise [37]. (See "Exercise-induced bronchoconstriction".)

Certain types of exertion (eg, swimming) appear to be less provocative of asthma than others (eg, running, skating), probably because they produce less airway cooling and drying, which are thought to be provocative of EIB [33]. In a systematic review, patients with stable asthma who participated in swimming training had improved lung function and physical fitness, with no change in asthma symptoms or exacerbations [38]. However, there is an ongoing debate about potential lung damage caused by repeated respiratory exposure to chlorine byproducts in recreational swimmers [39-42]. We allow our patients to swim in pools and only advise against it if chlorine appears to be an irritant trigger in a particular patient.

Short bursts of activity tend to be better tolerated than prolonged exercise. Repeated short periods of exercise tend to result in diminishing EIB with each episode. Nonetheless, children with asthma do not need to be steered toward particular sports, since they can participate in sports at any level (including the Olympics) with proper treatment, and improved exercise conditioning leads to lower respiratory rates with the same level of activity.

If untreated, longstanding EIB may result in poor overall fitness, decreased exercise stamina, a preference for a sedentary lifestyle, and exercise avoidance due to the distress brought on by physical activity. EIB that is difficult to control often indicates inadequately controlled underlying asthma.

Weather — Cold air; hot, humid air; changes in barometric pressure; rain; thunderstorms; or wind may be provocative factors for asthma in individual patients. (See "Trigger control to enhance asthma management", section on 'Atmospheric conditions'.)

Tobacco smoke — Exposure to secondhand cigarette smoke is the single, most common, external risk factor for the development and progression of asthma symptoms in children [43-45]. (See "Secondhand smoke exposure: Effects in children".)

Vaping — In a laboratory setting, e-cigarette use altered pulmonary function and inflammation in patients with asthma [46]. Adolescents with exposure to secondhand e-cigarette smoke had increased odds of self-reported asthma exacerbations [47,48].

Allergens — Indoor and outdoor allergens are an important trigger of childhood asthma for the 80 percent of children with asthma and allergies, particularly those older than three years of age (see "Allergen avoidance in the treatment of asthma and allergic rhinitis"). These include [49]:

House dust mites, cockroaches, and rodents [50-53]

Pet exposures; cats and dogs are especially provocative, but other furry animals (gerbils, rabbits, hamsters, etc) may be suspect, especially if symptoms only occur in settings where these animals reside [54]

Pollens [55]

Molds

Irritant exposures — Asthma symptoms that occur after prolonged time indoors (eg, winter months or during periods of inclement weather) should raise a suspicion of sensitivity to indoor exposures to allergens (see 'Allergens' above) or inhaled airway irritants, such as [49,56]:

Nitrogen dioxide (from gas stoves) [57]

Particulates and smoke from wood fires, pellet stoves, or kerosene space heaters

Exposure to chemicals via vaping

Propellant cleaning sprays

Perfumes, hair sprays

Paint

Room deodorizers

Cleaning products with strong odors

Stress — Various types of stress can trigger or exacerbate asthma [58], although asthma can also cause stress. However, asthma symptoms and exacerbations should not be attributed to stress unless all other exacerbating factors have been excluded. In addition, asthma should be sufficiently well controlled to allow patients to tolerate stressful situations and other unavoidable triggers without asthma exacerbations.

Additional history — Additional history that should be obtained in children with suspected asthma includes a personal history of other atopic diseases, family history of asthma or other atopic diseases (eg, allergic rhinitis, atopic dermatitis, and food allergy), environmental history, past medical history, medication use, medical utilization, school attendance, and psychosocial factors.

Allergic history — Allergic disease is associated with the development, severity, and persistence of asthma. As an example, up to 80 percent of children with atopic dermatitis develop asthma and/or allergic rhinitis later in childhood [59]. Approximately 30 percent of children with food allergy have asthma and respiratory allergy compared with 10 percent of children without food allergy [60]. Food allergy is also a risk factor for life-threatening asthma, as evidenced by a substantially higher rate of food allergy in children requiring intubation for asthma compared with a control group of asthmatic children [61]. Sensitivity to many mold allergens is associated with increased asthma severity and persistence [62,63]. (See "Role of allergy in atopic dermatitis (eczema)" and "Allergen avoidance in the treatment of asthma and allergic rhinitis" and "Risk factors for asthma", section on 'Atopy and allergens'.)

In a study of children who were hospitalized for wheezing (cases), total serum immunoglobulin E (IgE) concentrations in the subgroup <3 years of age were similar to hospitalized children without wheezing (controls) but were significantly elevated among the cases in the subgroup >3 years old [25]. In addition, a higher percentage of cases were sensitized to at least one inhaled allergen (84 versus 33 percent).

In atopic infants, sensitization to common foods, such as egg white and cow's milk, may occur and peaks at approximately eight months of age [64]. IgE antibodies to inhalant allergens generally appear beginning at two years of age and increase throughout childhood [64]. Food allergy and eczema are the most common manifestations of atopy in early life, whereas asthma and allergic rhinitis are more common in older children. (See "Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis" and "Clinical manifestations of food allergy: An overview" and "Food allergy in children: Prevalence, natural history, and monitoring for resolution".)

Sensitization to foods and the presence of atopic dermatitis represent an atopic diathesis, whereas sensitization to airborne allergens also represents a trigger for asthma exacerbations.

Family history — The influence of genetics in the development of asthma has not been fully defined [45,65-71]. Because families also share environments, determining the influence of the genetic contribution to asthma is complicated. Nonetheless, a family history of asthma or other atopic disease (ie, allergic rhinitis, atopic dermatitis, or food allergy) certainly strengthens the likelihood that a child with a compatible history has asthma.

Children with one asthmatic parent are 2.6 times more likely to have asthma; with two asthmatic parents, the odds ratio rises to 5.2 [65]. Maternal asthma appears to make a bigger contribution than paternal asthma to asthma in offspring, although this finding is inconsistent [67-69].

Environment — A thorough review of all regular environments, including home, school, daycare, and relatives' homes, is essential to evaluate possible provocative situations in the child with asthma. The table outlines some questions that may be helpful in obtaining this history (table 6). A strategy to avoid asthma triggers is one of the essential elements for managing the disease. (See "Trigger control to enhance asthma management" and "Allergen avoidance in the treatment of asthma and allergic rhinitis".)

Past medical history — A careful survey of all aspects of the child's medical history is critical to formulate a differential diagnosis of the child's complaint. Questions about the neonatal course, early respiratory symptoms, and the coexistence of systemic symptoms (failure to thrive, fever, developmental delay, recurrent infections) may point toward other diagnoses. Additional questioning may reveal evidence of comorbid conditions, such as obstructive sleep apnea (OSA), gastroesophageal reflux, or chronic rhinosinusitis.

Sleep disordered breathing, for example, was associated with a 3.6-fold increased risk of severe asthma in one study [72]. Another large, observational study found an improvement in asthma control (eg, decreased exacerbations, hospitalizations, and medication use) following adenotonsillectomy [73]. The latter results did not show, however, that adenotonsillectomy caused a reduction in the severity of childhood asthma. It is possible that the children who underwent adenotonsillectomy shared another unknown factor that led to improvements in their asthma over time, such as a reduction in upper respiratory tract infections. (See 'Differential diagnosis' below and "Evaluation of severe asthma in adolescents and adults", section on 'Assessing comorbid conditions'.)

Medications — A careful review of prior and present medications (including over-the-counter and alternative remedies) provides information on adherence to therapy, drug efficacy, drug delivery systems in use, accuracy of diagnosis, and control of asthma. Response to treatment with albuterol, as demonstrated by a decreased respiratory rate, diminished retractions, increased aeration, and/or decreased cough or wheezing, can be helpful in making the diagnosis of asthma, particularly in children unable to perform spirometry. The onset of action is within 20 minutes, and the benefits should last four to six hours.

Common reasons for poor response to asthma medications include:

Nonadherence to the prescribed regimen. Caregivers and children often overreport adherence with controller medications; objective measures (eg, confirmation of pharmacy refill rates or an inhaler with a dose counter) may be necessary to verify adherence [74]. Overuse of quick-relief medications (eg, short-acting beta agonists) with resultant tolerance can also be an issue. (See "Enhancing patient adherence to asthma therapy" and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Tolerance'.)

Improper inhaler technique. Since the efficacy of many asthma medications depends upon their deposition in the lung, inhalation technique figures strongly in the success or failure of inhaled therapies. Metered dose inhalers (MDIs) require a significant degree of coordination for optimal drug delivery, and there is considerable evidence that many patients and health care professionals do not regularly perform or teach proper inhalation technique [75,76]. Errors also can be made with dry powder inhalers (DPIs). Patient education materials, use of spacers (with MDIs), and frequent reappraisal of technique contribute to greater success with this form of therapy. Valved holding chambers, otherwise known as spacers, with masks are especially helpful to the very young child. (See "Delivery of inhaled medication in children" and "The use of inhaler devices in children".)

Ineffective drug dose or dosing interval. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies".)

Complicating medical problems (eg, chronic sinusitis, vocal cord dysfunction, gastroesophageal reflux, environmental allergies) [77,78]. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Inducible laryngeal obstruction (paradoxical vocal fold motion)" and "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents" and "Relationships between rhinosinusitis and asthma".)

Complicating psychosocial factors (which can interfere with regularly obtaining and properly using medications).

Inappropriate treatment (eg, antibiotics, antitussives, over-the-counter or alternative medications).

Different response to controller medications depending upon the child's intrinsic characteristics [79-82].

Health care utilization — The degree of asthma control is usually linked to health care utilization, such that more severe or poorly controlled patients with asthma tend to be treated more often in EDs, urgent care centers, or doctors' offices. A history of more than a few such interventions is often indicative of poorly controlled asthma, regardless of the level of chronic symptoms [83]. In addition, a history of prior hospitalizations, ED visits, or exacerbations requiring oral glucocorticoids confers an increased risk for future asthma exacerbations.

School attendance — One-third of children with asthma suffer noticeable disability [84]. Interference with regular school attendance or achievement is a good measure of disability from childhood asthma. A pattern of significant numbers of lost days from school and a deteriorating academic performance should prompt more aggressive asthma management.

Nearly 14 million school days are missed each year due to asthma, although the percent of children with asthma who reported one or more missed school days declined significantly from 2003 to 2013 (61.4 versus 49 percent) [3] and held steady at 49 percent in 2016 [10]. Childhood asthma is also a major cause of parent/caregiver work absenteeism [85,86].

Physical activity — Most children with asthma can have symptoms brought on by intensive activity; therefore, many children limit their level of exertion. In one study, children with newly diagnosed, untreated asthma were less fit and spent less time in vigorous activity than their healthy peers [87]. However, physical activities need not be restricted. Rather, appropriate treatment should allow full participation, which should be encouraged. With appropriate therapy, children with asthma can participate in all activities, including sports at every level up to and including participation in the Olympics [88], without restriction.

Psychosocial profile — Chronic asthma may create or exacerbate psychosocial problems for patients and their caregivers. Conversely, psychosocial factors can affect asthma symptoms and health behaviors [89]. Stressors surrounding asthma can include:

Anxiety about the often sudden, life-threatening nature of attacks

Fear of dying

Fear of peer rejection because of being "different"

Concern regarding the adverse effects of asthma drugs (particularly glucocorticoids, also called corticosteroids)

Sleep deprivation due to nocturnal symptoms

Poor school performance

Financial consequences

Disruption in family routines

Siblings' resentment of the patient’s special status within the family

Limitation of social or geographic venues because of potential triggering of asthma (eg, cannot visit places where environmental tobacco smoke or allergen exposure is likely)

Family discord over asthma treatment

Predictive tools — Parents/caregivers often ask if their young children with recurrent cough or wheeze have asthma and if they might outgrow it. Various predictive models or clinical indicators of risk have been studied to help the clinician identify young children who will continue wheezing later in childhood, although these tools were primarily designed to enrich study populations rather than actually predict asthma. These models have employed various risk factors associated with the development of asthma in longitudinal epidemiologic studies, such as baseline forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), parental history of allergic sensitization and asthma, wheezing history, atopic disease in the child, IgE levels, and cytokine secretion profiles. However, none of these clinical tools have been validated in populations different from the study group. These tools and risk factors are discussed in greater detail separately. (See "Wheezing phenotypes and prediction of asthma in young children", section on 'Predictive tools in children with wheezing' and "Natural history of asthma", section on 'Infants and children'.)

PHYSICAL EXAMINATION — Examination findings during an acute exacerbation include tachypnea, hypoxia, wheezing, accessory muscle use, retractions, and prolonged expiratory phase. These findings are discussed in detail separately. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)

Physical examination of a child with asthma is generally normal if performed when the patient does not have an acute exacerbation. Abnormal findings in the absence of an acute exacerbation may suggest severe disease, suboptimal control, or associated atopic conditions. Abnormalities that may be observed include [83]:

Decreased air entry or wheezing on auscultation

A prolonged expiratory phase on auscultation

Dry cough

Signs of rhinitis, conjunctivitis, and sinusitis (nasal discharge, inflamed nasal mucosa, Dennie-Morgan lines, transverse nasal crease, sinus tenderness, dark circles under the eyes) (see "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis")

Signs of an acute respiratory infection

Halitosis due to chronic rhinitis, sinusitis, and mouth breathing

Eczema/atopic dermatitis

Nasal polyps (picture 1 and picture 2) (glistening, gray, mucoid masses within the nasal cavities, which may be associated with asthma and aspirin sensitivity in adolescents and adults, but should prompt evaluation for cystic fibrosis and primary ciliary dyskinesia in children of any age) (see "Cystic fibrosis: Clinical manifestations and diagnosis" and "Primary ciliary dyskinesia (immotile-cilia syndrome)")

An increased anterior-posterior diameter of the chest due to air trapping

Obesity — Results are conflicting regarding the relationship between obesity and asthma severity [72,90-93]. Obesity and higher percent body fat are associated with an increased incidence of asthma [94] and are more commonly seen in children with newly diagnosed, untreated asthma than their healthy peers [87]. Higher body mass index (BMI) is also associated with greater asthma severity [90,94]. However, biologic causality has not been proven, and reverse causation may also occur (ie, asthma limiting physical activity leading to obesity). (See "Risk factors for asthma" and "Evaluation of severe asthma in adolescents and adults", section on 'Assessing comorbid conditions'.)

DIAGNOSIS — A history of intermittent or chronic symptoms typical of asthma plus the finding on physical examination of characteristic musical wheezing (present in association with symptoms and absent when symptoms resolve) strongly point to a diagnosis of asthma (see 'History' above and 'Physical examination' above). Confirmation of the diagnosis of asthma is based on three key additional elements [83,95,96]:

The demonstration of variable expiratory airflow limitation, preferably by spirometry, when possible

Documentation of reversible obstruction

Exclusion of alternative diagnoses (see 'Differential diagnosis' below)

Evidence of airway obstruction on spirometry, especially if acutely reversible with a bronchodilator, strongly supports the diagnosis of asthma. However, normal spirometry, or the lack of reversibility of obstruction in the setting of an acute exacerbation, does not exclude the diagnosis. A trial of asthma medication is warranted in patients with symptoms suggestive of asthma who have normal or near-normal spirometry or who are unable to perform spirometry due to age or other factors. Improvement on medications is sufficient to make the diagnosis in these patients. If a trial of asthma medication fails to improve symptoms, bronchoprovocation testing with methacholine, cold air, or exercise may be warranted. (See 'Spirometry' below and 'Medications' above and 'Ancillary studies' below.)

Spirometry — Demonstration of reversible airflow obstruction establishes the diagnosis of asthma and facilitates the assessment of severity (figure 1) [83]. Spirometry is the preferred method of diagnosis of airflow obstruction. The National Asthma Education and Prevention Program (NAEPP) expert panel recommends performing spirometry in patients five years of age and older if a diagnosis of asthma is suspected [83]. (See "Overview of pulmonary function testing in children".)

Spirometry measurements include forced vital capacity (FVC) and the forced expiratory volume in the first second (FEV1). Airflow obstruction is defined as FEV1 reduced to less than 80 percent predicted and an FEV1/FVC ratio of less than 0.85 (85 percent) (table 7A). Reference values are based on age, height, sex, and race [97]. FEV1/FVC appears to be a more sensitive measure of impairment than FEV1, whereas FEV1 may be a more useful measure of risk for future exacerbations [83,98-101] (see "Asthma in children younger than 12 years: Overview of initiating therapy and monitoring control", section on 'Assessment of control'). Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) less than 65 percent correlates with reversible airflow obstruction in children with normal FEV1 and may be a useful measure in this subgroup, although further studies are needed [102].

Spirometry should be performed before and after administration of a bronchodilator to assess for reversibility (bronchodilator response [BDR]) even in children with a normal baseline FEV1 because many of these children will still have a BDR (both within the normal range and sometimes also supranormal) after treatment. Significant reversibility is indicated by an increase in FEV1 of ≥12 percent from baseline after administration of a short-acting bronchodilator. This definition for BDR positivity was established primarily in adults. An increase in FEV1 of ≥8 percent may be a better definition for BDR in children [103-105]. (See "Overview of pulmonary function testing in children".)

There is some evidence from cross-sectional studies to suggest that the NAEPP criteria for percent predicted FEV1 (table 7A-B) do not accurately categorize asthma severity in children and that symptom frequency and rescue medication use may be more sensitive measures [98,99,106-108]. In the Childhood Asthma Management Program (CAMP) study, for example, the mean FEV1 of all children studied was 94 percent predicted [99], although this study included only children with mild-to-moderate asthma based upon symptoms, use of medications, and response to methacholine [109]. Nonetheless, percent predicted FEV1 remains a useful measure because it is strongly associated with the risk of asthma exacerbation in the 12 months after measurement [100,101].

Another potential spirometric measure of risk for asthma severity and poor control (asthma instability) is the air-trapping obstruction phenotype, defined as a FVC Z-score of <-1.64 (equivalent to fifth percentile in a healthy population) or a ≥10 percent change in the predicted value of FVC after bronchodilation. In a study of 560 children aged 6 to 17 years from low-income, urban areas who had physician-diagnosed asthma, the risk of ≥2 asthma exacerbations during the 12-month study period was more than fourfold higher (odds ratio 4.41, 95% CI 2.37-8.21) in those with this phenotype compared with those without any evidence of obstruction on spirometry [110]. Children with the air-trapping obstruction phenotype also had higher Composite Asthma Severity Index scores and asthma treatment steps, as well as greater sensitivity to methacholine challenge and variability in FEV1 over time.

Measurements of peak expiratory flow using a peak flow meter are more variable and effort dependent than spirometry. In addition, there is wide variability in the published predicted peak expiratory flow reference values and in the reference values from brand to brand [83]. Thus, peak flow measurements alone should not be used to diagnose asthma. Peak flow measurements may be more useful in monitoring a patient's symptoms and response to therapy over time, although serial spirometry is preferred (table 7B) [83]. (See "Peak expiratory flow monitoring in asthma".)

Children <5 years — In infants and children younger than five years of age, the diagnostic steps should remain the same as described above, except that spirometry often cannot be performed in this age group. A trial of asthma medications may help to establish the diagnosis in these children. Reversal of symptoms and signs in the time expected for albuterol to work is suggestive of the diagnosis of asthma. Impulse oscillometry (IOS) is an alternative to spirometry in younger children since it only requires passive cooperation [111-113]. However, it is not readily available to most clinicians treating children with asthma, limiting its clinical utility [114]. IOS measurements at baseline and postbronchodilator differed significantly between children aged three to six years with and without asthma, whereas no significant differences were seen with traditional spirometry [115-117]. IOS may detect alterations in respiratory mechanics not seen with spirometry even in older children [118-120]. (See 'Diagnosis' above and 'Medications' above.)

Debate is ongoing regarding how to best classify infants and young children with recurrent wheezing. The terms asthma, reactive airway disease, wheezy bronchitis, bronchiolitis, asthmatic bronchitis, wheezing-associated respiratory illness, and postinfectious bronchial hyperreactivity have all been employed. This jargon reflects an attempt to describe and define a subgroup of wheezing children with a more transient disorder than is implied by "asthma," which is, by definition, chronic. "Wheezy bronchitis" usually defines nonatopic babies or toddlers with recurrent, virus-induced wheezing (the majority of this group of wheezing young children) that tends to disappear by five years of age [121,122]. Asthma, on the other hand, has been taken to mean a chronic condition, frequently associated with atopy, provoked by a number of triggers in addition to viruses, and carrying a decreased likelihood for spontaneous resolution. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Definition' and "Natural history of asthma", section on 'Infants and children' and "Wheezing phenotypes and prediction of asthma in young children" and "Role of viruses in wheezing and asthma: An overview" and "Evaluation of wheezing in infants and children" and "Approach to chronic cough in children".)

Ancillary studies — The history and physical examination, in conjunction with spirometry, are usually adequate to establish the diagnosis of asthma. Ancillary studies are most helpful to exclude competing diagnoses or to identify comorbid conditions.

Allergy testing — Allergy testing, done either by skin or in vitro testing, is helpful even in the very young child when used selectively. Specifically, when the environmental history uncovers exposure to furry animals (pets or pests), molds, cockroaches, or dust mites, it is worthwhile to test for these or other limited allergens to formulate proper avoidance strategies. Outdoor aeroallergens are unusual triggers in infants and very young children but may be triggers in older children. Food allergy testing is not helpful unless there is a sound history of gastrointestinal complaints, worsening eczema, urticaria, shortness of breath, throat tightness, cough, hoarse voice, or asthma that is temporally associated with the ingestion of certain foods. Children with this type of history should be evaluated by a clinician familiar with food allergies and prescribed epinephrine since ingestion of a food allergen can be life threating in a patient with food allergies, particularly in a patient with concomitant asthma. In addition, when indicated testing reveals the presence of IgE antibody to any allergen, an atopic diathesis is demonstrated, increasing the likelihood that chest symptoms are due to asthma. (See "Overview of skin testing for IgE-mediated allergic disease".)

Exhaled nitric oxide — Measurement of the fraction of exhaled nitric oxide (FENO) may be used as an adjunct to other assessments when the diagnosis of asthma is uncertain [123]. The use of this test in diagnosing asthma is discussed in greater detail separately. (See "Exhaled nitric oxide analysis and applications", section on 'Clinical use of FENO in asthma'.)

Bronchoprovocation testing — We advise performing bronchoprovocation testing (with methacholine, cold air, or exercise) when the clinical features are suggestive of asthma but spirometry is normal and there is no significant response to asthma medications. An exercise challenge of sufficient magnitude may provoke symptoms in children with asthma [124-126]. A negative bronchoprovocation study may also be useful in reducing the likelihood that a child has asthma, although it cannot be used to exclude the diagnosis. For safety reasons, these tests should be conducted in a specialized facility with trained technicians and should not be performed if a patient has severe airflow limitation (FEV1 <50 percent predicted) [127]. Exercise challenge has a high specificity, whereas methacholine challenge had a high sensitivity. Bronchial challenge tests are discussed in greater detail separately. (See "Overview of pulmonary function testing in children" and "Bronchoprovocation testing".)

Chest radiograph — We advise performing a chest radiograph (chest x-ray [CXR]) only in children who do not respond to initial therapy. In those children, the chest radiograph may display findings suggestive of causes for wheezing other than asthma including congenital malformations (eg, a right aortic arch suggestive of a vascular ring); evidence of airspace disease consistent with aspiration or cystic fibrosis; or findings consistent with asthma, such as hyperinflation, peribronchial thickening, and mucoid impaction with atelectasis.

Sweat chloride test — A sweat chloride test below established cut-off values reduces the likelihood of the diagnosis of cystic fibrosis in children with respiratory complaints often in association with frequent foul-smelling stools or other evidence of malabsorption (eg, undigested food or oil), recurrent pneumonia, edema, and/or failure to thrive. There should be a low threshold to perform this test in children with this clinical picture, even if prenatal maternal screening or newborn screening was negative, since identifying a patient with cystic fibrosis has major implications for the patient, the family, and future reproductive decisions. Mutation analysis should be performed even if the sweat chloride is below established cut-off values if the suspicion for cystic fibrosis remains high. (See "Cystic fibrosis: Clinical manifestations and diagnosis".)

Barium swallow — A modified barium swallow should be included in the diagnostic evaluation if swallowing dysfunction with aspiration is a consideration. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents" and "Evaluation of wheezing in infants and children".)

DIFFERENTIAL DIAGNOSIS — Although wheezing is most commonly caused by asthma, it is not a pathognomonic finding. The lack of objective measures of pulmonary function in very young children and the relatively high prevalence of congenital infections and inherited disorders that present with wheezing make it imperative to consider the differential diagnosis of wheezing illnesses before making a diagnosis of asthma solely on the basis of wheezing (table 1 and table 2). In particular, other causes of wheezing in children must be excluded if there is a failure to respond to asthma therapy or if the history and/or physical examination suggest alternative diagnoses. Cough is the primary manifestation in some children with asthma; therefore, the differential diagnosis for chronic cough in children should also be considered (table 8 and algorithm 1). Clinical features suggestive of a diagnosis other than asthma are seen in the table (table 9) and are discussed in detail separately. (See "Evaluation of wheezing in infants and children" and "Approach to chronic cough in children" and "Causes of chronic cough in children".)

INDICATIONS FOR REFERRAL — Consultation with an asthma specialist, typically either a pulmonologist or an allergist, is warranted when the diagnosis of asthma is uncertain, the asthma is difficult to control, medication side effects are problematic, or a patient has frequent exacerbations. Pulmonologists may be most helpful if alternative pulmonary diseases are suspected or if further pulmonary testing or bronchoscopy may be needed. Referral to an allergist may be most helpful if allergic triggers need further evaluation if food allergy is suspected or if concomitant nasal and ocular allergy symptoms are difficult to control.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Cough in children (The Basics)")

Beyond the Basics topics (see "Patient education: Asthma symptoms and diagnosis in children (Beyond the Basics)" and "Patient education: Asthma treatment in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Overview of approach to diagnosis – Establishing a diagnosis of asthma involves a careful process of history taking, physical examination, and diagnostic studies; other causes of wheezing and/or cough must be excluded (table 1 and table 2 and table 3 and algorithm 1). (See 'Introduction' above.)

History – The history in a child with suspected asthma centers on the presence of symptoms (cough and wheeze are the most common), precipitating factors or conditions (table 4 and table 5), typical symptom patterns, and response to asthma therapy. (See 'History' above.)

Additional history that should be obtained in children with suspected asthma includes a history of atopy, family history of asthma, environmental history, and past medical history. (See 'Additional history' above.)

Important aspects of the history in a child with asthma who presents for monitoring include previous and current therapy, exposure to triggers, medical utilization, school attendance and performance, comorbidities, and psychosocial stressors. (See 'Additional history' above.)

Physical examination – The physical examination of a child with asthma is generally normal if performed in the absence of an acute exacerbation. Abnormal findings may suggest severe disease, suboptimal control, or associated atopic conditions. (See 'Physical examination' above.)

Diagnosis – The diagnosis of asthma requires a history of episodic symptoms of airflow obstruction or bronchial hyperresponsiveness (table 4), demonstration (with spirometry if possible) that airflow obstruction is reversible (figure 1), and exclusion of alternate diagnoses. If spirometry cannot be performed, a trial of medications may help to establish reversibility. (See 'Diagnosis' above.)

Differential diagnosis – Other causes of wheezing in children must be excluded if there is a failure to respond to asthma therapy or if the history and/or physical examination suggest alternative diagnoses (table 1 and table 2 and table 8 and algorithm 1 and table 9). (See 'Differential diagnosis' above and "Evaluation of wheezing in infants and children".)

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Topic 5742 Version 41.0

References

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