Asthma

Shilpa J. Patel, MD, MPH,* Stephen J. Teach, MD, MPH*

*Division of Emergency Medicine, Children’s National Medical Center, Washington, DC

Practice Gap
Asthma is the most common chronic respiratory disease of childhood, a
leading cause of emergency department visits, and 1 of the top 3
indications for hospitalization in children. Despite advances in the
AUTHOR DISCLOSURE Dr Patel has disclosed management of pediatric asthma, significant disparities in care and
that she receives research support from outcomes persist. To bridge these gaps, we must embrace the concept of
National Heart, Lung, and Blood Institute
awards for ORBEX (Oral Bacterial Extract)
asthma care across the continuum and extend our reach beyond the
study and for the ED-SAMS (ED-Intiated immediate patient-provider visit.
School-based Asthma Medication
Supervision) study. Dr Teach has disclosed
that he receives research support from a
National Institute of Child Health and Human
Development K12 career development
Objectives After completing this article, readers should be able to:
award and as part of ECHO (Environmental
1. Understand trends in prevalence, outcomes, and health disparities in
Influences on Child Health Outcomes), from a
National Institute of Allergy and Infectious pediatric asthma.
Diseases R38 career development award and
as part of the Inner City Asthma Consortium, 2. Describe advances in understanding the pathophysiology of asthma.
from a National Heart, Lung, and Blood
Institute R38 career development award and
3. Translate an understanding of asthma to a differential diagnosis in a
for the ORBEX (Oral Bacterial Extract) Study, child with wheeze.
and from the Patient-Centered Outcomes
Research Institute for investigator-initiated 4. Practice guideline-based management with accurate assessment of
research. This commentary does not contain asthma severity and control.
a discussion of an unapproved/investigative
use of a commercial product/device. 5. Apply recent evidence-based emerging trends in the treatment of
asthma.
ABBREVIATIONS
ARR at-risk rate 6. Identify community-based strategies and quality improvement
CDC Centers for Disease Control and
projects in your practice setting to ensure asthma care across the
Prevention
ED emergency department continuum for vulnerable children.
EILO exercise-induced laryngeal
obstruction
FeNO fractional excretion of nitric oxide
FEV1 forced expiratory volume in 1
second INTRODUCTION
ICS inhaled corticosteroid
Asthma is defined by episodic and reversible airway constriction and inflam-
IgE immunoglobulin E
IL interleukin mation in response to infection, environmental allergens, and irritants. It is a
LAIV live attenuated influenza vaccine complex, multifactorial, and immune-mediated process that presents with
LTRA leukotriene receptor antagonist various clinical phenotypes.
NAEPP National Asthma Education and Despite novel treatments and guideline-based care, asthma remains a signif-
Prevention Program
icant public health problem. Medical care, missed school, and missed work
PBR population-based rate
PEF peak expiratory flow
related to asthma continue to burden our communities, costing more than $80
PFT pulmonary function testing billion each year. (1) Furthermore, asthma disproportionately affects minori-
SABA short-acting inhaled b2-agonist ties and socioeconomically disadvantaged children. (2) Black children have the

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 highest asthma morbidity and mortality rates of any US database found that black children had the highest asthma
group, with twice the emergency department (ED) visit/ readmission rate (21.4%) of any race or ethnicity. (10) Finally,
hospitalization rate and 9 times the mortality rate as white because ARRs rely on prevalence estimates, any under-
children. (3)(4)(5) counting of "current asthma" in disadvantaged groups
In 2012, the President’s Task Force on Environmental could result in an overestimation of risk.
Health Risks and Safety Risks to Children commissioned a Disparities in asthma outcomes and prevalence also exist
cabinet-level, multiagency group to address overall asthma based on geographic location. (11)(12) In Washington, DC,
morbidity and its racial and ethnic disparities. (6) The group for example, 1 in 9 children, compared with 1 in 12 nation-
chose 4 integrated strategies. ally, had asthma in 2014. (13) In addition, children in DC
• Remove barriers to guideline-based care. with the highest rates of ED visits and hospitalizations
• Improve the identification of at-risk children. for asthma live in socioeconomically disadvantaged neigh-
• Build capacity for integrated, community-based care. borhoods. Geographic variation in DC is likely due to a
• Support efforts to prevent asthma. variety of factors, including but not limited to race and
socioeconomic status. Population health using geospatial
mapping, (2) disease-specific registries based on local
EPIDEMIOLOGY AND PREVALENCE
electronic health records, and higher-level data analytics
Asthma affects 1 in 12 US children aged 0 through 17 years. (machine learning, artificial intelligence, etc) (14) are prom-
(3) After decades of increases, the prevalence of asthma in ising tools to identify and decrease disparities in asthma
this group plateaued between 2010 and 2012, (2) decreased outcomes. Collaborative efforts should target hot spots to
in 2013 from 9.3% in 2012 to 8.3%, and remained stable address the causes of disparate outcomes. (15) Examples
through 2016. (2)(3) In contrast, pediatric asthma preva- include the following:
lence in black children increased between 2001 and 2009, • Map local asthma prevalence using geographic infor-
leveling off by 2013. (2) In 2016, asthma prevalence in black mation systems software to identify hot spots of poor
children rose sharply to 15.7% (a 2.3% increase from 2014 asthma control (ED visits, hospitalizations, readmissions,
and 2015), twice that of white children. (3) This rate surpassed ICU admission, or death). Investigate neighborhood-
that of Puerto Rican children, who previously had the highest specific factors (access to routine primary care, [16]
prevalence of asthma of all US children. (3) The prevalence housing conditions) through focus groups or needs
of asthma in children in poverty did not decrease between assessments and initiate quality improvement projects
2001 and 2013 and remained high in 2016 (10.5%). (2)(3) to improve asthma control.
• Create an asthma registry using data from a health
Outcomes system’s electronic health records to identify an at-
Asthma exacerbation is a leading cause of (ED) visits (7) and risk subpopulation. Initiate a systemwide collaborative
1 of the top 3 indications for hospitalization in children. (8) effort to address disparities in care (initiation of inhaled
Comparing asthma outcomes between subgroups, an at-risk corticosteroid [ICS], [17] ensuring follow-up after hos-
rate (ARR) is preferred over the traditional population-based pitalization and emergency care, [18] management
rate (PBR). (9) An ARR is the number of children with the of comorbid conditions). Consider education or elec-
outcome (eg, asthma hospitalization or death) divided by the tronic decision support as interventions for a qual-
total number of children at risk for that outcome (those with ity improvement project to reduce disparities in care.
asthma). Conversely, a PBR is the number of children with • Use machine learning to analyze large data sets (eg,
the asthma outcome divided by the total population. PBRs all ED visits, [19] asthma registry) to identify associations
measure the overall burden of disease in a particular pop- between risk factors and poor asthma outcomes pre-
ulation or subgroup, whereas an ARR accounts for dif- viously not considered. Collaborate with local resources
ferences in prevalence between subgroups to describe to mitigate risk (legal aid to assist with poor housing,
disparities.(4) Between 2001 and 2010, ARRs for black and care coordination to ensure medications prescribed are
white children revealed a decrease in racial disparities for covered and there is subspecialty follow-up).
ED visit and hospitalization rates and no change in death
rate due to asthma. (4) It is important to note, however, that
PATHOPHYSIOLOGY
ARRs do not account for differences in underlying asthma
severity. A 2013 analysis of hospitalizations for chronic Asthma is a highly complex, immune-mediated, inflamma-
conditions in the Pediatric Health Information System tory disease, with intermittent and reversible lower airway

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obstruction due to smooth muscle constriction and airway animal dander) the immune system will favor an allergic,
narrowing in response to an environmental trigger, often in inflammatory, ie, unhealthy, response. Studies support that
association with a viral upper airway infection. Numerous children exposed to microbes early in life (living on farms,
inflammatory pathways to airway swelling result in the with older siblings or pets) have a lower risk of developing
many clinical phenotypes of pediatric asthma. persistent wheeze later in life. Thus, the microbiome may be
Longitudinal studies attempting to further understand the intermediary step between the genetic risk of the host
the natural history of asthma have identified 3 distinct and clinical phenotype in asthma, and perhaps the key to
phenotypes: transient early wheezing, nonatopic wheezing, primary prevention of asthma. (25)
and atopy-associated wheezing. (20) Transient early wheez- Furthermore, allergen exposure and viral infections act
ing is characterized by resolution of wheeze by 3 years of life, synergistically in the development of asthma. (26) Children
a lack of association with family history of asthma or early with asthma, or at risk for asthma, sensitized and exposed to
allergic sensitization as well as a positive association with perennial allergens (ie, dust, mold, mouse, rat, or cock-
prematurity, exposure to other children at child care, mater- roach), often experience airway inflammation when infected
nal smoking during pregnancy, and environmental tobacco with rhinovirus. (27) Rhinovirus (subtype C) has specifically
smoke exposure during infancy. (20) Nonatopic wheezing is been implicated in connection with development of asthma
characterized by viral-induced wheeze during first the 2 to 3 and asthma exacerbation. (27)(28)
years of life, with respiratory syncytial virus infection being Cytokine-mediated inflammation in allergic asthma is
associated with persistent wheeze later in life. (20) In the most important recent discovery in asthma pathogen-
contrast, atopic wheezing is characterized by a family history esis. The airways of a sensitized child with asthma release
of atopy, early allergen sensitization, and a genetic predis- mediators, damaging the epithelium. Th2 lymphocytes
position for sensitization. (20) With any of these pheno- trigger the release of cytokines (interleukin [IL]-4, IL-5,
types, severe illness early in life is associated with IL-9, IL-13, among others), which upregulate or downregu-
progressive and persistent wheeze in later life. (20) late other cytokine receptors. (29)(30) Cytokines stimulate
Five distinct clusters of asthma phenotypes (character- IgE production, mast cells, basophils, and eosinophils,
ized by asthma and allergy severity, pulmonary physiology, which mediate inflammation via histamine, prostaglandins,
allergy sensitization, total serum immunoglobulin E [IgE], and leukotrienes. (30) Newer therapies interrupt the inflam-
and allergic inflammation) were recently described in a large matory pathway by inhibiting the actions of specific medi-
urban longitudinal cohort from 9 cities in disadvantaged ators (IgE and IL-5).
and largely minority children aged 6 to 17 years. (21) These Mechanistic analysis at an individual’s cellular level could
phenotypes were distinguishable by the intensity of the help guide targeted therapy. A precision medicine approach
allergic response. Similarly, a birth cohort study compared could reduce morbidity in disproportionately affected
multiple groups with documented IgE antibody responses subgroups. (31) A recent study identified pro-inflammatory
and found early exposure to multiple allergens predictive of monocytes and type 2 cytokine activity to be more com-
asthma later in life. (22) monly associated with poorly controlled asthma in socio-
The significance of variation in early exposures to aller- economically disadvantaged children than children with a
gens versus microbes in children with asthma has been an higher socioeconomic status after controlling for potential
area of speculation for some time. Ecologic data are sug- confounders (age, sex, racial group, BMI, asthma severity,
gestive of the "hygiene hypothesis" whereby countries with and medication use). These children also had reduced
higher rates of early microbial exposure have decreased expression of genes that coded for interferon. (32) Lower
prevalence of asthma, and, conversely, countries with less levels of interferon have previously been associated with
exposure during childhood have higher rates of asthma. (23) increased viral-induced exacerbations. (33)(34)(35)
Current understanding of cellular and molecular immunol-
ogy suggests that exposures very early in life shape the
TRIGGERS
development of a child’s immune system to favor either a
Th1 (nonallergic) or Th2 (allergic) lymphocyte predomi- Respiratory viral infections are the most common triggers
nance. (24) Theoretically, if a child is exposed to various of asthma exacerbation in children. (36)(37) Annual fall
microbes early in life, the immune system will favor a increases in asthma exacerbation, or the September epidemic,
nonallergic, infection-fighting, ie, healthy, response. On occur when many children returning to school have asthma
the other hand, if a child is not exposed to many microbes exacerbations triggered by rhinovirus infection. (38)(39)
and is instead exposed to certain allergens (eg, dust, mold, Specific viral infections have also been found to be

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 associated with increased exacerbation severity (rhinovirus Last, exercise and other strenuous activity are frequent
[subtype C] [27] and influenza A [H1N1] [40]) and treatment triggers. Exercise-induced symptoms are more common
failure (respiratory syncytial virus, influenza, and parain- with poorly controlled asthma. (43) Preexercise preventive
fluenza). (41) A study of influenza-related pediatric deaths short-acting inhaled b2-agonist (SABA) with or without a
between 2000 and 2016 found that 12% had asthma. (42) step-up in asthma control is standard management. (43)
Annual influenza vaccination for children with asthma is Exercise-induced asthma is a rare, often overdiagnosed
considered best practice and is recommended for patients phenotype, where a child wheezes or coughs only after a
with asthma. (43) The 2018-2019 recommendations from short period of vigorous activity and symptoms improve 20
the Advisory Committee on Immunization Practices rec- to 30 minutes after cessation of activity. Other comorbid
ommend against use of the live attenuated influenza vaccine conditions, such as severe uncontrolled allergic rhinitis,
(LAIV) in children aged 2 through 4 years who have a obesity, and vocal cord dysfunction, should be considered
diagnosis of asthma or have had a wheezing illness in when evaluating exercised-induced symptoms. Vocal cord
the preceding 12 months due to a concern that the LAIV dysfunction, or paradoxical vocal cord motion on inspira-
could induce exacerbation. (44) Although the 2018-2019 tion, typically presents with the following distinguishing
LAIV guidelines have not been changed, new evidence from features: rapid onset and offset, usually minutes to seconds;
a large trial showed improved protection and no increased dyspnea reported on inspiration (or inspiration and expira-
risk of exacerbation with the LAIV in children with asthma. tion); patient localization of the throat and not the chest as
(45) Of note, the 2017-2018 and 2018-2019 American Acad- the source of discomfort; SABA or rescue inhaler usually
emy of Pediatrics guidelines did not recommend the LAIV reported as not helping; symptoms induced by stress,
as the primary choice of influenza vaccination for all chil- anxiety, aerobic exercise, or irritants; and a flow-volume
dren 6 months and older owing to concerns of decreased loop with a classic appearance, ie, a truncated inspiratory
effectiveness of the LAIV against influenza A/H1N1 in past flow loop with a normal expiratory loop.
seasons and uncertainty regarding its effectiveness this Another entity often confused with asthma is exercise-
season. (46) Recently published 2019-2020 American Acad- induced laryngeal obstruction (EILO). Any concern for
emy of Pediatrics guidelines, consistent with Centers for vocal cord dysfunction and EILO should prompt referral
Disease Control and Prevention (CDC) recommendations, to otolaryngology for further testing. Continuous laryngos-
advise patients to get the LAIV. To be clear, however, details copy during exercise is the gold standard for diagnosis of
regarding recommendations for patients with asthma have EILO.
not been released. Families should be counseled on trigger identification
Other triggers can be organized into several categories. and avoidance at routine visits for asthma care. Efforts
First, irritants bother any airway and can induce broncho- should be made to mitigate exposure to perennial allergens
spasm when a child with asthma is exposed. These include (mold spores, dust mites, animal dander, cockroaches, rats,
environmental tobacco smoke (47)(48)(49) and other burnt and mice) for patients with asthma with evidence by clinical
substances (candles, incense, marijuana, and electronic history (symptoms with exposure) and allergen sensitiza-
cigarettes); air pollution, particulate matter (fractions of tion on skin prick testing or from serum specific IgE
particles with an aerodynamic diameter smaller than 2.5 measurements. The following is a list of recommendations
and 10 mm), and ozone (50); chemicals in certain cleaning by allergen:
products; particles in the air (construction sites, perfumes, • Dust mites—provide mattress and pillow encasements,
paints, soaps); and wood or charcoal fires. Allergens are (51) vacuum twice a week, consider removal of carpet
specific to the child and trigger asthma in children with in the bedroom if there are significant nighttime
atopy, sometimes referred to as allergic asthma. These are symptoms, remove any stuffed animals from the
divided into perennial allergens (mold spores, cockroaches, child’s bed or recommend machine washing of stuffed
rats, mice, dust mites, and pet dander) and seasonal aller- animals in hot water
gens (tree, weed, and grass pollens). • Mold spores—avoid humidifier use; remediate any
Weather (rapid changes or extreme cold/hot air) and water damage/mold in the home
strong emotions (laughter, crying, or anger) are other com- • Pests—keep food out of the bedroom and in closed
mon triggers of bronchospasm in children with asthma. trash containers, exterminate if needed (preference of
Also, medications such as b-blockers, aspirin, and non- traps over sprays)
steroidal anti-inflammatory drugs are associated with induc- • Animal dander—consider removal of animal if that is
ing asthma exacerbations in a subset of the population. an option or recommend special hypoallergenic breeds

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 Environmental triggers are a major contributor to health inflammation. (59) However, FeNO testing is not always
disparities in pediatric asthma. (6) Removal of allergens in covered by insurance, the equipment is seldom available in
homes of children younger than 6 years with associated the primary care office, and guidelines do not recommend
asthma could reduce asthma risk by 40%. (52) In addition, routine use. (43)(60) The 2018 Global Initiative for Asthma
poor mental health is associated with poor asthma con- guidelines did report on benefits in certain situations, (60)
trol. (53)(54) A thorough approach to potential exposures and the update for the next National Asthma Education and
includes care coordination of appropriate referrals (allergist, Prevention Program (NAEPP) guidelines has listed FeNO as
nutritionist, gastroenterologist, otolaryngologist, mental 1 of 5 areas for intensive future review. (61)
health consultant), connection to community partners (local Wheezing is the characteristic finding on lung auscul-
organizations that conduct home visits, provide vacuums or tation in a child experiencing asthma exacerbation, but it is
mattress and pillow encasements; local housing authority; 1- not specific to asthma. Wheezing results from airflow
800-QUITLINE or other smoking cessation assistance), legal obstruction in the lower airways and is present in many
advocacy (legal aid to assist the family in advocating for other conditions. Broad differential diagnoses of wheezing
housing remediation if the landlord is not being compliant should be considered for any child with an initial episode of
with housing regulations, local law schools may also have free wheeze or difficult-to-control asthma or if there is report of
legal services), social work, and close follow-up for at-risk little or no relief of symptoms with SABA rescue. When
children. Tailored, comprehensive interventions reduce considering an alternative diagnosis, it is important to
asthma morbidity rates in at-risk children. (15)(18)(55)(56) remember that a child could still have concomitant asthma.
Table 1 lists alternative diagnoses in a child with wheeze,
starting with more common entities, by age, typical find-
CLINICAL ASPECTS
ings, and testing recommendations. Another approach
Diagnosis would be to consider alternative diagnoses by system (infec-
Asthma in children remains largely a clinical diagnosis. A tious, cardiac, pulmonary, hematologic) or mechanical
child with a family history of asthma presenting with episodic obstruction causing wheeze. The latter approach is helpful
and recurring chest tightness, cough, difficulty breathing, or when eliciting a review of systems and completing a focused
wheeze in response to common triggers who also demon- physical examination in a child with first-time wheeze or
strates improvement with a SABA likely has asthma. In older difficult-to-control previously diagnosed asthma. Finally,
children, demonstration of reversible bronchospasm on pul- several key historical features are important to elicit to assess
monary function testing (PFT) is diagnostic for asthma. severity: family history of asthma/atopy or other illness, age at
The diagnosis of asthma in younger children remains onset of symptoms, episodic versus persistent disease, poten-
challenging. Children younger than 5 years are unable to tial triggers or exposures, responsiveness to SABA, position-
provide the effort required to reliably obtain PFTresults. The ality of symptoms, and systemic signs of illness (poor weight
Asthma Predictive Index is a clinical tool sometimes applied gain, fevers, fatigue, or pallor) (Fig 1). Occasionally, a dry
to children 3 years and younger with wheezing to assist with chronic cough is the only presenting symptom of asthma in
treatment and prediction of asthma. A combination of major children. These children warrant a detailed history and
criteria (doctor-diagnosed parental asthma or eczema) and examination, spirometry, and a trial of bronchodilators if
minor criteria (doctor-diagnosed allergic rhinitis, wheezing asthma is suspected. However, cough variant asthma is rare
without viral upper respiratory tract infections, or peripheral in children, and failure to improve with bronchodilator use
eosinophilia ‡4%) help determine risk. (57) In the original should prompt further investigation.
cohort, a child with wheezing and either 1 major or 2 minor Children with poor access to primary care often use
criteria was 2 to 5 times more likely to have active asthma at urgent or emergency care for wheezing episodes; the
age 6 to 13 years and 4 to 9 times more likely if they had both 1 chronic and recurrent nature of symptoms may lead to
minor and 2 major criteria. (57) A recent study developed a a delayed or missed asthma diagnosis. (63)
new clinical tool, the Pediatric Asthma Risk Score, which
performed better than the Asthma Predictive Index to predict Diagnostic Testing/Adjuncts in Asthma
mild to moderate asthma. (58) The tool is available online for Peak Flows. Measurement of peak expiratory flow (PEF) is
clinicians to use at https://pars.research.cchmc.org/. portable and relatively inexpensive and provides families of
In addition, measuring airway inflammation using frac- children older than 5 years with objective data to initiate
tional excretion of nitric oxide (FeNO) may help evaluate rescue medications. A child should determine his or her
asthma in children who have eosinophil-mediated lung personal best (the best of 3 measurements performed daily

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 TABLE 1. Differential Diagnosis of Asthma by Age and Characteristic
Findings
FINDINGS THAT DIFFERENTIATE
DIAGNOSIS AGE FROM ASTHMA DIAGNOSTIC TESTS

Bronchiolitis <24 mo No atopy, typically not responsive to SABA, context of Clinical diagnosis
fever and viral respiratory tract infection
Viral-induced Any age (<4 y Wheezing only with viral respiratory PFT if frequent or severe
wheeze more common) tract infections, less atopy; usually
resolves by age 4 y (62)
Bronchopulmonary <24 mo Symptoms since birth in premature infant Clinical diagnosis
dysplasia
Chronic Any Chronic cough especially after meals, gastrointestinal Gastroenterology referral,
aspiration/GERD symptoms endoscopy, pH probe
Tracheomalacia/ <24 mo Symptoms since birth, constant (as opposed to Laryngoscopy
bronchomalacia intermittent or triggered); stridor present with
tracheomalacia
Bronchiectasis Any Symptoms since birth, wet chronic cough, recurrent Chest CT, bronchoscopy
wheeze with focal lung findings, recurrent pneumonia
in same location on CXR, sometimes with hemoptysis
Food allergy Any First-time wheeze in context of new food exposure Allergy testing, PFT
and other signs of food allergy (lip swelling, vomiting,
hives, hypotension)
Anxiety/panic School age No wheezing, no improvement Clinical diagnosis, PFT results normal
attack or older with SABA
Vocal cord Adolescent þ Acute onset of symptoms within minutes of exercise PFT shows classic pattern of dynamic
dysfunction or exposure to an irritant, symptoms quickly resolve airflow obstruction: laryngoscopy
and do not respond to SABA, sensation of airway
closing, throat tightness, no symptoms during sleep;
occasionally will hear inspiratory stridor on
examination; hoarse voice
Heart failure Any Fever (viral myocarditis), missed congenital Echocardiography,
heart disease, failure to thrive, symptoms electrocardiography, CXR
worsen with feeding in young infant or
with laying down; murmur, poor central
pulses, hepatomegaly, crackles
Foreign body <4 y (could Acute onset of symptoms, unilateral Anteroposterior/posteroanterior or
aspiration be any age) findings, history of choking spell bilateral decubitus CXR;
bronchoscopy
Mass effect (from vascular Any Unilateral wheeze or stridor (may be Chest CT, bronchoscopy
anomaly or tumor) positional, if due to a mass, ring, or
sling around upper airways), symptoms
worse with laying down; weight loss
and other systemic signs if oncologic
Underlying Any Recurrent bacterial pneumonia CXR, immunology evaluation
immunodeficiency
Allergic Any Difficult-to-control asthma symptoms, Sputum, Aspergillus IgE and IgG, CXR
bronchopulmonary chronic cough and intermittent fevers
aspergillosis
Cystic fibrosis Any Failure to thrive (may still have a Sweat chloride testing, genetic
normal newborn screen) testing

CT¼computed tomography, CXR¼chest radiography, GERD¼gastroesophageal reflux disease, IgE¼immunoglobulin E, IgG¼immunoglobulin G,

PFT¼pulmonary function testing. SABA¼short-acting inhaled b2-agonist.

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for 2 weeks) and use this number to guide acute manage- effort, and inability to detect small airway obstruction.
ment. (43) If the PEF falls below 80% of the child’s personal Therefore, patients should use the same peak flow meter
best, the child or caregiver should initiate rescue medica- each time, and technique should be reviewed frequently.
tions per the asthma action plan. Generally, 70% to 80% of PFT/Spirometry. PFT is recommended in children older
personal best is equivalent to yellow zone management of than 5 years for routine management of asthma and when
asthma, and 40% to 70% is equivalent to red zone man- the diagnosis is in question. PFT is more accurate than PEF.
agement (Tables 2 and 3, Fig 2). (43) In practice, specialists The 2 readings important in the diagnosis and evaluation of
who have access to in-office spirometry sometimes correlate asthma are forced expiratory volume in 1 second (FEV1) and
a patient’s PFT to PEF and use that to guide the determi- the ratio of FEV1 to forced vital capacity or FEV1%. FEV1% is
nation of a child’s personal best. If a child does not know his the proportion of forced vital capacity a child is able to expire
or her personal best, charts based on age and height can be in 1 second. The goal of PFT in asthma is to document
used to provide general ranges. Symptoms (cough, short- expiratory flow limitation or obstruction with reversibility.
ness of breath, exercise intolerance) correlate with PEF and An FEV1% of less than 0.80 is diagnostic for airflow
should be used to guide acute management, especially in obstruction, and reversibility with administration of a bron-
younger children who are not able to reliably measure their chodilator is diagnostic for asthma. If a child is able to fully
PEF. When teaching patients how to use a peak flow meter, cooperate, an FEV1% greater than 0.8 is normal. The classic
it is important to demonstrate and ask that a tight seal is flow-volume curve for asthma shows a dampening and
made with the lips around the mouthpiece. After forcefully scooping out of the expiratory curve. Periodic spirometry
inhaling in, the child forcefully exhales with 1 quick breath measurements can also be helpful to measure lung function
to measure his or her PEF. Limitations of PEF include poor because a primary goal of asthma is to maintain healthy
reliability between devices, high dependence on patient lung function.

Figure 1. Diagnosis of asthma: basic approach to a child with respiratory symptoms consistent with asthma. 2019 Global Initiative for Asthma,
available from www.ginasthma.org [ginasthma.org], reprinted with permission.

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 TABLE 2. Asthma Medications (Quick Relief) (43)
MEDICATION DOSING RECOMMENDATION NOTES

INH Short-Acting b2-Agonists (to relax the smooth muscles; activates b2 adrenergic receptors in the lungs, resulting in bronchodilation)
Albuterol MDI (90 mg/puff; Preexercise dosing: 2 puffs INH 15 min before exercise Indicated for quick relief of
200 puffs/canister) bronchospasm or to prevent
bronchospasm related to exercise
For single dose (yellow zone management on AAP): 2–4 puffs INH Adverse effects include tachycardia
every 4–6 h as needed for symptoms and tachypnea
For acute exacerbation (red zone management on AAP): 4–8
puffs every 20 min  3 doses:
‡5 to <10 kg: 4 puffs INH every 20 min for 3 doses
‡10 to <30 kg: 6 puffs INH every 20 min for 3 doses
‡30 kg: 8 puffs INH every 20 min for 3 doses
Albuterol inhalation solution ‡5 to <30 kg: 2.5-mg neb INH for single dose OR 7.5-mg neb INH
(0.63 mg/3 mL, 1.25 mg/3 mL, for 1 h
2.5 mg/3 mL, or 5 mg/mL) ‡30 kg: 5-mg neb INH for single dose OR 15-mg neb INH for 1 h
If still wheezing and in distress after 2 h of short-acting b2-agonist,
consider continuous neb treatment (0.6 mg/kg per hour):
‡5 to <10 kg: 5-mg/h neb INH every 1 h
‡10 to <20 kg: 10-mg/h neb INH every 1 h
‡20 to <30 kg: 15-mg/h neb INH every 1 h
‡30 kg: 20-mg/h neb INH every 1 h
Anticholinergics (antimuscarinic agent [blocks action of acetylcholine], which results in decreased contractility of smooth muscle resulting in
bronchodilation)
Ipratropium bromide inhalation 0.25–0.5 mg neb INH every 20 min for 3 doses Indicated in the ED setting for
solution (0.25 mg/mL) moderate to severe exacerbation
‡5 to <30 kg: 0.5 mg neb INH once Can cause transient dilation of the
pupil(s) and blurry vision if neb
formulation is blown into the eyes
for a prolonged period
30 kg: 1 mg neb INH once
Ipatropium bromide MDI 4–8 puffs every 20 min INH for 3 doses
(18 mg/puff)
Systemic Corticosteroids (anti-inflammatory; reverses B2-receptor downregulation)
Dexamethasone Short course (burst): Indicated for treatment of moderate
‡7 to <10 kg: 6 mg PO once with repeat dose in 24 h to severe exacerbations
‡10 to <20 kg: 10 mg PO once with repeat dose in 24 h
‡30 kg: 16 mg PO once with repeat dose in 24 h
OR 0.6 mg/kg IV or IM (max, 16 mg) in children not tolerating
oral medications
Prednisone (1-, 2.5-, 5-, 10-, 20-, Short course (burst): 1–2 mg/kg per day PO (max, 60 mg) for Consider comorbidities, eg, studies
and 50-mg tablets) 3–10 d divided twice daily show patients with sickle cell
disease and asthma have rebound
acute chest syndrome with
systemic corticosteroids and,
hence, should be avoided (64)
Prednisolone (5 mg/5 mL or Short course (burst): 1–2 mg/kg per day PO (max, 60 mg) for Will raise serum glucose so use with
15 mg/5 mL) 3–10 d divided twice daily caution in diabetes
Methylprednisolone Short course (burst): 1–2 mg/kg per day IV (max, 60 mg) for
3–10 d divided every 6–12 h
Adjunct acute asthma medications
Magnesium sulfate 50 mg/kg per dose (max, 2,000 mg/dose) IV once over 20 min Consider after 1 h of short-acting
b2-agonists and after systemic
corticosteroids if still with
respiratory distress and wheezing
Continued

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TABLE 2. (Continued )

MEDICATION DOSING RECOMMENDATION NOTES

Epinephrine (1:1,000) (1 mg/mL) 0.01 mg/kg per dose (max, 0.5 mg/dose) IM once Consider in severe, life-threatening
asthma

AAP¼asthma action plan, ED¼emergency department, h¼hour, INH¼inhaled, IM¼intramuscular, IV¼intravenous, max¼maximum, MDI¼metered-
dose inhaler, neb¼nebulized, PO¼‘per os’ or by mouth.

Methacholine Challenge. Bronchoprovocation tests, such Control, using similar assessments of risk and impairment,
as the methacholine challenge, are not a common practice in should be assessed every 3 months at routine asthma visits
pediatrics and are usually performed only by specialists. In and is classified as well controlled, not well controlled, or
addition, methacholine challenge testing has high negative very poorly controlled. Figure 2 details the current approach
predictive power and, hence, performs well in establishing to initial assessment of disease severity and ongoing assess-
the lack of asthma, or ruling out disease. (66) ment of control. Classification and control designation of
Impulse Oscillometry. Impulse oscillometry is a newer asthma guides should be made at each visit per NAEPP
PFT that allows for passive measurement of lung function. guidelines.
It is useful for children as young as 3 years and other
children who have difficulty with traditional PFT because Longitudinal Care
minimal effort is required by the child. (67) However, Once asthma severity and level of control have been deter-
impulse oscillometry is only available in a pulmonologist’s mined, the guidelines specify initial therapy or change
office. of therapy in a stepwise manner. (43) The mainstay of asthma
Chest Radiography. Chest radiographs are low yield in therapy consists of bronchodilators (ie, SABA) for rescue
the acute setting and rarely change management. However, therapy to relax the smooth muscles surrounding the airway
obtaining a radiograph should be considered when a child (bronchodilation) and corticosteroids to help reduce inflam-
presents with hypoxia and high fever and is not improving mation inside the airway. A routine asthma visit should be
on albuterol and systemic corticosteroids. (68) scheduled every 3 to 6 months. Barriers to asthma control,
Furthermore, a chest radiograph may be indicated at the adherence, and demonstration of proper medication admin-
first presentation of wheeze or when considering alternative istration should be assessed and addressed at each visit.
diagnoses other than asthma (Table 1). Treatment decisions should be based on recommended step
level only after adherence has been assessed and triggers have
Management been identified in conjunction with a plan for trigger mod-
The overall goal in managing asthma in children is to reduce ification/avoidance (Fig 2). (69)
impairment (maintaining a good quality of life, allowing for Management of chronic asthma can be confusing for
normal activities without limitation, and reducing missed children and families. Education should be provided using
school days) and to reduce risk (keeping children off sys- lay terminology. Visual aids to illustrate narrowed airways
temic corticosteroids, out of the hospital and ED, and and explain which medications reverse bronchospasm and
maintaining healthy lung function to prevent airway remod- offer quick relief (SABAs) versus reduce and control inflam-
eling that is associated with chronic inflammation). mation (corticosteroids or leukotriene receptor antagonists
[LTRAs]) are helpful. A misunderstanding in the difference
Severity Classification between quick-relief medications and daily controller med-
The NAEPP guidelines, last revised in 2007, set age-based ications is a common barrier to adherence (Tables 2 and 3).
criteria to standardize the classification and management of The instructions should be clear, communicated verbally
asthma. The guidelines for classification are based on the and in writing (with a detailed asthma action plan), and
magnitude of a child’s risk (occurrence of acute severe reinforced at each visit. A typical asthma action plan is
exacerbations in the past 12 months) and impairment divided into 3 sections. The green zone provides instruc-
(day-to-day symptoms over the past 4 weeks). Based on risk tions on routine medications (ICSs, LTRAs, preexercise
and impairment, asthma is classified into intermittent, mild SABAs, allergy medications). The yellow zone provides
persistent, moderate persistent, and severe persistent. instructions about home management of acute, mild

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 558
TABLE 3. Asthma Medications (Maintenance or Controller Medications) (65)
DAILY DOSE, BY AGE
MEDICATION 0–4 Y 5–11 Y ‡12 Y ADVERSE EFFECTS

Leukotriene modifiers

Pediatrics in Review
Montelukast (leukotriene receptor antagonist) (1–5 y): 4 mg by mouth once before bedtime
4- or 5-mg chewable tablet (6–14 y): 5 mg by mouth once before bedtime
4-mg granules or 10-mg tablet (>14 y): 10 mg by mouth once before bedtime

Immunomodulators

Omalizumab (anti-IgE) SC injection, 150 mg/1.2 mL, after NA ‡6 y: 150–375 mg SC 150–375 mg SC every Pain and bruising at injection sites
reconstitution with 1.4 mL of sterile saline every 2–4 wk 2–4 wk (depends on Risk of anaphylaxis (0.2%)
(depends on bodyweight and
bodyweight and pretreatment serum
pretreatment IgE levels)
serum IgE levels)

Long-acting muscarinic antagonist

Tiotropium bromide*2.5 mg (2 actuations; 1.25 mg/actuation) NA ‡6 y: 2 actuations 2 Actuations inhaled Caution with use if creatinine clearance <60 ml/min
inhaled daily daily

Inhaled corticosteroids

Beclomethasone HFA: 40 or 80 mg/puff NA (L): 80–160 mg (L): 80–240 mg Must rinse mouth after each use to prevent oral thrush and
(M): >160–320 mg (M): >240–480 mg systemic absorption
(H): >320 mg (H): >480 mg

Budesonide DPI: 90 or 180 mg/inhalation NA (L): 180–360 mg (L): 180–540 mg

(M): 360–720 mg (M): 540–1080 mg
(H): >720 mg (H): >1,080 mg

Budesonide nebules: 0.25, 0.5, or 1 mg (L): 0.25–0.5 mg (L): 0.5 mg NA

(M): >0.5–1 mg (M): 1 mg
(H): >1 mg (H): 2 mg

Flunisolide HFA: 80 mg/puff NA (L): 160 mg (L): 320 mg

(M): 320–480 mg (M): >320–640 mg
(H): ‡480 mg (H): >640 mg

Fluticasone HFA/MDI: 44, 110, 220 mg/puff (L): 176 mg (L): 88–176 mg (L): 88–264 mg
(M): >176–352 mg (M): >176–352 mg (M): >264–440 mg
(H): >352 mg (H): >352 mg (H): >440 mg

Fluticasone DPI: 50, 100, or 250 mg/inhalation NA (L): 100–200 mg (L): 100–300 mg
(M): >200–400 mg (M): >300–500 mg

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(H): >400 mg (H): >500 mg

Mometasone NA (L): 110 mg (L): 100–220 mg

DPI: 110 mg, 220 mg/inhalation (M):>220–440 mg (M): >200–440 mg
HFA: 100 mg, 200 mg/puff (H): >440 mg (H): >440 mg

Continued
 exacerbations with escalation to red zone management

Doses are per National Asthma Education and Prevention Program update in September 2012 except for (*). Source: National Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and
Human Services. BID¼twice a day, DPI¼dry powder inhaler, (H)¼high daily dose, HFA¼hydrofluoroalkane, ICS¼inhaled corticosteroid, IgE¼immunoglobulin E, (L)¼low daily dose, (M)¼medium daily dose,
while seeking emergency medical care. Children with per-

Must rinse mouth after each use to prevent oral thrush

sistent asthma should be seen every 3 months to assess
ongoing control and to adjust controller medications. Pro-
viding tools (smartphone alarms, mobile applications, or
simply placing the daily inhaler and spacer next to the
toothbrush) may improve adherence. (70)
Adherence to medication is also affected by improper
delivery. Spacer use with a demonstration of appropriate
technique should be assessed at each visit. All patients,
ADVERSE EFFECTS

regardless of age, should use a spacer when using a

metered-dose inhaler rescue or controller medication.
The spacer ensures delivery of the medication to the lungs

MDI¼metered-dose inhaler, NA¼not available (not approved, no data available, or safety and efficacy not established in this age group), SC¼subcutaneous.
and reduces medication that deposits inside of the mouth
with subsequent systemic absorption. Both mask and
mouthpiece spacer should be appropriate, and the choice
Not well controlled and on low- to medium-dose ICS:

(depends on asthma
Not well controlled and on low- to medium-dose ICS:

Not well controlled and on medium- to high-dose ICS:

Not well controlled and on medium- to high-dose ICS:

is mostly based on age and ability to demonstrate proper

2 Inhalations BID

technique. Exceptions for spacer use include new devices

that either have a built-in spacer and devices with specific
severity)

instructions to not use a spacer (this should be included in

‡12 Y

the package insert). All children taking controller ICSs

250/50 DPI or 115/21 HFA
100/50 DPI or 45/21 HFA

should rinse their mouth after use to prevent oral thrush

and to minimize systemic absorption. A video demonstrat-
ing proper spacer technique is available online (https://
1 Inhalation BID

vimeo.com/channels/impactdc).
160/4.5

Frequent introductions of new delivery systems for asthma

80/4.5
5–11 Y

medications are common with changes in insurance for-

NA

mularies and the availability of new devices on the market.

Providers must be vigilant to ensure insurance coverage of
DAILY DOSE, BY AGE

prescribed medications and should check manufacturer

websites for online videos to familiarize themselves with
proper technique of new devices to teach their patients.
Inhaled corticosteroid D long-acting B2-agonist (combination medications)

Finally, it is crucial to assess parent and adolescent "buy-

0–4 Y

in" to chronic medication use. For a parent, it helps to

NA

NA

NA

explain the process inside the lungs in the context of

therapeutic effect and potential for airway remodeling
(71) if chronic uncontrolled asthma persists. For an adoles-
DPI: 100 mcg/50 mg, 250 mcg/50 mg, or 500 mcg/50 mg

cent, the consequences have to be more immediate, ie, the

HFA: 45 mcg/21 mg, 115 mcg/21 mg, 230 mcg/21 mg

ability to perform better at their specific sport or extracur-

Budesonide/formoterol HFA MDI: 80 mcg/4.5 mg,

ricular activity with regular use of controller medications.

Mometasone/formoterol MDI: 100 mg/5 mcg

Persistent asthma requires a thorough and ongoing

assessment of potential comorbid conditions. Addressing
potentially treatable comorbidities commonly seen with child-
hood asthma (obesity, [72] obstructive sleep apnea, allergic
TABLE 3. (Continued )

rhinitis, gastroesophageal reflux, and stress or depression)

Fluticasone/salmeterol

could avoid unnecessary escalation of asthma therapy. A

160 mcg/4.5 mg

complete review of symptoms should reveal these diagnoses.

MEDICATION

Finally, when prescribing controller medications, the

provider should ensure patient access to medications. In
addition to assessing insurance coverage of the ICS brand, a

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 Figure 2. Asthma control, severity classification, and treatment flow diagram for children 5 years and older. (43)(69)

family’s ability to pay or afford the co-pay should be con- results, and allergen avoidance should continue to be
sidered. Privately insured families with limited additional recommended.
funds may qualify for coupons available on the manufac- In addition, children with severe allergic rhinitis may
turer’s website. Also, if possible, one should obtain prior benefit from subspecialist referral to an allergist for con-
authorizations for additional spacers and rescue inhalers sideration of specific and targeted immunotherapy. Current
for school and multiple residences because a child may live evidence supports in-office subcutaneous immunotherapy
in multiple households. Routine follow-up appointments for single allergens in children with persistent asthma and
should be scheduled at the time of visits, and the importance a clear relationship between symptoms and exposure to a
of these visits with plans for step-up or step-down therapy specific allergen to which the patient has documented
should be communicated to families. Addressing barriers, sensitivity. Guidelines support immunotherapy for 3 spe-
(73) coordinating care, (15) and ensuring adherence to cific allergens: dust mites, animal dander, and pollen. (43)
guideline-based care (74) are imperative for reducing dis- Patients who receive immunotherapy are at risk for ana-
parities in asthma care. phylaxis and should be closely monitored. The update for
Allergy testing for indoor allergens (certain molds, ani- the 2007 NAEEP guidelines lists immunotherapy as 1 of the
mal dander, house dust mites, and cockroach) is recom- 5 specific areas of future in-depth review. (61)
mended for patients with persistent asthma and reported
exposure to allergens. (43)(60) Guidelines recommend tar- Severe Asthma
geted skin prick testing because it is low cost and accurate, Immunomodulatory medications, or biological agents, are
and targeted serum specific IgE if a child is uncooperative. emerging treatments in children with moderate to severe
(60) In practice, it is important to obtain a clinical history asthma. If a child is taking medium- to high-dose ICS and
of allergen exposure because any report of asthma symptoms long-acting inhaled b2-agonist and demonstrates poor con-
in reference to an exposure supersedes allergy testing trol despite proper technique and good adherence (frequent

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 TABLE 4. Recent Evidence for Emerging Trends in the Treatment of Asthma
EVIDENCE
PRACTICE CONSIDERATION POPULATION, NO. DESIGN FINDINGS (LIMITATIONS) RECOMMENDATION

School-based asthma therapy

Halterman et al (2011) (82) Children aged 3–10 y with Prospective RCT comparing home versus School administration of ICS Recommend partnership with local
asthma and Medicaid school administration of ICS effectively improves adherence school to see whether school-
insurance (n ¼ 530) (performed in conjunction with based asthma therapy is a feasible
dose adjustment as needed and alternative to home-based
tobacco smoke reduction program) therapy, especially for those
(single site) patients with poor adherence.
Consider direct delivery of
medications to the school.
Fall montelukast
Johnston et al (2007) (83) Children aged 2–14 y with RCT, double-blind, placebo-controlled trial 53% Decrease in “worse asthma Mixed results; could consider Fall
asthma (n ¼ 194) comparing a group started on age- symptoms” and 78% reduction in montelukast in a persistent
appropriate nightly dose of montelukast unscheduled asthma visits; boys 2– asthma population with poor ICS
from September 1 for 45 d 5 y and girls 10–14 y with most adherence (especially males aged
benefit (no minimum asthma 2–5 y and females aged 10–14 y)
severity for inclusion; pragmatic trial
with poor adherence to ICS in study
population)
Weiss et al (2010) (84) Children aged 6–14 y with RCT, multicenter, double blind, placebo No difference between placebo and
asthma (n ¼ 1162) controlled, comparing 5-mg montelukast montelukast groups (no minimum
night before day 1 of school for 8 wk; asthma severity for inclusion)
evaluated percent days with worse asthma
Preseasonal treatment with omalizumab
Teach et al (2015) (85) Inner-city asthmatic children 3-arm RCT, double blind, double placebo Compared to placebo, omalizumab Consider the addition of omalizumab
aged 6–17 y with ‡1 recent controlled, multicenter had a significantly lower rate of fall to guidelines-based therapy for
exacerbations (n ¼ 727) exacerbations, and omalizumab inner city children, aged 6-17 y,
boosted interferon levels with a before the fall season, especially if
decrease in rhinovirus infection in they have a recent history of
the omalizumab group exacerbation
Intermittent, extreme high-dose ICS dose for acute asthma
Jackson et al (2018) (86) Children aged 5–11 y with Double-blind RCT comparing low-dose ICS No difference between the groups in Good evidence to recommend

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mild to moderate persistent with quintupled-dose ICS for 7 d at early degree of asthma control against intermittent escalation in

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asthma, with 1 course of signs of loss of asthma control ICS for yellow zone management
systemic corticosteroids in in children; however, seasonal
previous year (n ¼ 254) increase may be supported in an
urban setting (87)(88)
Continued

NOVEMBER 2019
561
 562
TABLE 4. (Continued )

EVIDENCE
PRACTICE CONSIDERATION POPULATION, NO. DESIGN FINDINGS (LIMITATIONS) RECOMMENDATION

McKeever et al (2018) (89) ‡16 y on any dose of ICS with Pragmatic, randomized, unblinded trial Fewer severe exacerbations in high- * This contradicts current GINA
comparing self-increase in ICS to 4 times dose ICS group (no children in low- recommendations. (60)

Pediatrics in Review
‡1 exacerbation in previous
12 mo requiring systemic the dose with those that did not increase dose ICS group; subject to bias and
corticosteroids (n ¼ 1,922) baseline ICS dose for yellow zone found only 19% reduction in
management  14 d or peak flow normal increased ICS group) (87)(88)
Decision support for guideline-based care
Bell et al (2010) (17) Urban primary care clinics (n ¼ Cluster RCT trial of clinical decision support in Improved primary care provider Strong recommendation to consider
12) the electronic health record compliance with NAEPP guideline– implementation if feasible
based care (17)
Oral prednisolone in preschoolers with wheeze
Panickar et al (2009) (90) Children aged 10–24 mo RCT, double-blind, placebo-controlled, 5- No difference in LOS of hospitalization Good evidence to suggest against
hospitalized for viral- d course of oral prednisolone use of OCS in viral-induced
induced wheeze (n ¼ 700) wheeze
Foster et al (2018) (91) Children aged 24–72 mo RCT, double-blind, placebo-controlled, Placebo group with longer LOS (540
presenting to ED with viral- noninferiority trial, single dose of oral min) versus prednisone group
induced wheeze (n ¼ 605) prednisolone to reduce ED LOS (370 min), single center, baseline
very long LOS, unclear whether
generalizable to different settings,
unclear whether meaningful
outcome studied)
Dupilumab (anti–interleukin-4 receptor a monoclonal antibody) for moderate to severe uncontrolled asthma
Castro et al (2018) (92) Children aged ‡12 y, Randomized to 4 arms to receive add on Lower rates of severe exacerbation Promising results, good evidence for
uncontrolled asthma (n ¼ dupilumab every 2 weeks versus placebo and better lung function; results use of dupilumab in severe
1902) for 1 y at 2:2:1:1 ratio better in children with higher uncontrolled asthma (93)
baseline eosinophilia
Rabe et al (2018) (80) Children age ‡12 y; OCS- Random assignment of add-on dupilumab Improved lung function, decreased
dependent severe asthma every 2 wk versus placebo for 24 wk in an OCS dose, and fewer exacerbations
(n ¼ 210) attempt to reduce OCS dose in treatment group (small study)

ED¼emergency department, GINA¼Global Initiative for Asthma, ICS¼inhaled corticosteroid, LOS¼length of stay, NAEPP¼National Asthma Education and Prevention Program, OCS¼oral corticosteroid,
RCT¼randomized controlled trial.

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TABLE 5. Evidence-Based Management of Acute Asthma
PRACTICE RECOMMENDATION

Systemic corticosteroids Supports early administration of systemic corticosteroids in moderate to severe asthma exacerbations with
reduction in need for hospitalization if given within 1 h of ED presentation. (100) Oral route is preferred
route, and effects are considered equivalent. (43)
Short course (1–2 d) of dexamethasone equivalent to 3- to 5-d burst of prednisolone in acute asthma
exacerbation. (101) Equivocal data on single versus 2 doses of dexamethasone. (102)
Bronchodilator administration MDI with spacer equally effective as nebulized bronchodilator therapy in the ED. (103)(104) Additional
benefits include cost-savings (105) and decreased ED length of stay. (106)
Equivocal studies on continuous versus intermittent bronchodilator nebulization for severe asthma,
GINA guidelines recommend initial continuous therapy with spacing to intermittent in severe asthma.
(60)
Inhaled ipratropium bromide Supports use in moderate to severe exacerbations with SABA in preventing need for hospitalization, (107)
no additional benefit during hospitalization. (108) Not routinely recommended in mild exacerbations.
(43)(60)
Intravenous magnesium sulfate No clear support for routine use due to paucity of data; however, administration of intravenous magnesium
sulfate in moderate to severe asthma exacerbations if not improving after 1 h of bronchodilator and
systemic corticosteroid treatment may reduce need for admission. (43)(109) A recent trial showed
potential benefit for patients with severe asthma and pulse oximetry <92%. (95) More data needed.
Epinephrine Insufficient evidence; however, guidelines support administration for children with very poor effort unable
to adequately inhale nebulized bronchodilators or possibility of anaphylaxis and in life-threatening
situations. Although no significant detrimental effects either. (43)(60)
Noninvasive respiratory support Bilevel positive airway pressure has been studied more than HFNC in the management of severe asthma
exacerbation, however still with limited evidence to support or recommend against its use. (110)
Insufficient data in support of HFNC in setting of asthma to recommend use. Small pilot study using
HFNC for severe asthma compared it with nasal cannula oxygen with promising results. (111) Often used
in ICU settings to avoid intubation.
Heliox Consensus-based recommendation for severe exacerbations in conjunction with standard therapy, but
caution to not delay intubation if needed. (43)(60) Maximum oxygen content of heliox is 30% FiO2 and,
therefore, is not recommended in patients requiring higher % FiO2.
Terbutaline Insufficient evidence to support use. (112) Sometimes given to children with very poor effort unable to
adequately inhale nebulized bronchodilators, similar to epinephrine indicated in life-threatening
situations; however, has more adverse effects than epinephrine. (43)(60)
Ketamine Insufficient evidence for ventilated or nonventilated patients. (113)
Intravenous aminophylline Evidence recommends against use due to poor safety profile in children. (43)(60)(112)
Volatile anesthetics Used in ICU settings in ventilated patients, not mentioned in guidelines, with insufficient evidence for
routine use; no difference in outcomes in a large pediatric retrospective review. (114)
Chest radiography Low yield in the ED and rarely changes management, consider with hypoxia and high fever if not
improving on albuterol and systemic corticosteroids. (68)
ICS prescription at time of ICS should be initiated before ED discharge. (115) Regular use of low-dose ICS is associated with decreased
discharge from ED or risk of death from asthma. (116)
admission

ED¼emergency department, FiO2¼fraction of inspired oxygen, GINA¼Global Initiative for Asthma, HFNC¼high-flow nasal cannula, ICS¼inhaled
corticosteroid, MDI¼ metered-dose inhaler, SABA¼short-acting inhaled b2-agonist.

exacerbations requiring systemic corticosteroids, intensive (43)(60) Omalizumab, a monoclonal antibody that binds
care, or intubation), (43)(60) he or she should be referred to to IgE, is recommended for difficult-to-control moderate to
a specialist for treatment of severe asthma. The specialist severe persistent asthma in children 6 years and older with
should evaluate for other diagnoses that mimic asthma elevated IgE counts. (75) In a cohort of inner-city youth aged
(Table 1) before consideration of asthma treatment with 6 to 20 years with uncontrolled persistent asthma and elevated
biological agents (anti-IgE, anti–IL-5, or anti–IL-5a). IgE levels, omalizumab significantly decreased fall

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 exacerbations and improved overall control of asthma. (76) intravenous fluids, or ventilatory support, should be initi-
Mepolizumab (anti–IL-5), (77) benralizumab (anti–IL-5a), ated as needed. A lethargic or agitated child with asthma
(78)(79) and dupilumab (anti–IL-4a) (80) are options for exacerbation may have acidosis from hypercarbia second-
children with eosinophilia (eosinophil count >150 and ary to poor ventilation and would benefit from noninva-
300/mL [0.15 and 0.30109/L], respectively) who are 12 years sive positive pressure support or intubation. In addition,
and older. Early initiation of biological agents in poorly transient hypoxia secondary to ventilation-perfusion
controlled moderate to severe asthma is associated with mismatch is not uncommon after treatment with broncho-
reduced hospitalizations and ED visits for asthma. (81) dilator therapy.
Newer biological agents that target different mediators of ED management of asthma often relies on clinical path-
the inflammatory pathway and other emerging trends are ways using asthma severity scores to expedite initiation of
discussed in Table 4. treatment. (96) Multiple pediatric asthma severity scores
exist, with wide variation in rigor of validation and ability to
Acute Asthma predict response to treatment. (97)(98)(99) Evidence-based
The management of acute asthma includes early and management of acute asthma is discussed in Table 5.
repeated administration of SABA per the individual asthma Pharmacogenetics and Race/Ethnicity. As mentioned
action plan (usually 2–4 puffs inhaled with spacer every 4 previously, Puerto Rican children had the highest asthma
hours in the yellow zone) at the first symptoms of bron- prevalence of any group until 2016, when the prevalence in
chospasm for mild exacerbations. For moderate to severe black children increased to 15.7%. (3) Although it is likely
exacerbations (red zone on the asthma action plan), the multifactorial, there is some evidence of impaired response
typical asthma action plan usually recommends 4 to 8 puffs to SABAs in Puerto Rican children secondary to factors
inhaled with spacer every 15 minutes for 3 doses while on the involving the b2-adrenergic receptor genes. (117) In addi-
way to the ED. High-dose ICS for yellow zone management tion, a small cross-sectional study of children with persistent
of acute asthma is not effective and should not generally be asthma compared response to SABA in Mexican American
recommended. (86)(89) Specific guidelines for prescribing and Puerto Rican children and found improved responsive-
a home supply of emergency oral corticosteroids with ness in Puerto Rican children when an LTRA was added.
specific instructions for use with or without a telephone (118) Further investigation of asthma pharmacogenetics
consultation with a physician do not exist. However, a small comparing children from different ethnic groups may help
study did show decreased ED use in children with moderate address health disparities in asthma.
to severe asthma who had a home supply of emergency oral
corticosteroids. (94)
CONCLUSION
ED management of acute asthma includes prompt sys-
temic corticosteroids and higher doses of SABA mixed with Management of many other chronic diseases has benefited
2 to 3 doses of ipratropium bromide for moderate to severe from a coordinated approach extending beyond the clinic
exacerbations. It is important to assess response to therapy and into the community. Quality improvement efforts
after 1 hour of treatment and if there is no significant should focus on improving outcomes for vulnerable chil-
improvement to consider intravenous magnesium sulfate dren by ensuring adherence to guideline-based therapy,
because this has been shown to reduce risk of hospitaliza- correct assessment of severity and control, and a coordi-
tion. (95) SABA should be continued until there is clinical nated approach to care. Population health approaches and
evidence of reversal of obstruction (decreased respiratory novel therapies showing effectiveness in specific pheno-
effort and rate, improved oxygenation and ventilation) (Tables types present an opportunity to identify at-risk children with
2 and 3). In addition to reversing bronchoconstriction, asthma and to begin to decrease the health disparities in
supportive therapies, including supplemental oxygen, childhood asthma.

564 Pediatrics in Review

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 • Based on moderate recommendation, guideline-based care is
Summary
associated with improved outcomes in asthma. (74)
• Based on observation, health disparities in pediatric asthma exist.
• Based on moderate recommendation, children with moderate
(4) Based on expert opinion, providers should design and
implement quality improvement projects to help bridge the gap. to severe asthma often benefit from treatment with seasonal
(15) escalation of inhaled corticosteroid dose (although not higher
than recommended by the National Asthma Education and
• Based on observation, environmental triggers are a major
Prevention Program guidelines), (43)(85) leukotriene receptor
contributor to health disparities in pediatric asthma. Working to
antagonist (83) or novel immunomodulatory medications (85)
reduce exposure to individual triggers will improve asthma
to reduce fall exacerbations. There seems to be no benefit from
control. (52)(55)
high-dose inhaled corticosteroid use for yellow zone
• Based on observation, complex interactions between a child’s management of acute asthma. (86)(89)
genetic risk, environment (allergen sensitization, exposure to viral
infections), (26) and changes to the airway at the cellular level help
predict disease and target therapy. (31)
• Based on expert opinion, always consider alternative or
concomitant diagnoses in a child with new wheeze or difficult-to-
control asthma. (43)(60) References for this article are at http://pedsinreview.aappub-
lications.org/content/40/11/549.

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improving prevention strategies for childhood asthma in the population you serve with online only at: http://
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2. A 15-month-old girl is seen in the clinic with a 2-day history of upper respiratory tract If you score less than 60%
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weeks’ gestation and was in the nursery for 6 weeks, where she received supplemental will be given additional
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A. Atopic wheezing. Dec. 31, 2021, however, credit
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3. You are developing asthma education materials aimed at parents and school personnel. In
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2019 Pediatrics in Review now
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is approved for a total of 30
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566 Pediatrics in Review

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5. An 8-year-old girl is being evaluated by her primary care physician with pulmonary
function testing before and after bronchodilator administration for a suspected diagnosis
of asthma. Which of the following parameters is most important in the diagnosis and
evaluation of asthma?
A. Closing capacity.
B. Ratio of closing capacity to residual volume.
C. Ratio of forced expiratory volume in 1 second to forced vital capacity.
D. Residual volume.
E. Total lung capacity.

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 Asthma
Shilpa J. Patel and Stephen J. Teach
Pediatrics in Review 2019;40;549
DOI: 10.1542/pir.2018-0282

Updated Information & including high resolution figures, can be found at:
Services http://pedsinreview.aappublications.org/content/40/11/549
References This article cites 99 articles, 17 of which you can access for free at:
http://pedsinreview.aappublications.org/content/40/11/549.full#ref-li
st-1
Subspecialty Collections This article, along with others on similar topics, appears in the
following collection(s):
Critical Care
http://classic.pedsinreview.aappublications.org/cgi/collection/critical
_care_sub
Emergency Medicine
http://classic.pedsinreview.aappublications.org/cgi/collection/emerge
ncy_medicine_sub
Pulmonology
http://classic.pedsinreview.aappublications.org/cgi/collection/pulmo
nology_sub
Asthma
http://classic.pedsinreview.aappublications.org/cgi/collection/asthma
_subtopic
Allergy/Immunology
http://classic.pedsinreview.aappublications.org/cgi/collection/allergy
:immunology_sub
Asthma
http://classic.pedsinreview.aappublications.org/cgi/collection/asthma
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 Asthma
Shilpa J. Patel and Stephen J. Teach
Pediatrics in Review 2019;40;549
DOI: 10.1542/pir.2018-0282

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/content/40/11/549

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