ASTHMA/ANAPHYLAXIS
Educational Objectives
| The goal of this program is to improve the medical management of asthma and anaphylaxis in children. After hearing
and assimilating this program, the clinician will be better able to:
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 | 1. Describe the epidemiology of pediatric asthma.
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| 2. Answer commonly asked questions about asthma diagnosis and management.
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| 3. Describe at least 10 clinical pearls for managing asthma.
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| 4. Identify signs and symptoms of anaphylaxis.
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| 5. Implement appropriate interventions for managing and preventing episodes of anaphylaxis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning
committee reported nothing to disclose.
Acknowledgments
Dr. Schuberth was recorded at the 36th Annual Pediatric Trends, presented April 7-11, 2008, in Baltimore, MD, by
Johns Hopkins Children’s Center and the Office of Continuing Education, Johns Hopkins University School of Medicine;
Dr. Leonard was recorded at Pediatrics for the Primary Care Physician, presented June 27-29, 2008, in Amelia
Island, FL, by Nemours. The Audio-Digest Foundation thanks Drs. Schuberth and Leonard, and the Johns Hopkins
University School of Medicine for their cooperation in the production of this program.
| IMPROVING ASTHMA OUTCOMES —Kenneth C. Schuberth, MD, Associate Professor of Pediatrics, Johns Hopkins
University School of Medicine, Baltimore, MD
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| Epidemiology of pediatric asthma
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| Overview: 80% of cases have onset at <6 yr of age; affects 4% to 10% of population; ratio of affected boys to girls 2:1 (in
adulthood, ratio 1:2); majority of cases involve allergen sensitization; prevalence—increased until mid 1990s; hospitalization
rate—has reached plateau (in some areas, rate declining); mortality—from 1991 to 2004, deaths declined
from 3 per 1 million children per year to 2 to 3 deaths per 1 million; incidence in white population declining (not case
in black population; inner city asthma difficult to treat)
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| Impact by age group: 0 to 4 yr of age—hospitalization rate much higher than in any other age group; usually, first or
second hospitalization for wheezing occurs; death rate lowest; high rate of emergency department (ED) utilization;
5 to 10 yr of age—prevalence and death rate increased slightly; ED visits and hospitalizations decreased; 11 to 17
yr of age—prevalence and death rate up; ED visits and hospitalizations down
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| Inflammatory cascade: allergen exposure to B and T cells; IgE production by plasma cells and attachment to mast
cells; finally, cross-linking of IgE and release of chemicals that drive allergic/anaphylactic process
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| Points of intervention: remove irritant or allergens—cigarette smoke; industrial pollutants; seasonal and perennial
allergens (particularly animals); reduce inflammation—through mast-cell stabilizers and leukotriene antagonists, or
corticosteroids; relieve bronchospasm—through β-agonist therapy; reduce IgE—through allergen immunotherapy
or anti-IgE antibody therapy
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| Phenotypic patterns of early wheezing: transient early wheezers—wheeze before 3 yr of age resolves by 6 yr of
age in two-thirds of patients; nonatopic wheezers—wheezing may start with respiratory syncytial virus (RSV) infection;
prevalence declines with age; IgE-associated wheeze or asthma—prevalence low before 2 yr of age (eventually,
as patients age, prevalence highest in this group)
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| Asthma Predictive Index (API) at age 3 yr: history of early wheezing, plus 1 major or 2 minor criteria, associated
with 60% to 80% risk for persistent asthma; major criteria—history of parental asthma or atopic dermatitis; minor
criteria—allergic rhinitis; wheezing apart from colds; eosinophilia
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| Expert Panel Report 3 (EPR-3) Guidelines for the Diagnosis and Management of Asthma (National
Institutes of Health [NIH]): available at www.nhlbi.gov/guidelines/ asthma; emphasis on reduction of current
impairment and risk for future exacerbations or lung damage; key features—revised pharmacotherapy; use of objective
monitoring tools (eg, Asthma Control Test [ACT] questionnaire, pulmonary function tests [PFTs]); creation of
caregiver-patient alliance
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| Determining severity: components of impairment include symptoms, nighttime awakenings, need for short-acting
β-agonist, and interference with normal activity; risk for future exacerbations based on number of exacerbations requiring
oral systemic steroids in past year
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| Stepwise treatment approach for persistent asthma: 0 to 4 yr of age—1) short-acting β-agonist; 2) low-dose
inhaled corticosteroid (ICS) preferred; alternatives cromolyn and montelukast; 3) medium-dose ICS; 4) add long-
acting β-agonist (LABA) or montelukast; 5) high-dose ICS plus added medications; 6) add oral systemic corticosteroids;
before stepping up therapy, check adherence, inhaler technique, and environmental control measures; ≥12 yr of
age—1) ICS drug of choice at each step; 2) leukotriene receptor antagonists (LTRA), nedocromil, and theophylline
alternatives at each level; 3) add LABA (preferred); 4) step up to medium-dose ICS; 5) consider adding omalizumab
(Xolair) for patients with allergies; 6) add oral corticosteroid; patient education, environmental control, management
of comorbidities important at each step; make same checks in older patients as those described for younger patients
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| Principles of pharmacotherapy: use stepwise approach; provide adequate dosing; control exacerbations quickly
and maintain control for adequate period; taper medications to lowest effective dose; keep therapy as simple as possible
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| ICS options: beclomethasone—available as hydrofluoroalkane (HFA) preparation (Qvar); budesonide—dry powder
or nebulizer solution (eg, Pulmicort); fluticasone—HFA or dry-powder inhaler; mometasone—110 to 220 µg; approved
for children ≥6 yr of age; triamcinolone (eg, Azmacort)—built-in spacer biggest advantage; more steroid side
effects than with other medications
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| Monitoring tools: ACT questionnaire—available at www.asthmacontrol.com; separate forms for patients 4 to 11 yr
of age and those ≥12 yr of age; 5 questions (1-5 points each); score ≤19 means patient needs help; simple effective
tool; PFTs—caveat (peak flow monitoring significantly effort-dependent); spirometry helpful
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| Indications for adding controller therapy in infants: significant exacerbations (hospital visit or flare) within 6 wk; or, 3
episodes of wheezing and positive API
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| Choice of initial controller therapy for mild persistent asthma: guidelines recommend ICS, but many physicians use
LTRA (montelukast [Singulair]); selection depends on setting (some patients respond better to Singulair than to ICS);
indications for ICS—reduced pulmonary function; high levels of immunologic markers indicating allergy; positive
skin tests for many allergens; children without those features may go on either therapy for short trial
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| Do inhaled steroids prevent lung remodeling and decline of lung function? no; study—children ≈2 yr of age with
wheezing episodes; study group given inhaled fluticasone for 2 yr (controls treated as needed); treated group did
well while on medication, but when drug discontinued, lung status deteriorated quickly to that of controls
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| Do inhaled steroids influence growth? yes, transiently (not long term); in first 6 mo, slowing of growth rate minimal in
majority of patients (≤1 cm); Childhood Asthma Management Program (CAMP) study, 2000—subjects treated
with budesonide, nedocromil, or placebo; budesonide group had slower growth rate, but exceeded that of other
groups by end of study; conclusion—no long-term changes with use of ICS
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| Is regular β-agonist use dangerous? daily use of short-acting β-agonists not harmful, but may be indicator of uncontrolled
asthma; combined steroid and LABA—eg, fluticasone and salmeterol (Advair), budesonide and formoterol
(Symbicort) probably safe in children, but use caution
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| Top 10 tips to improve asthma outcomes
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| 10. Make sure diagnosis correct: differential diagnosis—cystic fibrosis (CF), immunodeficiency; sinusitis; anatomic
defect (eg, vascular ring); exercise hyperventilation
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| 9. Treat coexisting conditions: eg, sinusitis, adenoiditis, allergic rhinitis, gastroesophageal reflux
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| 8. Review environmental factors and consider allergy testing
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| 7. Assess patient knowledge and provide education
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| 6. Assess social and emotional environment: affects adherence; refill rates for controller medications low
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| 5. Provide written care plan, and make sure patient understands it
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| 4. Assess asthma control using, eg, ACT questionnaire, PFTs
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| 3. Observe and assess inhalation technique and demonstrate proper use
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| 2. Assess adherence (consider checking pharmacy records)
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| 1. Follow up at least monthly until asthma controlled, and at least every 3 mo thereafter (provides good picture of patient’s
status); with appropriate care, patients healthier and happier
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| ANAPHYLAXIS: MANAGEMENT AND PREVENTION —Sharon E. Leonard, MD, Staff Physician, Department of
Pediatrics, Division of Pediatric Allergy and Immunology, Nemours Children’s Clinic, Jacksonville, FL
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Diagnosis
| Defining anaphylaxis: no universally accepted definition; symptomatology—respiratory symptoms (wheezing,
shortness of breath); hypotension; angioedema of lips and tongue; hives; vomiting, diarrhea; pathophysiology—once
initial sensitization occurs, mast cell armed with IgE receptor; upon second presentation of antigen, IgE antibody
cross-links and mast cell degranulates, releasing internal components (mainly histamine and tryptase) causing symptoms
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| Epidemiology of anaphylaxis: difficult to study (no universal definition); 50 to 2000 episodes/100,000 people; lifetime
prevalence 0.05% to 2.0%; mortality—1500 to 2000 deaths/yr; causes include shock, asphyxia, disseminated intravascular
coagulation (DIC), and epinephrine (eg, EpiPen) overdose
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| Etiology: Kemp, 1995—266 patients 12 to 75 yr of age; largest group idiopathic (cause not determined); 34% caused
by foods; drugs, 20%; 7% exercise-induced; smaller percentage due to latex, hormones, and other causes; distribution
varies by population; Dibs, 1997—50 children 1 to 19 yr of age; large increase in latex allergy from 1978 to 1992, but
study population skewed (facility had large percentage of patients with, eg, spina bifida); 18% drug associated; 13%
idiopathic; 25% food-induced; 15% caused by venom; anaphylaxis due to poison ivy rare
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| Signs and symptoms of anaphylaxis: cutaneous findings—most common (>95% of cases); urticaria and angioedema;
flushing; pruritus without rash; respiratory symptoms—50% to 60% of cases; includes upper airway angioedema;
dizziness, syncope, hypotension, blurred vision—30% to 35%; abdominal findings—20% to 30%
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| Differential diagnosis: vasovagal reactions; flushing syndromes—carcinoid syndrome; vasointestinal polypeptide-
secreting tumors; “restaurant syndromes”—scombroidosis (rancid fish releases histamine); excess endogenous production
of histamine—systemic mastocytosis; patients can present with recurrent anaphylaxis; nonorganic
disease—panic attacks; miscellaneous—hereditary angioedema
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| Laboratory tests: most cases of anaphylaxis diagnosed via history and symptoms; total tryptase—most important
test in immediate phase; tryptase elevated in first 50 to 60 min and remains high for 4 to 6 hr; mature tryptase— β-
tryptase present during anaphylaxis (α-tryptase elevated in systemic mastocytosis only); histamine—not very useful
(returns to baseline within 30-40 min); detected acutely in urine or ≤24 hr later through metabolic breakdown components
of histamine; aids to differential diagnosis—consider measurement of urinary vanillylmandelic acid (VMA) or
serum vasointestinal polypeptide (VIP) levels
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| Biphasic reactions: incidence ≤20%—more common when antigen is food; may result from inadequate or delayed
dose of epinephrine; manifestations can be identical to, worse than, or less severe than initial phase; associated
fatalities—most occur ≤8 hr after resolution of first event, but some recorded ≤72 hr after first event (controversial);
no way to predict who will have biphasic reaction
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Treatment
| Acute management: check airway, breathing, and circulation (ABCs); check vital signs; administer epinephrine immediately;
administer oxygen (if needed); place patient in supine position with feet elevated; if response good, observe
2 hr before discharge; if response incomplete, epinephrine can be readministered every 10 to 15 min, up to 3 to 5
doses; if cutaneous symptoms present, give H1 - or H2 -receptor antagonist and consider steroids (frequently used to
prevent biphasic reaction; no studies to support); if patient wheezing, bronchodilators; if hypotensive, fluids and vasopressors;
patient on β-blockers may be resistant to epinephrine (may need glucagon or atropine)
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| Trendelenburg’s position: prevents empty ventricle syndrome (if syndrome occurs, epinephrine not helpful); Pumphrey,
2003—reviewed 214 deaths due to anaphylaxis; majority of deaths due to shock occurred after shifting from supine
to upright position, causing empty ventricle syndrome; if anaphylaxis occurs, lay patient down immediately, with feet
elevated (if episode occurs at school, send someone other than patient to nurse’s office to retrieve epinephrine)
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| Epinephrine: pediatric dose 0.01 mg/kg up to 0.30 mg of 1:1000 formulation (repeatable every 10-20 min); risks for
side effects increased in those with hypertension, arteriopathies, or ischemic heart disease (diseases of adulthood); no
absolute contraindications
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Specific Etiologies
| Evaluation: history most important component; ancillary tests include—skin testing; specific IgE antibodies; challenges;
other laboratory tests
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| Food-induced anaphylaxis: allergy to foods increased over past 2 decades; peanut allergy—incidence has doubled
(allergenicity of roasted forms increased); possibly related to early feeding when immune system immature or use of
topical ointments containing peanut; 80% of patients maintain sensitivity throughout life; more tips—allergies to tree
nuts, fish, and shellfish also persist; patients often outgrow allergy to milk, egg, and soybean (80% outgrow by 5 yr of
age; may take up to 12 to 13 yr of age); patient education and prescription for epinephrine (eg, EpiPen) essential
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| Natural latex rubber (NLR) allergy: prevalence markedly increased in past 15 yr; risk factors—presence of neural
tube defects; multiple surgeries increase exposure to latex gloves (health care workers also at increased risk);
atopy; preexisting hand dermatitis risk factor for occupational sensitization; laboratory testing—IgE-specific test (if
positive, prescription avoidance); cross-reactivity with banana, avocado, kiwi, and chestnut
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| Exercise-induced anaphylaxis: physical allergy that involves direct activation of mast cell; can occur with mild to
vigorous exercise; often associated with ingestion of specific food (eg, celery) or medication (however, mechanism
not IgE mediated); exercise not recommended 1 hr before or 4 hr after eating; antihistamines generally not helpful;
ephinephrine (EpiPen) and exercise partner recommended
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| Drug-induced anaphylaxis: penicillin—most common cause, but also overreported; aztreonam does not cross-react
with penicillin; nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin—second most common cause
(medication-specific); radiocontrast media—common cause of anaphylactoid reactions (incidence decreased with
lower osmolality); pretreatment with prednisone, diphenhydramine (eg, Benadryl), and ephedrine effective
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| Venom-induced anaphylaxis: causes 40 to 50 deaths/yr; treated effectively in >95% of cases with immunotherapy
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| Idiopathic anaphylaxis: represents majority of cases; may be due to autoantibody to IgE; may require steroids every
other day to manage frequent life-threatening reactions
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Prevention and Management
| Strategies: avoidance and education; pharmacologic prophylaxis; self-injectable epinephrine; medical alert jewelry;
immunotherapy; desensitization
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| Auto-injectable devices: life-saving tools; must be prescribed with instruction in correct use—in data from several
studies, only 40% to 71% of patients had nonexpired device; two-thirds used epinephrine for inappropriate indications
(including exposure without symptoms, isolated hives, or large local reaction); 7% to 44% would not give
epinephrine for shortness of breath or difficulty breathing; only 64% to 98% called 911 or went to ED after injection;
medical professionals—25% described or demonstrated proper technique; 35% gave patients instructions; specific
products Twinject, EpiPen (dose 0.15 or 0.30 mg); better education needed for medical professionals, patients, and
community
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Suggested Reading
[No authors listed]: Long-term effects of budesonide or nedocromil in children with asthma. The Childhood Asthma Management
Program Research Group. N Engl J Med 343:1054, 2000; Bacharier LB et al: Diagnosis and treatment of asthma in
childhood: a PRACTALL consensus report. Allergy 63:5, 2008; Dibs SD, Baker MD: Anaphylaxis in children: a 5-year experience.
Pediatrics 99:E7, 1997; Kemp SF et al: Anaphylaxis. A review of 266 cases. Arch Intern Med 155:1749, 1995;
Sampson HA: Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol
107:891, 2001; Szefler SJ et al: Characterization of within-subject responses to fluticasone and montelukast in childhood
asthma. J Allergy Clin Immunol 115:233, 2005; Urbano FL: Review of the NAEPP 2007 Expert Panel Report (EPR-3) on
Asthma Diagnosis and Treatment Guidelines. J Manag Care Pharm 14:41, 2008.
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