Asthma 169

yr, African Americans, women, and persons

BASIC INFORMATION below the poverty level.
-
BOX 1 Risk Factors for Severe
and Fatal Asthma in A
DEFINITION tions and 1.8 million emergency department Adults
The National Asthma Education and Prevention visits yearly in the U.S.
Program (NAEPP) guidelines define asthma as
“a chronic inflammatory disease of the airways closing because of a rapid increase in adult-
in which many cells and cellular elements play
a role: in particular mast cells, neutrophils, adults).
eosinophils, T lymphocytes, macrophages, and
epithelial cells. In susceptible individuals, this symptoms before 5 yr of age. Early childhood
inflammation causes recurrent episodes of risk factors for asthma are described in Table 1.

and Disorders
Diseases
coughing (particularly at night or early in the
morning), wheezing, breathlessness, and chest slightly improved to 11 per 1 million persons.
tightness. The episodes are usually associated
with widespread but variable airflow obstruc- asthma. An increase in prevalence to 400
tion that is reversible either spontaneously or million is anticipated by 2025.
as a result of treatment.” Status asthmaticus, Box 1 summarizes risk factors for severe and
or acute severe asthma, is a refractory state
that does not respond to standard therapy such
fatal asthma in adults.
I
PHYSICAL FINDINGS & CLINICAL
as inhaled beta-agonists or subcutaneous epi-
PRESENTATION
nephrine. It may persist for several hours.
Physical examination varies with the stage and
SYNONYMS severity of asthma and may reveal normal lung
Bronchospasm examination results in many patients. However,
Reactive airway disease some degree of wheezing and prolonged expira- -
Asthmatic bronchitis tory phases of respiration are seen with persis-
tent or acute disease. Box 2 summarizes signs
and symptoms of severe asthma. Physical exam-
From Parrillo JE, Dellinger RP: Critical care medicine,
ICD-10CM CODES ination during status asthmaticus may reveal: principles of diagnosis and management in the adult,
J45.20 Mild intermittent asthma, ed 5, Philadelphia, 2019, Elsevier.
uncomplicated
J45.21 Mild intermittent asthma with -
(acute) exacerbation tolic blood pressure >10 mm Hg)
J45.22 Mild intermittent asthma with
status asthmaticus decreased wheezing can indicate worsening BOX 2 Signs and Symptoms of
J45.30 Mild persistent asthma, obstruction Severe Asthma
uncomplicated
J45.31 Mild persistent asthma with to hypoxia and hypercapnia and constitute an
(acute) exacerbation indication for urgent intubation
J45.32 Mild persistent asthma with status
asthmaticus movement on inspiration (detected by palpa-
J45.40 Moderate persistent asthma, tion over the upper part of the abdomen in a
uncomplicated semirecumbent position) indicates diaphrag-
J45.41 Moderate persistent asthma with matic fatigue, another sign of impending -
(acute) exacerbation respiratory crisis -
J45.42 Moderate persistent asthma with
status asthmaticus
J45.50 Severe persistent asthma, TABLE 1 Early Childhood Risk *
uncomplicated -
Factors for Persistent Asthma *
J45.51 Severe persistent asthma with
(acute) exacerbation Parental asthma
J45.52 Severe persistent asthma with Allergy:
status asthmaticus Atopic dermatitis (eczema)
J45.901 Unspecified asthma with (acute) Allergic rhinitis
Food allergy
exacerbation
Inhalant allergen sensitization
J45.902 Unspecified asthma with status Food allergen sensitization
asthmaticus Severe lower respiratory tract infection:
J45.909 Unspecified asthma, Pneumonia
uncomplicated Bronchiolitis requiring hospitalization
J45.991 Cough variant asthma Wheezing apart from colds
J45.998 Other asthma Male gender
Low birthweight
Environmental tobacco smoke exposure
EPIDEMIOLOGY & Possible use of acetaminophen (paracetamol)
*These values are estimations because both peak
expiratory flow rate and forced expiratory volume in
DEMOGRAPHICS Exposure to chlorinated swimming pools 1 second (FEV1) vary with age, gender, and height.
Reduced lung function at birth From Parrillo JE, Dellinger RP: Critical care medicine,
population in the U.S., and its prevalence is principles of diagnosis and management in the adult,
From Kliegman RM et al: Nelson textbook of pediatrics, ed 19, ed 5, Philadelphia, 2019, Elsevier.
steadily rising among patients older than 65 Philadelphia, 2011, WB Saunders.
170 Asthma
recommended for prevention of allergies or group is characterized by eosinophilia, and
indicative of severe asthma: asthma. IL-5 is felt to be the most specific cytokine in
1. Pulsus paradoxus >18 mm Hg eosinophil regulatory pathways.
2. Respiratory rate >30 breaths/min with n-3 long-chain polyunsaturated fatty
3. Tachycardia with heart rate >120 beats/ acids (LCPUFAs, fish oil-derived fatty acids) in
min the third trimester of pregnancy reduced the
DIAGNOSIS
absolute risk of persistent wheeze or asthma
ETIOLOGY and infections of the lower respiratory tract DIFFERENTIAL DIAGNOSIS

complex interaction among various environ- points, or one third.1

-
notypic associations in asthma are described manifests as adult-onset asthma in response
in Box 3. to respiratory tract infection or psychological
stress. infections
various aeroallergens or nonspecific (e.g.,
dust, cigarette smoke, fumes, cold air, exer- nonorganic agents can trigger asthma. younger patients)
cise) exposures in patients who are prone to
develop IgE antibodies in response to various contribute to the risk of developing asthma
exposures. The pathogenesis of antigen- and that remediation of these in homes
induced asthma is illustrated in Fig. 1. reduces asthma symptoms and medication
use in adults.
that maternal intake of foods commonly - patients)
considered allergenic (peanut and milk) quently in adolescents and manifests with
was associated with a decrease in allergy bronchospasm after beginning of exer- WORKUP
and asthma in the offspring. No dietary cise and improves with discontinuation of
changes during pregnancy are therefore exercise. of airway obstruction and some degree of
reversibility of the obstruction, if and when
β-blockers, sulfites, and certain patient can participate.
BOX 3 Genetic and Phenotypic foods and beverages.
Associations in Asthma ADAM >5 yr who can perform spirometry, pre- and
33 gene with asthma and bronchial hyper- postbronchodilator spirometry is the recom-
ADAM33: mended test of choice.
ORMDL3/GSDMB responsiveness. Experimental, genetic, and
clinical studies support an important role for
ACSL3: Th2 immune pathways in the pathogenesis forced expiratory volume in 1 sec (FEV1 by at
- of severe asthma. Th2 cells are stimulated
by dendritic cells to produce IL-5, IL-13, and a short bronchodilator.
IL33 IL-4, the latter driving IgE synthesis. This -
IL2RB rometry correlates with airway inflammation,
1Bisgaard H et al: Fish oil-derived fatty acids in preg- and patients with a high degree of reversibil-
From Parrillo JE, Dellinger RP: Critical care medicine,
principles of diagnosis and management in the adult, nancy and wheeze and asthma in offspring, N Engl J ity have a greater risk of irreversible airflow
ed 5, Philadelphia, 2019, Elsevier. Med obstruction in subsequent years.

Local reflexes
(tachykinins)

Bronchoconstriction Cholinergic
stimulation

IgE-coated Mediator Mucous Irritant receptor

Ag +
mast cell release secretion stimulation

Airway inflammation Epithelial

(especially with late- injury
Recruitment of phase response)
eosinophils,
lymphocytes
Nonspecific bronchial
Chemoattractant hyperresponsiveness
cytokines

Increased epithelial
permeability to antigens

FIG. 1 Schematic diagram of events in pathogenesis of antigen-induced asthma. A hypothetical

series of complex interactions is shown, focusing on bronchoconstriction, mucus secretion, and airway inflam-
mation. Ag, Antigen; IgE, immunoglobulin E. (From Weinberger SE: Principles of pulmonary medicine,
Philadelphia, 2019, Elsevier.)
 Asthma 171

-
ally not feasible. Young children with asthma
symptoms should be treated as having sus-
clinical management should gear toward
achievement of asthma control. The level of
shift may indicate the existence of bacterial
infection. Elevated eosinophils point toward A
pected asthma after alternative diagnoses asthma control should be used to guide deci- allergic component of asthma.
are ruled out. sions either to maintain or adjust therapy.
assessment and at least every 1 to 2
asthma. Patients with high clinical suspi- patients who are just starting therapy or yr after treatment is initiated and when
cion should undergo bronchial challenge who require a step up in therapy to achieve the symptoms and peak expiratory flow
test using methacholine or other specific or regain asthma control. Schedule visits at have stabilized. Spirometry as a monitor-
agents. 6- to 12-mo intervals, after asthma control ing measure may be performed more
- is achieved, to monitor whether asthma con- frequently, if indicated, based on sever-
mental causes (e.g., house dust mites, indoor trol is maintained. The interval will depend ity of symptoms and the disease’s lack of
pets) and exposure to other allergens such on factors such as the duration of asthma response to treatment.

and Disorders
Diseases
as tobacco smoke. The degree of reversibility control or the level of treatment required.
measured by spirometry correlates with air- Consider scheduling visits at 3-mo intervals to assess severity of an acute exacerbation
way inflammation, and patients with a high if step-down therapy is anticipated. episode. Value should be compared with indi-
degree of reversibility have a greater risk of vidual’s personal best number (see asthma
irreversible airflow obstruction in subsequent LABORATORY TESTS action plan).
years.
-
Laboratory tests are usually not necessary and
the results can be normal if obtained during a patients with severe persistent asthma, and I
ity of peak flow measurements by a handheld stable period. they also help monitor response to treatment
device can be used to diagnose asthma. in the same group.
Fig. E2 describes an algorithm for diagnosing during acute bronchospasm in staging the
asthma. severity of an asthmatic attack: subgroup of patients.
After diagnosis, the severity of asthma should O2 and PaCO2, increased
be classified during the initial assessment pH IMAGING STUDIES
before initiating therapy. Patients are divided O2, normal PaCO2, -
into four groups based on the severity of their normal pH dence of thoracic hyperinflation (e.g., flatten-
asthma symptoms and number of exacerbations 3. Severe: Marked decreased PaO2, ing of the diaphragm, increased volume over
(see Table 2). increased PaCO2, and decreased pH the retrosternal air space).

TABLE 2 Classifying Asthma Severity and Initiating Treatment in Youths ≥12 Yr and Adults (Assessing severity and
initiating treatment for patients who are not currently taking long-term control medications)
CLASSIFICATION OF ASTHMA SEVERITY (≥12 YR)
PERSISTENT
Components of Severity Intermittent Mild Moderate Severe
Impairment Symptoms ≤2 days/wk >2 days/wk but not daily Throughout the day
Normal FEV1/ Nighttime awakenings ≤2x/mo 3-4x/mo >1x/wk but not nightly
Short-acting beta2-agonist ≤2 days/wk >2 days/wk but not daily, Several times per day
use for symptom control and not more than 1x
(not prevention of EIB) on any day
Interference with normal None Minor limitation Some limitation Extremely limited
activity
Lung function Normal FEV1 between
exacerbations
FEV1 FEV1 FEV1 FEV1
predicted
FEV1/FVC normal FEV1/FVC normal FEV1 FEV1
Risk Exacerbations 0-1 per yr ≥2 per yr
requiring oral systemic Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients
corticosteroids in any severity category.
Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Therapy Step 1 Step 2 Step 3 Step 4 or 5
and consider short course of oral systemic cortico-
steroids
In 2-6 wk, evaluate level of asthma control that is achieved and adjust therapy accordingly.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of previous 2 to 4 wk and spirometry. Assign severity to the most
severe category in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations (e.g., requiring urgent,
unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids
in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
To access the complete Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, go to www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
EIB, Exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care unit.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood
172 Asthma
GENERAL Rx long-acting beta-agonist (LABA), combination of
changes are common during an asthma Tables 2 to 10) inhaled steroids and LABA, leukotriene receptor
attack; may also show cor pulmonale, right provide treatment options by age groups: 0 to 4 antagonist (LTRA), cromolyn, zileuton, and the-
bundle branch block, right axial deviation, yr, 5 to 11 yr, and >12 yr. A step-up approach is ophylline. Oral corticosteroids are reserved as a
counterclockwise rotation. described based on the severity of symptoms. last resort for maintenance therapy for recalci-
An approach to home management of acute trant cases. Various studies have showed some
degree of benefit when adding LAMA to ICS +
TREATMENT asthma is described in Fig. E3. Short-acting
LABA in moderate to severe asthma. There are
beta-selective adrenergic agonists (SABAs)
administered by inhalation is the most effective several corticosteroid/LABA combination inhal-
NONPHARMACOLOGIC THERAPY ers available (fluticasone/salmeterol [Advair],
therapy for quick relief of asthmatic symptoms.
- They are recommended for use only as needed budesonide/formoterol [Symbicort], mometa-
lates, sulfites), environmental or occupational for relief of symptoms or before anticipated -
triggers exposure to known triggers such as exercise. casone furoate 200 mcg and vilanterol 25 mcg
They should not be use as a single agent inhalation powder [Breo Ellipta]) on the market.
swimming) except for intermittent asthma symptoms. When None of these combinations is indicated for the
symptoms become more frequent or more initial treatment of asthma or for acute therapy
of an attack and proper use of medications severe, step-up treatment with maintenance of asthma symptoms. There is no evidence that
(e.g., correct use of inhalers) inhalers is recommended (see Table 4). Inhaled one product is more effective than the others.
steroid is the mainstay of treatment for mainte- A large study investigating the safety of LABA
questionnaires nance therapy. Other treatment options include and ICS combination inhalers confirmed their

TABLE 3 Assessing Asthma Control and Adjusting Therapy in Youths ≥12 Yr and Adults
CLASSIFICATION OF ASTHMA CONTROL (≥12 YR)
Components of Control Well Controlled Not Well Controlled Very Poorly Controlled
Impairment Symptoms ≤2 days/wk >2 days/wk Throughout the day
Nighttime awakenings ≤2×/mo 1-3x/wk ≥4/wk
Interference with normal activity None Some limitation Extremely limited
Short-acting beta2-agonist use for ≤2 days/wk >2 days/wk Several times per day
symptom control (not preven-
tion of EIB)
FEV1 or peak flow -
sonal best personal best
Validated questionnaires
ATAQ 0 1-2 3-4
ACQ ≤ * ≥1.5 N/A
ACT™ ≥20 16-19 ≤15
Risk Exacerbations requiring oral sys- 0-1 per yr ≥2 per yr
temic corticosteroids Consider severity and interval since last exacerbation
Progressive loss of lung function Evaluation requires long-term follow-up care
Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of inten-
sity does not correlate to specific levels of control but should be considered in the overall assessment of risk.
Recommended Action for Treatment Maintain current step. Step up 1 step and Consider short course of oral systemic corticoste-
Regular follow-up every reevaluate in 2-6 wk. roids.
1-6 mo to maintain For side effects, con- Step up 1-2 steps.
control. sider alternative Reevaluate in 2 wk.
Consider step down if treatment options. For side effects, consider alternative treatment
well controlled for at options.
least 3 mo.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient’s recall of previous 2 to 4 wk and by spirometry or peak flow measures.
Symptom assessment for longer periods should reflect a global assessment, such as inquiring whether the patient’s asthma is better or worse since the last visit.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent,
unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past
year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma.
Validated questionnaires for the impairment domain (the questionnaires do not assess lung function or the risk domain):
ATAQ = Asthma Therapy Assessment Questionnaire
ACQ = Asthma Control Questionnaire (user package may be obtained at www.qoltech.co.uk or [email protected])
ACT = Asthma Control Test™

Before step up in therapy:

Review adherence to medication, inhaler technique, environmental control, and comorbid conditions
If an alternative treatment option was used in a step, discontinue and use the preferred treatment for that step
EIB, Exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; ICU, intensive care unit.
The Asthma Control Test is a trademark of QualityMetric Incorporated.

From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood
 Asthma 173

long-term safety and demonstrated a reduced thigh, or abdomen, 100 mg every 4 weeks.
risk of exacerbations and improved lung func-
tion, when compared with an equivalent dose
Hypersensitivity reactions have been reported
with mepolizumab. In addition, herpes zoster
Other adverse events include headache and
pharyngitis. A
of ICS alone. infections have led to the recommendation of -
the administration of the varicella zoster vac- body, is indicated for the treatment of mod-
IMMUNOLOGIC TARGETS cine to adults ages 50 or older 4 weeks prior erate and severe persistent asthma with
to initiation of mepolizumab (unless they are elevated IgE level, which is refractory to other
at risk for disseminated zoster). treatment noted earlier. It is administered
yr or older with moderate to severe asthma subcutaneously every 2 or 4 wk.
with an eosinophilic phenotype or with oral antibody, has a similar indication for eosino-
corticosteroid–dependent asthma. philic asthma and uses a higher eosinophil BRONCHIAL THERMOPLASTY
cutoff (400) based on a greater predictive Selected patients with severe persistent asthma
value for sputum eosinophilia. Benralizumab, who have failed medical treatment may benefit

and Disorders
Diseases
add-on for patients aged ≥12 yr with severe a monoclonal anti-IL5 receptor alpha anti- from bronchial thermoplasty. This requires the
eosinophilic asthma that is uncontrolled on insertion of a catheter via bronchoscopy and
Step 4 treatment. Mepolizumab is a monoclo- treatment to consider for patients 12 yr use of radiofrequency heat to reduce bron-
nal antibody to IL-5 that has been shown to or older with persistent severe eosinophilic chial smooth muscle. Long-term follow-up data
reduce exacerbations in patients with severe asthma. It is administered as a subcutaneous showed persistent reduction in asthma exacer-
asthma who have blood eosinophil counts of
150/µL or greater. Mepolizumab is admin-
injection every 4 wk for the first 3 doses then
every 8 wk after that. Hypersensitivity reac- I
istered subcutaneously into the upper arm, tions are more common than other anti-IL-5 inadequately controlled on ICS + LABA.”

TABLE 4 Stepwise Approach for Managing Asthma in Youths ≥12 Yr and Adults

Intermittent Persistent Asthma: Daily Medication

Asthma Consult with asthma specialist if step 4 care or higher is required. Consider consultation at step 3.

Step 6
Step 5 Step up if needed
Preferred:
Step 4
Preferred: S
Step 3 S A (first, check
Preferred:
Step 2 A oral adherence,
Preferred: environmental
AND corticosteroid
Preferred: control, and
Consider AND comorbid
OR Alternative:
omalizumab Consider conditions
S
Alternative: for patients who omalizumab
either LTRA,
Cromolyn, LTRA, have allergies for patients who Assess
theophylline,
Step 1 nedocromil, Alternative: have allergies control
or zileuton
or theophylline
Preferred: either LTRA, Step down
n theophylline, if possible
or zileuton
(and asthma is
well controlled
Each step: Patient education, environmental control, and management of comorbidities at least 3 months
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma

Quick-Relief Medication for All Patients

intervals as needed. Short course of oral systemic corticosteroids may be needed.

to step up treatment.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.
Zileuton is a less desirable alternative due to limited studies as adjunctive therapy and the need to monitor liver function. Theophylline requires monitoring of serum concentration levels. In step 6, before
oral systemic corticosteroids are introduced, a trial of high-dose ICS + LABA + either LTRA, theophylline, or zileuton may be considered, although this approach has not been studied in clinical trials.

Immunotherapy for steps 2 to 4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immu-
notherapy with single allergens. The role of allergy in asthma is greater in children than in adults.
Clinicians who administer immunotherapy or omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur.
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma and is not intended to promote or endorse any of the
listed products.
To access the complete Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, go to www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
EIB, Exercise-induced bronchospasm; ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; LTRA, leukotriene receptor antagonist; prn, as necessary; SABA, inhaled short-acting beta2-
agonist.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood
 TABLE 5 Classifying Asthma Severity and Initiating Treatment in Children 5-11 Yr (Assessing severity and initiating
treatment in children who are not currently taking long-term control medications)
CLASSIFICATION OF ASTHMA SEVERITY (5-11 YR OF AGE)
PERSISTENT
Components of Severity Intermittent Mild Moderate Severe
Impairment Symptoms ≤2 days/wk >2 days/wk but not daily Throughout the day
Nighttime awakenings ≤23/mo 3-4×/mo >1×/wk but not nightly
Short-acting beta2-agonist ≤2 days/wk >2 days/wk but not Several times per day
use for symptom control daily
(not prevention of EIB)
Interference with normal None Minor limitation Some limitation Extremely limited
activity
Lung function Normal FEV1 between
exacerbations
FEV1 FEV1 FEV1 FEV1
FEV1 FEV1 FEV1 FEV1
Risk Exacerbations requiring 0-1 per yr ≥2 per yr
oral systemic cortico- Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients
steroids in any severity category.
Relative annual risk of exacerbations may be related to FEV1.
Recommended Step for Initiating Therapy Step 1 Step 2 Step 3, medium-dose Step 3, medium-dose ICS option,
ICS option or Step 4
and consider short course of oral systemic corticosteroids
In 2-6 wk, evaluate level of asthma control that is achieved and adjust therapy accordingly.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
Level of severity is determined by both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of previous 2 to 4 wk and spirometry. Assign severity to the most severe category
in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations (e.g., requiring urgent,
unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids
in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
EIB, Exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICS, inhaled corticosteroid; ICU, intensive care unit.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood

TABLE 6 Assessing Asthma Control and Adjusting Therapy in Children 5-11 Yr

CLASSIFICATION OF ASTHMA CONTROL (5-11 YR OF AGE)
Components of Control Well Controlled Not Well Controlled Very Poorly Controlled
Impairment Symptoms ≤2 days/wk but not more than >2 days/wk or multiple Throughout the day
once on each day times on ≤2 days/wk
Nighttime awakenings ≤1×/mo ≥2×/mo ≥2×/wk
Interference with normal activity None Some limitation Extremely limited
Short-acting beta2-agonist use for symp- ≤2 days/wk >2 days/wk Several times per day
tom control (not prevention of EIB)
Lung function
FEV1 or peak flow -
sonal best
FEV1/FVC
Risk Exacerbations requiring oral systemic 0-1 per yr ≥2 per yr
corticosteroids Consider severity and interval since last exacerbation
Reduction in lung growth Evaluation requires long-term follow-up care
Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The
level of intensity does not correlate to specific levels of control but should be considered in the
overall assessment of risk.
Recommended Action for Treatment Maintain current step. Step up 1 step and reevalu- Consider short course of oral sys-
Regular follow-up every 1-6 ate in 2-6 wk. temic corticosteroids.
mo. For side effects, consider Step up 1-2 steps.
Consider step down if well con- alternative treatment Reevaluate in 2 wk.
trolled for at least 3 mo. options. For side effects, consider alterna-
tive treatment options.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
The level of control is based on the most severe impairment or risk category. Assess impairment domain by patient’s/caregiver’s recall of previous 2 to 4 wk and by spirometry or peak flow measures.
Symptom assessment for longer periods should reflect a global assessment such as inquiring whether the patient’s asthma is better or worse since the last visit.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent,
unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past
year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
Before step up in therapy:
Review adherence to medications, inhaler technique, environmental control, and comorbid conditions.
If an alternative treatment option was used in a step, discontinue it and use preferred treatment for that step.
EIB, Exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care unit.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood
 Asthma 175

TABLE 7 Stepwise Approach for Managing Asthma in Children 5-11 Yr

A
Intermittent Persistent Asthma: Daily Medication
Asthma Consult with asthma specialist if step 4 care or higher is required. Consider consultation at step 3.

Step 6
Step 5 Step up if needed
Preferred:
Step 4
Preferred: High-dose (first, check
Step 3
Preferred: adherence, inhaler
Step 2 Preferred: Medium-dose oral technique,
corticosteroid

and Disorders
Diseases
environmental
Preferred: Alternative: control, and
LTRA, or Alternative: Alternative: comorbid
theophylline either LTRA or
Alternative: theophylline either LTRA or
either LTRA or
Cromolyn, LTRA, theophylline
OR theophylline Assess
Step 1 nedocromil, oral systemic control
Preferred:
n
or theophylline
Medium-dose corticosteroid
Step down
I
if possible

(and asthma is well

controlled at least
Each step: Patient education, environmental control, and management of comorbidities
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have allergic asthma

Quick-Relief Medication for All Patients

intervals as needed. Short course of oral systemic corticosteroids may be needed.

inadequate control and the need to step up treatment.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
If alternative treatment is used and response is inadequate, discontinue it and use the preferred treatment before stepping up.
Theophylline is a less desirable alternative due to the need to monitor serum concentration levels.
Step 1 and step 2 medications are based on Evidence A. Step 3 ICS 1 adjunctive therapy and ICS are based on Evidence B for efficacy of each treatment and extrapolation from comparator trials in older
children and adults—comparator trials are not available for this age group; steps 4-6 are based on expert opinion and extrapolation from studies in older children and adults. Immunotherapy for steps
2 to 4 is based on Evidence B for house-dust mites, animal danders, and pollens; evidence is weak or lacking for molds and cockroaches. Evidence is strongest for immunotherapy with single allergens.
The role of allergy in asthma is greater in children than in adults. Clinicians who administer immunotherapy should be prepared and equipped to identify and treat anaphylaxis that may occur.
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma and is not intended to promote or endorse any of the
listed products.
EIB, Exercise-induced bronchoconstriction; ICS, inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; LTRA, leukotriene receptor antagonist; prn, as necessary; SABA, inhaled short-acting
beta2-agonist.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood

OTHER MEDICATIONS tions. More data are needed, but this result sug-
Tiotropium (Spiriva) has been used for gests azithromycin may be an effective option
and documented sensitivity to a perennial
LAMA is now approved for a second indication also neutrophilic). allergen, recommend adding omalizumab.
for the treatment of asthma and is included in Immunosuppressants such as methotrexate
can decrease long-term steroid requirements; exacerbations, and an eosinophilic pheno-
however, they have significant side effects, and type despite guideline-based therapy, con-
on at step 4. A systematic review including there is no evidence of persistent therapeutic sider add-on therapy with one of the anti-
effect after discontinuing them. interleukin (IL)-5 antibodies, mepolizumab,
LAMA compared with placebo as an add-on to reslizumab, or benralizumab.
inhaled corticosteroids was associated with TREATMENT OF SEVERE ASTHMA
lower risk of exacerbation. Adding LAMA to (ETS/ETA GUIDELINES) in selected adults with severe asthma that
a dual LABA-ICS regimen was not shown to - is not well controlled with inhaled glucocorti-
reduce exacerbation rates but can improve cation of “severe asthma” refers to patients coids and LABAs.
lung function. who require high-dose inhaled or near- -
Azithromycin: The AZISAST Trial randomized continuous oral glucocorticoid treatment to pies include immunomodulatory therapy and
109 patients on high-dose ICS/LABA (step 4 or maintain asthma control. macrolide antibiotics.a

with azithromycin or placebo. Overall, there was control with the combination of a high-dose
no benefit seen with azithromycin therapy with inhaled glucocorticoid and LABA, an addition- aRecent trials (AMAZES) in patients who have symp-
regard to any of the outcomes tested. However, al controller medication such as an antileu-
tomatic asthma despite inhaled maintenance therapy
subgroup analysis showed that patients with kotriene agent is recommended (tiotropium have shown that azithromycin 500 mg 3 times/week
noneosinophilic asthma had fewer exacerba- or theophylline). reduced exacerbations and improved quality of life.
176 Asthma

TABLE 8 Classifying Asthma Severity and Initiating Treatment in Children 0-4 Yr (Assessing severity and initiating
treatment in children who are not currently taking long-term control medications)
CLASSIFICATION OF ASTHMA SEVERITY (0-4 YR OF AGE)
PERSISTENT
Components of Severity Intermittent Mild Moderate Severe
Impairment Symptoms ≤2 days/wk >2 days/wk but not daily Throughout the day
Nighttime awakenings 0 1-2×/mo 3-4×/mo >1×/wk
Short-acting beta2-agonist ≤2 days/wk >2 days/wk but not daily Several times per day
use for symptom control
(not prevention of EIB)
Interference with normal None Minor limitation Some limitation Extremely limited
activity
Risk Exacerbations requiring 0-1 per yr ≥2 exacerbations in 6 mo requiring oral systemic corticosteroids, or ≥4 wheezing epi-
oral systemic cortico-
steroids Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time.
Exacerbations of any severity may occur in patients in any severity category.
Recommended Step for Initiating Therapy Step 1 Step 2 Step 3 and consider short course of oral systemic
corticosteroids
In 2-6 wk, depending on severity, evaluate level of asthma control that is achieved. If no clear benefit is observed
in 4-6 wk, consider adjusting therapy or alternative diagnoses.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
Level of severity is determined by assessment of both impairment and risk. Assess impairment domain by patient’s/caregiver’s recall of previous 2-4 wk. Symptom assessment for longer periods
should reflect a global assessment such as inquiring whether the patient’s asthma is better or worse since the last visit. Assign severity to the most severe category in which any feature occurs.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. For treatment purposes, patients who had ≥2 exacerbations requiring oral
systemic corticosteroids in the past six months, or ≥4 wheezing episodes in the past year, and who have risk factors for persistent asthma may be considered the same as patients who have
persistent asthma, even in the absence of impairment levels consistent with persistent asthma.
To access the complete Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, go to www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
EIB, Exercise-induced bronchospasm.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood

TABLE 9 Assessing Asthma Control and Adjusting Therapy in Children 0-4 Yr of Age
CLASSIFICATION OF ASTHMA CONTROL (0-4 YR OF AGE)
Components of Control Well Controlled Not Well Controlled Very Poorly Controlled
Impairment Symptoms ≤2 days/wk >2 days/wk Throughout the day
Nighttime awakenings ≤13/mo >1×/mo >1×/wk
Interference with normal activity None Some limitation Extremely limited
Short-acting beta2-agonist use for symp- ≤2 days/wk >2 days/wk Several times per day
tom control (not prevention of EIB)
Risk Exacerbations requiring oral systemic 0-1 per yr 2-3 per yr >3 per yr
corticosteroids
Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The
level of intensity does not correlate to specific levels of control but should be considered in the
overall assessment of risk.
Recommended Action for Treatment Maintain current step. Step up 1 step. Consider short course of oral sys-
Regular follow-up every 1-6 Reevaluate in 2-6 wk. temic corticosteroids.
mo. If no clear benefit in 4-6 Step up 1-2 steps.
Consider step down if well con- wk, consider alternative Reevaluate in 2 wk.
trolled for at least 3 mo. diagnoses or adjusting If no clear benefit in 4-6 wk, con-
therapy. sider alternative diagnoses or
For side effects, con- adjusting therapy.
sider alternative treatment For side effects, consider alterna-
options. tive treatment options.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
The level of control is based on the most severe impairment or risk category. Assess impairment domain by caregiver’s recall of previous 2 to 4 wk. Symptom assessment for longer periods should
reflect a global assessment such as inquiring whether the patient’s asthma is better or worse since the last visit.
At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (e.g., requiring urgent,
unscheduled care, hospitalization, or ICU admission) indicate poorer disease control. For treatment purposes, patients who had ≥2 exacerbations requiring oral systemic corticosteroids in the past
year may be considered the same as patients who have not-well-controlled asthma, even in the absence of impairment levels consistent with not-well-controlled asthma.
Before step up in therapy:
Review adherence to medications, inhaler technique, and environmental control.
If an alternative treatment option was used in a step, discontinue it and use preferred treatment for that step.
EIB, Exercise-induced bronchospasm; ICU, intensive care unit.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood
 Asthma 177

TABLE 10 Stepwise Approach for Managing Asthma in Children 0-4 Yr

A
Intermittent Persistent Asthma: Daily Medication
Asthma Consult with asthma specialist if step 3 care or higher is required. Consider consultation at step 2.

Step 6
Step 5
Preferred:
Step 4
Preferred:
Step 3 Preferred:
Step 2 Preferred: montelukast d
Preferred: montelukast l

and Disorders
Diseases
montelukast
corticosteroid
Alternative: Assess
control
Step 1 montelukast

I
Preferred: if possible
n

well controlled
Patient Education and Environmental Control at Each Step at least 3 months

Quick-Relief Medication for All Patients

t course of

g
.

The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs. If alternative treatment is used and response is inadequate, discontinue
it and use the preferred treatment before stepping up.
If clear benefit is not observed within 4 to 6 wk and patient/family medication technique and adherence are satisfactory, consider adjusting therapy or alternative diagnosis.
Studies on children 0 to 4 yr are limited. Step 2 preferred therapy is based on Evidence A. All other recommendations are based on expert opinion and extrapolation from studies in other children.
Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma and is not intended to promote or endorse any of the
listed products.
ICS, Inhaled corticosteroid; LABA, inhaled long-acting beta2-agonist; prn, as necessary; SABA, inhaled short-acting beta2-agonist.
From National Asthma Education and Prevention Program: Expert panel report 3: guidelines for diagnosis and management of asthma, National Institutes of Health, National Heart, Lung, and Blood

range is from 40-80 mg/day in one or two

phenotypes may improve asthma outcomes. divided doses, generally given until peak PEARLS &
Treatment of status asthmaticus is as follows: CONSIDERATIONS
value.
COMMENTS
2;
further adjustments are made according to wk there is no need to taper the dose.
oxygen saturations. be challenging. A history of atopy and inter-
to avoid congestive heart failure in elder- mittent, reactive symptoms points toward a
dose SABA plus ipratropium bromide admin- ly patients. Aggressive IV hydration is not diagnosis of asthma, whereas smoking and
istered by means of a nebulizer every 20 recommended.
min. Use of a metered-dose inhaler with Spirometry is useful in distinguishing asthma
valved holding chamber may be accept- suspicion of bacterial infection (e.g., infiltrate
able for patients with mild-to-moderate on chest radiograph, fever, or leukocytosis).
exacerbations. treat or prevent comorbid conditions (e.g.,
indicated when previous measures fail to rhinosinusitis, vocal cord dysfunction, gastro-
1.25 mg/3 ml, 2.5 mg/3 ml, or 5.0 mg/ml): produce significant improvement. Table 11 esophageal reflux disease). However, despite
2.5 to 5 mg every 20 min over the first hr, summarizes treatment of life-threatening the presumed association between asthma
then 2.5 to 10 mg every 1 to 4 hr as needed asthma.
or 10 to 15 mg/hr continuously. Other useful - poorly controlled asthma did not reveal any
medications are levalbuterol nebulizer solu- ment is appropriate if the FEV1 or PEF after beneficial effects.
tion (0.31 mg/3 ml, 0.63 mg/3 ml, 1.25 mg/3 -
ml) and ipratropium nebulizer solution (0.25/ best or predicted value and if there is sus- gle most effective therapy for adult patients
tained improvement in lung function and with asthma who require more than an occa-
symptoms for at least 1 hr. sional use of SABAs to control their asthma.
1. Early administration is advised, particu-
larly in patients using steroids at home. asthma is well controlled now has level A
REFERRAL evidence.
2. Patients may be started on systemic cor-
ticosteroids; methylprednisolone, predni- Box 4 describes indications for referral to an -
asthma specialist. resent a reasonable alternative in adults
178 Asthma

TABLE 11 Summary of Treatment for Life-Threatening Asthma

Treatment Dose and Frequency Comments
Oxygen 1-3 L/min by nasal cannula Transient drop in O2 tension with beta-adrenergic therapy
O2 Avoid hyperoxia (may be associated with hypercarbia)
Use heated cascade humidifier to avoid dry air–induced bron-
choconstriction
Bronchodilators
Beta2-selective ago- Albuterol Beta2-selective agonists are the cornerstone of therapy
nists: Albuterol or normal saline) by nebulizer every 20 min for 3 doses total Continuous nebulization used for a majority of severely ill patients
salbutamol, leval- (for optimal delivery, dilute aerosols to a minimum of 3 ml In study of continuous vs. intermittent therapy in severe exacerbations
buterol at gas flow of 6-8 L/min), followed by 2.5-10 mg q1-4h (excluding life-threatening asthma), no difference noted in pulmonary
as needed, or 10-15 mg/h continuously; titration based on function improvement or need for hospitalization
response and severity of symptoms Lower frequency of side effects with continuous treatment
Albuterol MDI, delivered with a spacer (each spacer dose takes Watch for hypokalemia, tremors, tachycardia, and lactic acidosis
1-2 min; 90 µg/puff), 4-8 puffs every 20 min for 4 h, then Oral or parenteral route: Loss of beta2-selectivity
q4h as needed
Albuterol Levalbuterol 0.63 mg = racemic albuterol 1.25 mg for efficacy and side
15-20 min) effects
Levalbuterol (0.63 mg/3 ml and 1.25 mg/3 ml nebulizer): 1.25- Intubated patients: Nebulizers are less efficient in delivering doses to
2.5 mg every 20 min for 3 doses total, then 1.25-5 mg

Levalbuterol MDI (45 µg/puff): 4-8 puffs every 20 min for 4 h,

followed by q1-4h as needed
Epinephrine Subcutaneous epinephrine dose for adults: 0.3-0.5 ml of a
1:1000 dilution (1 mg/ml), depending on age and weight;
repeat every 20 min for 3 doses total
Terbutaline Subcutaneous terbutaline, 0.25 mg; repeat every 20 min for 3 Terbutaline is the parenteral agent of choice in pregnancy
doses total For refractory life-threatening asthma: Intravenous epinephrine (high risk
for cardiac events, infarction, and arrhythmias) or racemic epinephrine
may be considered
Anticholinergics
Ipratropium (for acute Ipratropium bromide: 0.5 mg by nebulizer (0.25 mg/ml) every Ipratropium: Onset of action is slow (20 min), peak effectiveness at 60-90
severe asthma 20 min for 3 doses, then q2-4h as needed min, no systemic side effects, improved lung function and reduced
warranting visit to Ipratropium MDI (0.018 mg/puff): 4-8 puffs per treatment every recovery time
emergency depart- 20 min for up to 3 h Use a handheld mouthpiece nebulizer (contamination of the ocular area
ment) Combinations: with precipitation of narrow-angle glaucoma may occur if facemask is
Albuterol (2.5 mg/3 ml) + ipratropium (0.5 mg/3 ml): 3 ml used for delivery of anticholinergic agent)
every 20 min for 3 doses total, then as needed Ipratropium may be combined with nebulized albuterol dose in the emer-
µg + ipratropium 18 µg: 8 puffs gency room; no proven benefit shown in hospitalized patients
every 20 min for up to 3 h
Corticosteroids: 40-80 mg/day in 1 or 2 divided doses until peak expiratory No advantage of higher doses
Prednisone, pred- No advantage of IV therapy over oral if absorption and gut transit are not
nisolone, methyl- FEV1 impaired
prednisolone Methylprednisolone 40 mg IV q6h OR Hydrocortisone 200 mg IV
Inhaled steroids can be started at any time
Heliox Improves O2 and aerosolized medication delivery to distal lung
Routine use cannot be recommended at this time
Lower gas density facilitates exhalation, reduces air trapping and intrinsic
PEEP
Improves pulmonary function in subgroup of patients with most severe
airflow obstruction
Magnesium sulfate 2 g IV given over 20 min; may repeat Bronchodilatation from inhibition of the calcium channel and decreased
Monitor magnesium levels acetylcholine release
Avoid in renal insufficiency IV and inhaled or nebulized magnesium sulfate improves pulmonary func-
tion in acute severe asthma
IV magnesium widely used as adjunct therapy

FEV1, Forced expiratory flow in 1 second; IV, intravenous; MDI, metered-dose inhaler; PEEP, positive end-expiratory pressure; PEFR, peak expiratory flow rate.
Critical care medicine, principles of diagnosis and management in the adult, ed 4, Philadelphia, 2014, Elsevier.
 Asthma 179

unable or unwilling to use corticosteroids; anticholinergic bronchodilator approved for new treatments of severe asthma. Adjunct
however, these agents are less effective than
monotherapy with inhaled corticosteroids. first severe exacerbation and provided mod-
therapies for bronchospasm are summarized
in Table 12. A
est sustained bronchodilation.
term asthma medication, such as an inhaled - characterized by wide individual variability. A
corticosteroid, is contraindicated. LABAs erates the resolution of acute asthma and functional glucocorticoid-induced transcript
should also not be used in patients whose reduces the risk of relapse. There is no 1 gene (GLCCI1) variant is associated with
asthma is adequately controlled on low- evidence that doses >50-100 mg prednisone substantial decrements in the response to
or medium-dose inhaled corticosteroids. equivalent are beneficial. inhaled glucocorticoids in patients with asth-
Continued use of LABAs may cause down- ma. Another potential cause of the variability
regulation of the beta-2 receptor with loss immunoglobulin (Ig) E levels, use of anti-IgE in response to treatment is heterogeneity
of the bronchoprotective effect from rescue therapy is beneficial. in the role of interleukin-13 expression in
therapy with a SABA. the clinical asthma phenotype. Patients with

and Disorders
Diseases
in selective patients with severe persistent asthma who have a certain biochemical sig-
inhaled corticosteroids benefit from the addi- nature are more likely to respond to an anti–
tion of LABAs. Trials in patients with poorly visits. Biologic modifiers of the Th2 immune interleukin-13 monoclonal antibody than
controlled asthma despite the use of inhaled pathways (neutralizing monoclonal antibod- those without such a signature. Identification
glucocorticoids and LABAs have shown that ies, receptor antagonists, soluble receptors) of genetic variants can eventually lead to
the addition of tiotropium, a long-acting are potential options for the development of personalized asthma treatment. Failure of
pharmacologic treatment is often due to I
uncontrolled comorbid conditions (tobacco,
allergic rhinitis, pollutants), poor inhaler tech-
BOX 4 Possible Indications for Referral to an Asthma Specialist nique, or lack of adherence to prescribed
medication.

-
SUGGESTED READINGS
- Available at ExpertConsult.com
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RELATED CONTENT
- Asthma (Patient Information)

Topic)
-
AUTHORS: Kristin Dalphon, PA, and Samaan
Rafeq, MD

-
-

Modified from National Asthma Education and Prevention Program, National Heart, Lung, and Blood Institute:
Expert Panel Report 2: guidelines for the diagnosis and management of asthma, Bethesda, MD, 1997, National
Institutes of Health, NIH publication No 97-4051.

TABLE 12 Adjunct Therapies for Bronchospasm

Nontraditional Therapy for Severe Bronchospasm Comments
Intravenous beta2-agonists No data show any benefit in adding IV agent to nebulization
Avoid IV isoproterenol owing to danger of myocardial toxicity
Oral or IV leukotriene receptor antagonists (LTRAs): Montelukast 10 mg oral Rapid bronchodilation in impending respiratory failure
daily, zafirlukast Improves pulmonary function within 10 min
Oral LTRAs can be added as an adjunct in severe asthma
Noninvasive positive-pressure ventilation (NPPV) NPPV reduces the need for endotracheal intubation in severe asthma exacerbation
Inhaled nitric oxide (NO) (adding 15 ppm to the inspiratory circuit) Rapid improvement in ventilated patients with asthma refractory to medical treatment
Omalizumab (anti-IgE antibody) Role in acute asthma is unstudied
Improves asthma control in allergic asthmatics
Propofol relaxes the smooth muscles in arteries and veins and has bronchodilator effect
IV propofol, IV ketamine
Plasma exchange (during pregnancy) Case reports of adjunct therapies; used as salvage therapy for life-threatening asthma
Pumpless extracorporeal carbon dioxide removal
Extracorporeal life support (ECLS)
Rapid smooth muscle relaxant, short half-life; small study report
Case report of use in pregnant patient with rapid improvement
Bronchial lavage Anecdotal reports: Exacerbates auto-PEEP, decreases oxygenation

IgE, Immunoglobulin E; IV, intravenous; PEEP, positive end-expiratory pressure.

Critical care medicine, principles of diagnosis and management in the adult, ed 4, Philadelphia, 2014, Elsevier.