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CLINICAL OVERVIEW
Asthma in Adults
Elsevier Point of Care (see details)
Updated July 1, 2021. Copyright Elsevier BV. All rights reserved.
Synopsis
Key Points Urgent Action

Asthma in adults may be persistence of childhood- Quickly assess the
onset asthma (usually allergic) or may reflect new following in any patient
onset in adulthood (often nonallergic) with respiratory distress:
vital signs, signs of tiring
Presents with episodic wheezing, chest tightness,
from work of breathing,
difficulty breathing, and cough; cough-variant
lung function, and
asthma may present with coughing as primary
oxygen saturation. Give
symptom
supplemental oxygen to
maintain SaO₂ of at least
Diagnosis is based on appropriate history plus
90%
clinical picture and documented reversibility of
airflow obstruction (12% increase or more from
Consider alternative
baseline in FEV₁; minimum 200 mL) following
diagnoses, such as
treatment with an inhaled short-acting
foreign body aspiration
bronchodilator 1
or congestive heart
Classify the asthma initially by frequency of failure, that would
symptoms (intermittent or persistent) and their require other urgent
action
effect on daily functioning (ie, mild, moderate,
severe); initial pharmacotherapy is based on this
FEV₁ or peak expiratory
classification
flow measurement is
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After starting pharmacotherapy, classify the asthma helpful to assess severity

by level of control; pharmacotherapies are stepped of an exacerbation, but do
up or down based on this level not allow testing to delay
treatment
Persistent asthma requires use of a daily controller
medication, starting with a low-dose inhaled Begin treatment of mild
corticosteroid for mild persistent asthma. There is to moderate asthma
some evidence that starting inhaled corticosteroids exacerbation with short-
may be beneficial even for mild intermittent asthma acting β₂ agonist via
inhaler with spacer or
Step-up to an inhaled long-acting β₂ agonist with nebulizer; for severe
increasing doses of inhaled corticosteroids as asthma, continuous
needed. Leukotriene inhibitors are alternative add- administration via
on drugs nebulizer is
recommended
Begin treatment of an acute exacerbation with an
inhaled short-acting β₂ agonist; add systemic Give inhaled ipratropium
steroids and inhaled anticholinergics for in addition to short-
exacerbations classified as severe. On discharge from acting β₂ agonist for
emergency department, consider initiating exacerbations classified as
corticosteroids in patients who have not previously severe or life-threatening
used them 1
In emergency care setting, discharge goal is

improvement to 70% or more of predicted FEV₁ or peak expiratory flow
Education, home monitoring with a peak flow meter, and asthma action plans are as
important as medication
Smoking cessation is critical
Pitfalls
Physical examination is not a reliable indicator of the severity of airflow obstruction;
wheezing may be inaudible in severe asthma exacerbation
Athletes and elderly patients may underreport symptoms or attribute them to other
causes
Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge

may be useful when asthma is suspected and spirometry results are within reference
range or nearly so
Terminology
Clinical Clarification
Asthma is a chronic inflammatory airway disease causing episodic, acute airflow
obstruction and/or increased airway reactivity that is totally or partially reversible
(with or without therapy) in a patient who has normal laryngeal function and lacks
an alternative diagnosis 1
Clinically presents as recurrent episodes of cough and wheezing
Reversibility is defined as 12% increase or more from baseline in FEV₁ (minimum

200 mL) following treatment with an inhaled short-acting bronchodilator 1
Classification
Classification of asthma severity (patients not currently using controller medication)
1
Intermittent asthma 1
Symptoms occur 2 or fewer days per week
No interference with normal activity
Nighttime awakenings 2 times per month or less
Use of short-acting β₂ agonist for symptom control 2 days per week or less
Lung function
FEV₁ (predicted within reference range for patient between exacerbations)

greater than 80%
FEV₁/FVC within reference range
1 or fewer exacerbations per year requiring systemic corticosteroids
If patient otherwise meets criteria for intermittent asthma but has at least 2
exacerbations per year that require systemic corticosteroids, this is
considered persistent asthma
Mild persistent asthma 1
Symptoms occur more than 2 days per week, but not daily
Minor limitation to normal activity
Nighttime awakenings 3 to 4 times per month
Use of short-acting β₂ agonist for symptom control more than 2 days per week,
but not daily and not more than 1 time on any day
Lung function
FEV₁ 80% predicted or higher
FEV₁/FVC within reference range
2 or more exacerbations per year that require systemic corticosteroids
Moderate persistent asthma 1
Symptoms occur daily
Some limitation to normal activity
Nighttime awakenings more than once per week, but not nightly
Use of short-acting β₂ agonist for daily symptom control
Lung function
FEV₁ 60% to 80% predicted
FEV₁/FVC is reduced by 5%
Severe persistent asthma 1
Symptoms occur throughout the day on a daily basis
Extreme limitation of normal activity
Nightly awakenings
Use of short-acting β₂ agonist daily for symptom control multiple times per day
Lung function
FEV₁ less than 60% predicted
FEV₁/FVC reduced by more than 5%
Classification of asthma control (patients using controller medication)
Well controlled 1
Symptoms occur 2 or fewer days per week
No interference with normal activities
Nighttime awakenings 2 times per month or less
FEV₁ (predicted) or peak expiratory flow (personal best) greater than 80%
Not well controlled 1
Symptoms occur more than 2 days per week
Some limitation of normal activities
Nighttime awakenings 1 to 3 times per week
FEV₁ (predicted) or peak expiratory flow (personal best) 60% to 80%
Very poorly controlled 1
Symptoms occur throughout the day
Extreme limitation of normal activities
Nighttime awakenings 4 or more times per week
FEV₁ (predicted) or peak expiratory flow (personal best) less than 60%
Classification of acute exacerbations (worsening of baseline function)
Mild 1
Dyspnea only with activity
Peak expiratory flow of 70% or higher of predicted or personal best
Moderate 1
Dyspnea limits usual activity
Peak expiratory flow 40% to 69% of predicted or personal best
Severe 1
Dyspnea at rest
Peak expiratory flow lower than 40% predicted or personal best
Life threatening 1
Too dyspneic to speak
Peak expiratory flow lower than 25% of predicted or personal best
Status asthmaticus
Continuous, severe asthma exacerbation resistant to treatment
Classification by phenotype 2
Intrinsic (nonallergic) 1
Common phenotype in late/adult-onset asthma
Occurs in patients with no history of allergies
May be triggered by upper respiratory tract infection or other factors
Allergic asthma
Associated with elevated blood IgE
Early/childhood onset
Eosinophilic asthma
Late/adult onset
Associated with airway eosinophilia
Blood/sputum eosinophil count is a predictive biomarker for increased severity

of asthma attacks
Agents targeting eosinophils (interleukin-5) may improve asthma control
Aspirin-exacerbated respiratory disease
Presents as allergy to NSAIDs
Late/adult onset
Often severe and may be accompanied by sinusitis and nasal polyposis
Neutrophilic asthma
Associated with airway neutrophils (interleukin-8)
Late/adult onset
Neutrophils in the airways are associated with reduced lung function and
airway wall thickening
Usually occurs in patients treated with corticosteroids and presents challenge to

management
Obesity-associated asthma
Late/adult onset
Poor response to corticosteroid therapy
Weight loss may improve symptoms
Exercise-induced asthma
Early onset
May occur in patients with or without underlying asthma 3
Presents intermittently with strenuous exercise
FEV₁ or peak expiratory flow decreases 10% to 15% soon after onset of
vigorous activity (compared with measurement just before exercise) 1 3
May persist up to 30 minutes after exercise 3
Severe asthma phenotype
Subtype that is difficult to treat and control; estimated to affect approximately

5% to 10% of patients 2 4
50% of patients with severe asthma have evidence of type 2 inflammation and
may be candidates for treatment with type 2 targeting biologic agents 5
Cough variant asthma 6
Manifests with nonproductive cough, often without usual wheezing and

shortness of breath associated with asthma
Diagnosis
Clinical Presentation
History
Episodic dyspnea is the most common symptom
Present on exertion in mild to moderate asthma
Present at rest in severe asthma
Athletes may report decreased exercise tolerance
Nocturnal dyspnea with awakenings is common
Inability to take a deep breath
Cough, especially nocturnal or in the early morning
Usually nonproductive; sometimes produces sputum
Chest tightness
Wheezing may be audible to patient
Breathlessness, cough, wheezing, and/or sputum production that begin shortly after
onset of vigorous exercise are suggestive of exercise-induced asthma
Patient may report recent exposure to common allergic and nonallergic triggers
Baseline level of disease control may change owing to level of adherence to

treatment plans
Level of short-acting β₂ agonist use, steroid use, and number/severity of

exacerbations in the past year are indicative of disease control
Physical examination
Results are typically within reference range in a patient with well-controlled asthma
There may be evidence of associated diseases, such as nasal secretions and

mucosal edema (allergic rhinitis) or rash (atopic eczema)
Nasal polyps may be present
During exacerbation
General appearance
May be anxious
Labored breathing
Diaphoresis with increased respiratory effort
Cyanosis with significant hypoxia
Drowsiness with impending respiratory failure
Vital signs
Tachypnea and tachycardia
With severe exacerbation:
Sustained tachypnea exceeding 30 breaths per minute and tachycardia

exceeding 120 beats per minute
May eventually become apneic
Pulsus paradoxus (drop in systemic arterial pressure with inspiration higher

than 10 mm Hg) is often higher than 18 mm Hg but may disappear with
fatigue
Respiratory examination
Prolonged expiratory phase
Use of respiratory accessory muscles/intercostal muscle recession
Wheezing is usually present during exacerbation, but absence of wheezing does

not rule out significant bronchospasm
Causes and Risk Factors
Causes
Underlying cause is incompletely understood; may be environmental in
combination with genetic interaction
Exacerbation triggers
Aeroallergens (eg, pollen, pet dander, dust mites, mold)
Airborne irritants (eg, cigarette or wood smoke, air pollution, chemical

compounds, grain dust)
Drugs (eg, aspirin, NSAIDs, β-blockers)
Ingested substances (eg, foods, sulfites)
Respiratory infection
Exercise
Cold air
Psychological stress
Risk factors and/or associations
Age
Asthma in adults may be either persistent childhood-onset asthma or new-onset
asthma in adulthood
Sex
Higher prevalence in women
Genetics
Predisposed sensitivity to environmental allergens is strongest risk factor
Ethnicity/race
Higher prevalence in Hispanic and Black populations than in White population
Other risk factors/associations

In females, obesity or increased waist circumference
Large waist circumference (more than 88 cm) is associated with increased asthma
prevalence, even among women with a BMI within reference range 7
Adjusted odds ratio for adult-onset asthma increases from 1.4 for overweight women
7
to 3.3 for extremely obese women 7
Presence of the following risk factors increases risk for exacerbations, even if
patients have few symptoms 4
Previous intubation or intensive care unit admission for asthma
One or more severe exacerbations in the past year
Low FEV₁ (especially if lower than 60% predicted)
Exposures
Smoking
Allergens, if sensitized
Air pollution
Comorbidities
Chronic rhinosinusitis
Obesity
Food allergy
Pregnancy
Gastroesophageal reflux disease
Medications
Frequent use of short-acting β agonists
Not prescribed or inadequate dose of inhaled corticosteroids
Poor adherence or inhaler technique
Diagnostic Procedures
Primary diagnostic tools

New diagnosis
History and physical examination suggest the diagnosis 1
Perform spirometry. Obstruction (FEV₁/FVC ratio of 70% or less) with

reversibility after bronchodilator administration (12% increase or more from
baseline in FEV₁; minimum 200 mL) strongly supports the diagnosis 1
However, in an asymptomatic patient, normal spirometry does not rule out

an asthma diagnosis
Measurement of fractional nitric oxide concentration in exhaled breath

(FeNO) may be helpful in the initial diagnosis of asthma as a surrogate marker
of eosinophilic airway inflammation
2017 NICE guidelines 8 recommend that this be performed routinely in the

diagnostic evaluation of adults
Other guidelines suggest utility in confirming asthma when symptoms and

signs suggest asthma, but spirometry is not definitive 9
Measurement of fractional nitric oxide concentration in exhaled breath is

also sometimes used as an alternative strategy for guiding therapy, but
recent evidence is not supportive of this 4 10
Additional testing is not routinely necessary, but it may be helpful in some

situations 1
Repeated peak flow measures over a period of weeks; variability above 20%
within the measurement period supports the diagnosis of asthma 8
Bronchoprovocation when asthma is suspected and spirometry is within (or

nearly within) reference range 1
Full pulmonary function testing to differentiate from chronic obstructive

pulmonary disease in smokers 1
Skin testing or in vitro allergy testing to assess sensitivity to perennial

indoor allergens for patients with persistent asthma 1
Peripheral blood eosinophil count to assess for eosinophilic phenotype,

which may later guide therapy 11
Exercise-induced asthma, suggested by respiratory symptoms associated

with vigorous exercise, may be confirmed by serial changes in lung
function (FEV₁ preferred) after exercise or hyperpnea challenge 3
Acute exacerbation
History and physical examination suggest the diagnosis
Immediate FEV₁ or peak expiratory flow measurement to determine severity

of exacerbation
A peak flow rate below 200 L/min generally indicates severe airway
obstruction 1
Immediate assessment of oxygenation with pulse oximeter
Arterial blood gas measurement is not routine, but it may be helpful in

staging exacerbation to guide treatment or if there is poor response to
repeated treatments 1
Obtain chest radiograph if complicating chest infection suspected,

hospitalization required, or diagnosis is uncertain 4
Laboratory
Imaging
Functional testing
Differential Diagnosis
Most common
Chronic obstructive Difficult to clinically distinguish
pulmonary disease
(Related: Stable Chronic Perform pulmonary function tests with carbon

Obstructive Pulmonary monoxide–diffusing capacity
Disease)
Airway obstruction is more severe with less
reversibility in chronic obstructive pulmonary
disease
Diffusing capacity is lower in chronic obstructive

pulmonary disease
Congestive heart failure History of coronary artery disease, congestive heart

failure, or valvular disease
Physical examination may reveal wheezing, but other

findings (eg, rales, dependent edema, cardiac gallop)
suggest heart failure
Chest radiograph and ECG aid in diagnosis
Chronic cough due to History and physical examination may be suggestive

other cause (eg,
gastroesophageal reflux Discontinuing ACE inhibitor or initiating trial of
disease, rhinitis with medication for other conditions may eliminate
postnasal drip, ACE symptoms
inhibitor adverse effect)
Bronchoprovocation testing may be helpful when
(Related:
cough-variant asthma versus alternative cause of
Gastroesophageal
cough is a consideration (result will be negative with
Reflux Disease in nonasthma cause)
Adults)
Pulmonary embolus History is sometimes suggestive (eg, previous deep

(Related: Pulmonary vein thrombosis or pulmonary embolus, recent
Embolism) immobilization due to travel or surgery)
D-dimer testing and/or appropriate imaging to

diagnose
Mechanical obstruction Suggestive history may include constitutional

of airway due to benign symptoms, weight loss, difficulty swallowing, and
or malignant tumor hemoptysis
Chest radiograph, CT scan, soft tissue radiograph of

the neck, and/or endoscopic visualization to diagnose
Vocal cord dysfunction May mimic asthma, but will be unresponsive to

(paradoxical vocal cord bronchodilators
motion disorder)
Consider in atypical asthma and in athletes who have
exercise-related dyspnea that is unresponsive to
asthma medication
Spirometry demonstrates extrathoracic airway

obstruction on flow-volume loops (truncated
inspiratory loop)
Laryngoscopy confirms abnormal adduction
Treatment
Goals 1
Reduce current impairment
Prevent symptoms
Decrease need for short-acting β₂ agonist inhaler

to 2 or fewer days per week
Management of asthma
Maintain normal activity levels exacerbations: emergency
department and hospital-based
Maintain near-normal pulmonary function care.
(measured by FEV₁ or peak expiratory flow)
Reduce future risk
Prevent exacerbations
Prevent structural changes in airways and decline

in pulmonary function
Minimize risks/adverse effects of therapy

Stepwise approach for managing
asthma in youths aged 12 years or
older and adults.
Disposition
Admission criteria
Base admission decisions on serial assessment of lung function (using FEV₁ or peak
expiratory flow) after the patient receives 3 doses of an inhaled bronchodilator (at least
1 hour after initiation of treatment); use pulse oximetry if patient is unable to comply
with FEV₁ or peak expiratory flow measurement
Criteria for discharge from urgent care/emergency department
Patient is not in distress, physical examination results are normal, and FEV₁ is at
least 70% of personal best (or predicted value) 1
Response sustained at least 1 hour after last treatment 1
Criteria for keeping in observation unit (if available) or admitting to hospital ward
(individualized decision)
After 1 to 3 hours of treatment with short-acting β₂ agonist treatments and oral

corticosteroids, patient has mild to moderate symptoms and FEV₁ or peak
expiratory flow is 40% to 69%
More severe disease requires ICU admission
Criteria for ICU admission

Impending (or actual) respiratory arrest
Drowsiness or confusion
FEV₁ or peak expiratory flow less than 25% before treatment often predicts need for
1
ICU 1
FEV₁ or peak expiratory flow less than 40% after multiple or continuous nebulized
albuterol-ipratropium treatments with oral corticosteroids 1
PCO₂ of 42 mm Hg or higher on arterial blood gas after multiple treatments 1
Recommendations for specialist referral

Refer to asthma specialist (pulmonologist or allergist)
Severe, persistent asthma requiring step 4 care or higher 1
Poorly controlled asthma with frequent absence from school or work
Consideration of immunotherapy or omalizumab treatment
Patient has required more than 2 rounds of oral steroids or high-dose inhaled
corticosteroids in past year 1
Patient required hospitalization in past year
Diagnosis is uncertain or symptoms are atypical
Treatment Options
Acute asthma exacerbation
Exacerbation with peak expiratory flow remaining at 50% or more of personal best
can often be managed at home with use of inhaled short-acting β₂ agonist with or
without a short course of oral corticosteroids 1
Patients may be advised to quadruple maintenance dose of inhaled corticosteroids

at the onset of an asthma attack and for up to 14 days in order to reduce the risk of
needing oral corticosteroids 13
Exacerbation with peak expiratory flow less than 50% of predicted or personal best
requires immediate medical care in urgent care facility or emergency department; if
peak expiratory flow is less than 40%, patient should go to emergency department 1
Emergent clinical setting
For mild-moderate exacerbation
Supplemental oxygen by nasal cannula or face mask if SaO₂ is lower than 90% 1
Immediately start treatment with inhaled short-acting β₂ agonist drug; start

with repeated doses via metered dose inhaler 19
Give oral corticosteroids if there is no immediate response to inhaled short-

acting β₂ agonist drug or if patient recently took oral corticosteroids 1
Reassess
Continue inhaled short-acting β₂ agonist drug treatments for 1 to 3 hours;

make admission decision within 4 hours 1
For severe exacerbation
Provide supplemental oxygen by nasal cannula or face mask if SaO₂ is lower

than 90% 1
Immediately start treatment with inhaled short-acting β₂ agonist drug; give

continuous (instead of intermittent) nebulized short-acting β₂ agonist 20
Injected epinephrine or terbutaline is no more effective than inhaled short-

acting β₂ agonist 1 21
Give ipratropium by nebulizer along with short-acting β₂ agonist 1
Give oral corticosteroids 1
Reassess
Repeat administration of inhaled short-acting β₂ agonist with ipratropium as

necessary 1
Consider adjunctive therapies if FEV₁ remains lower than 40% 1
IV magnesium sulfate reduces hospital admissions and improves lung

function in adults when inhaled short-acting medications and IV steroids
have failed; not for routine use 22 23
For severe exacerbation with impending or actual respiratory arrest
Some authors advocate for noninvasive positive pressure ventilation for severe
exacerbation when attempting to avoid intubation; 24 12 however, evidence of
benefit is limited 25
Intubate and mechanically ventilate with 100% oxygen if respiratory arrest is

occurring or impending, signaled by:
Paradoxical thoracoabdominal movement
Absence of wheeze
Peak expiratory flow lower than 25% 1
If arterial blood gas is obtained, PCO₂ of 42 mm Hg or higher 1
Cyanosis
Drowsiness
Bradycardia
Immediately start treatment with continuous inhaled short-acting β₂ agonist

plus inhaled ipratropium 1
Give IV corticosteroids 1
Consider adjunctive therapies
Magnesium sulfate if FEV₁ remains less than 40% 1
Recent trials of nebulized inhaled magnesium sulfate have not shown

significant benefit 26
For all patients before discharge from emergency department or hospital
Ensure that the patient will receive these critical components of asthma
management as an outpatient: 1
Ongoing clinical assessment and home monitoring
Education and asthma action plan
Control of environmental factors and comorbid conditions

Ongoing controller medication
Chronic asthma
Pharmacotherapy is prescribed using stepwise approach; 17 1 initial step is

determined by disease severity classification (for newly diagnosed patients not on
controller medications) or by disease control classification (for patients currently
using controller medications)
Adjustments are based on the ongoing level of control
Therapy can be both stepped up and stepped down; step-down can be considered
after 3 months of good control
3 types of medications may be used 4
Controllers
Inhaled corticosteroid-containing controller medications reduce airway

inflammation and symptoms, reduce future exacerbations and decline in lung
function
The Single Maintenance and Reliever Treatment (SMART) strategy using a

combination of inhaled corticosteroid (ICS) plus formoterol in a single inhaler
therapy is the preferred treatment of steps 3 and 4 4 13 17
Relievers
Used as needed to alleviate breakthrough symptoms
Once a mainstay of asthma therapy, short-acting β agonists are no longer

recommended as the preferred reliever for symptomatic patients and should
not be used as monotherapy because of safety concerns and poor outcomes 27
A combined inhaled corticosteroid plus fast onset, long-acting β agonist (ie,

formoterol) is the preferred reliever
Reduction or elimination of need for use is a major goal of asthma treatment
Add-on medications
A variety of agents may be considered when symptoms persist or exacerbations

occur despite optimal therapy with controllers
Step 1 (Intermittent asthma; infrequent symptoms less than twice per month and no
risk factors for exacerbations) 1
Global Initiative for Asthma and National Asthma Education and Prevention
Program recommend using a low-dose inhaled corticosteroid plus the inhaled
long-acting β₂ agonist, formoterol, in a single inhaler, as required to alleviate
symptoms 4 17
Alternatively, give a dose of low-dose inhaled corticosteroid whenever inhaled

short-acting β₂ agonist is used to relieve symptoms
Inhaled corticosteroid-containing reliever medications are superior to short-

acting β₂ agonist reliever alone and significantly reduce risks of severe asthma
exacerbation 28 29
Global Initiative for Asthma no longer recommends as-needed inhaled short-

acting β₂ agonist monotherapy for such symptoms 30
British guidelines recommend use of an inhaled short-acting β₂ agonist as

reliever therapy for patients with symptomatic asthma who have infrequent, short-
lived wheeze and normal lung function 8 13
Step 2 (Asthma symptoms or need for reliever medication more than twice per
month)
Global Initiative for Asthma recommends either: 4
As-needed low-dose inhaled corticosteroid plus formoterol in a single inhaler,

to alleviate symptoms
Low-dose inhaled corticosteroid maintenance therapy plus as-needed inhaled

short-acting β₂ agonist to alleviate symptoms
Alternatives
Daily leukotriene receptor antagonist
Dose of low-dose inhaled corticosteroid whenever inhaled short-acting β₂

agonist is used to relieve symptoms
British guidelines recommend low-dose inhaled corticosteroids as maintenance

therapy for patients with asthma-related symptoms 3 times a week or more, or
causing waking at night or asthma that is uncontrolled with a reliever alone 8 13
Step 3 (Asthma symptoms on most days or waking due to asthma symptom once per
week or more)
Global Initiative for Asthma recommends either: 4
Low-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as

maintenance therapy and low-dose inhaled corticosteroid plus formoterol
single inhaler as needed to alleviate symptoms (preferred by National Asthma
Education and Prevention Program) 17
Low-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist as

maintenance therapy and as-needed inhaled short-acting β₂ agonist as reliever
Alternatives:
Medium-dose inhaled corticosteroid plus as-needed inhaled short-acting β₂

agonist to alleviate symptoms
Low-dose inhaled corticosteroid maintenance therapy plus leukotriene

receptor antagonist
Addition of house dust mite sublingual immunotherapy for sensitized

patients with allergic rhinitis and FEV₁ greater than 70% predicted
Low-dose inhaled corticosteroid plus a long-acting muscarinic antagonist,

tiotropium (National Asthma Education and Prevention Program
recommended) 17
British guidelines recommend add-on therapy with inhaled long-acting β₂ agonist

or a leukotriene receptor antagonist 8 13
If asthma control still remains suboptimal, then medium-dose inhaled

corticosteroid or combined low-dose inhaled corticosteroid plus inhaled long-
acting β₂ agonist as maintenance therapy and low-dose inhaled corticosteroid
plus formoterol single inhaler as needed to alleviate symptoms
Step 4 (Asthma symptoms on most days, or waking due to asthma symptoms once
per week or more, or low lung function)
Global Initiative for Asthma recommends medium-dose inhaled corticosteroid

plus inhaled long-acting β₂ agonist as maintenance therapy with as-needed low-
dose inhaled corticosteroid plus formoterol single inhaler (preferred by National
Asthma Education and Prevention Program) 17or inhaled short-acting β₂ agonist
4
to alleviate symptoms 4
Alternatives
High-dose inhaled corticosteroid
Add-on tiotropium bromide, a long-acting muscarinic antagonist 17
Add-on leukotriene receptor antagonist
Add-on house dust mite sublingual immunotherapy for sensitized patients

with allergic rhinitis and FEV₁ greater than 70% predicted
British guidelines recommend 1 of the following if asthma control remains

inadequate on medium-dose inhaled corticosteroid plus a long-acting β₂ agonist
or a leukotriene receptor antagonist: 13
High-dose inhaled corticosteroids
Addition of a leukotriene receptor antagonist (if not already using)
Addition of tiotropium bromide, a long-acting muscarinic antagonist
Addition of a theophylline (rarely used nowadays)
Step 5 (severe uncontrolled asthma) 1
Referral to asthma specialist is recommended
Address any factors that may contribute to suboptimal control (eg, poor adherence
to therapy, incorrect inhaler technique, comorbidities, modifiable risk factors
such as smoking) 5
Use high-dose inhaled corticosteroid plus inhaled long-acting β₂ agonist with as-
needed low-dose inhaled corticosteroid plus formoterol single inhaler or inhaled
short-acting β₂ agonist to alleviate symptoms
Assess asthma phenotype for type 2 airway inflammation during high-dose

inhaled corticosteroid treatment 5
Type 2 airway inflammation is defined by the presence of 1 or more of the

following:
Blood eosinophil count of 150/μL or more
Fractional nitric oxide concentration in exhaled breath of 20 ppb or more
Sputum eosinophil concentration of 2% or more
Asthma that is clinically allergen-driven
Oral corticosteroid dependent
If no evidence of type 2 inflammation, consider the following:
Add-on tiotropium bromide, a long-acting muscarinic antagonist 31
Add-on macrolide antibiotic (eg, azithromycin) 31
Consider in adults aged 50 to 70 years who have persistent symptoms

despite more than 80% adherence to high-dose inhaled steroids (over 800
mcg/day) and 1 or more exacerbation requiring oral steroids in the past
year 32
Treat for a minimum of 6 to 12 months to assess efficacy in reducing

exacerbations 32
Course of low-dose oral corticosteroid
Bronchial thermoplasty: may be considered for some patients with severe

asthma despite optimal medical therapy 4 5 13
If there is evidence of type 2 airway inflammation, consider addition of

biological agents (refer to local eligibility criteria and published guidelines for
use) 5 33
Evaluate response to the biological agent after 4 months and, if favorable,

continue treatment with reevaluation every 3 to 6 months; switch to a
different agent if response to the initial agent is inadequate 33
Anti-interleukin-5/interleukin-5 receptor monoclonal antibodies

(mepolizumab, benralizumab, reslizumab) for severe asthma with an
eosinophilic phenotype, ascertained by either sputum or peripheral
eosinophilia 34
Anti-interleukin-5 agents reduce exacerbations in patients with severe

eosinophilic asthma 31 35
Mepolizumab and benralizumab are effective in reducing oral steroid

doses in patients with corticosteroid-dependent asthma
A blood eosinophil count threshold of 150/μL or more can be used to

guide initiation of anti-interleukin-5 agents 31
Omalizumab, an anti-IgE monoclonal antibody, for allergic asthma with

documented sensitivity to a perennial aeroallergen and elevated total IgE
level
A blood eosinophil count of 260/μL or more and fractional nitric oxide

concentration in exhaled breath of 19.5 ppb or more identify patients most
likely to benefit from anti-IgE treatment 31
Dupilumab, an anti-interleukin-4 receptor monoclonal antibody, for patients

with severe eosinophilic asthma and those requiring maintenance oral
corticosteroids regardless of blood eosinophil levels 31
Guidelines have been developed to aid evaluation and management of difficult-to-

treat and severe asthma 5 31 33
Exercise-induced asthma 3
Use inhaled short-acting β₂ agonist 15 minutes before exercise 3 13
Combination low-dose inhaled corticosteroid plus formoterol used as required

and before exercise is an alternative
Ensure training and warm up is sufficient 4
For patients who require an inhaled short-acting β₂ agonist daily or more frequently,
add low-dose inhaled corticosteroids 4 13
Review and optimize asthma treatment for patients in whom exercise-induced

asthma reflected overall poorly controlled asthma 13
If exercise remains a specific problem in patients who are otherwise well controlled
on low-dose inhaled corticosteroids, consider adding 1 of the following therapies: 3
13
Daily leukotriene antagonist 3
Sodium cromoglicate (cromolyn) or nedocromil sodium before exercise
Long-acting β₂ agonists (only in conjunction with an inhaled corticosteroid)
Theophyllines
Use antihistamine only if there are definite allergies 3
Consider adding inhaled anticholinergic (weak evidence, but can be tried if other
options are inadequate) 3
Cough variant asthma 6
Low-dose inhaled corticosteroids are considered first line treatment
If response is incomplete, inhaled corticosteroid dose may be increased and/or

leukotriene antagonist added
Drug therapy
Chronic asthma
Relief of episodic wheezing (relievers)
Short-acting β₂ agonists
Albuterol
Albuterol Pressurized inhalation, suspension; Adults: 180 mcg (2

actuations of 90 mcg/actuation) via oral inhalation every 4 to 6 hours as
needed. In some patients, 90 mcg (1 actuation) every 4 hours may be
sufficient. Max: 12 actuations/day (1,080 mcg/day).
Albuterol Inhalation powder; Adults: 180 mcg (2 actuations of 90

mcg/actuation) via oral inhalation every 4 to 6 hours as needed. In some
patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 12
actuations/day (1,080 mcg/day).
Albuterol Sulfate Nebulizer solution; Adults: 2.5 mg via nebulizer 3 to 4

times daily as needed. Usual Max: 4 doses/day.
Some guidelines recommend simultaneous administration of low-dose

inhaled corticosteroids when albuterol is used to relieve symptoms
Fluticasone
Fluticasone Propionate Pressurized inhalation, suspension; Adults:

GINA recommends 88 mcg (2 oral inhalations of 44 mcg/actuation) or
110 mcg to 220 mcg (1 to 2 oral inhalations of 110 mcg/actuation) or
220 mcg (1 oral inhalation of 220 mcg/actuation) as needed whenever
short-acting beta-2 agonist (SABA) is given. NAEPP only recommends
as-needed ICS/SABA as an option for patients with mild persistent
asthma. FDA-approved Max: 1,760 mcg/day.
Fluticasone Furoate Inhalation powder; Adults: GINA recommends

100 mcg (1 oral inhalation of 100 mcg/actuation) as needed whenever
short-acting beta-2 agonist (SABA) is given. NAEPP only recommends
as-needed ICS/SABA as an option for patients with mild persistent
asthma. FDA-approved Max: 200 mcg/day.
Budesonide
Budesonide Inhalation powder; Adults: GINA recommends 180 to

360 mcg (1 to 2 oral inhalations of 180 mcg/actuation) as needed
whenever short-acting beta-2 agonist (SABA) is given. NAEPP only
recommends as-needed ICS/SABA as an option for patients with mild
persistent asthma. FDA-approved Max: 1,440 mcg/day.
Inhaled corticosteroid plus fast onset, long-acting β₂ agonist
Budesonide-formoterol combination product
Budesonide, Formoterol Fumarate Pressurized inhalation, powder;

Adults: 1 or 2 oral inhalations (total per dose = 160 to 320 mcg
budesonide with 4.5 to 9 mcg formoterol) as needed in addition to
daily maintenance dosing; may repeat after 5 minutes if needed. Max
per National Asthma Education and Prevention Program: formoterol
54 mcg/day or 12 oral inhalations of a product containing 4.5
mcg/actuation of formoterol.
Levalbuterol (for patients intolerant of albuterol)
Levalbuterol Tartrate Pressurized inhalation, suspension; Adults: 90 mcg

(2 actuations of 45 mcg/actuation) via oral inhalation every 4 to 6 hours as
needed; in some patients 45 mcg (1 actuation) every 4 hours may be
sufficient. Max: 12 actuations/day (540 mcg/day).
Levalbuterol Hydrochloride Nebulizer solution; Adults: 0.63 to 1.25 mg via
nebulizer 3 times daily (every 6 to 8 hours) as needed. Max: 3 doses/day.
Maintenance treatment (controllers)
Inhaled corticosteroids (preferred)
Fluticasone
Fluticasone Propionate Pressurized inhalation, suspension; Adults: 88 mcg

(2 oral inhalations of 44 mcg/actuation) twice daily for patients not
currently on an inhaled corticosteroid. Base starting dosage on previous
asthma therapy and asthma severity. Max: 4 oral inhalations of 220
mcg/actuation twice daily (880 mcg twice daily). Use the lowest effective
dose once stable.
Fluticasone Propionate Inhalation powder; Adults: 55 mcg (1 oral

inhalation of 55 mcg/actuation) twice daily is recommended for patients
not on an inhaled corticosteroid. Base starting dosage on previous asthma
therapy and asthma severity. After 2 weeks, may increase to 113 mcg twice
daily if not controlled. Max: 232 mcg (1 oral inhalation of 232
mcg/actuation) twice daily. Use lowest effective dose once stable.
Budesonide
Budesonide Inhalation powder; Adults: 360 mcg (2 oral inhalations of 180

mcg/actuation) twice daily is the recommended starting dosage; 180 mcg (1
actuation) twice daily may be appropriate for some patients. Max: 4 oral
inhalations of 180 mcg/actuation twice daily (720 mcg twice daily). Titrate
to lowest effective dose once stable.
Budesonide Nebulizer suspension; Adults†: Not FDA-approved in U.S. in

adults. European usual dose for severe asthma is 1 to 2 mg via nebulizer
twice daily. Usual maintenance dose is 0.5 to 1 mg via nebulizer twice
daily; may increase during exacerbations or severe asthma. Max: 4 mg/day.
Titrate to lowest effective dose once stable.
Inhaled corticosteroid plus long-acting β₂ agonists (preferred)
Budesonide, Formoterol Fumarate Pressurized inhalation, suspension;

Adults: 2 oral inhalations of either 80/4.5 (80 mcg budesonide with 4.5 mcg
formoterol per actuation) or 160/4.5 (160 mcg budesonide with 4.5 mcg
formoterol per actuation) twice daily. Choose dose based on asthma

severity and previous therapy. Max: 2 oral inhalations of 160/4.5 twice daily
(640 mcg budesonide with 18 mcg formoterol per day).
Single maintenance and reliever therapy (SMART); same inhaler is used

for both regular maintenance dosing and as needed to alleviate symptoms.
Only use Budesonide-formoterol as reliever when this combination is

also used as maintenance therapy. 17
Fluticasone-salmeterol combination product
Fluticasone Propionate, Salmeterol Pressurized inhalation, suspension;

Adults: 2 oral inhalations twice daily, of either 45/21 (45 mcg fluticasone/21
mcg salmeterol per inhalation), 115/21 (115 mcg fluticasone/21 mcg
salmeterol per inhalation), or 230/21 (230 mcg fluticasone/21 mcg
salmeterol per inhalation). Max: 2 oral inhalations of 230/21 twice daily
(920 mcg fluticasone with 84 mcg salmeterol per day).
Fluticasone Propionate, Salmeterol Inhalation powder; Adults: 1 oral

inhalation twice daily of either 100/50 (100 mcg fluticasone and 50 mcg
salmeterol per inhalation), 250/50 (250 mcg fluticasone and 50 mcg
salmeterol per inhalation), or 500/50 (500 mcg fluticasone and 50 mcg
salmeterol per inhalation). Max: 1 oral inhalation of 500/50 twice daily
(1,000 mcg fluticasone and 100 mcg salmeterol per day).
Fluticasone Propionate, Salmeterol Inhalation powder; Adults: 1 oral

inhalation of 55/14 (55 mcg fluticasone and 14 mcg salmeterol per
inhalation) twice daily is the usual initial dose if not previously on inhaled
corticosteroids (ICS). Do not use a spacer device or volume holding
chamber. Use higher dosages in patients with more severe asthma, either 1
oral inhalation of 113/14 (113 mcg fluticasone and 14 mcg salmeterol per
inhalation) or 232/14 (232 mcg fluticasone and 14 mcg salmeterol per
inhalation) twice daily. SWITCHING FROM ANOTHER ICS PRODUCT:
Select dose based on asthma severity and previous asthma therapy. Max: 1
oral inhalation of 232/14 twice daily (464 mcg fluticasone and 28 mcg
salmeterol per day).
Fluticasone-vilanterol combination product
Fluticasone Furoate Inhalation powder, Vilanterol Inhalation powder;

Adults: 1 oral inhalation of either 100/25 (100 mcg of fluticasone and 25
mcg of vilanterol per actuation) or 200/25 (200 mcg fluticasone and 25 mcg
vilanterol per actuation) once daily. Choose dose based on asthma severity
and previous therapy. Max: 200 mcg fluticasone with 25 mcg vilanterol per
day.
Leukotriene receptor antagonists (second line)
Montelukast
Montelukast Sodium Oral tablet; Adults: 10 mg PO once daily in the

evening. LIMIT OF USE: Montelukast is not indicated for treatment of an
acute asthma attack.
FDA has issued warning regarding serious neuropsychiatric adverse

effects. 4
Zafirlukast
Zafirlukast Oral tablet; Adults: 20 mg PO twice daily.
Maintenance therapy; add on agents for step 4 and 5
Long-acting muscarinic antagonist
Tiotropium
Tiotropium Respiratory spray, solution; Adults: 2 oral inhalations (1.25

mcg/actuation) for a total dose of 2.5 mcg once daily, at the same time each
day, is the usual and max dosage.
Leukotriene synthesis inhibitor
Zileuton
Zileuton Oral tablet; Adults: 600 mg PO 4 times per day, taken with meals
and at bedtime.
Zileuton Oral tablet, biphasic release; Adults: 1,200 mg PO twice daily,

within one hour after morning and evening meals.
Macrolide antibiotic
Azithromycin
Azithromycin Oral tablet; Adults: 250 to 500 mg PO 3 days per week.
Biologic agents 33
Benralizumab
Benralizumab Solution for injection; Adults: 30 mg subcutaneously once

every 4 weeks for the first 3 doses, followed by 30 mg subcutaneously once
every 8 weeks thereafter.
Mepolizumab
Mepolizumab Solution for injection; Adults: 100 mg subcutaneously once

every 4 weeks.
Omalizumab
Omalizumab (Hamster) Solution for injection; Adults: 150 to 375 mg

subcutaneously every 2 weeks or every 4 weeks. Dosage and frequency
determined by baseline IgE (units/mL) and weight (kg). Adjust doses for
significant changes in body weight. Do not administer more than 150 mg
per injection site.
Risk of serious hypersensitivity reactions or anaphylaxis, and

omalizumab hypersensitivity may occur after any dose of omalizumab.
Omalizumab is derived from Chinese hamster ovarian cells and may be
inappropriate for use by patients with known hamster protein
hypersensitivity. Omalizumab is contraindicated for use by patients who
have experienced a severe omalizumab hypersensitivity reaction,
including anaphylaxis or a history of angioedema with the drug.
Administration of omalizumab requires a specialized care setting that is
equipped and prepared to manage serious hypersensitivity reactions,
including anaphylaxis that can be life-threatening.
Reslizumab
Reslizumab Solution for injection; Adults: 3 mg/kg IV infusion once every

4 weeks. Discontinue the infusion immediately if the patient experiences a
severe systemic reaction, including anaphylaxis.
Dupilumab
For eosinophilic phenotype moderate-to-severe asthma
Dupilumab Solution for injection; Adults: 400 mg subcutaneously

initially (as two 200 mg injections), followed by 200 mg subcutaneously
every other week OR 600 mg subcutaneously initially (as two 300 mg
injections), followed by 300 mg subcutaneously every other week.
For oral corticosteroid-dependent moderate-to-severe asthma
Dupilumab Solution for injection; Adults: 600 mg subcutaneously

initially (as two 300 mg injections), followed by 300 mg subcutaneously
every other week.
Oral corticosteroid
Prednisone
Prednisone Oral tablet; Adults: 7.5 to 60 mg/day PO once daily in the

morning or every other day as needed for symptom control; use lowest
effective dose; alternate day therapy may produce less adrenal suppression.
Acute exacerbation of asthma
Inhaled short-acting β₂ agonist
Albuterol
Albuterol Pressurized inhalation, suspension; Adults: 4 to 10 oral inhalations

of 90 mcg/actuation (total: 360 to 900 mcg) every 20 minutes for the first hour
for mild to moderate exacerbations. After the first hour, the dose required
may vary from 4 to 10 oral inhalations (360 to 900 mcg) every 3 to 4 hours up
to 6 to 10 oral inhalations (540 to 900 mcg) every 1 to 2 hours, or more often.
Albuterol Sulfate Nebulizer solution; Adults: 2.5 mg via nebulizer every 20

minutes for the first hour for mild to moderate exacerbation. After the first
hour, 2.5 mg every 3 to 4 hours up to 2.5 mg every 1 to 2 hours, or more
often. Typical dose: 2.5 mg via nebulizer 3 to 4 times daily.
Levalbuterol Hydrochloride Nebulizer solution; Adults: 1.25 mg via nebulizer

every 20 minutes for the first hour for mild to moderate exacerbation. After
the first hour, 1.25 mg every 3 to 4 hours and up to 1.25 mg every 1 to 2

hours, or more often. Typical dose range: 0.63 mg to 1.25 mg via nebulizer 3
times daily, every 6 to 8 hours.
Mast cell stabilizer
Cromolyn
Cromolyn Sodium Nebulizer solution; Adults: 20 mg via nebulizer 4 times

per day. Once stabilized, may be able to reduce to 3 times per day.
Inhaled anticholinergics
Ipratropium
Ipratropium Bromide Pressurized inhalation, solution; Adults: 136 mcg (8

actuations of 17 mcg/actuation) via oral inhalation every 20 minutes as
needed for up to 3 hours has been recommended for severe asthma
exacerbation in the emergency care setting. Used in addition to SABA (e.g.,
albuterol).
Ipratropium Bromide Nebulizer solution; Adults: 500 mcg via nebulizer

every 20 minutes for 3 doses, then as needed (for up to 3 hours) has been
recommended for severe asthma exacerbation in the emergency care setting.
Used in addition to SABA (e.g., albuterol).
Ipratropium-albuterol combination product
Ipratropium Bromide, Albuterol Sulfate Nebulizer solution; Adults: 3 mL

(containing 0.5 mg ipratropium bromide; 2.5 mg albuterol per 3 mL) via
nebulizer every 20 minutes for 3 doses, then as needed (usually every 4 to 6
hours).
Smooth muscle relaxant
Magnesium sulfate
Magnesium Sulfate Solution for injection; Adults: 2 g IV once.
Systemic corticosteroids
Prednisone
For mild exacerbation (outpatient)
Prednisone Oral tablet; Adults: 40 to 60 mg/day PO in 1 to 2 divided doses

for 3 to 10 days or until the patient achieves peak expiratory flow (PEF) of
80% of personal best or symptoms resolve. Another recommendation is 40
to 50 mg/day usually for 5 to 7 days (or 1 mg/kg/day); Max: 50 mg/day.
For moderate to severe exacerbation (emergency department or inpatient)
Prednisone Oral tablet; Adults: One recommendation is 40 mg/day or 1

mg/kg/day for 5 to 7 days; Max: 50 mg/day. Alternatively, 40 to 80 mg/day
PO in 1 to 2 divided doses until peak expiratory flow is 70% of predicted
or personal best; total course: 3 to 10 days.
Methylprednisolone
For mild exacerbation (outpatient)
Methylprednisolone Oral tablet; Adult: 40 to 60 mg/day PO in 1 to 2

divided doses for 5 to 10 days.
For moderate to severe exacerbation (emergency department or inpatient)
Methylprednisolone Oral tablet; Adults: 40 mg PO once daily in the

morning for 5 to 7 days. Alternatively, 40 to 80 mg/day PO in 1 to 2 divided
doses until peak expiratory flow is 70% of predicted or personal best; total
course of treatment may range from 3 to 10 days.
Methylprednisolone Sodium Succinate Solution for injection; Adults: 40

mg IV/IM once daily each morning for 5 to 7 days is adequate for most
patients. Alternatively, 40 to 80 mg/day IV/IM in 1 to 2 divided doses until
peak expiratory flow is 70% of predicted or personal best. Change to oral
therapy as soon as feasible.
Exercise-induced asthma
Take as required before exercise; maintenance low-dose inhaled corticosteroids

may also be indicated
Inhaled short-acting β₂ agonist
Albuterol
Albuterol Pressurized inhalation, suspension; Adults: 180 mcg (2 actuations

of 90 mcg/actuation) via oral inhalation 15 to 30 minutes before exercise.
Albuterol Inhalation powder; Adults: 180 mcg (2 actuations of 90

mcg/actuation) via oral inhalation 15 to 30 minutes before exercise.
Levalbuterol Tartrate Pressurized inhalation, suspension; Adults: 90 mcg (2

actuations of 45 mcg/actuation) via oral inhalation 15 minutes (range, 5 to 20
minutes) before exercise.
Inhaled corticosteroid plus long-acting β₂ agonists
Budesonide, Formoterol Fumarate Pressurized inhalation, suspension;

Adults: 1 oral inhalation of 160/4.5 (160 mcg budesonide with 4.5 mcg
formoterol per actuation) 5 to 20 minutes before exercise has been used and
was efficacious in a clinical trial. FDA-approved Max: 2 oral inhalations of
160/4.5 twice daily.
Leukotriene receptor antagonists
Montelukast
Montelukast Sodium Oral tablet; Adults: 10 mg PO once, given at least 2

hours before exercise. Max: 10 mg/24 hours. Patients receiving daily
montelukast for another indication should not take an additional dose to
prevent EIB. Rescue medications (e.g., beta-agonists) should be available.
Mast cell stabilizer
Cromolyn
Cromolyn Sodium Nebulizer solution; Adults: Inhale 20 mg via nebulization

not more than 1 hour before anticipated exercise or other precipitating
factor. Effective prophylaxis lasts approximately 1 to 2 hours.
Nondrug and supportive care
Patient education about self-management establishes a partnership with the patient

and is a major component of care
Self-monitoring symptoms and peak flow meter use
Use of control chart (sample available within the National Asthma Education and
Prevention Program guidelines 1) and written asthma action plan, emphasizing
difference between controller and reliever medications (sample plan available from
the National Heart, Lung, and Blood Institute)
Supported self-management involving at least 2 hours of scheduled follow-up with

health providers significantly reduced healthcare use and improved quality of life
compared to less intensive review 36
Multidisciplinary case management may be needed for patients with severe,

difficult-to-treat disease
Reduce exposure to allergen, irritant, and air pollution triggers
Multicomponent allergen-specific intervention strategies are recommended over

single component interventions in patients who are known to be sensitized or
become symptomatic on exposure to specific allergen 17
For rodents and/or cockroaches, integrated pest management including measures

to block infestation (eg, filling holes in walls) and abatement (eg, traps)
For dust mites, combination of dust mite–impermeable pillow and mattress

covers, HEPA (high-efficiency particulate air) filter–equipped vacuum cleaner,
carpet and curtain removal, and cleaning products
For mold, use of HEPA (high-efficiency particulate air) purifiers and mold
abatement
Breathing exercises
Breathing exercise programs can be considered as an adjuvant to pharmacological

treatment 13
Smoking cessation
Weight-loss interventions
Weight loss may help overweight and obese patients to improve asthma control 13
Supplemental oxygen
Indicated for SaO₂ lower than 90%
Nasal cannula or Venturi mask (Ventimask) to maintain SaO₂ of at least 90%
Noninvasive positive pressure ventilation decreases admissions, but evidence base is

not strong 25
Procedures
Bronchial thermoplasty 17
General explanation
Procedure using radiofrequency energy to reduce airway smooth muscle mass
Administered in 3 sessions as part of a bronchoscopy
Variable outcomes; no consistent improvement in asthma control or reduction in

hospitalization, but improved quality of life and a small decrease in exacerbations
Moderate risk of adverse effects
National Asthma Education and Prevention Program recommends against its use in
patients with persistent asthma; however, it remains an option for treatment of
poorly controlled asthma
Comorbidities
Obesity
Associated with increased risk of asthma, worsening symptoms, and decreased

responsiveness to therapies 37
Weight loss may improve asthma control and should be encouraged
Allergic rhinitis
Common comorbidity that is managed with intranasal corticosteroids,
1
antihistamines, and/or immunotherapy 1
Chronic rhinosinusitis with nasal polyposis
In patients with this condition, better management of rhinosinusitis can decrease

asthma exacerbation
Subset of these patients have aspirin sensitivity that can result in severe
bronchospasm; referral to specialist is indicated
Gastroesophageal reflux disease
Unclear role in causing asthma; uncontrolled gastroesophageal reflux disease may

worsen asthma symptoms, and management of the disease is important
Allergic bronchopulmonary aspergillosis 1
Consider in patients who have asthma and a history of pulmonary infiltrates, IgE
sensitization to aspergillus, and/or corticosteroid dependency
Treat with prednisone and azole antifungal agents
COVID-19 infection
Asthma does not appear to significantly increase the risk of contracting COVID-19
infection or of more severe disease or death in most patients 38 39 40
However, some studies have found higher rates of intubation and prolonged
mechanical ventilation in patients with asthma 41
Regular asthma medications should be continued during the COVID-19

pandemic 4 42
Non-severe asthma exacerbations may be managed via telehealth with a low

threshold for face-to-face assessment 42
Usual guidelines for initiation of systemic corticosteroids for asthma

exacerbations should be followed
If possible, patients with COVID-19 infection should be given inhaled asthma

medications via inhaler rather than nebulizer to avoid aerosolizing the virus 4
Avoid spirometry in patients with known or suspected COVID-19 infection; if

possible, postpone spirometry and peak flow measurements while community
4
transmission rates are concerning 4
Special populations
Pregnant women
Asthma symptoms may change during pregnancy; can improve or worsen 43
Monthly monitoring is recommended due to the unpredictable course of asthma

during pregnancy 43
Asthma is undertreated during pregnancy compared with prepregnancy treatment

rates
Maternal asthma is associated with increased risk of low birthweight,

preeclampsia, gestational diabetes, cesarean delivery, perinatal mortality, and
neonatal hospitalization at birth 43
Uncontrolled asthma, in particular, is associated with poor perinatal outcomes
Use stepwise approach to therapy for chronic asthma 44
General principles
Inhaled medications should be continued; used for decades without

demonstrated adverse effects on the fetus 43
Albuterol is classified as a pregnancy risk category C drug but has good

safety profile 44
Guidelines recommend use of whichever inhaled corticosteroid

formulation was effective prepregnancy 44
Budesonide has the most safety documentation
Monoclonal antibodies should be continued during pregnancy if required

for asthma control 43
Minimal data exists on leukotriene receptor antagonists and long-acting β₂

agonists
Step 1 (mild intermittent asthma): short-acting β₂ agonist as needed 44
44
Step 2 (mild persistent asthma): low-dose inhaled corticosteroid 44
Step 3 (moderate persistent asthma): low-dose inhaled corticosteroid and a

long-acting β₂ agonist or low-dose inhaled corticosteroid and either
theophylline or leukotriene receptor antagonist 44
Step 4 (severe persistent asthma): high-dose inhaled corticosteroid and a long-

acting β₂ agonist; if needed, add long-term oral corticosteroid or high-dose
inhaled corticosteroid and sustained-release theophylline 44
Treat asthma exacerbations according to guidelines without modification; 45

undertreatment with avoidance of oral corticosteroids results in increased return
visits for exacerbation 46
Older adults (older than 65 years) 47
Asthma is associated with higher morbidity and mortality in this group; reasons
for this are not clearly understood
May not be recognized if overlapping with chronic obstructive pulmonary disease

(ie, asthma-chronic obstructive pulmonary disease overlap syndrome)
Diagnosis is the same as with younger adults
Use age-adjusted values when interpreting the FEV₁/FVC ratio to avoid

overdiagnosing respiratory impairment
Frail patients usually cannot adequately complete spirometric maneuvers;

alternative monitoring with effort-independent testing may be better (ie, forced
oscillation testing, if available)
Treatment guidelines were developed based on studies of younger adults, with

little data available on older patients
Carefully monitor inhaler technique as cognition and dexterity declines
Short-acting anticholinergic medications may be useful bronchodilators in

elderly patients without the cardiac adverse effects of β₂ agonists, but there are
other potential risks (eg, cognitive impairment, falls, symptomatic urinary
outlet obstruction, closed-angle glaucoma)
Inhaled corticosteroids appear to be underused and should be used as directed

by guidelines. Patients on higher doses should be monitored for cataracts and
decreased bone density
There are no studies specifically focused on the safety of inhaled long-acting β₂

agonists in elderly patients
Pharmacologic treatment of comorbidities may worsen asthma (eg, β-blockers,

aspirin and non-steroidal agents, cholinergic agents)
Monitoring
Periodic monitoring of asthma control guides decisions for maintaining or adjusting
therapy
Home self-monitoring 1
Instruct all patients to monitor at home; symptom-based monitoring or peak

flow monitoring are similarly beneficial
For patients with moderate or severe persistent asthma, peak flow monitoring
is preferred 1
Office monitoring
Assess asthma control, medication technique, asthma action plan, adherence,

and patient concerns at every patient visit
Schedule office visit at 2- to 6-week intervals when starting a new treatment or

changing treatment; perform spirometry when patient is stable after
medication change 1
Schedule office visit at 1- to 6-month intervals, after asthma control is achieved

1
Schedule office visit at 3-month intervals, if step-down therapy is likely 1
Review treatment of established stable patients regularly (eg, at least every 12

months) 30
Perform spirometry at least every 1 to 2 years 1
A Cochrane review suggests that adults with frequent exacerbations and severe
asthma may benefit from sputum eosinophil monitoring to guide need for
48
corticosteroid initiation or step-up therapy 48
Urgent asthma review is indicated in the following circumstances: 30
Patient's asthma symptoms worsen despite appropriate use of controller

medications
Patient experiences an asthma exacerbation, especially if associated with

emergency department visit or urgent care, hospitalization, nocturnal awakening,
difficulty in speaking, or marked impairment in activities of daily living
Patient has not had a routine review in the last 12 months
Patient has been prescribed more than 1 short-acting β agonist inhaler in the last
4 months or 3 or more during the previous year
Patient has been prescribed a new course of oral corticosteroids (eg, in secondary
care)
Consider periodic ophthalmologic monitoring for cataract and bone densitometry

for patients treated with high-dose inhaled corticosteroids (longer than 1 year)
and/or repeated courses of oral corticosteroids 1
Complications and Prognosis
Complications
Complications of disease
Respiratory failure
Pneumothorax
Pneumomediastinum
Airway remodeling over time with worsening airflow obstruction
Death
Complications during surgical procedures
Assess asthma control and maximize lung function before planned surgery
Make anesthesiologist aware of recent corticosteroid use
Complications of steroid pharmacotherapy
Inhaled corticosteroids
Increased incidence of pneumonia, especially at higher doses 49
May increase risk of cataracts and osteoporosis
Increased risk of oral candidiasis
Oral corticosteroids
Increased risk of oral candidiasis, osteoporosis, cataracts, and hyperglycemia
To reduce steroid complications: 1
Advise patient to use spacers with non–breath-activated metered dose inhalers
Advise patient to rinse mouth (rinse and spit) after inhalation
Use lowest dose of inhaled or oral corticosteroid that maintains asthma control
Consider calcium and vitamin D supplementation, especially for

perimenopausal women
Prognosis
Good with mild intermittent disease or persistent disease (if well controlled)
Risk factors for death from asthma include: 1
Previous exacerbations requiring ICU admission and/or intubation
3 or more emergency department visits for asthma and/or 2 or more

hospitalizations for asthma in the past year 1
Hospitalization or emergency department visit in the past 30 days 1

1
Use of more than 2 canisters of short-acting β₂ agonist per month 1
Current use or recent use of systemic corticosteroids
Patient has difficulty perceiving severity of exacerbations
Screening and Prevention
Screening
At-risk populations
A 2007 American Thoracic Society report concluded that there was insufficient
evidence to support the adoption of population-based asthma screening 50
No universally accepted screening guideline exists for exercise-induced asthma in

athletes, although some sporting organizations have established screening programs
for their internationally competitive athletes 3
Prevention
Avoid known triggers of exacerbation 1
Smoking cessation
Annual influenza vaccine to prevent influenza-induced exacerbation 1
Pneumococcal vaccination (PPSV23 unless patient has criteria for PCV13 as well) if
not previously administered 51
Education regarding the use of inhalers, peak flow meter, spacers, asthma action
plan, and adherence to recommended treatments
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Asthma in Adults - ClinicalKey 12/10/2021, 18:33

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Key Points Urgent Action

After starting pharmacotherapy, classify the asthma helpful to assess severity

In emergency care setting, discharge goal is

Smoking cessation is critical

Bronchoprovocation with methacholine, histamine, cold air, or exercise challenge

Clinically presents as recurrent episodes of cough and wheezing

Reversibility is defined as 12% increase or more from baseline in FEV₁ (minimum

Symptoms occur 2 or fewer days per week

No interference with normal activity

Nighttime awakenings 2 times per month or less

FEV₁ (predicted within reference range for patient between exacerbations)

FEV₁/FVC within reference range

1 or fewer exacerbations per year requiring systemic corticosteroids

Mild persistent asthma 1

Minor limitation to normal activity

Nighttime awakenings 3 to 4 times per month

FEV₁ 80% predicted or higher

FEV₁/FVC within reference range

2 or more exacerbations per year that require systemic corticosteroids

Moderate persistent asthma 1

Symptoms occur daily

Some limitation to normal activity

Use of short-acting β₂ agonist for daily symptom control

FEV₁ 60% to 80% predicted

2 or more exacerbations per year that require systemic corticosteroids

Severe persistent asthma 1

Symptoms occur throughout the day on a daily basis

Extreme limitation of normal activity

FEV₁ less than 60% predicted

FEV₁/FVC reduced by more than 5%

2 or more exacerbations per year that require systemic corticosteroids

Classification of asthma control (patients using controller medication)

Symptoms occur 2 or fewer days per week

No interference with normal activities

Nighttime awakenings 2 times per month or less

Not well controlled 1

Symptoms occur more than 2 days per week

Some limitation of normal activities

Nighttime awakenings 1 to 3 times per week

FEV₁ (predicted) or peak expiratory flow (personal best) 60% to 80%

Very poorly controlled 1

Symptoms occur throughout the day

Extreme limitation of normal activities

Nighttime awakenings 4 or more times per week

Classification of acute exacerbations (worsening of baseline function)

Dyspnea only with activity

Peak expiratory flow of 70% or higher of predicted or personal best

Dyspnea limits usual activity

Peak expiratory flow 40% to 69% of predicted or personal best

Peak expiratory flow lower than 40% predicted or personal best

Too dyspneic to speak

Peak expiratory flow lower than 25% of predicted or personal best

Continuous, severe asthma exacerbation resistant to treatment

Common phenotype in late/adult-onset asthma

Occurs in patients with no history of allergies

May be triggered by upper respiratory tract infection or other factors

Associated with elevated blood IgE