Confirmation of diagnosis if necessary

Symptom control and modifiable

Adults
risk factors (including lung function)
Comorbidities
E Inhaler technique and adherence
NS
Personalized asthma management: PO Patient goals

AS
S
RE
Assess, Adjust, Review response

S
ES
R EV I E W
Symptoms

S
Exacerbations
Side effects
Lung function
Patient satisfaction Treatment of modifiable risk factors
and comorbidities STEP 5
ADJUST
Nonpharmacologic strategies High-dose
Asthma medication options: Education and skills training ICS-LABA
Asthma medications STEP 4
Adjust treatment up and down for Refer for
individual patient needs Medium-dose phenotypic

PULMONARY DISORDERS
STEP 3
ICS-LABA assessment
STEP 2
Low-dose ± add-on
PREFERRED STEP 1 therapy,
Daily low-dose inhaled corticosteroid (ICS), ICS-LABA
CONTROLLER eg, tiotropium,
to prevent exacerbations As-needed or as-needed low-dose ICS-formoterol1 anti-IgE,
and control symptoms low-dose anti-IL5/5R,
ICS-formoterol1 anti-IL4R
Other Low-dose ICS Leukotriene receptor antagonist (LTRA), or Medium-dose High-dose Add low-dose
controller options low-dose ICS taken whenever SABA taken2 ICS, or low-dose ICS, add-on OCS, but
taken whenever
ICS+LTRA4 tiotropium, or consider
SABA is taken2
add-on LTRA4 side effects
PREFERRED As-needed low-dose ICS-formoterol1 As-needed low-dose ICS-formoterol for patients
RELIEVER prescribed maintenance and reliever therapy3

CMDT 2022
Other As-needed short-acting b2–agonist (SABA)
reliever option
1Off-label; data only with budesonide-formoterol (bud-form) 3Low-dose ICS-form is the reliever for patients prescribed
2Off-label; separate or combination ICS and SABA inhalers bud-form of BDP-form maintenance and reliever therapy
4Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV1 > 70% predicted

▲ Figure 9–1. Personalized management to control asthma symptoms and to minimize future risk. BDP, beclomethasone dipropionate; HDM SLIT, house dust mite
sublingual immunotherapy; LABA, long-acting beta-2-agonist; OCS, oral corticosteroids; SABA, short-acting beta-2-agonist. (Adapted with permission from Global Ini-
tiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019, ©2019 Global Initiative for Asthma. Available from: www.ginasthma.org.)

247
 248 CMDT 2022 CHAPTER 9

Table 92. Long-term controller medications for asthma.

Medication Dosage Form Adult Dose Comments

Inhaled Corticosteroids ICS See Table 9–4
Systemic Corticosteroids Applies to all three corticosteroids
Methylprednisolone 2-, 4-, 6-, 8-, 16-, 32-mg tablets 40–60 mg • Administer single dose in am either daily
or on alternate days (alternate-day ther-
Prednisolone 5-mg tablets; 5 mg/5 mL, 40–60 mg
apy may produce less adrenal suppres-
15 mg/5 mL oral solution
sion) as needed for control.
Prednisone 1-, 2.5-, 5-, 10-, 20-, 50-mg 7.5–60 mg • Short courses or “bursts” as single or two
tablets; 5 mg/mL oral divided doses for 3–10 days are effective
solution for establishing control when initiating
therapy or during a period of gradual
deterioration.
• There is no evidence that tapering the
dose following improvement in symp-
tom control and pulmonary function
prevents relapse.
Inhaled LABA Should not be used for symptom relief
or exacerbations. Use with inhaled
corticosteroids.
Formoterol Inhalation: 20 mcg/2 mL nebu- 20 mcg every 12 hours • Additional doses should not be adminis-
lizer (DPI discontinued by FDA tered for at least 12 hours.
in United States) • Agents should be used only with their
specific inhaler and should not be taken
Salmeterol DPI: 50 mcg/actuation 1 blister every 12 hours
orally.
• Decreased duration of protection against
EIB may occur with regular use.
Combined Medication
Budesonide/formoterol HFA MDI: 80 mcg/4.5 mcg 2 inhalations twice daily; dose • 80/4.5 mcg for asthma not controlled on
160 mcg/4.5 mcg depends on severity of low- to medium-dose ICS.
asthma • 160/4.5 mcg for asthma not controlled on
medium- to high-dose ICS.
Fluticasone/salmeterol DPI: 100 mcg/50 mcg 1 inhalation twice daily; dose • 100/50 mcg DPI or 45/21 mcg HFA for
250 mcg/50 mcg depends on severity of asthma not controlled on low- to
500 mcg/50 mcg asthma medium-dose ICS.
HFA: 45 mcg/21 mcg • 250/50 mcg DPI or 115/21 mcg HFA for
115 mcg/21 mcg asthma not controlled on medium- to
230 mcg/21 mcg high-dose ICS.
Fluticasone furoate/ DPI: 100 mcg/25 mcg or 1 puff inhaled daily • Once-daily asthma maintenance.
vilanterol 200 mcg’/25 mcg per blister
Mometasone/formoterol 100 mcg/5 mcg/spray 2 inhalations twice daily
200 mcg/5 mcg/spray
Cromolyn and Nedocromil
Cromolyn MDI: 0.8 mg/puff 2 puffs four times daily • 4- to 6-week trial may be needed to deter-
Nebulizer: 20 mg/ampule 1 ampule four times daily mine maximum benefit.
• Dose by MDI may be inadequate to affect
Nedocromil MDI: 1.75 mg/puff 2 puffs four times daily
hyperresponsiveness.
• One dose before exercise or allergen
exposure provides effective prophylaxis
for 1–2 hours. Not as effective for EIB as
SABA.
• Once control is achieved, the frequency of
dosing may be reduced.

(continued)
 PULMONARY DISORDERS CMDT 2022 249

Table 92. Long-term controller medications for asthma. (continued)

Medication Dosage Form Adult Dose Comments

Inhaled Long-Acting Anticholinergic Should not be used for symptom relief or
exacerbations. Use with ICS.
Tiotropium DPI: 18 mcg/blister 1 blister daily
Leukotriene Modifiers
Leukotriene Receptor Antagonists
Montelukast 4- or 5-mg chewable tablet; 10 mg daily at bedtime • Exhibits a flat dose-response curve. Doses
10-mg tablet > 10 mg will not produce a greater
response in adults.
Zafirlukast 10- or 20-mg tablet 20-mg tablet twice daily • Administration with meals decreases
bioavailability; take at least 1 hour before
or 2 hours after meals.
• Monitor for symptoms and signs of hepatic
dysfunction.
5-Lipoxygenase Inhibitor
Zileuton 600-mg tablet 600 mg four times daily • Monitor hepatic enzyme (ALT).
Methylxanthines
Theophylline Liquids, sustained-release tablets, Starting dose: 10 mg/kg/day • Adjust dose to achieve serum concentra-
and capsules up to 300 mg maximum tion of 5–15 mcg/mL after at least 48
Usual maximum dose: hours on same dose.
800 mg/day • Due to wide interpatient variability in
theophylline metabolic clearance, routine
serum theophylline level monitoring is
important.
Monoclonal Antibodies
Omalizumab Subcutaneous injection Dependent on pretreatment • Binds to IgE; prevents interaction with IgE
IgE level; up to 375 mg receptor on mast cells and basophils
every 2 weeks • Carries black-box warning of anaphylaxis
• Suggested IgE level 30–1500 international
units/mL
Mepolizumab Subcutaneous injection 100 mg every 4 weeks • Binds to IL-5; prevents interaction with
receptor
• Suggested AEC ≥ 150–300/mcL
(0.15–0.3 × 109/L)
Reslizumab Intravenous injection 3 mg/kg every 4 weeks • Binds to IL-5; prevents interaction with
receptor
• Carries black-box warning of anaphylaxis
• Suggested AEC ≥ 400/mcL (0.4 × 109/L)
Benralizumab Subcutaneous injection 30 mg every 4 weeks for • Binds to IL-5 receptor; blocks receptor-
3 doses, then every ligand interaction and also causes apopto-
8 weeks sis of basophils and eosinophils
• Suggested AEC ≥ 300/mcL (0.3 × 109/L)
Dupilumab Subcutaneous injection 200 or 300 mg every 2 weeks • Binds to IL-4Ralpha; blocks IL-4 and IL-13
signaling
• Suggested AEC ≥ 150/mcL (0.15 × 109/L)
and/or FENO ≥ 25 ppb

AEC, absolute eosinophil count; ALT, alanine aminotransferase; DPI, dry powder inhaler; EIB, exercise-induced bronchospasm; FDA, US Food
and Drug Administration; FENO, fractional exhaled nitric oxide; HFA, hydrofluoroalkane; LABA, long-acting beta-2-agonist; MDI, metered-
dose inhaler; SABA, short-acting beta-2-agonist.
 250 CMDT 2022 CHAPTER 9

Table 93. Reliever medications for asthma.

Medication Dosage Form Adult Dose Comments

Inhaled Short-Acting Beta-2-Agonists SABA
Albuterol CFC MDI: 90 mcg/puff, 2 puffs 5 minutes before exercise • An increasing use or lack of expected effect
200 puffs/canister 2 puffs every 4–6 hours as needed indicates diminished control of asthma.
Albuterol HFA MDI: 90 mcg/puff, 2 puffs 5 minutes before exercise • Not recommended for long-term daily treat-
200 puffs/canister 2 puffs every 4–6 hours as needed ment. Regular use exceeding 2 days/week for
symptom control (not prevention of EIB)
Pirbuterol CFC MDI: 200 mcg/puff, 2 puffs 5 minutes before exercise indicates the need to step up therapy.
400 puffs/canister 2 puffs every 4–6 hours as needed • Differences in potency exist, but all products
Levalbuterol HFA MDI: 45 mcg/puff, 2 puffs 5 minutes before exercise are essentially comparable on a per-puff
200 puffs/canister 2 puffs every 4–6 hours as needed basis.
• May double usual dose for mild
exacerbations.
• Prime the inhaler by releasing four actuations
prior to use.
• Periodically clean HFA activator, as drug may
block/plug orifice.
Albuterol Nebulizer solution: 1.25–5 mg in 3 mL of saline every • May mix with budesonide inhalant suspen-
0.63 mg/3 mL 4–8 hours as needed sion, cromolyn, or ipratropium nebulizer
1.25 mg/3 mL solutions.
2.5 mg/3 mL • May double dose for severe exacerbations.
5 mg/mL (0.5%)
Levalbuterol Nebulizer solution: 0.63–1.25 mg every 8 hours as • Compatible with budesonide inhalant
(R-albuterol) 0.31 mg/3 mL needed suspension. The product is a sterile-filled,
0.63 mg/3 mL preservative-free, unit dose vial.
1.25 mg/0.5 mL
1.25 mg/3 mL
Anticholinergics
Ipratropium HFA MDI: 17 mcg/puff, 2–3 puffs every 6 hours • Evidence is lacking for anticholinergics
200 puffs/canister producing added benefit to beta-2-agonists
in long-term asthma control therapy.
Nebulizer solution: 0.25 mg every 6 hours
0.25 mg/mL (0.025%)
Ipratropium with MDI: 18 mcg/puff of 2–3 puffs every 6 hours
albuterol ipratropium bromide
and 90 mcg/puff of
albuterol, 200 puffs/
canister
Nebulizer solution: 3 mL every 4–6 hours • Contains EDTA to prevent discolorations of the
0.5 mg/3 mL ipratro- solution. This additive does not induce
pium bromide and bronchospasm.
2.5 mg/3 mL albuterol
Systemic Corticosteroids
Methylprednisolone 2-, 4-, 6-, 8-, 16-, 32-mg 40–60 mg/day as single or • Short courses or “bursts” are effective for estab-
tablets 2 divided doses lishing control when initiating therapy or dur-
ing a period of gradual deterioration.
• The burst should be continued until symptoms
resolve and the PEF is at least 80% of personal
best. This usually requires 3–10 days but may
require longer. There is no evidence that taper-
ing the dose following improvements prevents
relapse.
Prednisolone 5-mg tablets; 40–60 mg/day as single or
5 mg/5 mL, 15 mg/ 2 divided doses
5 mL oral solution
(continued)
 254 CMDT 2022 CHAPTER 9

Table 95. Evaluation and classification of severity of asthma exacerbations.

Mild Moderate Severe Respiratory Arrest Imminent

Symptoms
Breathlessness While walking At rest, limits activity At rest, interferes with While at rest, mute
conversation
Talks in Sentences Phrases Words Silent
Alertness May be agitated Usually agitated Usually agitated Drowsy or confused
Signs
Respiratory rate Increased Increased Often > 30/minute > 30/minute
Body position Can lie down Prefers sitting Sits upright Unable to recline
Use of accessory muscles, Usually not Commonly Usually Paradoxical thoracoabdominal
suprasternal retractions movement
Wheeze Moderate, often only Loud; throughout Usually loud; throughout Absent
end expiratory exhalation inhalation and
exhalation
Pulse/minute < 100 100–120 > 120 Bradycardia
Pulsus paradoxus Absent < 10 mm Hg May be present Often present Absence suggests respiratory
10–25 mm Hg > 25 mm Hg muscle fatigue
Functional Assessment
PEF or FEV1 % predicted ≥ 70% 40–69% < 40% < 25%
or % personal best
Pao2 (on air, mm Hg) Normal1 ≥ 601 < 60: possible cyanosis < 60: possible cyanosis
1 1 1
Pco2 (mm Hg) < 42 < 42 ≥ 42 ≥ 421
1 1 1
Sao2 (on air) > 95% 90–95% < 90% < 90%1
1
Test not usually necessary.
FEV1, forced expiratory volume in 1 second; PEF, peak expiratory flow; Sao2, oxygen saturation.
Adapted from National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management
of Asthma. National Institutes of Health Pub. No. 08-4051. Bethesda, MD, 2007.

sef-assessment, (3) a fw-up appntment, and (4) an shud be gven n the frst hur f therapy. Sme studes
atn pan fr managng reurrene. suggest that ntnuus therapy s mre effetve than
ntermttent admnstratn f these agents, but there s
B. Severe Exacerbations n ear nsensus as ng as smar dses are admns-
tered. After the frst hur, the frequeny f admnstra-
Severe exaerbatns f asthma an be fe-threatenng, s tn vares ardng t mprvements n arfw and
treatment shud be started mmedatey. A patents wth a symptms and urrene f sde effets. Ipratrpum
severe exaerbatn shud mmedatey reeve xygen, hgh brmde redues the rate f hspta admssns when
dses f an nhaed SABA, and system rtsterds. A added t nhaed SABAs n patents wth mderate t
bref hstry pertnent t the exaerbatn an be m- severe asthma exaerbatns.
peted whe suh treatment s beng ntated. Mre Systemic corticosteroids are admnstered as
detaed assessments, nudng abratry studes, usuay detaed abve. Intravenous magnesium sulfate (2 g
add tte eary n and s shud be pstpned unt after ntravenusy ver 20 mnutes) s nt remmended fr
therapy s nsttuted. Eary ntatn f oxygen therapy s rutne use n asthma exaerbatns. Hwever, a 2-g
paramunt beause asphyxa s a mmn ause f asthma nfusn ver 20 mnutes may redue hsptazatn
deaths. Suppementa xygen shud be gven t mantan rates n aute severe asthma (FEV1 ess than 25% f pre-
an Sao2 greater than 90% r a Pao2 greater than 60 mm Hg. dted n presentatn r faure t respnd t nta
Oxygen-ndued hypventatn s extremey rare n asth- treatment).
mat patents, and nern fr hyperapna shud never Muyt agents (eg, aetyystene, ptassum dde)
deay rretn f hypxema. may wrsen ugh r arfw bstrutn. Anxyt and
Frequent hgh-dse devery f an inhaled SABA s hypnt drugs are generay ntrandated n severe
ndated and usuay we terated n severe arway asthma exaerbatns beause f ther ptenta respratry
bstrutn. At east three MDI r nebuzer treatments depressant effets.
 PULMONARY DISORDERS CMDT 2022 255

Primary Care Patient presents with acute or subacute asthma exacerbation

Is it asthma?
Assess the Patient Risk factors for asthma-related death?
Severity of exacerbation?

Mild or Moderate Severe Life-threatening

Talks in phrases, prefers Talks in words, sits hunched Drowsy, confused,
sitting to lying, not agitated forward, agitated or silent chest
Respiratory rate increased Respiratory rate > 30/min
Accessory muscles not used Accessory muscles in use
Pulse rate 100–120 bpm Pulse rate > 120 bpm
O2 saturation (on air) 90–95% O2 saturation (on air) < 90%
PEF > 50% predicted or best PEF ≤ 50% predicted or best
Urgent

Start Treatment
SABA: 4–10 puffs by MDI + spacer, Transfer to acute
repeat every 20 minutes for 1 hour care facility
Worsening
Prednisolone: adults 40–50 mg, While waiting: give SABA,
children 1–2 mg/kg. max. 40 mg ipratropium bromide,
Controlled O2 (if available): target O2, systemic corticosteroid
saturation 93–95% (children: 94–98%)

Continue treatment with SABA as needed Worsening

Assess response at 1 hour (or earlier)
Improving
Arrange at discharge
Assess for discharge
Reliever: continue as needed
Symptoms improved, not needing SABA
Controller: start, or step up.
PEF improving, and > 60–80% of personal
Check inhaler technique, adherence
best or predicted
Prednisolone: continue, usually for 5–7 days
Oxygen saturation > 94% (room air)
(3–5 days for children)
Resources at home adequate
Follow up: within 2–7 days (1–2 days for children)

Follow up
Review symptoms and signs: Is the exacerbation resolving? Should prednisolone be continued?
Reliever: Reduce to as-needed.
Controller: Continue higher dose for short term (1–2 weeks) or long term (3 months), depending on
background to exacerbation
Risk factors: Check and correct modifiable risk factors that may have contributed to exacerbation,
including inhaler technique and adherence. Refer if > 1–2 exacerbations in a year.
Action plan: Is it understood? Was it used appropriately? Does it need modification?

▲ Figure 9–2. Management of asthma exacerbations in primary care. O2, oxygen; PEF, peak expiratory flow; SABA,
short-acting beta-2-agonist (doses are for salbutamol). (Adapted with permission from Global Initiative for Asthma.
Global Strategy for Asthma Management and Prevention, 2019, ©2019 Global Initiative for Asthma. Available from:
www.ginasthma.org.)

Mutpe studes suggest that nfetns wth vruses Antbts shud be nsdered when there s a hgh
(rhnvrus) and batera (Mycoplasma pneumoniae, Chla- kehd f aute batera respratry trat nfetn,
mydophila pneumoniae) predspse t aute exaerbatns suh as when patents have fever r puruent sputum and
f asthma and may undere hrn, severe asthma. The evdene f pneumna r batera snusts.
use f empr antbts s, hwever, nt remmended In the emergency department setting, repeat assess-
n rutne asthma exaerbatns beause there s n n- ment f patents wth severe exaerbatns shud be dne
sstent evdene t supprt mprved na utmes. after the nta dse f an nhaed SABA and agan after
 256 CMDT 2022 CHAPTER 9

Initial Assessment Are any of the following present?

A: airway B: breathing C: circulation Drowsiness, Confusion, Silent chest

No
Yes

Further triage by clinical status Consult ICU, start SABA and O2,
according to worst feature and prepare patient for intubation

Mild or Moderate Severe

Talks in phrases Talks in words
Prefers sitting to lying Sits hunched forward
Not agitated Agitated
Respiratory rate increased Respiratory rate > 30/min
Accessory muscles not used Accessory muscles being used
Pulse rate 100–120 bpm Pulse rate > 120 bpm
O2 saturation (on air) 90–95% O2 saturation (on air) < 90%
PEF > 50% predicted or best PEF ≤ 50% predicted or best

Short-acting β2-agonists Short-acting β2-agonists

Consider ipratropium bromide Ipratropium bromide
Controlled O2 to maintain Controlled O2 to maintain
saturation 93–95% (children 94–98%) saturation 93–95% (children 94–98%)
Oral corticosteroids Oral or intravenous corticosteroids
Consider intravenous magnesium
Consider high-dose ICS

If continuing deterioration, treat as

severe and reassess for ICU

Assess clinical progress frequently

Measure lung function
in all patients 1 hour after initial treatment

FEV1 or PEF < 60% of predicted or

FEV1 or PEF 60–80% of predicted or
personal best, or lack of clinical response
personal best and symptoms improved
Severe
Moderate
Continue treatment as above
Consider for discharge planning
and reassess frequently

▲ Figure 9–3. Management of asthma exacerbations in acute care facility (eg, emergency department). FEV1, forced
expiratory volume in 1 second; ICS, inhaled corticosteroids; ICU, intensive care unit; O2, oxygen; PEF, peak expiratory
flow; SABA, short-acting beta-2-agonist. (Adapted with permission from Global Initiative for Asthma. Global Strategy for
Asthma Management and Prevention, 2019, ©2019 Global Initiative for Asthma. Available from: www.ginasthma.org.)

3 dses f an nhaed SABA (60–90 mnutes after ntatng ness. In genera, dsharge t hme s apprprate f the
treatment). The respnse t nta treatment s a better PEF r FEV1 has returned t 60% r mre f predted r
predtr f the need fr hsptazatn than s the severty persna best and f symptms are mnma r absent.
f the exaerbatn n presentatn. The desn t hsp- Patents wth a rapd respnse t treatment shud be
taze a patent shud be based n the duratn and sever- bserved fr 30 mnutes after the mst reent dse f brn-
ty f symptms, severty f arfw bstrutn, ABG hdatr t ensure stabty f respnse befre dsharge.
resuts (f avaabe), urse and severty f prr exaerba- In the intensive care setting, a sma subset f patents
tns, medatn use at the tme f the exaerbatn, w nt respnd t treatment and w prgress t
aess t meda are and medatns, adequay f sa mpendng respratry faure due t a mbnatn f
supprt and hme ndtns, and presene f psyhatr wrsenng arfw bstrutn and respratry muse fatgue