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
Inhaled Corticosteroids ICS
Systemic Corticosteroids
Methylprednisolone 2-, 4-, 6-, 8-, 16-, 32-mg tablets
Prednisolone 5-mg tablets; 5 mg/5 mL,
15 mg/5 mL oral solution
Prednisone 1-, 2.5-, 5-, 10-, 20-, 50-mg
tablets; 5 mg/mL oral
solution
Inhaled LABA
Formoterol Inhalation: 20 mcg/2 mL nebu-
lizer (DPI discontinued by FDA
in United States)
Salmeterol DPI: 50 mcg/actuation
Combined Medication
Budesonide/formoterol HFA MDI: 80 mcg/4.5 mcg
160 mcg/4.5 mcg
Fluticasone/salmeterol DPI: 100 mcg/50 mcg
250 mcg/50 mcg
500 mcg/50 mcg
HFA: 45 mcg/21 mcg
115 mcg/21 mcg
230 mcg/21 mcg
Fluticasone furoate/ DPI: 100 mcg/25 mcg or
vilanterol 200 mcg’/25 mcg per blister
Mometasone/formoterol 100 mcg/5 mcg/spray
200 mcg/5 mcg/spray
Cromolyn and Nedocromil
Cromolyn MDI: 0.8 mg/puff
Nebulizer: 20 mg/ampule
Nedocromil MDI: 1.75 mg/puff
Adult Dose
40–60 mg
40–60 mg
7.5–60 mg
20 mcg every 12 hours
1 blister every 12 hours
2 inhalations twice daily; dose
depends on severity of
asthma
1 inhalation twice daily; dose
depends on severity of
asthma
1 puff inhaled daily
2 inhalations twice daily
2 puffs four times daily
1 ampule four times daily
2 puffs four times daily
Comments
See Table 9–4
Applies to all three corticosteroids
• Administer single dose in am either daily
or on alternate days (alternate-day ther-
apy may produce less adrenal suppres-
sion) as needed for control.
• Short courses or “bursts” as single or two
divided doses for 3–10 days are effective
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.
Should not be used for symptom relief
or exacerbations. Use with inhaled
corticosteroids.
• Additional doses should not be adminis-
tered for at least 12 hours.
• Agents should be used only with their
specific inhaler and should not be taken
orally.
• Decreased duration of protection against
EIB may occur with regular use.
• 80/4.5 mcg for asthma not controlled on
low- to medium-dose ICS.
• 160/4.5 mcg for asthma not controlled on
medium- to high-dose ICS.
• 100/50 mcg DPI or 45/21 mcg HFA for
asthma not controlled on low- to
medium-dose ICS.
• 250/50 mcg DPI or 115/21 mcg HFA for
asthma not controlled on medium- to
high-dose ICS.
• Once-daily asthma maintenance.
• 4- to 6-week trial may be needed to deter-
mine maximum benefit.
• Dose by MDI may be inadequate to affect
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
Table 93. Reliever medications for asthma.
Medication Dosage Form
Inhaled Short-Acting Beta-2-Agonists SABA
Albuterol CFC MDI: 90 mcg/puff,
200 puffs/canister
Albuterol HFA MDI: 90 mcg/puff,
200 puffs/canister
Pirbuterol CFC MDI: 200 mcg/puff,
400 puffs/canister
Levalbuterol HFA MDI: 45 mcg/puff,
200 puffs/canister
Albuterol Nebulizer solution:
0.63 mg/3 mL
1.25 mg/3 mL
2.5 mg/3 mL
5 mg/mL (0.5%)
Levalbuterol Nebulizer solution:
(R-albuterol) 0.31 mg/3 mL
0.63 mg/3 mL
1.25 mg/0.5 mL
1.25 mg/3 mL
Anticholinergics
Ipratropium HFA MDI: 17 mcg/puff,
200 puffs/canister
Nebulizer solution:
0.25 mg/mL (0.025%)
Ipratropium with MDI: 18 mcg/puff of
albuterol ipratropium bromide
and 90 mcg/puff of
albuterol, 200 puffs/
canister
Nebulizer solution:
0.5 mg/3 mL ipratro-
pium bromide and
2.5 mg/3 mL albuterol
Systemic Corticosteroids
Methylprednisolone 2-, 4-, 6-, 8-, 16-, 32-mg
tablets
Prednisolone 5-mg tablets;
5 mg/5 mL, 15 mg/
5 mL oral solution
CHAPTER 9
Adult Dose
2 puffs 5 minutes before exercise
2 puffs every 4–6 hours as needed
2 puffs 5 minutes before exercise
2 puffs every 4–6 hours as needed
2 puffs 5 minutes before exercise
2 puffs every 4–6 hours as needed
2 puffs 5 minutes before exercise
2 puffs every 4–6 hours as needed
1.25–5 mg in 3 mL of saline every
4–8 hours as needed
0.63–1.25 mg every 8 hours as
needed
2–3 puffs every 6 hours
0.25 mg every 6 hours
2–3 puffs every 6 hours
3 mL every 4–6 hours
40–60 mg/day as single or
2 divided doses
40–60 mg/day as single or
2 divided doses
Comments
• An increasing use or lack of expected effect
indicates diminished control of asthma.
• Not recommended for long-term daily treat-
ment. Regular use exceeding 2 days/week for
symptom control (not prevention of EIB)
indicates the need to step up therapy.
• Differences in potency exist, but all products
are essentially comparable on a per-puff
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.
• May mix with budesonide inhalant suspen-
sion, cromolyn, or ipratropium nebulizer
solutions.
• May double dose for severe exacerbations.
• Compatible with budesonide inhalant
suspension. The product is a sterile-filled,
preservative-free, unit dose vial.
• Evidence is lacking for anticholinergics
producing added benefit to beta-2-agonists
in long-term asthma control therapy.
• Contains EDTA to prevent discolorations of the
solution. This additive does not induce
bronchospasm.
• Short courses or “bursts” are effective for estab-
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.
(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
atn pan fr managng reurrene.
B. Severe Exacerbations
Severe exaerbatns f asthma an be fe-threatenng, s
treatment shud be started mmedatey. A patents wth a
severe exaerbatn shud mmedatey reeve xygen, hgh
dses f an nhaed SABA, and system rtsterds. A
bref hstry pertnent t the exaerbatn an be m-
peted whe suh treatment s beng ntated. Mre
detaed assessments, nudng abratry studes, usuay
add tte eary n and s shud be pstpned unt after
therapy s nsttuted. Eary ntatn f oxygen therapy s
paramunt beause asphyxa s a mmn ause f asthma
deaths. Suppementa xygen shud be gven t mantan
an Sao2 greater than 90% r a Pao2 greater than 60 mm Hg.
Oxygen-ndued hypventatn s extremey rare n asth-
mat patents, and nern fr hyperapna shud never
deay rretn f hypxema.
Frequent hgh-dse devery f an inhaled SABA s
ndated and usuay we terated n severe arway
bstrutn. At east three MDI r nebuzer treatments
shud be gven n the frst hur f therapy. Sme studes
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
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-
tn vares ardng t mprvements n arfw and
symptms and urrene f sde effets. Ipratrpum
brmde redues the rate f hspta admssns when
added t nhaed SABAs n patents wth mderate t
severe asthma exaerbatns.
Systemic corticosteroids are admnstered as
detaed abve. Intravenous magnesium sulfate (2 g
ntravenusy ver 20 mnutes) s nt remmended fr
rutne use n asthma exaerbatns. Hwever, a 2-g
nfusn ver 20 mnutes may redue hsptazatn
rates n aute severe asthma (FEV1 ess than 25% f pre-
dted n presentatn r faure t respnd t nta
treatment).
Muyt agents (eg, aetyystene, ptassum dde)
may wrsen ugh r arfw bstrutn. Anxyt and
hypnt drugs are generay ntrandated n severe
asthma exaerbatns beause f ther ptenta respratry
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
sitting to lying, not agitated
Respiratory rate increased
Accessory muscles not used
Pulse rate 100–120 bpm
O2 saturation (on air) 90–95%
PEF > 50% predicted or best
Talks in words, sits hunched Drowsy, confused,
forward, agitated or silent chest
Respiratory rate > 30/min
Accessory muscles in use
Pulse rate > 120 bpm
O2 saturation (on air) < 90%
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
(rhnvrus) and batera (Mycoplasma pneumoniae, Chla-
mydophila pneumoniae) predspse t aute exaerbatns
f asthma and may undere hrn, severe asthma. The
use f empr antbts s, hwever, nt remmended
n rutne asthma exaerbatns beause there s n n-
sstent evdene t supprt mprved na utmes.
Antbts shud be nsdered when there s a hgh
kehd f aute batera respratry trat nfetn,
suh as when patents have fever r puruent sputum and
evdene f pneumna r batera snusts.
In the emergency department setting, repeat assess-
ment f patents wth severe exaerbatns shud be dne
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
Controlled O2 to maintain
saturation 93–95% (children 94–98%)
Oral corticosteroids
Ipratropium bromide
Controlled O2 to maintain
saturation 93–95% (children 94–98%)
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
treatment). The respnse t nta treatment s a better
predtr f the need fr hsptazatn than s the severty
f the exaerbatn n presentatn. The desn t hsp-
taze a patent shud be based n the duratn and sever-
ty f symptms, severty f arfw bstrutn, ABG
resuts (f avaabe), urse and severty f prr exaerba-
tns, medatn use at the tme f the exaerbatn,
aess t meda are and medatns, adequay f sa
supprt and hme ndtns, and presene f psyhatr
ness. In genera, dsharge t hme s apprprate f the
PEF r FEV1 has returned t 60% r mre f predted r
persna best and f symptms are mnma r absent.
Patents wth a rapd respnse t treatment shud be
bserved fr 30 mnutes after the mst reent dse f brn-
hdatr t ensure stabty f respnse befre dsharge.
In the intensive care setting, a sma subset f patents
w nt respnd t treatment and w prgress t
mpendng respratry faure due t a mbnatn f
wrsenng arfw bstrutn and respratry muse fatgue