Asthma in Adults

Alan Kaplan, MD, CCFP(EM), FCFP

CPhA acknowledges the contribution of Dr. David G. McCormack as the previous author of this chapter.

Introduction
Asthma is a respiratory disorder characterized by:

Paroxysmal or persistent symptoms, e.g., dyspnea, chest tightness, wheeze, sputum production
and cough
Variable airflow limitation
Airway inflammation
Airway hyperresponsiveness

Goals of Therapy
Prevent asthma-related mortality
Prevent exacerbations
Maintain asthma control:
maintain normal activity levels, e.g., avoid absence from work or school, maintain ability to
exercise without limitations
prevent daytime and nocturnal symptoms, e.g., cough, wheeze, dyspnea
maintain normal (or near normal) spirometry
Provide optimal pharmacotherapy and avoid side effects

The 2017 version of the Global Strategy for Asthma Management and Prevention (GINA Asthma)
defines asthma as a heterogeneous disease characterized by chronic airway inflammation resulting
in airflow limitation. Patients typically provide a history of wheeze, shortness of breath, chest
tightness and cough. The symptoms vary over time and in intensity as the inflammation and airflow
limitations worsen and improve.

GINA Asthma suggests aggressive control criteria: occurrence of symptoms <3 days per week or use
of reliever (fast-acting beta2-agonist) <3 doses per week.[1]

Investigations
Thorough history with particular attention to:
family history of asthma and atopy
symptoms, frequency and severity
pattern of symptoms, e.g., seasonal, perennial, diurnal variation
precipitating factors, e.g., environmental allergens, occupational exposures, irritants such
as smoke, exercise, drugs such as ASA or beta-blockers, preservatives such as sulfites,
viral respiratory infections, rhinitis, sinusitis, gastroesophageal reflux
previous prednisone use, hospitalizations, emergency room visits and intensive-care
admissions
Physical examination:
wheeze, nasal polyps
absence of findings such as crepitations, unilateral wheeze, fingernail clubbing
Objective measurements needed to confirm diagnosis and assess severity include:
spirometry (preferred method of diagnosis): reduced expiratory flow rates with reversibility
 home peak flow monitoring can be used to diagnose asthma or to monitor patients with
severe asthma or poor perception of airway obstruction
bronchoprovocation challenge test in lung function laboratories, using methacholine or
histamine, if diagnosis in doubt
other measurements can be used to predict treatment response to certain agents and
include blood eosinophil count (from CBC), FeNO (fractional exhaled nitric oxide), serum
IgE and sputum eosinophils; when commercially available, serum periostin may be helpful
office-based mannitol challenge testing, which may be available in the future
Sputum eosinophil counts may be used in specialized centres to monitor effectiveness of anti-
inflammatory therapy and guide dosage adjustments in individuals with moderate to severe
asthma[2]

Therapeutic Choices

Nonpharmacologic Choices

Advise patients to identify and avoid precipitating factors such as environmental allergens
and occupational irritants.
Smoking cessation is essential (see Tobacco Use Disorder: Smoking Cessation).[3] As well,
patients should avoid exposure to second-hand smoke whenever possible.
Hyposensitization therapy to allergens generally is not useful in the management of asthma.
[4]

Use of home air cleaners/purifiers is not supported by evidence.[5]

Pharmacologic Choices

Choose the initial level of treatment with medication after an assessment of asthma severity and
previous treatment (see Figure 1 and Figure 2).[2] Review treatment every 3–6 months and if
control is achieved, try a stepwise reduction in treatment (see Step-Up and Step-Down Therapy).

The cornerstone of asthma management is inhaled therapy that maximizes delivery of drugs to
the respiratory tract and minimizes systemic side effects. Pressurized metered dose inhalers
(pMDIs) with spacers or dry powder inhalers (DPIs) deliver drugs as effectively as nebulized
therapy, making the use of regular nebulized medications unnecessary, as it takes much longer
for patients and families to administer nebulized therapy. Inhaled medications include
bronchodilators and anti-inflammatory agents. Other medications are available by the oral route,
including anti-inflammatories and bronchodilators such as theophylline, or by injection, such as
biologic therapies. For more information, see Table 2.

Bronchodilator Agents

Short-Acting Inhaled Beta2-agonists

Salbutamol and terbutaline are short-acting beta2-adrenergic agonists (SABAs, also

known as beta2-agonists) and are agents of first choice for treatment of acute
exacerbations and for prevention of exercise-induced asthma. They are to be used as
required rather than on a fixed schedule. Although potent bronchodilators, they have little
effect on the late (inflammatory) phase of an exacerbation. If patients use a SABA 2 or
more times per week (including any doses used to prevent or treat exercise-induced
symptoms), initiate therapy with an anti-inflammatory agent.[1][6] Isoproterenol and
epinephrine have been used in the past but are not recommended for the treatment of
asthma because of lack of beta2-selectivity and potential for excessive cardiac stimulation,
especially at high doses.

Long-Acting Inhaled Beta2-agonists

Salmeterol and formoterol are long-acting beta2-agonists (LABAs) for regular twice-daily
treatment of asthma. These drugs should be used only in patients already taking inhaled
corticosteroids (ICS). Adding LABAs to ICS may permit decreasing the dose of the latter
and also has been clearly shown to reduce the incidence of exacerbations to a greater
extent in comparison with an increased dose of ICS without a LABA.[7][8] In adults,
consider adding a LABA when low-dose ICS fail to provide adequate control of asthma.[1]
[2] LABAs also help to prevent .[9]

Guidelines recommend use of LABA/ICS combination products in asthma to prevent the

use of LABAs as monotherapy. Regular use of LABA monotherapy has been associated
with an increased risk of death in asthmatics.[10]

Salmeterol has a slow onset of action and should not be used for immediate relief of
bronchospasm. Formoterol has a rapid onset and, although it is effective for rescue
therapy, it should be used only for rescue treatment when combined with budesonide due
to concerns about monotherapy with LABAs in asthma and the risk of mortality.[2][10] See
Combination Inhaled Corticosteroids and Long-Acting Bronchodilators.

Vilanterol is a LABA available only with fluticasone furoate in a combination dry powder
inhaler for once-daily administration. It is not commercially available as a single-entity
product.

Indacaterol and olodaterol are LABAs approved for use in chronic obstructive pulmonary
disease but are not indicated for asthma, as data on safety and efficacy are lacking.

Oral Beta2-agonists

Oral orciprenaline and salbutamol offer less bronchodilation, more systemic side effects
and a slower onset of action than the inhaled preparations and are not recommended.

Anticholinergic Agents

Ipratropium is a short-acting anticholinergic that is used as an add-on therapy to beta2-

agonists for management of acute asthma. It is a useful alternative for patients who are
unusually susceptible to tremor or tachycardia from beta2-agonists. Although the onset of
action is delayed compared to beta2-agonists, the bronchodilator effect lasts longer. It may
also be useful in beta-blocker-induced bronchospasm.[11]

Tiotropium is a long-acting (once-daily) bronchodilator with an indication for improvement

of lung function and a reduction of exacerbations. It has been shown to have value as an
add-on therapy to improve lung function and decrease exacerbations in patients with
symptomatic asthma despite maintenance treatment with high-dose ICS + LABA,[12]
medium-dose ICS,[13] low-dose ICS[14] and medium-dose ICS ± LABA.[15]

Methylxanthines

Oral theophylline is uncommonly used due to systemic toxicity and only mild
bronchodilator activity. Administer carefully according to standard regimens and monitor
blood levels. In theophylline-naïve patients, titrate the dose slowly to minimize side effects.
Aminophylline is no longer available in an oral formulation. Oxtriphylline is no longer
available as a single-ingredient product in Canada.

Anti-inflammatory Agents

Inhaled Corticosteroids

Inhaled beclomethasone, budesonide, ciclesonide, fluticasone and mometasone are

safe, effective, and cost-effective drugs that treat the inflammatory component of asthma.[1]
[2] They are the preferred agents for maintenance treatment and should be used regularly
at the lowest effective dose rather than “as needed” to maintain good asthma control.
Inhaled corticosteroids have a higher ratio of topical to systemic activity than do oral
corticosteroids. The incidence of pharyngeal candidiasis from deposition of the inhaled
corticosteroid in the pharynx can be reduced by rinsing the mouth after use and/or using a
spacer device. Ciclesonide is a prodrug that is biologically inert until activated by esterases
in the lung to the active medication; it may have fewer topical side effects such as thrush,
as it is inactive in the upper airway.[16] Dose equivalencies for inhaled corticosteroids are
listed in Table 1.

[1][2][5]
Table 1: Comparative Dosage for Inhaled Corticosteroids in Adults
Drug Dosage

beclomethasone pMDI (HFA) Low: ≤250 mcg/day

Moderate: 251–500 mcg/day
High: >500 mcg/day

budesonide DPI Low: ≤400 mcg/day

Moderate: 401–800 mcg/day
High: >800 mcg/day

budesonide nebules Low: ≤1000 mcg/day

Moderate: 1001–2000 mcg/day
High: >2000 mcg/day

ciclesonide pMDI Low: ≤200 mcg/day

Moderate: 201–400 mcg/day
High: >400 mcg/day

fluticasone propionate DPI or pMDI plus spacer Low: ≤250 mcg/day

Moderate: 251–500 mcg/day
High: >500 mcg/day

fluticasone furoate DPI Low: 100 mcg/day

Moderate: N/A
High: 200 mcg/day

mometasone furoate DPI Low: ≤200 mcg/day

Moderate: 400–800 mcg/day
High: >800 mcg/day

Abbreviations: DPI = dry powder inhaler; HFA = hydrofluoroalkane; N/A = not

available; pMDI = pressurized metered dose inhaler

Combination Inhaled Corticosteroids and Long-Acting Bronchodilators

As LABAs should be given only to patients already on ICS, combination products of ICS
and LABAs (ICS/LABA) have been developed. Fluticasonepropionate/salmeterol and
mometasone/formoterol are given on a regular BID schedule; fluticasone furoate/
vilanterol is used as a once-daily medication. Budesonide/formoterol can be used as
both maintenance (on a regular BID schedule) and as needed as a reliever medication.[17]
[18]
Systemic Corticosteroids

Systemic corticosteroids are useful in treating acute exacerbations. Optimal dosage has
not been established, but the Canadian guidelines suggest 25–50 mg of prednisone daily
for 7–14 days.[2] Reduce the risk of side effects by limiting treatment to short periods
(1–2 weeks) following an acute exacerbation. Less commonly, systemic corticosteroids can
be used as long-term maintenance therapy. Side effects can be significant: fluid retention,
glucose intolerance, increased blood pressure, increased appetite, mood alterations, and
weight gain in the short term, and adrenal axis suppression, avascular necrosis of the hip,
cataracts, dermal thinning, diabetes, glaucoma, hypertension, myopathy and osteoporosis
in the long term. Side effects with long-term use may be minimized by using alternate-day
dosing regimens. Newer therapeutic agents have the potential to minimize the need for use
of chronic systemic corticosteroids.

Leukotriene Receptor Antagonists

Leukotriene receptor antagonists (LTRAs, e.g., montelukast) have anti-inflammatory

properties; however, evidence suggests that they are not as effective as low-dose ICS for
improving symptoms or preventing exacerbations.[19] Consequently, they are second-line
monotherapy after ICS for asthma control.[6][19] Although ICS/LABA are more effective
than ICS with an LTRA for preventing exacerbations in adults,[20] LTRAs may be
considered as add-on therapy with an ICS (see Figure 1).[2] Zafirlukast is no longer
available in Canada.

Biologic Therapy

IgE-Neutralizing Antibody

Omalizumab, a monoclonal antibody that binds IgE, may be considered for patients
with moderate to severe persistent asthma who have had a positive skin test or in vitro
reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled
with high-dose ICS and add-on therapy. In these patients, omalizumab significantly
decreases the incidence of asthma exacerbations and improves overall asthma control.
[21][22] Therapy should be initiated by those with significant expertise in asthma
management.

Interleukin-5 Inhibitors

Mepolizumab is indicated for treatment of eosinophilic asthma. It is a subcutaneous

injection given once a month. It is indicated in patients with uncontrolled asthma or
exacerbations despite treatment with ICS and a second agent and who have a blood
eosinophil count >150 cells/mcL. Reslizumab[23] has received Notice of Compliance
(NOC) and is indicated for add-on therapy for adults with eosinophilic asthma who are
poorly controlled on ICS plus an additional agent and who have a blood eosinophil
count ≥400 cells/mcL. Reslizumab should be administered via IV infusion every
4 weeks.

Benralizumab is another interleukin-5 (IL-5) inhibitor medication that will be coming to

market in the near future with higher eosinophil blood count (>300 cells/mcL) as
prescribing criteria. It is administered every 8 weeks.[24]

IL-5 inhibitors should be used only by physicians with an expertise in asthma

management.

Immunotherapy

In a 2010 Cochrane review, subcutaneous immunotherapy (SCIT) was recommended

for asthmatic patients with identified allergies, as it reduces both asthma symptoms and the
use of asthma medications and improves bronchial hyperreactivity. One trial included in the
review found the benefit of SCIT is possibly comparable to ICS. The possibility of local or
systemic adverse effects (such as anaphylaxis) must be considered in deciding the benefit
in an individual.[25]

The role of sublingual immunotherapy (SLIT) in the treatment of asthma is less clear,
with most available evidence being in quite mild asthmatics. People receiving SLIT were no
more or less likely to experience serious unwanted side effects; these were generally very
rare, albeit the evidence in very severe asthma is lacking.[26] SLIT therapy is available for
ragweed and tree allergies. SLIT for house dust mite as a perennial allergen may be
beneficial for asthma symptoms, but further studies are necessary.

Macrolides

A 2015 Cochrane review[27] and the AZALEA study[28] found no benefit to chronic
administration of macrolides. Further research is needed to define a role for chronic
macrolide therapy due to methodologic failings of current studies and the high number of
AZALEA patients who were excluded due to previous antibiotic therapy.

Bronchial Thermoplasty

Bronchial thermoplasty is still considered an experimental therapy performed in only a few

localized centres in Canada. Thermoplasty can be considered in patients whose asthma is
uncontrolled due to persistent bronchial hyperreactivity, especially if they do not qualify for
biologic therapies.[29][30]

Inhaler Technique

All inhaler types are equally capable of delivering an appropriate medication dose.[31][32] In
daily use, however, a large majority of patients make inhalation errors.[33] Suboptimal
inhaler technique is associated with worsened health outcomes, worse asthma control and
increased risk of hospitalizations.[34] As such, inhaler technique needs to be reviewed at
every encounter to ensure optimization of pharmacotherapy.[1][2]

Adherence

Unfortunately, while first fills for ICS are quite good, this is not true for subsequent fills, with
adherence rates at approximately 36%.[35] Integrated care programs and close follow-up
can improve adherence rates.[36] Poor adherence is one of the major reasons patients
experience poor asthma control.[37] Asthma outcomes are clearly better in those who are
adherent to their medications.[38]

Asthma education programs have also clearly been shown to change patients’ behaviour
and improve adherence.[39]

The Canadian Network for Respiratory Care is a repository of Canadian Asthma Educators
available in Canada (www.cnrchome.net).

Step-Up and Step-Down Therapy

If a current level of medication is not providing sufficient asthma control, consider stepping
up therapy after 6–12 weeks. This could include stepping up reliever therapy from a low- to
medium-dose ICS, adding a LABA, adding an LTRA or theophylline, adding a long-acting
anticholinergic or considering the initiation of a biologic therapy, all depending on the
starting point. Step-up therapy is done after the diagnosis is confirmed, comorbidities such
as rhinitis and gastroesophageal reflux disease (GERD) are accounted for, triggers are
evaluated and removed, and inhaler technique has been optimized.
Similarly, once an asthmatic has attained total control (no exacerbations, no night
awakenings, near normal or normal lung function, relief of airway inflammation, if
measurable, and daytime symptoms or beta2-agonist use of less than twice per week), one
can consider step-down therapy. This should be done in 3-month intervals and can include
reducing ICS by 25–50%, reducing another agent or removing a bronchodilator. As there is
a Health Canada boxed warning against LABA monotherapy in asthma, LABA
discontinuation or reduction is often considered a desirable endpoint; however, a Cochrane
review examined studies where the LABA was withdrawn. Withdrawal may lead to more
exacerbations that need oral corticosteroids, worsened symptom control and decreased
quality of life.[40] Close follow-up is needed to prevent destabilizing these patients in the
attempt to reach the lowest effective dosages.

Asthma Action Plans

A written asthma action plan should be provided to patients to help them learn to recognize
and respond appropriately to worsening asthma. It should include specific instructions for
the patient about changes to reliever and controller medications, how and when to use oral
corticosteroids (OCS), and when to seek medical attention. The plan should be activated
when asthma symptoms are interfering with normal activities or peak expiratory flow (PEF)
has fallen by >20% for more than 2 days.

Though evidence is limited,[41] the Canadian Thoracic Society suggests that adults with a
history of severe exacerbations in the past year who required systemic corticosteroids may
initiate a trial with a 4-fold or 5-fold increase in ICS dose for 7–14 days as part of an action
plan for managing acute loss of asthma control.[2] Limited evidence has not shown any
benefit from doubling the ICS dose.[41]

The action plan should include how to step up therapy and respond to worsening control by
increasing bronchodilators and adding systemic corticosteroids as necessary. An example
of an adult asthma action plan can be found at www.asthmaactionplan.com.

Choices during Pregnancy and Breastfeeding

Asthma and Pregnancy

Pregnancy does not affect asthma in any predictable manner, with some patients noticing
worsening of symptoms, some noticing no change and others noticing improvement of symptoms
(roughly a third in each category, and usually the pattern persists in subsequent pregnancies).[1]
Much more important is the effect of asthma on the outcome of the pregnancy. Inadequate control
of asthma during pregnancy is associated with worse outcomes, such as preterm birth, low birth
weight, congenital anomalies, pre-eclampsia and placenta previa. Conversely, good control of
asthma during pregnancy is associated with a normal outcome.

Management of Asthma during Pregnancy

The best outcome for pregnancy complicated by asthma occurs with optimal management of
asthma using the same stepwise approach as in nonpregnant patients.[5] Short-acting inhaled
beta2-adrenergic agonists, theophylline and inhaled corticosteroids (particularly
budesonide) have been used extensively and are considered safe for use in pregnancy;[42]
however, theophylline may worsen gastroesophageal reflux and can cause nausea, so avoid if
possible. Accumulating evidence indicates montelukast may be used safely during pregnancy.
[43] Current experience with the use of LABAs during pregnancy has not shown adverse effects.
[44] It must be emphasized that the risk of poor outcomes due to uncontrolled asthma is vastly
higher than the risk posed by asthma medications. Consequently, clinicians and patients should
aim for the best control possible to optimize outcomes for both mother and child.[45]

Asthma and Breastfeeding

Breastfeeding has no known effect on the severity of asthma. When asthma medication is
required for a breastfeeding mother, bronchodilators (SABAs, LABAs and anticholinergics) are
considered safe.[46] Further, both inhaled and oral corticosteroids are considered safe for
breastfeeding mothers. Although theophylline is also considered safe, maintain blood
theophylline levels in the low end of the therapeutic range in the mother. There is no information
concerning the use of leukotriene receptor antagonist therapy during breastfeeding, so alternate
drugs for the control of asthma may be appropriate. Montelukast is transferred into breast milk;
[42] however, it should be noted that it is indicated for asthmatics as young as 6 months of age.

A discussion of general principles on the use of medications in these special populations can be
found in Drug Use during Pregnancy and Drug Use during Breastfeeding. Other specialized
reference sources are also provided in these appendices.

Emergency Treatment of Asthma

See Figure 3 for the emergency management of acute asthma.

Priorities include oxygenation, rehydration, bronchodilation and use of anti-inflammatory

medications.
oxygenation: use pulse oximetry to maintain oxygen saturation at 93–95%; it is not
necessary to increase to 100%
Bronchodilation using a metered dose inhaler with a spacer is equivalent to nebulized therapy.
[47][48]

Additive bronchodilator effect of ipratropium bromide and the beta2-adrenergic agonists

supports administering these 2 medications concomitantly.[49] This combination prevents
hospitalizations for adults with severe asthma exacerbations who are at higher risk of
hospitalization. Patients receiving the combination are more likely to experience adverse events,
which can include tremor, agitation and palpitations.[50]
Use oral or parenteral corticosteroids early in most patients.[51]
systemic corticosteroids should be administered to the patient within 1 hour of
presentation[52][53]
oral corticosteroids (OCS) are as effective as injectable and are quicker to administer and
less expensive; the onset of action may be slightly slower and oral formulations may be
poorly tolerated as they may cause vomiting[54][55]
consider urgent administration in acute-care settings if:
initial treatment with SABA fails to achieve lasting symptomatic improvement
current exacerbation develops in a patient taking OCS and potentially in those who
have used them within the last 3 months
the patient has required OCS for treatment of previous exacerbations
Avoid IV aminophylline in first few hours of acute asthma.[56][57]
IV magnesium sulfate is not recommended for routine administration; however, administration of
magnesium sulfate 2 g infused over 20 minutes may reduce hospital admissions in:[58][59][60]
[61]

adults with FEV1 <25–35% predicted upon presentation

adults not responding to initial treatment and continuing to have hypoxemia
Nebulized magnesium sulfate can be used in combination with nebulized salbutamol in patients
presenting with severe exacerbations (FEV1 <50% predicted).[62]

Therapeutic Tips
Avoid ASA and NSAIDs in patients with ASA-induced asthma and in high-risk patients (severe
asthma symptoms, nasal polyps, urticaria or chronic rhinitis).[63] Exercise caution in all patients.
Exercise caution with beta-blockers (including ophthalmic beta-blockers).
Treat conditions that may affect asthma control, such as rhinitis, sinusitis and GERD.
 Patient education about asthma symptoms and therapy is essential for optimal management:
review inhaler technique regularly
provide a written action plan for self-management based on peak expiratory flow rates
and/or signs and symptoms for each patient; examples of asthma action plans include:
Canadian Lung Association
www.lung.ca/sites/default/files/media/asthma_action_plan.pdf
Family Physician Airways Group of Canada www.asthmaactionplan.com

Algorithms

Figure 1: Pharmacologic Management of Asthma in Adults

[a]
For children 6–11 years of age, the preferred Step 3 treatment is medium dose ICS.
[b]
Not for children <12 years of age.
[c] Tiotropium by mist inhaler is indicated as an add-on treatment for adult patients with a history of
exacerbations; it may be used (off-label) in those 12–18 years of age.
[d]
Low-dose ICS/formoterol is the reliever medication for patients prescribed low-dose
budesonide/formoterol maintenance and reliever therapy.

Abbreviations: FEV1 = forced expiratory volume in 1 second; HDM = house dust mite; ICS = inhaled
corticosteroid; LABA = long-acting beta2-agonist; LTRA = leukotriene receptor antagonist; OCS = oral
corticosteroid; SABA = short-acting beta2-agonist; SLIT = sublingual immunotherapy
Reproduced with permission from Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017.
Available from: www.ginasthma.org.

Figure 2: GINA Assessment of Asthma Control in Adults, Adolescents and Children 6–11 Years of
Age

[a]
Excludes reliever taken before exercise.

Abbreviations: FENO = Fractional exhaled nitric oxide; FEV1 = forced expiratory volume in 1
second; ICS = inhaled corticosteroid; OCS = oral corticosteroids; SABA = short-acting beta2 agonist

Reproduced with permission from Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017.
Available from: www.ginasthma.org.

Figure 3: Management of Asthma Exacerbations in Acute Care Facility, e.g., Emergency

Department
Abbreviations FEV1 = forced expiratory volume in 1 second; ICS = inhaled corticosteroid; ICU
= intensive care unit; PEF = peak expiratory flow; SABA = short-acting beta2 agonist

Reproduced with permission from Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017.
Available from: www.ginasthma.org.

Drug Table
Table 2: Drug Therapy for Chronic Asthma in Adults

Drug/Cost[a] Dosage Adverse Effects Comments

Drug Class: Beta2-adrenergic Agonists, short-acting (SABAs)

Drug/Cost[a] Dosage Adverse Effects Comments

pMDI 100 mcg/puff: Nervousness, tremor,

Airomir, Ventolin 1–2 puffs TID–QID tachycardia, palpitations.
Diskus, Ventolin HFA, PRN; maximum
Ventolin Nebules P.F., 8 puffs/day
generics Diskus: 200 mcg
TID–QID PRN;
$
maximum
800 mcg/day
Nebules: 2.5–5 mg
QID PRN

DPI Nervousness, tremor,

Bricanyl Turbuhaler 0.5 mg/inhalation: tachycardia, palpitations.
1 inhalation Q4–6H
$ PRN; maximum
6 inhalations/day

Drug Class: Muscarinic Antagonists,[c] short-acting (SAMAs)

pMDI 20 mcg/puff: Dry mouth, metallic taste;

Atrovent HFA, generics 2 puffs Q6–8H PRN; mydriasis and glaucoma if
maximum released into eye.
$ 240 mcg/day
Nebules:
250–500 mcg Q4–6H
PRN

Drug Class: Muscarinic Antagonists/Beta2-adrenergic Agonists Combinations, short-acting

(SAMA/SABA)

Individualize dose Dry mouth, metallic taste;

Combivent UDV, Nebules: 2.5 mL mydriasis and glaucoma if
generics (0.5 mg/2.5 mg) Q6H released into eye.
PRN Nervousness, tremor,
$ tachycardia, palpitations.

Drug Class: Beta2-adrenergic Agonists, long-acting (LABAs)

DPI 12 mcg/capsule: Nervousness, tremor, Recommended

Foradil 1 capsule BID; tachycardia, palpitations. only if confident
maximum patient will use
$$ 48 mcg/day prescribed ICS
as well.
Combination
LABA/ICS
product
preferred.
Not for reliever
therapy.
Drug/Cost[a] Dosage Adverse Effects Comments

DPI: 6–12 mcg Nervousness, tremor, Recommended

Q12H; maximum tachycardia, palpitations. only if confident
Oxeze Turbuhaler 48 mcg/day patient will use
prescribed ICS
$$ as well.
Combination
LABA/ICS
product
preferred.
Not for reliever
therapy.

Diskhaler Nervousness, tremor, Recommended

Serevent 50 mcg/blister: tachycardia, palpitations. only if confident
1 blister BID patient will use
$$ prescribed ICS
Diskus
50 mcg/inhalation: as well.
1 inhalation BID Combination
LABA/ICS
product
preferred.
Not for reliever
therapy.

Drug Class: Corticosteroids, inhaled (ICS)

pMDI: Sore mouth, sore throat, Bone

Qvar 100–800 mcg/day dysphonia, oral thrush densitometry is
divided BID; usual (can be reduced by rinsing suggested in
$$$ starting dose mouth or using spacer). patients who
≤200 mcg/day[b] require high
doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Drug/Cost[a] Dosage Adverse Effects Comments

DPI: Sore mouth, sore throat, Bone

Pulmicort Turbuhaler, 400–2400 mcg/day dysphonia, oral thrush densitometry is
Pulmicort Nebuamp divided BID; usual (can be reduced by rinsing suggested in
starting dose mouth or using spacer). patients who
DPI: $$$$ 400 mcg/day[b] require high
Nebule: $$ doses or have
Nebules:
risk factors for
0.125–2 mg/dose;
osteoporosis.
dose is individualized
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.

pMDI: 100–800 mcg Sore mouth, sore throat, Bone

Alvesco daily; usual starting dysphonia, oral thrush densitometry is
dose 200 mcg/day[b] (can be reduced by rinsing suggested in
$$$ mouth or using spacer). patients who
At 800 mcg/day,
require high
divide dose BID
doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Drug/Cost[a] Dosage Adverse Effects Comments

pMDI/DPI: Sore mouth, sore throat, Bone

Flovent HFA, Flovent 200–1000 mcg/day dysphonia, oral thrush densitometry is
Diskus divided BID; may (can be reduced by rinsing suggested in
increase to 1000 mcg mouth or using spacer). patients who
$$ BID if very severe; require high
usual starting dose doses or have
200 or 250 mcg/day[b] risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.

DPI: 200 mcg daily Sore mouth, sore throat, Bone

Arnuity Ellipta dysphonia, oral thrush densitometry is
(can be reduced by rinsing suggested in
$$$ mouth or using spacer). patients who
require high
doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Drug/Cost[a] Dosage Adverse Effects Comments

DPI: 200–400 mcg Sore mouth, sore throat, Bone

Asmanex daily; usual starting dysphonia, oral thrush densitometry is
dose 200 mcg/day[b]; (can be reduced by rinsing suggested in
$$ maximum 400 mcg mouth or using spacer). patients who
BID require high
doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.

Drug Class: Muscarinic Antagonists,[c] long-acting (LAMAs)

SMI: Dry mouth, metallic taste;

Spiriva Respimat 2.5 mcg/actuation: mydriasis and glaucoma if
2 actuations inhaled released into eye.
$$ once daily

Drug Class: Inhaled Corticosteroid/Beta2-adrenergic Agonist Combinations, long-acting

(ICS/LABA)
Drug/Cost[a] Dosage Adverse Effects Comments

DPI 100/6 mcg or Sore mouth, sore throat, Bone

200/6 mcg: dysphonia, oral thrush densitometry is
Symbicort Maintenance therapy: (can be reduced by rinsing suggested in
1–2 inhalations daily– mouth or using spacer). patients who
$$$ Nervousness, tremor, require high
BID; maximum
4 inhalations/day. tachycardia, palpitations. doses or have
May temporarily risk factors for
increase to osteoporosis.
4 inhalations BID for Patients with
worsening asthma personal or
family history of
Maintenance and
glaucoma (and
reliever therapy:
need high-dose
1–2 inhalations BID
ICS) should
or 2 inhalations once
have IOP
daily. Inhale
checked soon
1 additional inhalation
after starting
PRN in response to
therapy and
symptoms; if
periodically
symptoms persist
thereafter.
after a few min, an
additional dose Fixed-dose
should be taken combination
inhalers are
Maximum more
6 inhalations on any convenient,
single occasion; enhance
8 inhalations/day adherence,
ensure the
patient receives
his/her ICS with
the LABA, and
are less
expensive than
the individual
agents
combined.
Drug/Cost[a] Dosage Adverse Effects Comments

DPI 100/25 mcg or Sore mouth, sore throat, Bone

200/25 mcg: dysphonia, oral thrush densitometry is
Breo Ellipta 1 inhalation once (can be reduced by rinsing suggested in
daily mouth or using spacer). patients who
$$$$-$$$$$ Nervousness, tremor, require high
tachycardia, palpitations. doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Fixed-dose
combination
inhalers are
more
convenient,
enhance
adherence,
ensure the
patient receives
his/her ICS with
the LABA, and
are less
expensive than
the individual
agents
combined.
A disadvantage
is a loss in
dosing
flexibility.
Not for reliever
therapy.
Drug/Cost[a] Dosage Adverse Effects Comments

pMDI 125/25 mcg or Sore mouth, sore throat, Bone

Advair pMDI, Advair 250/25 mcg: 2 puffs dysphonia, oral thrush densitometry is
Diskus BID (can be reduced by rinsing suggested in
Diskus 100/50 mcg, mouth or using spacer). patients who
$$$$-$$$$$ Nervousness, tremor, require high
250/50 mcg or
500/50 mcg: tachycardia, palpitations. doses or have
1 inhalation BID risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Fixed-dose
combination
inhalers are
more
convenient,
enhance
adherence,
ensure the
patient receives
his/her ICS with
the LABA, and
are less
expensive than
the individual
agents
combined.
A disadvantage
is a loss in
dosing
flexibility.
Not for reliever
therapy.
Drug/Cost[a] Dosage Adverse Effects Comments

pMDI 100/5 mcg or Sore mouth, sore throat, Bone

200/5 mcg: 2 puffs dysphonia, oral thrush densitometry is
Zenhale BID (can be reduced by rinsing suggested in
mouth or using spacer). patients who
$$$$ Nervousness, tremor, require high
tachycardia, palpitations. doses or have
risk factors for
osteoporosis.
Patients with
personal or
family history of
glaucoma (and
need high-dose
ICS) should
have IOP
checked soon
after starting
therapy and
periodically
thereafter.
Fixed-dose
combination
inhalers are
more
convenient,
enhance
adherence,
ensure the
patient receives
his/her ICS with
the LABA, and
are less
expensive than
the individual
agents
combined.
A disadvantage
is a loss in
dosing
flexibility.
Not for reliever
therapy.

Drug Class: IgE-Neutralizing Antibody

Drug/Cost[a] Dosage Adverse Effects Comments

150–375 mg SC Injection site reactions Store at 2–8°C.

Xolair every 2–4 wk (based (45%), viral infections Reconstituted
on patient's weight (24%), upper respiratory product may be
$660/150 mg vial and pretreatment tract infections (19%), stored for up to
serum IgE level) headache (15%), sinusitis 8 h at 2–8°C.
(16%), pharyngitis (10%). Do not inject
more than
150 mg at one
site. See
Product
Monograph for
details of
reconstitution
and
administration.
After start of
treatment, do
not use serum
IgE for dose
adjustment.
Omalizumab
raises IgE
levels, which
may persist for
up to a year
after ending the
treatment.

Drug Class: Interleukin-5 (IL-5) inhibitor

100 mg SC every Headache, injection site Administer

Nucala 4 wk reactions (pain, erythema, under
swelling, itching, burning supervision of
$2,000/100 mg vial sensation), back pain. health-care
Hypersensitivity reactions professional
may occur within hours or experienced in
days of treatment. management of
Symptoms include anaphylaxsis.
swelling of face, mouth
and tongue, fainting,
dizziness/lightheadedness,
hives, breathing problems,
rash.

Drug Class: Leukotriene Receptor Antagonists[d]

10 mg QHS PO Headache (common), Reduced

Singulair, generics abdominal pain, flulike montelukast
symptoms. levels:
$$ Neuropsychiatric effects carbamazepine,
(e.g., depression) and rifampin,
nightmares have been phenobarbital,
reported. phenytoin.

Drug Class: Methylxanthines[e]

 Drug/Cost[a] Dosage Adverse Effects Comments

Initial: Nausea, vomiting, Monitor serum

Uniphyl, Apo-Theo LA, 400–600 mg/day PO, abdominal cramps, levels.
other generics given in 1–3 divided headache, palpitations, Multiple drug
doses depending on CNS stimulation. interactions,
$ preparation used e.g., phenytoin,
carbamazepine
and rifampin
reduce
theophylline
levels, whereas
macrolides, oral
contraceptives
and quinolones
increase
theophylline
levels.
Theophylline
levels may
increase if
patient stops
smoking.
Extended-
release tablets
should not be
chewed,
crushed or
dissolved.

[a]
Cost of inhaled agents is per unit (1 inhaler, nebule or vial); cost of oral medications is per 30-day
supply; includes drug cost only.
[b] [1][6]
Usual starting dose based on published guidelines and may differ from product monographs.
[c]
Also referred to as anticholinergics.
[d] Zafirlukast is no longer available in Canada.
[e] Oxtriphylline (as a single-ingredient product) is no longer available in Canada.

Abbreviations: CNS = central nervous system; DPI = dry powder inhaler; ICS = inhaled corticosteroid; IOP
= intraocular pressure; LABA = long-acting beta2-agonist; LAMA = long-acting muscarinic antagonist; pMDI
= pressurized metered dose inhaler; SABA = short-acting beta2-agonist; SAMA = short-acting muscarinic
antagonist; SMI = soft mist inhaler

Legend: $ < $30 $$ $30–60 $$$ $60–90 $$$$ $90–120 $$$$-$$$$$ $90–150 $$$$$ $120–
150

Suggested Readings
Balter MS, Bell AD, Kaplan AG et al. Management of asthma in adults. 2009;181(12):915-22.

Ducharme FM, Dell SD, Radhakrishnan D et al. Diagnosis and management of asthma in
preschoolers: a Canadian Thoracic Society and Canadian Paediatric Society position paper.
2015;20(7):353-71.

Global Initiative for Asthma. . Updated 2017.

Available from: ginasthma.org/download/317/.

Global Initiative for Asthma.

. Updated 2017. Available from:
ginasthma.org/download/520/.

Lougheed MD, Lemiere C, Dell SD et al. Canadian Thoracic Society Asthma Management
Continuum—2010 Consensus Summary for children six years of age and over, and adults.
 2010;17(1):15-24.

Lougheed MD, Lemiere C, Ducharme FM et al. Canadian Thoracic Society 2012 guideline update:
diagnosis and management of asthma in preschoolers, children and adults.
2012;19(2):127-64.

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