Canadian Thoracic Society 2021 Guideline update: Diagnosis and management of asthma in preschoolers, children and adults

Figures & data

Table 1. Diagnosis of asthma.

CLINICAL HISTORY COMPATIBLE WITH ASTHMA Paroxysmal or persistent symptoms such as dyspnea, chest tightness, wheezing, sputum production, and cough and CONFIRMATION OF REVERSIBLE AIRFLOW OBSTRUCTION
Preferred	Children (1-5 years of age)	Children (6 years of age and over)	Adults (18 years of age and over)
	Documentation by trained health care provider of wheeze and other signs of airflow obstruction with documented improvement with SABA +/- oral corticosteroids	Spirometry showing reversible airflow obstruction FEV1/FVC < LLN (<0.8-0.9^a) AND increase in FEV1 after a bronchodilator or after a course of controller therapy of ≥12%	Spirometry showing reversible airflow obstruction FEV1/FVC < LLN (<0.75-0.8^a) AND increase in FEV1 after a bronchodilator or after a course of controller therapy of ≥12% and a minimum of ≥200mL
Alternative	Convincing caregiver report of wheezing or other symptoms of airflow obstruction with symptomatic response to a 3-month trial of a medium dose of ICS and as needed SABA or symptomatic response to SABA^b	Peak expiratory flow ≥20% increase after a bronchodilator or after a course of controller therapy^c	Peak expiratory flow 60L/min (minimum ≥20%) increase after a bronchodilator or after a course of controller therapy^c OR Diurnal variation >8% ^12 based on twice daily readings; >20% based on multiple daily readings^d
Alternative		Positive challenge test Methacholine PC20 <4 mg/ml or PD20 <0.5 µmol (100 mcg) PC20 4-16 mg/mL or PD20 0.2-2 µmol (100-400 mcg) is borderline PC20 >16 mg/mL or PD20 >2 µmol (>400 mcg) is negative ^13 OR Exercise challenge with ≥10-15% decrease in FEV1 post-exercise

Abbreviatons: SABA, short-acting beta-agonist; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LLN, lower limit of normal; ICS, inhaled corticosteroid; PC20, provocative concentration; PD20, provocative dose.

a Approximate lower limits of normal ratios for children and adults.

b In children with mild intermittent symptoms and mild exacerbations, the diagnosis is only suggested because the accuracy of parental report of response to treatment may be unreliable due to misperception and spontaneous improvement of symptoms, which is why confirmation of reversible obstruction by direct observation from a health care provider is preferred.

c Comparison of peak expiratory flows should be done on the same device given the variability between devices.

d Difference between minimum AM pre-bronchodilator value in 1 week and maximum PM value as % of recent maximum.

Figure 1. Diagnosis algorithm for children 1 to 5 years of age.

^aDocumentation by a physician or trained health care practitioner.^bEpisodes of wheezing with/without difficulty breathing.^cSeverity of an exacerbation documented by clinical assessment of signs of airflow obstruction, preferably with the addition of objective measures such oxygen saturation and respiratory rate, and/or validated score such as the Pediatric Respiratory Assessment Measure (PRAM) score.^dBased on marked improvement in signs of airflow obstruction before and after therapy or a reduction of ≥ 3 points on the PRAM score, recognizing the expected time response to therapy.^eA conclusive therapeutic trial hinges on adequate dose of asthma medication, adequate inhalation technique, diligent documentation of the signs and/or symptoms, and timely medical reassessment; if these conditions are not met, consider repeating the treatment or therapeutic trial.^fThe diagnosis of asthma is based on recurrent (≥ 2) episodes of asthma-like exacerbations (documented signs) and/or symptoms. In case of a first occurrence of exacerbation with no previous asthma-like symptoms, the diagnostic of asthma is suspected and can be confirmed with re-occurrence of asthma-like symptoms or exacerbations with response to asthma therapy.^g>8 days/month with asthma-like symptoms.^hSevere exacerbations require any of the following: systemic steroids, hospitalization; or an emergency department visit.^IIn this age group, the diagnostic accuracy of parental report of a short-term response to as-needed short-acting β₂-agonist (SABA) may be unreliable due to misperception and/or spontaneous improvement of another condition. Documentation of airflow obstruction and reversibility when symptomatic, by a physician or trained health care practitioner, is preferred.^jBased on 50% fewer severe exacerbations, shorter and milder exacerbations, and fewer, milder symptoms between episodes.

Figure 2. 2021 Asthma continuum.

Management relies on an accurate diagnosis of asthma and regular reassessment of control and risk of exacerbation. All individuals with asthma should be provided with self-management education, including a written action plan. Adherence to treatment, inhaler technique, exposure to environmental triggers, and the presence of comorbidities should be reassessed at each visit and optimized.

Individuals with well controlled asthma on no medication or PRN SABA at lower risk of exacerbation can use PRN SABA, daily ICS + PRN SABA, and if ≥ 12 years of age PRN bud/form*.

Individuals at higher risk of exacerbation even if well-controlled on PRN SABA or no medication, and those with poorly-controlled asthma on PRN SABA or no medication should be started on daily ICS + PRN SABA. In individuals ≥ 12 years old with poor adherence despite substantial asthma education and support, PRN bud/form* can be considered. LTRA are second-line monotherapy for asthma. If asthma is not adequately controlled by daily low doses of ICS with good technique and adherence, additional therapy should be considered. In children 1-11 years old, ICS should be increased to medium dose and if still not controlled in children 6-11 years old, the addition of a LABA or LTRA should be considered. In individuals 12 years of age and over, a LABA in the same inhaler as an ICS is first line adjunct therapy. If still not controlled, the addition of a LTRA or tiotropium should be considered.

In children who are not well-controlled on medium dose ICS, a referral to an asthma specialist is recommended. After achieving asthma control, including no severe exacerbations, for at least 3-6 months, medication should be reduced to the minimum necessary dose to maintain asthma control and prevent future exacerbations.

HFA, hydrofluoroalkane; SABA, short-acting beta-agonist, LABA, long-acting beta-agonist, ICS, inhaled corticosteroid, LTRA, leukotriene receptor antagonist, bud/form: budesonide-formoterol in a single inhaler

Table 2. Well-controlled asthma criteria.

Characteristic	Frequency or value
Daytime symptoms	≤ 2 days/week
Nighttime symptoms	< 1 night/week and mild
Physical activity	Normal
Exacerbations	Mild and infrequent*
Absence from work or school due to asthma	None
Need for a reliever (SABA or bud/form)^†	≤ 2 doses per week
FEV1 or PEF	≥ 90% of personal best
PEF diurnal variation	< 10-15%^#
Sputum eosinophils	< 2-3%^●

A patient who meets all of the above criteria would be considered to have well-controlled asthma.

* A mild exacerbation is an increase in asthma symptoms from baseline that does not require systemic steroids, an ED visit, or a hospitalization. “Infrequent” is not specifically defined, since the frequency of mild exacerbations that patients consider an impairment to quality of life varies. If the patient feels that the frequency of mild exacerbations is impairing their quality of life, then their asthma should be considered poorly-controlled. If a patient is having frequent mild exacerbations, they should be assessed to determine if at baseline, they have poorly-controlled asthma.

† There are no established criteria for control when using bud/form as a reliever,; however, use of a reliever often indicates that a patient is having symptoms and is a criterion that can be objectively assessed.

# Diurnal variation is calculated as the highest peak expiratory flow (PEF) minus the lowest divided by the highest peak flow multiplied by 100, for morning and night (determined over a 2-week period).

● Consider in adults ≥ 18 years of age with uncontrolled moderate to severe asthma who are assessed in specialist centers.

Table 3. Assessing risk for severe exacerbation.

Individuals with any one of these risk factors are at higher risk for asthma exacerbation:
any history of a previous severe asthma exacerbation (requiring any of the following: systemic steroids, ED visit, or hospitalization)
poorly controlled asthma as per CTS criteria
overuse of SABA (defined as use of more than 2 inhalers of SABA in a year)
current smoker

These risk factors were chosen based on OR of >1.5 for severe exacerbations, certainty of the effect and ease of use in clinical practice. ¹ , ¹⁴

Table 4. Risk factors associated with severe asthma exacerbations.

Greatly increased risk (Odds Ratio (OR) > 2.5*)
≥ 12 years of age	6-11 years of age	< 6 years of age
History of previous severe exacerbation	History of previous severe exacerbation Poorly-controlled asthma FEV1 < 60% predicted	History of previous severe exacerbation
Moderate increased risk (OR 1.5-2.5*)
Poorly-controlled asthma Excessive SABA use (> 2 inhalers/year ^16 ) Current smoker**	Excessive SABA use (> 2 inhalers/year) Comorbid atopic/allergic disease Low socioeconomic status Vitamin D deficiency (< 30 nmol/L) FEV1 60-80% predicted
Slightly increased risk (OR 1.1-1.5*)
Older age (especially > 55 years of age) Female sex FEV1 < 70% predicted Obesity Previous smoker** Depression	Exposure to environmental tobacco smoke** Younger age Obesity Low parental education	Comorbid atopic/allergic disease Raised blood eosinophils (> 300/μL) Younger age Low socioeconomic status Male sex Underweight

Note. This table is adapted from SIGN 158 - British guideline on the management of asthma by kind permission of the Scottish Intercollegiate Guidelines Network. ¹⁵

* OR reported represent the OR found in the majority of studies examining the risk factor. ^{14 , 15}

** Studies have examined the risk of tobacco smoking; however, vaping and smoking of other substances should also be considered risk factors.17,18

Table 5. Risk factors associated with near-fatal or fatal asthma. ^{19 , 20}

Any previous near-fatal asthma exacerbation (eg, previous intensive care unit (ICU) admission, ventilation, respiratory acidosis)
Recurrent hospitalizations or ED visits in last year
Severe asthma
Overuse of SABA
Poor adherence to treatment plans
Failure to attend clinic appointments
Depression, anxiety or other psychiatric illness
Alcohol or other substance use
Obesity
Severe domestic, marital, employment, local stress
Denial of illness or severity of illness

Note. This table is adapted from SIGN 158 - British guideline on the management of asthma by kind permission of the Scottish Intercollegiate Guidelines Network. ¹⁵

Table 6. Components of an asthma education program.

1. Asthma pathophysiology: A chronic inflammatory condition in which airways are hyper-reactive (sensitive) to environmental (allergic, irritant or infectious) and/or intrinsic factors.
2. Identify triggers: Identification and avoidance of environmental triggers specific to the patients.
3. Asthma control for all patients: Asthma can be controlled and all patients with asthma can lead a normal life. Regular symptoms, poor lung function and asthma exacerbations indicate treatment failure.
4. Minimal to no exacerbations for all patients: Identify risk factors for asthma exacerbations.
5. Reliever vs. controller: The difference between reliever and controller medications and their use in the written action plan.
6. Written action plan: Provision and explanation of a written action plan comprising: How and how often to assess asthma control (self-monitoring) Instructions to maintain good control emphasizing adherence to controller medication and making specific environmental changes Signs and symptoms indicating poorly-controlled asthma, with instructions on what to do during loss of control (medication to add or increase, how much and how long; when and how to seek additional help (eg, when to go to the hospital or call the health care provider)
7. Medication safety and side effects: Expected onset of action and potential side effects of medications.
8. Inhaler teaching: Teaching and verification of the inhalation technique specific to the devices prescribed for the patient. Ensuring patients know how to tell when an inhaler is empty.

Table 7. Recommendations for asthma devices by age. ³⁷

Age	Device	Tips for use
1-3 years old	pMDI + VHC with mask	Ensure good seal of face mask
4-6 years old	pMDI + VHC with mouthpiece	To use a VHC with mouthpiece, patient needs to form a seal around the mouthpiece and cooperate with instructions. Tidal breathing* can be used with a VHC with mouthpiece.
> 6 years old	pMDI + VHC with mouthpiece or dry powder inhaler	To use a dry powder inhaler, patient needs to be able to inhale deeply and forcefully. Breath-hold technique** with VHC with mouthpiece improves lung deposition compared to tidal breathing, and is preferred if patient is able.
>12 years old and adults	Dry powder inhaler or pMDI + VHC with mouthpiece	VHC with masks are also available for adults unable to use a dry powder inhaler or VHC with mouthpiece.

Abbreviations: pMDI, pressurized meter dose inhaler; VHC, valved holding chamber.

Age recommendations are approximate as device technique needs to be individually assessed.

* Tidal breathing: 5-10 tidal breaths per actuation.

** Breath-hold technique: Exhale slowly, actuate pMDI, slowly inhale and hold breath for 5 to 10 seconds.

Table 8. Comparative inhaled corticosteroids (ICS) dosing categories in preschoolers, children and adults.

	Preschoolers (1-5 years of age)		Children (6-11 years of age)			Adults and Adolescents (12 years of age and over)
Corticosteroid (tradename)	Low	Medium	Low	Medium	High	Low	Medium	High **
Beclomethasone dipropionate HFA (QVAR)	100	200	≤ 200	201-400	> 400	≤ 200	201-500	> 500 (max 800)
Budesonide* (Pulmicort)	n/a	n/a	≤ 400	401-800	> 800	≤ 400	401-800	> 800 (max 2400)
Ciclesonide* (Alvesco)	100	200	≤ 200	201-400	> 400	≤ 200	201-400	> 400 (max 800)
Fluticasone furoate* (Arnuity)	n/a	n/a	n/a	n/a	n/a	100		200 (max 200)
Fluticasone propionate (Flovent)	< 200	200-250	≤ 200	201-400	> 400	≤ 250	251-500	> 500 (max 2000)
Mometasone furoate* (Asmanex)	n/a	n/a	100	≥ 200- < 400	≥ 400	100-200	> 200-400	> 400 (max 800)

Note. Dosing is in micrograms (mcg), dosing categories are approximate, based on a combination of approximate dose equivalency as well as safety and efficacy data.

*Licensed for once daily dosing in Canada

**Maximum (max) doses are the maximum doses approved for use in Canada.

Doses highlighted are not approved for use in Canada with the following exceptions: Beclomethasone is approved for children ≥ 5 years of age; Mometasone is approved for children ≥ 4 years of age; Maximum dose of fluticasone propionate is 200 mcg/day in children 1-4 years of age (250 mcg was included in this age group because the 125 mcg inhaler is often used for adherence and cost), Maximum dose of fluticasone propionate is 400 mcg/day in children 4-16 years of age.

Table 9. Yellow Zone action plan recommendations based on age and maintenance controller therapy.

Maintenance therapy	Recommended controller step-up therapy
Preschoolers (under 6 years of age) and children (6 to 11 years of age)
No maintenance	No step up in controller medication Consider starting regular controller therapy
ICS or LTRA or ICS/LABA**	No step up in controller medication In children with a history of severe exacerbation in last year and who fail to respond to SABA, consider prednisone/prednisolone 1 mg/kg x 3-5 days*
Adults (12 years of age and older)
No maintenance	No step up in controller Consider starting regular controller therapy or PRN bud/form
As needed bud/form	Increase bud/form to a maximum of 8 inhalations per day
Daily ICS or LTRA	In individuals ≥16 years of age and older with a history of a severe exacerbation in the last year: 1^st choice: trial of ≥4 fold increase in ICS for 7 to 14 days 2^nd choice: Prednisone 30-50 mg for at least 5 days* Otherwise no step up in controller medication.
Daily bud/form	1^st choice: Increase bud/form to a maximum of 4 inhalations twice daily for 7 to 14 days (≥16 years of age and older) or use bud/form as reliever and a controller (maximum 8 inhalations per day) (≥12 years of age and older) 2^nd choice: Prednisone 30-50 mg for at least 5 days*
Daily fluticasone propionate/salmeterol, mometasone/formoterol, fluticasone furoate/vilanterol	In individuals ≥16 years of age with a history of a severe exacerbation in the last year: 1^st choice: trial of ≥4 fold increase in ICS (higher ICS strength of ICS/LABA combination or extra ICS) for 7 to 14 days 2^nd choice: Prednisone 30-50 mg for at least 5 days* Otherwise no step up in controller medication.

* If regular need for step up therapy or need for a course of systemic steroids, address reasons for poor control and reassess/initiate controller therapy.

** Does not apply to preschoolers.

Figure 3. Treatment approach for patients on PRN SABA or no medication.

Table 10. Severity classification.

Asthma severity	Treatment required 1999	Treatment required 2021
Very mild	Well-controlled on no medication or inhaled SABA rarely	Well-controlled on PRN SABA
Mild	Well-controlled on SABA (occasionally) and low dose ICS	Well-controlled on: Low dose ICS (or LTRA) and PRN SABA or PRN bud/form
Moderate	Well-controlled on SABA and low to moderate dose ICS +/- additional therapy	Well-controlled on: Low dose ICS + second controller and PRN SABA or Moderate doses of ICS +/- second controller medication and PRN SABA or Low-moderate dose bud/form + PRN bud/form
Severe	Well-controlled on SABA and high dose ICS + additional therapy	High doses of ICS + second controller for the previous year or systemic steroids for 50% of the previous year to prevent it from becoming uncontrolled, or is uncontrolled despite this therapy
Very severe	Well- or poorly-controlled on SABA and high dose ICS + additional therapy + oral steroids	Category removed

Abbreviations: SABA, short-acting beta-agonist; PRN, as needed; ICS, inhaled corticosteroid; LTRA, leukotriene receptor antagonists; bud/form, budesonide/formoterol.

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