TABLE 1

Definitions of uncontrolled and severe asthma

Report [ref.]Uncontrolled asthmaSevere asthma
GINA report [2]At least one of the following:
1) Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma)
2) Frequent exacerbations (≥2/year) requiring OCS treatment, or serious exacerbations (≥1/year) requiring hospitalisation		Asthma that is difficult to treat (not controlled despite GINA Step 4 or 5 treatment,# or that requires such treatment to maintain good symptom control) and despite good adherence and inhaler technique, or that worsens when high-dose treatment is decreased
International ERS/ATS guidelines [18]At least one of the following:
1) ACQ consistently ≥1.5 or ACT <20
2) Frequent severe exacerbations (≥2 courses of SCS in the previous year)
3) Serious exacerbations (≥1 hospitalisation in the previous year)
Predicted post-bronchodilator FEV1 of <80% (in the face of reduced FEV1/FVC defined as less than the lower limit of normal)		Asthma requiring treatment with high-dose ICS and ≥1 maintenance treatment (LABA, LAMA, leukotriene modifier or theophylline) or SCS for ≥50% of the previous year to prevent it from becoming uncontrolled, or remains uncontrolled despite this therapy
NHLBI and NEAPP Guidelines for the Diagnosis and Management of Asthma (EPR-3) [27, 28]1) Symptoms >2 days·week−1
2) Night-time awakening ≥1/week
3) Limitations with normal activity
4) SABA use >2 days·week−1
5) FEV1 or peak flow ≤80% predicted/personal best
6) ATAQ ≥1
7) ACQ ≥1.5
8) ACT ≤19
Exacerbations ≥2/year		Asthma with EPR-3 Step 5 or 6# as the lowest level of treatment required to maintain control
Canadian Thoracic Society position statement [19]At least one of the following:
1) Poor symptom control: as per CTS asthma control criteria or other standardised questionnaires: ACQ consistently >1.5, ACT <20, or cACT <20
2) Frequent severe exacerbations: ≥2 courses of SCS (3 days each) in the previous year
3) Serious exacerbations: ≥1 hospitalisation, ICU stay or mechanical ventilation in the previous year
4) Airflow limitation: after appropriate bronchodilator withhold FEV1 <80% of personal best (or <the LLN, in the face of reduced FEV1/FVC defined as less than the LLN)		Asthma requiring treatment with high-dose ICS and a second controller for the previous year, or SCS for 50% of the previous year to prevent it from becoming uncontrolled, or remains uncontrolled despite this therapy
BTS/SIGN British Guideline on the Management of Asthma [20]“Difficult asthma” is defined as at least one of the following:
1) Persistent symptoms
2) Frequent asthma exacerbations despite treatment with:
a) High-dose ICS (adults) or medium-dose ICS (children) plus a LABA (age ≥5 years) or an LTRA
b) Medium-dose ICS (adults) or low-dose ICS (children) plus LABA (age ≥5 years) or LTRA and an appropriate additional therapy
c) Continuous or frequent use of OCS		ND
NICE guidelines [26]At least one of the following:
1) ≥3 days a week with symptoms
2) ≥3 days a week with required use of a SABA for symptomatic relief
3) ≥1 nights a week with awakening due to asthma		ND
Japanese Guidelines for Adult Asthma [21]NDAsthma controlled by, or uncontrolled despite administration of high doses of ICS, LABA, LTRA, theophylline, anti-IgE antibody or OCS. Also known as intractable asthma
Brazilian Thoracic Association [22]Three to four of the following:
1) Diurnal symptoms ≥2 times a week
2) Nocturnal awakenings due to asthma
3) Rescue medication ≥2 times a week
4) Limitation of activities due to asthma or ACQ-7 >1.5 or ACT ≤15		Asthma that remains uncontrolled on high-dose ICS and a second controller medication within the previous year or the use of OCS on ≥50% of the days in the last year, or that needs this treatment to prevent the disease from becoming uncontrolled (in an attempt to reduce the dose of ICS or OCS), despite the suppression or minimisation of factors that impair asthma control
The Saudi Initiative for Asthma [24]1) Symptoms and/or SABA use required throughout the day
2) ≥2 exacerbations a week
3) Extremely limited daily activities
4) FEV1 or peak flow <60% of predicted/personal best
5) ACT <16
>2 exacerbations per year requiring OCS or hospitalisation		Asthma that requires treatment
SINA Step 4 or 5#
Australian Asthma Handbook [23]“Poor control” defined as three or more, and “partial control” as two or more of:
1) Daytime symptoms >2 days per week
2) Need for SABA reliever >2 days per week
3) Any limitation of activities
4) Any symptoms during night or on waking		Asthma that is uncontrolled despite treatment with high-dose ICS/LABA (with correct inhaler technique and good adherence) or maintenance OCS, or that requires such treatment to prevent it becoming uncontrolled
NZ Adolescent and Adult Asthma Guidelines [25]“Poor control” defined as three or more, and “partial control” as two or more of:
1) Daytime symptoms >2 days per week
2) Need for SABA reliever >2 days per week
3) Any limitation of activities
4) Any symptoms during night or on waking		ND

GINA: Global Initiative for Asthma; OCS: oral corticosteroid; ERS/ATS: European Respiratory Society/American Thoracic Society; ACQ: asthma control questionnaire; ACT: asthma control test; SCS: systemic corticosteroid; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; ICS: inhaled corticosteroids; LABA: long-acting β2 agonist; LAMA: long-acting muscarinic antagonist; NHLBI: National Heart, Lung, and Blood Institute; NEAPP: National Asthma Education and Prevention Program; EPR 3: expert panel report 3; SABA: short-acting β-agonist; ATAQ: Asthma Therapy Assessment Questionnaire; CTS: Canadian Thoracic Society; cACT: child asthma control test; ICU: Intensive Care Unit; LLN: lower limits of normal; BTS: British Thoracic Society; SIGN: Scottish Intercollegiate Guidelines Network; LTRA: leukotriene receptor antagonist; ND: no definition; NICE: National Institute for Health and Care Excellence; SINA: Saudi Initiative for Asthma; NZ: New Zealand. #: medium- or high-dose ICS/LABA ± add-on therapy (LAMA, LTRA, OCS, biologics).