Guideline approaches to initial asthma therapy in adolescents and adults

National Asthma Education and Prevention Program: Expert Panel Working Group^[1,2]		Global Initiative for Asthma (GINA)^[3]
Asthma symptoms/lung function	Therapy^*	Asthma symptoms	Therapy
Step 1		Step 1
All of the following: Daytime symptoms ≤2 days/week Nocturnal awakenings ≤2/month Normal FEV₁ Exacerbations ≤1/year	SABA, as needed	Infrequent asthma symptoms (eg, <2 times/week) No risk factors for exacerbations^¶	Low-dose ICS-formoterol as needed (preferred)^Δ or Low-dose ICS whenever SABA used or as-needed low-dose ICS-SABA^Δ
Step 2		Step 2
Any of the following: Daytime symptoms >2 but <7 days/week Nocturnal awakenings up to 3 to 4 nights/month Minor interference with activities Exacerbations ≥2/year	Low-dose ICS daily and SABA as needed or Low-dose ICS-SABA or ICS plus SABA, concomitantly administered, as needed^Δ Alternative option(s) Daily LTRA and SABA as needed	Asthma symptoms or need for reliever inhaler ≥2 times/week, but without troublesome daily symptoms	Low-dose ICS-formoterol as needed (preferred) or Low-dose ICS daily and SABA as needed Other options Low-dose ICS-SABA or ICS plus SABA, concomitantly administered, as needed or (less preferred) LTRA daily and SABA as needed
Step 3		Step 3
Any of the following: Daily symptoms Nocturnal awakenings >1/week Daily need for reliever Some activity limitation FEV₁ 60 to 80% predicted Exacerbations ≥2/year	Low-dose ICS-formoterol as maintenance and reliever therapy^◊ (preferred) Alternative option(s) Medium-dose ICS daily and SABA as needed or Low-dose ICS-LABA combination daily or low-dose ICS plus LAMA daily or low-dose ICS plus anti-leukotriene daily and SABA as needed	Troublesome asthma symptoms most days, nocturnal awakening due to asthma ≥1 time/month, multiple risk factors for exacerbations^¶	Low-dose ICS-formoterol as maintenance and reliever therapy^◊ (preferred) or Low-dose ICS-LABA combination daily and SABA as needed Other options Medium-dose ICS daily and SABA or ICS-SABA^Δ as needed or Low-dose ICS plus LTRA daily and SABA or ICS-SABA^Δ as needed
Step 4		Step 4
Any of the following: Symptoms all day Nocturnal awakenings nightly Need for SABA several times/day Extreme limitation in activity FEV₁ <60% predicted Exacerbations ≥2/year An acute exacerbation	Medium-dose ICS-formoterol as maintenance and reliever therapy^◊ (preferred) Alternative option(s) Medium-dose ICS-LABA daily or medium-dose ICS plus LAMA daily or Medium-dose ICS daily plus anti-leukotriene and SABA as needed^*	Severely uncontrolled asthma with ≥3 of the following: Daytime asthma symptoms >2 times/week Nocturnal awakening due to asthma Reliever needed for symptoms >2 times/week Activity limitation due to asthma	Medium-dose ICS-formoterol as maintenance and reliever therapy^◊ (preferred) or Medium dose ICS-LABA daily and SABA or ICS-SABA^Δ as needed Other options Possible add-on LAMA or switch to ICS-LAMA-LABA Possible add-on LTRA

This table illustrates major guideline recommendations for initial asthma therapy. These recommendations are used for newly diagnosed patients or for patients using SABA therapy alone. For additional information, please refer to UpToDate content on initial treatment of asthma.

DPI: dry powder inhaler; FEV₁: forced expiratory volume in one second; ICS: inhaled corticosteroid (glucocorticoid); IgE: immunoglobulin E; IL: interleukin; LABA: long-acting beta-agonist; LAMA: long-acting muscarinic antagonist; LTRA: leukotriene receptor antagonist; MDI: metered-dose inhaler; SABA: short-acting beta-agonist.

* Theophylline and cromolyn are not included in the table even though they were included in NAEPP-EPR 3 (2007), and theophylline is included in NAEPP (2020). These agents are rarely used now, due to availability of more effective options.

¶ Risk factors for exacerbations include: frequent asthma symptoms, prior asthma exacerbations, smoking, allergen exposure if sensitized, previous intubation or intensive care unit stay for asthma, low FEV₁ (especially <60% predicted), obesity, food allergy, chronic rhinosinusitis, and poor adherence/inhaler technique. Please refer to UpToDate asthma treatment content and separate graphic on risk factors for asthma exacerbation.

Δ When prescribed for use as-needed for acute asthma symptoms, ICS-formoterol, ICS-SABA, and concomitant ICS and SABA are referred to as anti-inflammatory reliever therapy (AIR). Compared with SABA relievers, use of AIR has demonstrated decreased exacerbation risk in patients with all degrees of asthma severity. Choice of therapy is also guided by patient preference, cost, and medication availability.

◊ ICS-formoterol prescribed for use as both maintenance therapy and for acute relief of symptoms is referred to as Maintenance and Reliever Therapy (MART). MART has been shown to be more effective in terms of exacerbation reduction and symptom relief compared with ICS-formoterol and SABA alone as reliever therapy. Choice of therapy is also guided by patient preference, cost, and medication availability.

References:

National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051). https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma.
2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol 2020;146:1217-70. https://www.nhlbi.nih.gov/health-topics/asthma-management-guidelines-2020-updates.
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA). www.ginasthma.org.

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Guideline approaches to initial asthma therapy in adolescents and adults