Simplified approach to stepping up asthma therapy in adolescents and adults

		Step 1	Step 2	Step 3	Step 4	Step 5^*
	Qualifying criteria	All of the following: Daytime symptoms ≤2 days/week Nocturnal awakenings ≤2/month Near personal best FEV₁ Exacerbations ≤1/year	Poor asthma symptom control,^¶ exacerbations requiring systemic glucocorticoids, or high risk of exacerbation^Δ on step 1 therapy despite: Addressing modifiable environmental factors and comorbidities Good adherence and inhaler technique	Poor asthma symptom control,^¶ exacerbations requiring systemic glucocorticoids, or high risk of exacerbation^Δ on step 2 therapy despite: Addressing modifiable environmental factors and comorbidities Good adherence and inhaler technique	Poor asthma symptom control,^¶ exacerbations requiring systemic glucocorticoids, or high risk of exacerbation^Δ on step 3 therapy despite: Addressing modifiable environmental factors and comorbidities Good adherence and inhaler technique	Poor asthma symptom control,^¶ exacerbations requiring systemic glucocorticoids, or high risk of exacerbation^Δ on step 4 therapy despite: Addressing modifiable environmental factors and comorbidities Good adherence and inhaler technique
Option 1	ICS-formoterol-based regimen	Low-dose ICS-formoterol^◊ as needed	Low-dose ICS-formoterol^◊ as needed	Low-dose ICS-formoterol as maintenance and reliever therapy (preferred)^§	Medium-dose ICS-formoterol as maintenance and reliever therapy (preferred)^§	Medium-dose ICS-formoterol as maintenance and reliever therapy plus LAMA daily with Evaluation for biologic therapies^*
Option 2	Alternative maintenance regimens	(No maintenance regimen)	(Anti-inflammatory reliever therapy without a maintenance regimen)^◊¥ or Low-dose ICS (daily or twice daily)	Low-dose ICS-LABA (preferred alternative) or Low-dose ICS plus LAMA or LTRA	Medium-dose ICS-LABA (preferred alternative) or Medium-dose ICS plus LAMA or LTRA	Medium-dose ICS-LABA daily plus LAMA daily (or ICS-LAMA-LABA daily) or Medium-dose ICS-LABA daily plus LTRA daily with Evaluation for biologic therapies^*
	and	and	and	and	and	and
	Alternative reliever regimens	ICS-SABA as needed^◊ or ICS plus SABA as needed^◊ (preferred alternative reliever options) or SABA, as needed	ICS-SABA as needed^◊¥ or ICS plus SABA as needed^◊¥ (preferred alternative reliever options) or SABA, as needed	ICS-SABA as needed^◊ or ICS plus SABA as needed^◊ (preferred alternative reliever options) or SABA, as needed	ICS-SABA as needed^◊ or ICS plus SABA as needed^◊ (preferred alternative reliever options) or SABA, as needed	ICS-SABA as needed^◊ or ICS plus SABA as needed^◊ (preferred alternative reliever options) or SABA, as needed

This table illustrates simplified recommendations for stepping up asthma therapy. At follow-up visits, check adherence, inhaler technique, environmental factors, and comorbid conditions. Subcutaneous immunotherapy is suggested as an adjunct to standard pharmacotherapy in individuals who have demonstrated allergy to the included allergens and whose asthma is well-controlled whenever immunotherapy is administered. Consultation with an asthma specialist is recommended if step 4 or higher is required.

Therapeutic strategies for newly diagnosed patients or for patients using SABA therapy alone are covered separately. Additional strategies for ongoing asthma treatment may be found in the accompanying graphic on guideline approaches to asthma controller therapy. Dosing information can be found in separate dosing tables for SABAs, AIR, MART, inhaled glucocorticoids, and inhaled glucocorticoids combined with bronchodilators. For additional information, please refer to UpToDate content on initial and ongoing 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.

* Initiation of step 5 therapy should prompt assessment of asthma phenotype and evaluation for possible addition of asthma biologics. Asthma biologic therapies include anti-IgE, anti-IL-5, anti-IL-5R, anti-IL-4R (anti-IL-4/IL-13), and antithymic stromal lymphopoietin (anti-TSLP). Refer to UpToDate content on severe asthma and UpToDate graphic on our approach to selection of biologic agents for add-on therapy for severe asthma in adolescents and adults.

¶ Good asthma symptom control is generally defined as bothersome asthma symptoms or need for SABA inhaler less than twice a week, no nocturnal awakenings, and no activity limitations due to asthma. For patients on ICS-formoterol, ICS-SABA, or ICS plus SABA reliever therapy (aka, anti-inflammatory reliever therapy), reliever use more frequently (but less than daily) is reasonable as long as other symptoms are well-controlled.

Δ Risk factors for exacerbations include: poor asthma symptom control, a history of asthma exacerbation on the current regimen, 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 for additional information.

◊ When prescribed for use as-needed for acute asthma symptoms, ICS-formoterol, ICS-SABA, and concomitant ICS and SABA use are referred to as anti-inflammatory reliever therapy. Compared with SABA relievers, use of anti-inflammatory reliever therapy 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. LABAs other than formoterol cannot be used for anti-inflammatory reliever therapy due to their more prolonged onset of action. Patients with risk factors for exacerbations, variable symptoms, or poor adherence to maintenance therapies are particularly likely to benefit from anti-inflammatory reliever therapy, but 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. LABAs other than formoterol cannot be used for MART due to their more prolonged onset of action.

¥ For patients qualifying for step 2 therapy, only anti-inflammatory relievers (ICS-formoterol, ICS-SABA, and concomitant ICS and SABA) should be used without concomitant maintenance low-dose inhaled glucocorticoid therapy. These patients should not be treated with SABA alone.

References:

National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Revised August 2007 (NIH publication no. 07-4051). Available at: https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma (Accessed November 3, 2023).
National Heart, Lung, and Blood Institute. 2020 focused updates to the asthma management guidelines: A report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. December 2020 (NIH publication no. 20-HL-8140). Available at: https://www.nhlbi.nih.gov/health-topics/asthma-management-guidelines-2020-updates (Accessed November 3, 2023).
Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2023. Updated July 2023. Available at: https://ginasthma.org/2023-gina-main-report/ (Accessed November 8, 2023).

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Simplified approach to stepping up asthma therapy in adolescents and adults