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Simplified approach to initial asthma therapy for adolescents and adults

Asthma symptoms	Initial therapy
Intermittent asthma (step 1)
Infrequent asthma symptoms (eg, <2 times/week)	Low-dose ICS-formoterol combination inhaler (eg, budesonide-formoterol MDI or DPI) as needed or SABA as needed
Mild persistent asthma (step 2)
Asthma symptoms or need for reliever inhaler ≥2 times/week but <4-5 days/week	Preferred options* Low-dose ICS-formoterol combination inhaler as needed or Low-dose ICS daily and separate SABA as reliever
Moderate persistent asthma (step 3)
Troublesome asthma symptoms most days Nocturnal awakening due to asthma ≥1 time/week Risk factors for exacerbations^¶	Preferred options^Δ Low-dose ICS-formoterol combination inhaler as maintenance and reliever therapy or Low-dose ICS-LABA combination inhaler daily and separate SABA as reliever
Severe persistent asthma (step 4)
Daily asthma symptoms (≥1/week) Nocturnal awakening due to asthma ≥1 time/week Low lung function	Preferred options^◊ Medium-dose ICS-formoterol combination inhaler as maintenance and reliever therapy or Medium-dose ICS-LABA combination inhaler daily and separate SABA as reliever Evaluate for add-on therapies^§
Severe persistent asthma (steps 5-6)
Ongoing asthma symptoms and waking with asthma despite step 4 therapy	Medium- to high-dose ICS-LABA combination inhaler daily plus LAMA daily and separate SABA as reliever Evaluate for add-on therapies^§

Initial therapy for asthma is based on the frequency and severity of asthma symptoms. Patients who present with an acute exacerbation may need oral glucocorticoids in addition. The response to therapy should be assessed in 2 to 12 weeks depending on clinical urgency. Treatment may be stepped down if asthma is well controlled for at least three months, or stepped up 1 or 2 steps if asthma is not well controlled or is very poorly controlled. 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. Consult with an asthma specialist if step 4 or higher is required.

DPI: dry powder inhaler; FEV₁: forced expiratory volume in one second; ICS: inhaled corticosteroid (glucocorticoid); LABA: long-acting beta-agonist; LMA: leukotriene modifying agent (eg, zileuton); LTRA: leukotriene receptor antagonist (eg, montelukast, zafirlukast); MDI: metered dose inhaler; SABA: short-acting beta-agonist; LAMA: long-acting muscarinic antagonist.

* Other options for mild persistent asthma (step 2): Low-dose ICS plus SABA concomitantly administered, as needed; or LTRA daily with SABA as needed.

¶ Risk factors for exacerbations include the following: 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.

Δ Other options for moderate persistent asthma (step 3): Medium-dose ICS daily, with SABA as reliever; or Low-dose ICS-LABA plus LTRA daily, with SABA as reliever.

◊ Other options for severe persistent asthma (step 4): High-dose ICS with SABA as reliever; medium-dose ICS and substitute tiotropium (or other LAMA depending on availability and regulatory approval) for LABA; or High-dose ICS daily with SABA as reliever.

§ Add-on therapies may include:

Tiotropium (or other LAMA depending on availability and regulatory approval) may be substituted for LABA or added on (step 4).
LTRA/LMA are more commonly added on for concomitant nasal polyposis or aspirin-exacerbated respiratory disease. The US Food and Drug Administration issued a boxed warning for montelukast in March 2020.
Asthma biologics include anti-immunoglobulin E, anti-interleukin (IL)-5, anti-IL-5R, anti-IL-4R (anti-IL-4/IL-13), and anti-thymic stromal lymphopoietin (anti-TSLP). Refer to UpToDate graphic on approach to selection of biologic agents for add-on therapy.
Theophylline, cromolyn, and nedocromil are additional options that are not included in the table as they are rarely used, due to more effective options with fewer adverse effects (theophylline) or limited availability (cromolyn, nedocromil).

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. 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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