Sections

Asthma

Guidelines

Guidelines Summary

The following organizations have issued guidelines for the management of asthma:

National Asthma Education and Prevention Program (NAEPP)^[2]
Veteran’s Administration/Department of Defense (VA/DoD)^[45]
Global Initiative for Asthma (GINA)^[109]
Japanese Society of Allergology (JSA)^[111]

Classification Guidelines

The 2020 NAEPP guidelines^[2]and the 2009 VA/DoD asthma management guidelines^[45]use the severity of asthma classification below, with features of asthma severity divided into three charts to reflect classification in different age groups (0-4 y, 5-11 y, and 12 y and older). Classification includes (1) intermittent asthma, (2) mild persistent asthma, (3) moderate persistent asthma, (4) and severe persistent asthma.

Intermittent asthma is characterized as follows:

Symptoms of cough, wheezing, chest tightness, or difficulty breathing less than twice a week
Flare-ups are brief, but intensity may vary
Nighttime symptoms less than twice a month
No symptoms between flare-ups
Lung function test FEV ₁ is 80% or more above normal values
Peak flow has less than 20% variability am-to-am or am-to-pm, day-to-day

Mild persistent asthma is characterized as follows:

Symptoms of cough, wheezing, chest tightness, or difficulty breathing 3-6 times a week
Flare-ups may affect activity level
Nighttime symptoms 3-4 times a month
Lung function test FEV ₁ is 80% or more above normal values
Peak flow has less than 20-30% variability

Moderate persistent asthma is characterized as follows:

Symptoms of cough, wheezing, chest tightness, or difficulty breathing daily
Flare-ups may affect activity level
Nighttime symptoms 5 or more times a month
Lung function test FEV ₁ is above 60% but below 80% of normal values
Peak flow has more than 30% variability

Severe persistent asthma is characterized as follows:

Symptoms of cough, wheezing, chest tightness, or difficulty breathing that are continual
Frequent nighttime symptoms
Lung function test FEV ₁ is 60% or less of normal values
Peak flow has more than 30% variability

In contrast, the 2019 Global Initiative for Asthma (GINA) guidelines categorize asthma severity as mild, moderate, or severe. Severity is assessed retrospectively from the level of treatment required to control symptoms and exacerbations, as follows:^[109]

Mild asthma: Well-controlled with as-needed reliever medication alone or with low-intensity controller treatment such as low-dose inhaled corticosteroids (ICSs), leukotriene receptor antagonists, or chromones
Moderate asthma: Well-controlled with low-dose ICS/long-acting beta2-agonists (LABA)
Severe asthma: Requires high-dose ICS/LABA to prevent it from becoming uncontrolled, or asthma that remains uncontrolled despite this treatment

The 2020 joint European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines on evaluation and treatment of severe asthma reserves the definition of severe asthma for patients with refractory asthma and those in whom response to treatment of comorbidities is incomplete.^[112]

The 2022 GINA guidelines stress the importance of distinguishing between severe asthma and uncontrolled asthma, as the latter is a much more common reason for persistent symptoms and exacerbations, and it may be more easily improved. The most common problems that need to be excluded before a diagnosis of severe asthma can be made are the following:^{[109, 113]}

Poor inhaler technique
Poor medication adherence
Incorrect diagnosis of asthma, with symptoms due to alternative conditions such as upper airway dysfunction, cardiac failure, or lack of fitness
Comorbidities and complicating conditions such as rhinosinusitis, gastroesophageal reflux, obesity, and obstructive sleep apnea
Ongoing exposure to sensitizing or irritant agents in the home or work environment.

Management Guidelines

The goals for successful management of asthma outlined in the 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. 2007 NHLBI publication "Global Strategy for Asthma Management and Prevention" (see the images below) include the following:^[2]

Achieve and maintain control of asthma symptoms
Maintain normal activity levels, including exercise
Maintain pulmonary function as close to normal as possible
Prevent asthma exacerbations
Avoid adverse effects from asthma medications
Prevent asthma mortality

Asthma symptoms and severity. Recommended guidelines for determination of asthma severity based on clinical symptoms, exacerbations, and measurements of airway function. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.

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Stepwise approach to pharmacological management of asthma based on asthma severity. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.

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Stepwise pharmacologic therapy

The pharmacologic treatment of asthma is based on stepwise therapy. Asthma medications should be added or deleted as the frequency and severity of the patient's symptoms change. The 2020 NAEPP guidelines offer the recommendations below.^[2]

Step 1 for intermittent asthma is as follows:

Controller medication not indicated
Reliever medication is a short-acting beta-agonist (SABA) as needed for symptoms

Step 2 for mild persistent asthma is as follows:

Preferred controller medication is a low-dose inhaled corticosteroid
Alternatives include cromolyn, leukotriene receptor antagonist (LTRA), ^[114]or theophylline

Step 3 for moderate persistent asthma is as follows:

Preferred controller medication is either a low-dose inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA) (combination medication is the preferred choice to improve compliance) ^[115]or an inhaled medium-dose corticosteroid
Alternatives include a low-dose ICS plus either an LTRA or theophylline

Step 4 for moderate-to-severe persistent asthma is as follows:

Preferred controller medication is an inhaled medium-dose corticosteroid plus a LABA (combination therapy)
Alternatives include an inhaled medium-dose corticosteroid plus either an LTRA or theophylline

Step 5 for severe persistent asthma is as follows:

Preferred controller medication is an inhaled high-dose corticosteroid plus LABA

Step 6 for severe persistent asthma is as follows:

Preferred controller medication is an inhaled high-dose corticosteroid plus LABA plus oral corticosteroid

The 2019 GINA guidelines include the stepwise recommendations below for medication and symptom control.^[109]

The preferred reliever medication is specified as low-dose ICS-formoterol, which is an off-label use. Other reliever options include as-needed SABA. See the following stepwise approach:

Step 1: As-needed low-dose ICS-formoterol (off-label); other options are low dose ICS taken whenever SABA is taken
Step 2: Daily low-dose ICS, or as-needed low-dose ICS-formoterol (off-label); other options are leukotriene receptor antagonist (LTRA) or low-dose ICS taken whenever SABA is taken
Step 3: Low-dose ICS/LABA; other options include medium-dose ICS or low-dose ICS + LTRA
Step 4: Medium-dose ICS-LABA; other options are high-dose ICS, add-on tiotropium, or add-on LTRA
Step 5: High-dose ICS-LABA; refer for phenotypic assessment with or without add-on therapy (eg, tiotropium, anti-IgE, anti-IL5/5R, and IL4R; other options are to add low-dose OCS, but consider adverse effects

The change in GINA guidelines from SABA to ICS-formoterol as the recommended as-needed inhaler was based on the SYGMA I/II trials published in 2018. SYGMA I showed that as-needed budesonide-formoterol was superior to as-needed terbutaline but was inferior to budesonide maintenance therapy. Exacerbation rates were similar for budesonide-containing strategies, both of which were lower than terbutaline. SYGMA II concluded that as needed budesonide-formoterol was noninferior to budesonide maintenance therapy for the rate of severe exacerbations but was inferior for controlling asthma symptoms. Both trials showed a reduction in overall ICS exposure with as-needed budesonide/formoterol.

The 2020 joint European Respiratory Society/American Thoracic Society (ERS/ATS) guidelines include the following additional recommendations for treatment of severe asthma:^[112]

For severe allergic asthma, a therapeutic trial of omalizumab
Do not use methotrexate or macrolide antibiotics to treat severe asthma
For severe asthma and recurrent exacerbations of allergic bronchopulmonary aspergillosis (ABPA), antifungal agents should be given
Do not use antifungal agents for severe asthma without ABPA irrespective of sensitization to fungi (ie, positive skin prick test or fungus-specific immunoglobulin E in serum)

Japanese Society of Allergology

Guidelines for adult asthma were published in October 2020 by the Japanese Society of Allergology (JSA).^[111]

Diagnosis

The JSA recommends spirometry for assessing the extent of airflow limitation or airway reversibility.

The JSA recommends daily measurement of peak expiratory flow for unstable asthma and patients lacking obvious dyspnea during attack.

Although useful for diagnosing asthma, the JSA does not recommend assessing bronchial hyperresponsiveness in patients with low FEV₁(≤1 L) or low %FEV₁(≤50%) since excess airway narrowing may occur due to irritant inhalation.

Treatment of long-term adult asthma

The JSA recommends using a jet nebulizer for budesonide (BUD) inhalation suspension.

The JSA recommends adding one or more agents other than inhaled corticosteroids (ICSs), as opposed to increasing the dose of an ICS, to control asthma.

The JSA recommends long-acting β₂-agonists (LABAs), leukotriene receptor antagonists (LTRAs), sustained-release theophylline, and long-acting muscarinic antagonists as add-on drugs.

The JSA recommends that anti-immunoglobulin E antibodies and other biologics as well as oral steroids be reserved for very severe and persistent asthma related to allergic reactions.

The JSA recommends inhaled β₂-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches be used as needed during acute exacerbations.

Treatment during pregnancy

The JSA recommends ICSs as first-line treatment for long-term management of pregnant women with asthma.

The JSA recommends a short-acting beta-agonist (SABA) as needed for pregnant women with mild intermittent asthma.

The JSA recommends low-dose ICS; LTRA, controlled-release theophylline, and/or disodium cromoglycate (DSCG) as needed in pregnant women with mild persistent asthma.

The JSA recommends low-dose ICS and LABA or moderate-dose ICS and LABA in combination with LTRA or controlled-release theophylline as needed in pregnant women with moderate persistent asthma.

The JSA recommends high-dose ICS and LABA; oral steroids as needed for pregnant women with severe persistent asthma.

Exercise-Induced Asthma Guidelines

In 2013, the American Thoracic Society released clinical guidelines for the management of exercise-induced bronchoconstriction (EIB), which included the following recommendations^[116]:

Administration of an inhaled SABA before exercise (strong recommendation); the SABA is typically administered 15 minutes before exercise
A controller agent is added whenever SABA therapy is used daily or more frequently
Interval or combination warm-up exercise before planned exercise (strong recommendation)
Recommend against daily use of an inhaled long-acting beta2-agonist as single therapy (strong recommendation)
For patients who continue to have symptoms despite using an inhaled SABA before exercise or who require an inhaled SABA daily or more frequently: (1) Daily ICS (strong recommendation), (2) Daily administration of an LTRA (strong recommendation), (3) Administration of a mast cell‒stabilizing agent before exercise (strong recommendation), and (4) Inhaled anticholinergic agent before exercise (weak recommendation)
For patients with EIB and allergies who continue to have symptoms despite using an inhaled SABA before exercise or who require an inhaled SABA daily or more frequently consider administration of an antihistamine (weak recommendation)
For exercise in cold weather, routine use of a device (eg, mask) that warms and humidifies the air during exercise (weak recommendation)

Medication

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Media Gallery

Pathogenesis of asthma. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.
Asthma symptoms and severity. Recommended guidelines for determination of asthma severity based on clinical symptoms, exacerbations, and measurements of airway function. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.
Stepwise approach to pharmacological management of asthma based on asthma severity. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.
Asthma. High-resolution CT scan of the thorax obtained during inspiration in a patient with recurrent left lower lobe pneumonia shows a bronchial mucoepidermoid carcinoma (arrow).
Asthma. High-resolution CT scan of the thorax obtained during expiration in a patient with recurrent left lower lobe pneumonia shows a bronchial mucoepidermoid carcinoma. Note the normal increase in right lung attenuation during expiration (right arrow). The left lung remains lucent, especially the upper lobe, secondary to bronchial obstruction with airtrapping (left upper arrow). The vasculature on the left is diminutive, secondary to reflex vasoconstriction. Left pleural thickening and abnormal linear opacities are noted in the left lower lobe; these are the result of prior episodes of postobstructive pneumonia (left lower arrow).
High-resolution CT scan of the thorax obtained during inspiration demonstrates airtrapping in a patient with asthma. Inspiratory findings are normal.
High-resolution CT scan of the thorax obtained during expiration demonstrates a mosaic pattern of lung attenuation in a patient with asthma. Lucent areas (arrows) represent areas of airtrapping (same patient as in the previous image).
Posteroanterior chest radiograph demonstrates a pneumomediastinum in bronchial asthma. Mediastinal air is noted adjacent to the anteroposterior window and airtrapping extends to the neck, especially on the right side.
Lateral chest radiograph demonstrates a pneumomediastinum in bronchial asthma. Air is noted anterior to the trachea (same patient as in the previous image).
Asthma. High-resolution CT scan of the thorax obtained during inspiration in a patient with recurrent left lower lobe pneumonia shows a bronchial mucoepidermoid carcinoma (arrow).
Asthma. High-resolution CT scan of the thorax obtained during expiration in a patient with recurrent left lower lobe pneumonia shows a bronchial mucoepidermoid carcinoma (same patient as in the previous image). Note the normal increase in right lung attenuation during expiration (right arrow). The left lung remains lucent, especially the upper lobe, secondary to bronchial obstruction with airtrapping (left upper arrow). The vasculature on the left is diminutive, secondary to reflex vasoconstriction. Left pleural thickening and abnormal linear opacities are noted in the left lower lobe; these are the result of prior episodes of postobstructive pneumonia (left lower arrow).
Asthma. High-resolution CT scan of the thorax demonstrates mild bronchial thickening and dilatation in a patient with bilateral lung transplants and bronchial asthma.
Asthma. High-resolution CT scan of the thorax demonstrates central bronchiectasis, a hallmark of allergic bronchopulmonary aspergillosis (right arrow), and the peripheral tree-in-bud appearance of centrilobular opacities (left arrow), which represent mucoid impaction of the small bronchioles.
Asthma is characterized by chronic inflammation and asthma exacerbations, where an environmental trigger initiates inflammation, which makes it difficult to breathe. This video covers the pathophysiology of asthma, signs and symptoms, types, and treatment.

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Author

Michael J Morris, MD, FACP, FCCP Clinical Faculty, Pulmonary Disease/Critical Care Service, Department of Medicine, Brooke Army Medical Center; Assistant Dean for Research, SAUSHEC, Brooke Army Medical Center; Clinical Professor, niversity of Texas Health Science Center at San Antonio, Joe R and Teresa Lozano Long School of Medicine; Professor, Uniformed Services University of the Health Sciences

Michael J Morris, MD, FACP, FCCP is a member of the following medical societies: American Association for Respiratory Care, American College of Chest Physicians, American College of Physicians, The Society of Federal Health Professionals (AMSUS)

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Janssen Pharmaceuticals.

Coauthor(s)

Daniel J Pearson, MD, FCCP ICU Medical Director, Respiratory Therapy Medical Director, Soin Medical Center

Daniel J Pearson, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Acknowledgements

Edward Bessman, MD, MBA Chairman and Clinical Director, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine

Edward Bessman, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine