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Am Fam Physician. 2023;107(4):358-368

Related editorial: Recent Changes in International Asthma Guidelines May Be Influenced by Pharmaceutical Industry Conflicts of Interest

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Author disclosure: No relevant financial relationships.

Asthma affects more than 25 million people in the United States, and 62% of adults with asthma do not have adequately controlled symptoms. Asthma severity and level of control should be assessed at diagnosis and evaluated at subsequent visits using validated tools such as the Asthma Control Test or the asthma APGAR (activities, persistent, triggers, asthma medications, response to therapy) tools. Short-acting beta2 agonists are preferred asthma reliever medications. Controller medications consist of inhaled corticosteroids, long-acting beta2 agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists. Treatment typically begins with inhaled corticosteroids, and additional medications or dosage increases should be added in a stepwise fashion according to guideline-directed therapy recommendations from the National Asthma Education and Prevention Program or the Global Initiative for Asthma when symptoms are inadequately controlled. Single maintenance and reliever therapy combines an inhaled corticosteroid and long-acting beta2 agonist for controller and reliever treatments. This therapy is preferred for adults and adolescents because of its effectiveness in reducing severe exacerbations. Subcutaneous immunotherapy may be considered for those five years and older with mild to moderate allergic asthma; however, sublingual immunotherapy is not recommended. Patients with severe uncontrolled asthma despite appropriate treatment should be reassessed and considered for specialty referral. Biologic agents may be considered for patients with severe allergic and eosinophilic asthma.

Asthma is one of the most common chronic diseases in primary care. It affects more than 25 million people in the United States with a prevalence of 7.8% among adults and children.1 The range of evidence-based treatments has become better defined, although nuances and differences between guidelines exist. This article reviews common questions about outpatient asthma treatment and provides evidence-based answers.

Clinical recommendation Evidence rating Comments
Adding a long-acting betaagonist to inhaled corticosteroid therapy is preferred over adding long-acting muscarinic antagonists; however, long-acting muscarinic antagonists may be added as triple therapy for severe persistent asthma.3,13,14 B Mixed evidence from multiple randomized controlled trials evaluating patient-oriented outcomes
Single maintenance and reliever therapy is the preferred treatment for moderate asthma in adolescents and adults.2,31,36 A Consistent results in multiple meta-analyses showing reduced rates of asthma exacerbations
Subcutaneous immunotherapy should be considered as an adjunct treatment for individuals five years and older with mild to moderate allergic asthma, but sublingual immunotherapy is not recommended.4043 A Consistent evidence showing reduced symptom scores and rescue medication use with subcutaneous immunotherapy and lack of evidence for sublingual immunotherapy for patient-oriented outcomes
Omalizumab (Xolair) may be used to decrease severe exacerbations and oral corticosteroid use in patients with allergic asthma.47 B Consistent results from multiple observational studies evaluating both patient-oriented and disease-oriented outcomes
Interleukin-5 and interleukin-4/13 antagonists may be used in patients with severe asthma and a blood eosinophil count of 300 per μL (0.3 × 109 per L) or more.45,49,50 B Consistent limited-quality studies showing reduced rates of asthma exacerbations
RecommendationSponsoring organization
Do not diagnose or manage asthma without spirometry.American Academy of Allergy, Asthma & Immunology
Do not use long-acting beta2 agonist/corticosteroid combination drugs as initial therapy for intermittent or mild persistent asthma in children.American Academy of Pediatrics
Avoid stepping up asthma therapy (i.e., adding new drugs or going to higher doses) before assessing adherence, appropriateness of device, and technique with current asthma medications.American Academy of Pediatrics

How Should Clinicians Assess Asthma Severity to Guide a Stepwise Approach to Treatment?

Asthma severity and control should be assessed at diagnosis and at subsequent visits by analyzing the level of impairment and the risk of future exacerbations. Once a diagnosis and treatment plan has been made, several validated tools may be used to assess control, including the Asthma Control Test and the asthma APGAR (activities, persistent, triggers, asthma medications, response to therapy) tools. Spirometry should be performed in all patients at diagnosis. There is weak evidence for repeating spirometry in patients with worsening symptom control.2,3 Evidence is limited for the use of adjuncts such as fractional excretion of nitric oxide and sputum eosinophils.

EVIDENCE SUMMARY

The regular assessment of asthma control is crucial because 62% of adults with the disease do not have adequately controlled asthma.4 The National Asthma Education and Prevention Program (NAEPP) Expert Panel Report recommends classifying asthma severity based on reported symptoms at diagnosis to determine initial therapy (Table 1).2 The degree of control should be assessed using decision support tools such as the Asthma Control Test or the asthma APGAR.5 The Asthma Control Test is a validated questionnaire consisting of five to seven items with a sensitivity and specificity of 70% when using a cutoff value greater than 19 to classify patients as having well-controlled asthma. The questionnaire can be found at https://www.asthmacontroltest.com/welcome/. The asthma APGAR tools perform similarly to the Asthma Control Test and are available from the American Academy of Family Physicians at https://www.aafp.org/dam/AAFP/documents/patient_care/nrn/nrn19-asthma-apgar.pdf. One randomized controlled trial (RCT) demonstrated improved asthma control, fewer hospital admissions, and increased adherence to treatment guidelines; however, this finding may have limited generalizability, especially to patients attending inner-city clinics.6

Patients not currently receiving long-term control medication*
Components of severityClassification of asthma severity

IntermittentPersistent

MildModerateSevere
Impairment
Normal FEV1/FVC:
8 to 19 years = 85%
20 to 39 years = 80%
40 to 59 years = 75%
60 to 80 years = 70%
Symptoms≤ 2 days per week> 2 days per week but not dailyDailyThroughout the day
Nighttime awakenings≤ 2 times per month3 to 4 times per month> 1 time per week but not nightlyEvery night
Short-acting beta2 agonist use for symptom control (not prevention of EIB)≤ 2 days per week> 2 days per week but not > 1 time per dayDailySeveral times per day
Interface with normal activityNoneMinor limitationSome limitationExtremely limited
Lung functionNormal FEV1 between exacerbations
FEV1 > 80% of predicted
FEV1/FVC normal
FEV1 ≥ 80% of predicted
FEV1/FVC normal
FEV1 > 60% but < 80% of predicted
FEV1/FVC normal
FEV1 < 60% of predicted
FEV1/FVC reduced > 5%
RiskExacerbations requiring oral systemic corticosteroids0 to 1 per year≥ 2 per year≥ 2 per year≥ 2 per year
Consider severity and interval since last exacerbation; frequency and severity may fluctuate over time for patients in any severity category
Relative annual risk of exacerbations may be related to FEV1
Patients after asthma becomes well controlled, by lowest level of treatment required to maintain control

Classification of asthma severity

IntermittentPersistent

MildModerateSevere
Lowest level of treatment required to maintain control (see Figure 1 for treatment steps)Step 1Step 2Step 3 or 4Step 5 or 6

After severity and control are evaluated, a stepwise treatment plan may be implemented using the Global Initiative for Asthma (GINA) or NAEPP guidelines (Figure 12,5,7). Spirometry is recommended for all patients at diagnosis; weak evidence supports repeating spirometry in patients with worsening symptom control.2,3 Forced expiratory volume in one second (FEV1) is an independent predictor of asthma exacerbations. Patients with an FEV1 of less than 60% are twice as likely to experience an exacerbation compared with those who have an FEV1 of more than 80%.5

Other objective measures of asthma severity show limited effectiveness in guiding treatment. Therapy guided by fractional excretion of nitric oxide reduced asthma exacerbations in children and adults (odds ratio [OR] = 0.67; 95% CI, 0.51 to 0.90).3 However, because strategies based on fractional excretion of nitric oxide showed no correlation with improvements in symptom control or quality of life, this therapy is not recommended for use without other adjuncts.7 Treatment guided by sputum eosinophils reduces exacerbations in adults (OR = 0.57; 95% CI, 0.38 to 0.86), although this outcome is questionable because there were no group differences in clinical symptoms, quality of life, or spirometry.8

What Are the Benefits and Harms of Each Major Class of Asthma Medications?

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