Difficult-to-Treat and Severe Asthma: Management Strategies

 

Asthma is a common chronic inflammatory disease in the United States. Up to 17% of asthma cases are classified as difficult to treat, and 3.7% of these are considered severe. Uncontrolled asthma is characterized by poor symptom control or frequent exacerbations. In difficult-to-treat asthma, the asthma is uncontrolled despite adherence to inhaled corticosteroid therapy in combination with a second controller, an oral corticosteroid is needed to achieve control, or it is uncontrolled despite oral corticosteroid therapy. Severe asthma is a subset of difficult-to-treat asthma in which the disease is uncontrolled despite adherence to optimal management or it worsens when high-intensity therapy is decreased. The diagnosis of asthma should be confirmed and modifiable factors and comorbidities addressed in patients with difficult-to-treat asthma. An adequate trial of an inhaled corticosteroid and long-acting beta agonist should be implemented with nonbiologic add-on therapies, such as a long-acting muscarinic agent or leukotriene receptor antagonist. Evaluation of severe asthma involves assessment of asthma phenotype. Evidence of type 2 inflammation indicates that the patient may benefit from newer biologic agents. Breathing exercises may improve quality of life, asthma symptoms, lung function, and number of exacerbations. Vitamin D and soy supplementation are ineffective. Bronchial thermoplasty is a procedural option that may be considered if there is inadequate response to other therapies.

Asthma is a common chronic inflammatory disease in the United States, affecting 40 million people in their lifetime.1 Primary care physicians manage most patients with asthma, with 22% regularly treated by a specialist.2 Up to 17% of asthma cases are classified as difficult to treat, and 3.7% of these are considered severe.3 Severe asthma accounts for up to 60% of the cost of asthma.4 The costs for individuals with severe asthma are approximately 1.7-fold to fivefold greater than that for individuals with mild asthma.5 Patients with severe asthma experience significant disruptions in work, school, family life, and activities.2

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

The first steps in the evaluation of difficult-to-treat asthma are confirming the diagnosis and addressing contributing factors.9

C

Evidence-based guideline

Adding a long-acting muscarinic antagonist to inhaled corticosteroid monotherapy improves asthma control in patients with severe asthma; however, there is no benefit to adding a long-acting muscarinic antagonist to long-acting beta agonist plus inhaled corticosteroid combination therapy.13

A

Systematic review and meta-analysis of RCTs

Omalizumab (Xolair) is effective in reducing exacerbations, hospitalizations, and inhaled corticosteroid dosage in patients with allergic asthma based on positive results on skin testing or elevated immunoglobulin E on a respiratory allergen panel.15

A

Cochrane review of RCTs with consistent findings

Bronchial thermoplasty modestly improves quality of life and lowers rates of asthma exacerbation in patients with moderate to severe asthma.20

B

Cochrane review of limited-quality patient-oriented evidence


RCT = randomized controlled trial.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Author

KRISHNAN NARASIMHAN, MD, is an associate professor in the Department of Community and Family Medicine at Howard University College of Medicine, Washington, DC.

Author disclosure: No relevant financial affiliations.

Address correspondence to Krishnan Narasimhan, MD (email: krishnanmd1@gmail.com). Reprints are not available from the author.

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