Approach Considerations
The introduction of omalizumab in 2003 as a novel approach for asthma control was a trailblazer for immunologic intervention for respiratory diseases such as asthma by reducing the necessity for chronic oral corticosteroid use, thereby reducing subsequent side effects (eg, early cataracts, osteoporosis, unwanted weight gain).
After a 13-year gap, innovations toward a solution for improved immunologic agents with a mild side effect profile have resulted in improved asthma control and include four novel biologic agents for subcutaneous (mepolizumab, benralizumab, and dupilumab) or intravenous (reslizumab) administration. These novel biologic agents have also been shown to be clinically important in decreasing overall atopic inflammation in patients with moderate to severe asthma; some of the clinical endpoints also showed reduced atopic dermatitis as well as reduced chronic rhinosinusitis with nasal polyposis, the last particularly with dupilumab. [1, 2, 3, 4]
Asthma symptoms usually persist despite avoidance measures; therefore, medications are often needed. The goal of treatment is to prevent fatalities, hospitalizations, and emergency room encounters. The long-term control of asthma with reduction of symptoms, maintenance of normal activity levels, prevention of exacerbations, and preservation of pulmonary function are the goals of therapy. Comorbidities should be treated and modifiable risk factors reduced (ie, smoking cessation, vaccinations).
Consultations
Consultations with the following are indicated:
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Allergist
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Pulmonologist
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Otolaryngologist
Medical Care
Inhaled corticosteroids (ICS) are the initial first-line therapy for treatment of asthma. For patients with eosinophilic asthma, ICS, even at very high doses, are not sufficient to control the disease. Specific therapeutics targeting components of the inflammatory response have been developed or are currently under investigation.
Omalizumab
Omalizumab is a monoclonal antibody that binds IgE. Although total serum IgE levels do not correlate with the degree of tissue eosinophilia, treatment with anti-IgE therapy has been shown to reduce airway and blood eosinophils and effectively reduce exacerbations. However, there are patients with uncontrolled asthma who do not respond to anti-IgE therapy and show persistent eosinophilic inflammation. [10]
Mepolizumab
Mepolizumab is a humanized monoclonal antibody against interleukin-5 that selectively inhibits eosinophilic inflammation and reduces the number of eosinophils in both sputum and blood. Studies have shown mepolizumab significantly reduces asthma exacerbations and improves markers of asthma control in patients with severe eosinophilic asthma whose asthma is not adequately controlled by standard regimens for asthma treatment. [19, 20]
Dupilumab
Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. [4] Studies have shown that patients taking dupilumab had significantly lower rates of severe asthma exacerbation than those who received placebo, as well as better lung function and asthma control. [4, 21]
Benralizumab
In 2017, both the European Medicines Agency Committee for Medicinal Products for Human Use and the FDA approved benralizumab as adjunctive maintenance treatment for adults and children aged 12 years and older with severe eosinophilic asthma. Benralizumab is an antieosinophil humanized monoclonal antibody that selectively targets the interleukin-5 receptor expressed on the surface of eosinophils. The FDA approved benralizumab based on three phase 3 studies, which demonstrated the following [22, 23] :
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Up to 51% reduction in the annual asthma exacerbation rate vs placebo
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Significant improvement in lung function as measured by forced expiratory volume in 1 second of up to 159 mL vs placebo, with differences seen as early as 4 weeks after the first dose
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A 75% median reduction in daily oral corticosteroid use and discontinuation of oral corticosteroid use in 52% of eligible patients
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An overall adverse event profile similar to that of placebo
Reslizumab
Reslizumab is a humanized anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death. Castro et al conducted parallel multicenter, double-blind phase 3 clinical trials with 1185 patients with inadequately controlled, moderate-to-severe asthma. In both studies, patients receiving reslizumab had a significant reduction in the frequency of asthma exacerbations. The adverse event profile was similar to that of placebo. Two patients were withdrawn from the study because of anaphylactic reactions. [24]
Long-Term Monitoring
Asthma is chronic medical condition that requires ongoing monitoring to assess its control and to detect early signs of undertreatment or poor adherence to treatment. Good control in the adult population directly impacts physical function and quality of life, as well as reduces costs by improving the health of older patients with asthma.
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Asthma in older adults. Lung tissue normal versus constricted.
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Asthma in older adults. Airway histology and pathology.
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Asthma in older adults. Allergic and nonallergic triggers.
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Asthma in older adults. Spirometric data plot. Pre-bronchodilator forced expiratory volume-one second (FEV1) = 1.77 L, post-bronchodilator FEV1 = 3.11 L, approximating a 75% change or airway reversibility.
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There has been an upward trend in the prevalence of asthma across all age groups since 2001. Courtesy of the CDC (https://www.cdc.gov/asthma/data-visualizations/prevalence.htm).
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Asthma prevalence by age, 2017. Courtesy of the CDC (https://www.cdc.gov/asthma/data-visualizations/prevalence.htm).
