Background
Asthma is a chronic inflammatory disease characterized by hyperresponsiveness of airways to various stimuli. This condition has evolved rapidly over the past few years into an immunologic condition that is a responsive target for precision medicine. The US Food and Drug Administration (FDA) recently approved three anti-interleukin (IL)-5 agents to treat eosinophilic asthma (reslizumab, benralizumab, and mepolizumab) as well as an anti-IL4Ra biologic agent (dupilumab) for the indication of moderate to severe asthma in patients 12 years and older.
The new standard of care in asthma is to immunologically phenotype the patient, assess the total immunoglobulin (Ig) E level, and obtain a complete blood cell (CBC) count with differential to ascertain the absolute eosinophil count. Based on the elevation of total IgE or the absolute eosinophil count, a targeted precision biologic agent is usually selected. [1, 2, 3, 4]
Asthma is complex disease that affects patients of all ages. Although asthma has an equal incidence across all age groups, asthma in the elderly is often underdiagnosed and undertreated. A case-control cohort study showed that older adults with asthma have a higher rate of allergic sensitization, decreased lung function, and significantly worse quality of life when compared to controls. [5]
Some of the stimuli or triggers may generally be subdivided into allergic (allergens such as pollen, molds and fungi, dust mites, pet dander, and insects) or nonallergic (eg, cold air, infections, diesel exhaust, indoor/outdoor air pollution, perfume, tobacco smoke, and other irritants). See the image below.
Medical conditions such as rhinosinusitis, gastroesophageal reflux, and aspirin or nonsteroidal anti-inflammatory drug (NSAID) sensitivity may also trigger or exacerbate asthma.
Elderly patients with asthma face disproportionate morbidity, mortality, and cost when compared with younger patient groups. They represent a higher number of unscheduled outpatient visits, emergency room visits, and asthma-related hospitalizations; once hospitalized, the death rate attributable to asthma for patients older than 65 years is 14 times higher than that of patients aged 18-35 years. [6, 7, 8, 9]
Some of the independent risk factors for asthma in older adults include house dust mite sensitization and maternal smoking. [5]
Normal lung tissue and constricted lung tissue are demonstrated in the image below.
Pathophysiology
Airway inflammation, smooth muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema are some of the common pathophysiologic mechanisms seen in asthma. The chronic persistent inflammation may result in airway remodeling and structural changes of the airway wall. These changes include an epithelial thickening and subepithelial fibrosis; changes of extracellular matrix are linked to deposition of collagen and fibronectin in the subepithelial basement membrane.
Clinical trial data suggest an improved clinical outcome for those older than 12 years with moderate to severe persistent asthma, with important endpoints an objective increased forced expiratory volume in 1 second (FEV1) and subjective decreased exacerbations of asthma, with an improved quality of life and reduced dependency on oral corticosteroids.
These novel immunologic molecules target type 2 T-helper cell (Th2) inflammation by communicating sterically with the interleukin (IL)-5 and IL-4 receptors, as well as modifying IL-13 signaling. Decreased IL-4, IL-5, and IL-13 signaling has had clinical endpoints such as decreased moderate to severe persistent asthma, decreased eczema, and a decreased incidence of chronic rhinosinusitis with nasal polyposis (this latter entity is seen with the use of dupilumab).
These data suggest a bright clinical horizon opening for the discovery of novel agents targeting atopic Th2 inflammation that may consequently mount a pragmatic approach to the reduction of asthma, eczema, or atopic dermatitis, chronic rhinosinusitis with nasal polyposis and, potentially, over the atopic diathesis. [1, 2, 3, 4]
Various stimuli and factors may trigger asthma; this is evident by the recruitment and infiltration of proinflammatory cells within the airways. Cells such as eosinophils, neutrophils, lymphocytes, and degranulated mast cells, lead to occlusion of the bronchial lumen by mucus. See the image below.
Etiology
Allergic triggers include the following:
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Pollen: Trees, grasses, weeds
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Mold: Fungi
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Dust mites
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Animal proteins
Allergic triggers usually cause asthma symptoms by dimerizing or bridging the high-affinity immunoglobulin E (IgE) receptors located on the mast cells in the lungs. See the image below.
Non-allergic triggers include the following:
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Cold air
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Infections: Influenza, Mycoplasma pneumonia, viruses/upper respiratory infections
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Tobacco smoke
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Nonsteroidal anti-inflammatory drugs or aspirin [10]
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Exercise
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Irritants: Perfumes, paint
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Pollutants: Diesel exhaust, industrial chemicals
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Occupational exposures
Epidemiology
There has been an upward trend in the prevalence of asthma across all age groups. [11] The prevalence of asthma in adults older than 65 years is similar to that found in other age groups, particularly those aged 20 to 34 years (see the images below). [6, 11]
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).
Asthma prevalence by age, 2017. Courtesy of the CDC (https://www.cdc.gov/asthma/data-visualizations/prevalence.htm).
Asthma prevalence is higher among females (9.8%) compared with males (5.4%). [12]
Prognosis
The asthma death rate is highest among persons aged 65 years and older (30.4 per million) compared with persons aged 0-4 years (1.4 per million), 5-11 years (3.3 per million), 12-17 years (2.5 per million), 18-24 years (4.5 per million), 25-34 years (5.9 per million), and 35-64 years (11.4 per million) and are most common among women and blacks. [12] Nevertheless, asthma deaths are relatively rare event and largely preventable. Increased hospitalizations and emergency department visits are risks for death due to asthma.
Several studies have shown that late-onset eosinophilic asthma is associated with more severe disease than noneosinophilic asthma. High levels of eosinophils in sputum and bronchial biopsies are associated with poor asthma control, more severe asthma and fatal or near-fatal asthma attacks. Patients with eosinophilic inflammation despite systemic corticosteroid treatment have almost 20 times higher odds of being intubated than those without eosinophilic inflammation. In patients who died from asthma, significantly more eosinophils have been found in large and small airways, as compared to biopsies from patients with milder exacerbations.
Patients may suffer from both asthma and COPD, so called asthma-chronic obstructive pulmonary disease (COPD) overlap. It is still an open question whether this overlap syndrome represents the coexistence of two distinct airway diseases or whether there are common underlying pathogenic mechanisms leading to this phenotype. Patients who have asthma-COPD overlap have a more rapid disease progression, a worse health-related quality of life, more frequent respiratory exacerbations, increased co-morbidities and health care utilization than those with either disease alone. [13]
Patient Education
Adult patients with asthma often stop their medications when they feel well. These patients must be monitored on a regular basis to assess their symptoms and to intervene with appropriate asthma control. Adults generally expect to be treated as adults, with a respect and an appreciation for the skills they bring as they have different educational levels, backgrounds, life experiences, and expectations. Adults have established values, beliefs and opinions that must be identified and respected in order to set goals for management. [14]
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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).
