Supplements Advancements in Asthma Therapy and Their Impact on Managed Care
Clinical Updates on the Management of Asthma
Introduction and Epidemiology
Asthma is a chronic condition of the airways defined by complex interactions of inflammation, airflow obstruction, and bronchial hyperresponsiveness.1 The disease is characterized by variable and recurring symptoms that differ both within and among patients.1 Asthma attacks or episodes vary in degree and can range from mild to severe enough to be life threatening. As such, asthma can influence quality of life and cause significant morbidity and mortality. In 1999, the CDC created the National Asthma Control Program. Some of the goals of the program include reducing the number of asthma-related deaths, hospitalizations, emergency department (ED) visits, and school or work days missed, and increasing the number of people receiving guideline-appropriate care. The program has improved asthma treatment and management in the United States.2
According to the 2014 National Health Interview Survey published by the CDC, approximately 40 million individuals (12.9%), including 10 million children (13.5%), were diagnosed with asthma.3 The Global Initiative for Asthma (GINA) estimates that 300 million people in the world suffer from asthma, and an additional 100 million are expected to have asthma by 2025.4
Current reports indicate that asthma prevalence among adults and children is approximately 7.4% and 8.6%, respectively.3 This equates to approximately 1 in 11 adults and 1 in 12 children with asthma.5 Prevalence is highest among adults aged 18 to 24 years. Prevalence is also higher in black adults and adult females.2 Black Americans are 2 to 3 times more likely to die from asthma than any other ethnic group.5 Further, adults who have not completed high school are more likely to have asthma than adults who have graduated high school or college, as are adults with lower annual household incomes compared with adults with higher incomes.5
Approximately 11 million individuals (44.7%), including 3 million children (48%), experienced an asthma episode in 2014.3 In 2011, asthma accounted for 1.8 million ED visits, and in 2014, it accounted for 3651 deaths in the United States.6 Nonadherence with controller agents increases the risk of deteriorating asthma and asthma episodes. Additionally, suboptimal adherence to prescribed controller medications is often a factor in patients with difficult-to-control asthma.7 Pharmacists can help improve patient adherence with controller agents by providing education about medications and ensuring proper device technique.8,9 Pharmacists are also well positioned within the healthcare team to identify and monitor nonadherence to controller medications or overreliance on quick-acting reliever agents.
Although these statistics demonstrate that asthma is associated with a high disease burden, it remains important for healthcare practitioners to realize that many patients with asthma suffer from comorbid conditions. Comorbidities can greatly affect the severity of asthma that patients experience. In one study, 54% of patients with a diagnosis of asthma had 1 or more comorbid conditions.10 Having asthma was associated with a greater prevalence of arthritis, heart disease, cancer, diabetes, and hypertension.10 For every additional comorbid condition, there was a reported increase in the prevalence of asthma symptom episodes, activity limitation, sleep disturbances, and asthma-related ED visits.10 Quality of life is also affected in patients with asthma. A disability-adjusted life year (DALY) can be thought of as a year lost due to disability, or 1 lost year of “healthy” life.11 Worldwide, it is estimated that the number of DALYs lost due to asthma is approximately 15 million per year and that asthma accounts for 1% of all DALYs lost.4 Interestingly, the number of lost DALYs due to asthma is similar to that of diabetes, cirrhosis, or schizophrenia.4
Given the large burden of disease, asthma has a significant financial impact on the healthcare system and patients. This economic impact includes direct and indirect costs. Examples of direct costs include hospital admissions, medications, and diagnostic tests.4,12 Indirect costs include those secondary to lost productivity due to asthma. These include missed days of school or work (for both patients and caregivers), waiting time, traveling to take care of someone with asthma, or premature death.4,12,13 A Canadian study discovered that there is a 14% increase in the odds of reporting productivity loss in patients suffering from more comorbidities compared with those suffering from fewer comorbidities.14 A report by the CDC estimated that in 2013, the number of reported school absences among children 5 to 17 years old with asthma was 13.8 million.15 The economic costs of asthma are reportedly the highest among chronic health diseases.13 One review attempting to assess the true financial impact of asthma cited the main drivers for direct costs as medications and hospital admissions.13 The cost of asthma was also found to strongly correlate to comorbidities, age, and severity of disease.13
Due to a multitude of factors affecting the financial impact of asthma, including the significant impact of indirect costs, assessing the true financial impact of asthma can be difficult. However, according to the CDC, asthma costs in the United States approximate to $56 billion each year.5 Increased provider knowledge about the disease and therapeutic options will help to improve overall treatment goals and may reduce costs. The results of one study showed that patients with controlled asthma who were treated appropriately according to guidelines had fewer costs than those with uncontrolled asthma who may not have been treated according to the guidelines.16 It is clear that asthma poses a significant financial burden on society. The financial cost of not treating asthma is also significant. Therefore, a clear understanding of the pathophysiology of asthma and the role of novel therapies is crucial in order to provide safe and efficacious management.
The dominant event leading to clinical symptoms in asthma is bronchoconstriction. Many factors, including allergens, medications, or other stimuli, such as exercise or cold air, can contribute to or trigger acute airway obstruction.1 Currently, there is no definitive answer as to what truly initiates the initial inflammatory process. Innate immunity, genetics, sex, and environmental factors are all thought to play roles. However, once the disease becomes more persistent or chronic, inflammation progresses and edema and mucus hypersecretion can affect airway smooth muscle. If left untreated, structural changes can cause airway remodeling and make responsiveness to usual treatments more challenging.1
Although there are many symptoms of asthma, airway inflammation is a hallmark sign. Many cell types and mediators are responsible for the inflammatory features of asthma; the inflammatory reaction is highly complex. Figure 117-20 and Figure 217-20 provide visual representations of the inflammatory cascade. In short, inhaled antigens presented to naïve T cells result in T helper 2 (Th2) cell differentiation.18 Th2 lymphocytes produce interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13). These interleukins lead to activation of B lymphocytes, which then secrete immunoglobulin E (IgE). IgE attaches to cell surfaces, and its receptors are found on mast cells, basophils, dendritic cells, and lymphocytes.1 Mast cell-bound IgE binds allergens and causes degranulation and the release of further chemical mediators, such as histamines, prostaglandins, and leukotrienes.18 All of these processes result in bronchoconstriction and can further potentiate the immune response.18 IL-5 eventually leads to further differentiation of eosinophils. Eosinophils migrate to the site of inflammation and attach to the endothelium via binding of adhesion proteins called vascular cell adhesion molecule-1 and intercellular adhesion molecule-1.1 When eosinophils are activated, leukotrienes and other proteins are released that ultimately damage the airway.1 As the inflammatory process in the airway has many components and is highly complex, researchers have developed new targets for asthma that focus on this allergic inflammatory component of the disease.
Advancements in Asthma Therapies
Asthma Management Guidelines
The assessment, diagnosis, and treatment of asthma is governed by 2 major guidelines: the Expert Panel Report 3 (EPR-3), published by the National Heart, Lung, and Blood Institute (last updated in 2007), and GINA, which is updated yearly.1,19 Both guidelines recommend an initial assessment to help characterize the patient’s asthma, which includes evaluation of precipitating factors, comorbidities that may aggravate asthma, and a review of asthma control to help classify asthma severity.1,19
Based on the severity of symptoms, lung function test results, and the level of asthma control, patients are first classified as having intermittent or persistent asthma. Persistent asthma is further stratified as mild, moderate, or severe.1 Patients should receive quick-relief medication and possibly long-term controller medication, depending on their asthma classification. Based on the pathophysiology, treatment is centered on anti-inflammatory therapy. Periodic assessment of patients facilitates ongoing control of the disease. Patients are classified as being well controlled, not well controlled, or very poorly controlled based on the frequency of symptoms, quick-relief medication use, pulmonary function, and validated questionnaire scores.1
Therapy may be stepped up (increased) or stepped down (decreased) within the treatment algorithm. Table 11,19 provides a summary of the EPR-3 and GINA guidelines. Table 11,19 correlates medication therapies with the type of asthma. Medications are classified as being controller (regular maintenance), rescue (breakthrough relief), or add-on therapies (for severe asthma).19 Recommendations are based on both EPR-3 and GINA guidelines unless otherwise indicated. Of note, this article focuses on the medications that are long acting and used for long-term management. The importance of short-acting quick relief medications cannot be overlooked; however, they are not the highlight of this manuscript.
Treatment Options and the Need for New Therapies