Going Back to the Basics: An Asthma Review

Asthma is a common chronic lung airway inflammatory disease with hallmark respiratory signs and symptoms such as shortness of breath, wheezing, chest tightness, and cough.¹ According to the latest asthma surveillance data from the CDC, approximately 25 million people (7% of the US population) are affected by asthma, with a significant portion of 4.6 million children affected.² Asthma prevalence amongst the population also varies, with a higher incidence among women who are Black or Puerto Rican.³ Across the United States, in 2021, Maine had the highest asthma prevalence, followed closely by West Virginia and New Hampshire.² However, California, New York, and Texas had the highest number of reported asthma-related deaths during the same year.²

Asthma-related costs pose a significant health-related economic burden in the United States.² In 2020, around 1 million emergency department (ED) visits were asthma-related, while 94,560 people were hospitalized due to asthma diagnosis.² In 2021, the CDC reported around 10 million cases of asthma attacks among children and adults.² In a US asthma economic analysis by the American Thoracic Society, the cumulative cost of asthma in 2013 was $81.9 billion, encompassing asthma-related deaths, ED visits, medication cost, and loss of productivity due to the disease exacerbation.³

Pathophysiology, Presentation, and Diagnosis

Multiple factors can cause asthma, and various stimuli can trigger it. The most prevalent physiological cause of asthma is bronchoconstriction of the airways in an immunoglobulin E (IgE) antibodies-mediated inflammatory response to allergens or other stimuli.⁴ This synergistic response combines inflammatory cell responses from lymphocytes, mast cells, eosinophils, neutrophils, basophils, and macrophages, increasing the release of inflammatory mediators such as histamines, prostaglandins, and leukotrienes.^4-5 As the disease progresses, other factors such as airway edema, hyperresponsiveness to stimuli, and airway remodeling occur, leading to severe asthma and increased exacerbations.^4-5

Common asthma environmental triggers include house dust mites, cockroaches, mold, animal danders from cats and dogs, exercise, smoking (including secondhand), cold air, indoor and outdoor allergens, anxiety, and obstructive sleep apnea.^3-4 In a European questionnaire and diary-based study by Price et al about environmental asthma determinants, data suggested that environmental factors such as dust, respiratory infections, smoking, air pollution, weather changes, and pets exposure were the main contributors to asthma exacerbations that significantly impacted individuals’ quality of life and job selections.⁷ In an observational, patient-questionnaire study in the United States by Chipps et al, data demonstrated that the most common triggers amongst patients with severe asthma were weather or air changes, viral infections, seasonal allergies, perennial allergies, and exercise.⁸ Among this cohort, patients reported poor quality of life due to uncontrolled asthma and reduced work productivity.⁸ As both studies showed, poorly controlled asthma significantly and negatively impacted patients' daily lives and overall quality of life.

The most common signs and symptoms of asthma include shortness of breath, wheezing, chest tightness, and cough.¹ These symptoms are nonspecific; therefore, evaluating respiratory symptoms and expiratory airflow obstruction via spirometry is recommended for diagnosing asthma.⁶ Spirometry can assess airway obstruction via forced expiratory volume 1 (FEV1) and force vital capacity (FVC) parameters.¹ A positive indicator of airway obstruction is an FEV1 less than 80% and FEV1/FVC ratio less than 75-80%.^1,5 Other tests, such as a bronchial provocation test, are less specific due to other comorbidities affected by bronchoconstriction.¹

The most common signs and symptoms of asthma include shortness of breath, wheezing, chest tightness, and cough. Image Credit: © mi_viri - stock.adobe.com

Pharmacotherapy

The main goals of asthma management are controlling respiratory symptoms, reducing exacerbations and hospitalizations, and decreasing medication-related adverse effects.¹ The Global Initiative for Asthma (GINA) guideline, a comprehensive and evidence-based resource, provides optimal strategies for asthma management. This guideline emphasizes a continual cycle of asthma assessment, treatment adjustment, and close follow-up by a trained professional, which is crucial for achieving and maintaining asthma control.

Before therapy initiation, it is essential to determine asthma severity based on how frequently patients experience daytime symptoms and nighttime awakenings attributed to asthma, as shown in Table 1.¹ In asthma management, a stepwise approach, as demonstrated in Figure 1, is utilized depending on how well-controlled a patient’s symptoms are or how often the patients are having worsening asthma-related symptoms. The GINA guideline recommends a step-up in therapy in patients with uncontrolled symptoms, which may involve increasing medication dose or frequency. Conversely, a treatment step-down is recommended in patients with well-controlled symptoms for at least 3 months, which may include reducing the medication dose or frequency.¹ This approach allows for personalized and targeted treatment, leading to improved symptom control and reduced risk of exacerbations. The criteria for stepping up or down in therapy are based on the frequency and severity of symptoms, as well as the patient's response to current treatment.

In the 2023 GINA stepwise treatment approach, inhaled corticosteroids and beta-2 agonists for reliever therapies are recommended for asthma symptom control.¹ Although a low-dose ICS-LABA therapy is preferred (as in Track-1) due to the reduced risk of exacerbations, cost and availability must be considered. For a controller or maintenance therapy, a low-dose ICS-LABA can be used daily, and the ICS component of the therapy may be increased to medium- or high-dose ICS, depending on the corresponding treatment step and asthma severity. An ICS-LABA can equally be utilized as both Maintenance And Reliever Therapy (MART) as needed for breakthrough symptoms. This strategy is instrumental in enhancing patient adherence and reducing severe asthma exacerbations.

Medication Adherence Barriers and the Role of Pharmacists in Overcoming Them

Common barriers to asthma management are directly related to an inadequate understanding of the disease state, the associated medications (Table 2), and overall medication cost. In an international patient-reported literature review, the main barriers to asthma management included disease state knowledge, medication knowledge, device cost, and access to health insurance.⁹ In another observational study by McQuaid in the United States, common medication barrier factors included cultural factors related to medication perception, depressive symptoms, and language barriers when communicating with healthcare professionals.¹⁰ Medication costs via copays or deductibles also hindered asthma medication adherence.¹⁰

Pharmacists play a crucial and valued role in asthma management (Figure 2). Pharmacists are instrumental in addressing barriers to medication adherence, such as device selection, education, and cost. Additionally, pharmacists can guide patients in understanding the asthma self-action plans and assess exacerbating triggers and symptoms that directly impact ED visits and hospitalizations. Appropriate device selection and administration techniques are vital to achieving asthma management goals. Patients with a higher number of maintenance inhalers, doses, and frequency have been shown to have decreased medication adherence.¹¹ Medication education is also critical in engaging patients in adherence to their asthma agent, especially regarding maintenance medications. Factors such as asymptomatic asthma are a significant contributor to patients becoming non-adherent to their maintenance medications due to the lack of immediate worsening symptoms.¹¹ Educating patients on the difference between reliever and maintenance medication is imperative to bridge the gap between medication adherence and lack of exacerbating symptoms. Patients also benefit from education on the consequences of stopping maintenance therapy, the implications of higher reliever medication use, the importance of proactively acting on exacerbating asthma symptoms, as well as the correlation between medication adherence, ED visits, and hospitalizations.

Conclusion

Asthma is a common inflammatory disease that directly impacts people’s quality of life and overall health-related costs. Appropriate asthma management via a step-wise approach, medication education, and device selection are essential to optimal disease state management. Multiple diseases and medication-related factors can impact medication adherence. Pharmacists play a crucial role in medication management by enlightening patients about symptom control and addressing device selection and cost.

REFERENCES

1. Global Strategy For Asthma Management and Prevention. Global Initiative For Asthma. 2022 Update. Accessed May 17, 2024. https://ginasthma.org/gina-reports/

2. Data, Statistics, and Surveillance. Centers for Disease Control and Prevention. March 29, 2023.Access May 17, 2024. https://www.cdc.gov/asthma/asthmadata.htm

3. Nurmagambetov T, Kuwahara R, Garbe P. The Economic Burden of Asthma in the United States, 2008-2013. Ann Am Thorac Soc. 2018;15(3):348-356. doi:10.1513/AnnalsATS.201703-259OC

4. National Asthma Education and Prevention Program, Third Expert Panel on the Diagnosis and Management of Asthma. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Bethesda (MD): National Heart, Lung, and Blood Institute (US); 2007 Aug. Section 2, Definition, Pathophysiology and Pathogenesis of Asthma, and Natural History of Asthma. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7223/

5. Sinyor B, Concepcion Perez L. Pathophysiology Of Asthma. [Updated 2023 Jun 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551579/

6. Monsnaim, G. Asthma in Adults. N Engl J Med 2023;389:1023-1031. DOI: 10.1056/NEJMcp23048

7. Price D, Dale P, Elder E, Chapman KR. Types, frequency, and impact of asthma triggers on patients' lives: a quantitative study in five European countries. J Asthma. 2014;51(2):127-135. doi:10.3109/02770903.2013.846369

8. Chipps BE, Soong W, Panettieri RA Jr, et al. Several patient-reported asthma triggers predict uncontrolled disease among specialist-treated patients with severe asthma. Ann Allergy Asthma Immunol. 2023;130(6):784-790.e5. doi:10.1016/j.anai.2023.03.001

9. Riley IL, Jackson B, Crabtree D, et al. A Scoping Review of International Barriers to Asthma Medication Adherence Mapped to the Theoretical Domains Framework. J Allergy Clin Immunol Pract. 2021;9(1):410-418.e4. doi:10.1016/j.jaip.2020.08.021

10. McQuaid EL. Barriers to medication adherence in asthma: The importance of culture and context. Ann Allergy Asthma Immunol. 2018;121(1):37-42. doi:10.1016/j.anai.2018.03.024

11. Bender BG. Overcoming barriers to nonadherence in asthma treatment. J Allergy Clin Immunol. 2002;109(6 Suppl):S554-S559. doi:10.1067/mai.2002.124570