Asthma Disease Background

Introduction

A heterogeneous disease characterized by chronic airway inflammation that results in recurrent episodes of wheezing, shortness of breath (SOB), chest tightness, and cough that vary over time and in intensity, with variable expiratory airflow limitation.

Epidemiology

Asthma is a common chronic, noncommunicable respiratory condition that affects 1-18% of the population in various countries. Worldwide, it affects approximately 300 million people and is associated with significant morbidity and mortality. It affects 7.9% of the population in the United States, with the greatest prevalence among Puerto Ricans. In Asia, it is considered a major chronic disease, especially in low- to moderate-income countries.  

The China Asthma and Risk Factors Epidemiologic (CARE) survey in 2010-2012 reported a prevalence rate of 1.24% in Mainland China among those aged ≥14 years old. More recently, the Chinese Pulmonary Health reported that the prevalence of the disease was 4.2% from 2012-2015 among those aged ≥14 years old.  

The Indian Study on Epidemiology of Asthma, Respiratory Symptoms and Chronic Bronchitis (INSEARCH) reported that the estimated national burden of the disease was at 17.23 million people with an overall prevalence of 2.05% among individuals aged >15 years old. According to the report by the Global Asthma Network (GAN) in 2022, approximately 35 million people were diagnosed with asthma in India.  

In Thailand, the prevalence of asthma remained high in the country despite improved access to asthma controllers and progressive asthma guidelines according to GAN. A study reported that the prevalence in the country from 2001-2002 was 3% among those aged 20-44 years old. Based on the National Health and Morbidity Survey in Malaysia in 2006, the prevalence of asthma was 4.5% among those aged ≥18 years old. The latest National Nutrition and Health Survey in the Philippines reported that the overall prevalence of the disease was 8.7%.  

The Global Initiative for Asthma in 2004 reported that the prevalence in Korea was 3.9%. According to the Korean National Health and Nutrition Examination Survey (KNHANES), the prevalence of asthma was 2.0% in 2008, although the Korean National Insurance data reported that the prevalence of the disease was 4.7% in the same year.  

Asthma is more common among children than adults. In children, boys are affected more than girls, however, it becomes more common among women in adulthood. 

Pathophysiology

The pathophysiologic hallmark of asthma is airway hyperresponsiveness which is defined as acute airway narrowing as a response to agents that do not normally elicit airway responses in unaffected individuals. Hyperresponsiveness specifically occurs at the level of the airway smooth muscles. Inflammatory cells (eg eosinophils, neutrophils, mast cells), histamine, leukotrienes, and sensory nerves all play a role in airway hyperresponsiveness and bronchoconstriction. Structurally, airway wall thickening also contributes to the narrowing and is a result of smooth muscle hypertrophy and hyperplasia, airway inflammation, submucosal edema, and collagen deposition on the subepithelial basement membrane.  Epithelial goblet cell metaplasia and mucus hypersecretion, resulting from chronic inflammation, form mucus plugs that can obstruct small- and medium-sized airways.  

Airway inflammation (particularly type 2 Inflammation) is also a significant hallmark in the pathophysiology of asthma. It similarly follows the early and late phase reactions involved in hypersensitivity reactions wherein the initial allergen exposure triggers the formation of specific IgE antibodies. These antibodies then bind to the receptors on mast cells wherein subsequent exposure to the same allergen crosslinks with the allergen specific IgE antibodies on mast cells triggering a rapid mast cell degranulation, releasing chemical mediators of inflammation causing asthma symptoms.  

Airway inflammation is also mediated by the type 2 subset of CD4+ T-helper cells which produce interleukins 4, 5, and 13. Interleukin-4 is responsible for B-cell isotype switching to produce IgE, interleukin-5 mainly regulates eosinophils, and interleukin-13 contributes to airway hyperresponsiveness and remodeling, goblet cell metaplasia, and mucus hypersecretion.  

Recent studies have shown the involvement of innate lymphoid cells (ILC2) or non-type 2 inflammation which are stimulated by non-allergic exposure to irritants, pollutants, viruses, etc. These cells also produce interleukins 5 and 13. 

Risk Factors

Risk Factors for Poor Asthma Outcomes  

Assess patients for risk factors at diagnosis and periodically especially if with exacerbations. Measure the forced expiratory volume in 1 second (FEV₁) at the beginning of treatment and after 3-6 months of controller treatment.  

Risk Factors for Exacerbation  

The following are the risk factors for asthma exacerbation:

• Medications: Frequent short-acting beta₂-agonist, inadequate inhaled corticosteroids (not prescribed or poor adherence), beta-blockers, NSAIDs, incorrect inhaler technique
• Medical conditions: Obesity, gastroesophageal reflux disease, chronic rhinosinusitis, food allergy
• Exposures: Allergen, tobacco & e-cigarette smoke, air pollution, sulfites
• Lung function: Low FEV₁ (especially if <60% predicted), high bronchodilator reversibility
• Tests (in patients with type 2 inflammation): Blood eosinophils, elevated fractional concentration of exhaled nitric oxide (FENO)
• Psychological or socioeconomic problems
• Other independent risk factors: History of intubation or intensive care unit admission for asthma, ≥1 severe exacerbation in the last 12 months

Risk Factors for Development of Persistent Airflow Limitation

The following are risk factors for the development of persistent airflow limitation:

• History: Preterm birth, low birth weight, and greater infant weight gain, chronic mucus hypersecretion
• Medications: Lack of inhaled corticosteroids in treating patients who had a severe exacerbation 
• Exposures: Tobacco and e-cigarette smoke, occupational exposures
• Investigations: Low initial FEV₁, sputum, or blood eosinophilia

Risk Factors for Medication Side Effects

The following are risk factors for medication side effects:

• Systemic: Frequent oral corticosteroids, long-term use of high-dose inhaled corticosteroids, concomitant intake of P450 inhibitors
• Local: High-dose inhaled corticosteroids, poor inhaler technique

Classification

Classification by asthma phenotypes (clusters of asthma characteristics) differ in clinical manifestations, pathophysiology, and demographic location of the patient:

• Allergic asthma: Present in childhood, with a positive family history of asthma, and previous history of allergies such as eczema, food allergy, allergic rhinitis, etc. 
• Non-allergic asthma: Asthma without an allergic component
• Late-onset asthma: Also called adult-onset; asthma presenting and diagnosed for the first time in adult years
• Asthma with fixed airflow limitation: Airway wall remodeling due to chronic airway inflammation causing irreversible airflow obstruction
• Asthma with obesity: The prevalence of symptomatic asthma is increased in those suffering from obesity 

The following is the classification of asthma by severity, assessed when a patient has been on controller treatment for several months:

• Mild Asthma: Well-controlled with step 1 or step 2 treatment, although GINA 2022 suggests avoiding using this term because of the common assumption that it is of low risk. However, if clinically warranted to use the term, clinicians must be reminded that patients with mild asthma symptoms can still have severe or fatal exacerbations.
• Moderate Asthma: Well-controlled with step 3 or step 4 treatment.
• Severe Asthma: Requires or uncontrolled with high-dose inhaled corticosteroids with long-acting beta₂-agonist