Asthma Uncovered: A Comprehensive Look at Epidemiology, Pathophysiology, and Diagnosis

Asthma is the most common chronic respiratory disease in children. Advances in understanding its pathophysiology, along with emerging therapies and updated treatment strategies, underscore the importance of staying current with evidence-based care. However, many primary care professionals may still rely on outdated guidelines.After completing this article, readers should be able to: Describe the underlying pathophysiology of asthma.Identify key clinical and diagnostic features of asthma in children and adolescents.Recognize other conditions in the differential diagnosis of asthma.Asthma affects nearly 5 million children and over 20 million adults in the United States (US), making it one of the leading chronic diseases.1 Asthma is characterized by chronic airway inflammation and reversible obstruction triggered by factors such as allergens, infections, and irritants. Signs and symptoms include wheezing, shortness of breath, chest tightness, and coughing, which can vary in severity. Asthma is controllable through trigger avoidance and by adhering to appropriate medical care.Guidelines, including those from the National Heart, Lung, and Blood Institute (NHLBI) and Global Initiative for Asthma (GINA), offer evidence-based recommendations for the diagnosis and management of asthma.2–4 Key updates include single maintenance and reliever therapy (SMART) with inhaled corticosteroid-formoterol combination inhalers. Additionally, there are several predictive tools and diagnostic tests that can assist the provider in identifying asthma.Despite the availability of guidelines, predictive tools, and effective treatments, asthma imposes a significant burden on patients, caregivers, schools, and the health care system. Asthma-related costs in the US—including missed school and work, health care expenses, and mortality—exceed $80 billion annually.5 Over the next 20 years, uncontrolled asthma is projected to contribute an estimated $964 billion in additional costs.6 Racial and ethnic disparities persist, with Non-Hispanic Black children and those with lower socioeconomic status experiencing more severe asthma symptoms.7,8 Clearly, there is much more to be done to reduce the impact of asthma.According to the most recent data from the Centers for Disease Control and Prevention (CDC), asthma affects one in every 12 children aged 0 to 17 years, which amounts to over 4.6 million children in the US.8 In childhood, asthma prevalence is higher among males (9%) than females (7%), whereas in adulthood, both the prevalence and severity are greater among women.9,10 Asthma prevalence shows significant disparities, with higher rates among children with limited resources, those in urban areas, and specific racial and ethnic groups. Asthma is more common in children ≥5 years (10%) compared with those <5 years (4%), among Non-Hispanic Black children (16%), American Indian/Alaska Native children (9%), and Puerto Rican children (13%) vs Non-Hispanic white children (6%), and in low-income families (10%) compared with families with incomes ≥250% of the Federal Poverty Level (about 7%).8,11More than half of children with asthma have experienced an asthma exacerbation within the past year, with racial and ethnic disparities in asthma-related emergency department (ED) visits and hospitalizations. The prevalence of asthma exacerbations, ED visits, and hospitalizations is higher among Non-Hispanic Black children (23%) and Hispanic children (16%) than among white children (12%).11 These racial differences in asthma outcomes may be explained by differences in health-related social needs or social drivers of health.12,13Asthma is a leading cause of school absenteeism. Children who have asthma miss more school days than their peers without asthma. Nearly half of school-aged children with asthma report at least one asthma-related missed school day annually.11 These absences may be because of a variety of factors, including symptoms, medical appointments, hospitalizations, and sleep disruptions from nighttime respiratory symptoms. Uncontrolled asthma can negatively impact academic performance, with more severe asthma often linked to poorer academic outcomes.14During the COVID-19 pandemic, the epidemiology of asthma in the US underwent notable changes. Health care systems observed reductions in asthma exacerbations, ED visits related to asthma, and asthma-related hospitalizations.15,16 Multiple factors likely contributed to these decreases, including pandemic response measures such as stay-at-home orders, widespread mask usage, social distancing, as well as a decline in viral infections because of reduced social contact and shifts in patient behaviors.17 Data on asthma prevalence in the postpandemic period remains limited, with the latest available data from the CDC extending only to 2021.18Asthma is a complex chronic disease characterized by lower airway inflammation, leading to bronchospasm, mucus hypersecretion, airway edema, and long-term airway remodeling, including structural changes such as subepithelial fibrosis, airway smooth muscle hypertrophy, and goblet cell metaplasia that can result in persistent airflow limitation.19 The development of asthma is influenced by diverse biological mechanisms (endotypes), clinical presentations (phenotypes), and treatment responses (theratypes), shaped by genetic predisposition, epigenetic changes, microbial exposures, and environmental triggers such as pollutants and tobacco smoke.20–22Asthma phenotypes include transient early wheezing, nonatopic wheezing, and atopic wheezing. Transient early wheezing typically resolves by age 3 years and is linked to prematurity, childcare exposure, and tobacco smoke.23–25 Nonatopic wheezing refers to viral-induced wheezing in early childhood, with respiratory syncytial virus (RSV) often associated with persistent wheezing.26 Persistent wheezing is defined as ongoing or recurrent wheezing beyond early childhood, frequently linked to airway inflammation or chronic conditions such as asthma. Atopic wheezing is characterized by early allergen sensitization, a family history of atopy, and genetic predisposition. Severe early life illnesses can lead to persistent wheezing across phenotypes.27Allergic asthma is driven by a T-helper (Th) 2-dominant response, with cytokines like interleukin (IL) 4, IL-5, IL-9, and IL-13 inducing immunoglobulin (Ig) E production, recruiting immune cells like mast cells, basophils, and eosinophils into the lungs, and amplifying airway inflammation.28 These insights have led to biologic therapies targeting specific immune pathways, offering more personalized treatment options.29 Other mechanisms, including viral-induced Th1 responses and Th17-mediated neutrophilic inflammation, also contribute to inflammation, especially in nonallergic asthma.29Environmental and social factors heavily influence asthma risk and severity. Early life microbial exposure promotes a Th1 response, reducing allergic inflammation, while insufficient exposure favors Th2 dominance and asthma risk, according to the “hygiene hypothesis.”30 Prenatal and postnatal exposure to pollutants, including particulate matter, nitrogen dioxide (NO2), ozone, and tobacco smoke, disrupts lung development and exacerbates airway inflammation.21,31–33 Socioeconomic disparities, poor housing, urbanization, chronic stress, and neighborhood violence further worsen asthma outcomes by increasing exposure to triggers and causing immune dysregulation.34–36Additional factors, including household food insecurity and childhood obesity, are associated with increased asthma risk. Food insecurity experienced before kindergarten is linked to higher odds of developing asthma.37 Obesity in childhood is also associated with a higher prevalence of asthma and may contribute to more severe disease.38,39Pediatric asthma management requires recognition of potential asthma triggers and management of exposures to minimize the resultant increased airway inflammation, frequency of symptoms, and acute exacerbations. Effective asthma management involves targeting these triggers across home, school, and community environments. Through interventions, education, and collaboration with community organizations, health care professionals can help mitigate exposures and improve health outcomes for children with asthma.Viral infections are a frequent cause of asthma exacerbations in children, as respiratory viruses can inflame the airways, intensifying asthma symptoms. Additionally, indoor allergens such as dust mites, animal dander, rodents, mold, and cockroach allergens are widespread and linked to increased asthma morbidity, particularly in urban and low-income settings. Exposure to indoor pollutants, including tobacco smoke and NO2 from cooking stoves, can lead to the aggravation of asthma and respiratory symptoms. Similarly, outdoor allergens and air pollutants—such as pollen, fine particulate matter (PM2.5), which refers to inhalable particles 2.5 μm or less in diameter; wildfire smoke; ground-level ozone; and traffic-related air pollution—play a significant role in exacerbating asthma.40 The risk of asthma exacerbation from outdoor allergens and air pollutants is especially high in communities with high levels of pollution and limited access to clean air environments.40Table 1 lists common asthma triggers and suggested management strategies.An in-depth review of the home environment is important, as children spend considerable time indoors, where allergens and pollutants are often concentrated. For example, in homes with high levels of indoor allergens or among children sensitized to allergens, implementing targeted interventions such as using HEPA air purifiers, mite-proof bedding covers, and removal of carpeting can reduce allergen levels and improve asthma outcomes. Keeping homes and cars smoke-free, along with the use of dehumidifiers and integrated pest management strategies, can further reduce the presence of asthma triggers. In individuals with sensitization or symptoms related to identified indoor allergens, home-based multicomponent interventions, particularly for low-income families, have shown substantial benefits in reducing hospital visits and improving asthma control.3,41 Addressing these environmental and social factors through targeted public health interventions and comprehensive environmental health-related policies is crucial to reducing the burden of asthma and improving long-term outcomes.42,43Asthma management also requires a focus on the school setting, where children may be exposed to potential triggers, such as cockroaches, dust, mold, pet allergens on carpets and students’ clothing, rodents (including furry classroom pets), as well as pollution from idling buses.44 Schools located near major roadways may expose children to higher levels of airborne pollutants, which contribute to poorer asthma control and increased ED visits.45 Climate change can affect the school environment by increasing exposure to extreme heat or cold. Additionally, children with asthma may face increased risks from air pollution—including wildfire smoke, which contains PM2.5, a pollutant known to exacerbate asthma symptoms—especially during outdoor activities such as recess and physical education. Educating school staff on managing indoor air quality, monitoring the local air quality index (AQI), and ensuring children with asthma have access to quick-relief medication and a written asthma action plan (AAP) can help mitigate these exposures and promote a safer school environment.Climate change is a growing concern in pediatric asthma, as it amplifies environmental factors that contribute to asthma exacerbations.46 Higher temperatures and altered weather patterns increase airborne allergens and pollutants, while more frequent wildfires and severe weather events worsen air quality. These changes disproportionately affect children with asthma, particularly those in urban and low-income areas.21,47 This further highlights the growing importance of integrating environmental health strategies into asthma management by health care professionals. This comprehensive approach includes educating families on air quality awareness and advocating for cleaner environments, which is crucial in reducing asthma-related health disparities.The diagnosis of asthma in children and adolescents is based on the history of recurrent symptoms, evidence of reversible expiratory airflow limitation (obstruction), and/or response to inhaled beta-agonists and/or inhaled corticosteroids (ICS). Signs and symptoms include cough, wheezing, shortness of breath, exercise intolerance, and/or chest tightness/discomfort. Symptoms vary over time and in intensity. Nighttime or early morning symptoms are common. Asthma triggers such as viral respiratory tract infections, exercise, exposure to allergens or irritants, changes in weather, air pollution, and strong emotions may worsen symptoms.The initial evaluation should begin with a detailed medical history, including the pattern of symptoms, presence of asthma triggers, and response to previous treatments, if given. Past medical history should include an evaluation for any atopy such as allergic rhinitis, atopic dermatitis, food allergies, prior exacerbations including ED visits and/or hospitalizations, and other medical conditions that may aggravate or mimic symptoms of asthma, such as obesity, gastroesophageal reflux disease (GERD), vocal cord dysfunction, anxiety, or other chronic respiratory conditions like cystic fibrosis or bronchopulmonary dysplasia in certain populations. The environmental history should include factors such as the condition of the home; the presence of carpeting, mold, or mildew; pests; pets; and exposure to pollutants such as tobacco smoke, vaping, or proximity to heavy traffic. The family history should be assessed for asthma or atopy. The social history should include factors that may affect asthma control, such as housing instability, access to medications, transportation barriers to medical care, and psychosocial stressors like family conflict or financial hardship.The physical examination is often normal, but may reveal signs of atopic conditions, such as allergic conjunctivitis, allergic rhinitis, or atopic dermatitis. In children with obesity—who have a higher prevalence of asthma in a dose-dependent relationship with body mass index (BMI)—physical examination findings may be complicated by overlapping symptoms such as dyspnea or reduced exercise tolerance, which can mimic or mask asthma.38 Children experiencing an acute asthma exacerbation may have variable symptoms and signs of respiratory distress, including wheezing on lung auscultation and/or a prolonged expiratory phase. Wheezing is a high-pitched sound, usually present during exhalation, that results from lower airway airflow obstruction. Inspiratory wheezing or difficulty is suggestive of vocal cord dysfunction, and not asthma.A diagnosis of asthma is clinical and is often supported by a patient’s improvement in symptoms following appropriate treatment. In children presenting with chronic or recurrent respiratory symptoms consistent with asthma, the diagnosis is established if there is clear clinical improvement and, when available, objective evidence such as improved spirometry after 1 to 3 months of therapy. Once diagnosed, these patients should receive ongoing management aligned with current asthma care guidelines. Figure 1 outlines a basic approach to evaluating a child with respiratory symptoms consistent with asthma.Asthma in children and adolescents is a clinical diagnosis, supported by several tools that can aid in both confirming the diagnosis and monitoring disease control and progression over time.Pulmonary Function Testing (PFT) is a broad term that encompasses a variety of different specialized breathing tests used to assess how well the lungs are functioning, including spirometry, lung volume measurements, diffusion capacity tests, peak flows, methacholine challenge, impulse oscillation, cardiopulmonary exercise testing, and fractional exhaled nitric oxide (FeNO), among others. In most outpatient primary and specialty care settings, spirometry is the most commonly used PFT, as it provides objective measures of airflow obstruction and bronchodilator response. Peak flow measurement and FeNO testing may also be used in some settings, whereas more advanced tests such as lung volumes, diffusion capacity, or bronchoprovocation (eg, methacholine are typically for specialty is used in both primary and specialty care to help the clinical diagnosis of asthma in patients with suggestive symptoms and to asthma control over spirometry is most in children years of age and and spirometry may be in children when by experienced pediatric in asthma management is to expiratory airflow limitation or obstruction with Key include capacity expiratory volume in 1 and expiratory flow at to the and are typically the lower of which is the for a with asthma may lung with a reduced the with a in the increase in of at least or an increase in of over is of a reversible lung a diagnosis of asthma should be that this of bronchodilator response established in recent evidence using an increase in of over in adults and an increase in of at least of the in children, which have to be updated in current or results are often in children with asthma, particularly when are at the time of Asthma remains a clinical diagnosis that suggestive symptoms, a history, and objective evidence of variable airflow obstruction when asthma spirometry at the time of diagnosis, and every 1 to years or more frequently if is for primary care professionals to that spirometry can reveal a greater severity of asthma than clinical appropriate therapy asthma and is to disease spirometry results can help more therapy for patients with asthma. primary care should have access to spirometry in their and be to and However, if spirometry is not patients may to be to a or who can this testing to diagnosis and appropriate ongoing For a detailed review of spirometry, to the FeNO is a that measures the of nitric oxide in a patient’s exhaled oxide is by cells in the respiratory tract and is often in patients with airway inflammation, particularly inflammation associated with allergic asthma. FeNO results can also be in conditions (eg, allergic rhinitis, atopic and are not in some of asthma (eg, neutrophilic asthma, asthma with In FeNO levels vary by factors, including and time of day in the day than in the of FeNO can be done in an The asthma its use in patients 5 years and diagnosis be by history, physical and spirometry with bronchodilator FeNO be before spirometry to of during FeNO levels can a diagnosis of airway inflammation, but are not specific to asthma and may be in other conditions, such as allergic or atopic key to using FeNO is the of FeNO is used in asthma specialty settings, where it can help treatment especially in patients with more severe or Peak expiratory flow are not for asthma management in children because of with and limited diagnostic can be are influenced by or and are less than spirometry, which is the objective when Peak flow monitoring is typically only when spirometry is used to aid in asthma diagnosis, a in peak flow over may asthma in can their peak flow at home, usually the of 3 is as the the and by the of these For example, if the is and the is the that day is is a that on in the airway smooth in In the asthma setting, the methacholine is for asthma in patients diagnosis not by Health care professionals should be that the may significant asthma symptoms, the risks and benefits should be in from is a Testing For children experiencing symptoms, a can be using a or exercise is before and after a exercise This is particularly for patients who not asthma or are to have obstruction with symptoms asthma. in of to is a result for This into the lungs during volume to airway and is for patients as as years and shown improvement in airway following a of in children with This is typically available only in specialty and is not commonly used in primary care is not for the diagnosis or management of asthma in children. are for managing asthma exacerbations in primary or acute care settings, as the of treatment. 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