What are the causes of pediatric asthma?

Causes of Asthma in Children

Pediatric asthma develops through a complex interaction between genetic predisposition and environmental exposures, with the most critical causative factors being atopy and family history, viral respiratory infections (especially in infants), allergic sensitization to house dust mites and Alternaria, and tobacco smoke exposure. 1

Genetic and Host Factors

Genetics represent the strongest foundation for asthma development in children. The disease has a clear inheritable component—children with two asthmatic parents have an 80% risk of developing asthma, compared to 40% with one asthmatic parent and only 10% with no asthmatic parents. 2 This genetic susceptibility involves multiple genes rather than a single mutation, making it a complex polygenic condition. 3, 2

Key Host Risk Factors:

• Atopy (genetic susceptibility to produce IgE) is one of the strongest predisposing factors, found in 30-50% of the general population but frequently associated with childhood asthma development. 3
• Positive family history of asthma and atopy represents a major susceptibility factor. 3
• Genetic polymorphisms and epigenetic markers established during perinatal periods have lasting effects on asthma risk. 3
• Lung function deficits present early in life predict persistent asthma symptoms into adulthood. 3

Environmental Triggers and Exposures

Environmental factors interact with genetic susceptibility during critical developmental windows to cause asthma, with timing of exposure substantially modifying genetic risk. 1

Primary Environmental Causes:

Viral Respiratory Infections:

• Among children 5 years and younger, viral respiratory infections are the most common cause of asthma symptoms. 3, 4
• Respiratory syncytial virus (RSV) and rhinovirus are the predominant viral triggers for both asthma development and exacerbations. 1, 4
• Early respiratory tract infections are important determinants of persisting asthma symptoms. 3

Allergen Sensitization and Exposure:

• Sensitization and exposure to house dust mites and Alternaria are among the two most important factors in asthma development, persistence, and severity. 1
• Common environmental allergens include house-dust mites, animal proteins, and fungi. 3
• Allergic comorbidities such as eczema and allergic rhinitis are important determinants of persistent asthma. 3

Tobacco Smoke Exposure:

• Environmental tobacco smoke exposure, particularly maternal smoking during pregnancy, increases risk of wheezing and subsequent asthma development in a dose-dependent pattern. 1, 2
• Active smoking in adolescence contributes to persistent asthma symptoms. 3

Air Pollution:

• Exposure to ozone, particulate matter, and NO2 increases asthma risk and triggers exacerbations. 1

Critical Developmental Windows

Exposures during fetal and early infant life represent critical windows when environmental factors most strongly influence asthma development. 1 In utero exposures can significantly impact asthma development, with maternal smoking during pregnancy increasing childhood asthma risk. 2 Early life is a critical period for immune system development, with exposures during this time having long-lasting effects on asthma risk. 2

Predictive Factors in Young Children

For children less than 3 years of age who have more than 3 episodes of wheezing per year (lasting more than 1 day and affecting sleep), the following predictive index identifies high risk (76% probability) for persistent asthma after 6 years of age: 3

Either:

• Physician diagnosis of atopic dermatitis, OR
• Parental history of asthma

Plus two of the following:

• Physician-diagnosed allergic rhinitis
• Greater than 4% peripheral blood eosinophilia
• Wheezing apart from colds

Immunologic Mechanisms

Childhood asthma is predominantly characterized by T2-high endotype with eosinophilic airway inflammation and allergic sensitization, driven by IgE and cytokines IL-4, IL-5, and IL-13. 3 This differs from adult-onset asthma, which more commonly exhibits T2-low endotype with neutrophilic inflammation. 3

The asthmatic response involves elevated production of IgE, cytokines, and chemokines; mucus hypersecretion; airway obstruction; eosinophilia; and enhanced airway hyperreactivity. 5

Socioeconomic and Lifestyle Factors

• Low socioeconomic status and inner-city residence increase asthma risk through multiple mechanisms including increased environmental exposures, reduced healthcare access, and higher stress levels. 1
• Low intake of antioxidants and omega-3 fatty acids may increase asthma risk. 1

Important Clinical Pitfall

The most dangerous error is assuming that well-controlled baseline asthma indicates low causative risk—asthma represents a dysfunctional interaction between genes and environmental exposures, with effects depending on concurrent influences within specific developmental windows. 1 The current "asthma epidemic" cannot be explained by genetic factors alone, indicating the critical role of environmental influences in causation. 2