Pediatric Reactive Airway Disease

Updated: Feb 23, 2016
  • Author: Eric S Chin, MD; Chief Editor: Kirsten A Bechtel, MD  more...
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Overview

Background

Not all children who wheeze have asthma. Most children younger than 3 years who wheeze are not predisposed to asthma. Only 30% of infants who wheeze go on to develop asthma. Reactive airway disease has a large differential diagnosis and must not be confused with asthma.

To establish the diagnosis of asthma, certain criteria should be met [1] :

  1. At least 5 years of age
  2. Episodic symptoms of airflow obstruction or airway hyperresponsiveness
  3. Reversible airflow obstruction of at least 10% of predicted forced expiratory volume in one second (FEV1) after use of short-acting beta2-agonist
  4. Alternative diagnoses have been excluded

On June 25, 2009, The American Thoracic Society and the European Respiratory Society jointly released new official standards on asthma evaluation for clinical trials and practice. [2] The Medscape Medical News article, New Guidelines Issued for Asthma Assessment, has a more detailed discussion.

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Pathophysiology

Numerous environmental stimuli induce an allergen-antibody interaction, causing a release of mediators that create airway inflammation. Airway inflammation is the primary factor responsible for smooth muscle hyperresponsiveness, edema, and increased mucous production. A complex interaction occurs between inflammatory cells and airway epithelium. Mast cells, eosinophils and lymphocytes secrete mediators include histamine, tryptase, heparin, leukotrienes, platelet-activating factor, cytokines, interleukins, and tumor necrosis factor and create an environment toxic to respiratory epithelial cells by causing edema, mucous secretion, bronchospasm and increased work of breathing.

Speculation exists that all infants are born with highly responsive airways. Increased immunoglobulin E (IgE) levels have been found in those younger than 2 years. A decrease in airway responsiveness may be associated with environmental allergens, viral respiratory diseases, and hereditary factors. In children younger than 3 years, the intrapulmonary airways are so small that any lower airway infection results in diminished airway function. Other anatomical factors, such as poor collateral ventilation, decreased elastic recoil pressure, and a partially developed diaphragm, may predispose the very young child to respiratory compromise.

Rhinovirus infections are an important contributor to asthma exacerbations in children. Hence, therapies against rhinovirus might reduce the risk of severe exacerbations. [3] Fever and bronchospasm are not associated with a more severe clinical course. In fact, fever as a response to infection may have a beneficial effect and can be seen as a good prognostic indicator. [4] Recently, it has been hypothesized that severe infection with Respiratory Syncytial Virus (RSV) may be a marker of a predisposing factor for asthma. [5]

There are several theories as to prevention of bronchospasm and asthma in children. The hygiene hypothesis suggests that early exposure to infections and allergens might protect children from developing asthma later in life because of improved immune system. [4]

Breastfeeding might protect children younger than 24 months of age against recurrent wheezing. The cytokine, TGF-B1, in human milk may have both suppression and enhancement functions in the immune reaction.

Exposure to maternal environmental tobacco smoke during pregnancy or the first year appears to predispose children to reactive airway disease.

Current research on the genetic basis for the pathogenesis of asthma may lead to new diagnostic and preventive treatments. The ADAM33 gene on the short arm of chromosome 20 is hypothesized as being important in the development and pathogenesis of asthma.

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Epidemiology

Frequency

United States

Pediatric asthma is a chronic, multifactorial, lower airway disease that affects 5-15% of children (2.7 million children in the United States alone). In the United States, approximately one half of all ED and clinic visits for asthma are children younger than 18 years. ED visits peak in the fall while school holidays disrupt the spread of infections resulting in a subsequent decrease in ED visits and hospitalizations. Status asthmaticus appears to be on the rise; several retrospective studies reflect an increase in hospital admissions, particularly in those younger than 4 years. Fewer hospital and ED visits occur in children using inhaled corticosteroid therapy.

Asthma prevalence appears to be increasing worldwide. Air pollutants may play a role in the prevalence increase. Higher prevalence occurs in poverty stricken urban areas where children are less likely to have routine doctor visits and access to the availability of medications.

A correlation may exist between high levels of exposure to cockroach allergen and the frequency of asthma-related health problems in inner-city children. [6] Homes in poverty areas were more likely to have high cockroach allergen levels. Asthma may develop in children from early exposure to cockroach allergen. [7] An association may exist between obesity and childhood asthma. Increased resistin, an adipokine produced by adipose tissue, may play a negative predictive role in asthma. [8]

An algorithm has been developed to determine the risk factors for developing persistent asthma symptoms among children younger than 3 years of age who had 4 or more episodes of wheezing during the previous year. [9] The Asthma Predictive Index included either (1) one of the following: parental history of asthma, a physician diagnosis of atopic dermatitis, or evidence of sensitization to aeroallergens; or (2) two of the following: evidence of sensitization to foods, ≥4% peripheral blood eosinophilia, or wheezing apart from colds.

International

Worldwide, the prevalence of asthma is increasing. Asthma is found to be more common in Western countries than in developing countries. Asthma is more prevalent in English-speaking countries. Prevalence increases as a developing country becomes more Westernized and urbanized.

Mortality/Morbidity

See the list below:

  • One third of all children younger than 18 years are significantly affected.
  • Reactive airway disease accounts for 13 million health care visits annually in the United States and 200,000 hospitalizations for which approximately $1.8 billion is spent annually.
  • Mortality rates are increasing despite new pharmacologist advances.
  • European Respiratory Society (ERS) and American Thoracic Society (ATS), created a task force to evaluate and provide management recommendations for severe or therapy-resistant asthma, recognized as a major unmet need. Severe asthma is defined as requiring treatment with high-dose inhaler plus a second controller and-or systemic corticosteroids to prevent it from becoming "uncontrolled" or that remains "uncontrolled" despite this therapy. Current research based on phenotyping (epidemiology, pathogenesis, pathobiology, structure and physiology) to allow better diagnosis and targeted treatment. [10]

Race

Reactive airway disease is more common in black and Hispanic children; hospitalization rates in African Americans are 4 times greater than in the white population. A correlation may exist between high levels of exposure to cockroach allergen and the frequency of asthma-related health problems in inner-city children. [6]

No correlation exists between education levels from a retrospective review.

Sex

The male-to-female ratio is 1.5:1.

Age

The peak prevalence of asthma is in those aged 6-11 years.

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Prognosis

Childhood asthma and wheezy bronchitis persisting into adulthood could lead to chronic obstructive lung disease (COPD) in later decades of life. [11]   

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