Asthma in Children

Introduction and Epidemiology

Definition

Asthma is defined as the episodic obstruction of lung airways resulting from a chronic inflammatory condition.

Classification

• Based on natural course:
  • Recurrent wheezing: caused by viral infections; usually resolves before patients are school-aged
  • Chronic asthma: allergy associated; usually persists into adulthood 
  • Asthma with declining lung function: associated with hyperinflation in childhood and male sex
• Based on disease severity while not on asthma medication (see Table 1):
  • Intermittent
  • Persistent:
    • Mild
    • Moderate
    • Severe
• Based on response to treatment (see Table 2):
  • Well controlled
  • Not well controlled
  • Very poorly controlled

Epidemiology

• The most common chronic disease in childhood in developed countries
• Prevalence in the US (0–17 years): approximately 9%
• Among the most common causes of childhood emergency department visits, hospitalizations, and missed school days
• 80% of all asthmatic patients report disease onset prior to 6 years of age, but only a minority have persistent asthma later in life.

Etiology and Pathophysiology

Etiology

• A combination of genetic and environmental factors cause asthma
• Genetic factors: > 100 gene associations (no monogenicity)
• Environmental factors associated with asthma: 
  • Recurrent childhood wheezing: common respiratory viruses such as rhinoviruses, respiratory syncytial virus, adenovirus, influenza virus, parainfluenza virus, and human metapneumovirus
  • Home allergens can initiate airway inflammation in susceptible children.
• Early childhood risk factors for persistent asthma:
  • Asthma in parents
  • Allergy including atopic dermatitis, allergic rhinitis, and food allergy
  • Severe lower respiratory tract infection such as pneumonia or bronchiolitis
  • Wheezing (not as a result of colds)
  • Male sex
  • Low birth weight 
  • Passive tobacco smoking
• Asthma triggers: 
  • Allergens: 
    • Dust mites
    • Animal dander
    • Molds
    • Cockroaches
    • Seasonal pollens
    • Seasonal molds
  • Air pollutants:
    • Environmental tobacco smoke
    • Ozone
    • Nitrogen dioxide
    • Dust
    • Sulfur dioxide
  • Strong odors such as perfumes
  • Occupational/lifestyle exposures:
    • Farms and barns
    • Paint fumes
    • Cold, dry air
    • Physical exercise
    • Emotional stress
    • Hyperventilation
  • Comorbid conditions:
    • Rhinitis
    • Sinusitis
    • Gastroesophageal reflux
  • Drugs:
    • Beta blockers
    • Aspirin and nonsteroidal anti-inflammatory drugs

Pathophysiology

• Complex interactions between the following 2 components lead to airway obstruction:  
  • Increased smooth muscle tone
  • Airway inflammation, edema and exudate with eosinophils and other inflammatory cells such as neutrophils, monocytes, lymphocytes, mast cells, and basophils
• Inflammation is mediated by helper T cells that produce proinflammatory cytokines (interleukin 4 [IL-4], IL-5, and IL-13) and chemokines.
• Exposure to triggers and lack of appropriate therapy further induces a combination of the following (see image below)
  • Inflammation
  • Airway hypersensitivity response
  • Basement membrane thickening
  • Subepithelial collagen deposition and fibrosis
  • Smooth muscle hypertrophy
  • Mucus hypersecretion

Clinical Presentation

History of chronic asthma

• Most common symptoms: intermittent dry coughing and expiratory wheezing
• Other symptoms: 
  • Shortness of breath
  • Chest tightness
  • Chest pain 
  • Self-imposed activity restrictions
  • General fatigue (possibly from poor sleep)
  • Limited physical activity
  • Worsening of symptoms at night or with triggers (see above)
  • Improvement of symptoms with asthma medications
  • Atopic dermatitis

Physical signs during exacerbations of asthma

• Prolonged expiration with wheezing
• Decreased peripheral breath sounds
• Rhonchi or occasional crackles may be heard due to excess mucus production
• Segmental crackles + decreased breath sounds may indicate asthma-induced atelectasis or lobar pneumonia
• Peak expiratory flow in mild to moderate cases > 40%–70%
• Severe exacerbations:
  • Respiratory distress
  • Suprasternal and intercostal retractions and nasal flaring
  • Expiratory and inspiratory wheezing
  • Markedly decreased breath sounds
  • Peak expiratory flow < 40%
• Signs of imminent respiratory arrest:
  • Drowsiness or confusion
  • Paradoxical thoracoabdominal movement
  • Bradycardia
  • Absent wheezing
  • Peak expiratory flow < 25% (may not be required for evaluation)

Diagnosis

• A diagnosis of asthma in children often involves a combination of careful history taking, physical examination, pulmonary function tests (usually feasible in children > 6 years), and radiologic studies to rule out other conditions. 
• Spirometry findings consistent with asthma: 
  • Low forced expiratory volume in 1 second (FEV1) relative to predicted norms
  • FEV1:FVC (forced vital capacity) < 0.80
• Main laboratory criteria consistent with asthma:
  • Reversibility in FEV1 with inhaled beta agonists by ≥ 12% or ≥ 200 mL
  • Worsening in FEV1 with exercise by ≥ 15%
  • Variation in peak flow (see Image 3) or FEV1 from day to day or AM to PM by ≥ 20% 
• Chest X-ray: 
  • Typically normal in asthma
  • May show hyperinflation with flattening of the diaphragms during exacerbations or severe chronic asthma
  • Helps rule out other diagnoses such as aspiration pneumonia
  • Helps investigate complications such as atelectasis and pneumothorax during asthma exacerbations
• Chest computed tomography scan: further delineates comorbidities, differential diagnosis, and complications
• Skin prick testing for allergen sensitization
• Genetic testing: only for exclusion of monogenic obstructive lung diseases that could be misdiagnosed as asthma (cystic fibrosis, primary ciliary dyskinesia), especially in patients with recurrent bronchitis and/or chronic productive cough

Management

The goal of asthma management is to prevent/minimize symptoms, exacerbations, and functional and psychological morbidity to provide a healthy lifestyle appropriate for the age of the child.

The management of asthma has 4 components:

1. Continued assessment and monitoring (initially every 2–6 weeks, later every 1–6 months) made through an assessment of impairment and risk:
   • Impairment: frequency and intensity of symptoms and resulting functional limitations
   • Risk: likelihood of exacerbations, adverse events from medication, and long-term deterioration of lung function
2. Education for self-management (includes exploiting nurses, pharmacists, clinics, schools, etc., in the education process):
   • Helping patients recognize their own level of control and signs of disease progression by peak-flow and/or symptom monitoring
   • Educating patients on environmental control, avoiding triggers and tobacco smoke, correct use of and adherence to medications, and difference between long-term and quick-relief medications
3. Identification and management of precipitating factors and comorbidities:
   • Identifying allergens through skin testing and counseling on avoidance strategies
   • Comorbidities may include bronchopulmonary aspergillosis, gastroesophageal reflux disease, obesity, obstructive sleep apnea, rhinitis, sinusitis, depression, stress, low vitamin D levels.
   • Influenza vaccination in all children > 6 months old with asthma
4. Appropriate selection of medications:
   • A step-up approach in pharmacotherapy is recommended to control impairment and risk. Once controlled, a step-down approach is implemented to maintain control on the minimum amount of medication (see Table 1 and image below).
   • Before every step up: assessment of adherence, appropriate inhaler technique, and environmental control for avoidance of triggers/allergens
   • Inhalers are best given with a spacer device to maximize efficacy.
   • Asthma medications are used for relief and control.
   • Medications for relief:
     • Short-acting beta 2 agonists (SABA; e.g., albuterol)
     • Systemic corticosteroids
     • Short-acting muscarinic antagonist (SAMA; e.g., ipratropium)
   • Medications for control:
     • Inhaled corticosteroids
     • Long-acting beta 2 agonists (LABA; e.g., formoterol, salmeterol)
     • Theophylline
     • Leukotriene modifiers
     • Anti-immunoglobulin E (IgE) antibody (omalizumab)
     • IL-5 monoclonal antibodies (mepolizumab, benralizumab)
     • IL-4 receptor alpha monoclonal antibody (dupilumab)
     • Inhaled cromolyn or nedocromil (not available in the United States)

Acute Exacerbation of Asthma

Definition

Acute exacerbation of asthma is the acute or subacute progressive worsening of airway inflammation and obstruction in an asthmatic patient.

General features

• Often occurs at night, during sleep
• Decreased/absent response to SABA may result in a vicious cycle of shunting and further bronchoconstriction, leading to hypoxemia.
• Exacerbations must be immediately assessed for severity (See table 3).

Management of acute exacerbations

• At home:
  Parents/guardians must have a written action plan and act early to prevent further worsening of symptoms:
  • Repeat SABAs 3 times in 1 hour (appropriate response: resolution of symptoms in 1 hour and PEF > 80%).
  • Contact physician if further exacerbations within 24–48 hours.
  • Use short course of oral corticosteroids and contact physician if partial response.
  • Call 911 if any sign of severe and persistent symptoms.
  • Use of home epinephrine autoinjectors and portable oxygen therapy may be indicated in extreme cases.
• Emergency department:
  • Goals:
    • Correct hypoxemia with oxygen therapy
    • Rapid reversal of airflow obstruction with repeated doses of SABA and early use of systemic corticosteroids + SAMA (inhaled ipratropium)
    • Consider adjunctive treatments, such as intravenous magnesium sulfate or heliox, in severe exacerbations unresponsive to treatment.
    • Prevent recurrence by intensification of therapy ± short-term systemic corticosteroid therapy.
  • Requirements for patients with persistent severe symptoms and high-flow oxygen requirements:
    • Laboratory evaluation with complete blood count, comprehensive metabolic panel, and arterial blood gases
    • Chest X-ray
    • Monitoring for dehydration
  • Patients with any signs of imminent respiratory failure require endotracheal intubation and admission to a pediatric intensive care unit.

Differential Diagnosis

• Rhinosinusitis: difficult to diagnose in younger children due to absence of localized sinus pressure or tenderness; may be a comorbid condition 
• Gastroesophageal reflux: can present with intermittent cough and wheezing; may be a comorbid condition
• Younger children:
  • Recurrent aspirations
  • Tracheobronchomalacia
  • Foreign-body aspiration
  • Bronchopulmonary dysplasia
  • Cystic fibrosis
  • Primary ciliary dyskinesia
• Older children and adolescents:
  • Vocal cord dysfunction: may present with daytime wheezing and stridor with coughing due to involuntary closure of vocal cords; spirometry and flexible rhinolaryngoscopy may confirm the diagnosis
  • Hypersensitivity pneumonitis in farms or bird-owner homes
  • Parasitic infestations or tuberculosis more commonly in rural developing countries
  • Chronic pulmonary disease, many of which may cause digital clubbing (absent in asthma)