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
- Allergens:
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
Flow-volume loop demonstrating improved airflow (green loop) following the administration of a short-acting bronchodilator in a patient with acute asthma attack (red loop)
Image by Lecturio.A child using a peak flow meter in a clinic
Image: A child using a peak expiratory flow meter in a pediatric clinic. By: National Heart, Lung and Blood Institute. License: Public domain
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:
- 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
- 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
- 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
- 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)
Component of severity | Classification of asthma severity | |||
---|---|---|---|---|
Intermittent | Persistent | |||
Mild | Moderate | Severe | ||
Symptoms | ≤ 2 days/week | > 2 days/week | Daily | Throughout the day |
SABA use | ≤ 2 days/week | > 2 days/week | Daily | Several times/day |
Nighttime awakenings | ≤ 2/month | 3–4/month | ≥ 1/week | Nightly |
Activity limitation | None | Minor | Some | Extreme |
Lung function (only in children > 5 years) |
|
|
|
|
Exacerbation requiring oral corticosteroid use | 0–1 times/year | ≥ 2 times/year | ||
Recommended action for treatment | Step 1 | Step 2 | Step 3 + medium-dose inhalded corticosteroids (ICS) | Step 3 + medium-dose ICS, or Step 4 or 5 |
Consider a short course of oral corticosteroids. | ||||
In 2–6 weeks, evaluate for control and adjust dose accordingly. |
Component of control | Well controlled | Not well controlled | Very poorly controlled |
---|---|---|---|
Symptoms | ≤ 2 days/week | > 2 days/week or multiple times on ≤ 2 days/week | Throughout the day |
SABA use | ≤ 2 days/week | > 2 days/week or multiple times on ≤ 2 days/week | Several times/day |
Symptoms | ≤ 2 days/week | > 2 days/week | Throughout the day |
Nighttime awakenings | ≤ 1/month | ≥ 2/month | ≥ 2/week |
Activity limitation | None | Some | Extreme |
Lung function | |||
FEV1 | > 80% | 60%–80% | < 60% |
FEV1/FVC | > 80% | 75%–80% | < 75% |
Exacerbation requiring oral corticosteroid use | 0–1/year | ≥ 2/year |
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.
- Goals:
Mild | Moderate | Severe | Respiratory arrest imminent | |
---|---|---|---|---|
Alertness | Normal | Usually agitated | Agitated | Drowsy or confused |
Respiratory rate (breaths/minute) | Increased | Increased | > 30 | Paradoxical thoracoabdominal movement or normal-low respiratory rate |
Pulse (beats/minute) | < 100 | 100–120 | >120 | Bradycardia |
Wheeze | End expiratory only | Throughout expiration | Throughout inhalation and expiration | Absent |
Inspiratory/expiratory ratio (normally 2:1) | Inspiratory/expiratory ratio of 1:1 | Inspiratory/expiratory ratio of 1:2 | < 1:2 | N/A |
Accessory muscle use | None | Common | Present | Present, but decreasing |
O2 saturation | > 95% | 90%–95% | < 90% ± cyanosis | < 90% ± cyanosis |
PCO2 (mm Hg) | < 42 | < 42 | < 42 | < 42 |
Peak expiratory flow | ≥ 70% | 40%–69% | 25%–39% | ≤ 25% |
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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)