Introduction and Epidemiology

Definition

Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma is defined as the episodic obstruction of lung airways resulting from a chronic inflammatory condition.

Classification

• Based on natural course:
  • Recurrent wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing: caused by viral infections; usually resolves before patients are school-aged
  • Chronic asthma: allergy associated; usually persists into adulthood 
  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. 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 Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing: common respiratory viruses such as rhinoviruses, respiratory syncytial virus Respiratory Syncytial Virus Respiratory syncytial virus (RSV) is an enveloped, single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae and the genus Orthopneumovirus. Two subtypes (A and B) are present in outbreaks, but type A causes more severe disease. Respiratory syncytial virus causes infections of the lungs and respiratory tract. Respiratory Syncytial Virus, adenovirus Adenovirus Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Adenovirus, influenza virus Influenza virus Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza, parainfluenza virus Parainfluenza virus Human parainfluenza viruses (HPIVs) are single-stranded, linear, negative-sense RNA viruses of the family Paramyxoviridae and the genus Paramyxovirus. Human parainfluenza viruses are the 2nd most common cause of lower respiratory disease in children, after the respiratory syncytial virus. Parainfluenza Virus, and human metapneumovirus
  • Home allergens can initiate airway inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation in susceptible children.
• Early childhood risk factors for persistent asthma:
  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma in parents
  • Allergy including atopic dermatitis Atopic Dermatitis Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Atopic Dermatitis (Eczema), allergic rhinitis Rhinitis Rhinitis refers to inflammation of the nasal mucosa. The condition is classified into allergic, nonallergic, and infectious rhinitis. Allergic rhinitis is due to a type I hypersensitivity reaction. Non-allergic rhinitis is due to increased blood flow to the nasal mucosa. Infectious rhinitis is caused by an upper respiratory tract infection. Rhinitis, and food allergy
  • Severe lower respiratory tract infection such as pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia or bronchiolitis
  • Wheezing (not as a result of colds)
  • Male sex
  • Low birth weight 
  • Passive tobacco smoking
• Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. 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 Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis
    • Gastroesophageal reflux
  • Drugs:
    • Beta blockers
    • Aspirin and nonsteroidal anti-inflammatory drugs

Pathophysiology

• Complex interactions between the following 2 components lead to airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction:  
  • Increased smooth muscle tone
  • Airway inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and exudate with eosinophils and other inflammatory cells such as neutrophils, monocytes, lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes, mast cells, and basophils
• Inflammation is mediated by helper T cells T cells T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. 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 Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing
• Other symptoms: 
  • Shortness of breath
  • Chest tightness
  • Chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain 
  • Self-imposed activity restrictions
  • General fatigue (possibly from poor sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep)
  • Limited physical activity
  • Worsening of symptoms at night or with triggers (see above)
  • Improvement of symptoms with asthma medications Asthma medications Management of asthma aims to reduce symptoms and minimize future risks and adverse outcomes (hospitalizations, loss of lung function, etc.). Medications commonly utilized include inhalers that allow bronchodilation and inflammatory control. Biologic agents are available for severe asthma. Asthma Medications
  • Atopic dermatitis

Physical signs during exacerbations of asthma

• Prolonged expiration with wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. 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 Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis or lobar pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. 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 Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing
  • Markedly decreased breath sounds
  • Peak expiratory flow < 40%
• Signs of imminent respiratory arrest:
  • Drowsiness or confusion
  • Paradoxical thoracoabdominal movement
  • Bradycardia
  • Absent wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. 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 Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Helps investigate complications such as atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis and pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. 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 Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis, primary ciliary dyskinesia Primary Ciliary Dyskinesia Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is an autosomal recessive disorder leading to an impairment that affects mucociliary clearance. Primary ciliary dyskinesia is caused by defective ciliary function in the airways and is characterized by the loss of oscillation (immotility), abnormal oscillation (dyskinesia), or absence of cilia (aplasia). Primary Ciliary Dyskinesia), especially in patients with recurrent bronchitis and/or chronic productive cough

Acute Exacerbation of Asthma

Definition

Acute exacerbation of asthma is the acute or subacute progressive worsening of airway inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and obstruction in an asthmatic patient.

General features

• Often occurs at night, during sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of 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 Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. 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 Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. 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 Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing and stridor with coughing due to involuntary closure of vocal cords; spirometry and flexible rhinolaryngoscopy may confirm the diagnosis
  • Hypersensitivity pneumonitis Hypersensitivity Pneumonitis Hypersensitivity pneumonitis (HP), previously called extrinsic allergic alveolitis, is an immunologically induced inflammatory disease affecting the alveoli, bronchioles, and lung parenchyma. It is caused by repeated inhalation of an inciting agent in a susceptible host that triggers first a type III (complement-mediated) hypersensitivity reaction in the acute phase and then a type IV (delayed) reaction in the subacute and chronic phases. Hypersensitivity Pneumonitis in farms or bird-owner homes
  • Parasitic infestations or tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis more commonly in rural developing countries
  • Chronic pulmonary disease, many of which may cause digital clubbing (absent in asthma)