Asthma Overview and Definition

Asthma

• Asthma is characterized by episodic wheezing and/or coughing with variable airway obstruction, often responsive to bronchodilator therapy.
• Asthma is a heterogeneous condition influenced by hereditary/genetic and environmental factors.
• Asthma primarily affects the small and medium-sized bronchi (2-5mm in diameter).
• Airflow limitation in asthma results from bronchial spasm, mucosal edema, and excessive tenacious secretions.
• Asthma presents with various symptoms, none of which are specific to the condition.

Definition of Asthma

• Asthma is a chronic inflammatory condition of the lung airways, causing episodic airflow obstruction.
• Key characteristics of asthma are:
  • Airway inflammation and remodeling
  • Airway hyper-responsiveness
  • Variable but reversible airway/airflow obstruction

Burden of Asthma

• Asthma is a major non-communicable disease affecting children and adults.
• In Nigeria, asthma is ranked second only to pulmonary tuberculosis as a common childhood chronic disease.
• Asthma is often underdiagnosed and undertreated in low- and middle-income countries.
• Approximately 13 million people in Nigeria have clinical asthma.
• Asthma is prevalent in industrialized nations, urban areas, and affluent populations.
• The male-to-female ratio for asthma is approximately 1.3:1.

Aetiology of Asthma

• Environmental exposures and inherent biological/genetic vulnerabilities contribute to asthma.
• Respiratory exposures in asthma include allergens, respiratory viral infections, and chemical/biological pollutants (e.g., environmental tobacco smoke).
• Immune responses to these exposures in a predisposed host can trigger prolonged, pathogenic inflammation and impaired repair of injured airways.
• Key factors increasing the risk of asthma development include:
  • Family history of asthma (parents and siblings)
  • Allergic conditions (eczema, rhinitis, etc.)
  • Urbanization
  • Low birth weight
  • Prematurity
  • Viral respiratory tract infections
  • Overweight or Obesity
  • Environmental allergens and irritants (indoor/outdoor pollution, house dust mites, molds, chemicals, etc.)

Genetic Basis of Asthma

• Studies have shown variable results in linking specific loci on chromosomes to asthma.
• Asthma has been significantly linked to the interleukin-4 (IL-4) gene cluster on chromosome 5.
• Other genes associated with asthma include ADAM-33, postanoid receptor genes, and those located on chromosome 5q31.
• Some studies suggest dominant inheritance patterns.
• Other studies link the gene locus to the B subunit of high-affinity IgE receptors.
• Major gene locus for asthma expression is likely located on chromosome 11q13.
• The expression of the genetic component of asthma is linked to increased IgE concentration.
• Linkage is predominantly observed in maternal alleles.
• Binding of IgE to the high-affinity IgE receptor on mast cells leads to increased IgE production.

Environmental Basis

• The "hygiene hypothesis" suggests an observed increase in asthma prevalence in industrialized societies, possibly due to reduced exposure to microbes in early life.
• Abundance of microbial fauna at birth may protect against hyperactivity disorders.
• Exposure to microorganisms during early development may drive immune responses towards Th1 responses, which are protective against atopic asthma.

Pathogenesis of Asthma

• Chronic inflammation is the major characteristic of asthma.
• The inflammatory process begins with altered maturation of helper T (Th) lymphocytes, specifically to the Th2 subtype.
• Th2 cells release soluble cytokines (e.g., interleukin-3, GM-CSF), which lead to the recruitment of IgE, mast cells, basophils, and eosinophils.
• In the presence of antigens, various toxic substances (e.g., leukotrienes, eosinophil cationic protein) are released.
• These toxic substances cause denudation of bronchial epithelium, exposing sub-epithelial nerves to external factors.
• The established Th2 response is difficult to reverse, resulting in ongoing damage to the epithelium.
• Other inflammatory mediators (e.g., cysteinyl leukotrienes), via the arachidonic acid cascade, promote epithelial shedding, plasma exudation, and basement membrane thickening.
• Substances like protein kinase C activation and neuropeptide release cause bronchoconstriction and increased mucus secretion.

Pathophysiology of Asthma

• The hallmark of asthma is airflow obstruction, primarily impacting small and medium-sized bronchi (2-5mm).
• Resting bronchial hyper-reactivity (BHR) is triggered by various factors.
• Following exposure to trigger factors, bronchoconstriction, mucosal edema, and increased mucus secretion occur.
• Airway obstruction reduces oxygen supply, leading to lower oxygen saturation during asthma episodes.
• Other consequences include atelectasis and varying degrees of abnormal lung function.
• Persistent obstruction can lead to hypercapnea, acidosis, respiratory failure, and ultimately death.
• A ball-valve obstructive phenomenon (like barrel chest) is observed during acute asthma exacerbations.
• Trigger factors for asthma include viral infections, dust and pollutants (cigarette smoke), allergens (dust mites, pollen, molds, animal danders, certain foods, spores), exercise, drugs, weather changes (cold dry air), and psychological factors (stress, emotion). Perfumes also trigger asthma attacks.

Asthma Phenotypes

• Phenotype refers to the outward, physical manifestation of an organism.

• Disease phenotype represents a cluster of clinical/pathological features that are useful for patient management and understanding disease mechanisms.

• Established Asthma Phenotypes in Children:

  • Transient wheezing
  • Non-atopic wheezing in toddlers
  • IgE-mediated wheeze/asthma
  • Late-onset childhood asthma

• Asthma phenotypes can predict response to treatment and propensity for accelerated loss of pulmonary function.

Features of Childhood Asthma

• Asthma is characterized by dual components including inflammation and bronchospasm.
• Symptoms depend on severity and include wheezing, shortness of breath, chest tightness, and cough.
• Asthma symptoms are typically variable, intermittent, and worse at night or with triggers like exercise.
• Historical factors (personal and family history of asthma or other atopic conditions) also worsen symptoms in response to triggers.
• Signs of asthma include rhonchi (bilateral, diffuse, expiratory, polyphonic), reduced lung function (decreased peak flow, obstructive pattern on spirometry), and evidence of hyperinflation (e.g., wide AP diameter, hyperresonance, diminished breath sounds).

Asthma Mimics

• Asthma mimics are conditions that can present with similar symptoms as asthma but have different underlying causes.
• Age-dependent conditions that can mimic asthma include reflux esophagitis, tracheosophageal fistula, bronchiolitis, pneumonia, sinusitis, pulmonary tuberculosis, laryngeal papilomatosis, cardiac failure, dilated cardiomyopathies, inhaled foreign bodies, tracheomalacia, bronchomalacia, and vocal cord dysfunction.

Asthma Diagnosis

• Definitive diagnosis of asthma, particularly in young children, can be challenging.
• The majority (43.45%) of children with asthma present between the ages of 2 and 6.
• Asthma can be diagnosed in infancy.
• Diagnostic methods include:
  • History/clinical features
  • Basic investigations (eosinophils, IgE levels, prick skin test, blood gas analysis)
  • Lung function tests (pulse oximetry, chest radiography, stool for ova/parasites, PEFR, spirometry, provocation tests)
  • Objective measures (bronchodilator responsiveness, diurnal variability in airway caliber/volume, free running exercise)

Asthma Diagnosis (Objective Measures)

• Asthma diagnosis relies on demonstrating airway reversibility and variable airflow limitations.
• This can be measured with spirometry (FEV1 and FVC) or a peak expiratory flow (PEF) meter.
• Criteria for objective measurements include:
  • FEV1/FVC ratio less than 75% (or PEFR less than 80% predicted)
  • PEFR increase of more than 15%, 15–20 minutes after inhalation of a rapid acting B2 agonist.
  • PEFR decrease of more than 15% (or 12.5% in some studies) after 6 minutes of sustained running or other exercise.

Severity of Asthma

• Asthma severity is categorized based on GINA guidelines, commonly into:
  • Intermittent
  • Mild persistent
  • Moderate persistent
  • Severe persistent.
• The majority (65% in some studies) of children have intermittent asthma.
• Severe persistent asthma (1%) is associated with growth stunting, activity limitations, and various chest deformities.

Assessment of Asthma Severity

• Severity levels are assessed based on daily/night-time symptoms, exacerbations, and responsiveness to treatment. Example criteria include:

  • daytime/night-time symptoms, exacerbations in a week, PEF or FEV1 variability, peak flows and other clinical parameters.

• This assessment assists in determining the appropriate treatment approach.

Severity of Asthma Episode

• Severity of asthma episodes helps clinicians tailor treatment strategies.
• Severity levels include mild (PEFR >75% predicted), moderate (PEFR 50-75% predicted), severe (PEFR 33-50% predicted), and life-threatening (PEFR <33% predicted).

Initial Assessment of Acute Asthma

• Initial assessment involves evaluating symptoms and physical signs to determine severity (mild, moderate, severe/life-threatening).
• Key parameters include:
  • Confusion
  • Pulse oximetry (SaO2)
  • Respiratory rate
  • Speech
  • Pulse rate
  • Central cyanosis
  • Wheeze intensity
  • PEFR
  • FEV1 (Tables with severity criteria in the text)

Management of Childhood Asthma

• Management goals include reducing symptoms (especially at night), improving activity at home/school/leisure, using treatments with minimal side effects, optimizing growth/development, improving quality of life, and reducing asthma mortality.
• Management stages encompass:
  • Environmental manipulation
  • Partnership in asthma management
  • Pharmacotherapy
  • Immunotherapy

Environmental Manipulation

• Identify and manage environmental triggers (e.g., allergens, pollutants).
• Educate children and parents on avoidance strategies (e.g., eliminating house dust, avoiding cigarette smoke).
• Consider removing patients from environments with high allergen exposure when feasible.

Partnership in Asthma Management

• Establish strong partnerships with patients, parents, and teachers.
• Educate children and parents on asthma management strategies, including use of medications and devices.
• Encourage children/parents to take the initiative in asthma care, if possible.

Pharmacotherapy

• Medications for asthma management include both relievers (for immediate relief) and preventers (to control long-term symptoms).
• Ideal drugs:
  • B2 agonists: bronchodilators for relieving bronchoconstriction.
  • Corticosteroids: anti-inflammatory agents.
• Inhaler administration: the preferred delivery method for asthma medications in children.
• Spacer devices are recommended with MDI's for optimal delivery.
• Recent therapeutic developments include combinations of long-acting B2 agonists and inhaled corticosteroids in a single inhaler (e.g. Seretide).
• Polypharmacy should be avoided; two inhalers (a B2 agonist and a corticosteroid) are often sufficient.
• Drug dose is tailored to the severity and disease progression.

Immunotherapy

• Allergen-specific immunotherapy (allergy shots) involves repeated administration of increasing allergen doses to build tolerance.
• Methods of delivery include subcutaneous (SCIT) and sublingual immunotherapy (SLIT).
• Immunotherapy reduces the need for quick-relief and long-term medications and improves quality of life and FEV1.
• Anaphylaxis is a rare complication.

Initial Management of Children with Acute Asthma

• Treatment strategies based on the severity of the acute asthma episode (mild, moderate, severe/life-threatening).
• Table of treatment options (such as supplemental oxygen, inhalers, systemic corticosteroids, etc) for each severity level.

Assessment of Asthma Control

• Parameters to assess asthma control:
  • Daytime symptoms (frequency)
  • Nighttime symptoms (frequency)
  • Physical activity
  • Asthma exacerbations
  • School/work missed
  • Reliever use
  • FEV1/FVC ratio or PEF
• Evaluation tools for assessing asthma control (e.g., questionnaires, lung function tests).

Prognosis of Childhood Asthma

• Most children with asthma cease wheezing within 10-20 years after initial diagnosis.
• 5-10% of children continue to have severe asthma exacerbations.
• Concurrent or antecedent atopic dermatitis may indicate a poor prognosis.

Fatal Asthma in Childhood

• Low case fatality rate (generally less than 1%).
• Fatalities are usually in pubescent girls.
• Death often sudden and associated with extreme excitement or agitation.
• In many fatal cases, severity was underestimated by the patient or caregiver.
• Inapproriately low corticosteroid use is also a frequent factor in fatal episodes.
• Most cases of fatal Asthma are preventable with appropriate treatment.

Risk Factors for Asthma-Related Death

• Previous near-fatal asthma events.
• Severe asthma exacerbations requiring intensive care or intubation.
• Use of 2 or more canisters of short-acting bronchodilators in a month.
• Poverty
• Two or more hospital admissions or 3+ emergency room visits for asthma within the previous year.
• Significant psychiatric disease.

This quiz covers essential concepts related to asthma, including its characteristics, definition, and the burden it poses globally. You'll learn about the factors influencing asthma and the symptoms associated with this chronic condition. Test your understanding of airway inflammation and the impact of asthma on individuals.