Asthma- Finals

• Asthma


  Clinically identified by recurring episodes of breathlessness, chest tightness, wheezing, often accompanied by coughing. It is a reversible airflow obstruction.
• Asthma (from a physiological perspective)


  • Involves reversible constriction of the bronchial airways and an evident increase in bronchial responsiveness to inhaled stimuli
• Asthma (pathologically)


  • Marked by inflammation of the bronchial mucosa, characterized by the presence of lymphocytes and eosinophils. Additionally, there is a pathological feature known as "remodeling," involving the thickening of the lamina reticularis beneath the airway epithelium and the hyperplasia of cells in all structural components of the airway wall, including vessels, smooth muscle, secretory glands, and goblet cells

  
• Types of asthma


  • Allergic (extrinsic)
  • Non-allergic (intrinsic)
• Allergic Asthma (Extrinsic)


  Often referred to as classic allergic asthma, and is characterized by immune responses mediated by immunoglobulin E (IgE). The production of IgE is triggered by exposure to foreign proteins known as allergens.
• Non-allergic Asthma (Intrinsic)


  Provoked by factors unrelated to allergies. Stress, anxiety, certain viral infections, exposure to smoke, and adverse weather conditions like cold or dry air are non-allergic elements that can act as triggers.
• According to the Global Burden of Disease (GBD) in 2019, there are approximately 262 million people afflicted with asthma, or around 3416 cases per 100,000 population worldwide
• Asthma is the top 24th leading cause of years lived with disability and top 34th leading cause of burden of disease in relation to disability adjusted life years (DALYs)
• Populations most prevalent with self-reported asthma in the United States


  • Populations whose poverty level is 100% to less than 250% of the poverty threshold
  • Adults
  • Females
  • Non-Hispanic American Indian/Alaska Native and non-Hispanic Black people
• Asthma is more prevalent in boys compared to girls, but in terms of adults, it is 20% more prevalent in women than men
• The GBD stated approximately 461,000 people died from asthma globally in 2019 alone, and the overall rate of asthma deaths were higher in lower-income countries, which may be attributed to the limited accessibility of asthma management interventions
• In 2017, the asthma death rate in the Philippines was 19.47 per 100,000 population, placing it in the top 15th of countries with most asthma deaths
• Causes of asthma


  • Genetics
  • Exposure to risk factors, such as allergens, at an early childhood age is suspected to lead to development of asthma due to the activation of the immune system
  • Microbiological exposures such as respiratory viral infections and bacterial pathogens
• ORMDL3


  The gene which is highly associated with asthma
• Patients with asthma have shown differences from the lower airway microbiota of healthy individuals. Altered nasal microbiota, such as those with persistent Moraxella sparsity, was found to have a higher risk of having asthma.
• Viral respiratory infections


  • Exacerbate asthmatic attacks in younger children who experience wheezing associated with upper respiratory tract infections (URTIs)
  • The most frequently associated virus with asthma is rhinovirus which directly activates the eosinophils, an inflammatory mediator associated with asthma
  • Other viruses, namely RSV and parainfluenza virus, are capable of triggering the IgE antibodies that are most responsible for the pathophysiology of the disease
• There is still no evidence supporting the association of COVID-19 and asthma. However, it is still important to note the history for asthma is COVID-19 patients. This is because patients with comorbidities increase the risk for hospitalization.

  
• Environmental factors triggering asthma


  • Tobacco
  • Smoke
  • Pollution
  • Allergens. Airborne pollens, dust mites, animal dander, rodents, cockroaches, fungal spores
  • Environment. Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide
  • Meteorological conditions
  • Occupational stimuli
• Other agents which could trigger asthma exacerbations


  • Host factors. Obesity, African American race, Hispanic ethnicity, Low socioeconomic status
  • Emotions. Anxiety, Stress, Laughter
  • Exercise
  • Drugs/ Preservatives. Acetaminophen, Aspirin, NSAIDs, Sulfites, Benzalkonium chloride, Nonselective β blockers, higher airway reversibility to β2 agonist
  • Diseases. Chronic Rhinosinusitis, Gastroesophageal Reflux Disease (GERD)
• Early Response (in the pathophysiology of asthma)

  1. Production of IgE as a response to "allergens"

  2. IgE binds to the mast cells in the airway mucosa causing the release of mediators such as histamine, tryptase, leukotrienes C4 and D4, and prostaglandin D2 in the airway mucosa

  3. Diffusion of these mediators induces muscle contraction, mucus secretion, and edema
• Late Response (in the pathophysiology of asthma)

  1. Influx of inflammatory cells modulated by the TH2-related cytokines sustaining inflammation, specifically interleukins 5, 9, and 13

  2. These cytokines recruit eosinophils, B lymphocytes for IgE production, and bronchial epithelial cells causing mucus production
• Bronchial Hyperreactivity


  • Presence of inflammatory mediators in the lungs causes bronchospasm characterized by a worsening and exaggerated airway obstruction
  • Increased histamine from mast cells, increased airway smooth muscle mass, increased vagal tone, and/or increased intracellular free calcium
• Airway Remodeling


  • Non-asthmatic stimuli such as viral infections play a role in the pathophysiology of the disease due to the presence of granular white blood cells (WBC), exudate, and mucus in the bronchiolar trees
  • Conversion of epithelial cells to mesenchymal cells through reduction of cell adhesion and its functional polarity with tight junctions
  • Increase in mesenchymal cells increases the smooth muscle content thus leading to airway remodeling
• Most common signs and symptoms of asthma

  • Wheezing
  • Breathlessness
  • A tight chest
  • Coughing
• Asthma may experience a temporary worsening referred to as an asthma attack. This can occur suddenly or develop gradually over a few days.
• Signs and symptoms of an asthma attack


  • Wheezing, coughing, and chest tightness becoming severe and constant
  • Being too breathless to eat, speak, or sleep
  • Breathing faster
  • A fast heartbeat
  • Drowsiness, confusion, exhaustion, or dizziness
  • Blue lips or fingers
  • Fainting
• Tests that can be done or requested when a patient shows signs of asthma


  • Physical Exam
  • Medical History
  • Spirometry
  • Spirometry with Bronchodilator Tests
  • Bronchoprovocation Tests
  • Peak Expiratory Flow (PEF) Tests
  • Fraction Exhaled Nitric Oxide (FeNNO) Tests
  • Allergy Skin or Blood Tests
• Inhaled Corticosteroids (ICS)


  In the management of persistent asthma, ICS serve as the fundamental therapeutic approach and stand as the most potent anti-inflammatory medications currently available. ICS are generally safe, with low to moderate doses rarely causing clinically significant side effects.
• Allergy skin or blood tests


  Can inform the physician about the specific allergens, such as pet dander or pollen, that trigger a bodily reaction when the patient is exposed to these substances
• Physicians may conduct these tests for individuals with a history of allergies
• Inhaled corticosteroids (ICS)


  Serve as the fundamental therapeutic approach and stand as the most potent anti-inflammatory medications currently available in the management of persistent asthma
• Inhaled corticosteroids (ICS)


  • Efficacy in alleviating symptoms, enhancing quality of life, reducing the frequency of exacerbations, decreasing reliance on bronchodilator rescue therapy, improving lung function, and lowering asthma-related mortality
  • Generally safe, with low to moderate doses rarely causing clinically significant side effects
• Doses of inhaled corticosteroids (ICS)


  Categorized as low, medium, and high, taking into account clinical comparability
• Once a stable symptom control has been achieved for a duration of 3 months, a cautious titration of the ICS dose is recommended
• Goal of ICS dose titration


  Maintain good symptom control, minimize the risk of exacerbations, and mitigate potential side effects by using the minimum effective dose consistently
• Patients requiring a high dose of ICS should be referred to a specialist for thorough assessment and expert guidance
• Aside from symptom management, ICS also offer additional advantages such as modifying airway remodeling and preventing an accelerated decline in lung function

  
• Systemic corticosteroids


  Administering them early in the emergency room (ER) treatment of asthma exacerbations has been proven effective in alleviating symptoms and reducing hospitalization rates

  
• The most significant advantage of systemic corticosteroids in lowering the rate of hospital admission was evident in patients with more severe symptoms who were not on any corticosteroid therapy
• Typical dose of systemic corticosteroids


  Calculated at 1-2 mg/kg/day of prednisone