BA

• Asthma


  A chronic inflammatory disorder of the airways involving complex interactions between many cells and inflammatory mediators that result in inflammation, obstruction, increased airway responsiveness, and episodic asthma symptoms

  
• Asthma classification (according to National Heart, Lung, and Blood Institute)

  • Intermittent
  • Mild
  • Moderate
  • Severe
• Asthma symptoms


  • ≤ 2 days/week
  • 3-4x/month
  • ≥ 1x/week but not nightly
  • Often 7x/week
• Short-acting B2-agonist use for symptom control

  • ≤ 2 days/week
  • Daily
  • Several times per day
• Interference with normal activity


  • None
  • Minor limitation
  • Some limitation
  • Extremely limited
• Causes of asthma


  • Allergens (e.g., pollen, house dust mite, animal dander, mold, cockroaches, food)
  • Occupational exposures (e.g., chemical irritants, flour, wood, textile dusts)
  • Viral respiratory tract infections
  • Exercise
  • Emotions (e.g., anxiety, stress, hard laughter, crying)
  • Exposure to irritants (e.g., strong odors, chemicals, fumes)
  • Environmental exposures (e.g., weather changes, cold air, sulfur dioxide, cigarette smoke)
  • Drugs
• Pathology of asthma


  • Hypertrophy of smooth muscle
  • Airways containing plugs consisting of inflammatory cells and their debris, proteins, and mucus
  • Inflammatory cellular infiltrate with vasodilation, denuded airway epithelium, and microvascular leakage

  
• Pathophysiology of asthma


  1. Inflammatory cells (i.e., mast cells, eosinophils, activated T cells, macrophages, and epithelial cells) secrete mediators and influence the airways directly or via neural mechanisms

  2. Airway obstruction is responsible for many of the clinical manifestations of asthma (bronchoconstriction, airway wall edema, airway remodeling, smooth muscle hypertrophy and hyperplasia)

  3. Airway obstruction reduces ventilation to some lung regions

  4. Hyperresponsiveness, an exaggerated response to certain stimuli, is an important feature of asthma and appears to correlate with clinical severity and medication requirements

  5. Airway inflammation is crucial to the development of asthma and contributes to airway hyperresponsiveness, airflow obstruction, respiratory symptoms, and disease chronicity

  6. Alteration in autonomic neural control also contributes to obstruction (elevated parasympathetic tone and reflex bronchoconstriction, increased smooth muscle responsiveness)

  7. Airway remodeling can result from persistent inflammation to chronic asthma

  
• Sequencing of events in asthma

  1. Triggering (IgE)

  2. Early asthmatic response (bronchoconstriction, bronchospasm, asthma symptoms)

  3. Late asthmatic response (persistent airflow obstruction, airway inflammation, bronchial hyperresponsiveness)

  
• Physical findings in chronic, poorly controlled, severe asthma

  • Hyperinflation
  • Barrel chest
  • Decreased diaphragmatic excursion

  
• Physical findings in acute asthma exacerbations

  • Shortness of breath
  • Wheezing
  • Chest tightness
  • Cough
  • Tachypnea and tachycardia (moderate-to-severe exacerbations)
  • Pulsus paradoxus (severe exacerbations)

  
• Between acute asthma exacerbations, the patient may be asymptomatic
• Diagnostic tests for asthma

  • Pulmonary function tests (FEV1, FVC, RV, TLC, PEFR, provocation testing)
  • Sputum analysis (Curschmann's spiral, Charcot-Leyden crystals)
  • Blood analysis
  • Pulse oximetry
  • Arterial blood gas measurements
  • Electrocardiogram
  • Chest x-ray
• Signs of respiratory distress in asthma


  • Use of accessory muscles
  • Dyspnea
  • PEFR <50%
  • Cyanosis
  • Suprasternal retractions
  • Absence of respiratory sounds
  • Increased PaCO2
  • Unable to sleep for extended time
• Treatment objectives for asthma

  • Provide symptomatic control with normalization of lifestyle
  • Return pulmonary function as close to normal as possible

  
• Treatment goals for asthma

  • Prevent chronic and troublesome symptoms
  • Maintain normal pulmonary function
  • Maintain normal activity levels
  • Minimal use of short-acting inhaled B2 agonists
• Nonpharmacological treatments for asthma

  • Humidified oxygen
  • Intravenous fluids
  • Environmental control
  • Vaccines
• Bronchodilators: β-adrenoreceptor agonists


  • Act by stimulating the adenylyl cyclase and increasing cAMP in smooth muscle cells
  • Short-acting (SABA) for acute episodes
  • Long-acting (LABA) for prophylaxis (salmeterol, formoterol)
  • Adverse effects: muscle tremor, tachycardia, tolerance and tachyphylaxis, arrhythmia
• Bronchodilators: Methylxanthines


  • Inhibit PDE4 resulting in increased concentrations of cAMP
  • Bronchodilating effects, increase diaphragm contraction, and some CNS stimulant effects
  • Examples: Theophylline, Aminophylline, Oxtriphylline, Dyphylline
• Bronchodilators: Anticholinergics


  • Competitively block muscarinic receptors in the airways and prevent bronchoconstriction mediated by vagal discharge
  • Examples: Ipratropium, Tiotropium
  • Adverse effects: urinary retention, dry cough, constipation, dry eyes, blurred vision

  
• Anti-inflammatory agents: Mast cell stabilizers


  • Reduce the release of inflammatory mediators from mast cells
  • Examples: Cromolyn, Nedocromil
  • Adverse effects: coughing and irritation of the airways
• Anti-inflammatory agents: Corticosteroids


  • Reduce the synthesis of arachidonic acid by inhibiting phospholipase A2
  • Inhaled steroids are given in most cases of moderate asthma
  • May be given parenterally
  • Examples: Beclomethasone, Budesonide, Dexamethasone, Flunisolide, Fluticasone, Mometasone, Triamcinolone
  • Adverse effects: minimal adrenal suppression, increased susceptibility to candidiasis, growth inhibition, salt retention, muscle wasting
• Leukotriene antagonists: Leukotriene receptor blockers


  • LTD4 and LTE4 receptor antagonists
  • Examples: Zafirlukast, Montelukast
• Leukotriene antagonists: LOX inhibitor


  • Selectively inhibits 5-lipoxygenase
  • Example: Zileuton
  • Adverse effect: occasional elevation of liver enzymes
• Leukotriene antagonists: Anti-IgE antibody

  • Prevents IgE activation and release of inflammatory mediators
  • Example: Omalizumab
• Drug delivery options for asthma

  • MDI
  • Spacers and holding chambers
  • Nebulizers
  • DPI
• Asthma care quick reference guide


  Helps clinicians provide quality care to people who have asthma
• Quality asthma care


  • Involves initial diagnosis and treatment to achieve asthma control
  • Involves long-term, regular follow-up care to maintain control
• Asthma control


  Focuses on reducing impairment (frequency and intensity of symptoms and functional limitations) and reducing risk (likelihood of future asthma attacks, progressive decline in lung function, or medication side effects)
• Achieving and maintaining asthma control

  1. Providing appropriate medication

  2. Addressing environmental factors that cause worsening symptoms

  3. Helping patients learn self-management skills

  4. Monitoring over the long term to assess control and adjust therapy accordingly
• Initial visit


  1. Diagnose asthma

  2. Schedule follow-up appointment

  3. Develop written asthma action plan

  4. Initiate medication & demonstrate use

  5. Assess asthma severity
• Follow-up visits


  1. Assess & monitor asthma control

  2. Schedule next follow-up appointment

  3. Review asthma action plan, revise as needed

  4. Maintain, step up, or step down medication

  5. Review medication technique & adherence; assess side effects; review environmental control
• This guide summarizes recommendations developed by the National Asthma Education and Prevention Program's expert panel after conducting a systematic review of the scientific literature on asthma care
• Asthma diagnosis


  • Determine that symptoms of recurrent airway obstruction are present, based on history and exam
  • Use spirometry to determine that airway obstruction is at least partially reversible in all patients ≥5 years of age
  • Consider other causes of obstruction
• Asthma control goal


  • Reduce impairment (prevent chronic symptoms, require infrequent use of short-acting beta2-agonist, maintain (near) normal lung function and normal activity levels)
  • Reduce risk (prevent exacerbations, minimize need for emergency care and hospitalization, prevent loss of lung function or reduced lung growth, minimize adverse effects of therapy)
• Assessing and monitoring asthma

  1. Assess asthma severity at initial visit to initiate treatment

  2. Assess asthma control at follow-up visits to determine if therapy should be adjusted

  3. Assess at each visit: asthma control, proper medication technique, written asthma action plan, patient adherence, patient concerns

  4. Obtain lung function measures by spirometry at least every 1–2 years; more frequently for asthma that is not well controlled

  5. Determine if therapy should be adjusted: maintain treatment, step up if needed, step down if possible

  6. Schedule follow-up care: every 2–6 weeks while gaining control, every 1–6 months to monitor control, every 3 months if step down in therapy is anticipated
• Coiled, basophilic mucinous fibrils


  • Sometimes found in the sputum and bronchial washings
• Hexagonal bipyramidal structures


  • Localized in the primary granules of the cytoplasm of eosinophils
• Use of medications


  • Select medication and delivery devices that meet patient's needs and circumstances
  • Use stepwise approach to identify appropriate treatment options
  • Inhaled corticosteroids are the most effective long-term control therapy
  • Consider domain of relevance to the patient (risk, impairment, or both), patient's history of response, and willingness and ability to use the medication
  • Review medications, technique, and adherence at each follow-up visit
• Eosinophilic Granulomatosis with Polyangiitis


  An inflammatory disease of small and medium sized blood vessels