L3 Asthma

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Author:
jknell
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198462
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L3 Asthma
Updated:
2013-02-06 18:02:13
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Pulm II
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Pulm II
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  1. Asthma: Epidemiology
    • -1/13 Americans (7.7%)
    • -prevalence has doubled in the last 20 years
    • -50% concordance in monozygotic twins
    • -4000+ deaths annually
    • -huge healthcare costs and ED visits
  2. Asthma Definitions
    Reversible cough, wheeze, dyspnea, chest tightness

    Reversible airflow obstruction and non-specific bronchial hyper-reactivity

    Eosinophilic inflammation

    Airway Remodeling
  3. Asthma: Etiology
    • 1. Genetics:
    • -many genes involved in risk and modulation

    • 2. Environment
    • -exposures (irritants, allergens, endotoxin)

    3. Epigenetics

    4. Immune Responses (atopy)

    5. Viral Infection

    6. NSAID hypersensitivity
  4. Hygiene Hypothesis
    -asthma and other autoimmune diseases have been increasing steadily since the 1960s

    -this correlates with a decrease in infection

    • Evidence to support:
    • -lower incidence of asthma in children with TB or BCG vaccine
    • -lower incidence of asthma in children with older siblings (parents less neurotic)
    • -lower incidence of asthma in children raised on farms
  5. Asthma: Pathology
    -epithelial damage and fragility

    -mucus gland hypertrophy

    -mucus cell hyperplasia

    • -smooth muscle hypertrophy

    -sub-basement collagen deposition

    • -cellular infiltration (eosinophils, T cells)

    • -hyperplasia of resident mast cells
    • Disrupted architecture
  6. Asthma: Airway Remodeling
    • -occurs very early
    • -poorly if at all reversible
    • -may be the cause of decline in lung function see in asthmatics
    • *** decline in lung function in chronic asthma may approach that seen in smoking-related COPD!
  7. Asthma: Dual Phase Response
    • Early Phase:
    • -immediate fall in airway function
    • -spontaneously recovers (5-15m)
    • -can be blocked by antihistamines and beta blockers

    • Late Phase:
    • -infiltration of airways by eosinophils and other inflammatory cells
    • -can only be treated by corticosteroids
  8. Asthma: Pathophysiology
    • 1. Airway obstruction and air trapping
    • 2. Impaired gas exchange
    • 3. Sputum production
    • 4. Cellular infiltration into tissues (eosinophils early, neutrophils in exacerbation)
    • 5. Atopy (allergen responsiveness)
    • 6. Non-specific airway hyper-reactivity
    • 7. Loss of lung function: reversible and permanent
  9. Asthma: Biochemical Mediators
    • 1. Vasoactive and Bronchoconstrictive Mediators (mast cells, eosinophils)
    • -histamine
    • -leukotrienes

    • 2. Cytokines and Chemokines (Mast cells, T cells)
    • -IL4, 5, 9, 13
    • -TNFa

    • 3. Eosinophil Mediators
    • -Luekotrienes
    • -PAF
    • -MBP (what makes up the pink crystals in eosinophil granules, can crystallize in epithelial cells and cause damage)
  10. Asthma: Clinical Manifestations
    • -dyspnea
    • -cough
    • -wheeze
    • -associate upper airway symptoms and signs
    • -multiple phenotypes
    •      -in elderly
    •      -allergic asthma
    •      -viral induced
    •      -exercise induced
    •      -pediatric
    • -loss of airway function over time
  11. Asthma: Diagnosis
    • Clinical:
    • 1. History (reversible sx)
    • 2. Triggers of episodes (viral, allergen, exercise, cold, NSAIDs)
    • 3. Exacerbating factors (smoking, irritants, occupational exposures)

    • Labs:
    • 1. PFTs (usually with agent to reverse asthma)
    • 2. Airway challenge test (methycholine, allergen etc)
    • 3. Exhaled breath NO2, pH
    • 4. Induced sputum (eosinophils, neutrophils) --> rule out infection
  12. Sputum Cellularity in Asthma
    • Persistent Eosinophils > 2%
    • -steroid sensitive

    • Persistent Neutrophils > 65%
    • -older, more likely to be female, non-atopic
    • -poorly responsive to steroids

    • Non abnormal cell concentrations
    • -half of patients
  13. Asthma: Ddx
    • Wheeze/Dyspnea
    • -foreign body
    • -bronchial tumor
    • -PE
    • -pneumothorax
    • -vocal card dysfxn
    • -CHF

    • Cough
    • -infection
    • -irritants
    • -post-nasal drip
    • -GI reflux
  14. Asthma: Treatment Options
    • 1. Bronchodilators
    •      -beta2 agonists (short/long acting)
    •      -methylxanthines
    •      -anticholinergics (short/long acting)

    • 2. Anti-inflammatories
    •      -inhaled GCs
    •      -cromones
    •      -anti-LT agents

    3. Anti-IgE monoclonal Abs
  15. Asthma: Classifying Severity
    • -sx
    • -night time awakening
    • -rescue inhaler use
    • -interference with normal activity
    • -lung fxn
  16. Beta-2 Agonists
    • SABA
    • -increased mortality and poor control with long term use (esp in Arg/Arg16 phenotype)
    • -best used as rescue inhaler

    • LABA
    • -onset in 30 min, last all day
    • -should not be used alone
    • -should be used with ICS
  17. Corticosteroids
    • Oral Agents
    • -effective
    • -poor side effect profile

    • Inhaled Agents
    • -effective
    • -flat dose response once effective dose reached
    • -increased risk of cataracts and glaucoma
    • -mild, transient growth retardation in children
    • -oral thrush

    **more effective to add another agent than to double the dose of ICS
  18. Leukotriene Receptor Antagonists
    • -effective and relatively safe
    • -use in eosinophilic disease
    • -more effective than steroids in asthmatics who smoke
    • -associated with Churg-Strauss eosinophilic vasculitis
    • -effective in NSAID exacerbated asthma
    • -not as effective as LABA, LAMA or theophylline when added to ICS
    • -only blocks LTD4 receptor
  19. Theophylline
    • -related to caffeine
    • -narrow therapeutic window

    • Adverse Effects:
    • -nausea
    • -HA
    • -seizure
    • -death
    • --> blood level monitoring

    • MOA:
    • -thought to block adenosine Rs (instead of inhibiting phosphodiesterase inhibition)
    • -may be especially effective in patients who smoke
  20. Anti-Muscarinics
    • SAMA
    • -as effective as beta2 agonists acutely
    • -well tolerated

    • LAMA
    • -not yet approved for use in asthma
    • -has effective as LABA when added to ICS
  21. Omalizumab
    • -anti-IgE monoclonal antibody
    • -shown to be effective
  22. Mepolizumab
    • -anti-IL5
    • -decreases production and survival of eosinophils
  23. Etanercept
    -anti-TNF
  24. Asthma Management:
    • 1. Avoid triggers
    • 2. Smoking cessation
    • 3. Treatment based on severity
    •      -ICS (for all but trivial)
    •      -LABA only with ICS
    •      -SABA as rescue agents

    Adherence is a big issue

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