Research Noon Conference

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Research Noon Conference

• Kate Sowerwine, PGY 3
• September 29, 2008

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Aspirin Sensitivity

• Aspirin is one of the world's most commonly used
  medications and its use benefits many diverse
  conditions. Adverse reactions, however, are
  relatively common as well. Hypersensitivity to
  aspirin can be manifested as acute asthma,
  urticaria and/or angioedema, or a systemic
  anaphylactoid reaction.

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What patients would benefit from aspirin
desensitization?

• Pt that are sensitive to aspirin or NSAIDS (100
  cross-sensitivity also should avoid COX-2
  inhibitors)
• Those who need aspirin for coronary artery
  disease, stents, aspirin-induced asthma/rhinitis,
  chronic sinusitis, or nasal polyps
• Aspirin desensitization has not been proven
  beneficial for aspirin sensitive urticaria

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How does it work?

• The hypersensitivity reaction is mediated through
  aspirin-directed AB or by excessive leukotriene
  (LT) production.
• The desensitization depletes these mediators as
  well as down-regulates LT receptors. This is down
  by gradual dose escalation of aspirin to exhaust
  LT and therefore down regulate receptors. Another
  hypothesis is gradual saturation of AB binding
  sites and therefore depleting inflammatory
  cytokines.

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Current Methods for Aspirin Desensitization

• Uses aspirin oral challenge (nasally sprayed
  aspirin is not FDA approved only available in
  Europe)
• Oral aspirin provocation may induce
  life-threatening asthma and IgE reactions and is
  not suitable for in-office desensitization
• A better method is needed to accurately predict
  patients that will have severe asthma attacks or
  anaphylaxis

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Why use ketorolac challenge?

• Ketorolac eye drops (Acular) can be easily
  sprayed into each nostril
• Ketorolac will therefore be able to initiate
  upper airway hypersensitivity and if present the
  severity will help predict adverse reactions to
  desensitization and subsequently make the
  protocol safer

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Ketorolac Nasal Provocation in Aspirin Sensitivity

• The NSAID ketorolac has been associated with
  severe asthma (Toradol injection) and
  conjunctivitis (Acular). A dose ranging study of
  Acular eye drops applied to the nasal mucosa was
  performed to determine if this was an effective
  drug and route to assess aspirin sensitivity.

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Ketorolac Nasal Provocation in Aspirin Sensitivity

• METHODSAcular was diluted with saline. Doses of
  0, 1, 10, 100 and 500 mcg in 100mcL were sprayed
  into both nostrils of aspirin sensitive (n7) and
  healthy control (n7) subjects. After 5 min,
  nasal lavage (1 ml) was collected for biochemical
  analysis, symptoms were scored, and airway
  function tested.
• RESULTSThe aspirin-sensitive group showed
  significant (plt0.05) dose-dependent increases in
  (i) perceptions of nasal irritation (ii) sore
  throat and (iii) secretion of glandular mucins,
  lysozyme and urea. In contrast, there were no
  changes in albumin secretion (no stimulation of
  vascular permeability), nasal acoustic rhinometry
  (no vasodilation with nasal airflow obstruction)
  or pulmonary function tests. Reactions to
  ketorolac were confirmed by (a) rapid clearance
  of symptoms by sublingual zileuton (Zyflo) and
  (b) oral aspirin challenges.

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Ketorolac Nasal Provocation in Aspirin
Sensitivity

• CONCLUSIONS
• Ketorolac nasal provocation is a safe way to test
  for systemic aspirin sensitivity. These low doses
  (0, 1, 10, 100 and 500 mcg) suggest that
  glandular exocytosis without vascular engorgement
  or exudation may contribute to the
  pathophysiology of NSAID-induced airflow
  obstruction. Starting at higher doses (Wong et
  al. 2005) may provoke systemic reactions in very
  sensitive patients

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Current Study Open for Recruitment

• Ketorolac and Aspirin Desensitization (KAD) IRB
  08-336 subjects are seen and evaluated in G-CRC
  Main Bldg 7th Floor
• Uses higher doses of ketorolac (100mcg, 1mg, 5mg,
  10mg) and is followed by aspirin desensitization
  in all subjects (starts at ASA 5mg to 650mg)
• We expect to see changes in symptoms (nose,
  throat irritation) and secretions as well as
  PFTs, acoustic rhinometry (detects changes in
  nasal patency), and identify more accurately
  patients that will have adverse reactions to
  aspirin desensitization.

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Expected Results

• Ketorolac at higher doses will cause more
  objective differences in the aspirin sensitive
  asthmatic group than control and non aspirin
  sensitive subjects
• Demonstrate that ketorolac is safe to use and
  reactions are easily reversed with rescue
  medications
• Provide a protocol that can be followed for safe
  in-office rapid aspirin desensitization

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• Thank You