3/23/2015. What is Aspirin-Exacerbated Respiratory Disease (AERD)? Aspirin-Exacerbated Respiratory Disease in Spol<ane - An Update

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1 Aspirin-Exacerbated Respiratory Disease in Spol<ane - An Update Steven Kernerman, DO Spokane Allergy and Asthnna Clinic Friday, May 1, 2015 Clinical tetrad of nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma and sensitivity to any medication that inhibits cyclooxygenase-1 (COX-1) enzymes Ingestion of aspirin, and most NSAIDs, results in a spectrum of upper and/or lower respiratory reactions including rhinitis, conjunctivitis, laryngospasm and bronchospasm Disclosures Speakers Bureau: TEVA No other relevant disclosures AERD affects % of the general population, however Prevalence rises to % of patients with asthma. Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% and 8.7%, respectively and. Can occur in up to 30-40% of asthmatic patients with nasal polyps Objectives: upon completion of this activity participants should be able to: Understand recognition of, and treatment options for, aspirin-exacerbated respiratory disease Learn outcomes of treatment with aspirin desensitization for aspirin-exacerbated respiratory disease Average age of onset is 34 years old (US No ethnic predilection Rare familial associations study) More commonly reported In females (57% vs. 43%) 1

2 Tolerance of ASA/NSAIDs in AERD How is AERD Diagnosed? COX-1 > COX-2 (not tolerated): Acetylsalicyltc acid Piroxicam Indomethacin Sulindac Tolmetin ibuprofen Naproxen Fenoprofen Oxaprozin Mefanamicacid Fiubiprofen Difluinisal Ketoprofen Diclofenac Ketorolac Etodolac Nabumetone COX-2 > COX-1 (better tolerated): Acetaminophen Salsalate Nimesulide Meioxicam Selective COX-2 inhibitor (tolerated*): Celecoxib Gold standard is aspirin challenge History of an asthma exacerbation following ingestion of aspirin or other NSAIDs is suggestive and sometimes diagnostic What are the Clinical Features of AERD? Also described as, Samter's triad, aspirin induced asthma, aspirin sensitive asthma aspirin hypersensitivity and First described in 1922 by Widel, Abrami and Lermeyez (referred to as Idiosyncratic Anaphylaxis) How is AERD Diagnosed? Currently being investigated: Serum periostin levels are significantly elevated in AERD patients and associated with AERD phenotype and disease severity What are the Clinical Features of AERD? Severe persistent asthma Complete anosmia Pansinusitis on imaging Nasal polyposis refractory to sinus surgery (multiple surgeries) Age of onset in fourth decade Incomplete response to antibiotics or corticosteroids Respiratory reaction to any NSAID or aspirin Avoidance or Desensitization? Complete avoidance of COX-1 inhibiting drugs; or aspirin desensitization then continuous aspirin therapy Unfortunately, even with avoidance of aspirin and NSAIDs (including following a salicylate free diet), AERD patients usually experience progressive airways disease, This is despite aggressive surgical interventions and topical and/or systemic anti-inflammatory treatment with corticosteroids and leukotriene modifiers 2

3 Why Recommend Aspirin Desensitization and Therapy? Multiple studies have now shown that desensitization and daily aspirin treatment can: Significantly improve overall symptoms and quality of life Decrease formation of nasal polyps and sinus infections Reduce need for oral corticosteroids and sinus surgery Improve nasal and asthma scores in patients with AERD at both 6 months and after one year of therapy (p<0.0001) Is Aspirin Desensitization Cost Effective? shaker et al found desensitization to be costeffective, even when factoring in the up front cost of the aspirin desensitization procedure Substantial reduction of medical and surgical costs in the years following aspirin desensitization and daily aspirin treatment Why Recommend Aspirin Desensitization and Therapy? In a study from an ENT clinic (McMains, Kountakis; 2006) comparing outcomes of AERD patients who had surgery with aspirin desensitization vs. surgery alone: None of the aspirin desensitized patients needed revision of their surgeries, 80% of the patients who did not undergo desensitization required additional surgery over a 2-year period (p=0.003) Who Should be Desensitized? Most AERD patients will benefit clinically from desensitization; More so in those with suboptimal medical control, multiple prior FESS, and intractable sinus disease Desensitization also indicated if AERD patient requires aspirin or NSAIDs for cardiovascular disease, arthritis How Soon Can One Expect Clinical Improvement? Significant clinical improvement is seen in as few as 4 weeks after treatment for: Nasal scores, sense of smell, and asthma scores improving significantly (P>0.0001); Prednisone doses decrease from average of 10.7 mg to 5.9 mg daily (P=0.0003) Optimizing Safety Prior to Desensitization stable asthma (FEV1>60%, >1.5 L, and within 10% of best prior value) Pretreatment Regime (continue all prior upper/lower airways medications and make sure taking double-controller anti-asthma medication and leukotriene modifier drug; oral corticosteroids, if necessary) No antihistamines/decongestants within 48 hours of procedure and no short acting inhaled bronchodilators on the day of desensitization 3

4 Inpatient or Outpatient Oral Aspirin Desensitization? Vast majority are completed in the outpatient setting Historical reaction severity has not been shown to be predictive of the degree of bronchospasm during aspirin challenge Inpatient desensitization encouraged for patients receiving beta-blockers, recent Ml or severe or uncontrolled asthma Majority (30/55) receiving 650 mg bid of entericcoated aspirin Lowest dosing 325 mg once daily Naso-ocular provocations in 58 of 62 patients (94%) Lower airway reactions (bronchial/laryngeal) in 25 of 62 (40%) Gastrointestinal 5/62 (8%), Cutaneous 4/62 (6%) One patient experienced a systemic reaction Contraindications to Desensitization Pregnancy Unstable asthma Gastric ulcers Bleeding disorders Many patients have required elective surgeries after desensitization (20 patients, 26 procedures). With known refractory period of about 48 to 72 hours, all but 2 able to taper/suspend/restart ASA without complication around surgery Five patients re-desensitized One patient suspended ASA when entering 3'^*^ trimester of pregnancy (not yet re-desensitized) Experience with Aspirin Desensitization Sixty-two patients since October 2004 Average age 47.8 years at time of desensitization (range years old); 36 of 52 female (58%) First 10 patients had 1^' day of desensitization done in inpatient setting All 62 completed the three day desensitization procedure 55 of the 62 still known to be receiving daily dosing of aspirin (4 lost to follow-up and 3 stopped) Of the 3 that stopped ASA desensitization, 1 due to recurring hives, 2 with Gl symptoms Spokane experience mirrors national experience with ASA desensitization with, Higher retention rate noted here Less patients lost to follow up 4

5 AERD is generally Summary under-recognized ASA desensitization is the treatment of choice for AERD ASA desensitization has been shown to be cost and clinically effective The experience with ASA desensitization at Spokane Allergy and Asthma Clinic is comparable to that reported in the literature 5