xRead - Nasal Obstruction (September 2024) Full Articles

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International consensus statement on rhinosinusitis

X.D.15 Management of CRSwNP: Aspirin Desensitization for AERD ESS today still is the mainstay treatment for NP removal in individuals suffering from AERD. However, in this particular subset of patients, recurrence of inflammatory mucosal changes and ultimately NPs can be seen early on, often within months of surgery, and a high percentage of patients undergo revision surgeries. 1530,1531 Consequently, there is a need for additional treatment options to opti mize postoperative results and to minimize the recurrence rate of NPs after sinus surgery. Several researchers have described aspirin desensitization protocols, the respec tive impact on LT and PG release, and their clinical results. 1668,1669 There is variation in the route of aspirin administration, especially with regard to oral vs intranasal application during the initial desensitization phase. 1670–1672 Where controversy between authors is most prominent is with regard to the best possible maintenance dose, one that is both effective and yet well tolerated. There is agreement between researchers that the best timing to start aspirin desensitization is a few weeks after surgical removal of polyps in an effort to reduce inflammation, mitigate the possibility of polyp relapse, and improve QoL. It is impor tant to perform thorough evaluation of pulmonary func tion, which should not be worse than 75% of the expected FEV1 for the individual. In several publications, including a DBRCT in the early 1980s, Stevenson et al. 1670,1673 were able to demonstrate the efficacy of aspirin desensitization using a daily aspirin maintenance dose of up to 1300 mg. The authors observed a significant reduction in sinus infections, revision surg eries, and INCS use during this high-dose aspirin desen sitization regimen. However, severe aspirin-related side effects including gastric bleeding and gastric pain were observed as well as impaired renal function, nausea and blood-clotting disorders. 1520,1673 These adverse effects led to high dropout rates around 50% after just several months. Unfortunately, aspirin desensitization only offers thera peutic benefit for as long as the daily aspirin is contin ued. Interruption of the maintenance dose for longer than 48 hours might end the refractory state of tolerance and jeopardize the beneficial effect. Therefore, successful long term maintenance therapy with aspirin should be con tinued over years, potentially decades, if benefits are to remain. Data in the literature with regard to long-term aspirin dosage following desensitization have been as variable as the respective LOE. Rozsasi et al. 1674 recommended a maintenance dose of 300 mg daily to reduce NP recurrence and improve sense of smell, whereas several earlier single armed investigations could demonstrate an obvious reduc

tion of NP recurrence, an improvement of the sense of smell, and a reduction of asthma-related complaints with a maintenance aspirin dose of 100 mg daily. 1517,1669 Several cohort studies have been performed with variable main tenance doses ranging from 300 mg daily to 650 mg BID. These studies assess a wide variety of outcomes includ ing nasal symptom scores, smell scores, revision surgery rates, and polyp scores, and all studies note significant improvement in these outcomes regardless of the mainte nance dose utilized. 1675–1680 The optimal protocol to estab lish efficacious and well tolerable desensitization with the lowest possible maintenance dose of oral aspirin is yet to be determined. Lee et al. 1681 recommend an aspirin intake dose of at least 325 mg twice daily for optimal symptom control, but studies have shown that even aspirin doses of 650 mg/d are associated with a considerable risk of gas trointestinal bleeding. 1682,1683 In 2013, the first DBRCT was published, investigat ing aspirin desensitization with an initial challenge dose reaching 800 mg aspirin over 1 day followed by a main tenance dose of just 100 mg daily. This low-dose proto col was noted to be safe, with less than 3% of patients in the treatment group experiencing gastric irritation, all of whom could continue the treatment after adding a PPI. 1684 This study showed that 100 mg as a maintenance dose could significantly reduce the clinical key symptoms of nasal obstruction, discharge and headache ( p = 0.001). QoL was also significantly improved over a three-year fol low up period in the treatment group ( p = 0.03), along with a lower polyp score after 36 months. Conclusions drawn from this first study providing high level evidence for a 100 mg protocol are that low-dose daily aspirin therapy leads to a significant decrease in respiratory inflammation and helps reduce the need for systemic corticosteroids and sur gical revisions in this group of patients. More recently, additional small randomized, DBRCTs have been performed investigating the efficacy of daily aspirin therapy. In a study of 12 patients who underwent desensitization with oral aspirin (ASA) followed by a main tenance dose of 624 mg daily for 6 months compared to 8 patients treated with placebo, patients in the experimen tal group showed improved nasal symptoms and QoL. 1367 Two additional trials of patients randomized to an aspirin maintenance dose of 650 mg BID for 1 month followed by 325 mg BID for 5 months vs placebo also showed improved symptoms and QoL. 1685,1686 Two of these studies showed increased rates of adverse events in the ASA-desensitized group compared to placebo. 1367,1685 In a systematic review, Klimek and coauthors con cluded that based on the currently available clinical and pathophysiological data, aspirin desensitization followed by daily aspirin therapy has been proven to be effica cious, safe and suitable to reduce the need for other