AERD Associated Nasal Polyposis: Efficacy of Postoperative Antileukotriene Therapy in Comparison with Aspirin Desensitization. A Retrospective Study.

INTRODUCTION: AERD (aspirin-exacerbated respiratory disease) is a severe form of an inflammatory disease of the upper airway system. Therapy remains challenging due to a complex underlying pathophysiology. OBJECTIVE: To evaluate the efficacy of postoperative antileukotriene therapy concerning recurrence of nasal polyposis in patients with AERD and to compare it with AD (aspirin desensitization) over time. METHODS: In this retrospective study we analyzed AERD patients (N = 61) after functional endoscopic sinus surgery (FESS). Patients were treated at our institution postoperatively with topical mometasone (control group, N = 22), leukotriene-receptor-antagonists (montelukast [MT], N = 18) or underwent an aspirin desensitization (N = 21). Subjective parameters as assessed by SNOT (sinonasal outcome test) questionnaire and endoscopic endonasal examination (polyposis grading) were evaluated throughout a follow-up period of 6-9 and >12 (long-term) months after surgery. RESULTS: Endoscopic endonasal examinations 6-9 months after sinus surgery showed a good disease control in all 3 groups with significant reduction in polyp grading in the AD group. After a follow-up period of more than 12 months, MT and AD patients had significantly less polyp recurrences as compared to the topical treatment group. Subjective sinonasal symptoms revealed that hyposmia and nasal obstruction were prominent factors in all 3 groups throughout the follow-up period. MT group showed significant improvement in sinonasal symptoms over time. CONCLUSION: Postoperative treatment with leukotriene-receptor-antagonists and aspirin desensitization both significantly reduce nasal polyp recurrence. MT has a positive effect on subjective sinonasal outcomes and patients' quality of life over time.

NSAID-ERD Syndrome: the New Hope from Prevention, Early Diagnosis, and New Therapeutic Targets.

PURPOSE OF REVIEW: This review summarizes the latest information on the appropriate identification, evaluation, and treatment of patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD), also known as aspirin-exacerbated respiratory disease (AERD). Within the framework of our understanding of the underlying pathophysiology of NSAID-ERD, we also provide an update regarding new surgical techniques and newly available or upcoming medical therapies that may benefit these patients. RECENT FINDINGS: There have been considerable developments regarding recommendations for both the extent and timing of sinus surgery for NSAID-ERD. The last few years have also given us several new biologic medications that warrant consideration in the treatment of patients with recalcitrant NSAID-ERD. Further clinical trials are underway to investigate additional medications that may decrease the type 2 inflammation that dominates this disease. Despite the severe lower respiratory inflammation and recurrent nature of the nasal polyps in patients with NSAID-ERD, significant recent advances now afford much-improved quality of life for these patients. Careful collaboration between Allergy/Immunology and Rhinology specialists is imperative to ensure proper treatment of patients with NSAID-ERD.

Endoscopic sinus surgery improves aspirin treatment response in aspirin-exacerbated respiratory disease patients.

BACKGROUND: Aspirin desensitization and treatment benefits most patients with aspirin-exacerbated respiratory disease (AERD), although some patients fail therapy. Our objective was to assess whether recent endoscopic sinus surgery (ESS) improved aspirin treatment outcomes in AERD patients who initially failed aspirin therapy. METHODS: Outcomes of aspirin desensitization and treatment in AERD patients prospectively enrolled were assessed preoperatively and at 4, 12, and 24 weeks after ESS by determining changes in Asthma Control Test (ACT) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and respiratory function. Biomarkers, including fractional excretion of nitric oxide (FeNO), spirometry, nasal inspiratory peak flow (NPF), immunoglobulin E (IgE), and eosinophil count, were measured. RESULTS: Nineteen patients who benefited (responders) and 21 patients who failed (nonresponders) preoperative aspirin treatment with a distant history of ESS (mean, 48 months) were identified. Nonresponders were more likely to be African American (71%, p < 0.01) and have higher baseline IgE levels (252 kU/L vs 87 kU/L in responders, p < 0.01). 24 of the 40 patients (nine responders and 15 non-responders) required subsequent ESS and underwent another aspirin desensitization 3-4 weeks after ESS. All 24 patients tolerated a second round of aspirin desensitization and treatment. The primary aspirin therapy was associated with a significant increase in IgE in nonresponders, but there was no significant increase in IgE after the second aspirin desensitization and treatment. CONCLUSION: Antecedent ESS enhances aspirin treatment responses in AERD patients and may convert patients who failed aspirin treatment before surgery to a more responsive phenotype after ESS. Patients with higher baseline serum IgE levels may benefit from ESS performed shortly before aspirin desensitization and therapy.

Central compartment involvement in aspirin-exacerbated respiratory disease: the role of allergy and previous sinus surgery.

BACKGROUND: Evidence for a relationship between allergy and chronic rhinosinusitus with nasal polyps (CRSwNP) is equivocal. Central compartment (CC) atopic disease is a nasal inflammatory condition related to inhalant allergy. CC involvement is common in aspirin-exacerbated respiratory disease (AERD), a subset of CRSwNP, and we hypothesize it is related to allergic status. METHODS: This study was a retrospective analysis of a single-institution database for the January 2016 to February 2019 time period. Data regarding endoscopic CC findings, clinical allergy history, and results of allergy testing were collected. Statistical analysis was performed, with significance set at p < 0.05. RESULTS: Seventy-two AERD patients met the inclusion criteria. Fifty-nine patients had CC involvement (53 bilateral, 6 unilateral). For patients with documented allergy status, 100% of patients with endoscopic CC disease had clinical allergic rhinitis (AR), and 45 of 48 (93.8%) had positive allergy testing. Thirteen patients had no CC involvement (4 with clinical AR; 3 of 7 with positive allergy testing). CC endoscopic findings in AERD were significantly associated with clinical allergy (p < 0.0001, phi = 0.771). Overall, patients with CC involvement averaged 3.8 surgeries vs 3.2 for those without CC involvement (p = not statistically significant). However, patients with septal involvement averaged 4.2 surgeries vs 2.0 for those without septal involvement (p = 0.004). As the number of sinus surgeries increases, middle turbinate (MT) resection (r = 0.300, p = 0.022) and septal involvement (r = 0.372, p = 0.004) significantly increase. All patients with MT resection had septal disease, whereas none without CC disease had MT resection. CONCLUSION: Most AERD patients exhibit AR, and this correlates with CC disease. As the number of surgeries increases, MT resection may predispose to polyposis of the septum.

The Effect of Antileukotrienes on the Results of Postoperative Treatment of Paranasal Sinuses in Patients with Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease.

BACKGROUND: Based on endoscopic examination, chronic rhinosinusitis (CRS) is divided into chronic inflammation with (CRSwNP) or without nasal polyps (CRSsNP). On the basis of the pathomechanism of inflammation, CRS is divided into endotypes. Eosinophilic CRSwNP with coexisting bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) is a real therapeutic challenge. AIM: Comparative analysis of the results of treatment of patients with CRSwNP, bronchial asthma, or hypersensitivity to NSAIDs (NSAID-exacerbated respiratory disease, NERD), using antileukotrienes (leukotriene receptor antagonists, LTRAs) or intranasal glucocorticoids or both drugs together after endoscopic sinus surgery (ESS). MATERIAL AND METHODS: 33 patients (11 male, 33%) with NERD divided into three groups treated with LTRAs or intranasal glucocorticoids or both drugs together were assessed in terms of general well-being, state of pathological changes, and olfactory disorders using the following tools: Sino-Nasal Outcome Test, Visual Analogue Scale, Brief Identification Smell Test, and Lund-Kennedy score before and at 12 months after surgery. CT assessments were made prior to surgery using the Lund-MacKay scale. RESULTS: Comparable efficacy of treatment with nasal steroids and antileukotrienes was found after 12 months of observation of patients. CONCLUSIONS: The results suggest comparable efficacy of treatment with nasal steroids and antileukotrienes in patients with NERD after ESS. Treatment with montelukast and mometasone has not been shown to be superior to both drugs administered separately.

Draf IIB with superior septectomy: finding the "middle ground".

BACKGROUND: Previous studies have demonstrated a high failure rate of endoscopic sinus surgery (ESS) with Draf IIa in patients with diffuse polyposis, asthma, and aspirin-exacerbated respiratory disease. A high percentage of these patients progress to endoscopic modified Lothrop procedure (EMLP). We describe a modification of the Draf IIb with a superior septectomy (IIb+SS), which may provide similar therapeutic benefit as demonstrated by the distribution of sinus irrigations in the sinus cavity with ESS with IIb+SS vs ESS with EMLP. METHODS: ESS with IIb+SS was performed on 6 cadaver heads. Fluorescein-dyed irrigations were performed on each head and penetration was recorded using video endoscopy. EMLP was subsequently performed on each head with repeat dye-irrigation and video endoscopy. The videos were reviewed by 4 blinded fellowship-trained rhinologists, and irrigant penetration of the maxillary, ethmoid, frontal, sphenoid sinuses, and olfactory cleft was graded 0 to 3 (3 implying complete staining). RESULTS: The mean scores when comparing IIb+SS to EMLP were as follows: overall 1.99 vs 1.97 (p = 0.816), maxillary sinus 2.67 vs 2.38 (p = 0.128), ethmoid sinus 1.88 vs 1.98 (p = 0.536), sphenoid sinus 2.58 vs 2.50 (p = 0.467), frontal sinus 1.13 vs 1.38 (p = 0.073), and olfactory cleft 1.71 vs 1.63 (p = 0.529). There was no significant difference between subsites. Interrater reliability was good (Cronbach's alpha = 0.781). CONCLUSION: Performing ESS with IIb+SS provides similar irrigation delivery benefits to ESS with EMLP, without the need for altering natural sinus outflow and creating circumferential scarring. Further studies evaluating its use in patients that are high risk for revision surgery are needed.

Outcomes of modified endoscopic Lothrop in aspirin-exacerbated respiratory disease with nasal polyposis.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) and chronic rhinosinusitis with nasal polyps (CRSwNP) are often reported to be recalcitrant to standard medical and surgical intervention. Failure rates of standard endoscopic sinus surgery in these patients are reported to be as high as 90%. We review the outcomes for our cohort of AERD patients undergoing endoscopic sinus surgery and endoscopic modified Lothrop procedure (EMLP). METHODS: Data was collected prospectively between January 2001 and December 2013. Information including demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay scores, and endoscopic ostium assessment were collected for up to 5 years. Minimum follow-up was 6 months. RESULTS: A total of 31 AERD patients underwent complete sphenoethmoidectomy, maxillary antrostomy and EMLP during the study period with an average follow-up of 36 months. Polyp recurrence was seen in a total of 18 patients (58%). Seven patients required revision EMLP following initial surgery demonstrating a failure rate of 22.5%. AERD patients had a statistically significant increased risk of both nasal polyps recurrence and need for revision surgery. Revision EMLP was needed due to recurrence of nasal polyps in 6 cases and frontal ostium stenosis in a single case. Time to revision EMLP was similar between the groups. CONCLUSION: Complete sphenoethmoidectomy, maxillary antrostomy, and EMLP is successful in a significant majority of patients with AERD and CRSwNP. It is well tolerated with a low complication rate and facilitates successful ongoing medical management of the condition in patients with AERD.

State of the art: a systematic review of the surgical management of aspirin exacerbated respiratory disease.

BACKGROUND: Endoscopic sinus surgery is an important modality to the armamentarium of the otolaryngologist managing chronic rhinosinusitis (CRS). Within the spectrum of CRS, there exists a subset of patients who are recalcitrant to conventional treatment strategies, including those with aspirin-exacerbated respiratory disease (AERD). Although surgery is frequently undertaken in this group, there has been no general consensus on the efficacy or optimal extent of surgery. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of published studies was conducted. Inclusion criteria included original publications of adult patients with AERD undergoing surgery, cohorts of greater than five subjects, a minimum follow-up of 3 months, and measurable clinical outcomes. An electronic search was performed using OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. RESULTS: Sixteen studies met the criteria for analysis. For our primary objective, sinus surgery appeared to improve patient-reported quality of life (QoL) and symptom profile in AERD. Overall, most studies reported a decrease in radiographic grading, endoscopy scores, and asthma severity. Compared with aspirin-tolerant asthmatic patients, AERD patients may have worse objective measures of disease severity both pre- and postoperatively; however, patient-reported QoL and symptom improvement may be similar after sinus surgery. Finally, this review showed that patients with AERD required revision surgeries sooner and more frequently compared with other subtypes of CRS. We also discussed the role of maximal surgical techniques and additional benefit of postoperative adjunctive therapies in the management of this disease entity. CONCLUSION: The state of the art in the management of AERD patients suggests that surgery does play an important role in helping establish symptomatic control. In the future, more rigorous studies evaluating the comprehensiveness of surgery and postoperative adjuncts are required to understand their impact on long-term patient outcomes.