[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

Medical ID use by international patients with Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Patients widely use medical identification (ID) to indicate their food and drug allergies, and chronic medical conditions. One chronic condition for which patients are recommended to use a form of medical ID is Aspirin-Exacerbated Respiratory Disease (AERD), a disease characterized by the presence of asthma, chronic rhinosinusitis with nasal polyps and sensitivity to aspirin and other COX-1 inhibitors, including nonsteroidal anti-inflammatory drugs (NSAIDs). The uptake of medical ID use in AERD is unknown and has not been widely studied in this population. METHODS: We conducted a cross-sectional survey study to measure the perception of the need to use a medical ID and its use by patients with AERD internationally. RESULTS: 245 members of an online AERD support group completed an online survey. The majority (80%, n = 198) of the participants did not use any form of medical ID. The participants reported that the lack of knowledge and awareness about the importance of using a medical ID was the most common reason for not using it. CONCLUSION: This international survey found that the majority of the AERD patient respondents did not use a medical ID. The most common reasons for nonuse were not knowing that it is recommended for their condition and that the patients did not consider it necessary. The results highlight the need for further patient and health care provider education.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-ß1 and IL-8.

Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor ß1 (TGF-ß1). Methods A total of 74 subjects were divided in the following groups: control group ( n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group ( n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group ( n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-ß1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-ß1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-ß1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Meta-analysis Exploring Sinopulmonary Outcomes of Aspirin Desensitization in Aspirin-Exacerbated Respiratory Disease.

OBJECTIVE: The objective of this study is to explore the sinopulmonary outcomes of aspirin desensitization through a systematic review and meta-analysis. DATA SOURCES: Embase and OVID Medline databases. REVIEW METHODS: A systematic review of published articles on outcomes following aspirin desensitization in any language for relevant articles was performed in February 2019. Outcomes included sinonasal quality-of-life assessment, sense-of-smell scores, FEV-1 (forced expiratory volume in 1 second), and medication/steroid use. RESULTS: Thirteen studies met the inclusion criteria out of 6055 articles screened. Aspirin desensitization resulted in significant improvement in FEV-1 and reduction in asthma medication/steroid use (P < .05). There was no significant improvement in the sinonasal quality of life of patients who underwent aspirin desensitization (P = .098). CONCLUSION: Aspirin desensitization appears to be effective in improving pulmonary outcomes and should be considered in the treatment of patients with aspirin-exacerbated respiratory disease. However, good-quality studies are still needed to determine the ideal protocol tailored to individual patients.

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.

Serum level of stem cell factor and its soluble receptor in aspirin-exacerbated respiratory disease.

Aim: Stem cell factor (SCF) may be associated with inflammatory processes leading to aspirin-induced asthma. This study evaluated the relationship between serum level of SCF and its soluble receptor with aspirin-induced asthma. Methods & materials: Twenty-five patients and 25 healthy controls were enrolled in this study. The concentration of SCF and mast/stem cell growth factor receptor (C-kit) was determined in serum samples. Spirometry and rhinometry were performed to determine the severity of the disease. p < 0.05 were considered significant. Results: The serum levels of SCF and C-kit receptor were significantly higher in the case group. The serum SCF and C-kit level had a significant positive correlation with the severity of asthma, disease duration and nasal obstruction. Conclusion: Our findings suggest that SCF and C-kit receptors have a direct effect on the severity of aspirin-induced asthma.

Benefits and harms of aspirin desensitization for aspirin-exacerbated respiratory disease: a systematic review and meta-analysis.

BACKGROUND: Aspirin desensitization is increasingly recommended for the treatment of aspirin-exacerbated respiratory disease (AERD). The objective of this study is to systematically review the efficacy and safety of aspirin desensitization in patients with AERD. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to January 5, 2019. We included randomized trials and comparative observational studies in any language. Data extraction and risk of bias assessment were performed in duplicate independently. RESULTS: Five randomized controlled trials (RCTs) enrolled 233 patients with AERD. Compared to placebo, aspirin desensitization (mean daily dose 800 mg) improved quality of life (risk ratio [RR] 2.00; 95% confidence interval [CI], 1.31 to 3.06; heterogeneity measure [I2 ] = 0%; risk difference [RD] +24%; 22-item Sino-Nasal Outcome Test [SNOT-22] scale [0 to 110, higher worse]; mean difference [MD] -10.27 [95% CI, -6.39 to -14.15]; moderate-certainty); and respiratory symptoms (RR 2.20 [95% CI, 1.55 to 2.73], I2 = 34%, RD +36%; American Academy of Otolaryngology (AAO) scale [0 to 20, higher worse]; MD -2.56 [95% CI,-1.12 to -3.92]; high-certainty). Aspirin desensitization increased adverse events severe enough to cause treatment discontinuation (major bleeding, gastritis, asthma exacerbation, or rash causing drug discontinuation, RR 4.39 [95% CI, 1.43 to 13.50], I2 = 0%, RD +11%, moderate-certainty), and gastritis (RR 3.84 [95% CI, 1.12 to 13.19], I2 = 0%, RD +9%, low-certainty). Findings were robust to sensitivity analyses. Two available observational studies were not informative because they lacked adjustment for confounders and/or contemporaneous controls. CONCLUSION: In patients with AERD, moderate-certainty and high-certainty evidence shows that aspirin desensitization meaningfully reduces symptoms of rhinosinusitis and improves quality of life, but results in a significant increase in adverse events.

Mepolizumabe na doença respiratória exacerbada por aspirina - DREA / Mepolizumab in aspirin-exacerbated respiratory disease - AERD

Relato de caso que ilustra a eficácia e a segurança do uso do mepolizumabe na doença respiratória exacerbada por aspirina (DREA). A utilização de anticorpo monoclonal no tratamento desta doença respiratória de difícil tratamento tem possibilitado o controle da inflamação crônica e o maior conhecimento sobre a fisiopatogenia da doença.

This case report shows the efficacy and safety of mepolizumab in aspirin-exacerbated respiratory disease (AERD). The use of monoclonal antibodies in the treatment of this severe disease has provided improved control of chronic inflammation and greater understanding about the pathophysiology of the disease.

Endocannabinoid receptor CB2R is significantly expressed in aspirin-exacerbated respiratory disease: a pilot study.

BACKGROUND: The endocannabinoid system represents a highly conserved, innate signaling network with direct and indirect control of eicosanoid-mediated inflammation. Activation of the type 2 cannabinoid receptor (CB2R) leads to decreased type 2 inflammation and reduced production of arachidonic acid (AA). Given that altered AA metabolism is associated with aspirin-exacerbated respiratory disease (AERD), we hypothesized that expression of the CB2R gene CNR2 is increased in AERD. METHODS: Nasal polyps from consecutive patients undergoing endoscopic sinus surgery for AERD or allergic fungal rhinosinusitis (AFRS) were prospectively evaluated. Control sphenoid mucosa was collected from patients undergoing endoscopic skull base procedures. Expression and localization of endocannabinoid receptors were evaluated by quantitative reverse transcript-polymerase chain reaction (qRT-PCR) and immunohistochemistry. A 2-group unpaired t test with unequal variances was used to evaluate group differences. RESULTS: Thirteen subjects were included in this pilot study, including 5 controls, 5 AFRS patients, and 3 AERD patients. Upregulated expression of CNR2 was detected in subjects with AERD vs both AFRS (p = 0.049) and controls (p = 0.047), with a mean increase of 5.2-fold. No significant differences in expression of the CB1R gene CNR1 were detected between control and AFRS groups. Immunohistochemistry predominantly localized CB1R and CB2R expression to the surface epithelium in all subjects. CONCLUSION: The endocannabinoid system is an emerging immunomodulatory network that may be involved in AERD. This is the first study of CB2R in sinonasal disease, showing significantly increased transcription in nasal polyps from subjects with AERD. Additional study is warranted to further evaluate the contribution and therapeutic potential of this novel finding in chronic rhinosinusitis.

Avaliação do fenótipo atópico nos pacientes com DREA / Evaluation of atopic phenotype in patients with DREA

Introdução: A doença respiratória exacerbada por anti-inflamatórios (DREA) é uma síndrome bem caracterizada, composta por asma, polipose nasal e intolerância a aspirina e anti-inflamatórios não esteroidais (AINEs). Apesar de já bem definida, há uma heterogeneidade entre a população de pacientes com diagnóstico de DREA. O objetivo desse trabalho foi avaliar o fenótipo atópico nos pacientes com DREA. Métodos: Foi realizado um estudo retrospectivo com pacientes com DREA acompanhados em um serviço terciário. Esses pacientes foram classificados em dois grupos: atópicos e não atópicos. Foram avaliados também dados como gravidade da asma, AINEs envolvidos na reação, e IgE sérica total. Resultados: Foram analisados 70 pacientes, destes 55 (78,6%) eram mulheres. A média de idade era de 54 anos. Do total de pacientes, 32 (45,7%) eram atópicos. Os pacientes atópicos apresentavam média de início de asma mais precoce (22 anos) e maior tempo de doença (31 anos) do que os não atópicos. A média de IgE sérica total era maior nos atópicos (742,1 UI/mL). No grupo dos pacientes com DREA e atopia, a pesquisa de IgE sérica específica mostrou-se positiva para os ácaros em 90,6% dos pacientes. A maioria dos pacientes atópicos (71%) relatava reação a múltiplos AINEs. Os principais medicamentos relacionados às exacerbações respiratórias nos pacientes com DREA foram: AAS em 72,1% dos casos; dipirona em 61,8%; diclofenaco em 45,6%; e cetoprofeno e ibuprofeno em 27,9% dos casos cada um. Conclusões: Existem diferenças entre os pacientes com DREA conforme a presença ou não de atopia. Os atópicos apresentam início de sintomas mais precoce, maior tempo de duração de asma, necessitam de mais medicação para controle e apresentam hipersensibilidade a um número maior de AINEs, sendo que o principal medicamento causador de sintomas também varia entre os dois grupos.

Introduction: Aspirin-exacerbated respiratory disease (AERD) is a well characterized syndrome in which asthma, nasal polyposis, and intolerance to aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) coexist. Even though it is well defined, the population of patients diagnosed with AERD is very heterogeneous. The aim of this study was to evaluate atopic phenotype in patients with AERD. Methods: A retrospective study was performed with patients with AERD followed at a tertiary hospital. These patients were classified into two groups: atopic and non-atopic. Clinical characteristics and data such as asthma severity, NSAIDs involved in the reaction and total serum IgE were also evaluated. Results: Seventy patients were analyzed, of which 55 (78.6%) were women. Mean age was 54 years. Of the total sample, 32 (45.7%) were atopic. Atopic patients had a lower mean age at the onset of asthma (22 years) and presented a longer mean disease duration (31 years) than non-atopic patients. Mean total serum IgE was higher in atopic patients (742.1 IU/ mL). In the group with AERD and atopy, the specific serum IgE test was positive for mites in 90.6% of the patients. Most atopic patients (71%) reported reaction to multiple NSAIDs. The main drugs related to respiratory exacerbations in patients with AERD were: aspirin in 72.1% of cases; dipyrone in 61.8%; diclofenac in 45.6%; ketoprofen and ibuprofen in 27.9% each. Conclusions: There are differences between patients with AERD according to the presence or absence of atopy. Atopic patients have an earlier onset of symptoms and a longer duration of asthma, they require more medication to control the condition and are hypersensitive to a greater number of NSAIDs; the drug that most commonly triggered symptoms also differed between the two groups.

[Is celecoxib a safe alternative for the Fernand Widal syndrome?] / Célécoxib, une alternative sûre pour les syndromes de Fernand Widal ?

The Fernand Widal syndrome is a set of associations between asthma, nasal polyposis and aspirin sensitivity. Selective cyclo-oxygenase 2 (COX 2) inhibitors are recognized as being a therapeutic alternative in cases needing analgesic or anti-inflammatory treatment. In a retrospective study, we have compiled data concerning oral provocation tests (OPT) undertaken with celecoxib, one of most the selective COX 2 inhibitors, in eight patients with the Fernand Widal syndrome. They were compared with twenty-seven control patients with sensitivity to aspirin or non-steroidal anti-inflammatories, manifesting as asthma, urticaria or rhino-conjunctivitis. Four patients with the Fernand Widal syndrome developed bronchospasm after taking the usually recommended daily dose of celecoxib while all the control patients tolerated it. The Fernand Widal patients who reacted during the OPT had a lower threshold of reactivity to aspirin, a more severe reaction with aspirin, and/or more severe asthma. In patients with the Fernand Widal syndrome, celecoxib is not always a possible alternative to non-steroidal anti-inflammatory drugs. Its introduction must be carried out in a hospital environment under medical supervision.

Current complications and treatment of aspirin-exacerbated respiratory disease.

INTRODUCTION: Aspirin-exacerbated respiratory disease is defined by the clinical tetrad of aspirin sensitivity, nasal polyps, asthma, and chronic rhinosinusitis. Patients experience acute upper and lower airway reactions with exposure to aspirin and other cyclooxygenase-1 inhibiting medications. However, airway inflammation and disease progression occur even in the absence of exposure to these medications, often leading to aggressive polyp formation and need for systemic corticosteroids to treat exacerbations in asthma and rhinosinusitis. Areas covered: This review focuses on the direct and indirect complications of aspirin-exacerbated respiratory disease. Current and potential management strategies are discussed with emphasis on aspirin desensitization. Expert commentary: Aspirin desensitization remains the gold standard of treatment. Demonstrated benefits of desensitization include improved symptom scores, reduction in use of systemic corticosteroids, slowing of polyp regrowth, and tolerance of aspirin and other NSAIDs for various therapeutic purposes. Continued investigation into the pathogenic mechanisms of AERD is likely to yield new diagnostic and therapeutic approaches.

Does aspirin-induced oxidative stress cause asthma exacerbation?

Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.

Survey-Defined Patient Experiences With Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a chronic illness of progressive recurrent sinus disease with nasal polyps and asthma. No population-based comprehensive surveys of patients with AERD have been carried out to assess specific quality-of-life impact or perceptions of treatment benefit. OBJECTIVE: This survey analyzed perceptions and quality of life in those living with AERD and queried patient observations of treatment effectiveness. The survey assessed whether dietary and nutritional support was used to manage AERD, and if so, whether there was a perceived benefit. METHODS: This survey was publicized through clinics that treat patients with AERD, Web sites, and online blogs. RESULTS: Results are reported for 190 patients. Most subjects reported an adverse effect of AERD on quality of life. Chronic nasal symptoms followed by decreased sense of smell were reported to have the greatest impact on quality of life­in 81 (43%) and 74 (39%), respectively. Those who lost their ability to smell (n = 65; 34%) reported that they missed the enjoyment of food and eating the most. A minority indicated that a combination of medications (aspirin, leukotriene receptor antagonist, zileuton, or omalizumab) was more effective than 1 alone. Of those surveyed, 120 (63%) respondents felt that components of their diet contributed to their disease and 147 (77%) respondents reported having reactions after alcohol consumption. CONCLUSIONS: Patients with AERD live with frustration and report a poor quality of life in spite of several pharmacologic treatments including aspirin desensitization followed by daily aspirin. Despite ongoing medical therapy, the burden of disease in AERD remains high.

Prevalence of aspirin-exacerbated respiratory disease among asthmatic patients: A meta-analysis of the literature.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is manifested by adult-onset asthma, nasal polyposis, chronic rhinosinusitis, and aspirin sensitivity. Previously reported prevalence rates have been widely variable based on the population studied, method of diagnosis, and definition of aspirin sensitivity. OBJECTIVE: We sought to determine the prevalence of AERD among asthmatic adults. METHODS: A systematic review of databases was performed to identify all clinical trials published on or before June 16, 2013, that evaluated the prevalence of AERD. The studies were clustered into 7 different groups based on underlying disease (asthma, nasal polyps or chronic rhinosinusitis, or both), as well as on the methodology of prevalence determination. RESULTS: A total of 1770 articles were identified, with 27 considered appropriate for inclusion. Prevalence rates of AERD ranged from 5.5% to 12.4% based on study type. Among all studies in asthmatic patients, regardless of method, the prevalence of AERD was 7.15% (95% CI, 5.26% to 9.03%). The prevalence of AERD was highest among patients with severe asthma (14.89% [95% CI, 6.48% to 23.29%]). Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% (95% CI, 2.16% to 17.22%) and 8.7% (95% CI, -1.02% to 18.34%), respectively. CONCLUSION: AERD is a distinct and important subtype of asthma and polypoid sinus disease. The prevalence of AERD is 7% in typical adult asthmatic patients and twice that number in patients with severe asthma, which underscores the importance of recognizing this disorder. Early identification of this syndrome is critical in view of the increased morbidity and costs associated with asthma exacerbations and the option to treat patients with AERD with long-term aspirin treatment after desensitization.

Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma: a double-blind study.

BACKGROUND: Numerous open trials have demonstrated the beneficial clinical effects of aspirin desensitization (AD) in patients with aspirin-induced asthma (AIA). These beneficial effects might be attributable to aspirin's potent anti-inflammatory properties, but that supposition requires further corroboration. OBJECTIVE: We sought to compare the clinical and biochemical responses to chronic oral AD in 20 patients with AIA and 14 patients with aspirin-tolerant asthma (ATA). All of the patients had chronic rhinosinusitis and nasal polyposis, and these responses were investigated in a pilot, double-blind, placebo-controlled study. METHODS: Twelve patients with AIA and 6 patients with ATA were randomly assigned to receive 624 mg of aspirin, and 8 patients with AIA and 8 patients with ATA received placebo. Both aspirin and placebo were administered once daily for 6 months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20) scores, peak nasal inspiratory flows, Asthma Control Questionnaire scores, spirometric parameters, peak expiratory flows, blood eosinophilia, and corticosteroid doses were assessed on a monthly basis. Levels of urinary leukotriene E4 and the stable plasma prostaglandin (PG) D2 metabolite 9α,11ß-PGF2 were evaluated at baseline and after 1, 3, 5, and 6 months. RESULTS: Only the patients with AIA subjected to AD reported improvements in smell and reductions in sneezing and nasal blockade. The SNOT20 and Asthma Control Questionnaire scores of these patients decreased, and their peak nasal inspiratory flows increased. The dosages of inhaled corticosteroids were reduced. There were no changes in leukotriene E(4) or 9α,11ß-PGF(2) levels after AD. CONCLUSION: The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA.

Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm in susceptible patients with asthma, often termed aspirin-exacerbated respiratory disease (AERD), with the risk being greatest after acute exposure. Selective NSAIDs that preferentially inhibit COX-2 might be safer. OBJECTIVE: We sought to systematically evaluate changes in symptoms and pulmonary function after acute selective NSAID or COX-2 inhibitor exposure in patients with the AERD phenotype. METHODS: A systematic review of databases was performed to identify all blinded, placebo-controlled clinical trials evaluating acute selective NSAID or COX-2 inhibitor exposure in patients with AERD. Effect estimates for changes in respiratory function and symptoms were pooled by using fixed-effects meta-analysis, with heterogeneity investigated. RESULTS: No significant difference in respiratory symptoms (risk difference, -0.01; 95% CI, -0.03 to 0.01; P = .57), decrease in FEV1 of 20% or greater (RD, 0.00; 95% CI, -0.02 to 0.02; P = .77), or nasal symptoms (RD, -0.01; 95% CI, -0.04 to 0.02; P = .42) occurred with COX-2 inhibitors (eg, celecoxib). Selective NSAID exposure caused respiratory symptoms in approximately 1 in 13 patients with AERD (RD, 0.08; 95% CI, 0.02 to 0.14; P = .01). No significant differences were found according to leukotriene antagonist exposure or whether NSAIDs were randomly allocated. CONCLUSION: According to clinical trial evidence in patients with stable mild-to-moderate asthma with AERD, acute exposure to COX-2 inhibitors is safe, and selective NSAIDs exhibit a small risk. Thus COX-2 inhibitors could be used in patients with AERD or in patients with general asthma unwilling to risk nonselective NSAID exposure when oral challenge tests are unavailable.

Systemic prednisone administration selectively alters granulocyte subsets in nasal polyps from aspirin-exacerbated respiratory disease and chronic rhinosinusitis patients.

BACKGROUND: Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis. Despite the spectrum of NP conditions, cellular differences between NPs from patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) are poorly understood. NPs are associated with abundant eosinophils; the contributions of neutrophil and basophil granulocytes are less defined. We therefore sought to assess granulocyte subpopulations, and differential effects following prednisone pretreatment, within NPs of CRSwNP and AERD patients. METHODS: NPs, adjacent ethmoid sinus tissue, and peripheral blood mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus surgery. Samples from 5 cohorts: CRSwNP ± prednisone (n = 6 each), AERD ± prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional flow cytometry to gate granulocyte populations. Specimens were also assessed using immunohistochemistry (IHC) staining. RESULTS: Systemic prednisone administration was associated with a lower frequency of eosinophils (p < 0.0001, n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n = 6) within NPs from either group. No significant shift in granulocyte subsets after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs from the same patients. Immunohistochemistry (IHC) staining supported these findings. CONCLUSION: Granulocyte subpopulations are focally affected within NPs by systemic steroid exposure, without notable granulocyte alterations in the surrounding regional tissues. These data provide direct insights into the cellular effects of routine prednisone exposure in CRS patients, and highlight a unique microenvironment present within NP lesions.