Aspirin-exacerbated Respiratory Disease Patients Research Articles

IL-4Rα signaling promotes barrier-altering oncostatin M and IL-6 production in aspirin-exacerbated respiratory disease

Aspirin-exacerbated respiratory disease (AERD) is a severe disease involving dysregulated type 2 inflammation. However, the role other inflammatory pathways play in AERD is poorly understood. We sought to broadly define the inflammatory milieu of the upper respiratory tract in AERD and to determine the effects of IL-4Rα inhibition on mediators of nasal inflammation. Twenty-two AERD patients treated with dupilumab for 3 months were followed over 3 visits and compared to 10 healthy controls. Nasal fluid was assessed for 45 cytokines and chemokines using Olink Target 48. Blood neutrophils and cultured human mast cells, monocytes/macrophages, and nasal fibroblasts were assessed for response to IL-4/13 stimulation invitro. Of the nasal fluid cytokines measured, nearly one third were higher in AERD patients compared to healthy controls, including IL-6 and the IL-6 family-related cytokine oncostatin M (OSM), both of which correlated with nasal albumin levels, a marker of epithelial barrier dysregulation. Dupilumab significantly decreased many nasal mediators, including OSM and IL-6. IL-4 stimulation induced OSM production from mast cells and macrophages but not from neutrophils, and OSM and IL-13 stimulation induced IL-6 production from nasal fibroblasts. In addition to type 2 inflammation, innate and IL-6-related cytokines are also elevated in the respiratory tract in AERD. Both OSM and IL-6 are locally produced in nasal polyps and likely promote pathology by negatively affecting epithelial barrier function. IL-4Rα blockade, although seemingly directed at type 2 inflammation, also decreases mediators of innate inflammation and epithelial dysregulation, which may contribute to dupilumab's therapeutic efficacy in AERD.

Adult-onset asthma, allergy, and aspirin hypersensitivity associate with self-reported food avoidance

ABSTRACT Background The adoption of avoidance diets by adult-onset asthmatics has not previously been studied. We hypothesized that avoidance diets would associate with adult-onset asthma, allergy, and aspirin-exacerbated respiratory disease (AERD). Methods A total of 1247 subjects with adult-onset asthma (age range: 31–91) from the Finnish national registry, and age- and sex-matched controls (n = 1970) participated in a questionnaire study in 1997. We estimated the association between asthma/allergy/AERD and avoidance diets, adjusting for potential confounding factors and validated the results in two retrospective cohorts of 5080 rhinitis/rhinosinusitis patients and 167 AERD patients from 2019 to 2020. Results The presence of asthma positively associated with adoption of any avoidance diet (adjusted OR [CI95%] 1.24 [1.02–1.51], p = 0.029) as did allergic disease and self-reported AERD within the asthmatic group (1.79 [1.29–2.48], p = 0.001 and 1.69 [1.15–2.49], p = 0.007, respectively). Asthmatics and allergic asthmatics were more likely to report avoidance of fish, fruits and vegetables, and spices (p ≤ 0.03) compared to controls and non-allergic asthmatics. The adjusted OR for multiple diets among AERD patients was 2.57 [1.34–4.95] p = 0.005. In the validation, 26.2% of the allergic asthmatics and 10.8% of AERD patients had documented avoidance diets. Conclusions Our study shows a positive association between avoidance diets and adult-onset asthma, and with allergic disease or AERD within asthmatic patients. Although we lack information on the reason patients chose to observe a specific diet, our results reinforce the importance of asking patients about their diet and if needed, giving dietary advice for adult asthma patients to help them avoid the adoption of unnecessarily restrictive diets.

Sleep dysfunction in aspirin exacerbated respiratory disease: A prospective cohort study

AbstractObjectiveStudies have described sleep dysfunction (SD) in patients with chronic rhinosinusitis (CRS). However, there is a paucity of literature describing sleep dysfunction in the context of aspirin‐exacerbated respiratory disease (AERD). The purpose of this study was to evaluate the prevalence and severity of SD in patients with AERD relative to CRS.MethodsThis study is a prospective cohort study. Patients diagnosed with CRS without polyposis (CRSsNP, n = 206), CRS with nasal polyposis (CRSwNP, n = 38), and AERD (n = 28) were recruited prospectively in academic center rhinology clinic. SD was assessed using the Neuro‐QOL Short Form v1.0‐Sleep Disturbance (sleep‐QOL), for which severe SD is defined as a score >2.0 standard deviations from the normalized mean. Demographic and patient‐reported outcome measures (including SNOT‐22 and PHQ‐2) were collected to adjust for sleep confounders. Comparisons were made between groups using univariate and multivariate analyses.ResultsThe prevalence of severe SD was significantly higher in AERD (57.1%) than in CRSsNP (32.5%) or CRSwNP (34.2%), p = 0.038. After adjusting for sleep confounders, the risk of sleep dysfunction remained higher among patients with AERD (odds ratio [OR] = 2.72 vs. CRSsNP, 95% confidence interval [CI] = 1.18–6.27, p = 0.02; OR = 3.06 vs. CRSwNP, 95% CI = 1.06–8.82, p = 0.04). SNOT‐22 total score and the sleep subdomain showed no correlation with sleep‐QOL score.ConclusionsThe frequency and severity of SD are greater in AERD patients than in patients with CRS with or without nasal polyposis, independent of confounders of sleep quality. While the putative link between AERD and SD remains elusive, this study suggests that SD in AERD may be greater than previously recognized.

Aspirin Challenge-Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease.

Genetic variation and epigenetic factors are thought to contribute to the development of hypersensitivity to aspirin. DNA methylation fluctuates dynamically throughout the day. To discover new CpG methylation in lymphocytes associated with aspirin-exacerbated respiratory disease (AERD), we evaluated changes in global CpG methylation profiles from before to after an oral aspirin challenge in patients with AERD and aspirin-tolerant asthma (ATA). Whole-genome CpG methylation levels of peripheral blood mononuclear cells were quantified with an Illumina 860K Infinium Methylation EPIC BeadChip array and then adjusted for inferred lymphocyte fraction (ILF) with GLINT and Tensor Composition Analysis. Among the 866,091 CpGs in the array, differentially methylated CpGs (DMCs) were found in 6 CpGs in samples from all 12 patients with asthma included in the study (AERD, n = 6; ATA, n = 6). DMCs were found in 3 CpGs in the 6 ATA samples and in 615 CpGs in the 6 AERD samples. A total of 663 DMCs in 415 genes and 214 intergenic regions differed significantly in the AERD compared with the ATA. In promoters, 126 CpG loci were predicted to bind to 38 transcription factors (TFs), many of which were factors already known to be involved in the pathogenesis of asthma and immune responses. In conclusion, we identified 615 new CpGs methylated in peripheral blood lymphocytes by oral aspirin challenge in AERD but not in ATA. These findings indicate that oral aspirin challenge induces epigenetic changes in ILFs, specifically in AERD patients, possibly via changes in TF binding, which may have epigenetic effects on the development of AERD.

Angiogenesis and eosinophilia in the nasal mucosa of patients with different clinical phenotypes of chronic rhinosinusitis

Introduction: Dense inflammatory cell infiltration and vascularization of the nasal mucosa are histological characteristics of chronic rhinosinusitis (CRS). We aimed to evaluate the association between eosinophilia and vascularization in the stroma of mucosal layer/nasal polyps (NP) and clinical parameters in patients with different phenotypes of CRS. Methodology: This cross-sectional study involved 33 patients who had CRS with NP without aspirin sensitivity (CRSwNP), 20 NP patients as a part of aspirin-exacerbated respiratory disease (AERD), and 10 patients who had CRS without NP (CRSsNP), selected for surgery. Control group consisted of 31 subjects without nasal/sinus inflammation, selected for surgery of pneumatized middle turbinate. All patients were clinically scored before surgery for nasal symptoms, quality of life (QoL) outcome and findings from computed tomography scans. NP/nasal mucosa samples of participants were immunohistochemically stained for eosinophil infiltration marker BMK13 and angiogenesis markers CD31 and CD34. Results: AERD patients had the highest level of immunoexpression for BMK13. The strongest staining pattern of CD34 was found in AERD group and the highest expression level for CD31 in CRSwNP group. We found a positive correlation between BMK13, impaired QoL and radiologically evaluated disease extent in patients with CRSwNP. Excepting CRSsNP patients, no correlation was found between the marker of tissue eosinophilia and markers of vascular proliferation. Conclusions: Patients from AERD phenotype have the highest degree of stromal eosinophilic infiltration and endothelial proliferation in comparison to other CRS phenotypes. Eosininophil infiltration marker BMK13 correlates better with the clinical parameters of CRS in comparison to the vascular proliferation markers.

Is endoscopic sinus surgery sufficient to modify the evolution of adult AERD? Aspirin desensitization as a maintenance factor: systematic review.

Aspirin desensitization (AD) and aspirin therapy after desensitization (ATAD) are therapeutic interventions for patients with aspirin-exacerbated respiratory disease (AERD). Our aim is to investigate whether its addition to endoscopic sinus surgery (ESS) improves the overall prognosis of the disease. A systematic review of the current literature including adult patients with a positive diagnosis of AERD undergoing endoscopic sinus surgery (ESS) in the context or in absence of upper airway comorbidity, prior to AD + ATAD. This review concludes that the surgical approach is beneficial in AERD, but its effects are short-lived. Surgery should be considered initially with subsequent AD + ATAD in AERD patients, due to the sustained improvement achieved compared to those receiving ESS alone.

Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD

Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D2, and low levels of prostaglandin E2. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown. We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD. Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis. Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r= -0.6667; P= .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r= 0.7143; P= .0305) and clinical symptom scores (r= 0.5000; P= .0081). Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.

Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.

Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). This study aimed to investigate the long-term clinical outcomes between AERD and ATA. AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.

Blood Basophils Relevance in Chronic Rhinosinusitis with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and intolerance to cyclooxygenase-1 inhibitors. Interest is emerging in studying the role of circulating inflammatory cells in CRSwNP pathogenesis and its course, as well as their potential use for a patient-tailored approach. By releasing IL-4, basophils play a crucial role in activating the Th2-mediated response. The main aim of this study was to, first, investigate the level of the pre-operative blood basophils' values, blood basophil/lymphocyte ratio (bBLR) and blood eosinophil-to-basophil ratio (bEBR) as predictors of recurrent polyps after endoscopic sinus surgery (ESS) in AERD patients. The secondary aim was to compare the blood basophil-related variables of the AERD series (study group) with those of a control group of 95 consecutive cases of histologically non-eosinophilic CRSwNP. The AERD group showed a higher recurrence rate than the control group (p < 0.0001). The pre-operative blood basophil count and pre-operative bEBR were higher in AERD patients than in the control group (p = 0.0364 and p = 0.0006, respectively). The results of this study support the hypothesis that polyps removal may contribute to reducing the inflammation and activation of basophils.

Omalizumab ameliorates extrarespiratory symptoms in patients with aspirin-exacerbated respiratory disease

Omalizumab, an anti-immunoglobulin E antibody, has clinical efficacy against respiratory symptoms of aspirin-exacerbated respiratory disease (AERD). However, some patients with AERD also present with extra-respiratory (chest, gastrointestinal, and/or cutaneous) symptoms, which are resistant to conventional treatment but can be alleviated by systemic corticosteroids. To evaluate the efficacy of omalizumab on extra-respiratory symptoms related to AERD. In Study 1, 27 consecutive patients with AERD initially prescribed omalizumab at Sagamihara National Hospital between July 2009 and March 2019 were studied retrospectively. The frequency of exacerbations of AERD-related extra-respiratory symptoms was compared before and after the initiation of omalizumab treatment. In Study 2, we reported three AERD cases with aspirin challenge-induced extra-respiratory symptoms among patients studied in our previous randomized trial (registration number: UMIN000018777), which evaluated the effects of omalizumab on hypersensitivity reactions during aspirin challenge to AERD patients. The extra-respiratory symptoms induced during the aspirin challenge were compared between the placebo and omalizumab phases. In Study 1, omalizumab treatment was associated with a decrease in the frequency of exacerbation of chest pain (n [%] of patients with exacerbation frequency ≥1 time per year, 6 [22.2%] vs. 0 [0%]; P<0.001), gastrointestinal symptoms (9 [33.3%] vs. 2 [7.4%]; P=0.016), and cutaneous symptoms (16 [59.3%] vs. 2 [7.4%]; P<0.001), even under conditions of a treatment-related reduction in systemic corticosteroid dose. Omalizumab also attenuated all the extra-respiratory symptoms during the aspirin challenge in Study 2. Omalizumab ameliorated the extra-respiratory symptoms at baseline (without aspirin exposure) and during aspirin challenge.

Association of eosinophil-derived neurotoxin levels with asthma control status in patients with aspirin-exacerbated respiratory disease.

The long-term goals of asthma treatment are to achieve well control of symptoms and to minimize the future risk of asthma exacerbation. Identifying biomarkers for uncontrolled asthma is important for improving the asthma outcome. This study aimed to investigate the association of the levels of eosinophil-derived neurotoxin (EDN) with asthma control status in specific asthma phenotype, aspirin-exacerbated respiratory disease (AERD), and aspirin-tolerant asthma (ATA). A total of 136 adult asthmatics, including 47 asthmatics with AERD and 89 asthmatics with ATA, were enrolled. Plasma, sputum, and urine were collected at enrollment and the levels of EDN were measured by the K-EDN ELISA kit. Urinary leukotriene E4 (LTE4 ) level was measured using liquid chromatography-mass spectrometry (LC-MS)/MS methods. Asthma control status was evaluated according to the GINA guideline, asthma control test and asthma control questionnaire scores. In the total study subjects, sputum levels of EDN as well as of urine and plasma EDN showed significantly higher levels in patients with uncontrolled asthma than in those with well-controlled or partly-controlled asthma (ANOVA, p<0.001); in patients with AERD, the sputum EDN levels showed significant correlations with ACT, ACQ, and AQLQ scores (p=0.010, r=-0.536, p=0.001, r=0.665, and p<0.001, r=-0.691, respectively), while no differences were noted in patients with ATA. Sputum EDN level was the only significant factor for ACT, ACQ, and AQLQ scores in patients with AERD (p=0.001, p<0.001, and p<0.001, respectively) in the multivariate analysis adjusting for age, sex, peripheral eosinophil count, and urine LTE4 . The ROC curve analysis demonstrated that sputum EDN can predict uncontrolled asthma with 80% sensitivity and 88.2% specificity for ACT≤19 (area under the ROC curve [AUC]=0.824, p=0.019); 71.4% sensitivity and 86.7% specificity for ACQ≥1.5 (AUC=0.752, p=0.049) only in AERD patients. The level of sputum EDN may be a potential biomarker for identifying the asthma control status in patients with AERD.

Inflammatory mediators in nasal secretions of patients with nasal polyposis with and without aspirin sensitivity.

The aim of this cross-sectional study was to compare the levels of inflammatory mediators in nasal secretions in patients with aspirin-exacerbated respiratory disease (AERD) and in those with nasal polyposis (NP) without aspirin-sensitivity and to correlate nasal fluid mediator concentrations with clinical parameters of the disease. A total of 30 patients with AERD, 30 chronic rhinosinusitis (CRS) with NP patients without aspirin sensitivity (CRSwNP), and 30 control subjects without inflammation of the nasal mucosa (C), selected for surgical treatment entered the study. The total nasal symptom score (TNSS), endoscopic score (ES), and Lund-Mackay score (LMS), were evaluated. The concentrations of eosinophil cationic protein (ECP), tryptase, heat shock protein 70 (HSP70), substance P and Clara cell protein 16 (CC16) were determined in nasal secretions. Higher concentrations of ECP, tryptase, and HSP70 were measured in the AERD patients than in the CRSwNP patients and the C group (p < .001; p < .001, respectively for all mediators). However, levels of CC16 were higher in the C group than in the AERD and CRSwNP groups (p < .001; p < .001, respectively). A positive correlation between the TNSS and CC16 and a negative one between CC16 and tryptase levels were found in the C group. The CRSwNP group showed positive correlations between ECP, HSP70, and tryptase and negative correlations between substance P, ES, and LMS, as well as between CC16 and tryptase levels. In the AERD group, we found a positive correlation between HSP70 and ECP levels and a negative correlation between the TNSS and CC16 concentration. The obtained results indicate the increased production of mediators of eosinophil and mast cell function, and the decreased production of biomarker of respiratory epithelial function in AERD patients. Clinical and biochemical parameters correlate in different ways in the AERD and CRSwNP patients.

Algorithmic Identification of Patients With Aspirin-Exacerbated Respiratory Disease Using an Electronic Health Record.

To determine whether an electronic health record (EHR) system can be used to identify cases of aspirin-exacerbated respiratory disease (AERD) in an area outside of a regional referral center with low rates of aspirin desensitization therapy. Retrospective chart review single academic tertiary care hospital. Single-site academic tertiary care hospital. Using Epic's SlicerDicer function, an algorithm was created and applied to all patient charts from 2013 to 2021. The algorithm was as follows: "Allergy/Contraindication to NSAIDs OR aspirin" AND "Diagnosis of Nasal polyp AND "Diagnosis of Asthma." Clinical data including demographics, NSAID reaction, and specialist involvement was collected. A total of 54 potential cases of AERD were identified. Thirty-twowere determined to have AERD after chart review, yet 12 of these patients (37.5%) had no mention of AERD within the chart. The 54 patients were stratified into 2 cohorts based on reaction to NSAIDs: respiratory (n = 29) or unspecified (n = 25). Of the patients in the respiratory reaction group, 26 were found to have clinical AERD, demonstrating a positive predictive values (PPV) of 89.7%. The overall PPV was 59.3%. Those with a respiratory reaction to NSAIDS listed in the EHR were more likely to have clinical AERD (odds ratio27.44; confidence interval6.08-123.85; p < 0.0001). Only 2 patients (6.3%) underwent aspirin desensitization. AERD remains under-diagnosed in the study population. The informatics algorithm presented here has a high positive predictive value for identifying clinical AERD patients in a geographical area with low rates of aspirin desensitization and may aid in identifying candidates for expanded treatment options.

SNIFFING AROUND FOR CLINICAL SCREENING MARKERS TO PREDICT AERD IN CRSWNP PATIENTS

<h3>Introduction</h3> Aspirin-exacerbated respiratory disease(AERD) is a sub-group of chronic rhinosinusitis with nasal polyps(CRSwNP) associated with asthma and cyclooxygenase-1 inhibitor sensitivity. AERD pathogenesis involves dysregulation of arachidonic acid metabolism which favors pro-inflammatory mediator overproduction. A significant proportion of AERD patients are suspected to be undiagnosed, as aspirin sensitivity is frequently unreported. There are no standard AERD screening modalities but aspirin challenge(AC) is an effective diagnostic tool. <h3>Methods</h3> A retrospective, observational study was conducted from 1/1/2016-12/29/2021. 210 subjects met inclusion criteria of CRSwNP patients who underwent AC, desensitization or had clinically diagnosed AERD. Baseline level of serum eosinophils(EOS), basophils, immunoglobulins, complements, tryptase, spot urine leukotriene E4(LTE4), fractional exhaled nitric oxide(FeNO) and Lund-Mackay CT-sinus score(LMCT) were evaluated. 33 subjects on biologic therapy were excluded. <h3>Results</h3> AERD was diagnosed in 74/177(41.80%) subjects. 61 subjects denied NSAID sensitivity and then completed AC, from which 14/61(22.95%) were positive. Several markers showed significant correlation with positive AC including LMCT, EOS and LTE4. Total complement(CH50) showed a slight but significant negative trend with positive AC but values remained within normal range. Other markers showed no correlation. <h3>Conclusion</h3> Contemporary literature reports different AERD endotypes which may obscure clinical phenotypes and hamper diagnosis. Clinical markers could prove valuable screening tools for atypical phenotypes. Prior studies have correlated AERD with serum basophils, EOS, IgE, LTE4 and LMCT. Our data correlates AERD diagnosis with LMCT, EOS, LTE4 and CH50. Further studies are needed to confirm our CH50 results. These clinical, laboratory and radiologic markers could prove useful screening tools for identifying candidates for AC.

Endoscopic outcomes in patients with AERD treated with topical antibiotics and intranasal corticosteroids.

BackgroundIdentifying effective therapy for recalcitrant chronic rhinosinusitis with nasal polyposis (CRSwNP) is a major challenge; and subtypes such as aspirin-exacerbated respiratory disease (AERD) are even more difficult to treat. Evidence on topical antibiotics use in (CRSwNP) is lacking. Current consensus guidelines recommend against its routine use, but recent reviews show some benefit when managing recalcitrant disease after endoscopic sinus surgery (ESS).ObjectiveEvaluate the effect of culture-directed topical antibiotics on sinonasal outcomes in AERD patients with a positive perioperative sinonasal bacterial culture who have undergone ESS.MethodsA retrospective cohort study of AERD patients with positive sinonasal culture, who underwent ESS from 2016 to 2021 was performed. Forty-four patients were identified and stratified based on their postoperative medical treatment. Twenty-six underwent postoperative intranasal corticosteroids (INCS) alone, while eighteen underwent INCS plus a 4-weeks treatment with topical antibiotics. SNOT-22 and Lund-Kennedy score (LKS) were assessed preoperatively and at 4-weeks and 4-6 months after ESS.ResultsA statistically significant improvement in the 4-weeks and 4-6 months postoperative SNOT-22 and LKS were noted within both groups (p<0.05). However, only a statistically significant difference was found in the 4-weeks postoperative LKS when comparing between treatment groups (p=0.01). Our linear regression model demonstrated a relationship between the use of combined therapy with INCS and topical antibiotics and the LKS 4-weeks post ESS (p=0.015).ConclusionIn AERD patients with a confirmed sinus infection, the combination of culture-directed topical antibiotics and intranasal corticosteroid irrigations in the postoperative period can provide a short-term improvement in endoscopic scores.

Evaluation of substance P and bradykinin levels in nasal secretions of patients with nasal polyposis with and without sensitivity to non-steroidal anti-inflammatory drugs.

ObjectiveThe role of neurogenic inflammation in pathogenesis of chronic rhinitis is well known. However, very little is known about its importance in pathogenesis of nasal polyposis (NP), especially in form of NP which appears as a part of aspirin‐exacerbated respiratory disease (AERD). The aim of this study was to examine the concentrations of neuropeptides substance P (SP) and bradykinin (BK) in nasal secretions of patients with NP.MethodsFourteen patients with NP as a part of AERD with mild persistent asthma, 14 patients with NP without aspirin sensitivity, and 14 control subjects without nasal inflammation (C) entered this cross‐sectional study. Clinical parameters (symptoms, endoscopic, and radiological findings) were assessed. The concentrations of SP and BK were measured in the nasal secretion samples using commercial human enzyme immunoassay kits.ResultsThe concentration of SP in nasal secretions was significantly higher in NP patients without aspirin sensitivity and AERD patients compared to controls (p = .022; p < .0001, respectively), but higher in AERD than in non‐AERD patients (p = .018). The level of BK in nasal fluid was higher in non‐AERD and AERD NP patients than in controls (p < .0001; p < .0001, respectively), but also higher in AERD than in non‐AERD patients (p < .0001). We found high positive correlations between BK in nasal fluid and Lund–Mackay computed tomography (CT) score in both non‐AERD and AERD groups of NP patients.ConclusionOur results suggest more intense release of SP and BK from the nasal mucosa in patients with AERD than in patients with NP who do not have aspirin sensitivity. The strong correlation between concentration of BK in nasal secretions and CT score suggests that BK in nasal fluid could be used as a marker for disease severity as measured by the Lund–Mackay score.

Loss of smell in patients with aspirin-exacerbated respiratory disease impacts mental health and quality of life.

The impact of anosmia on quality-of-life (QoL) for patients with aspirin-exacerbated respiratory disease (AERD) is poorly understood. We aimed to investigate how the severity of smell loss and olfactory dysfunction (OD) in patients with AERD affects their QoL, mental health and physical well-being. Five validated QoL questionnaires (Sinonasal Outcome Test-22, Asthma Control Test, Healthy Days Core Module-4, Short Form-36 and Patient Health Questionnaire-4) and two newly developed questionnaires assessing severity and consequences of OD were electronically sent to all 2913 patients in the Brigham and Women's Hospital AERD registry. Responses were received from 853 participants for analysis. Overall, 85% of participants reported a present diminished sense of smell and/or taste, and 30% categorized their OD severity was, "as bad as it can be." There were significant relationships between the severity of self-reported OD and both psychological distress and general health scores, even after adjusting for asthma control. Additionally, incidence rates for physically and mentally unhealthy days in the prior month were higher for patients with moderate or severe OD than for normosmic patients. Patients with diminished smell responded that they could not identify spoiled food (86%), did not enjoy food (71%), felt unsafe (63%) and had encountered dangerous situations (51%) as consequences of their OD. Anosmia and hyposmia severely impact the physical, emotional and mental health of AERD patients, and lead to safety concerns in their daily lives. The importance of olfaction and the relevance of OD to patients' QoL should be acknowledged and evaluated by clinicians caring for these patients.

Local and Systemic Production of Pro-Inflammatory Eicosanoids Is Inversely Related to Sensitization to Aeroallergens in Patients with Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is characterized by overproduction of the pro-inflammatory eicosanoids. Although immunoglobulin E-mediated sensitization to aeroallergens is common among AERD patients, it does not belong to the defining disease characteristics. In this study of 133 AERD patients, we sought to find a relationship between sensitization to aeroallergens and local (leukotriene E4, prostaglandin E2 and prostaglandin D2) and/or systemic (leukotriene E4) production of arachidonic acid metabolites. Interestingly, a negative association between pro-inflammatory eicosanoid levels in induced sputum supernatant or urine and sensitization to aeroallergens was observed. This inverse relationship might suggest the presence of a protective effect of atopic sensitization to aeroallergens against stronger local airway inflammation and higher systemic AERD-related inflammatory activity.

Characterization Of Alcohol Induced Respiratory Symptoms In Aspirin Exacerbated Respiratory Disease (AERD): The Happy Hour Study

AERD patients have high rates of upper and lower airway reactions with alcohol ingestion. I We hypothesized that alcohol ingestion will cause upper and lower airway reactivity that is diminished with montelukast and cetirizine pretreatment.

Prevalence Of Acetaminophen Intolerance Among Patients With Aspirin Exacerbated Respiratory Disease At A Tertiary Care Institution

Aspirin Exacerbated Respiratory Disease (AERD) is the clinical triad of chronic rhinosinusitis with nasal polyps, asthma, and intolerance to medications that inhibit the cyclooxygenase-1 enzyme. Historically, acetaminophen has been recommended as a safe alternative analgesic but clinically, some AERD patients cannot tolerate acetaminophen. This study examined the prevalence and clinical characteristics associated with acetaminophen intolerance among a cohort of AERD patients.