Aspirin-exacerbated Respiratory Disease Research Articles

Endoscopic Sinus Surgery for Chronic Rhino Sinusitis with Nasal Polyps: Predictive Factors of Recurrence.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition which may have a significant impact on quality of life. Endoscopic sinus surgery (ESS) is usually indicated for patients' refractory to maximal medical treatment and presents high recurrence and revision surgery rates. Objective: The aims of this study are to evaluate ESS outcome in CRSwNP management and to assess independent predictive factors for recurrence. Methods: Retrospective medical chart review of patients who underwent ESS for recalcitrant CRSwNP, from January 2002 to December 2021, with a minimum follow-up time of 12 months. Results: This study enrolled 280 patients; 52.5% of whom were males, with a mean age of 41.44 ± 14.25 years. Asthma was the most common comorbidity (36.4%, n = 102) and aspirin exacerbated respiratory disease was present in 16.8% (n = 47) of the study population. We found a recurrence rate of 20.7% (n = 58) and 8.9% (n = 25) of patients required revision surgery. Multivariate analysis identified as independent variables of recurrence (95% CI): no compliance with medication after surgery using topical steroids (OR = 16.056; CI 7.887-32.684; P < .001). Conclusions: ESS proved to be an effective treatment in CRSwNP but with a considerable rate of recurrence. These results indicated an important correlation of postoperative topical steroids compliance with disease recurrence.

Introduction of asingle-nucleotide variant, rs16851030, into the ADORA1 gene increased cellular susceptibility to hypoxia.

Aim: Rs16851030, a single-nucleotide variant located in the 3'-untranslated region of the ADORA1 gene, has been proposed as a potential marker of caffeine sensitivity in apnea of prematurity. Besides, it is associated with aspirin-induced asthma and the development of acute chest syndrome. However, its functional significance is still unconfirmed. This study aimed to elucidate the functional impact of rs16851030 by using CRISPR/Cas9 approach to induce the DNA variant and attendant physiological changes.Methods: Rs16851030 was introduced into HEK293 cells via homology-directed repair (HDR). Edited cells were fluorescence-enriched, sorted, isolated, and expanded into single-cell-derived clones. The edit was confirmed by Sanger sequencing. RNA sequencing was used to analyze affected pathways.Results: Rs16851030-mutant cells showed increased susceptibility to hypoxia, a condition related to apnea of prematurity. After 24h of hypoxia, the viability of mutant clones 1 and 2 was low compared with wild-type cells (75.45% and 74.47% vs. 96.34%). RNA sequencing revealed transcriptomic changes linked to this increased vulnerability.Conclusion: Rs16851030 impairs cellular resistance to hypoxia, suggesting its role in conditions like apnea of prematurity. Further research should investigate the molecular mechanisms and transcriptomic alterations caused by rs16851030 under hypoxic conditions.

Practice Patterns of Biologics Prescriptions and Surgery in Chronic Rhinosinusitis With Nasal Polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) remains challenging to manage effectively, with high symptom recurrence rates and significant impacts on quality of life, prompting a need to evaluate the real-world use of biologics and optimize treatment strategies. To assess the real-world application and perspectives of American Rhinologic Society (ARS) members on biologic treatments and surgical interventions for CRSwNP, focusing on clinical practice patterns, adoption of biologics, and their impact on surgical practices. A standardized questionnaire evaluated clinical practice patterns of biologics prescriptions and surgery in treating CRSwNP between July 2022 and August 2023. Data collected from 162 ARS members were analyzed. Of 162 participants, a substantial majority (95.06%, n = 154) reported prescribing biologics in their practice. Notably, 45.45% (n = 70) found biologics easily accessible, although accessibility challenges remained for some. The impact of biologics on surgical practices was significant, with 36.36% (n = 56) observing a marked reduction in revision sinus surgeries. Among the participants, 47.16% (n = 71) agreed that aspirin-exacerbated respiratory disease (AERD) was the highest phenotype that tended to increase the possibility of biological treatment by more than 20%. Adopting Patient-Reported Outcome Measures (PROMs) was prevalent, with 57.79% (n = 89) utilizing them in patient management. The study highlights the evolving landscape in managing CRSwNP, with a marked trend toward integrating biological treatments into clinical practice. It underscores the necessity for continued research, updates to clinical guidelines, and enhanced practitioner education to optimize treatment outcomes for CRSwNP patients.

Cysteinyl Leukotrienes in Allergic Inflammation.

The cysteinyl leukotrienes (CysLTs), LTC4, LTD4, and LTE4, are potent lipid mediators derived from arachidonic acid through the 5-lipoxygenase pathway. These mediators produce both inflammation and bronchoconstriction through three distinct G protein-coupled receptors (GPCRs)-CysLT1, CysLT2, and OXGR1 (also known as CysLT3 or GPR99). While CysLT-mediated functions in the effector phase of allergic inflammation and asthma have been established for some time, recent work has demonstrated novel roles for these mediators and their receptors in the induction and amplification of type 2 inflammation. Additionally, in vitro studies and murine models have uncovered diverse regulatory mechanisms that restrain or amplify CysLT receptor activation and CysLT receptor function. This review provides an overview of CysLT biosynthesis and its regulation, the molecular and functional pharmacology of CysLT receptors, and an overview of the established and emerging roles of CysLTs in asthma, aspirin-exacerbated respiratory disease, and type 2 inflammation.

The effect of allergen immunotherapy in patients with central compartment atopic disease post-surgery.

To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post-surgery. A retrospective cohort of surgically treated, HDM-sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22-item sino-nasal outcome test (SNOT-22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin-exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell×109/L), tissue eosinophilia (%>100/HPF), and serum IgE (kU/L) were also recorded. Eighty-six CCAD patients were assessed (41±14yrs, 64% female). AIT was applied in 37% (n=32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p=0.02) in the AIT group. At 12 months post-surgery, the AIT group has less MT edema (%≥diffuse 15.6 vs. 52.9, p<0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (%≥4/week, 37.5 vs. 79.6%, p<0.01). The rhinologic symptoms were similar (21.1±17.1 vs. 20.1±21.6, p=0.83). Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de-escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation.

Mucosal LTE4, PGD2 and 15(S)-HETE as potential prognostic markers for polyp recurrence in chronic rhinosinusitis

BackgroundAltered biosynthesis of eicosanoids is linked to type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP), but their role in recalcitrant NPs is unclear. ObjectivesWe sought to identify endotypes that are linked to recalcitrant CRSwNP, based on eicosanoids, their biosynthetic enzymes, and receptors as well as cytokines and the presence of eosinophils and mast cells in recurrent NPs. MethodsMucosal tissue collected at the time of sinus surgery from 54 patients with CRSwNP and 12 non-CRS controls were analysed for leukotriene (LT) E4, prostaglandin (PG) D2, 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 17 cytokines with ELISAs and Bio-Plex immunoassays. Patient subgroups were identified by cluster analysis and the probability of NP recurrence were tested with logistic regression analyses. Gene expressions were analysed with qPCR. Tryptase and eosinophil-derived neurotoxin (EDN) were measured with ELISAs as indications of the presence of mast cells and eosinophils, respectively. ResultsClustering of patients showed that an inflammatory signature characterised by elevated LTE4, PGD2, 15(S)-HETE and IL-13 was associated with NP recurrence. Previous NP surgery as well as aspirin-exacerbated respiratory disease were significantly more common among these patients. Expression of cyclooxygenase 1 was the only gene associated with NP recurrence. Levels of EDN, but not tryptase, were significantly higher in patients with recurrent NPs. ConclusionDistinguishing endotypes that include LTE4, PGD2, 15HETE and conventional biomarkers of type 2 inflammation could help predict recurrent nasal polyposis and thus identify cases of recalcitrant CRSwNP.

Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy.

The indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy. Retrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease-specific outcomes were measured using the sinonasal outcomes test (SNOT-22). Within 87 patients with CRSwNP, 24.1% had aspirin-exacerbated respiratory disease (AERD). Significant improvement in SNOT-22 score was found in CRSwNP with AERD (p<0.001) and without AERD (p=0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p=0.02), prior aspirin desensitization (p=0.02), and worse preoperative Lund-MacKay scores (p<0.001). No association between biologic rescue and frontal recess antero-posterior diameter was found (p=0.20). Draf 3 surgery in CRSwNP was associated with significant improvement in SNOT-22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study

Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

IgG4-Rich Lesions Associated With Intranasal Drug Use Can Mimic IgG4-Related Disease.

Manifestations of immunoglobulin G4-related disease (IgG4-RD) occur in several organ systems and anatomic locations, including the nasal cavity and paranasal sinuses. Other processes affecting the sinonasal tract, such as chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyposis, also involve IgG4. To characterize an association between IgG4 and nasal lesions arising in the clinical context of intranasal drug use. The cases of 3 patients (2 with histories of intranasal cocaine abuse, and 1 with intranasal heroin abuse) were evaluated. Clinical features of each case were compiled from the electronic medical record. Histologic morphology of surgical specimens was examined. Immunohistochemical staining was performed to assess involvement of/association with IgG4. Clinical features of these lesions included diffuse necrotic fibrinous debris, scarring, and endoscopically evident inflammation. Tissue sections showed acutely and chronically inflamed respiratory-type mucosa with abundant IgG4-positive plasma cells. Although these cases share some aspects in common with IgG4-RD, other definitive characteristics are absent, and notable differences exist. This series provides the first demonstration of increased IgG4 expression in nasal lesions associated with intranasal drug use. Despite some similarities, the pathologic processes and IgG4-rich infiltrates in these 3 cases seem to represent a different phenomenon that is not IgG4-RD. Although these lesions contain abundant IgG4-positive cells, they should not be mistaken for or conflated with IgG4-RD.

Real-World Evaluation of Asthma Severity Following Endoscopic Sinus Surgery in Chronic Rhinosinusitis Patients.

This study aimed to evaluate the impact of endoscopic sinus surgery (ESS) on asthma severity up to 12 months after surgical intervention. Retrospective cohort. Tertiary care center. Patients with a history of asthma and Chronic Rhinosinusitis (CRS) who underwent ESS between 2013 and 2023 were included. Asthma severity was assessed according to current Global Initiative for Asthma (GINA) guidelines, classifying patients into mild, moderate, and severe based on medication requirements. Asthma severity was evaluated up to 3 months prior to ESS and 1-year post-ESS. Patients with aspirin-exacerbated respiratory disease (AERD) were excluded. Statistical analysis was performed using McNemar test and Wilcoxon signed-rank test to assess differences in asthma severity, medication doses, and number of medications. Sixty-five patients were included, of which 44 (67.7%) had CRS with nasal polyps (CRSwNP) and 21 (32.3%) had CRS without nasal polyps (CRSsNP). No significant differences were found in asthma severity pre- and post-ESS (P = .175). Similarly, no differences were found in ICS doses (P = .999), total number of prescribed medications (P = .157) or presence of exacerbations before and after ESS (P = .078). However, a significant increase in time from last rescue inhaler use was noted after ESS, increasing from a median of 6.71 to 23.1 weeks (P = .004). This study is the first to assess the impact of ESS on asthma severity in a real-world setting. Our findings suggest that ESS does not impact asthma severity classification. However, it might provide relief of asthma symptoms in the early postoperative period.

Activation of the PGE2-EP2 pathway as a potential drug target for treating eosinophilic rhinosinusitis.

Current treatments of eosinophilic chronic rhinosinusitis (ECRS) involve corticosteroids with various adverse effects and costly therapies such as dupilumab, highlighting the need for improved treatments. However, because of the lack of a proper mouse ECRS model that recapitulates human ECRS, molecular mechanisms underlying this disease are incompletely understood. ECRS is often associated with aspirin-induced asthma, suggesting that dysregulation of lipid mediators in the nasal mucosa may underlie ECRS pathology. We herein found that the expression of microsomal PGE synthase-1 (encoded by PTGES) was significantly lower in the nasal mucosa of ECRS patients than that of non-ECRS subjects. Histological, transcriptional, and lipidomics analyses of Ptges-deficient mice revealed that defective PGE2 biosynthesis facilitated eosinophil recruitment into the nasal mucosa, elevated expression of type-2 cytokines and chemokines, and increased pro-allergic and decreased anti-allergic lipid mediators following challenges with Aspergillus protease and ovalbumin. A nasal spray containing agonists for the PGE2 receptor EP2 or EP4, including omidenepag isopropyl that has been clinically used for treatment of glaucoma, markedly reduced intranasal eosinophil infiltration in Ptges-deficient mice. These results suggest that the present model using Ptges-deficient mice is more relevant to human ECRS than are previously reported models and that eosinophilic inflammation in the nasal mucosa can be efficiently blocked by activation of the PGE2-EP2 pathway. Furthermore, our findings suggest that drug repositioning of omidenepag isopropyl may be useful for treatment of patients with ECRS.

Type 1 Kounis syndrome: recurrent myocardial infarctions in a patient with aspirin-exacerbated respiratory disease: a case report

Introduction. We present a case of type 1 Kounis syndrome in a patient with recurrent myocardial infarction with non-obstructive coronary arteries (MINOCA) due to allergic coronary vasospasm. Awareness of doctors about this pathology will allow identifying the MINOCA causes and prescribing pathogenetic treatment.Brief description. A 51-year-old woman with aspirin-exacerbated respiratory disease (asthma, rhinosinusitis with nasal polyposis, aspirin hypersensitivity, eosinophilia) without cardiovascular risk factors developed three recurrent myocardial infarctions against the background of vasospastic angina over a 6-month period. Despite the typical clinical performance, stable ST segment elevation, unchanged coronary arteries on coronary angiography, the vasospastic MI was not immediately established. The patient received long-term treatment for type 1 MI, including beta-blockers. Recurrent MI occurred against the background of an asthma attack. During the second and third hospitalization for MI, coronary angiography revealed a spasm of the right coronary artery, which completely resolved with the nitroglycerin administration. Intracoronary ultrasound made it possible to rule out atherosclerotic involvement of the infarct-related artery. Subsequently, microvascular angina developed, which was confirmed by positron emission tomography. Vasospastic angina in combination with microvascular angina, MIBOCA with asthma attacks, were regarded as type 1 Kounis syndrome. Over the next 2 years, the patient received pathogenetic treatment, and no recurrent cardiovascular events were observed.Discussion. Lack of awareness about Kounis syndrome led to incomplete examination of the patient with MIBOCA and the prescription of pathogenetically unreasonable tehrapy, which could contribute to recurrent MI within 6 months.

Efficacy and safety of dupilumab in the treatment of CRSwNP in the real-life setting: a review of the literature.

The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking. A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment. 15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic. Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.

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 &gt;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 hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

Biologic Therapies across Nasal Polyp Subtypes.

Chronic rhinosinusitis with nasal polyposis is a common inflammatory condition, with subtypes like aspirin-exacerbated respiratory disease, allergic fungal rhinosinusitis, and central compartment atopic disease sharing a common type 2 inflammatory pathway. Respiratory biologic therapies have been developed that target type 2 inflammation. In this article, we discuss the use of respiratory biologic therapies for nasal polyposis in general, as well as within the various subtypes of nasal polyps. Further, we discuss future roles of novel biologic therapies targeting type 2 inflammation in nasal polyposis.

Management of chronic rhinosinusitis with nasal polyps in the Asia-Pacific region and Russia: Recommendations from an expert working group.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory condition of the nasal and paranasal tissues, characterized by the presence of bilateral nasal polyps. An expert panel of specialists from the Asian-Pacific region and Russia was convened to develop regional guidance on the management of CRSwNP through a consensus approach. The present article presents the chief observations and recommendations from this panel to provide guidance for clinicians in these areas. Etiology and pathogenetic mechanisms in CRSwNP are heterogeneous and complex. In many patients, CRSwNP is primarily driven by type 2 inflammation, although this may be less important in Asian populations. Frequent comorbidities include asthma and other inflammatory diseases such as non-steroidal anti-inflammatory drug (NSAID)/aspirin-exacerbated respiratory disease or atopic dermatitis. Clinical management of CRSwNP is challenging, and a multidisciplinary approach to evaluation and treatment is recommended. While many patients respond to medical treatment (topical irrigation and intranasal corticosteroids, and adjunctive short-term use of systemic corticosteroids), those with more severe/uncontrolled disease usually require endoscopic sinus surgery (ESS), although outcomes can be unsatisfactory, requiring revision surgery. Biological therapies targeting underlying type 2 inflammation offer additional, effective treatment options in uncontrolled disease, either as an alternative to ESS or for those patients with persistent symptoms despite ESS.

Utilization of protocols to lower daily aspirin dose before surgical procedures for patients with aspirin-exacerbated respiratory disease

Utilization of protocols to lower daily aspirin dose before surgical procedures for patients with aspirin-exacerbated respiratory disease