NSAID-exacerbated Respiratory Disease Research Articles

Tolerance to acetyl-salicylic acid in NSAID-exacerbated respiratory disease after biological therapies with benralizumab, dupilumab, mepolizumab or omalizumab.

There are no head-to-head studies comparing the efficacy or effectiveness of biological therapies in patients with non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). We aim to study the induction of NSAID tolerance after biologic therapy in NSAID-ERD patients.

The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A2 is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D2 metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E2 leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.

Investigation of the Relationship between Aspirin-Sensitivity and Poor Response to Medical Management in NSAIDs-exacerbated Respiratory Disease Patients with Sinonasal Polyposis.

NSAID-exacerbated respiratory disease (N-ERD) is a highly heterogeneous disorder with various clinical symptoms. The aspirin challenge test is a gold standard method for its diagnosis, and there are still no reliable in vitro diagnostic biomarkers yet. Oral challenge tests are time-consuming and may be associated with a risk of severe systemic reactions. This study aimed to evaluate whether patients with poor responses to medical management are more susceptible to being aspirin-sensitive. In this cohort study, after CT scanning of all patients and subject selection, conventional medical treatment was started as follows and continued for three consecutive months: at first, saline nose wash twice per day, intranasal beclomethasone spray one puff in each nostril twice per day, montelukast 10 mg tablet once daily, a ten-day course of oral prednisolone starting with the dose of 25 mg per day and taper and discontinued thereafter. Sinonasal outcome test 22 (SNOT22) was used for the evaluation of symptom severity. Statistical analyses were performed with SPSS version 23, and data were analyzed using an independent samples T-test, paired T-test, and Receiver operating curve analysis. 25 males and 53 females were enrolled in this study, with an average age of 41.56 ± 11.74 years old (18-36). Aspirin challenge test results were positive in 29 (37.2%) patients. The average SNOT22 scores before the treatment were 52.97 ± 17.73 and 47.04 ± 18.30 in aspirin-sensitive and aspirin-tolerant patients, respectively, and decreased to 27.41 ± 16.61 and 24.88 ± 16.72 in aspirin-sensitive and aspirin-tolerant patients after the treatment, respectively. There was no significant difference in SNOT22 scores between the groups. The severity of symptoms before treatment and clinical improvement after treatment are not good predictors of N-ERD.

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease.

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma and intolerance to NSAIDs. Dupilumab treatment, targeting the interleukin-4 (IL-4) receptor α, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease and nasal cytokine profiles in patients with N-ERD. In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for 6 months. Clinical parameters (e.g. total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing and blood, nasal and urine sampling were monitored at regular intervals for up to 6 months after starting dupilumab therapy. Of the 31 patients included in the study, 30 completed both aspirin provocation tests. After 6 months of treatment with dupilumab, 23% of patients (n=7 of 30) developed complete aspirin tolerance and an additional 33% of patients (n=10 of 30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: -2.68±1.84, p<0.001), while pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001) and olfactory performance improved (University of Pennsylvania Smell Identification Test: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urinary leukotriene E4 levels and their improvement in clinical parameters was associated with a reduction of eotaxin-1, C-C motif chemokine ligand 17, IL-5, IL-17A and IL-6. In this study, 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

Which non-steroidal anti-inflammatory drug (NSAID) is safer in patients with Non-steroids Exacerbated Respiratory Disease (N-ERD)? A single-center retrospective study.

In patients with NSAID-Exacerbated Respiratory Disease (N-ERD), respiratory symptoms occur as a result of the use of cyclooxygenase (COX)-1 inhibitor non-steroidal anti-inflammatory drugs (NSAIDs). Patients with N-ERD generally tolerate selective COX-2 inhibitor NSAIDs. However, respiratory symptoms may be exacerbated in patients with N-ERD due to the intake of selective COX-2 inhibitor NSAIDs. The aim of this study was to evaluate which selective or partial COX-2 inhibitor NSAID is safer in patients with N-ERD. Forty-nine patients with a history of respiratory hypersensitivity reactions to NSAIDs (N-ERD) who underwent a drug challenge test with celecoxib, nimesulide, meloxicam, and paracetamol between January 2021-April 2022 were retrospectively evaluated. Of the 49 patients who underwent the drug challenge tests, 16 (32.7%) were male and 33 (67.3%) were female and the mean age was 37.67 ± 11.62 years. The most common comorbidities were chronic urticaria [n= 21 (42.9%)] and allergic rhinitis [n= 21 (42.9%)]. As a result of drug challenge tests, celecoxib, nimesulide, meloxicam, and paracetamol drug challenge tests were positive in 2 (4.1%), 8 (16.3%), 7 (14.3%) and 11 (22.4) patients, respectively. The rate of allergic reaction to celecoxib was statistically significantly lower than other drugs (p= 0.001). In paired comparisons of the drugs, the allergic reaction rate with celecoxib was statistically significantly lower than with nimesulide (p= 0.031) and paracetamol (p= 0.004). Selective COX-2 inhibitor NSAIDs are safe in patients with N-ERD. NSAIDs should be prescribed to these patients following general medical precautions and drug challenge tests.

Urinary Leukotriene E4 as a Biomarker in NSAID-Exacerbated Respiratory Disease (N-ERD): a Systematic Review and Meta-analysis.

Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE4) has been extensively investigated as potential biomarker in N-ERD. We aimed to assess the usefulness of uLTE4 as a biomarker in the diagnosis of N-ERD. N-ERD, formerly known as aspirin-intolerant asthma (AIA), is characterised by increased leukotriene production. uLTE4 indicates cysteinyl leukotriene production, and a potential biomarker in N-ERD. Although several studies and have examined the relationship between uLTE4 and N-ERD, the usefulness of uLTE4 as a biomarker in a clinical setting remains unclear. Our literature search identified 38 unique eligible studies, 35 were included in the meta-analysis. Meta-analysis was performed (i.e. pooled standardised mean difference (SMD) with 95% confidence intervals (95% CI)) and risk of bias assessed (implementing Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Cochrane DTA)). Data from 3376 subjects was analysed (1354N-ERD, 1420 ATA, and 602 HC). uLTE4 was higher in N-ERD vs ATA (n = 35, SMD 0.80; 95% CI 0.72-0.89). uLTE4 increased following aspirin challenge in N-ERD (n = 12, SMD 0.56; 95% CI 0.26-0.85) but not ATA (n = 8, SMD 0.12; CI - 0.08-0.33). This systematic review and meta-analysis showed that uLTE4 is higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE4 following aspirin challenge. However, due to the varied uLTE4 measurement and result reporting practice, clinical utility of these findings is limited. Future studies should be standardised to increase clinical significance and interpretability of the results.

A new classification option for NSAID hypersensitivity: Kalyoncu classification.

The European Network for Drug Allergy (ENDA) proposed a consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in 2011. A subgroup of patients with NSAIDs-exacerbated respiratory disease (NERD) develop urticaria/angioedema type reactions in response to NSAIDs. The Kalyoncu classification might be a novel option to classify patients with NSAID hypersensitivity (NH). In this study, we compare the ENDA and the Kalyoncu classifications. This study enrolled a total of 196 patients. NH reaction types were categorized as asthma, rhinitis, urticaria/angioedema and anaphylaxis. Based on the reaction history and oral provocation test findings, patients were grouped according to ENDA and Kalyoncu classifications. The mean age of the 196 patients was 40.32±13.28 years, and 130 (66.3%) of them were female. Under the ENDA and Kalyoncu classifications, the most common NH subgroups were NERD (32%), and isolated NH (34.2%), the least prevalent NH subgroups were single NSAID-induced delayed reactions (SNIDR) (1.5%), and pseudo Samter's syndrome (11.7%). Our research revealed that the Kalyoncu classification is more descriptive of patients with NERD exhibiting urticaria/angioedema-type reactions. It also provides future risk assessment for development of NERD. For controversial cases, the Kalyoncu classification can be utilized as a new complimentary option alone or in conjunction with ENDA classification.

SAMTER'S TRIAD IN A 9 YEARS-OLD PATIENT: A CASE REPORT

<h3>Introduction</h3> Samter's triad, associating asthma, nasal polyposis, and NSAIDs hypersensitivity, is rarely documented in children. The pathophysiology of such condition is probably related to a dysregulation of arachidonic acid metabolism, with a consequent imbalance between pro-inflammatory and anti-inflammatory mediators. <h3>Case Description</h3> A 9 years-old boy came to our clinic with partially controlled non atopic asthma. Suffering from a concomitant chronic rhinosinusitis, a sinus CT scan was performed, revealing the presence of nasal polyposis. Genetic disorders, and other different etiologies were excluded. Polyp surgery allowed the disappearance of local symptoms and the control of asthma symptoms. The same patient also presented an anaphylactic reaction (hypotonia, vomiting, urticaria and asthma) immediately after taking 400 mg of Ibuprofen. Oral challenges were positive for ibuprofen and diclofenac, and he was diagnosed as suffering from NSAID-exacerbated respiratory disease (NERD), and, consequently, from Samter's triad. <h3>Discussion</h3> Such condition is extremely rare in pediatrics. In fact, nasal polyposis is rarely described in the pediatric population, in children non-suffering from other underlying systemic diseases, mainly cystic fibrosis. Also, the most common form of NSAIDs hypersensitivity in children is the one associated with induced urticaria/oedema, while NERD remains less common. For these reasons, the clinical report we presented needs to be considered as a rare presentation of Samter's triad in a young, non-adolescent child and make us underline that, pediatricians, should look for such diagnosis even in younger patients.

Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease.

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical trials for omalizumab, dupilumab, mepolizumab and benralizumab in CRSwNP have demonstrated favourable outcomes. Moving forward, direct comparisons among biologicals, refining patient selection criteria for specific biologicals, determining optimal treatment duration and monitoring long-term outcomes are areas of emerging interest. This review summarizes the clinical evidence from the recent 2 years on the role of biologicals in severe CRSwNP and N-ERD, and proposes an approach towards decision-making in their use.

Concurrent management of nasal bone expansion from nasal polyposis (Woakes' disease)

BackgroundWoakes' disease is the eponymous name for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) leading to thinning and expansion of the nasal pyramid. The endoscopic treatment of the sinus disease, while extensive, is standard practice for the rhinologist. Management of their external nasal deformities, for many, is not. Simultaneous closed rhinoplasty in these patients is straightforward, easy to perform and achieves an excellent esthetic outcome.MethodsThree patients with CRSwNP and notable nasal pyramid expansion are reviewed. All patients had eosinophilic disease, with two having NSAID‐exacerbated respiratory disease (N‐ERD). All three patients underwent full house endoscopic sinus surgery from May 2018 to September 2019 along with simultaneous closed rhinoplasty. Two of these patients required only external digital pressure to fracture the nasal bones for gentle Boies elevator repositioning, while the third had osteotomies with minimal force to aid reduction.ResultsPostoperatively, patients had excellent nasal airway symptom improvement, and the cosmetic results following rhinoplasty demonstrated normalization of symmetry, profile, and contour of the nose with high‐patient satisfaction.ConclusionBased on our experience, simultaneous rhinoplasty on the thinned nasal bones of Woakes' Disease patients is not only easy to perform, but provides excellent cosmetic and functional results by allowing bone to remodel in the appropriate position, and avoids a second‐stage rhinoplasty.

The Role of Omalizumab in NSAID-Exacerbated Respiratory Disease: A Narrative Review

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is a condition characterized by the triad of chronic rhinosinusitis with nasal polyps, bronchial asthma, and hypersensitivity to nonsteroidal anti-inflammatory drugs. This article explores the current knowledge on the various pathological mechanism(s) of N-ERD-such as arachidonic acid metabolism, cysteinyl leukotrienes, prostaglandins, platelets, IgE, mast cells, eosinophils, basophils, and innate immune system-and the role of omalizumab in its management. The authors dive deep into the role of IgE in N-ERD and its potential as a therapeutic target. IgE plays a significant role in mediating allergic reactions, is intricately linked with mast cells, interacts with multiple immunopathological pathways involved in N-ERD, and tends to be elevated in patients with N-ERD. Multiple real-world studies, observational studies, and case series, as well as 2 phase III trials, have demonstrated the effectiveness of omalizumab in the management of N-ERD. For a disease with such a well-documented history, the pathophysiology of N-ERD and the most effective ways to manage it remain a mystery. With this background, the authors ask-is IgE a missing piece of the N-ERD puzzle, thus explaining the efficacy of omalizumab in the treatment of the disease?

Polymorphisms in Human IL4, IL10, and TNF Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease.

Background: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. Methods: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. Results: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. Conclusions: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.

Investigating the secondary care system burden of CRSwNP in sinus surgery patients with clinically relevant comorbidities using the HES database.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic condition that can adversely affect quality of life for patients. There is no cure for CRSwNP, and patients may require intermittent systemic corticosteroids (SCS) and surgery in addition to intranasal treatment throughout their lifetime. This places a significant burden on the NHS which can be compounded by comorbid conditions such as asthma or NSAID-exacerbated respiratory disease (NERD). Patients with comorbidities are likely to experience higher rates of surgery and more secondary care visits. The aim of this study was to evaluate revision rates and the associated burden for patients with CRSwNP undergoing surgery and compare this to sub-cohorts of patients with comorbidities. This study has utilised the Hospital Episodes Statistics (HES) database across a ten-year time period (April 2010 to March 2020) to investigate the NHS resource use attributable to CRSwNP for all patients with the condition who have undergone sinus surgery, and to examine the burden of clinically relevant sub-groups. Our results showed that 101,054 patients underwent at least one sinus surgery in relation to their nasal polyps, with Kaplan Meier survival analysis estimating that the 10-year probability of revision is between 71-90% for comorbid patients, and 51% for non-comorbid patients. Patients with a relevant comorbid condition in addition to their CRSwNP were up to 4.7 times more likely to undergo at least one revision surgery during the ten-year analytical time window when compared to patients without a comorbidity. Further to this, comorbid patients had a higher tariff associated with their CRSwNP care across the analytical time window and were therefore likely to be more costly to the healthcare system. In conclusion, this study demonstrates that there is a high burden attached to CRSwNP-related sinus surgery and that comorbidities are a key driver of NHS resource use.

Effects of non-steroidal anti-inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID-19.

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research.

Preoperative Sinonasal Computed Tomography Score in Chronic Rhinosinusitis with Nasal Polyps.

This study investigated the relationship between sinonasal inflammatory involvement according to the computed tomography (CT) staging system (Lund–Mackay score) with clinical, laboratory, histopathological and prognostic features of chronic rhinosinusitis with nasal polyps (CRSwNP). Seventy-eight patients with CRSwNP who had undergone surgery were enrolled. Total (p = 0.0062), ethmoid (p = 0.0496), sphenoid (p = 0.0335), ostiomeatal complex (OMC) (p = 0.0235) and frontal (p = 0.0164) CT scores were predictive of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD) in the univariate analysis. Total (p = 0.0022), ethmoid (p = 0.0290), sphenoid (p = 0.0370), frontal (p = 0.0116), maxillary (p = 0.0357) and OMC (p = 0.0058) CT scores were predictve of asthma at the univariate analysis. No significant differences were found between patients with vs. without allergy in terms of total and partial CT scores. High blood eosinophil counts (>0.24 vs. ≤0.24 cells × 109/L) resulted in being associated with total (p = 0.0213), maxillary (p = 0.0227) and ethmoid (p = 0.0491) CT scores in the univariate analysis. Higher ethmoid (p = 0.0006) and total sinonasal (p = 0.0027) CT scores were found to predict histopathologically eosinophil CRSwNPs in the univariate analysis. CT scores did not result as predictive of NSAID-exacerbated respiratory disease, asthma, or blood eosinophil count at the multivariate analysis. Risk of relapse was related to the presence of NERD (p = 0.0207, HR [95% CI] 3.914 [1.232–12.435]), higher preoperative total (HR = 1.098 95%CI: 1.001–1.204, p = 0.0486) and frontal sinus CT scores (HR = 1.555 95%CI: 1.006–1.886, p = 0.0218), but these results were not confirmed by the multivariable analysis. Sinonasal CT scores showed significant differences in this heterogeneous inflammatory condition. Identifying CRSwNP characteristics is necessary to avoid generic treatments with poor outcomes.

NSAID-exacerbated respiratory disease: a population study.

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) may exacerbate respiratory symptoms. A recent European Academy of Allergy and Clinical Immunology position paper recommended the use of an acronym, N-ERD (NSAID-exacerbated respiratory disease), for this hypersensitivity associated with asthma or chronic rhinosinusitis with or without nasal polyposis. Our aim was to estimate the prevalence of N-ERD and identify factors associated with N-ERD.MethodsIn 2016, a cross-sectional questionnaire survey of a random adult population of 16 000 subjects aged 20–69 years was performed in Helsinki and Western Finland. The response rate was 51.5%.ResultsThe prevalence was 1.4% for N-ERD, and 0.7% for aspirin-exacerbated respiratory disease (AERD). The prevalence of N-ERD was 6.9% among subjects with asthma and 2.7% among subjects with rhinitis. The risk factors for N-ERD were older age, family history of asthma or allergic rhinitis, long-term smoking and exposure to environmental pollutants. Asthmatic subjects with N-ERD had a higher risk of respiratory symptoms, severe hypersensitivity reactions and hospitalisations than asthmatic subjects without N-ERD. The subphenotype of N-ERD with asthma was most symptomatic. Subjects with rhinitis associated with N-ERD, which would not be included in AERD, had the fewest symptoms.ConclusionWe conclude that the prevalence of N-ERD was 1.4% in a representative Finnish adult population sample. Older age, family history of asthma or allergic rhinitis, cumulative exposure to tobacco smoke, secondhand smoke, and occupational exposures increased odds of N-ERD. N-ERD was associated with significant morbidity.

POSB143 The Financial Burden of Surgically Managing Chronic Rhinosinusitis with Nasal Polyposis in England

Chronic rhinosinusitis with nasal polyposis (CRSwNP) characterised by type 2 inflammation imposes significant burden of illness. Many patients whose symptoms are uncontrolled by intranasal corticosteroids need repeated surgeries to alleviate rhinorrhea, nasal congestion, hyposmia and/or facial pressure. The objective of this study was to determine the financial burden due to surgically managed CRSwNP from an NHS perspective. Hospital Episode Statistics (HES) were used to capture the characteristics and costs for all CRSwNP patients with ≥1 sinus surgery in England between April 2010 and March 2020. Patients were stratified into subgroups based on the absence (NP-No Comorbidities (NC)) or presence of relevant comorbidities such as asthma only (NP-Asthma) or asthma with NSAID exacerbated respiratory disease, known as Samter’s triad (NP-ST). 101,054 patients were included in the study (64% (n=64,461) NP-NC, 31.7% (n=32,049) NP-Asthma, 4.5% (n=4,544) NP-ST). The total cost of treating these patients was £260 million, with surgery tariffs, inpatient tariffs and outpatient tariffs accounting for 66.8% (£173.8million), 11.3% (£29.3 million) and 21.9% (£57 million) respectively. The average surgery tariff for an NP-ST patient was £2,089, significantly higher than the tariff associated with the NP-Asthma (£1,755), and NP-NC (£1,676) subgroups (p<0.01). Both inpatient and outpatient average tariffs were numerically and statistically significantly higher for NP-ST and NP-Asthma patients compared to NP-NC patients. Combined inpatient and outpatient tariffs were £631 per NP-NC patient, rising to £1,103 and £2,253 for NP-Asthma and NP-ST patients respectively. Surgical management of CRSwNP constitutes a significant direct financial burden on the English healthcare system, particulary for patients with comorbidities. These patients, or those with a poor surgical prognosis, may benefit from the emerging novel biologic therapies which can reduce the clinical burden of disease. Such treatment strategies may also contribute to a reduction in the significant financial burden associated with surgical costs.

Clinical characteristics and aspirin desensitization in Thai patients with a suggestive history of NSAID-exacerbated respiratory disease.

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is characterized by the triad of chronic rhinosinusitis with nasal polyp, asthma, and aspirin (ASA) or NSAID hypersensitivity. Previous study of NERD has rarely been reported in Asian population. To investigate the clinical characteristics and outcomes of aspirin desensitization (ASAD) in Thai NERD. This retrospective chart review included patients with a suggestive history of NERD with or without ASAD from the Adult Allergy Clinic of Siriraj Hospital (Bangkok, Thailand) during January 2008 to December 2018. Ten NERD patients were recruited. The median age of onset was 30 years. Comorbid atopic diseases were found in 4 patients. Asthma control level was step 3 of the Global Initiative for Asthma (GINA) guideline or greater in all patients. Five patients had reactions to more than one NSAIDs. Ibuprofen was the most common culprit agent. Reactions frequently involved the respiratory and cutaneous systems. Four patients underwent ASAD followed by ingestion of ASA 300-600 mg daily. One patient discontinued ASA after taking ASA 600 mg daily for 3 months due to severe gastrointestinal side effect. The remaining three patients successfully continued ASA 300 mg daily as maintenance to control sino-nasal inflammation and to prevent recurrence of nasal polyp. None of the 4 patients required sinus surgery revision. NERD is a difficult-to-treat disease with unique clinical characteristics. ASAD followed by a maintenance dose of ASA 300 mg daily was found to be effective and well-tolerated in most patients.

Pathomechanisms of AERD—Recent Advances

The pathomechanisms behind NSAID-exacerbated respiratory disease are complex and still largely unknown. They are presumed to involve genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, altered cellular interactions involving transmetabolism, and continuous and chronic inflammation in the respiratory track. Here, we go through the recent advances on the topic and sum up the current understanding of the background of this illness that broadly effects the patients' lives.

A retrospective study on long-term efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease

PurposeAspirin treatment after desensitization (ATAD) represents an effective therapeutic option suitable for NSAID-exacerbated respiratory disease (N-ERD) patients with recalcitrant disease. Intranasal administration of lysine-aspirin (LAS) has been suggested as a safer and faster route than oral ATAD but evidence for its use is less strong. We investigated nasal LAS therapy long-term efficacy based on objective outcomes, smell function, polyp recurrence and need for surgery or rescue therapy. Clinical biomarkers predicting response to intranasal LAS, long-term side effects and consequences of discontinuing treatment have been evaluated.MethodsA retrospective analysis of a database of 60 N-ERD patients seen between 2012 and 2020 was performed in March 2021. They were followed up at 3-months, 1-, 2- and 3-years with upper and lower airway functions assessed at each follow-up.ResultsHigher nasal airflow and smell scores were found at each follow-up in patients taking LAS (p < 0.001 and p = 0.048 respectively). No influence of LAS on pulmonary function measurements was observed. Patient on intranasal LAS showed a lower rate of revision sinus surgery when compared to those who discontinued the treatment (p < 0.001). None of the variables studied was found to influence LAS treatment response.ConclusionOur study demonstrates the clinical effectiveness of long-term intranasal LAS in the management of N-ERD in terms of improved nasal airflow and olfaction and a reduced need for revision sinus surgery. Intranasal LAS is safe, being associated with a lower rate of side effects when compared to oral ATAD. However, discontinuation of the treatment at any stage is associated with a loss of clinical benefit.