NSAID-exacerbated Respiratory Disease Research Articles

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.

Contribution of dipeptidyl peptidase 10 to airway dysfunction in patients with NSAID-exacerbated respiratory disease.

Genetic variants of dipeptidyl peptidase 10 (DPP10) have been suggested to contribute to the development of NSAID-exacerbated respiratory disease (NERD). However, the mechanisms of how DPP10 contributes to NERD phenotypes remain unclear. To demonstrate the exact role of DPP10 in the pathogenesis of NERD. Patients with NERD (n=110), those with aspirin-tolerant asthma (ATA, n=130) and healthy control subjects (HCs, n=80) were enrolled. Clinical characteristics were analysed according to the serum DPP10levels in both NERD and ATA groups. The function of DPP10 in airway inflammation and remodelling was investigated with in vitro, ex vivo and in vivo experiments. NERD patients had higher levels of serum DPP10 and TGF-β1 with lower FEV1 than ATA patients or HCs (p<.05 for each). NERD patients with higher DPP10levels had higher TGF-β1, but lower FEV1 (p<.05 for all), whilst no differences were noted in ATA patients. Moreover, the seum DPP10levels had a positive correlation with TGF-β1 (r=0.384, p<.001), but a negative correlation with FEV1 (r=-0.230, p=.016) in NERD patients. In in vitro studies, expression of DPP10 in airway epithelial cells was enhanced by TGF-β1 treatments. Furthermore, DPP10 was found to be produced from immune cells and this molecule induced the ERK phosphorylation in airway epithelial cells, which was suppressed by anti-DPP10 treatment. In asthmatic mouse models, increased levels of DPP10 in the serum and TGF-β1 in the bronchoalveolar lavage fluid were noted, which were suppressed by anti-DPP10 treatment. Moreover, anti-DPP10 treatment inhibited the ERK phosphorylation and extracellular matrix deposition in the lungs. These findings suggest that increased production of DPP10may contribute to TGF-β1-mediated airway dysfunction in NERD patients, where blockade of DPP10may have potential benefits.

Evaluating the Safety of Non-Steroidal Anti-inflammatory Drugs use in Asthmatic Patients: A Systematic, Critical Review of Literature

Background: Evidence suggest avoidance of Non-steroidal anti-inflammatory drugs (NSAID) in aspirinintolerantasthmatics due to the risk of triggering exacerbation attack; however, evidence around avoidingNSAIDs in all other asthmatic patients are unclear. This study aimed to evaluate the evidence surroundingthe safety of using NSAIDs, including selective COX-2 inhibitors, among asthmatic patients.Methods: A systematic review used Medline (OVID), Scopus and Embasefrom January-2008 toJanuary-2019. Inclusion criteria includedEnglish, and human studies that evaluated the use of NSAID inasthmatics. Data was screened/extracted using a pre-designed data extraction form using Covidence®,thenwere critically appraised.Conclusion: Of the 49 identified studies,eight were eligible. Prevalence of NSAID-induced asthmaexacerbation was 9%(95%CI:6.0–12.0%)-9.9% (95%CI:9.4-10.5%). Asthmatics who were aspirin/NSAIDintolerant had 37% higher risk of hospitalisation compared to tolerant patients (RR:1.37; 95%CI:1.12–1.67).Use of COX-2 inhibitors showed non-significant associations with worsening respiratory symptoms/exacerbation. Only low-quality evidence was found for the safety of topical NSAID. NSAIDs-inducedrespiratory reactions/symptoms is relatively uncommon with the majority of asthmatic patients couldtolerate NSAIDs therapy. Asthmatic patients who suffer from aspirin-induced asthma or NSAIDsexacerbatedrespiratory disease (NSAIDs intolerant) should be avoided NSAIDs prescribing but could besafely prescribed selective COX-2 inhibitors as an alternative.

Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity. To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA. Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction. The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002). Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.

Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease.

Non-steroidal Anti-inflammatory drugs (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyposis, chronic rhinosinusitis, adult-onset asthma and hypersensitive reactions to cyclooxygenase-1 (COX-1) inhibitors. Among the available treatments for this disease, a combination of endoscopic sinus surgery followed by aspirin desensitization and aspirin maintenance therapy has been an effective approach. Studies have shown that long-term aspirin maintenance therapy can reduce the rate of nasal polyp recurrence in patients with N-ERD. However, the exact mechanism by which aspirin can both trigger and suppress airway disease in N-ERD remains poorly understood. In this review, we summarize current knowledge of aspirin effects in N-ERD, cardiovascular disease, and cancer, and consider potential mechanistic pathways accounting for the effects of aspirin in N-ERD.

Baseline Conservative and Surgical Management in the Treatment of NSAID-Exacerbated Respiratory Disease.

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a chronic medical condition that includes asthma, chronic rhinosinusitis with nasal polyposis, and hypersensitivity to aspirin and other NSAIDs. Eosinophilic inflammation in the upper and lower airways is treated with local corticosteroids, repeated antibiotics, oral corticosteroid courses, endoscopic sinus surgery, and in some cases aspirin treatment after desensitization (ATAD). Nevertheless, the disease may be uncontrolled and it has a great impact on quality of life. A better understanding of the pathomechanisms of the disease and the development of medications that target type 2 inflammation mediators may have a crucial role in achieving better disease control in patients with N-ERD.

Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug-Induced Acute Urticaria/Angioedema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity reactions, probably due to their high consumption worldwide. The most frequent type of NSAID hypersensitivity is NSAID cross-hypersensitivity, in which patients react to NSAIDs from different chemical groups in the absence of a specific immunological response. The underlying mechanism of NSAID cross-hypersensitivity has been linked to cyclooxygenase (COX)-1 inhibition causing an imbalance in the arachidonic acid pathway. Despite NSAID-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype, most studies have focused on NSAID-exacerbated respiratory disease. As NSAID cross-hypersensitivity reactions are idiosyncratic, only appearing in some subjects, it is believed that individual susceptibility is under the influence of genetic factors. Although associations with polymorphisms in genes from the AA pathway have been described, no previous study has evaluated the potential role of cytosolic phospholipase A2 (cPLA2) variants. This enzyme catalyzes the initial hydrolysis of membrane phospholipids to release AA, which can be subsequently metabolized into eicosanoids. Here, we analyzed for the first time the overall genetic variation in the cPLA2 gene (PLA2G4A) in NIUA patients. For this purpose, a set of tagging single nucleotide polymorphisms (tagSNPs) in PLA2G4A were selected using data from Europeans subjects in the 1,000 Genomes Project, and genotyped with the iPlex Sequenom MassArray technology. Two independent populations, each comprising NIUA patients and NSAID-tolerant controls, were recruited in Spain, for the purposes of discovery and replication, comprising a total of 1,128 individuals. Fifty-eight tagSNPs were successfully genotyped in the discovery cohort, of which four were significantly associated with NIUA after Bonferroni correction (rs2049963, rs2064471, rs12088010, and rs12746200). These polymorphisms were then genotyped in the replication cohort: rs2049963 was associated with increased risk for NIUA after Bonferroni correction under the dominant and additive models, whereas rs12088010 and rs12746200 were protective under these two inheritance models. Our results suggest a role for PLA2G4A polymorphisms in NIUA. However, further studies are required to replicate our findings, elucidate the mechanistic role, and evaluate the participation of PLA2G4A variants in other phenotypes induced by NSAID cross-hypersensitivity.

Aspirin desensitization in NSAID-exacerbated respiratory disease and its outcomes in the clinical course of asthma: A systematic review of the literature and meta-analysis

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) might benefit from aspirin desensitization (AD) as an alternative treatment to standard care. However, there is conflicting evidence regarding its role in bronchial symptoms and asthma exacerbations. To analyze the clinical effects of AD in terms of lung function, systemic and inhaled steroid use, the frequency of acute asthma exacerbations, and adverse effects in patients with NERD and asthma. We identified randomized clinical trials (RCTs) from PubMed, EMBASE, SCOPUS, and EBSCO. We also searched the RCT references for additional studies. Studies comparing AD to placebo in patients with a previous history of pulmonary symptoms triggered by ASA or other NSAIDs or with a positive provocation test to ASA were included. Five studies with 210 participants with NERD were included in this review. The study duration ranged from 3 to 6 months. Overall, the risk of bias across the included RCTs was low. We identified 3 studies evaluating lung function, 2 of which reported a significant improvement in FEV1 in the AD group after 6 months, while the other reported no difference among the treatments. Due to high heterogeneity, we did not pool the results. The remaining primary outcomes were reported only in a single study each, hindering their interpretation. Secondary outcomes revealed reduced symptom and medication scores in patients with AD. Due to the small number of studies included in this systematic review, conclusions should be made with caution. AD shows a trend towards improving lung function (FEV1) following 6 months of treatment, although no conclusions can be made regarding the use of corticosteroids or the frequency of acute exacerbations. AD appears to reduce both symptom and medication scores. Additional RCTs are needed to fully assess the efficacy of AD in reducing bronchial symptoms in patients with NERD.

NSAID-Exacerbated Respiratory Disease in Patients with Nasosinusal Polyposis in the Othorhynolaringology service at Hospital de Clinicas, Paraguay, from January, 2016 to June, 2020.

NSAID-Exacerbated Respiratory Disease in Patients with Nasosinusal Polyposis in the Othorhynolaringology service at Hospital de Clinicas, Paraguay, from January, 2016 to June, 2020.

Cytosolic Phospholipase A2 (PLA2G4A) Polymorphisms Associated with Acute Urticaria/angioedema Induced by Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the main triggers of drug hypersensitivity, probably due to their high consume worldwide, with NSAIDs-induced acute urticaria/angioedema (NIUA) being the most frequent clinical phenotype. Nevertheless, most studies have focused on NSAIDs-exacerbated respiratory disease. NSAID-hypersensitivity occurs only in some individuals, mainly by the increased release of cysteinyl-leukotrienes from arachidonic acid due to COX-1 inhibition. Thus, individual susceptibility to NSAID-hypersensitivity may be under the influence of genetic factors.

Clinical Characteristics, Urinary Leukotriene E4 Levels, and Aspirin Desensitization Results in Patients With NSAID-Induced Blended Reactions.

PurposeData on non-steroidal anti-inflammatory drug (NSAID) hypersensitivity in Southeast Asia are scarce. Increased urinary leukotriene E4 (uLTE4) levels have been suggested as a biomarker of NSAID-exacerbated respiratory disease (NERD). This study investigated clinical patterns of NSAID sensitivity in Thailand and the diagnostic roles of uLTE4 measurement in various phenotypes.MethodsThe clinical phenotypes in 92 Thai adults with cross-reactive NSAID hypersensitivity were characterized based on the clinical history and drug provocation. The uLTE4 levels were measured at baseline, after aspirin provocation and after desensitization.ResultsMore than half of the patients (56.5%) presented with cutaneous symptoms (NSAID-exacerbated cutaneous disease), while one-third (33.7%) developed symptoms in at least 2 systems (NSAID-induced blended reactions; NIBR). Fifty-two patients underwent drug provocation and 59.6% of them yielded positive results. After drug provocation, a significant number of patients with confirmed NSAID cross-reactivity experienced clinical symptoms in more than one organ system. The uLTE4 levels at baseline were comparable between the NSAID-tolerant and NSAID-sensitive groups, but were substantially increased after aspirin provocation predominantly in NERD (983.4 pg/mg creatinine) and NIBR (501.0 pg/mg creatinine) compared to NSAID-tolerant subjects (122.1 pg/mg creatinine, P < 0.01 and 0.05, respectively). The uLTE4 levels were elevated after aspirin desensitization, although nasal polyposis and asthma were under control in 3 NERD and 3 NIBR subjects.ConclusionsNIBR is not uncommon among NSAID-sensitive patients in Thailand. The diagnostic value of basal uLTE4 levels was limited, but increased uLTE4 levels upon aspirin provocation suggest NSAID cross-reactivity with respiratory components. This study indicates that aspirin desensitization, if necessary, might be effective in both NERD and NIBR.Trial RegistrationClinicalTrials.gov Identifier: NCT03849625

Lung function and side effects of Aspirin desensitization: a real world study

ABSTRACT Introduction: NSAID-exacerbated respiratory disease (N-ERD) is mainly treated with topical and oral corticosteroids, as well as acetylsalicylic acid (ASA) treatment after desensitization (ATAD). During desensitization and ATAD, it is common to experience an exacerbation of respiratory symptoms and other side effects, which may lead to cessation of treatment. Objectives: The aim of this retrospective follow-up study was to evaluate the effect of ATAD on lung functions and respiratory symptoms, and to clarify the occurrence of adverse events. Methods: We analysed the patient data of 67 patients treated with ASA desensitization between 2006 and 2016 in three hospitals, concerning adverse events, respiratory symptoms, lung function tests, and reasons for discontinuation. Results: 26 patients discontinued AD or ATAD. The most common reasons for discontinuation were lack of response (9%) and side effects (18%). ATAD did not affect lung function values in the follow-up of up to 5 years. Upper respiratory symptoms improved in 31 (52%) and lower respiratory symptoms (LRS) in 7 (10%) cases. Side effects occurred in 42 (63%) cases, the most common being dyspepsia and lower respiratory symptoms. Conclusion: Our study suggests that ATAD has little effect on lower airway functions. Side effects were common, and discontinuation rates high.

Role of systemic immune-inflammation index in asthma and NSAID-exacerbated respiratory disease.

Asthma is a heterogeneous disease characterized by chronic progressive airway inflammation. Although the disease has numerous phenotypes, there are no practical biomarkers for distinguishing the phenotypes from one another. To address this challenge, we aimed to reveal whether the systemic immune-inflammation index (SII), an important indicator of systemic inflammation and prognosis in various malignancies and vasculitis, can be used for distinguishing between asthma and NSAID-exacerbated respiratory disease (NERD). The study enrolled 105 patients (asthma: n = 69; NERD: n = 36). SII was calculated using the formula of neutrophil X platelet/lymphocyte number. Major risk factors, namely ACT score, eosinophil level, total IgE level, N-L ratio (NLR), P-L ratio (PLR), and SII, were evaluated by logistic regression analysis. No significant differences were found between the clinical features of the two study groups. Patients with an SII value ≥895.6 had a probability of having NERD with a sensitivity of 30.56%, whereas those with a lower SII had a probability of having asthma with a sensitivity of 92.65%. In the logistic regression analysis, no risk factor was determined for identifying asthma or NERD. The N-L ratio was found to be the risk factor affecting categorized SII (OR=264.2, 95% CI 9.9-7046.5, P=0.001). This is the first study to evaluate SII as a tool for differentiating asthma phenotypes. The presence of SII below the cutoff value can help exclude the diagnosis of NERD. There is a need for large-scale prospective studies to compare different phenotypes and determine the optimal cutoff value.