NSAID-exacerbated Respiratory Disease Research Articles

Assessment of pediatric patients with suspected nonsteroidal anti-inflammatory drug hypersensitivity.

Background: Beta-lactam antibiotics are the most common cause of hypersensitivity reactions to medications, followed by nonsteroidal anti-inflammatory drugs (NSAID). Objective: The aim of this study was to classify children with hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAID-H) according to the latest updates. Methods: ENDA recommendations were used to evaluate all patients with suspected NSAID-H. Children were classified as either selective responders (SR) or cross-intolerant based on the results of the drug provocation test (DPT). Results: Sixty-seven patients with suspected NSAID-H were evaluated in this study. NSAID-H was confirmed in 20 patients (29.9%). Among the 20 patients diagnosed with NSAID-H, 15 were classified according to the 2018 EAACI/ENDA Position Paper. Twelve patients (80%) were classified as cross-intolerant and 3 (20%) as SRs. NSAID-H was confirmed in 4 of 37 patients (10.8%) ages <10 years and 16 of 30 patients (53.3%) ages >10 years (p < 0.001). Twelve patients ages >10 years were classified. Cross-intolerance was detected in nine patients (66.6%). In patients >10 years of age, NSAID-induced urticaria/angioedema (NIUA) (16.7%) was the most common type in the group with classifiable cross-intolerant. In addition, NSAID-exacerbated respiratory disease was detected in one patient. Conculsion: Ibuprofen is the most common NSAID-H drug used in children. NIUA is the most common reaction. In pediatric allergy, hypersensitivity to NSAIDs is a challenging diagnostic issue. Hypersensitivity to NSAIDs poses a challenging diagnostic issue in pediatric allergies. The oral challenge test is the main diagnostic tool; however, in clinical practice, performing multiple challenge tests is difficult.

Real-world effectiveness of dupilumab in a European cohort of CRSwNP (CHRINOSOR)

BackgroundPivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score (NPS), symptom and quality of life scores in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). ObjectiveWe evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary care centres. MethodologyNPS, SinoNasal Outcome Test (SNOT)-22 score, visual analogue scale (VAS) for total sinus symptoms, loss of smell (LoS) and nasal blockage (NB), and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline, 24 and 52 weeks of treatment of dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities and blood eosinophil counts (BEC). Treatment response was evaluated according to EUFOREA 2021 criteria. ResultsAll patient outcomes improved at 24 and 52 weeks of treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, NSAID exacerbated respiratory disease (NERD), allergy or baseline BEC. 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks respectively. 54.4% and 68.2% reached all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks respectively. ConclusionsReal-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks of treatment. Favourable treatment response was independent of the number of sinus surgery procedures, major comorbidities or baseline systemic levels of type 2 inflammation.

Efficacy of Biologics in NSAID-ERD: United Airways From the Nose to the Bronchi

NSAID-exacerbated respiratory disease (NSAID-ERD), the clinical triad of severe chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and respiratory reactions to cyclooxygenase 1 inhibitors, is often challenging to manage, with many patients failing first line therapies for CRSwNP and asthma. There are now six biologic mediations approved for asthma and/or severe CRSwNP: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab. With the availability of respiratory biologic treatment for both asthma and CRSwNP, clinicians now have a multitude of additional management options for patients with NSAID-ERD. Herein we will review the currently available clinical trial and real-world evidence for biologic efficacy and safety patients with NSAID-ERD, discuss the mechanisms of biologic therapy specific to NSAID-ERD, and review evidence regarding the use of biologic therapy versus endoscopic sinus surgery therapy for CRSwNP and NSAID-ERD. We will propose a management approach for choosing biologic therapy or endoscopic sinus surgery with aspirin therapy after desensitization for patients with NSAID-ERD.

Low-Salicylate Diet in Patients with Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease: Personalization of Indications to Dietary Treatment

Introduction: A particularly aggressive course of chronic sinusitis with nasal polyps is seen in patients with bronchial asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). These patients often report exacerbation associated with consumption of foods reach in salicylates. Therefore, the authors analyzed the effect of a low-salicylate diet (LSD) on the course of chronic sinusitis with polyps in patients with NSAID-exacerbated respiratory disease (N-ERD) to answer the question: which patients would obtain the best therapeutic benefit? Methods: Adult patients with N-ERD were selected for dietary intervention with LSD. Patients were seen on two occasions: at an initial visit and a follow-up after 12 weeks of diet. At both visits, an evaluation was performed with total nasal symptom score (TNSS) and modified Lund-Kennedy (L-K) endoscopy score. Results: Forty patients (21 female, 52.5%, median and IQR of age 52; 43.5–61) used LSD for 12 weeks. Initial analysis of dietary intervention in the whole group revealed a significant decrease in TNSS and each symptom assessed separately, and the L-K score. The group was further divided into two subgroups based on the distance between NSAID intake and the beginning of symptoms: patients with immediate (n = 9; 22.5%) or non-immediate (n = 31; 77.5%) symptoms. The absolute change in nasal obstruction, itching, TNSS, and L-K scores were significantly higher in patients with immediate than with non-immediate symptoms. Conclusion: Results of the study indicate that patients with N-ERD and immediate symptoms may clinically benefit more from an LSD as an additional therapeutic option than patients with non-immediate symptoms.

Being born in autumn or winter is associated with asthma and allergic rhinitis in Finland.

Our population-based study has previously shown that being born in winter or spring was associated with adult-onset asthma. The aim was to study if season of birth (SOB) is associated with airway allergy and related diseases: NSAID exacerbated respiratory disease (N-ERD), asthma, allergic rhinitis (AR), nonallergic rhinitis (NAR), chronic rhinosinusitis with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP) in Finland. A randomly sampled retrospective registry-based follow-up data (n=74,868) of patients visiting Hospital District of Helsinki and Uusimaa (HUS) in Finland was used. The birth date, sex, visit date and comorbidities were collected from electronic health record data during visits from 2005 to 2019. The mean (SD, range) age of the sample was 34.53 (25.47, 0-102) years, with 48.7 % being men. We divided the whole population in four groups based on the season they were born (SOB-groups). When observing these four SOB-groups, the proportion of those having asthma was 43.1%, 42.1%, 41.1%, 42.7%, in winter, spring, summer, and autumn SOB-groups, respectively. The proportion of those having AR was 12.6%, 12.0%, 10.7%, 12.1%, respectively. When having summer as a reference, being born in any other time of year was significantly associated with AR and, being born in autumn or winter was associated with asthma. No significant association was observed in CRS or N-ERD or NAR groups in adjusted models. The study suggests that early life immunological events may have a role a role in pathogenesis of asthma and AR. As no association was observed between SOB and CRSsNP, CRSwNP, N-ERD or NAR, further studies on this are warranted.

The Burden of Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease: Interplay Between Quality of Life and Economic Implications

NSAID-Exacerbated Respiratory Disease (NSAID-ERD) presents a significant challenge in clinical management, owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Though asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal complaints, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated healthcare burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps (CRSwNP) where available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. While some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes.

Review of NSAID Hypersensitivity Reactions Based on Clinical Phenotyping

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, antipyretic, and anti-inflammatory properties. However, they are also associated with a broad spectrum of hypersensitivity reactions, ranging from mild cutaneous manifestations to severe systemic responses. The complex nature of these reactions and their underlying mechanisms pose challenges in diagnosis and management. We review the clinical evidence to six distinct clinical phenotypes of NSAID hypersensitivity, including: NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA), NSAID-exacerbated respiratory disease (NERD), NSAID-exacerbated cutaneous disease (NECD), NSAID-induced urticaria/angioedema (NIUA), food-dependent NSAID-induced hypersensitivity reactions (FDNIH), and selective NSAID-induced delayed reactions (SNIDR). This review aims to provide a comprehensive review of NSAID hypersensitivity reactions based on clinical phenotyping, which can aid in understanding and managing these adverse events.

An update on nonsteroidal anti-inflammatory drug-induced urticaria.

Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management. The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles. Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed. HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

Beyond type 2 asthma biomarkers: risk stratification for NSAID-exacerbated respiratory disease.

Type 2 (T2) asthma is often associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Additionally, nonsteroidal anti-inflammatory drug (NSAID) intolerance leads to NSAID-exacerbated respiratory disease (N-ERD). Previous transcriptomic data in non-CRSwNP T2 asthma patients showed differentially expressed genes. We focused on ALOX15, CLC, CYSLTR2, HRH4 and SMPD3 to investigate their role in T2 asthma. The study included 100 healthy controls and 103 T2 asthma patients, divided into patients with asthma (n=54), patients with asthma and CRSwNP (n=29) and patients with N-ERD (n=20). Quantitative PCR analysis was performed on blood-derived RNA samples first to validate the five differentially expressed genes. The data were further analysed to find potential associations and biomarkers. Patients, regardless of stratification, exhibited significantly higher gene expression than healthy controls. The patterns of association revealed that ALOX15 was exclusively present in the non-comorbidity group, SMPD3 and CLC in the comorbidity groups, and HRH4 in all patient groups. ALOX15, CYSLTR2 and SMPD3 expression showed potential as biomarkers to confirm the diagnosis of T2 asthma using peripheral blood eosinophils as the initial criterion. Peripheral blood eosinophils combined with gene expression, especially SMPD3, may improve the diagnosis. CLC and CYSLTR2 expression play a specific role in discriminating N-ERD. We validated the transcriptomic data of five differentially expressed genes in T2 asthma. Different patterns of association were identified in patient stratification, suggesting that different molecular mechanisms underlie the spectrum of T2 asthma. Potential biomarkers were also found and used to design an algorithm with practical diagnostic utility for T2 asthma, including risk stratification for N-ERD.

Importance of aspirin challenges in patients with NSAID-exacerbated respiratory disease

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is often characterized by asevere course of chronic rhinosinusitis with nasal polyps (CRSwNP), comorbid asthma, and NSAID hypersensitivity. The gold standard for N-ERD diagnosis is challenge with acetylsalicylic acid (ASA). In expert recommendations, the diagnosis of N-ERD is established based on aplausible positive history of NSAID hypersensitivity and CRSwNP with asthma. The following review describes the performance of ASA challenges and their sensitivity and specificity. It also examines the extent to which apositive history of NSAID hypersensitivity correlates with ASA challenge results in clinical trials and when ASA challenges should be performed. ASA challenges have high sensitivity and specificity. In clinical ASA challenge studies, there is ahigh concordance between apositive history of NSAID hypersensitivity obtained by rhinologists and the measured data of ASA challenge in patients with CRSwNP and comorbid asthma. Therefore, ASA challenge is primarily indicated in patients with an unclear history of NSAID hypersensitivity.

Extracellular vesicle miRNAs drive aberrant macrophage responses in NSAID-exacerbated respiratory disease.

Extracellular vesicles (EVs) have been implicated in the pathogenesis of asthma, however, how EVs contribute to immune dysfunction and type 2 airway inflammation remains incompletely understood. We aimed to elucidate roles of airway EVs and their miRNA cargo in the pathogenesis of NSAID-exacerbated respiratory disease (N-ERD), a severe type 2 inflammatory condition. EVs were isolated from induced sputum or supernatants of cultured nasal polyp or turbinate tissues of N-ERD patients or healthy controls by size-exclusion chromatography and characterized by particle tracking, electron microscopy and miRNA sequencing. Functional effects of EV miRNAs on gene expression and mediator release by human macrophages or normal human bronchial epithelial cells (NHBEs) were studied by RNA sequencing, LC-MS/MS and multiplex cytokine assays. EVs were highly abundant in secretions from the upper and lower airways of N-ERD patients. N-ERD airway EVs displayed profoundly altered immunostimulatory capacities and miRNA profiles compared to airway EVs of healthy individuals. Airway EVs of N-ERD patients, but not of healthy individuals induced inflammatory cytokine (GM-CSF and IL-8) production by NHBEs. In macrophages, N-ERD airway EVs exhibited an impaired potential to induce cytokine and prostanoid production, while enhancing M2 macrophage activation. Let-7 family miRNAs were highly enriched in sputum EVs from N-ERD patients and mimicked suppressive effects of N-ERD EVs on macrophage activation. Aberrant airway EV miRNA profiles may contribute to immune dysfunction and chronic type 2 inflammation in N-ERD. Let-7 family miRNAs represent targets for correcting aberrant macrophage activation and mediator responses in N-ERD.

Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study

Chronic rhinosinusitis with nasal polyps (CRSwNP) is atype‑2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on amulticenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. This is aretrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. Treatment was commenced in 122patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B‑SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry

Chronic rhinosinusitis (CRS) is a persistent nasal and paranasal sinus mucosa inflammation comprising two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drug (NSAID) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS frequently intertwines with respiratory allergies. This study investigated levels of 33 different nasal and serum cytokines and phenotypic characteristics of peripheral blood mononuclear cells (PBMCs) within cohorts of CRS patients (n = 24), additionally examining the influence of comorbid respiratory allergies by mass cytometry. N-ERD patients showed heightened type 2 nasal cytokine levels. Mass cytometry revealed increased activated naive B cell levels in CRSwNP and N-ERD, while resting naive B cells were higher in CRSsNP. Th2a cell levels were significantly elevated in allergic subjects, but not in CRS groups. In conclusion, there are distinct immunological features in PBMCs of CRS phenotypes and allergy.

Does aspirin therapy after desensitization still have a role in treatment of chronic rhinosinusitis with nasal polyposis in the era of biologics?

The prevalence of analgesic intolerance syndrome (AIS), internationally known as NSAID-exacerbated respiratory disease (NERD), is reported to be 0.5-5.7% in the general population. The disease often begins with nasal symptoms, which are later joined by chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and respiratory hypersensitivity reactions following use of nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of chronic respiratory disease, the type2 inflammatory endotype is predominant in approximately 80% of patients with CRSwNP, rendering biologics directed against interleukin (IL)-4, IL‑5, IL-13, and IgE of high clinical interest, particularly in patients with severe CRSwNP and NERD. NERD is often associated with CRSwNP and asthma. Patients with CRSwNP and NERD have been treated, among other therapies, with aspirin therapy after desensitization (ATAD). With the approval of monoclonal antibodies for CRSwNP and asthma, the question arises as to what extent ATAD, which is associated with undesirable side effects, is still useful in the treatment of CRSwNP. In this manuscript, the use of ATAD in CRSwNP patients is discussed from different medical and socioeconomic points of view, both alternatively to or in combination with monoclonal antibodies. Accordingly, both ATAD and biologics continue to play asupporting role in modern treatment of CRSwNP in NERD patients, and should be used judiciously to complement each other.

Quality of Life in NSAIDs-Exacerbated Respiratory Disease on or off Intranasal Lysine Aspirin Therapy

Quality of Life in NSAIDs-Exacerbated Respiratory Disease on or off Intranasal Lysine Aspirin Therapy

Multidisciplinary management of type 2 inflammation diseases using a screening tool.

Dysregulation of type 2 (T2) immune response leads to an aberrant inflammatory reaction that constitutes the pathophysiological basis of diseases involving various organs. For this reason, several disorders can coexist in a single patient; however, as different specialists often treat these pathologies, T2 dysregulation, particularly when mild, is not always the first diagnostic suspicion. A breakdown in interdisciplinary communication or the lack of adequate tools to detect these entities can delay diagnosis, and this, together with a lack of coordination, can lead to suboptimal care. In this context, a multidisciplinary group of specialists in pneumology, immunology, allergology, dermatology and otorhinolaryngology compiled a list of the cardinal symptoms reported by patients presenting with T2 inflammation-related diseases: asthma, chronic rhinosinusitis, allergic rhinitis, allergic conjunctivitis, IgE-mediated food allergy, atopic dermatitis, eosinophilic oesophagitis, and NSAID-exacerbated respiratory disease (NERD). Using this information, we propose a simple, patient-friendly questionnaire that can be administered at any level of care to initially screen patients for suspected coexisting T2 diseases and referral to the appropriate specialist.

Upregulation of Platelet-Activating Factor Receptor Expression and Lyso-Platelet-Activating Factor Isoforms in Human Nasal Polyp Tissues

Background: The Platelet-Activating Factor (PAF)/receptor (PAFR) system is involved in asthma and allergic rhinitis; however, its role in chronic rhinosinusitis (CRS) is still unclear. This study aimed to assess the expression of PAFR and the concentration of Lyso-PAF isoforms in the nasal polyps (NP) of patients suffering from CRS with/without comorbidities such as asthma and NSAID-exacerbated respiratory disease (N-ERD) compared to healthy nasal mucosa (NM) from control subjects. Methods: NM (n = 8) and NP tissues were obtained from patients undergoing surgery for septal deviation/turbinate hypertrophy or endoscopic sinus surgery, respectively. Three phenotypes were studied: CRSwNP with no asthma (n = 6), CRSwNP with non-steroidal anti-inflammatory drug (NSAID)-tolerant asthma (n = 6), and CRSwNP with NSAID-exacerbated respiratory disease (n = 6). PAFR protein and mRNA were assessed via immunochemistry, immunofluorescence, Western blot, and real-time quantitative PCR. Lyso-PAF isoforms (C16, C18, and C18:1) were quantified via mass spectrometry. Results: PAFR protein was expressed in the NM and NP, concretely in epithelial cells and submucosal glands. Compared to NM, PAFR mRNA expression was higher in all NP phenotypes (p &lt; 0.05) while all Lyso-PAF isoform concentrations were higher in the NP from asthmatic patients (p &lt; 0.05). Lyso-PAF C16 and C18 concentrations were higher in the NP from asthmatic patients than in the NP from patients without asthma. Conclusions: The PAF/PAFR system could play a pathophysiological role in CRSwNP pathogenesis.

Does NSAID exacerbated respiratory disease (N-ERD) accompanying severe asthma affect biological treatment response? Efficacy of omalizumab and mepolizumab in N-ERD

IntroductionNon-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) accompanies severe asthma in about 15% of the patients and may adversely affect the prognosis. Omalizumab and mepolizumab are biologics used in patients with severe asthma. The objective of this study is to assess the respiratory improvements, after these biologics in severe asthmatic patients stratifed by the presence of concomitant Non-erosive reflux disease (N-ERD) and the effect of omalizumab and mepolizumab in severe asthmatics with N-ERD. Material & methodThe population of this three-center, retrospective, cross-sectional, observational study comprised patients using omalizumab or mepolizumab for severe asthma. Patients administered these biologics for severe asthma were comparatively analyzed for the presence of N-ERD; asthma control test (ACT) scores, number of attacks, and the changes in forced expiratory volume in 1 s (FEV1) were assessed. Subsequently, patients who were found to have N-ERD were analyzed using visual analog scale (VAS) in terms of the changes in their nasal parameters (ie, nasal obstruction, facial pain, anterior-posterior rhinitis, and hyposmia), according to whether they use omalizumab or mepolizumab. ResultsThe use of biologics resulted in a significant improvement in ACT and FEV1 and reduction in attacks in 28 severe asthmatics with N-ERD and 125 without N-ERD. Although both biologics resulted in a significant improvement in the respiratory parameters, omalizumab treatment resulted in a significant improvement in nasal parameters except hyposmia, mepolizumab treatment resulted in a significant improvement only in posterior rhinitis, and nasal obstruction among the nasal parameters. ConclusionThis study is the first to address both omalizumab and mepolizumab treatments in severe asthmatics with N-ERD. The improvement in nasal parameters was more pronounced in patients who were administered omalizumab. Large-scale randomized controlled studies are needed to corroborate the findings of this study.

Sex, Ethnicity, Body Mass Index, and Environmental Exposures Associated With NSAID-Exacerbated Respiratory Disease Symptom Sequence

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) has a triad of symptoms: nasal polyposis, asthma, and NSAID hypersensitivity. Little is known about symptom timing and disease progression. The aim of this study is to characterize disease progression in N-ERD. Patients with N-ERD were prospectively interviewed and classified into 4 groups based on their first symptom at initial N-ERD onset (asthma, nasal polyps, NSAID hypersensitivity, or all concurrently). Associations of patient characteristics with the 4 groups were examined, along with associations within the "asthma first" group. Patients (N= 240) were mostly female (68%) and self-identified as non-White (77%). Half (N= 119) reported asthma as the earliest symptom in the N-ERD triad. Compared with other groups, "asthma first" was associated with younger age of onset (25 years, standard error ±1.3, P < .001) and higher body mass index (BMI) (odds ratio [OR]= 1.3, 95% confidence interval [CI]: 1.06-1.7, P= .02). In this group, age of onset <20 years was associated with female sex, Latino ethnicity, and higher BMI (all P < .05). The "NSAID sensitivity first" group was significantly associated with male sex (OR= 3.3, 95% CI: 1.5-7.4, P= .004) and pollution exposure (OR= 4.4, 95% CI: 1.6-11.9, P= .003). At the initial presentation, 27% of patients were unaware of their N-ERD diagnosis. Black and Latino patients were more likely to be unaware of their N-ERD diagnosis compared with White (P= .003). The median diagnostic delay was 3 years (interquartile range: 0-5 years). In this cohort, N-ERD is highly variable in onset and progression, with sex, BMI, race and ethnicity, and environmental exposures significantly associated with disease patterns and diagnostic delay.

Risk factors of NSAID-exacerbated respiratory disease: Apopulation-based study.

Asthma with NSAID-exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non-NERD-asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult-onset asthma. We used data from 1350 population-based adult asthmatics with adult-onset asthma from Finnish national registers. NERD was defined as self-reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty-six covariates covering several domains (personal characteristics, life-style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. The study population included 153 (11.3%) asthmatics with NERD. Thirty-six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p<0.05). These variables were entered in a multivariable logistic regression model in which allergic respiratory symptoms, female sex, osteoarthritis, difficult asthma, nasal polyps, second-hand smoke exposure at home, having 3 or more older siblings and being overweight were significantly associated with asthma with NERD (p<0.05). Overweight decreased the risk of NERD, other factors increased it. According to our study, risk factors of NERD in part are associated with female sex, BMI, exposure to tobacco smoke, allergy, orthopaedic disorders and infection history, and their early recognition might thus be important to manage the burden of NERD.