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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Basophil Activation Test Is Inferior to Provocation Test in Diagnosing Aspirin Hypersensitivity.

INTRODUCTION: Diagnostic of aspirin (ASA) hypersensitivity is largely based on provocation tests. However, they have significant limitations including influence of medications, necessity of hospitalization, and safety issues. Basophil activation test (BAT) seems to be a promising in vitro alternative. It has already proven to be a useful tool for diagnosing IgE-mediated allergy to certain food and airborne allergens as well as insects venoms. The aim of the study was to assess performance of BAT in diagnosing aspirin hypersensitivity in comparison with current golden standard (oral provocation test, OPT). METHODS: The study group comprised 148 adult patients with suspicion of aspirin hypersensitivity, including 51 (36%) with chronic urticaria, 73 (51%) with asthma, and 55 (39%) with chronic sinusitis. The control group was 10 healthy adult patients who used NSAIDs during preceding year with good tolerance. BAT with ASA was conducted in all the participants. Additionally, in the study group, OPT was performed with cumulative dose of 1,000 mg of ASA. RESULTS: Out of 148 study group participants, 114 underwent BAT and ASA provocation with conclusive results acquired in both tests. In this group, the threshold for positive BAT was 4.9%. Sensitivity and specificity of BAT were found to be 55.9% and 75%, respectively, with a positive predictive value of 77% and a negative predictive value of 54%. The highest sensitivity (78%) was found in subgroup patients with chronic urticaria, while specificity was highest in the subgroup with chronic respiratory diseases (87%). CONCLUSION: Despite significant advantages of BAT such as safety, no influence of drugs, and objectivity, its performance makes it inferior to current standard in ASA hypersensitivity.

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

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

Biologics Reduce Symptoms of Alcohol Intolerance Better than Aspirin Desensitization in Patients with N-ERD and Nasal Polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). METHODS: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3-6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). RESULTS: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). CONCLUSIONS: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Patients with gastroesophageal reflux disease (both reflux oesophagitis and non-erosive reflux disease): Prevalence and severity of erosive tooth wear and saliva properties.

BACKGROUND: The prevalence between erosive tooth wear (ETW) in association with reflux oesophagitis (RO) has been reported. However, the severity of both diseases and the relationship between ETW and non-erosive reflux disease (NERD) is unclear. OBJECTIVES: The prevalence and severity of ETW were investigated in RO, NERD and healthy controls. METHODS: 135 patients with RO, 65 with NERD and 40 healthy controls were recruited for this case-control study. A modified tooth wear index was used to evaluate the prevalence and severity of ETW. Salivary secretion and buffer capacity were assessed prior to endoscopy. The prevalence and severity of ETW, saliva properties among each group were analysed using Pearson's chi-squared test. RESULTS: A total of 135 cases (56.3%) were categorised as the patient with ETW (55 with mild RO, 49 with severe RO and 31 with NERD). There was a significant relationship between the prevalence of RO and ETW, while there was no significant correlation between the prevalence of NERD and ETW. There was a significant difference related to the severity between RO and ETW. For salivary secretion, there was a significant difference between with and without ETW in patients with mild RO, severe RO and NERD. There was a significant difference between with and without ETW for salivary buffer capacity in patients with mild and severe RO. CONCLUSION: There was a significant association of the prevalence and severity between RO and ETW. Clinical signs such as ETW and salivary buffer capacity depended on the severity of RO.

Ziverel for PPI-refractory reflux symptoms: efficacy and mechanisms of action in humans.

OBJECTIVES: It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function. METHODS: We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes. RESULTS: Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73-115)) and placebo (102 (67-110)) (p = 0.508) along with total RDQ score (2.6 (1.9-3.3) vs 2.8 (1.6-3.5) p = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846-19734)Ω·m) and placebo (13217 (9127-24942)Ω·m (p = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163-267) Ω.cm2 vs 205 (176-240) Ω.cm2 (p = 0.445) and fluorescein flux 775 (17-6964) nmol/cm2/h vs 187 (4-12209) nmol/cm2/h (p = 0.638). CONCLUSION: Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms.Trial registration: Netherlands Trial Register number: NL7670.

Hypersensitivity to intravenous succinate corticosteroids in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

Although there are many case reports of asthma exacerbations with intravenous corticosteroids, especially hydrocortisone succinate, in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), the frequency and mechanism remain unclear. We hypothesized that N-ERD patients are potentially hypersensitive to succinates, especially succinate corticosteroids, based on the results of previous provocation studies and considered specific mechanisms. The objective of this study was to determine the frequency and mechanism of succinate corticosteroids hypersensitivity in patients with N-ERD. Eleven patients with stable, moderate to severe N-ERD were tested with hydrocortisone sodium succinate (HCs), hydrocortisone sodium phosphate (HCp), methylprednisolone sodium succinate (MPSLs), prednisolone sodium succinate (PSLs), and chloramphenicol sodium succinate (CPs, without a steroidal chemical structure) at doses below the normal dose through intravenous administration using a single-blind test. As a comparison, seven patients with aspirin-tolerant asthma (ATA) also underwent an intravenous provocation test of HCs. The positive intravenous provocation test rates of HCs 100-500 mg, HCp 500 mg, MPSLs 80 mg, PSLs 20 mg, and CPs 500 mg in N-ERD patients were 82% (9/11), 9% (1/11), 50% (5/10), 33% (1/3), and 86% (6/7), respectively. Most positive reactions began with a severe cough within 5 min of intravenous injection. The course of these hypersensitivity symptoms differed from those seen with the usual aspirin challenge test. The HCs 100-500 mg intravenous test was negative in all seven patients with ATA. In conclusion, patients with N-ERD have high rates of potential hypersensitivity to the succinate ester structure, which is not linked to the corticosteroid structure, but to the succinate ester structure. We hypothesized that the mechanism of hypersensitivity observed during rapid intravenous administration of succinate corticosteroids is mast cell activation via succinate receptor stimulation, rather than due to the corticosteroid itself.

Lung Function and Asthma Clinical Control in N-ERD Patients, Three-Year Follow-Up in the Context of Real-World Evidence.

Purpose: To describe the lung function and clinical control of asthma in patients with N-ERD during three years of medical follow-up using GINA guidelines. Methods: We evaluated 75 N-ERD and 68 asthma patients (AG). Clinical control, lung function, and asthma treatment were evaluated according to GINA-2014. We compared all variables at baseline and one, two, and three years after treatment. Results: At baseline, the N-ERD group had better basal lung function (LF) than the AG group (p<0.01), and the AG group used higher doses of inhaled corticosteroids than the N-ERD group (52.4% vs 30.5%, p=0.01) and short-term oral corticosteroid (OCS) use (52.4% vs 30.5%, p<0.01). Instead, N-ERD patients needed more use of leukotriene receptor antagonists (LTRA) (29.3% vs 5.9%, p<0.01). This group had better clinical control than the AG group (62.1% vs 34.1%, p<0.01). During the medical follow-up, the LF of the N-ERD group remained at normal values; however, these parameters improved in AG from one year (p<0.01). Likewise, there was a diminished use of high doses of ICS (52.4% vs 33%, p<0.05) and short-term OCS (67.6% vs 20.6%, p<0.01) in asthma patients. However, N-ERD patients still needed more use of LTRAs (p<0.02) during the study. In this context, one-third of N-ERD patients had to use a combination of two drugs to maintain this control. From the second year on, clinical control of asthma was similar in both groups (p>0.05). Conclusion: According to GINA guidelines, only one-third of patients with N-ERD can gradually achieve adequate lung function and good asthma control with a high ICS dosage. Only a very small portion of patients will require the continued use of a second medication as an LTRA to keep their asthma under control.

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

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

Risk factors for functional dyspepsia, erosive and non-erosive gastroesophageal reflux disease: A cross-sectional study / Factores de riesgo en dispepsia funcional y enfermedad por reflujo gastroesofágico: un estudio transversal

Background: Conflicting data exists regarding risk factors associated with Gastroesophageal Reflux Disease (GERD) and Functional Dyspepsia (FD). Few studies examine anxiety/depression in relation to GERD phenotypes (Esophagitis/EE, and Non-Erosive Reflux Disease/NERD), FD, and Rome-IV syndromes. Our aim was to evaluate the association between epidemiological factors and comorbidities with GERD phenotypes, FD, and Rome-IV syndromes, as well as their relationship with anxiety/depression. Methods: 338 subjects were selected from 357 patients referred to three tertiary-centers for endoscopic evaluation. Every subject was interviewed individually to administer three validated questionnaires: GERD-Q, Rome-IV and HADS. Results: 45/338 patients were controls, 198/58.6% classified as GERD, 81/24.0% EE (49/14.5% symptomatic, and 32/9.5% asymptomatic), 117/34.6% NERD, 176/52.1% FD (43/12.7% epigastric pain syndrome, 36/10.7% postprandial distress syndrome, and 97/28.7% overlapping syndrome). 81 patients were mixed GERD-FD. Multivariate analysis found significant independent associations: age in NERD and FD; sex in EE, asymptomatic EE and FD; body mass index in NERD and FD; alcohol in EE; anxiety/depression in FD; use of calcium channel antagonists in EE; and inhalers in FD. We compared controls vs different groups/subgroups finding significantly more anxiety in NERD, FD, all Rome-IV syndromes, and mixed GERD-FD; more depression in FD, overlapping syndrome, and mixed GERD-FD; and higher levels of anxiety+depression in NERD, FD, overlapping syndrome, and mixed GERD-FD. Conclusions: NERD and FD share demographic and psychopathological risk factors which suggests that they may form part of the same pathophysiological spectrum. Regarding NERD anxiety was predominant, and in FD anxiety+depression, suggesting that both processes may require complementary psychological therapy.(AU)

Antecedentes: Existen datos controvertidos sobre los factores de riesgo asociados a la enfermedad por reflujo gastroesofágico (ERGE) y la dispepsia funcional (DF). Pocos estudios han evaluado la relación entre ansiedad/depresión y los diferentes fenotipos de la DF (criterios Roma IV) y de la ERGE (erosiva [EE] y no erosiva [NERD]). Nuestro objetivo fue valorar la asociación entre diferentes factores epidemiológicos y comorbilidades y los fenotipos de la ERGE, la DF y sus síndromes, y su relación con la ansiedad/depresión. Métodos: Se seleccionaron 338 pacientes entre 357 remitidos para estudio endoscópico en 3 hospitales terciarios. Cada uno fue entrevistado individualmente y completó 3 cuestionarios validados: GERD-Q, Roma IV y HADS. Resultados: Cuarenta y cinco de los 338 pacientes fueron controles. Se clasificaron 198/58,6% como ERGE, 81/24,0% como EE (49/14,5% sintomática y 32/9,5% asintomática), 117/34,6% como NERD y 176/52,1% como DF (43/12,7% síndrome de dolor epigástrico, 36/10,7% síndrome de molestias posprandiales y 97/28,7% solapamiento epigastralgia-molestias posprandiales). Ochenta y uno solapaban ERGE-DF. El análisis multivariante encontró las siguientes asociaciones significativas: edad en NERD y DF; sexo en EE, EE asintomática y DF; IMC en NERD y DF; alcohol en EE; ansiedad/depresión en DF; toma de antagonistas del calcio en EE e inhaladores en DF. Al comparar el grupo control vs. diferentes grupos/subgrupos encontramos significativamente más ansiedad en NERD, solapamiento DF-ERGE, DF y todos sus síndromes Roma IV; más depresión en DF, solapamientos epigastralgia-molestias posprandiales y ERGE-DF; y más ansiedad+depresión en NERD, DF y solapamientos epigastralgia-molestias posprandiales y ERGE-DF. Conclusiones: La DF y la NERD comparten factores de riesgo demográficos y psicopatológicos, lo que evidencia que forman parte de un mismo espectro fisiopatológico...(AU)

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

BACKGROUND: 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. OBJECTIVE: The aim of this study is to characterize disease progression in N-ERD. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

Background: 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. Methods: 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. Results: 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. Conclusion: The severity of symptoms before treatment and clinical improvement after treatment are not good predictors of N-ERD.

The role of histology in the diagnosis of non-erosive reflux disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Non-erosive reflux disease (NERD) accounts for over half of all gastroesophageal reflux cases and is characterized by reflux symptoms with pathologic acid exposure on pH monitoring but no evidence of erosions on upper endoscopy. Ambulatory pH monitoring is limited by availability and patient tolerance. The utility of performing esophageal mucosal biopsies in diagnosing NERD is unclear. We conducted a systematic review and meta-analysis to determine the sensitivity of esophageal mucosal biopsies in diagnosing NERD. METHODS: Data were obtained from Embase and Ovid MEDLINE from inception to April 2021. Studies were included if esophageal mucosal biopsies were taken and analyzed using conventional histopathologic analysis in symptomatic NERD patients. Relevant data was including histologic abnormalities and location of the biopsy. Sensitivity and specificity were calculated against healthy controls or those with functional heartburn. RESULTS: The search yielded 2871 studies, of which 10 studies met our inclusion criteria and contained raw data. Histological abnormalities included histologic sum scores, papillary elongation, basal cell hyperplasia, and dilated intraepithelial spaces. When assessing for the presence of any abnormality, biopsies taken <3 cm from the lower esophageal sphincter (LES) had a pooled sensitivity of 0.71 (95% CI 0.64-0.77) and specificity of 0.64 (95% 0.54-0.73); however, analysis of individual histologic features such as the presence of eosinophils improved the sensitivity. CONCLUSIONS: Although esophageal mucosal biopsies had poor sensitivity at diagnosing NERD, biopsies taken within 3 cm of the LES had higher sensitivity when pathologists reported upon eosinophils and dilated intraepithelial spaces.

Readability and quality analysis of patient education materials in aspirin-exacerbated respiratory disease.

KEY POINTS: Patients are increasingly turning to online education materials to aid with disease management. Patient education materials on aspirin-exacerbated respiratory disease are of poor readability with significant room for improvement.

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.

The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease phenotypically classified by the absence (CRSsNP) or presence of nasal polyps (CRSwNP). The latter may also be associated with asthma and hypersensitivity towards non-steroidal anti-inflammatory drugs (NSAID) as a triad termed NSAID-exacerbated respiratory disease (N-ERD). The role of the microbiome in these different disease entities with regard to the underlying inflammatory process and disease burden is yet not fully understood. To address this question, we measured clinical parameters and collected nasal samples (nasal mucosal fluids, microbiome swabs from middle meatus and anterior naris) of patients suffering from CRSsNP (n=20), CRSwNP (n=20) or N-ERD (n=20) as well as from patients without CRS (=disease controls, n=20). Importantly, all subjects refrained from taking local or systemic corticosteroids or immunosuppressants for at least two weeks prior to sampling. The nasal microbiome was analyzed using 16S rRNA gene amplicon sequencing, and levels of 33 inflammatory cytokines were determined in nasal mucosal fluids using the MSD platform. Patients suffering from N-ERD and CRSwNP showed significantly worse smell perception and significantly higher levels of type 2 associated cytokines IL-5, IL-9, Eotaxin and CCL17. Across all 4 patient groups, Corynebacteria and Staphylococci showed the highest relative abundances. Although no significant difference in alpha and beta diversity was observed between the control and the CRS groups, pairwise testing revealed a higher relative abundance of Staphylococci in the middle meatus in N-ERD patients as compared to CRSwNP (p<0.001), CRSsNP (p<0.01) and disease controls (p<0.05) and of Lawsonella in patients suffering from CRSwNP in middle meatus and anterior naris in comparison to CRSsNP (p<0.0001 for both locations) and disease controls (p<0.01 and p<0.0001). Furthermore, we observed a positive correlation of Staphylococci with IL-5 (Pearson r=0.548) and a negative correlation for Corynebacteria and Eotaxin-3 (r=-0.540). Thus, in patients refraining from oral and nasal corticosteroid therapy for at least two weeks known to alter microbiome composition, we did not observe differences in microbiome alpha or beta diversity between various CRS entities and disease controls. However, our data suggest a close association between increased bacterial colonization with Staphylococci and decreased colonization by Corynebacteria as well as increased type 2 inflammation.

Tegoprazan as a New Remedy for Gastrointestinal Diseases in Comparison with its Therapeutic Predecessors: A Mini-Review.

BACKGROUND: Potassium-competitive acid blockers (P-CABs), such as tegoprazan, are a new and diverse class of drugs that can completely block the potassium-binding site of gastric H+/K+ ATPase, potentially overcoming the limitations of proton-pump inhibitors (PPIs). A number of studies have compared the effectiveness as well as the safety profile of tegoprazan to PPIs and other P-CABs for the treatment of gastrointestinal diseases. OBJECTIVE: The current review study evaluates the published works of literature related to clinical pharmacology and clinical trials of tegoprazan for the treatment of diseases related to the gastrointestinal tract. CONCLUSION: The findings of this study revealed that tegoprazan is safe and well-tolerated and can be used to treat a group of gastrointestinal diseases, including gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), and H. pylori infection.