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Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have high incidence of sleep impairment. We evaluated the impact of omalizumab treatment on sleep characteristics and associated health status in patients with CRSwNP. Methods: Prespecified exploratory analysis assessed outcomes from patients included in the POLYP 1 and POLYP 2 phase 3 clinical trials and the open‐label extension. Sleep was assessed by the sleep domain of the Sino‐Nasal Outcome Test‐22 (SNOT‐22; MCID > 4 in patients with CRS) and the Medical Outcomes Study Sleep Scale (MOS‐Sleep). Health status was assessed by Healthy Days Core Module (HDCM) and sinonasal‐specific Patient Global Impression of Change (PGIC). Results: Omalizumab improved sleep as assessed by the SNOT‐22 sleep domain. At week 24, adjusted mean (95%CI) SNOT‐22 sleep scores had reduced from baseline by −8.5 (–9.9 to –7.1) with omalizumab versus –2.7 (–4.1 to –1.3) with placebo. At week 52 (all patents on OMA), adjusted mean (95%CI) SNOT‐22 sleep scores had reduced from baseline by −10.1 (–11.4 to –8.7) with omalizumab. Improvements were observed in all eight items of the SNOT‐22 sleep domain: difficulty falling asleep, fatigue, frustration/restlessness/irritability, lack good night's sleep, reduced concentration, reduced productivity, wake up tired, and wake up at night. In addition, omalizumab improved six of eight sleep outcomes on the MOS‐Sleep scale. There were concurrent improvements in HDCM and PGIC. Conclusion: Omalizumab improved sleep and self‐reported health status in patients with CRSwNP. This contributes to evidence that omalizumab provides value for patients beyond the reduction of sinonasal symptoms. [ABSTRACT FROM AUTHOR]

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in‐depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double‐blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. Conclusions: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed. [ABSTRACT FROM AUTHOR]

Background: About one‐tenth of patients with difficult‐to‐treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)‐4/IL‐13 receptor component, is an approved add‐on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID‐ERD. Methods: Data were pooled from the phase 3 SINUS‐24 and SINUS‐52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment–subgroup interactions were assessed for patients with and without NSAID‐ERD. Results: Of 724 patients, 204 (28.2%) had a diagnosis of NSAID‐ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund–Mackay computed tomography, 22‐item Sinonasal Outcome Test (SNOT‐22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six‐item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p <.0001) in patients with NSAID‐ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID‐ERD for NC (p =.0044), SNOT‐22 (p =.0313), TSS (p =.0425), and PNIF (p =.0123). Conclusions: In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient‐reported symptoms to a greater extent in the presence of comorbid NSAID‐ERD than without. Dupilumab was well tolerated in patients with/without NSAID‐ERD. [ABSTRACT FROM AUTHOR]

This article presents the findings of a population-based study on atopic dermatitis (AD) in children in Catalonia, Spain. The study found that the overall prevalence of AD in this population was 27.2%, with higher rates among females. The most common comorbidities associated with AD were acute bronchitis, asthma, allergic rhinitis, and overweight. The study acknowledges limitations and was funded by the UIC Real-World Evidence Chair. [Extracted from the article]

Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used. [ABSTRACT FROM AUTHOR]

The vast majority of patients with allergic rhinitis (AR) do not receive the proper management which is recommended by the guidelines, but they frequently self-medicate. MASK (Mobile Airways Sentinel Network) is an integral part of a project that is supported by the European Union against chronic diseases and focused on active and healthy aging. MASK represents the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma), in which, by using a mobile application in a smart device, the objective is to guide the patient in the control of his/her multi-morbidity, AR and/or allergic conjunctivitis (AC) and/or asthma. The mobile app Allergy Diary by MACVIA-ARIA is free and it is available for both Android and iOS platforms. After it is downloaded to the patient's cell phone, it first requests some information about the patient's profile, allergic pathologies and medication; afterwards, through a visual analog scale, the patient is invited to determine the degree of affectation in the nose, eyes, and bronchi, and its influence on their productivity at work/school. After analyzing the data generated by filling the Allergy Diary, it became clear there is a new clinical entity: allergic rhinitis+ allergic conjunctivitis +asthma, with greater effect; in addition to a high level of self-medication: in general, the patient takes medication on days when symptoms are present. The app has already been deployed in 23 countries, including several Spanish-speaking countries. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airways frequently associated with asthma. Bacterial infection is a feature of CRSwNP that can aggravate the disease and the response to glucocorticoid treatment. Objective: We examined whether the bacterial product lipopolysaccharide (LPS) reduces glucocorticoid receptor (GR) function in control nasal mucosa (NM) fibroblasts and in nasal polyp (NP) fibroblasts from patients with CRSwNP and asthma. Methods: NP (n = 12) and NM fibroblasts (n = 10) were in vitro pre-incubated with LPS (24 hours) prior to the addition of dexamethasone. Cytokine/chemokine secretion was measured by ELISA and Cytometric Bead Array. GRα, GRβ, mitogen-activated protein-kinase phosphatase-1 (MKP-1) and glucocorticoid-induced leucine zipper (GILZ) expression was measured by RT-PCR and immunoblotting, GRα nuclear translocation by immunocytochemistry, and GRβ localization by immunoblotting. The role of MKP-1 and GILZ on dexamethasone-mediated cytokine inhibition was analyzed by small interfering RNA silencing. Results: Pre-incubation of nasal fibroblasts with LPS enhanced the secretion of IL-6, CXCL8, RANTES, and GM-CSF induced by FBS. FBS-induced CXCL8 secretion was higher in NP than in NM fibroblasts. LPS effects on IL-6 and CXCL8 were mediated via activation of p38α/β MAPK and IKK/NF-κB pathways. Additionally, LPS pre-incubation: 1) reduced dexamethasone’s capacity to inhibit FBS-induced IL-6, CXCL8 and RANTES, 2) reduced dexamethasone-induced GRα nuclear translocation (only in NM fibroblasts), 3) did not alter GRα/GRβ expression, 4) decreased GILZ expression, and 5) did not affect dexamethasone’s capacity to induce MKP-1 and GILZ expression. MKP-1 knockdown reduced dexamethasone’s capacity to suppress FBS-induced CXCL8 release. Conclusion: The bacterial product LPS negatively affects GR function in control NM and NP fibroblasts by interfering with the capacity of the activated receptor to inhibit the production of pro-inflammatory mediators. This study contributes to the understanding of how bacterial infection of the upper airways may limit the efficacy of glucocorticoid treatment. [ABSTRACT FROM AUTHOR]

Background: Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells. Methods: Epithelial cells obtained from nasal mucosa were stimulated with 10% fetal bovine serum (FBS) in the presence of FF (from 10-12 to 10-7M) for 6-24 h. Cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-8] concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated for 4 days with epithelial cell secretions in the presence or absence of FF (from 10-12 to 10-7M) and survival was assessed by Trypan blue dye exclusion. Results are expressed as medians of the minimum effective concentration and IC values. Results: FBS stimulated the secretion of GM-CSF, IL-6 and IL-8. FF significantly inhibited GM-CSF (up to 10-10M, IC25 = 12.6 pM), IL-6 (up to 10-10M, IC25 = 65.8 pM) and IL-8 (up to 10-11M, IC25 = 8.6 pM) secretion induced by FBS (n = 8). Epithelial cell secretions induced eosinophil survival from day 1 to day 4 (n = 6). This effect was significantly inhibited by FF (up to 10-12M) at day 3 (IC50 = 3.22 nM) and day 4 (IC50 = 1.29 nM). Conclusions: The results obtained in this in vitro model suggest that FF may reduce upper airway eosinophilic inflammation through decreasing cytokine secretion from epithelial cells and reducing eosinophil survival. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recent studies have revealed that cyclooxygenase-2 (COX-2) expression is down-regulated in aspirin-induced asthma (AIA). Various signal pathways (MAPKs, NF-κB and C/EBP) are involved in COX-2 regulation. Objective: To investigate the regulation of COX-2 expression through MAP-kinase pathway activation and nuclear factor translocation in aspirin-induced asthma (AIA). Methods: Fibroblasts were isolated from specimens of nasal mucosa (NM, N = 5) and nasal polyps (NP, N = 5). After IL-1β (1 ng/ml) incubation, COX-2 and phosphorylated forms of ERK, JNK and p38 MAPK were measured by Western blot. MAPK's role in IL-1β-induced COX-2 expression was assessed by treating cells with ERK (PD98059), JNK (SP600125) and p38 MAPK (SB203580) inhibitors (0.1-10 μM) prior to IL-1β exposure. NF-κB and C/EBP nuclear translocation was measured by Western blot and TransAMH after IL-1β (10 ng/ml) exposure. Results: No differences were observed in the MAPK phosphorylation time-course between NM and NP-AIA fibroblasts. The p38 MAPK inhibitor at 10 μM significantly reduced IL-1b-induced COX-2 expression in NM fibroblasts (85%). In NP-AIA fibroblasts the COX-2 inhibition (65%) at 1 and 10 μM was not statistically significant compared to non-treated cells. ERK and JNK inhibitors had no significant effect in either the NM or NP-AIA cultures. The effect of IL-1β on NF-κB and C/EBP subunits' nuclear translocation was similar between NM and NP-AIA fibroblasts. Conclusions: These results suggest that p38 MAPK is the only MAPK involved in IL-1β-induced COX-2 expression. NM and NP-AIA fibroblasts have similar MAPK phosphorylation dynamics and nuclear factor translocation (NF-κB and C/EBP). COX-2 downregulation observed in AIA patients appears not to be caused by differences in MAPK dynamics or transcription factor translocation. [ABSTRACT FROM AUTHOR]

Summary Allergic rhinitis ( AR) is a major health problem with high and ever-increasing prevalence worldwide. At least one-fifth of adults in industrialized countries are estimated to have AR, defined as nasal and eye symptoms that are sufficiently severe to have a substantial negative impact on the quality of life ( QoL). The former classification of AR comprised seasonal AR ( SAR) and perennial AR ( PAR), which did not adequately reflect the presentation and clinical course of the disease. The Allergic Rhinitis and its Impact on Asthma ( ARIA) classification is based on the duration of symptoms and the disease severity. Both intermittent AR ( IAR: symptoms ≤ 4 days/week or ≤ 4 consecutive weeks) and persistent AR ( PER: symptoms > 4 days/week and > 4 consecutive weeks) may be mild, moderate, or severe based on the QOL impairment (sleep, daily activities/leisure, work productivity/school performance) and bothersome symptoms. Despite its disabling effects, AR remains a condition where affected individuals do not seek appropriate treatment, are undertreated and do not adhere well to treatment, which all lead to low disease control and high societal costs. The four pillars of AR treatment are allergen and pollutant avoidance, patient education, pharmacotherapy and allergen-specific immunotherapy. Oral antihistamines, together with intranasal corticosteroids and leucotriene antagonists, constitute important pharmacological options for the treatment of AR at all levels of severity. New second-generation antihistamines are H1-receptor antagonists with high efficacy (rapid onset of action for AR symptoms, sometimes even on nasal congestion, improvement of QoL and additional anti-allergic effects) and safety (low sedation rates). Although new antihistamines have been studied and approved for SAR and PAR, only some of them have been reported to show efficacy and safety for treatment of AR under the ARIA classification: levocetirizine (high efficacy) and rupatadine (dual antihistamine and anti- PAF effects) for PER, and desloratadine (high safety) for both IAR and PER. [ABSTRACT FROM AUTHOR]

The authors reflect on the efficiency of combined oral and intranasal corticosteroid therapy in nasal polyposis management. They note that corticosteroids exert anti-inflammatory effect by acting on particular receptors in human cells. They mention studies demonstrating that patients with nasal polyps who are sensitive to aspirin are susceptible to resist steroid treatment without glucocorticoid receptors' downregulation.

Background: Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps. Methods: Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control. Results: Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone. Conclusions: These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone. [ABSTRACT FROM AUTHOR]

Background: Although antihistamines and topical corticosteroids are used in combination to treat allergic rhinitis, their additive effect has not been yet demonstrated. The aim was investigate the antiinflammatory additive effect of mometasone and desloratadine on cytokine and sICAM-1 secretion by epithelial cells, and on eosinophil survival stimulated by human epithelial cells secretions from nasal mucosa and polyps. Methods: Epithelial cells obtained from nasal mucosa or polyps were stimulated with 10% fetal bovine serum in presence of mometasone (10-11M-10-5M) with/without desloratadine (10-5M). Cytokine and sICAM-1 concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated during 4 days with epithelial cell secretions with (10-11M-10-5M) and/or desloratadine (10-5M) and survival assessed by Trypan blue. Results are expressed as percentage (mean ± SEM) compared to control. Results: Fetal bovine serum stimulated IL-6, IL-8, GM-CSF and sICAM-1 secretion. In mucosa and polyp epithelial cells, mometasone inhibited this induced secretion while desloratadine inhibited IL-6 and IL-8. The combination of 10-5M desloratadine and 10-9M mometasone reduced IL-6 secretion (48 ± 11%, p < 0.05) greater extent than mometasone alone (68 ± 10%) compared to control (100%). Epithelial cell secretions induced eosinophil survival from day 1 to 4, this effect being inhibited by mometasone. At day 4, the combination of mometasone (10-11M) and desloratadine (10-5M) provoked an increased inhibition of eosinophil survival induced by cell secretions (27 ± 5%, p < 0.01) than mometasone (44 ± 7%) or desloratadine (46 ± 7%) alone. Conclusions: These results suggest that the combination of desloratadine and mometasone furoate have a greater antinflammatory effect in an in vitro model of eosinophil inflammation than those drugs administered alone. [ABSTRACT FROM AUTHOR]

Background: No control tools for nasal congestion (NC) are currently available in Spanish. This study aimed to adapt and validate the Congestion Quantifier Seven Item Test (CQ7) for Spain. Methods: CQ7 was adapted from English following international guidelines. The instrument was validated in an observational, prospective study in allergic rhinitis patients with NC (N = 166) and a control group without NC (N = 35). Participants completed the CQ7, MOS sleep questionnaire, and a measure of psychological well-being (PGWBI). Clinical data included NC severity rating, acoustic rhinometry, and total symptom score (TSS). Internal consistency was assessed using Cronbach's alpha and test-retest reliability using the intraclass correlation coefficient (ICC). Construct validity was tested by examining correlations with other outcome measures and ability to discriminate between groups classified by NC severity. Sensitivity and specificity were assessed using Area under the Receiver Operating Curve (AUC) and responsiveness over time using effect sizes (ES). Results: Cronbach's alpha for the CQ7 was 0.92, and the ICC was 0.81, indicating good reliability. CQ7 correlated most strongly with the TSS (r = 0.60, p < 0.01), the PGWBI general health dimension (r = 0.56, p < 0.01), and the MOS Sleep scale 'sleep short of breath' dimension (r = 0.49, p < 0.01). Correlations with acoustic rhinometry were generally low. The instrument discriminated well between NC severity groups (ES 0.33-2.07) and AUC was 0.93, indicating excellent sensitivity and specificity. The measure was responsive to change (ES = 1.1) in patients reporting improvement in NC. Conclusions: The Spanish version of the CQ7 is appropriate for detecting, measuring, and monitoring NC in allergic rhinitis patients. [ABSTRACT FROM AUTHOR]

Examines the expression of glucocorticoid receptor α and β-isoforms in human cells and tissues. Generation of two proteins isoforms; Mechanism for gene activation; Transrepression of target dates.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2‐mediated inflammatory disease with high symptom burden and reduced health‐related quality of life (HRQoL). This report aimed to comprehensively understand the effects of dupilumab on domains of HRQoL, their individual elements, and health status in patients with severe CRSwNP from phase 3 SINUS‐24 (NCT02912468) and SINUS‐52 (NCT02898454) trials. Methods: Patients were randomized to dupilumab (n = 438) or placebo (n = 286) for 24 weeks (SINUS‐24), or 52 weeks (SINUS‐52). Disease‐specific HRQoL using 22‐item sino‐nasal outcome test (SNOT‐22), and health status using EuroQoL‐visual analog scale (EQ‐VAS) was evaluated in the pooled intention‐to‐treat (ITT) population (Week 24), SINUS‐52 ITT (Week 52) and in the subgroups with/without asthma; non‐steroidal anti‐inflammatory drug‐exacerbated respiratory disease (NSAID‐ERD); and prior sinus surgery. Results: At baseline, patients had poor disease‐specific HRQoL and general health status and identified "Decreased sense of smell/taste" and "Nasal blockage" as the most important symptoms. Dupilumab significantly improved SNOT‐22 total, domain (Nasal, Sleep, Function, Emotion, and Ear/facial), and 22‐item scores, and EQ‐VAS, at Week 24 vs placebo (all p <.0001), with continued improvements to Week 52 in SINUS‐52. Improvements occurred irrespective of comorbid asthma, NSAID‐ERD, or prior surgery. A significantly greater proportion of dupilumab‐treated patients exceeded clinically meaningful thresholds for SNOT‐22 total score and EQ‐VAS vs placebo (all subgroups p <.05 except patients without surgery at Week 24). Conclusions: Dupilumab treatment led to significant clinically meaningful improvements across all aspects of disease‐specific HRQoL, and general health status in patients with severe CRSwNP. [ABSTRACT FROM AUTHOR]

No abstract available [ABSTRACT FROM AUTHOR]

Background: Different clinical trials showed the superior efficacy of rupatadine compared to placebo at improving seasonal allergic rhinitis (SAR) symptoms, but no study has assessed if the response promoted is clinically meaningful. Methods: This study is a pooled analysis of data of seven randomized, double-blind, placebo-controlled SAR studies comparing responder proportions upon treatment with rupatadine (10 or 20 mg) or placebo. We evaluated the following symptom scores at baseline (Visit 1) and over 14 days of treatment: Total 4 Nasal Symptom Score (T4NSS), Total 2 Ocular Symptom Score (T2OSS) and Total 6 Symptom Score (T6SS). The proportion of responders (50% and 75% response) and the time to response were compared between groups on days 7 (Visit 2) and 14 (Visit 3). Responder rates were compared between groups on days 7 and 14 for the complete/near-to-complete response for T4NSS (TN4SS score ≤ 2 and each symptom score ≤ 1) and T6SS (T6SS score ≤ 3 and each symptom score ≤ 1). Results: Data from 1470 patients were analyzed: 332 treated with placebo, 662 with rupatadine 10 mg and 476 with rupatadine 20 mg. The reduction in T4NSS, T2OSS and T6SS over 14 days of treatment relative to baseline was statistically higher in rupatadine groups vs the placebo group, with greater improvements in the 20 mg group. A statistically higher proportion of patients reached the 50% and 75% response for T4NSS, T2OSS and T6SS in rupatadine groups compared to the placebo group across the visits. Among rupatadine-treated patients, those receiving 20 mg compared favourably for both cut-off responses. The time to achieve a proportion of responders was shorter in the rupatadine 20 mg group than in the rupatadine 10 mg and placebo groups for all the symptom scores. The number of patients who achieved a complete/near-to-complete response for both symptom scores was higher in rupatadine groups than in the placebo group, with higher proportions in the 20 mg group. Conclusions: This responder analysis confirms the superior efficacy of rupatadine vs placebo to treat SAR. Rupatadine promoted higher proportions of responders according to stringent response criteria and in a dose-dependent manner, with faster and higher response rates in the 20 mg group. [ABSTRACT FROM AUTHOR]

Background: Type 2 inflammation has been described as a pathophysiological basis common to some diseases, such as atopic dermatitis (AD), chronic rhinosinusitis with nasal polyps, and asthma (CRSwNP). Objective: The present study used population‐based prevalence in Catalonia to analyse the coexistence of type 2 inflammatory diseases in patients primarily diagnosed with the above mentioned conditions. Results: We found a high degree of coexistence of type 2 inflammatory diseases among these patients, with the prevalence being higher in the severe forms, except for AD. For the severe forms of primary diseases, the proportion of patients with coexisting type 2 inflammatory diseases (severe or non‐severe) was 16.2% for AD, 19.8% for asthma, and a striking 62.4% for CRSwNP. This patient population has the highest proportion of coexisting type 2 inflammatory diseases, both severe (48.9%) and non‐severe (13.5%). Conclusion: Our findings have significant implications for the management of patients with AD, asthma, and CRSwNP. [ABSTRACT FROM AUTHOR]

Objectives: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. Design: Anonymous online questionnaire with cross‐sectional non‐probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non‐rhinologists') was performed, with geographical comparisons only made according to subgroup. Participants: ENT surgeons who assess olfaction. Results: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country‐specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios—though rhinologists did so more often than non‐rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. Conclusions: To our knowledge, this is the most comprehensive UK‐based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health‐related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient‐reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. Methods: Following a 4‐week mometasone furoate nasal spray run‐in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), 5‐dimension EuroQoL (EQ‐5D) general health status VAS, and 36‐item Short‐Form Health Survey (SF‐36) for HRQoL and nasal polyp‐related healthcare resource use questionnaires. Results: Following 16 weeks of treatment, the proportion of patients with moderate‐to‐severe CRSwNP (VAS > 3‐10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT‐22, SF‐36, and EQ‐5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P =.015) and significantly greater improvement (vs placebo) in the SNOT‐22 item "reduced productivity." Conclusions: In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity. [ABSTRACT FROM AUTHOR]

Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) are frequent coexisting conditions and share type 2 inflammatory pathophysiology, with interleukin (IL)-4 and IL-13 as key cytokines. Dupilumab is a monoclonal antibody that blocks the shared receptor for IL-4 and IL-13. The objective of this analysis was to evaluate dupilumab's effect on type 2 inflammation biomarkers in patients with CRSwNP with/without coexisting asthma or NSAID-ERD from the SINUS-52 (NCT02898454) study. Methods: Patients received treatment with dupilumab or placebo for 52 weeks. Blood and urinary biomarkers were evaluated through 52 weeks, and nasal secretions and mucosa brushings through 24 weeks. Results: Of 447 patients, 60% had coexisting asthma and 27% had coexisting NSAID-ERD. At baseline, blood eotaxin-3, eosinophils, and periostin, nasal secretion eotaxin-3, and urinary leukotriene E4 were significantly higher in patients with coexisting NSAID-ERD than without. Dupilumab reduced eotaxin-3, thymus and activation-regulated chemokine, periostin, and total immunoglobulin E in blood, eotaxin-3, periostin, IL-5, and eosinophil cationic protein in nasal secretions, and leukotriene E4 in urine. Reductions were generally similar or greater in the subgroups with asthma and NSAID-ERD than without. Dupilumab also reduced MUC5AC and mast cell counts in nasal mucosa brushings. Conclusion: Dupilumab reduced local and systemic type 2 inflammatory biomarkers in patients with CRSwNP, including mast cells in nasal mucosa and cysteinyl leukotrienes in urine. These findings provide insight into the processes driving CRSwNP and the mechanisms of dupilumab's therapeutic effects. Clinical Trial Registry Name: SINUS-52 https://www.clinicaltrials.gov/ct2/show/NCT02898454 ClinicalTrials.gov Identifier: NCT02898454 [ABSTRACT FROM AUTHOR]

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 < 0.05) while all Lyso-PAF isoform concentrations were higher in the NP from asthmatic patients (p < 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. [ABSTRACT FROM AUTHOR]

MJ reports personal fees from ALK-Abello, personal fees from Allergopharma, personal fees from Stallergenes, personal fees from Anergis, personal fees from Allergy Therapeutics, personal fees from Leti, personal fees from HAL, during the conduct of the study; personal fees from GSK, personal fees from Novartis, personal fees from Teva, personal fees from Takeda, personal fees from Chiesi, outside the submitted work. JS reports grants and personal fees from SANOFI, personal fees from GSK, personal fees from NOVARTIS, personal fees from ASTRA ZENECA, personal fees from MUNDIPHARMA, personal fees from FAES FARMA, outside the submitted work. LC reports personal fees from Thermofisher, personal fees from Sanofi, personal fees from Astra Zeneca, personal fees from Novartis, outside the submitted work. PK reports personal fees from Adamed, personal fees from Berlin Chemie Menarini, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Celon Pharma, personal fees from Polpharma, personal fees from Teva, personal fees from Novartis, personal fees from Glenmark, personal fees from Zentiva, outside the submitted work. [Extracted from the article]

Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10, MSR1, PHLDA1, SERPINB2, and CD86) and underexpressed genes (CHI3L1, CPA3, IL-8, and PI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of MSR1 and PHLDA1 and had no effects on CD86, IL-10, and SERPINB2. In underexpressed genes, obesity did not affect PI3, CHI3L1, and IL-8 and significantly reduced CPA3 expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma. [ABSTRACT FROM AUTHOR]

Background: Scientific evidence on patients with multimorbid type 2 asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a united airways disease (UAD) perspective remains scarce, despite the frequent coexistence of these entities. We aimed to generate expert consensus-based recommendations for the management of UAD patients. Methods: Using a two-round Delphi method, Spanish expert allergists, pulmonologists and otolaryngologists expressed their agreement on 32 statements (52 items) on a 9-point Likert scale, classified as appropriate (median 7–9), uncertain (4–6) or inappropriate (1–3). Consensus was considered when at least two-thirds of the panel scored within the range containing the median. Results: A panel of 30 experts reached consensus on the appropriateness of 43 out of the 52 (82.7%) items. The usefulness of certain biomarkers (tissue and peripheral blood eosinophil count, serum total IgE, and fraction of exhaled nitric oxide [FeNO]) in the identification and follow-up of type 2 inflammation, and assessment of the response to biologics, were agreed. Some of these biomarkers were also associated with disease severity and/or recurrence after endoscopic sinus surgery (ESS). Consensus was achieved on treatment strategies related to the prescription of anti-IL-4/IL-13 or anti-IgE agents, concomitant treatment with systemic corticosteroids, and combining or switching to biologics with a different mechanism of action, considering a number of UAD clinical scenarios. Conclusion: We provide expert-based recommendations to assist in clinical decision-making for the management of patients with multimorbid type 2 asthma and CRSwNP. Specific clinical trials and real-world studies focusing on the single-entity UAD are required to address controversial items. [ABSTRACT FROM AUTHOR]

Nasal endoscopy is not only used for the diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP), but also for monitoring the response to therapy playing an important role in both daily practice and research. In contrast to patient‐reported outcomes, endoscopic nasal polyp scoring by independent blinded readers is an objective measurement, not influenced by the placebo effect. It is safer and cheaper compared with computed tomography imaging and therefore, better suited for regular assessments of the extent of the disease. Since the early 90s, a variety of endoscopic staging methods have been proposed and used in clinical research, making it hard to compare results from different studies. This paper resulted from a task force with experts in the field of CRSwNP, originated by the Ear, Nose and Throat section of the European Academy of Allergy and Clinical Immunology and aims to provide a unified endoscopic NP scoring system that can serve as a reference standard for researchers, but also as a useful tool for practitioners involved in the management of CRSwNP. [ABSTRACT FROM AUTHOR]

Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK‐air®, these data have only been analyzed cross‐sectionally, without considering the changes of symptoms over time. We analyzed data from MASK‐air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK‐air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k‐means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly‐variable control. Clusters with poorly‐controlled rhinitis displayed a higher frequency of rhinitis co‐medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co‐medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms. [ABSTRACT FROM AUTHOR]

MP-AzeFlu (intranasal fluticasone and azelastine) has been widely studied and has demonstrated efficacy in Allergic rhinitis with a superior effect compared to these drugs administered individually; however, the mechanism by which MP-AzeFlu produces this improved clinical effect has not yet been fully explained. In this study, we investigated the effect of MP-AzeFlu and fluticasone propionate (FP) on arachidonic acid metabolism as measured by changes in regulation of cyclooxygenase (COX) isoforms, prostaglandin (PG) D2, PGE2, PGE2 receptor (EP) 2, and EP3. Expression of these key inflammation markers was assessed through an in vitro model of upper airway inflammation using fibroblasts derived from both healthy and inflamed upper airway mucosa. Both MP-AzeFlu and FP inhibited interleukin-1β-induced COX-2 messenger RNA (mRNA) and protein expression and PGE2 secretion in vitro. MP-AzeFlu and FP both upregulated EP2 mRNA expression, though neither upregulated EP2 protein expression. This downregulation of COX-2 and PGE2 coupled with upregulation of EP2 receptor expression reinforces the anti-inflammatory effect of MP-AzeFlu in upper airway inflammation. [ABSTRACT FROM AUTHOR]

Background: No control tools for nasal congestion (NC) are currently available in Spanish. This study aimed to adapt and validate the Congestion Quantifier Seven Item Test (CQ7) for Spain.Methods: CQ7 was adapted from English following international guidelines. The instrument was validated in an observational, prospective study in allergic rhinitis patients with NC (N = 166) and a control group without NC (N = 35). Participants completed the CQ7, MOS sleep questionnaire, and a measure of psychological well-being (PGWBI). Clinical data included NC severity rating, acoustic rhinometry, and total symptom score (TSS). Internal consistency was assessed using Cronbach's alpha and test-retest reliability using the intraclass correlation coefficient (ICC). Construct validity was tested by examining correlations with other outcome measures and ability to discriminate between groups classified by NC severity. Sensitivity and specificity were assessed using Area under the Receiver Operating Curve (AUC) and responsiveness over time using effect sizes (ES).Results: Cronbach's alpha for the CQ7 was 0.92, and the ICC was 0.81, indicating good reliability. CQ7 correlated most strongly with the TSS (r = 0.60, p < 0.01), the PGWBI general health dimension (r = 0.56, p < 0.01), and the MOS Sleep scale 'sleep short of breath' dimension (r = 0.49, p < 0.01). Correlations with acoustic rhinometry were generally low. The instrument discriminated well between NC severity groups (ES 0.33-2.07) and AUC was 0.93, indicating excellent sensitivity and specificity. The measure was responsive to change (ES = 1.1) in patients reporting improvement in NC.Conclusions: The Spanish version of the CQ7 is appropriate for detecting, measuring, and monitoring NC in allergic rhinitis patients. [ABSTRACT FROM AUTHOR]

VOC Omicron induce "common cold symptoms" and sore throat more often than wild-type and VOC Delta infections (Figures 2 and 3). Presentation of airway and general symptoms in COVID-19 caused by dominant SARS-CoV-2 variants: A follow-up on ARIA consensus GLO:1X5/01nov22:all15416-fig-0001.jpg PHOTO (COLOR): 1 Expected symptom intensity on analogue scale (0: no symptom and 10: strongest symptoms) for wild-type and virus variants of SARS-CoV-2, rated by ARIA specialists. Symptom groups A/B/C/D are explained in the main text and referred to Figure 2 gl Significantly differing symptoms were grouped concerning common cold and sore throat, chemosensory, bronchial and pulmonary, as well as systemic (Figure 2). [Extracted from the article]

Background: Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication‐related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods: Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence‐based, integrated care approach. Results: This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence‐based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion: This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation. [ABSTRACT FROM AUTHOR]

Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real‐world data"). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co‐medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods: We assessed the MASK‐air® app data (May 2015–December 2020) by users self‐reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co‐medication. Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co‐medication than in monotherapy (including the fixed combination azelastine‐fluticasone) schemes. In adjusted models, azelastine‐fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine‐fluticasone was the drug class with the lowest chance of being used in co‐medication (adjusted OR = 0.75; 95% CI = 0.71–0.80). Conclusion: Median VAS levels were higher in co‐medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Loss of smell is one of the most difficult-totreat symptoms in patients with severe CRSwNP. Objectives: Assess the impact of mepolizumab on loss of smell in patients with severe CRSwNP enrolled in the SYNAPSE study Methods: SYNAPSE, a randomized, double-blind, placebocontrolled, 52-week study, enrolled 407 adults with severe bilateral CRSwNP in need of repeat NP surgery. Efficacy and safety of 4-weekly mepolizumab 100 mg SC plus SOC were assessed. Post hoc analyses: change from baseline in loss of smell Visual Analog Scale (VAS) symptom score at Weeks 49-52, and demographics of patients with a =3-point improvement. Results: At baseline, patients had impaired sense of smell (mean [SD] loss of smell VAS symptom scores: mepolizumab 9.63[0.830]; placebo 9.68[0.596]). Mepolizumab-treated patients had greater mean (SE) change from baseline in their loss of smell VAS symptom scores between Weeks 49-52 versus placebo (-3.00[0.231] vs -1.49[0.234], treatment difference [95% CI] -1.51[-2.15, -0.87; p<0.001]). At Weeks 49-52, a =3-point improvement in loss of smell VAS symptom score was achieved by 36% of mepolizumab-treated versus 19% of placebo-treated patients (OR [95% CI]: 2.33[1.48, 3.68];p<0.001). These mepolizumabtreated patients were more likely to have had =2 surgeries prior to study entry versus those who did not achieve a =3-point improvement in loss of smell VAS score (84% vs 70%). Conclusions: By Week 52, mepolizumab-treated patients with fewer surgeries at baseline had greater improvements in their sense of smell versus those with more surgeries. [ABSTRACT FROM AUTHOR]

Background and Aims: Asthma is a heterogeneous respiratory disease that encompasses different inflammatory and functional endophenotypes. Many non‐invasive biomarkers has been investigated to its pathobiology. Heany et al proposed a clinical algorithm that classifies severe asthmatic patients into likely‐eosinophilic phenotypes, based on accessible biomarkers: PBE, current treatment, FeNO, presence of nasal polyps (NP) and age of onset. Materials and Methods: We assessed the concordance between the algorithm proposed by Heany et al. with sputum examination, the gold standard, in 145 asthmatic patients of the MEGA cohort with varying grades of severity. Results: No correlation was found between both classifications 0.025 (CI = 0.013–0.037). Moreover, no relationship was found between sputum eosinophilia and peripheral blood eosinophilia count in the total studied population. Discussion and Conclusion: In conclusion, our results suggest that grouping the biomarkers proposed by Heany et al. are insufficient to diagnose eosinophilic phenotypes in asthmatic patients. Sputum analysis remains the gold standard to assess airway inflammation. [ABSTRACT FROM AUTHOR]

Obesity and asthma are associated with systemic inflammation maintained by mediators released by adipose tissue and lung. This study investigated the inflammatory serum mediator profile in obese subjects (O) (n = 35), non-obese asthma (NOA) patients (n = 14), obese asthmatics (OA) (n = 21) and healthy controls (HC) (n = 33). The effect of weight loss after bariatric surgery (BS) was examined in 10 OA and 31 O subjects. We analyzed serum markers including leptin, adiponectin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, ST2, IL-5, IL-9, and IL-18. Compared with HC subjects, the O group showed increased levels of leptin, TGF-β1, TNFR2, MCP-1, ezrin, YKL-40, and ST2; the OA group presented increased levels of MCP-1, ezrin, YKL-40, and IL-18, and the NOA group had increased levels of ezrin, YKL-40, IL-5, and IL-18. The higher adiponectin/leptin ratio in NOA with respect to OA subjects was the only significant difference between the two groups. IL-9 was the only cytokine with significantly higher levels in OA with respect to O subjects. TNFR2, ezrin, MCP-1, and IL-18 concentrations significantly decreased in O subjects after BS. O, OA, and NOA showed distinct patterns of systemic inflammation. Leptin and adiponectin are regulated in asthma by obesity-dependent and -independent mechanisms. Combination of asthma and obesity does not result in significant additive effects on circulating cytokine levels. [ABSTRACT FROM AUTHOR]

The superior clinical effect of MP-AzeFlu compared to FP and AZE monotherapy may be related to greater up-regulation of anti-inflammatory GILZ gene expression and, to a lesser extent, MKP-1 and TTP. Keywords: azelastine; fluticasone; gene expression; GILZ; MKP-1; MP-AzeFlu; TTP EN azelastine fluticasone gene expression GILZ MKP-1 MP-AzeFlu TTP 788 791 4 06/01/22 20220601 NES 220601 Key Messages MP-AzeFlu has demonstrated efficacy in allergic rhinitis, and a superior effect compared with FP and AZE administered in monotherapy. Superior effect of MP-AzeFlu compared to monotherapy with fluticasone propionate or azelastine on GILZ, MKP-1 and TTP anti-inflammatory gene expression in healthy and inflamed upper airway mucosa. [Extracted from the article]

There is increasing preclinical and clinical data supporting a potential association between Traumatic Brain Injury (TBI) and Parkinson's disease (PD). It has been suggested that the glutamate-induced excitotoxicity underlying TBI secondary neuronal degeneration (SND) might be associated with further development of PD. Interestingly, an accumulation of extracellular glutamate and olfactory dysfunction are both sharing pathological conditions in TBI and PD. The possible involvement of glutamate excitotoxicity in olfactory dysfunction has been recently described, however, the role of olfactory bulbs (OB) glutamate excitotoxicity as a possible mechanism involved in the association between TBI and PD-related neurodegeneration has not been investigated yet. We examined the number of nigral dopaminergic neurons (TH +), nigral α-synuclein expression, the striatal dopamine transporter (DAT) expression, and motor performance after bilateral OB N-Methyl-D-Aspartate (NMDA)-induced excitotoxic lesions in rodents. Bulbar NMDA administration induced a decrease in the number of correct choices in the discrimination tests one week after lesions (p < 0.01) and a significant decrease in the number of nigral DAergic neurons (p < 0.01) associated with an increase in α-synuclein expression (p < 0.01). No significant striatal changes in DAT expression or motor alterations were observed. Our results show an association between TBI-induced SND and PD-related neurodegeneration suggesting that the OB excitotoxicity occurring in TBI SND may be a filling gap mechanism underlying the link between TBI and PD-like pathology. [ABSTRACT FROM AUTHOR]

Purpose: Patient perspective is an important and increasingly sought-after complement to clinical assessment. The aim of this study was to transcribe individual patients' experience of treatment in a dupilumab clinical trial through free-text responses with analysis using natural language processing (NLP) to obtain the unique perspective of patients on disease impact and unmet needs with existing treatment to inform future trial design. Patients and Methods: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) who were enrolled in a Phase IIa randomized controlled trial comparing dupilumab with placebo (NCT01920893) were invited to complete a self-assessment of treatment (SAT) tool at the end of treatment, asking, "What is your opinion on the treatment you had during the trial? What did you like or dislike about the treatment?" Free-text responses were analyzed for the overall cohort and according to treatment assignment using natural language processing including sentiment scoring. In a mixed-methods approach, quantitative patient-reported outcome (PRO) results were utilized to complement the qualitative analysis of free-text responses. Results: Of 60 patients enrolled in the study, 43 (71.6%) completed the SAT and responses from 37 patients were analyzed (placebo, n = 16; dupilumab, n = 21). Word analyses showed that the most common words were "smell," "improve," "staff," "great," "time," and "good." Across the whole cohort, "smell" was the most common symptom-related word. The words "smell" and "experience" were more likely to occur in patients treated with dupilumab. Patients treated with dupilumab also had more positive sentiment in their SAT responses than those who received placebo. The results from this qualitative analysis were reflected in quantitative PRO results. Conclusion: "Smell" was important to patients with CRSwNP, highlighting its importance as a patient-centric efficacy outcome measure in the context of clinical trials in CRSwNP. Trial Registration: ClinicalTrials.gov, NCT01920893. Registered 12 August 2013, https://www.clinicaltrials.gov/ct2/show/NCT01920893. [ABSTRACT FROM AUTHOR]

Keywords: ACE2; chronic rhinosinusitis; COVID-19; eosinophil; olfactory neuroepithelium; SARS-CoV-2; TMPRSS2 EN ACE2 chronic rhinosinusitis COVID-19 eosinophil olfactory neuroepithelium SARS-CoV-2 TMPRSS2 2904 2907 4 09/03/21 20210901 NES 210901 ACKNOWLEDGMENTS This study was partially sponsored by a research grant (FIS PI19/00806) from Instituto Carlos III, Ministerio de Ciencia, Innovación y Universidades, Spain. (G) mRNA expression levels, as revealed by RT-PCR, of genes encoding for SARS-CoV-2 entry protein (ACE2 and TMPRSS2) in olfactory mucosa from CRSwNP patients and control cases. However, ACE2/TMPRSS2 expressions in the ONE from CRSwNP patients, that may be a risk factor for SARS-CoV-2 infection of the olfactory bulbs and brain entry, remain to be investigated. [Extracted from the article]

We sought to identify and correlate the severity of traumatic brain injuries (TBIs) associated with olfactory dysfunction with cognitive and behavioral profiles. Patients with TBI undergoing treatment in a specialized neuro-rehabilitation hospital. Prospective study. Glasgow Coma Scale (GCS) at the time of injury and during posttraumatic amnesia. Motor functions were assessed with the Functional Instrument Measure and Disability Rating Scales. The Wechsler Adult Intelligence test was used for neuropsychologic assessment and the Neuropsychiatric Inventory was used to assess behavioral changes. The Barcelona Smell Test-24 was used to study subjective smell loss. A total of 111 patients with TBI were enrolled (33 females; mean age 32.86 years); 38.73% exhibited smell loss. Patients with no olfactory impairment (OI) had worse TBIs than those with OI (GCS scores 5.65 and 7.74, respectively); no significant differences in cognitive behaviors, such as attention memory, visuoperception, and visuoconstruction, were observed. However, patients with TBI and olfactory dysfunction showed statistically significant alterations in neuropsychiatric behavioral performances such as feeding when compared with patients with TBI without smell loss. Olfactory dysfunction in patients with a TBI correlates with altered neuropsychiatric behavioral performances such as feeding, sleeping, and motor behavior. [ABSTRACT FROM AUTHOR]

Background: Although there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA‐EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods: A modified Delphi process was used. The ARIA members who were seeing COVID‐19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID‐19, common cold and allergic rhinitis. Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two‐way ANOVA revealed significant differences in the symptom intensity between the three diseases (p <.001). Conclusions: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID‐19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire. [ABSTRACT FROM AUTHOR]

Background: The practice of allergology varies widely between countries, and the costs and sales for the treatment of rhinitis differ depending on practices and health systems. To understand these differences and their implications, the rhinitis market was studied in some of the EU countries. Methods: We conducted a pharmaco‐epidemiological database analysis to assess the medications that were being prescribed for allergic rhinitis in the years 2016, 2017 and 2018. We used the IQVIA platforms for prescribed medicines (MIDAS®—Meaningful Integration of Data, Analytics and Services) and for OTC medicines (OTC International Market Tracking—OTCims). We selected the five most important markets in the EU (France, Germany, Italy, Poland and Spain). Results: Intranasal decongestants were excluded from the analyses because they are rarely prescribed for allergic rhinitis. For both Standard Units (SU) and costs, France is leading the other countries. In terms of SU, the four other countries are similar. For costs, Poland is lower than the three others. However, medication use differs largely. For 2018, in SU, intranasal corticosteroid is the first treatment in Poland (70.0%), France (51.3%), Spain (51.1%) and Germany (50.3%), whereas the Italian market is dominated by systemic antihistamines (41.4%) followed by intranasal corticosteroids (30.1%). Results of other years were similar. Discussion: There are major differences between countries in terms of rhinoconjunctivitis medication usage. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a conserved family of small endogenous noncoding RNA molecules that modulate post‐transcriptional gene expression in physiological and pathological processes. miRNAs can silence target mRNAs through degradation or inhibition of translation, showing their pivotal role in the pathogenesis of many human diseases. miRNAs play a role in regulating immune functions and inflammation and are implicated in controlling the development and activation of T and B cells. Inflammatory chronic upper airway diseases, such as rhinitis and rhinosinusitis, are spread all over the world and characterized by an exaggerated inflammation involving a complex interaction between immune and resident cells. Until now and despite allergy, little is known about their etiology and the processes implicated in the immune response and tuning inflammation of these diseases. This review highlights the knowledge of the current literature about miRNAs in inflammatory chronic upper airways diseases and how this may be exploited in the development of new clinical and therapeutic strategies. [ABSTRACT FROM AUTHOR]

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway. [ABSTRACT FROM AUTHOR]

In this article, we propose that differences in COVID-19 morbidity may be associated with transient receptor potential ankyrin 1 (TRPA1) and/or transient receptor potential vanilloid 1 (TRPV1) activation as well as desensitization. TRPA1 and TRPV1 induce inflammation and play a key role in the physiology of almost all organs. They may augment sensory or vagal nerve discharges to evoke pain and several symptoms of COVID-19, including cough, nasal obstruction, vomiting, diarrhea, and, at least partly, sudden and severe loss of smell and taste. TRPA1 can be activated by reactive oxygen species and may therefore be up-regulated in COVID-19. TRPA1 and TRPV1 channels can be activated by pungent compounds including many nuclear factor (erythroid-derived 2) (Nrf2)-interacting foods leading to channel desensitization. Interactions between Nrf2-associated nutrients and TRPA1/TRPV1 may be partly responsible for the severity of some of the COVID-19 symptoms. The regulation by Nrf2 of TRPA1/TRPV1 is still unclear, but suggested from very limited clinical evidence. In COVID-19, it is proposed that rapid desensitization of TRAP1/TRPV1 by some ingredients in foods could reduce symptom severity and provide new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: The MEGA (MEchanism underlying the Genesis and evolution of Asthma) project is a multicenter cohort study carried out in eight Spanish hospitals, gathering clinical, physiological, and molecular data from patients with asthma and multimorbidities in order to gain insight into the different physiopathological mechanisms involved in this disorder. Material and Methods: We report the baseline clinical and physiological characteristics and biomarker measures of adult participants in the project with the aim of better understanding the natural history and underlying mechanisms of asthma as well as the associated multimorbidities across different levels of severity. We carried out a detailed clinical examination, pulmonary function testing, measurement of fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick tests, chest computed tomography scan, asthma questionnaires, and multimorbidity assessment in 512 asthmatic patients. Results: When compared to patients with milder disease, severe asthmatic patients showed greater presence of symptoms, more exacerbations, lower asthma control, increased airflow obstruction, and higher frequency of chronic rhinosinusitis with nasal polyps, severe rhinitis, anxiety and depression, gastroesophageal reflux, and bronchiectasis. Conclusion: The MEGA project succeeded in recruiting a high number of asthma patients, especially those with severe disease, who showed lower control and higher frequency of multimorbidities. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak in China due to coronavirus disease 2019 (COVID-19) various studies have been published describing olfactory and gustatory dysfunction (OGD). Objective: The aim was to investigate the frequency and severity of OGD in SARS-CoV-2 (+) out-patients compared to controls with common cold/flu like symptoms and two negative RT-PCR. Methods: A multicenter cross-sectional study on SARS-CoV-2-positive out-patients (n = 197) and controls (n = 107) from five Spanish Hospitals. Severity of OGD was categorized by visual analogue scale (VAS). Frequency and severity of the chemosensory impairment were analyzed. Results: The frequencies of smell (70.1%) and taste loss (65%) were significantly higher among COVID-19 subjects than in the controls (20.6% and 19.6%, respectively). Simultaneous OGD was more frequent in the COVID-19 group (61.9% vs 10.3%) and they scored higher in VAS for severity of OGD than controls. In the COVID-19 group, OGD was predominant in young subjects 46.5 ± 14.5 and females (63.5%). Subjects with severe loss of smell were younger (42.7 years old vs 45.5 years old), and recovered later (median = 7, IQR = 5.5 vs median = 4, IQR = 3) than those with mild loss of smell. Subjects with severe loss of taste, recovered later in days (median = 7, IQR = 6 vs median = 2, IQR = 2), compared to those with mild loss. Conclusion: OGD is a prevalent symptom in COVID-19 subjects with significant differences compared to controls. It was predominant in young and females subjects. Stratified analysis by the severity of OGD showed that more than 60% of COVID-19 subjects presented a severe OGD who took a longer time to recover compared to those with mild symptoms. [ABSTRACT FROM AUTHOR]

Background: Idiopathic hyposmia (IH) is a prodromal marker of Parkinson disease (PD). However, IH is common in the general population and only a minority will develop PD. Identification of individuals with IH at prodromal stage of PD would serve to select them to implement neuroprotective agents, when available. Objective: To identify prodromal PD in IH patients using the Movement Disorders Society (MDS) research criteria for prodromal PD. Methods: We applied the MDS research criteria for prodromal PD to 25 consecutive patients older than 50 years who were self-referred for smell loss and had IH, and to 18 controls. A number of risk and prodromal PD markers were assessed in all participants including REM sleep behavior disorder (RBD) by video-polysomnography and nigrostriatal dopaminergic dysfunction by DAT-SPECT. After follow-up of 4.7 ± 2.2 years, participants were re-assessed to look for incident PD. Results: Prodromal PD probability was higher in patients than in controls (19.45 ± 34.9% versus 1.74 ± 4.48%; p = 0.019). Four (16%) patients met the criteria of prodromal PD surpassing 80% probability (99.8%, 99.5%, 88.3%, 86.4%). Three (12%) patients had RBD and four (16%) abnormal DAT-SPECT. At the end of follow-up, one (4%) IH patient who had RBD and baseline prodromal PD probability of 86.4% developed PD, while all controls remained disease free. Conclusions: Prodromal PD is infrequent among IH patients. MDS research criteria for prodromal PD are useful to identify a subgroup of IH patients at high risk of PD when RBD is assessed by video-polysomnography and nigrostriatal dopamine deficiency with DAT-SPECT. [ABSTRACT FROM AUTHOR]