Real-Life Study of Patient Preference for Dupilumab or Revision Surgery for Recurrent Chronic Rhinosinusitis with Nasal Polyps.

(1) Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a high rate of recurrence in patients, despite therapy with local corticosteroids and functional endoscopic sinus surgery. Dupilumab, a recombinant monoclonal human IgG4 antibody directed against the IL-4 receptor α that inhibits both IL-4 and IL-13 signal transduction, is available for symptomatic therapy. Patient preference between repeated surgery and injection therapy with Dupilumab is not known. (2) Methods: Patients who had experienced at least one surgical intervention for nasal polyps and were treated with Dupilumab for at least 3 months completed a retrospective patient questionnaire. (3) Results: In a cohort of 75 previously operated CRSwNP patients, 91.5% preferred therapy with Dupilumab to repeated surgery for nasal polyps. Preference for Dupilumab in the subgroups of patients with concomitant Non-steroidal Anti-inflammatory Drugs Exacerbated Respiratory Disease (N-ERD) (n = 32), patients with concomitant asthma (n = 25), and patients without concomitant disease (n = 18) was 100%, 96%, and 72%, respectively. (4) Conclusions: Patient preference for Dupilumab over repeat surgery is strongest in previously operated CRSwNP patients with concomitant asthma or N-ERD, but remains very high in patients without concomitant disease.

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

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

The role of sociodemographic, psychosocial, and behavioral factors in the use of preventive healthcare services in children and adolescents: results of the KiGGS Wave 2 study.

BACKGROUND: In Germany, various preventive services are offered to children and adolescents. These include regular standardized examinations (so called U/J examinations) and several vaccinations. Although strongly recommended, most of them are not mandatory. Our aim is to identify factors associated with the use of U/J examinations and vaccination against diphtheria, hepatitis B, Hib, pertussis, polio, and tetanus. While previous research has focused on sociodemographic factors, we also include socioeconomic, behavioral, and psychosocial factors. METHODS: We analyzed cross-sectional data from 15,023 participants (aged 0-17 years) of the nationwide representative KiGGS Wave 2 Survey. Participation in U/J examinations was assessed using a questionnaire, filled out by participants and/or their parents. Information on vaccination status was drawn from the participants' vaccination booklets. To identify relevant determinants for the use of preventive examinations and vaccinations, unadjusted and adjusted logistic regression models were employed with up to 16 different independent variables. RESULTS: Various independent variables showed an association with the use of preventive services. Higher socioeconomic status, absence of migration background, and lower household size were associated with significantly higher utilization of U examinations. Parents' marital status, area of residence, behavioral and psychosocial factors yielded insignificant results for most U/J examinations. Higher vaccination rates were found for children with no migration background, with residence in eastern Germany, lower household size, and with married parents. CONCLUSION: This study attempted to depict the influence of sociodemographic, psychosocial, and behavioral factors on the use of several preventive services. Our results indicate that predominantly sociodemographic variables influence the use of preventive services. Further efforts should be made to investigate the interplay of different determinants of healthcare use in children and adolescents.

[Update on point-of-care-based coagulation treatment : Systems, reagents, device-specific treatment algorithms]. / Update der Point-of-care-basierten Gerinnungstherapie : Systeme, Reagenzien, gerätespezifische Behandlungsalgorithmen.

Viscoelastic test (VET) procedures suitable for point-of-care (POC) testing are in widespread clinical use. Due to the expanded range of available devices and in particular due to the development of new test approaches and methods, the authors believe that an update of the current treatment algorithms is necessary. The aim of this article is to provide an overview of the currently available VET devices and the associated reagents. In addition, two treatment algorithms for the VET devices most commonly used in German-speaking countries are presented.

How can outdoor sports protect themselves against climate change-related health risks? - A prevention model based on an expert Delphi study.

OBJECTIVES: To systematically develop an adaptation model to reduce climate change-related health risks for outdoor athletes. DESIGN: Delphi Method study. METHODS: A classic asynchronous Delphi study was conducted with a total of three survey rounds. 24 experts from the eight largest outdoor sport associations by membership in the German Olympic Sports Confederation were included as well as 24 medical experts with expertise in sport medicine, internal medicine, allergology, dermatology, infectiology, or toxicology. Based on open-ended questions, panelists were asked to consider prevention measures for sport organizations and clubs. Free text responses were analyzed by qualitative content analysis according to Mayring. RESULTS: Experts recommended establishing the following eight fields of prevention measures: technical and structural measures; organizational measures; personalized measures; basic, advanced, and continuing education; concepts of action, warning concepts, and financial concepts; cooperation and coordination; campaigns; and evaluation measures. CONCLUSIONS: The pyramid model presented in this study systematizes possible sport-specific adaptation measures on climate change by empirical aggregation of knowledge from scientists, sport organizations, clubs, trainers, and professional athletes. To assess the effectiveness of these prevention measures, sport organizations may incorporate them not only into broader operations but also everyday training routines.

C-H Bond Activation by Iridium(III) and Iridium(IV) Oxo Complexes.

Oxidation of an iridium(III) oxo precursor enabled the structural, spectroscopic, and quantum-chemical characterization of the first well-defined iridium(IV) oxo complex. Side-by-side examination of the proton-coupled electron transfer thermochemistry revealed similar driving forces for the isostructural oxo complexes in two redox states due to compensating contributions from H+ and e- transfer. However, C-H activation of dihydroanthracene revealed significant hydrogen tunneling for the distinctly more basic iridium(III) oxo complex. Our findings complement the growing body of data that relate tunneling to ground state properties as predictors for the selectivity of C-H bond activation.

Platelet-to-lymphocyte ratio might predict the response to dupilumab treatment for patients with nasal polyposis.

BACKGROUND: Dupilumab is a monoclonal antibody against interleukin 4 receptor alpha and has proven to be clinically effective in treating patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, a certain number of patients are non- or partial responders. This study aims to investigate the relevance of inflammatory markers with regard to therapy response to dupilumab in CRSwNP patients. METHODS: All patients with CRSwNP treated with dupilumab at a tertiary healthcare center with available pretreatment inflammatory markers were included. The values of pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with the outcome. Patients were stratified according to the respective median value (> median was considered high). The binary logistic regression was performed with regard to total treatment response (post-treatment total nasal polyp score (NPS) 0). RESULTS: A total of 65 CRSwNP patients with available pretreatment peripheral blood values were included in the study. The mean pre- and post-treatment total NPS values were 4.3 ± 1.9 and 1.2 ± 1.6, respectively. High PLR (> 131.2) was independently associated with a 3.9-fold higher probability of reaching the NPS value of 0 in the multivariable analysis. On the other hand, High NLR (> 1.9) did not significantly associate with the outcome. CONCLUSIONS: The current study provides insights into the potential positive predictive value of the high PLR (> 131.2) in CRSwNP patients regarding treatment with dupilumab. There is a need for further prospective studies for validation of these results, especially in cohorts of patients with severe CRSwNP.

Patient perspectives on recall period and response options in patient-reported outcome measures for chronic rhinosinusitis symptomatology: An international multi-centered study.

BACKGROUND: Existing patient-reported outcome measures (PROMs) for chronic rhinosinusitis (CRS) use a variety of recall periods and response scales to assess CRS symptom burden. Global perspectives of CRS patients regarding optimal recall periods and response scales for CRS PROMs are unknown. METHODS: This was a multi-center, cross-sectional study recruiting 461 CRS patients from sites across the United States, Saudi Arabia, New Zealand, and Austria. Participants chose which CRS symptom recall period (1 day, 2 weeks, 1 month, >1 month) was most reflective of their current disease state and upon which to best base treatment recommendations (including surgery). Participants also chose which of six response scales (one visual analogue scale and five Likert scales ranging from four to eight items) was easiest to use, understand, and preferred. RESULTS: A plurality of participants (40.0%) felt their CRS symptoms' current state was best reflected by a 1-month recall period. However, most patients (56.9%) preferred treatment recommendations to be determined by symptoms experienced over a >1 month period. The four- and five-item Likert scales were the easiest to understand (26.0% and 25.4%, respectively) and use (23.4% and 26.7%, respectively). The five-item (26.4% rating it most preferred and 70.9% rating it preferred) and four-item Likert (22.3% rating it most preferred and 56.4% rating it preferred) response scales were most preferred. CONCLUSION: Future PROMs for CRS should consider assessment of symptoms over a 1-month period and use a four- or five-item Likert response scale to reflect global patient preferences. These findings also inform interpretation of current CRS PROMs.

The "real life" efficacy of dupilumab is independent of initial polyp size and concomitant steroids in CRSwNP.

BACKGROUND: Dupilumab significantly improves symptom control in chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with large polyps at the initiation of treatment (total polyp score (TPS) ≥ 5) have been the focus in published studies. Patients with significant burden of disease but small polyps (TPS ≤ 4) have not yet been evaluated for clinical response. This study set out to evaluate the benefit of dupilumab treatment on cohorts of small (TPS ≤ 4) compared to large polyps (TPS ≥ 5). Furthermore, benefit of concomitant oral and/or nasal steroid therapy has been evaluated. METHODS: 97 patients with CRSwNP, who were begun on dupilumab between January 2020 and October 2021, were included. All patients were followed-up for 6 months. At each visit they underwent nasal endoscopy, smell identification tests and filled out validated patient questionnaires. RESULTS: Significant drops in TPS were seen in both patient groups after 6 months of therapy, dropping from a median score of 3 to 0 and from 6 to 2 in patients with small and large polyps respectively. Furthermore, a linear mixed model calculated a drop of 22% and 24% in TPS per month in patients with small and large polyps respectively with no significant difference in rate of decline. Finally the model showed that neither oral nor nasal steroids influenced the rate of response to dupilumab therapy. CONCLUSIONS: Polyp size at the initiation of dupilumab therapy and whether patients continue to take steroid therapy does not appear to influence effectiveness of dupilumab treatment.

Photoinduced Metallonitrene Formation by N2 Elimination from Azide Diradical Ligands.

Transition-metal nitrides/nitrenes are highly promising reagents for catalytic nitrogen-atom-transfer reactivity. They are typically prepared in situ upon optically induced N2 elimination from azido precursors. A full exploitation of their catalytic potential, however, requires in-depth knowledge of the primary photo-induced processes and the structural/electronic factors mediating the N2 loss with birth of the terminal metal-nitrogen core. Using femtosecond infrared spectroscopy, we elucidate here the primary molecular-level mechanisms responsible for the formation of a unique platinum(II) nitrene with a triplet ground state from a closed-shell platinum(II) azide precursor. The spectroscopic data in combination with quantum-chemical calculations provide compelling evidence that product formation requires the initial occupation of a singlet excited state with an anionic azide diradical ligand that is bound to a low-spin d8 -configured PtII ion. Subsequent intersystem crossing generates the Pt-bound triplet azide diradical, which smoothly evolves into the triplet nitrene via N2 loss in a near barrierless adiabatic dissociation. Our data highlight the importance of the productive, N2 -releasing state possessing azide ππ* character as a design principle for accessing efficient N-atom-transfer catalysts.

Nasal IL-13 production identifies patients with late-phase allergic responses.

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy. OBJECTIVE: We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response. METHODS: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours. CONCLUSIONS: IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.

Socio-economic inequalities in body mass index among preschool children: do sports programs in early childhood education and care centers make a difference?

Background: Overweight in childhood is considered to be one of the most serious public health challenges. Many studies have investigated individual-level determinants of children's body mass index (BMI), yet studies exploring determinants at the meso-level are sparse. The aim of our study was to examine how a sports focus at early childhood education and care (ECEC) centers moderates the effect of parental socio-economic position (SEP) on children's BMI. Methods: We used data from the German National Educational Panel Study and included 1,891 children (955 boys and 936 girls) from 224 ECEC centers in our analysis. Linear multilevel regressions were used to estimate the main effects of family SEP and the ECEC center sports focus, as well as their interaction, on children's BMI. All analyses were stratified by sex and adjusted for age, migration background, number of siblings, and employment status of parents. Results: Our analysis confirmed the wellknown health inequalities in childhood overweight with a social gradient toward a higher BMI for children from lower SEP families. An interactive effect between family SEP and ECEC center sports focus was found. Boys with low family SEP not attending a sports-focused ECEC center had the highest BMI among all boys. In contrast, boys with low family SEP attending a sports-focused ECEC center had the lowest BMI. For girls, no association regarding ECEC center focus or interactive effects emerged. Girls with a high SEP had the lowest BMI, independent of the ECEC center focus. Conclusion: We provided evidence for the gender-specific relevance of sports-focused ECEC centers for the prevention of overweight. Especially boys from low SEP families benefited from a sports focus, whereas for girls the family's SEP was more relevant. As a consequence, gender differences in determinants for BMI at different levels and their interaction should be considered in further research and preventive measures. Our research indicates that ECEC centers may decrease health inequalities by providing opportunities for physical activity.

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.

Dimethyl fumarate treatment in relapsed and refractory cutaneous T-cell lymphoma: a multicenter phase 2 study.

Targeted therapies for cutaneous T-cell lymphoma (CTCL) are limited and curative approaches are lacking. Furthermore, relapses and drug induced side effects are major challenges in the therapeutic management of patients with CTCL, creating an urgent need for new and effective therapies. Pathologic constitutive NF-κB activity leads to apoptosis resistance in CTCL cells and, thus, represents a promising therapeutic target in CTCL. In a preclinical study we showed the potential of dimethyl fumarate (DMF) to block NF-κB and, specifically, kill CTCL cells. To translate these findings to applications in a clinical setting, we performed a multicentric phase 2 study evaluating oral DMF therapy in 25 patients with CTCL stages Ib to IV over 24 weeks (EudraCT number 2014-000924-11/NCT number NCT02546440). End points were safety and efficacy. We evaluated skin involvement (using a modified severity weighted assessment tool [mSWAT]), pruritus, quality of life, and blood involvement, if applicable, as well as translational data. Upon skin analysis, 7 of 23 (30.4%) patients showed a response with >50% reduction in the mSWAT score. Patients with high tumor burden in the skin and blood responded best to DMF therapy. Although not generally significant, DMF also improved pruritus in several patients. Response in the blood was mixed, but we confirmed the NF-κB-inhibiting mechanism of DMF in the blood. The overall tolerability of the DMF therapy was very favorable, with mostly mild side effects. In conclusion, our study presents DMF as an effective and excellently tolerable therapeutic option in CTCL to be further evaluated in a phase 3 study or real-life patient care as well as in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT02546440.

Do family characteristics contribute to a socioeconomic gradient in overweight in early childhood? - Single mediation analyses of data from German preschool children.

Children's overweight is strongly associated with family socioeconomic position (SEP) and family characteristics (FC). There is limited research on the extent to which FC account for a socioeconomic gradient in childhood overweight. This study examined whether FC explain SEP differences in the prevalence of overweight. The study used baseline data of preschool-aged children from the German 'PReschool INtervention Study'. The sample (n = 872, 48% girls) was recruited at kindergartens in Baden-Württemberg, Germany. Data included children's measured weight status and parents' reports on socioeconomic indicators (e.g., school education, vocational education, income) and FC. Variables represent main determinants of overweight (nutrition: sweets consumption in front of TV, soft drink consumption, regular breakfast, child sets table; physical activity: outdoor sports; parental role model). In single mediation analyses indirect effects of SEP on overweight were analysed (OR[95%CI]). Preschool girls and boys with low parental education had higher odds for overweight than children with high parental education. Among boys, low levels of parental education contributed to the odds of overweight via indirect effects by both factors 'sweets consumption in front of TV' (OR = 1.31[1.05-1.59]) and 'no sports' (OR = 1.14[1.01-1.38]). Among girls, FC measured did not explain SEP differences in overweight. Family nutrition and parental/family physical activity contribute to inequalities in overweight among preschool boys, but not girls. Research is needed to identify FC that explain inequalities in overweight for both.

Understanding perceived addiction to and addictiveness of electronic cigarettes among electronic cigarette users: a cross-sectional analysis of the International Tobacco Control Smoking and Vaping (ITC 4CV) England Survey.

BACKGROUND AND AIMS: The addictive potential of electronic cigarettes (e-cigarettes) remains to be fully understood. We identified patterns and correlates of perceived addiction to e-cigarettes and perceived addictiveness of e-cigarettes relative to tobacco cigarettes (relative addictiveness) in dual users as well as exclusive e-cigarette users. DESIGN, SETTING AND PARTICIPANTS: Observational study using cross-sectional survey data from England (2016) from the International Tobacco Control Project (ITC) Four Country Smoking and Vaping (4CV) survey. The study comprised 832 current e-cigarette users who had been vaping for at least 4 months. MEASUREMENTS: Perceived addiction to e-cigarettes and relative addictiveness of e-cigarettes were examined. Socio-demographic factors were age, gender and education; markers of addiction included urge to vape, time to first vape after waking and nicotine strength used; vaping and smoking characteristics included frequency and duration of e-cigarette use, intention to quit, adjustable power or temperature, enjoyment, satisfaction relative to tobacco cigarettes and tobacco cigarette smoking status. FINDINGS: A total of 17% of participants reported feeling very addicted to e-cigarettes, while 40% considered e-cigarettes equally/more addictive than tobacco cigarettes. Those who felt very addicted had higher odds of regarding e-cigarettes as more addictive than tobacco cigarettes (odds ratio 3.4, 95% confidence interval 2.3-5.1). All markers of addiction, daily use and enjoyment were associated with higher perceived addiction, whereas time to first vape after waking, daily vaping and perceiving vaping as less satisfying than smoking were associated with relative addictiveness. CONCLUSIONS: Markers of addiction to e-cigarettes appear to correspond with perceived addiction to e-cigarettes, suggesting that self-reported perceived addiction might serve as an indicator of addiction. Prevalence both of markers of addiction and perceived addiction were comparatively low overall, suggesting a limited but relevant addictive potential of e-cigarettes. Additionally, positive and negative reinforcement, reflected here by enjoyment and relative satisfaction, might play a role in e-cigarette addiction.

Addictive Potential of e-Cigarettes as Reported in e-Cigarette Online Forums: Netnographic Analysis of Subjective Experiences.

BACKGROUND: While e-cigarettes usually contain nicotine, their addictive potential is not yet fully understood. We hypothesized that if e-cigarettes are addictive, users will experience typical symptoms of addiction. OBJECTIVE: The aim of our study was to investigate whether and how e-cigarette users report signs of addiction. METHODS: We identified 3 large German-language e-cigarette online forums via a systematic Google search. Based on a netnographic approach, we used deductive content analysis to investigate relevant posts in these forums. Netnography has the advantage of limiting the social desirability bias that prevails in face-to-face research, such as focus groups. The data were coded according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for tobacco use disorder, adapted for e-cigarettes. The DSM-5 criteria were used to portray a broad spectrum of possible experiences of addiction. RESULTS: Overall, 5337 threads in 3 forums were screened, and 451 threads containing relevant information were included in the analysis. Users reported experiences consistent with the DSM-5 criteria, such as craving e-cigarettes, excessive time spent vaping, and health issues related to e-cigarette use. However, our analysis also showed that users reported the absence of typical tobacco use disorder criteria, such as successful attempts to reduce the nicotine dosage. For most themes, reports of their absence were more frequent than of their presence. The absence of perceived addiction was mostly reported in contrast to prior tobacco smoking. CONCLUSIONS: This is the first study to use a netnographic approach to explore unfiltered self-reports of experiences of e-cigarette addiction by users in online forums. As hypothesized, some but not all users reported subjective experiences that corresponded to the criteria of tobacco use disorder as defined by the DSM-5. Nevertheless, subjective reports also indicated that many e-cigarette users felt in control of their behavior, especially in contrast to their prior use of tobacco cigarettes. The finding that some e-cigarette users subjectively experience addiction highlights the need for effective cessation programs to support users who experience their e-cigarette use as burdensome. This research can guide the refinement of instruments to assess e-cigarette addiction and guide cessation programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s40359-021-00682-8.

Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease.

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