Search

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma., Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021., Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients., Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated., Competing Interests: Conflict of interest: A. Bossios reports support from Novartis for attending meetings, outside the submitted work; participation on a data safety monitoring or advisory board for AstraZeneca, GSK, Novartis, Teva and Sanofi, outside the submitted work; and is a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society and Vice-chair of the Nordic Severe Asthma Network, outside the submitted work. K. Katsoulis reports payment or honoraria for lectures presentations, speakers bureaus, manuscript writing or educational events from GSK, Novartis and AstraZeneca; and support received from Menarini and Novartis for attending meetings and/or travel, outside the submitted work. K. Kostikas reports grants or contracts from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir, outside the submitted work; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, ELPEN, GSK, Menarini, Novartis and Sanofi-Genzyme, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Menarini, Novartis, Sanofi-Genzyme and WebMD, outside the submitted work; and is a member of the GOLD Assembly, disclosures made outside the submitted work. N. Rovina reports receiving honoraria for lectures and presentations from Chiesi, AstraZeneca, Menarini, Gilead and Baxter, outside the submitted work. K. Bieksienė reports receiving lecture honoraria from Berlin-Chemie, AstraZeneca and Norameda, outside the submitted work. A. ten Brinke reports grants from Teva and GSK, outside the submitted work; consulting fees from AstraZeneca, GSK, Novartis, Sanofi-Genzyme and Teva, outside the submitted work; and payment or honoraria for lectures received from AstraZeneca, GSK, Sanofi-Genzyme and Teva, outside the submitted work; and is Chair of the Dutch severe asthma registry RAPSODI, outside the submitted work, and ERS SHARP CRC national lead for the Netherlands. R. Chaudhuri reports grants or contracts from AstraZeneca, outside the submitted work; payment of honoraria for lectures from GSK, AstraZeneca, Teva, Chiesi, Sanofi and Novartis, outside the submitted work; support for attending meetings and/or travel from Chiesi, Sanofi and GSK, outside the submitted work; and participation in advisory board meetings for GSK, AstraZeneca, Teva, Chiesi and Novartis, outside the submitted work. H. Rupani reports grant funding from GSK and AstraZeneca, outside the submitted work; payments for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GSK, Novartis and Teva, outside the submitted work; and is an associate editor of this journal. P. Howarth is an employee of GSK, disclosure made outside the submitted work. C. Porsbjerg reports grants or contracts from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; consulting fees from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; personal honoraria from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work; participation on a data safety monitoring or advisory board for AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, outside the submitted work. E.H. Bel reports research grants from GSK and Teva, outside the submitted work; and consulting fees from AstraZeneca, GSK, Sterna Biologicals, Chiesi Pharmaceuticals, Sanofi/Regeneron and Teva, outside the submitted work. M.E. Hyland reports grants or contracts from Teva outside the submitted work; and payment received from GSK for writing educational material for respiratory nurses, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs., Materials and Methods: We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies., Results: Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids., Conclusion: A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma., Competing Interests: Conflict of interest: S. Principe is an employee of the University of Palermo with co-EU research funds EU-REACT FESR o FSE, PON Ricerca e Innovazione 2014–2020 - DM 1062/2021. Conflict of interest: A. Ten Brinke reports grants from AstraZeneca, GSK and TEVA, fees for advisory boards and lectures from AstraZeneca, GSK, Novartis, TEVA and Sanofi Genzyme. Conflict of interest: I. Grisle declares honoraria for lectures from AZ, Novartis, GSK, Berlin Chemie, Boehringer Ingelheim and Norameda. Conflict of interest: P. Kuna declares honoraria for lectures/presentations from AstraZeneca, GSK, Boehringer Ingelheim, Berlin Chemie, Menarini, FAES, Adamed, Polpharma, Glenmark, Novartis and Teva, and support for attending meetings from AstraZeneca, Berlin Chemie and Menarini. Conflict of interest: S. Popović-Grle declares consulting fees from AZ, GSK, Novartis, Pliva Teva, Sanofi and ALK, and honoraria for lectures from AZ, GSK, Novartis, Pliva TEVA, Sanofi and ALK. Conflict of interest: S. Škgrat declares, in the past 36 months, honoraria for lectures and educational events from AstraZeneca (AZ), Pliva Teva, Berlin Chemie, Chiesi and Medis, and participation on advisory boards for AZ and Berlin Chemie. Conflict of interest: C. Porsbjerg declares, in the past 36 months, grants from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK, consulting fees from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK, honoraria for lectures from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK, participation for advisory boards AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK. Conflict of interest: All the other authors declare that they have no conflicts of interest., (Copyright ©The authors 2023.)

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns., Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately., Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day -1 , 95% CI -5.24-2.62 mg·day -1 ) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns., Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner., Competing Interests: Conflict of interest: Z. Csoma reports lecture honoraria from AstraZenca, Sanofi, Teva and GSK outside the submitted work. A. ten Brinke reports grants and payment for expert testimony from GlaxoSmithKline, AstraZeneca, TEVA and Sanofi-Genzyme Regeneron outside the submitted work. B. Gemicioglu reports support for the present work from GSK; lecture honoraria from GSK, Novartis, Deva, Chiesi, Abdi İbrahim and Sandoz; travel support from GSK, AstraZeneca and Novartis; and leadership positions with SHARP (Turkey Coordinator), GARD (Turkey Coordinator) and Turkish Board of Pulmonology (Chair), outside the submitted work. C.C. Loureiro reports grants from GSK; consulting fees from AstraZeneca, GSK, Novartis and Sanofi; lecture honoraria from AstraZeneca, GSK, Novartis, Sanofi and Teva; and travel support from AstraZeneca, Novartis and Sanofi, outside the submitted work. D. Ramos-Barbón reports honoraria and institutional research funding from GSK, outside the submitted work. E.H. Bel reports grants from GlaxoSmithKline and TEVA; lecture honoraria from GlaxoSmithKline, TEVA, AstraZeneca, Sanofi-Genzyme, Regeneron, Chiesi and Sterna, outside the submitted work. J.A. Kroes reports grants from AstraZeneca, outside the submitted work. K. Samitas reports lecture honoraria from MSD, GSK, Chiesi, Novartis, AstraZeneca, ELPEN, Menarini, BMS, Specialty Therapeutics, Boehringer and Rontis; travel support from Boehringer; advisory board participation with AstraZeneca, GSK and Specialty Therapeutics; and a leadership position with the Hellenic Thoracic Society, outside the submitted work. L. Pérez de Llano reports support for the present work from AstraZeneca; grants from AstraZeneca, Faes, TEVA and Sanofi; lecture honoraria from AstraZeneca, TEVA, Sanofi, MSD, Leo Pharma, Gebro, GSK, Novartis, Chiesi, Techdow Pharma and Gilead; patents from AstraZeneca, Novartis, Faes, TEVA, GSK, Sanofi and Chiesi; and advisory board participation with AstraZeneca, outside the submitted work. R.W. Jakes reports support for the present work from GSK, as an employee and shareholder. S. Škrgat reports honoraria for lectures and educational events, supported by AstraZeneca, Sanofi, Chiesi, Pliva Teva and Medis; and participation on advisory boards of AstraZeneca, Chiesi and Sanofi, outside the submitted work. A. Bourdin reports support for the present work from GSK; grants from AstraZeneca, GSK and Boehringer Ingelheim; lecture honoraria, nonfinancial support and other support from AstraZeneca, GSK, Boehringer Ingelheim, Novartis, TEVA, Chiesi Farmaceuticals, Actelion, Gilead, Roche and Regeneron, outside the submitted work. B. Dahlén reports grants from Novartis and GSK; and consulting fees from AstraZeneca, Teva and Sanofi, outside the submitted work. E. Zervas reports advisory board fees from Astra, Chiesi, Elpen, GSK, Menarini, MSD and Novartis; honoraria and fees for lectures from Astra, Boehringer, Bristol-Myers, Chiesi, Elpen, GSK, Menarini, MSD and Novartis; travel accommodations and meeting expenses from Astra, Boehringer, Chiezi, Galenica, GSK, Elpen, MSD, Novartis and Roche; and holds a leadership role as Secretary General of Hellenic Thoracic Society, outside the submitted work. E. Heffler reports consulting fees and lecture honoraria from AstraZeneca, Sanofi, Regeneron, Novartis, GSK, Stallergenes-Greer and Circassia outside the submitted work. F. Schleich reports grants from GSK and AstraZeneca; and consulting fees and lecture honoraria from GSK, AstraZeneca and Chiesi, outside the submitted work. K. Eger reports that TEVA sponsored printing their PhD thesis, outside the submitted work. K. Bieksiene reports lecture honoraria from AstraZeneca and Berlin Chemie, outside the submitted work. M. Paula Rezelj reports lecture honoraria from AstraZeneca, Novartis, GSK and Stallergenes, outside the submitted work. M. Masoli reports an investigator-led nonpromotional grant from GlakoSmithKline and an advisory board fee from AstraZeneca outside the submitted work. N. Kwon reports support for the present work from GSK, as an employee and shareholder. P. Howarth reports support for the present work from GSK, as an employee and shareholder. P. Kopač reports lecture honoraria and advisory board participation from AstraZeneca, GSK and Berlin-Chemie outside the submitted work. R. Alfonso-Cristancho reports support for the present work from GSK, as an employee and shareholder. G. Celik reports consulting fees and lecture honoraria from Novartis and GSK outside the submitted work. J.K. Sont reports grants from AstraZeneca; outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown., Materials and Methods: The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies., Results: Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity., Conclusion: Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation., Competing Interests: Conflict of interest: L.G. Heaney reports the following relationships outside the submitted work: academic lead for the UK MRC Consortium for Stratified Medicine in Severe Asthma (industrial pharma partners: Amgen, AstraZeneca, Medimmune, Janssen, Novartis, Roche/Genentech, GlaxoSmithKline and Boehringer Ingelheim); project grant funding from Medimmune, Novartis UK, Roche/Genentech and GlaxoSmithKline; travel funding support to international respiratory meetings received from AstraZeneca, Chiesi, Novartis, Boehringer Ingelheim, Teva and GlaxoSmithKline; participated on advisory boards for AstraZeneca, Novartis, GlaxoSmithKline, Chiesi, Teva, Theravance and Vectura. Conflict of interest: B. Dahlén reports the following relationships outside the submitted work: grant received from GSK and Novartis to support Karolinska Severe Asthma Centre; personal consulting fees received from GSK, Novartis, Teva and AstraZeneca; consulting fees, paid to the institution, received from Region Stockholm; personal honoraria received from GSK, Novartis, Teva and AstraZeneca. Conflict of interest: S. Popović-Grle reports the following relationships outside the submitted work: payment for educational events from Abbot, Alkaloid, AstraZeneca, BerlinChemie Menarini, Boehringer Ingelheim, Medis, Novartis, Pliva-Teva, PharmaS, Providens, Salvus, Sandoz, Sanofi-Aventis and SwixxPharma; participation on advisory boards for AstraZeneca, Boehringer Ingelheim, BerlinChemie Menarini, GSK, Novartis, Pliva-Teva, PharmaS, Sanofi-Aventis and SwixxPharma. Conflict of interest: V. Sedlák reports the following relationships outside the submitted work: payment for presentations received from AstraZeneca, Novartis, GlaxoSmithKline, TEVA and Sanofi; payment for expert testimony payments received from AstraZeneca, Novartis, GlaxoSmithKline, TEVA and Sanofi; payment for participation on a data safety monitoring board or advisory board received from AstraZeneca, Novartis, GlaxoSmithKline, TEVA and Sanofi. Conflict of interest: L. Lehtimäki reports the following relationships outside the submitted work: fees for lectures or advisory board meetings received from ALK, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, GSK, Mundipharma, Novartis, Orion Pharma and Sanofi; owner of shares for Ausculthing OY. Conflict of interest: A. Bourdin reports the following relationships outside the submitted work: unrestricted grants received from AstraZeneca and Boehringer Ingelheim; consulting fees received from Astra Zeneca, GSK, Novartis, Sanofi Regeneron, Boehringer Ingelheim and Chiesi; payment or honoraria received for lectures, presentations, speakers bureaus, manuscript writing or educational events received from AstraZeneca, GSK, Novartis, Sanofi Regeneron, Boehringer Ingelheim and Chiesi; support for attending meetings and/or travel received from Astra Zeneca, GSK, Novartis, Sanofi Regeneron, Boehringer Ingelheim and Chiesi. Conflict of interest: S. Korn reports the following relationships outside the submitted work: consulting fees received from AstraZeneca, Novartis, GlaxoSmithKline and Sanofi; payment or honoraria received for lectures and presentations from AstraZeneca, Novartis, GlaxoSmithKline and Sanofi; participation on a data safety monitoring board or advisory board for AstraZeneca, Novartis and GlaxoSmithKline. Conflict of interest: M.W. Butler reports the following relationships outside the submitted work: payment or honoraria received for lectures and presentations from AstraZeneca, Novartis and GlaxoSmithKline; support received for international meeting attendance received from AstraZeneca; participation on Advisory Boards for ALK Abello, AstraZeneca, GlaxoSmithKline and Novartis; Chair of Medical Advisory Group, board member of Asthma Society of Ireland, Ireland member of GINA Assembly, President of Irish Thoracic Society (2022 to present). Conflict of interest: G.W. Canonica reports the following relationships outside the submitted work: payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from AstraZeneca, GSK, Novartis and Sanofi; participation on a data safety monitoring board or advisory board for AstraZeneca, GSK, Novartis and Sanofi; leadership or fiduciary role in other board, society, committee or advocacy group for EAACI Methodology Committee, REG Vice President and SANI Steering Committee. Conflict of interest: K. Beiksiene reports the following relationships outside the submitted work: payment or honoraria received for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from AstraZeneca and Berlin Chemie. Conflict of interest: A. ten Brinke reports the following relationships outside the submitted work: unrestricted grants received from TEVA, GSK and AstraZeneca; consulting fees paid to the institution from GSK, Sanofi, TEVA, AstraZeneca and Boehringer Ingelheim; payments for lectures, paid to the institution, received from GSK, TEVA, AstraZeneca and Sanofi; participation on research advisory boards for GSK, Sanofi, AstraZeneca, Boehringer Ingelheim and TEVA; Chair of Dutch severe asthma registry RAPSODI. Conflict of interest: P. Kuna reports the following relationships outside the submitted work: personal fees received for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Adamed, AstraZeneca, Boehringer Ingelheim, Berlin Chemie Menarini, Alvogen, Glenmark, Novartis, GSK, Chiesi, Polpharma and Teva. Conflict of interest: C. Chaves Loureiro reports the following relationships outside the submitted work: Consulting fees received from AstraZeneca and GSK. Payment for r presentations and speakers bureaus received from AstraZeneca, GSK, Novartis and Sanofi-Aventis. Support for attending meetings received from AstraZeneca, Novartis, Nippon, Sanofi-Aventis, Tecnifarma and VitalAire. Participation on Advisory Boards for AstraZeneca, GSK, Novartis and Sanofi-Aventis. Conflict of interest: Z. Lazic reports the following relationships outside the submitted work: payment or honoraria for educational events received from AstraZeneca, BerlinChemie Menarini, Boehringer Ingelheim, Novartis, PharmaS, Providens, Sandoz and Actavis-Teva Serbia; participation on Advisory Boards for AstraZeneca, Boehringer Ingelheim, BerlinChemie Menarini, Novartis and Actavis-Teva Serbia. Conflict of interest: S. Škrgat reports the following relationships outside the submitted work: honoraria received for lectures and educational events from Astra Zeneca, Pliva Teva, Berlin Chemie, Chiesi and Medis; participation on local advisory boards organized by AstraZeneca. Conflict of interest: J. Leuppi reports the following relationships outside the submitted work: J. Leuppi is supported by grants from the Swiss National Science Foundation (SNF 160072 and 185592) and by Swiss Personalised Health Network (SPHN 2018DR108); J. Leuppi has also received unrestricted grants from AstraZeneca AG Switzerland, Boehringer Ingelheim GmbH Switzerland, GSK AG Switzerland, and Novartis AG Switzerland. Conflict of interest: B. Gemicioglu reports the following relationships outside the submitted work: grants or contracts received from AstraZeneca, Novartis, GlaxoSmithKline and Sanofi; payment or honoraria received for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Novartis; support for attending meetings received from Novartis; participation on a data safety monitoring board or advisory board for GlaxoSmithKline. Conflict of interest: A. Bossios reports the following relationships outside the submitted work: payment or honoraria received for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Astra Zeneca, GSK and TEVA; support for attending meetings and/or travel received from Novartis; participation on a data safety monitoring board or advisory board for AstraZeneca, Novartis, GlaxoSmithKline, TEVA and Sanofi; member of the steering committee of SHARP, Secretary of Assembly 5 (Airway diseases, asthma, COPD and chronic cough), European Respiratory Society; vice-chair of Nordic Severe Asthma Network (NSAN). Conflict of interest: C.M. Porsbjerg reports the following relationships outside the submitted work: grants or contracts, paid to the institution, received from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK; consulting fees received from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK; participation on a data safety monitoring board or advisory board for AZ, GSK, Novartis, TEVA, Sanofi, Chiesi and ALK. Conflict of interest: E.H. Bel reports the following relationships outside the submitted work: research grants received from GSK and Teva; consulting fees received from Teva, Sanofi, AstraZeneca, GSK, Sterna and Chiesi; participation on a data safety monitoring board or advisory board for AstraZeneca. Conflict of interest: R. Djukanovic reports the following relationships outside the submitted work: funding received for the SHARP CRC from ERS, TEVA, GSK, Novartis, Sanofi and Chiesi; consultancy fees paid to the author received from Synairgen plc, Sanofi-Genzyme Corporation and Galapagos; honorarium for lectures paid to the author received from GlaxoSmithKline, Congress of Interasma, AstraZeneca and Airways Vista, Seoul; personal shares owned for Synairgen. Conflict of interest: L. Renaud reports receiving support for the present manuscript from SHARP CRC supported by GSK, Novartis, Sanofi, Chiesi and Teva. The following relationships are reported outside the submitted work: grants or contracts received from GSK, AZ and Chiesi; consulting fees received from AZ and Sanofi; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, received from AZ, GSK and Chiesi; patents planned, issued or pending WO 2017/050527 A1 “Method for the diagnosis of airway disease inflammatory subtype”. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care., Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021., Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%)., Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic., Competing Interests: Conflict of interest: A. Bourdin reports receiving grants or contracts outside the submitted work from AstraZeneca and Boeringher Ingelheim; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events as well as support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Chiesi and Amgen, outside the submitted work. Z. Csoma reports receiving honoraria for presentations from Astra/Zeneca, TEVA and Sanofi/Aventis (Hungary) outside the submitted work. E. Heffler reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Sanofi-Genzyme, Regeneron, Novartis, GSK, Circassia; Stallergenes-Greer and Nestlè Purina outside the submitted work. G.W. Canonica reports receiving consulting fees from AstraZeneca GSK, Novartis, Sanofi and Stallergenes Greer; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GSK, Novartis, Sanofi, Stallergenes Greer, Menarini, Chiesi and Mylan; participation on data safety monitoring or advisory boards for AstraZeneca, GSK, Novartis, Sanofi, Stallergenes Greer and Chiesi; all disclosures made outside the submitted work. G-J. Braunstahl reports grants or contracts from GSK, AstraZeneca and ALK Abello; consulting fees from GSK, Sanofi, ALK Abello, AstraZeneca and Novartis; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from GSK, Sanofi, ALK Abello, AstraZeneca and Novartis; and is on the scientific board of the Dutch Lung Foundation, task force Asthma NVALT and editorial board NTVAAKI; all disclosures made outside the submitted work. S. van der Sar reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca and GSK; and support received from ALK for attending meetings and/or travel; all disclosures made outside the submitted work. N. Nenasheva reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca plc., Sanofi S.A., Teva Pharmaceuticals, Novartis International AG and Chiesi Farmaceutici S.p.A., outside the submitted work. A. Bossios reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AZ, GSK and Teva; support for attending meetings and/or travel received from Novartis; and participation on a data safety monitoring or advisory boards for AZ, GSK, Novartis, Teva and Sanofi; and is a member of the steering Committee of SHARP, Secretary of Assembly 5 (Airway diseases, asthma, COPD and chronic cough) of the European Respiratory Society and vice-chair of Nordic Severe Asthma Network; all disclosures made outside the submitted work. D. Aronsson reports receiving grants or contracts from ALK-Abello outside the submitted work. A. Egesten reports receiving honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, outside the submitted work. L. Ahlbeck reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca; and participation on data safety monitoring or advisory boards for AstraZeneca, Sanofi and GSK; all disclosures made outside the submitted work. S. Škrgat reports receiving honoraria for lectures and educational events supported by GSK, AstraZeneca, Sanofi, Chiesi, Pliva Teva and Medis; and participation on advisory boards of GSK, AstraZeneca, Chiesi and Sanofi; all disclosures made outside the submitted work. N. Edelbaher reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, Astra Zeneca, Chiesi, Pliva Teva, Krka, Novartis, Boehringer Ingelheim and Sanofi; and participation on advisory boards of GSK, Astra Zeneca, Chiesi, Novartis and Boehringer Ingelheim; all disclosures made outside the submitted work. J. Rüdiger reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from the Education of Swiss Emergency physicians; and participation on a data safety monitoring board or board for Boehringer Ingelheim; and is a member of the Board of the Swiss Society of Pneumology and President of the Thorax section of the Swiss Ultrasound Society; all disclosures made outside the submitted work. N. Pavlov reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, Novartis and OM Pharma; support for attending meetings and/or travel received from Boehringer Ingelheim; participation on data safety monitoring or advisory boards for AstraZeneca, GSK, Novartis and Sanofi; all disclosures made outside the submitted work. P. Gianella reports participation on an advisory board for Novartis about Xolair for nasal polyps, outside the submitted work. F. Charbonnier reports receiving payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi, Novartis, Mundipharma, AstraZeneca and GSK; participation on data safety monitoring or advisory boards for Sanofi, Novartis, Mundipharma, AstraZeneca and GSK; all disclosures made outside the submitted work. R. Chaudhuri reports receiving grants or contracts from AstraZeneca; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GSK, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; support for attending meetings and/or travel received from Chiesi, Napp, Sanofi, Boehringer, GSK and AZ; and participation on data safety monitoring or advisory boards for GSK, AstraZeneca, Teva, Chiesi and Novartis; all disclosures made outside the submitted work. S.J. Smith is supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 for Taxonomy, Targets, Treatment, and Remission; the JU receives support from the European Union's Horizon 2020 research and innovation programme, and the European Federation of Pharmaceutical Industries and Associates; all disclosures made outside the submitted work. S. Doe reports receiving support for attending meetings and/or travel from GSK and Sanofi, outside the submitted work. L. Heaney reports grants or contracts from Medimmune, Novartis UK, Roche/Genentech Inc., GlaxoSmithKline, Amgen, Genentech/Hoffman la Roche, AstraZeneca, Medimmune, Aerocrine and Vitalograph; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for Novartis, Hoffman la Roche/Genentech Inc., Sanofi, GlaxoSmithKline, AstraZeneca, Teva and Circassia; support for attending meetings and/or travel from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Napp Pharmaceuticals; participation on data safety monitoring or advisory board for Novartis, Hoffman la Roche/Genentech Inc., Sanofi, Evelo Biosciences, GlaxoSmithKline, AstraZeneca, Teva, Theravance and Circassia; all disclosures made outside the submitted work. M. Masoli reports receiving grants or contracts from ERS SHARP to support the study “The burden of severe asthma on HRQoL across Europe”, outside the submitted work. P. Howarth is an employee of GSK. R. Djukanovic reports support for the present manuscript received from ERS, TEVA, GSK, Novartis, Sanofi and Chiesi; consulting fees from Synairgen for which the author is a co-founder and consultant and owns shares, outside the submitted work; and participation on a data safety monitoring or advisory board for Kymab (Cambridge), outside the submitted work. E. Bel reports support for the present manuscript from the ERS; grants or contracts received from GlaxoSmithKline and Teva, outside the submitted work; consulting fees received from AstraZeneca, GlaxoSmithKline, Sanofi, Sterna and Chiesi, outside the submitted work; honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from Teva; participation on a data safety monitoring or advisory board for AstraZeneca, outside the submitted work; and leadership or fiduciary roles, unpaid, for SHARP-CRC and RAPSODI (Dutch registry), outside the submitted work. M. Hyland reports receiving grants or contracts from TEVA; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events for GSK; all disclosures made outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

The treatment of microcystic and combined lymphangiomas, especially in the head and neck region, is still a challenge because the lymphangiomas do not respond to conventional therapies and their recurrence rate is high, regardless of the treatment choice. Complete surgical resection is the main treatment of lymphangiomas, but because of localization perioperative complications, such as bleeding, neural damage and airway obstruction are common disadvantages of this method. Bleomycin-based sclerotherapy is another common therapeutic approach, in which the lymphocysts are aspirated, and 25% to 50% of their volumes are replaced with a sclerotisant drug. This is an effective treatment in cases in which the vessels are large enough for an intravascular or intracystic injection, but because of the small size of vessels and cysts, the microcystic and combined lymphangiomas are not suitable for sclerotherapy. Delivery of drugs for treating sclerosis to endothelial cells can be achieved by electroporation (electrochemotherapy), even for capillary malformations. A congenital, rapidly growing combined lymphangioma of the left cervicofacial region was treated with one session of bleomycin-based electrochemotherapy. Seven months after treatment, the growth-corrected target volume decrease was 63% and the dislocation of the trachea and blood vessels previously observed had ceased. We suggest that bleomycin-based electrochemotherapy is a feasible alternative treatment option for capillary malformations., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases., Methods: In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma. It was evaluated whether these lncRNAs can be used as diagnostic biomarkers for any studied disease. With systems biology analysis the biological functions of the selected lncRNAs were predicted., Results: In the discovery cohort, the mean expression of 27 lncRNAs showed nominally significant differences in at least one comparison. OIP5-AS1, HNRNPU, RP11-325K4.3, JPX, RP11-282O18.3, MZF1-AS1 were selected for measurement in the replication cohort. Three lncRNAs (HNRNPU, RP11-325K4.3, JPX) expressed significantly higher in healthy children than in adult controls. All the mean expression level of the 6 lncRNAs differed significantly between adult allergic rhinitis patients and controls. RP11-325K4.3, HNRNPU and OIP5-AS1 expressed higher in allergic asthma than in non-allergic asthma. COPD and asthma differed in the expression of RP11-325K4.3 from each other. In examining of the lncRNAs as biomarkers the weighted accuracy (WA) values were especially high in the comparison of healthy controls and patients with allergic rhinitis. OIP5-AS1 and JPX achieved 0.98 and 0.9 WA values, respectively, and the combination of the selected lncRNAs also resulted in a high performance (WA = 0.98). Altogether, OIP5-AS1 had the highest discriminative power in case of three out of six comparisons., Conclusion: Differences were detected in the expression of circulating lncRNAs in chronic respiratory diseases. Some of these differences might be utilized as biomarkers and also suggest a possible role of these lncRNAs in the pathomechanism of these diseases. The lncRNAs and the associated pathways are potential therapeutic targets in these diseases, but naturally additional studies are needed for the confirmation of these results.

Background: Severe asthma (SA) database was established in Hungary to estimate the prevalence of SA and to define and analyze clinical phenotypes of the patients., Methods: SA questionnaires were sent out to 143 public pulmonary dispensaries specialized for diagnosing and caring pulmonary patients. Data of 520 SA patients were evaluated., Results: The prevalence of SA within the asthmatic population in Hungary was 0.89%. The mean age of patients were 56.4 ± 13.4 years, SA were more frequent in females (64%), the prevalence of allergy was 56.6%, 72.1% of patients had persistent airflow limitation (FEV1 < 80%), 37.9% severe airway obstruction (FEV1 ≤ 60%), 33.6% required systemic corticosteroid maintenance therapy, 21.5% had salicylate intolerance and 43.2% rhinosinusitis. A Bayesian dependency network was calculated which revealed several interdependencies between the characteristics. E.g. there was a strong association between salicylate intolerance and rhinosinusitis, more patients received regular systemic corticosteroid treatment who had salicylate intolerance and the proportion of salicylate intolerance was significantly higher in females., Conclusion: The prevalence of SA was determined in Hungary which was lower than in other studies. Using a Bayesian-based network analysis several interdependencies were revealed between patient characteristics.

A flow cytometry-based method was developed to quantify in vivo circulating neutrophil extracellular trap (NET) levels in plasma and compare them in patients with different chronic inflammatory lung diseases. Seventeen asthmatic and 11 control children, 12 adult controls, 46 asthmatic, 6 COPD and 6 adult patients with asthma-COPD overlap syndrome (ACOS) were recruited in the study. The presence of NETs in unstimulated cell-free plasma was confirmed and visualized by confocal laser-scanning microscopy. No significant differences were found in plasma NET levels between children and adults, children with or without asthma and adults with or without asthma, COPD or ACOS. When asthmatic patients were stratified according to their disease severity the average plasma NET level was significantly higher in asthmatic patients with more serious symptoms (adjusted p = 0.027). Patients with poorer pulmonary functions had higher plasma NET levels which negatively correlated with the FEV1 values (r = -0.39, p = 0.002). Patients who were medicated daily with inhaled corticosteroids (ICS) had significantly lower average plasma NET level than patients who did not or just occasionally used ICS (p = 0.027). If further studies confirm the NET-lowering effect of ICS in the circulation, it can be utilized in diseases where NETosis contributes to the pathogenesis.

Tie2, coded by the TEK gene, is a tyrosine kinase receptor and plays a central role in vascular stability. It was suggested that variations in the TEK gene might influence the susceptibility to asthma and allergic conjunctivitis. The aim of this study was to further investigate these suggestions, involving different populations and to study the Tie2 related pathway on a mouse model of asthma. The discovery, stage I cohort involved 306 patients with moderate and severe allergic rhinitis, the stage II study consisted of four cohorts, namely, adult and pediatric asthmatics and corresponding controls. Altogether, there were 1,258 unrelated individuals in these cohorts, out of which 63.9% were children and 36.1% were adults. In stage I, 112 SNPs were screened in the TEK gene of the patients in order to search for associations with asthma and allergic conjunctivitis. The top associated SNPs were selected for association studies on the replication cohorts. The rs3824410 SNP was nominally associated with a reduced risk of asthma in the stage I cohort and with severe asthma within the asthmatic population (p=0.009; OR=0.48) in the replication cohort. In the stage I study, 5 SNPs were selected in conjunctivitis. Due to the low number of adult patients with conjunctivitis, only children were involved in stage II. Within the asthmatic children, the rs622232 SNP was associated with conjunctivitis in boys in the dominant model (p=0.004; OR=4.76), while the rs7034505 showed association to conjunctivitis in girls (p=0.012; OR=2.42). In the lung of a mouse model of asthma, expression changes of 10 Tie2 pathway-related genes were evaluated at three points in time. Eighty percent of the selected genes showed significant changes in their expressions at least at one time point during the process, leading from sensitization to allergic airway inflammation. The expressions of both the Tek gene and its ligands showed a reduced level at all time points. In conclusion, our results provide additional proof that the Tie2 pathway, the TEK gene and its variations might have a role in asthma and allergic conjunctivitis. The gene and its associated pathways can be potential therapeutic targets in both diseases., (Copyright © 2020 Gál, Gézsi, Molnár, Nagy, Kiss, Sultész, Csoma, Tamási, Gálffy, Bálint, Póliska and Szalai.)

The principles and mechanisms of adsorption of Ni(ii) ions by well characterized pristine and oxidized N-doped multi-walled carbon nanotubes (N-CNTs) are described and discussed. The samples were synthesized by CCVD method using n -butylamine as the carbon source and Ni(NO 3 ) 2 + MgO as the catalyst and purified by treatment with HCl. The surface functionalization was performed using oxidation with a mixture of concentrated H 2 SO 4 and HNO 3 . The morphology, nature and charge of surface groups were characterized by HRTEM, XPS, FTIR and micro-electrophoresis methods. It has been shown that: adsorption of Ni(ii) reaches an equilibrium value within 20-30 min; the degree of extraction of nickel ions from the solution increases with its dilution; adsorption of Ni(ii) results in an insufficient decrease in the suspension pH for pristine N-CNTs (0.5-0.6 pH unit) and considerable lowering of the pH for the oxidized sample (up to 2.5 pH unit); the adsorption isotherms are described by the Langmuir equation; the plateau amounts of adsorption (35-40 mg g -1 ) are almost the same for both as-prepared and oxidized samples; at pH 8 and higher a sharp increase in adsorption is observed which is caused by nickel hydroxide precipitation. The spectroscopic, adsorption, electrophoretic and pH measurement data testify that below pH 8 the major mechanism of adsorption by as-prepared N-CNTs is the donor-acceptor interaction between the free electron pair of N atoms incorporated into the nanotube lattice and vacant d-orbital of the adsorbing Ni(ii) ions. For the oxidized N-CNTs ion-exchange processes with a release of H + play a decisive role., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m -2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day -1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day -1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries., Competing Interests: Conflict of interest: J.J.M.H. van Bragt has nothing to disclose. Conflict of interest: I.M. Adcock has nothing to disclose. Conflict of interest: E.H.D. Bel reports grants and personal fees from AstraZeneca, GSK and Novartis, grants from Teva, and personal fees from Boehringer Ingelheim, Sanofi/Regeneron, Vectura and Sterna, outside the submitted work. Conflict of interest: G-J. Braunstahl reports grants from GSK, Novartis, AstraZeneca and Chiesi, outside the submitted work. Conflict of interest: A. Ten Brinke reports institutional fees for research advisory boards and lectures from GSK, Teva and AstraZeneca, institutional fees for research advisory boards from Sanofi, Novartis and Boehringer Ingelheim, outside the submitted work. Conflict of interest: J. Busby has nothing to disclose. Conflict of interest: G.W. Canonica reports personal fees from A. Menarini, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, Circassia, GSK, MSD, Novartis, Roche, Sanofi-Aventis and Teva, during the conduct of the study. Conflict of interest: H. Cao is an employee of Novartis, which is one of the funding pharmaceutical companies of SHARP. Conflict of interest: K.F. Chung has received honoraria for participating in advisory board meetings from GSK, AstraZeneca, Novartis, Merck, Boehringer Ingelheim and Teva regarding treatments for asthma and chronic obstructive pulmonary disease and has also been remunerated for speaking engagements. Conflict of interest: Z. Csoma has nothing to disclose. Conflict of interest: B. Dahlén reports advisory board membership for Teva, GSK and Sanofi, personal fees for lectures from AstraZeneca, outside the submitted work. Conflict of interest: E. Davin has nothing to disclose. Conflict of interest: S. Hansen has nothing to disclose. Conflict of interest: E. Heffler reports personal fees from AstraZeneca, Sanofi Genzyme, Teva, Novartis, GSK, Circassia and Nestle Purina, outside the submitted work. Conflict of interest: I. Horvath reports personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Chiesi, Berlin-Chemie, Roche, MSD, CSL and Sager Pharma, outside the submitted work. Conflict of interest: S. Korn reports personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Teva and Roche, grants and personal fees from GSK and Novartis, during the conduct of the study. Conflict of interest: M. Kots is a full time Chiesi Famaceutici SpA employee, Global clinical development department. Conflict of interest: P. Kuna reports personal fees for lectures and advisory board work from AstraZeneca and Novartis, personal fees for lectures and nonfinancial support for meeting attendance from Berlin-Chemie, Menarini and Boehringer Ingelheim, outside the submitted work. Conflict of interest: N. Kwon is an employee of GSK. Conflict of interest: R. Louis reports grants and personal fees for advisory board work from GSK, AstraZeneca and Novartis, grants from Chiesi, outside the submitted work. Conflict of interest: V. Plaza reports grants, personal fees and nonfinancial support from Chiesi, grants and personal fees from AstraZeneca, personal fees from ALK, Mundipharma and Sanofi, grants from Menarini, outside the submitted work. Conflict of interest: C. Porsbjerg has nothing to disclose. Conflict of interest: D. Ramos-Barbon has nothing to disclose. Conflict of interest: L.B. Richards has nothing to disclose. Conflict of interest: S. Škrgat reports personal fees for lectures and scientific discussion at symposia from Teva and Boehringer, personal fees for lectures and advisory boards from AstraZeneca, Glaxo, Berlin-Chemie and Chiesi, outside the submitted work. Conflict of interest: J.K. Sont has nothing to disclose. Conflict of interest: S.J.H. Vijverberg has nothing to disclose. Conflict of interest: E.J. Weersink has nothing to disclose. Conflict of interest: V. Yasinska has nothing to disclose. Conflict of interest: S.S. Wagers reports consultancy fees from the European Respiratory Society, during the conduct of the study; consultancy fees from King's College Hospital NHS Foundation Trust, Academic Medical Research, AMC Medical Research BV, Asthma UK, Athens Medical School, Boehringer Ingelheim International GmbH, CHU de Toulouse, CIRO, DS Biologicals Ltd, École Polytechnique Fédérale de Lausanne, European Respiratory Society, FISEVI, Fluidic Analytics Ltd, Fraunhofer IGB, Fraunhofer ITEM, GSK R&D Ltd, Holland and Knight, Karolinska Institutet Fakturor, KU Leuven, Longfonds, National Heart and Lung Institute, Novartis Pharma AG, Owlstone Medical Ltd, PExA AB, UCB Biopharma SPRL, UCB Biosciences GmbH, Umeå University, University Hospital Southampton NHS Foundation Trust, Università Campus Bio-Medico di Roma, Universita Cattolica Del Sacro Cuore, Universität Ulm, University of Bern, University of Edinburgh, University of Hull, University of Leicester, University of Loughborough, University of Luxembourg, University of Manchester, University of Nottingham, Vlaams Brabant, Dienst Europa, Imperial College London, Boehringer Ingelheim, Breathomix, Gossamer Bio, AstraZeneca and CIBER, outside the submitted work. Conflict of interest: R. Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and Teva, consultation for Teva and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GSK; and is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company. Conflict of interest: A.H. Maitland-van der Zee reports personal fees for participating in an advisory board from AstraZeneca and Boehringer Ingelheim, unrestricted research grants from Boehringer Ingelheim and GSK., (Copyright ©ERS 2020.)

During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and maximize its benefits for the society. To provide a comprehensive phenome-wide overview in sublingual immunotherapy, using ragweed allergy as a target, we planned and carried out a longitudinal, prospective, observational, open-label study (DesensIT). In this paper we present challenges of using deep and comprehensive phenotypes embracing biological, clinical and patient-reported outcomes in allergen-specific immunotherapy and show how we designed the DesensIT project to optimize data collection, processing and evaluation.

Background: Oculocutaneous albinism (OCA) is a clinically and genetically heterogenic group of pigmentation abnormalities characterized by variable hair, skin, and ocular hypopigmentation. Six known genes and a locus on human chromosome 4q24 have been implicated in the etiology of isolated OCA forms (OCA 1-7)., Methods: The most frequent OCA types among Caucasians are OCA1, OCA2, and OCA4. We aimed to investigate genes responsible for the development of these OCA forms in Hungarian OCA patients (n = 13). Mutation screening and polymorphism analysis were performed by direct sequencing on TYR, OCA2, SLC45A2 genes., Results: Although the clinical features of the investigated Hungarian OCA patients were identical, the molecular genetic data suggested OCA1 subtype in eight cases and OCA4 subtype in two cases. The molecular diagnosis was not clearly identifiable in three cases. In four patients, two different heterozygous known pathogenic or predicted to be pathogenic mutations were present. Seven patients had only one pathogenic mutation, which was associated with non-pathogenic variants in six cases. In two patients no pathogenic mutation was identified., Conclusions: Our results suggest that the concomitant screening of the non-pathogenic variants-which alone do not cause the development of OCA, but might have clinical significance in association with a pathogenic variant-is important. Our results also show significant variation in the disease spectrum compared to other populations. These data also confirm that the concomitant analysis of OCA genes is critical, providing new insights to the phenotypic diversity of OCA and expanding the mutation spectrum of OCA genes in Hungarian patients.

The most important function of the skin is to form a barrier between the body and the external environment. The epidermal barrier prevents transepidermal water loss from the skin, but also serves as a barrier to the entry of harmful environmental allergic, toxic or infectious substances. Inherited defects in the genes encoding the components of the epidermal barrier result in the development of rare genetic disorders, whereas polymorphisms in these genes together with environmental factors cause frequent inflammatory skin diseases, such as atopic dermatitis. In this review, components of the skin-barrier function will be reviewed with special emphasis on how the altered epidermal barrier might be repaired. The different strategies to increase the transdermal penetration of drugs is also discussed.

The immaturity and vulnerability of the skin and epidermal barrier function and the frequent iatrogenic complications following diagnostic and therapeutic procedures are often associated with skin manifestations in infants in neonatal intensive care units (NICUs). The aim of the current study was to investigate dermatologic disorders in neonates in our NICU. A prospective cohort study was conducted in the NICU at the Department of Pediatrics at the University of Szeged between January 2012 and January 2013. All full- and preterm infants hospitalized in the NICU underwent whole-body skin examinations and all dermatologic disorders and treatment modalities were recorded. Eighty-nine dermatologic conditions were detected in 64 of the 211 neonates admitted to the NICU. A wide variety of clinical symptoms accompanied these conditions in these preterm and severely ill full-term infants. A considerable proportion of the disorders that were seen resulted from the immaturity of the skin and various iatrogenic complications. Dermatologic disorders are frequent in neonates requiring intensive care. Prevention, early detection, and optimal treatment of these disorders with modern, standardized skin care management strategies can result in significant improvements in barrier function and in the integrity of the skin, increasing the overall efficacy of neonatal intensive care., (© 2014 Wiley Periodicals, Inc.)

Papillon-Lefèvre syndrome (PLS; OMIM 245000) is an autosomal recessive condition characterized by palmoplantar hyperkeratosis and periodontitis. In 1997, the gene locus for PLS was mapped to 11q14-21, and in 1999, variants in the cathepsin C gene (CTSC) were identified as causing PLS. To date, a total of 75 different disease-causing mutations have been published for the CTSC gene. A summary of recurrent mutations identified in Hungarian patients and a review of published mutations is presented in this update. Comparison of clinical features in affected families with the same mutation strongly confirm that identical mutations of the CTSC gene can give rise to multiple different phenotypes, making genotype-phenotype correlations difficult. Variable expression of the phenotype associated with the same CTSC mutation may reflect the influence of other genetic and/or environmental factors. Most mutations are missense (53%), nonsense (23%), or frameshift (17%); however, in-frame deletions, one splicing variant, and one 5' untranslated region (UTR) mutation have also been reported. The majority of the mutations are located in exons 5-7, which encodes the heavy chain of the cathepsin C protein, suggesting that tetramerization is important for cathepsin C enzymatic activity. All the data reviewed here have been submitted to the CTSC base, a mutation registry for PLS at http://bioinf.uta.fi/CTSCbase/.

Introduction: At present there are no exact epidemiologic data on the prevalence of neonatal skin disorders and birth marks in Hungary., Aim: The aim of the authors was to investigate the prevalence of skin disorders in mature healthy neonates after birth., Method: The survey was carried out in the Neonatal Care Unit at the Department of Obstetrics and Gynaecology at the University of Szeged between April, 2012 and May, 2013., Results: A total of 2289 newborn infants underwent whole-body screening skin examinations. At least one skin manifestation was found in 63% of the neonates. The major groups of skin disorders were transient benign cutaneous lesions, vascular lesions, pigmented lesions, traumatic, iatrogenic, congenital or acquired disorders with skin injuries, developmental abnormalities and benign skin tumours. The most frequent transient cutaneous lesions were erythema toxicum neonatorum, sebaceous hyperplasia and desquamation. The most common vascular lesions were naevus simplex, haemangioma and haemangioma precursor lesion, while the most frequently observed pigmented lesions were congenital melanocytic naevi and Mongolian spot., Conclusions: In the vast majority of cases, special treatment was not necessary, but 5.27% of the neonates required local dermatologic therapy, and in 9.2% of neonates follow up was recommended.

Wound care in neonates demands special awareness of the anatomical and physiological characteristics of their skin, and the danger of adverse mechanical and toxicological events. Here, we present the case of a full-term neonate born with myelomeningocele. Following the closing surgery on the 3rd day of postuterine life, the operated region became inflamed, the sutures opened and a necrotic discharging ulcer developed. Besides parenteral antibiotic treatment based on the microbiological findings, intelligent hydrofiber dressings were applied to the wound with regard to the special characteristics of wound care in neonates. After 72 days, the ulcer had healed with a small residual scar, and the infant is currently demonstrating normal physical and mental development.

Blue-light phototherapy has been an essential therapeutic tool in the management of neonatal jaundice for decades. Rarely, it is accompanied by acute dermatological and systemic side-effects, but fortunately these are reversible and can be adequately and promptly treated in routine neonatal practice. In contrast, much less is known about the potential long-term side-effects of neonatal blue-light phototherapy (NBLP). Many of the data that are currently available on how NBLP influences melanocytic naevus (MN) development are controversial. The results of recent well-designed epidemiological surveys suggest that NBLP could well be a risk factor for MN formation, and highlight the need for additional in vivo and in vitro studies. NBLP is at present the mainstay of treatment for neonatal jaundice, but in the future greater consideration should be given to its long-term side-effects when phototherapy is indicated. It is relevant to emphasize the importance of appropriately restricted and adequate clinical guidelines, and strict monitoring of the management of hyperbilirubinaemia, in order to avoid the unnecessary overtreatment of newborn infants., (© 2013 The Authors BJD © 2013 British Association of Dermatologists.)

Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives.

Background: Neonatal blue light phototherapy (NBLP) has been widely and successfully used for the treatment of neonatal jaundice to reduce the plasma concentration of bilirubin and, hence, to prevent kernicterus. Only a few and controversial data are available in the literature as to how NBLP influences melanocytic nevus development., Objective: Our goal was to conduct a twin study with the aim of better understanding the role of NBLP in melanocytic nevus development. We also investigated the roles of other environmental and constitutional factors in nevus formation., Methods: Fifty-nine monozygotic and dizygotic twins were included in this cross-sectional study. One of the twin members received NBLP, and the other did not. A whole-body skin examination was performed to determine the density of melanocytic skin lesions. The prevalence of benign pigmented uveal lesions was evaluated during a detailed ophthalmologic examination. A standardized questionnaire was used to assess data relating to constitutional, sun-exposure, and other variables. To search for possible gene-environmental interactions involved in the appearance of pigmented lesions, the melanocortin 1 receptor variants and the I439V polymorphism of histidine ammonia-lyase genes were also determined in the enrolled twins., Results: NBLP was associated with a significantly higher prevalence of both cutaneous and uveal melanocytic lesions. No association was found between the examined gene polymorphisms and the number of pigmented alterations in the examined study group., Conclusions: Our data suggest that NBLP could well be a risk factor for melanocytic nevus development. Phototherapy with blue-light lamps is a standard and essential therapeutic modality in neonatal care; therefore, additional in vivo and in vitro studies are necessary to establish its potential long-term adverse effects.

We recently showed that intranasal phototherapy represents an efficient therapeutic modality for the treatment of patients with seasonal allergic rhinitis (SAR). The aim of this pilot study was to compare the efficacy of intranasal phototherapy with that of the new generation antihistamine fexofenadine HCl in SAR. A randomized open study was conducted in patients with a history of moderate-to-severe ragweed-induced SAR. Thirty-one patients were randomly assigned to receive either intranasal irradiation three times a week for 2 weeks, or 180 mg fexofenadine HCl per day for 2 weeks. Each patient kept a diary of symptoms for nasal obstruction, nasal itching, rhinorrhea, sneezing and palate itching. Total nasal score (TNS), a sum of scores for nasal symptoms, was also calculated. In the rhinophototherapy group the individual scores significantly decreased compared with baseline for all of the parameters. In the fexofenadine HCl group none of the scores improved significantly at the end of the treatment except sneezing. TNS was significantly decreased in the rhinophototherapy group, but no significant change was observed in the fexofenadine HCl group after 2 weeks of treatment. In conclusion, we found that intranasal phototherapy is more efficient than fexofenadine HCl in reducing clinical symptoms for SAR., (© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.)

Background: One of the major technological breakthroughs in the last decade is represented by the diversified medical applications of light-emitting diodes (LEDs). LEDs emitting in the ultraviolet (UV) B spectrum might serve as a more convenient alternative for targeted delivery of phototherapy in inflammatory skin diseases such as psoriasis., Objectives: We investigated the efficacy and safety of a new UVB-LED phototherapeutic device in chronic plaque-type psoriasis., Methods: Twenty patients with stable plaque-type psoriasis were enrolled into a prospective, right-left comparative, open study. Symmetrical lesions located on extremities or trunk were chosen; one lesion was treated with the study device, whereas the other lesion served as an untreated control. Two treatment regimens were used in the study, one with an aggressive dose escalation similar to those used for outpatient treatment and one with slow increase in dose, similar to those used for treatment at home., Results: Patients in both groups responded rapidly to the UVB-LED therapy. Early disease resolution was observed in 11 patients (seven in the first group and four in the second group). Overall improvement at end of therapy was 93% in the high-dose group and 84% in the low-dose group. Four patients from the high-dose group and five from the low-dose group were still in remission at the 6-month follow-up visit., Conclusions: These results suggest that this innovative UVB-LED device is effective in the treatment of localized psoriasis and may be useful in other UV-responsive skin diseases.

Background: Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts., Objectives: This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors., Patients/methods: A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables., Results: One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10-100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi., Conclusion: Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.

Unlabelled: Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, are indispensable steps in all primary prevention efforts., Aim: The objective of the present study was to assess the prevalence of different pigmented lesions among schoolchildren, and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors., Methods: A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables., Results: Between 1-10 common melanocytic naevi were found in 27% of the participants, and naevi numbers were in the range between 10-100 in 67%. 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Congenital naevi were detected in 6.2% of the schoolchildren. A statistically significant association was found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, the history of severe painful sunburns, and the family history of a large number of melanocytic naevi., Conclusions: Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.

Background: Narrow-band ultraviolet B phototherapy is an effictive and safe treatment for atopic dermatitis. We have previously found that the 308 nm xenon chloride excimer laser was more effective than the narrow-band ultraviolet B light for the treatment of psoriasis, suggesting that ultraviolet B laser might offer advantages over narrow-band ultraviolet B., Objective: The purpose of this study was to evaluate the therapeutic efficacy of the 308 nm excimer laser in atopic dermatitis., Patients and Methods: Fifteen patients with atopic dermatitis (less than 20% body area involvement) were treated with a xenon chloride excimer laser (XTRAC laser, Photomedex Inc.) twice weekly. The severity of the atopic dermatitis was assessed via (i) a clinical score characterizing the intensity of erythema, infiltration, lichenification and excoriation; (ii) the quality of life, determined by means of a questionnaire; and (iii) a visual linear analogue scale, with which the patients scored the severity of their pruritus., Results: After 1 month of laser therapy, the clinical scores were significantly lower than the initial values. Similar decreases were observed for the quality of life and pruritus scores. No serious or unpleasant side-effects were observed., Conclusion: These results suggest that the xenon chloride excimer laser is an effective and well-tolerated treatment for localized atopic dermatitis.

We earlier reported that intranasal irradiation with the 308 nm xenon chloride (XeCl) ultraviolet-B laser and irradiation with a combination of ultraviolet-B (UVB), ultraviolet-A (UVA) and visible light (VIS) is highly effective in the treatment of allergic rhinitis and inhibit the immediate-type hypersensitivity reaction in the skin. Since photochemotherapy with 8-methoxypsoralen (8-MOP) plus UVA light (PUVA) is widely used in the treatment of different inflammatory skin disorders due to its immunosuppressive effect, in the present study we investigated the efficacy of intranasal PUVA treatment in allergic rhinitis and the effect of PUVA treatment on the skin prick test (SPT) reaction. An open study was performed in 17 patients with hay fever. Intranasal PUVA therapy was given four times weekly for 3 weeks. The treatment was started with a fluence of 0.5x of the individual minimal phototoxic dose (MPD) and the dosages were gradually increased. Evaluation was based on the symptom scores. The effect of PUVA treatment on the allergen-induced wheal formation was also studied in the SPT. PUVA treatment of the nasal cavity significantly decreased the nasal symptoms of the patients with allergic rhinitis. Treatment of the skin with PUVA also significantly suppressed the allergen-induced wheal formation in the SPT reaction. These data suggest that intranasal PUVA phototherapy is also an effective modality in the treatment of allergic rhinitis.

Introduction: Allergic rhinitis is a frequent disease, accompanied by significant social-economic costs and a negative impact on the quality of life. Phototherapy has a profound immunosuppressive effect and is effectively used in the treatment of several immune mediated skin diseases such as atopic dermatitis., Aims: The authors investigated the efficacy of intranasal phototherapy with a combination of low doses of ultraviolet-B, ultraviolet-A and visible light in allergic rhinitis., Methods: A randomized, double-blind, placebo-controlled study was conducted in patients with a history of at least 2 years of moderate to severe ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs. Intranasal phototherapy was performed 3 times a week for 3 weeks. As placebo low intensity visible light was used., Results: Phototherapy resulted in a significant improvement of clinical symptoms for nasal itching, rhinorrhea, sneezing and total nasal score. Scores for nasal obstruction slightly improved during phototherapy while a significant increased was found in the placebo group. In the overall efficacy assessment, both patients and investigators found phototherapy significantly more efficient than placebo. Phototherapy was well tolerated, the only side effect was the slight dryness of the nasal mucosa., Conclusions: These results suggest that intranasal phototherapy is effective for the treatment of allergic rhinitis, and opens up new opportunities for the treatment of immune-mediated mucosal diseases.

Background: Phototherapy has a profound immunosuppressive effect and is able to inhibit hypersensibility reactions in the skin., Objective: We evaluated whether phototherapy using a combination of UV-B (5%), UV-A (25%), and visible light (70%), referred to as mUV/VIS, is effective in treating allergic rhinitis., Methods: We conducted a randomized, double-blind study, in 49 patients with hay fever. The study was performed during the ragweed season. Each intranasal cavity was illuminated 3 times a week for 3 weeks with mUV/VIS or with low-intensity visible light. Symptom scores, inflammatory cells, and their mediators were assessed in nasal lavages. In vitro effects of mUV/VIS irradiation on T-cell and eosinophil apoptosis and its inhibitory effect on mediator release from basophils were examined., Results: Rhinophototherapy was tolerated well and resulted in a significant improvement of clinical symptoms for sneezing (P < .016), rhinorrhea (P < .007), nasal itching (P < .014), and total nasal score (P < .004). None of the scores improved significantly in the control group. Scores for nasal obstruction slightly improved after mUV/VIS treatment and significantly increased in the control group (P < .017). In the nasal lavage, phototherapy significantly reduced the number of eosinophils and the level of eosinophil cationic protein and IL-5. In vitro irradiation of T cells and eosinophils with mUV/VIS light dose-dependently induced apoptosis. Furthermore, mUV/VIS irradiation inhibited the mediator release from RBL-2H3 basophils., Conclusion: These results suggest that phototherapy is an effective modality to treat allergic rhinitis and offer new options for the treatment of immune-mediated mucosal diseases.

Recently we found that ultraviolet B (UVB) irradiation in erythematous doses significantly inhibited the immediate type hypersensibility reaction in the skin. In the present study we investigated the effects of different wavelengths on the skin prick test reaction (SPT). The forearm of ragweed allergic patients was irradiated with increasing doses of ultraviolet A (UVA), visible light (VIS) or combined UVB, UVA and VIS light, referred to as mUV/VIS. SPTs were performed 24 h after irradiation both on irradiated and non-irradiated control skin areas using ragweed extract. UVA and VIS irradiation led to a slight, not significant inhibition of allergen-induced wheal formation. Mixed irradiation with mUV/VIS light resulted in a dose-dependent inhibition of the allergen-induced wheal formation. The inhibition was significant already at suberythematous doses. As there is a good correlation between SPT and the nasal symptoms in patients with hay fever these data suggest that phototherapy with mUV/VIS light might be an effective and safe treatment modality for immediate type hypersensibility reactions in the skin and nasal mucosa.

We earlier reported that the 308 nm xenon chloride (XeCl) ultraviolet B (UVB) laser is highly effective for the treatment of inflammatory skin diseases. Since UVB irradiation has been shown to exert both local and systemic immunosuppression, we investigated the clinical efficacy of UVB irradiation in allergic rhinitis. In an open study, groups of patients with severe allergic rhinitis received intranasal irradiation with a 308 nm XeCl UVB excimer laser for two weeks. In the low-dose group (n=10), treatment was given twice weekly, starting with 0.25x the individual minimal erythema dose (MED), whereas patients in the medium-dose group (n=8) were treated four times weekly, starting with 0.4x MED. In each group, the dosage was gradually increased. Evaluation was based on the symptom scores. The effect of the XeCl laser on the skin prick test reaction was also studied. In the low-dose group, seven patients completed the study, and there was no improvement in the nasal symptoms. In the medium-dose group, the XeCl UVB irradiation significantly inhibited the rhinorrhoea, the sneezing, the nasal obstruction and the total nasal score (p<0.05). The XeCl UVB excimer laser also inhibited the allergen-induced skin prick test in a dose-dependent manner. These results suggest that the XeCl UVB excimer laser might serve as a new therapeutic tool in the treatment of allergic rhinitis.

Hyperresponsiveness (AHR) is a key physiological abnormality in asthma. In clinical and research studies AHR is measured bronchial challenge, with methacholine (MCh), but more recently with adenosine-5'-monophosphate (AMP). In the search for markers of airway inflammation in asthmatic patients, we measured the concentrations of histamine and cysteinyl-leukotrienes (cys-LTs) before and after MCh and AMP challenges in the exhaled breath condensate of 13 patients with mild asthma (FEV1 78.5%pred) and nine healthy non-smokers, using specific enzyme immunoassays. With methacholine challenge we did not find any differences between asthmatics and normal subjects in the pre- and post-challenge concentrations of cys-LTs: 27.2+/-1.4 vs. 29.2+/-1.2 pg/ml and 26.3+/-2.2 vs. 27.5+/-4.2 pg/ml, respectively or histamine: 5.1+/-0.4 vs. 5.1+/-0.6 nM and 4.5+/-0.4 vs. 4.4+/-0.3 nM; P>0.05). In asthmatic patients cys-LT levels were significantly higher after AMP challenge (56.2+/-9.7 vs. 31.7+/-6.9 pg/ml; P<0.05); but there was no difference in healthy subjects (27.2+/-4.6 vs. 30.3+/-4.7 pg/ml). There was no difference in histamine concentrations in asthmatic (5.9+/-1.8 vs. 4.5+/-0.5 nM), or healthy subjects (5.5+/-0.4 vs.5.7+/-0.9 nM) after AMP challenge. In conclusion, our results show that the cys-LTs are increased in exhaled breath condensate after AMP challenge, which may indicate that the AMP acts indirectly by releasing cys-LTs from primed mast cells. The detection of LTs and histamine in exhaled breath condensate may be useful in monitoring asthma.

Study Objectives: To investigate whether nitric oxide (NO) metabolites would be reduced in children affected by primary ciliary dyskinesia (PCD)., Design: Single-center observational study., Patients: Fifteen children with PCD (seven boys; mean [+/- SEM] age, 10.3 +/- 0.7 years; mean FEV(1), 73 +/- 2.1% predicted) were recruited along with 14 healthy age-matched subjects (seven boys; mean age, 11.5 +/- 0.4 years; mean FEV(1), 103 +/- 5% predicted)., Interventions: We assessed the levels of nitrite (NO(2)(-)), NO(2)(-)/NO(3)(-) (NO(2)(-)/NO(3)(-)), and S-nitrosothiol in exhaled breath condensate, exhaled NO, and nasal NO from children with PCD compared to those in healthy children., Measurements and Results: The mean exhaled and nasal NO levels were markedly decreased in children with PCD compared to those without PCD (3.2 +/- 0.2 vs 8.5 +/- 0.9 parts per billion [ppb], respectively [p < 0.0001]; 59.6 +/- 12.2 vs 505.5 +/- 66.8 ppb, respectively [p < 0.001]). Despite the lower levels of exhaled NO in children with PCD, no differences were found in the mean levels of NO(2)(-) (2.9 +/- 0.4 vs 3.5 +/- 0.3 microM, respectively), NO(2)(-)/NO(3)(-) (35.2 +/- 5.0 vs 34.3 +/- 4.5 microM, respectively), or S-nitrosothiol (1.0 +/- 0.2 vs 0.6 +/- 0.1 microM, respectively) between children with PCD and healthy subjects., Conclusion: These findings suggest that NO synthase activity may not be decreased as much as might be expected on the basis of low exhaled and nasal NO levels.