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Background: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)., Objective: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary-care centers., Methodology: Nasal polyp score, Sinonasal Outcome Test 22 score, visual analog scale for total sinus symptoms, loss of smell, and nasal blockage, and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline and again at 24 and 52 weeks' treatment with dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities, and blood eosinophil counts (BEC). Treatment response was evaluated according to European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) 2021 criteria., Results: All patient outcomes improved at 24 and 52 weeks' treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergy, or baseline BEC. A total of 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks, respectively; 54.4% and 68.2% met all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks, respectively., Conclusions: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks' treatment. Favorable treatment response was independent of the number of sinus surgery procedures, major comorbidities, or baseline systemic levels of type 2 inflammation., Competing Interests: Disclosure statement This study was in part financially supported by Sanofi &Regeneron. Disclosure of potential conflict of interest: C. Bachert reports grants or contracts from GSK, Sanofi, Novartis, and Galenus Health. G. Bettio is an employee of Galenus Health. C. Cavaliere reports consulting fees from GSK, Sanofi, Novartis, and AstraZeneca, participation on advisory board from GSK, Sanofi, and Novartis. A. Ciofalo reports participation on advisory board and lecture from Sanofi, GSK, and Recordati. Z. Diamant reports consulting fees and/or payment for lectures from Sanofi-Genzyme, GSK, Galenus Health, Antabio, Arcede, Biosion, Foresee Pharmaceuticals, Hippo-Dx, QPS-NL, and EUFOREA; leadership role in EUFOREA (asthma expert panel chair 2020-2024); and associate editorships at Springer (MedNet), Respiratory Medicine and Allergy. J. Eckl-Dorna reports grants (to institution) from AstraZeneca, Novartis, and Sanofi; payment for lectures from Allergopharma and Sanofi; and participation on advisory boards from GSK, AstraZeneca, and Bencard. W. Fokkens reports grants (to institution) from GSK, Novartis, and Sanofi; consulting fees from Dianosic, Sanofi, GSK, and Novartis; payment for lectures from Sanofi, GSK, and Novartis; participation on advisory board from Lyra; and leadership roles in the European Respiratory Society (ERS; secretary general), Rhinology (editor in chief), and Allergy (associate editor). J. de Kinderen and G. Mariën are partners and shareholders of Galenus Health. S. Masieri reports consulting fees from GSK, Sanofi, Novartis, and AstraZeneca; support for attending meetings from LoFarma and Sanofi; and participation on advisory boards from AstraZeneca, Sanofi, and Novartis. G. Mortuaire reports payments for lectures from Sanofi, GSK, Novartis, Dianosic, and Medtronic; support for travel from Audika; participation in advisory boards of Sanofi, GSK, Novartis, and Dianosic; and board role in ALK. J. Otten reports grants (to institution) from GSK, Sanofi, and Novartis; and payment for lectures from Sanofi. S. Reitsma reports grants (to institution) from GSK, Sanofi, and Novartis; and advisory board fees from Sanofi, Novartis, and GSK. S. Seys is an employee of Galenus Health; and reports payment for lectures from Teva Pharmaceutical. S. Schneider reports grants (to institution), payment for lectures, and participation on advisory board from Sanofi, AstraZeneca, Novartis, GSK, and Menarini. M. Wagenmann reports grants from ALK-Abello, GSK, Regeneron, AstraZeneca, Novartis, Sanofi, and Takeda; consulting fees from ALK, Genzyme, Novartis, Stallergenes, AstraZeneca, GSK, and Sanofi; payment for lectures from ALK-Abello, AstraZeneca, GSK, Leti Pharma, Sanofi, Allergopharma, Bencard Allergie, Infectopharm, Novartis, Stallergenes; and leadership role in the German Society for Allergology and Clinical Immunology (DGAKI; executive committee). The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti-inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy-driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non-immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non-specific eosinophil-targeting therapies. Despite the overall favourable safety profile of the currently available anti-eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The skin prick test (SPT) is the gold standard for identifying allergic sensitization in individuals suspected of having an inhalant allergy. Recently, it was demonstrated that SPT using a novel skin prick automated test (SPAT) device showed increased reproducibility and tolerability compared to the conventional SPT, among other benefits., Objective: This study aimed to evaluate prick location bias using the novel SPAT device., Methods: A total of 118 volunteers were enrolled in this study and underwent SPATs with histamine (nine pricks) and glycerol control (one prick) solutions on the volar side of their forearms. Imaging of the skin reactions was performed using the SPAT device, and the physician determined the longest wheal diameter by visually inspecting the images using a web interface. Prick location bias was assessed along the medial vs. lateral and proximal vs. distal axes of the forearm., Results: In total, 944 histamine pricks were analyzed. Four medial and four lateral histamine pricks were grouped, and wheal sizes were compared. The longest wheal diameters were not significantly different between the medial and lateral prick locations ( p  = 0.41). Furthermore, the pricks were grouped by two based on their position on the proximal-distal axis of the forearm. No significant difference was observed among the four groups of analyzed prick locations ( p  = 0.73)., Conclusion: The prick location on the volar side of the forearm did not influence wheal size in SPAT-pricked individuals., Competing Interests: SS, SG, RD, DL, and LV hold shares of Hippocreates. PH has a first-line relative who holds shares of Hippocreates. SS, SG, RD, and DL are employees of Hippocreates. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Seys, Gorris, Uyttebroek, Backaert, Jorissen, Schrijvers, Daems, Loeckx, Van Gerven and Hellings.)

The development of monoclonal antibody therapies targeting specific components of the pathways relevant to asthma pathophysiology has revolutionized treatment of severe asthma both in adults and children and helped to further unravel the heterogeneity of this disease. However, the availability of multiple agents, often with overlapping eligibility criteria, creates a need for pragmatic guidance for specialists undertaking care of patients with severe asthma. In this review, we provide an overview of the data supporting the clinical efficacy of biologics in distinct asthma phenotypes/endotypes. We also focus on the role of biomarkers and treatable traits, including comorbidities, in the choice of asthma biologics, highlight which treatments have been demonstrated to be steroid sparing in corticosteroid dependent asthma, and provide practical guidance that can drive shared decision making on treatment choice with patients. In addition, we summarize what is known to date regarding long-term safety of these drugs, and lastly, discuss future directions in biologics research., Competing Interests: Declaration of competing interest Dr. Linda Rogers receives research funding including salary support from Sanofi (Global) and Gene DX (formerly Sema 4). She has served on advisory boards and performed consulting work for Astra Zeneca, Sanofi (US) and Teva Pharmaceuticals. She has received travel funding and lecture honoraria from the American College of Chest Physicians. Dr. Sven Seys company receives grants/contracts from Sanofi, Novartis, GSK, and is an employee of Galenus Health and Hippo Dx, and received speakers fee from Teva Pharmaceuticals. Dr. Milos Jenesak has performed consulting for Novartis, Sanofi Genzyme, Astra Zeneca, and GSK, has received payment/honoraria for lectures, presentatinos, speakers bureaus, manuscript writing or educational events from Sanofi Genzyme and Novartis. Dr. Hanania's institution receives grants or contract from Astra Zeneca, GSK, Sanofi, Genentech, and Teva and consulting fees from Astra Zeneca, GSK, Sanofi, Genentech, Teva, and Amgen, andspeaking fees from Regeneron. Dr. Bjermer has no conflicts to declare in relation to this manuscript. Dr. Zuzana Diamant received speaker or consultant honoraria and/or served on advisory boards at: Antabio, Arcede, Foresee Pharmaceuticals, GlaxoSmithKline, Hippo-Dx, QPS-Netherlands, Sanofi-Genzyme-Regeneron, all outside the submitted work. During the last 3 years of her assignment as Research Director Respiratory and Allergy, QPS-Netherlands received European grant from ERA4TB and funding from Foresee Pharmaceuticals for early clinical studies. She serves as associate editor for Allergy and Respiratory Medicine and acts as Chair of the Asthma Expert Panel at EUFOREA. submitted work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of competing interest There is no conflict of interest.

Rationale: Participation in high-intensity exercise in early life might act as stressor to the airway barrier., Objectives: To investigate the effect of intense exercise and associated exposure to air pollution on the airway barrier in adolescent elite athletes compared with healthy controls and to study exercise-induced bronchoconstriction (EIB) in this population., Methods: Early-career elite athletes attending 'Flemish-Elite-Sports-Schools' (12-18 years) of 4 different sport disciplines (n=90) and control subjects (n=25) were recruited. Presence of EIB was tested by the eucapnic voluntary hyperventilation (EVH) test. Markers at mRNA and protein level; RNA-sequencing; carbon load in airway macrophages were studied on induced sputum samples., Results: 444 genes were differentially expressed in sputum from athletes compared with controls, which were related to inflammation and epithelial cell damage and sputum samples of athletes contained significantly more carbon loaded airway macrophages compared with controls (24%, 95% CI 20% to 36%, p<0.0004). Athletes had significantly higher substance P (13.3 pg/mL, 95% CI 2.0 to 19.2) and calprotectin (1237 ng/mL, 95% CI 531 to 2490) levels as well as IL-6, IL-8 and TNF-α mRNA levels compared with controls (p<0.05). The incidence of EIB in athletes was 9%. The maximal fall in forced expiratory volume in 1 s (%) after EVH test in athletes was significantly associated with prior PM 10 and PM 2.5 exposure., Conclusion: Early-career elite athletes showed increased markers of air pollution exposure, epithelial damage and airway inflammation compared with controls. Acute exposure to increased air pollution PM 10 levels was linked to increased airway hyper-reactivity., Trial Registration Number: NCT03587675., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics., Objective: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology., Methodology: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion., Results: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included., Conclusions: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Regulatory T cells (Tregs) that express the transcription factor Foxp3 have a critical role in limiting inflammatory processes and tissue damage. Whether Tregs are functional in maintaining epithelial barriers and in control of tight junction expression has not yet been explored. In this study, we investigated the effect of Treg deficiency on the airway epithelial barrier in an experimental murine model in which diphtheria toxin was repeatedly injected in Foxp3-diphtheria toxin receptor (DTR) mice to deplete Tregs. This resulted in spontaneous peribronchial inflammation and led to a systemic and local increase of IL-4, IL-5, CCL3, IFN-γ, and IL-10 and a local (lung) increase of IL-6 and IL-33 and decreased amphiregulin levels. Moreover, Treg depletion increased airway permeability and decreased epithelial tight junction (protein and mRNA) expression. CTLA4-Ig treatment of Treg-depleted mice almost completely prevented barrier dysfunction together with suppression of lung inflammation and cytokine secretion. Treatment with anti-IL-4 partly reversed the effects of Treg depletion on tight junction expression, whereas neutralization of IL-6 of IFN-γ had either no effect or only a limited effect. We conclude that Tregs are essential to protect the epithelial barrier at the level of tight junctions by restricting spontaneous T cell activation and uncontrolled secretion of cytokines, in particular IL-4, in the bronchi., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Rationale: Non-allergic asthma is driven by multiple endotypes of which neutrophilic and pauci-granulocytic asthma have been best established. However, it is still puzzling what drives inflammation and airway hyperreactivity (AHR) in these patients and how it can be treated effectively. Recently, a potential role of the innate immune system and especially the innate lymphoid cells (ILC) has been proposed., Objective: In this study, we investigated the effects of LPS inhalation on airway inflammation and AHR as a potential model for elucidating the pathogenesis of non-allergic asthma., Methods: Wild-type (BALB/c), SCID, IL-17A -/- , and Rag2 -/- γC -/- mice were endonasally exposed to lipopolysaccharide (LPS, 2 µg) on four consecutive days. Twenty-four hours after the last exposure, AHR to methacholine was assessed. Cytokine levels and ILC subpopulations were determined in lung tissue. Cellular differential analysis was performed in BAL fluid., Main Results: In this study, we developed a murine model for non-allergic neutrophilic asthma. We found that repeated endonasal applications of low-dose LPS in BALB/c mice led to AHR, BAL neutrophilia, and a significant increase in lung ILC3 as well as a significant increase in lung chemokines KC and MIP-2 and cytokines IL-1β, IL-17A, IL-22, and TNF. The adoptive transfer of ILC in Rag2 -/- γC -/- mice showed that ILC played a causal role in the induction of AHR in this model. Antagonising IL-1β, but not IL-17A or neutrophils, resulted in a partial reduction in LPS-induced AHR., Conclusion: In conclusion, we report here a murine model for neutrophilic asthma where ILC are required to induce airway hyperreactivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jonckheere, Seys, Steelant, Decaesteker, Dekoster, Cremer, Dilissen, Schols, Iwakura, Vande Velde, Breynaert, Schrijvers, Vanoirbeek, Ceuppens, Dupont and Bullens.)

Purpose of Review: The development and progression of chronic respiratory diseases are impacted by a complex interplay between genetic, microbial, and environmental factors. Here we specifically summarize the effects of environmental exposure on asthma, allergic rhinitis, and chronic rhinosinusitis. We furthermore discuss how digital health technology may aid in the assessment of the environmental exposure of patients and how it may be of added value for them., Recent Findings: It is well established that one gets allergic symptoms if sensitized and exposed to the same allergen. Viruses, bacteria, pollutants, irritants, and lifestyle-related factors modify the risk of getting sensitized and develop symptoms or may induce symptoms themselves. Understanding these processes and how the various factors interact with each other and the human body require big data and advanced statistics. Mobile health technology enables integration of multiple sources of data of the patients' exposome and link these to patient outcomes. Such technologies may contribute to the increased understanding of the development of chronic respiratory disease., Summary: Implementation of digital technologies in clinical practice may in future guide the development of preventive strategies to tackle chronic respiratory diseases and eventually improve outcomes of the patient., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: A defective epithelial barrier has been demonstrated in chronic rhinosinusitis with nasal polyps (CRSwNP). Lactobacilli are shown to restore epithelial barrier defects in gastrointestinal disorders, but their effect on the airway epithelial barrier is unknown. In this study, hence, we evaluated whether the nasopharyngeal isolates Lacticaseibacillus casei AMBR2 and Latilactobacillus sakei AMBR8 could restore nasal epithelial barrier integrity in CRSwNP., Methods: Ex vivo trans-epithelial tissue resistance and fluorescein isothiocyanate-dextran 4 kDa (FD4) permeability of nasal mucosal explants were measured. The relative abundance of lactobacilli in the maxillary sinus of CRSwNP patients was analyzed by amplicon sequencing of the V4 region of the 16S rRNA gene. The effect of spray-dried L. casei AMBR2 and L. sakei AMBR8 on epithelial integrity was investigated in vitro in primary nasal epithelial cells (pNECs) from healthy controls and patients with CRSwNP as well as in vivo in a murine model of interleukin (IL)-4 induced barrier dysfunction. The activation of Toll-like receptor 2 (TLR2) was explored in vitro by using polyclonal antibodies., Results: Patients with CRSwNP had a defective epithelial barrier which positively correlated with the relative abundance of lactobacilli-specific amplicons in the maxillary sinus. L. casei AMBR2, but not L. sakei AMBR8, increased the trans-epithelial electrical resistance (TEER) of pNECs from CRSwNP patients in a time-dependent manner. Treatment of epithelial cells with L. casei AMBR2 promoted the tight junction proteins occludin and zonula occludens-1 reorganization. Furthermore, L. casei AMBR2 prevented IL-4-induced nasal permeability in vivo and in vitro . Finally, the beneficial effect of L. casei AMBR2 on nasal epithelial cells in vitro was TLR2-dependent as blocking TLR2 receptors prevented the increase in TEER., Conclusions: A defective epithelial barrier in CRSwNP may be associated with a decrease in relative abundance of lactobacilli-specific amplicons. L. casei AMBR2 would restore nasal epithelial integrity and can be a novel therapeutic strategy for CRSwNP., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: Staphylococcus aureus colonization and release of enterotoxin B (SEB) has been associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP). The pathogenic mechanism of SEB on epithelial barriers, however, is largely unexplored., Objective: We investigated the effect of SEB on nasal epithelial barrier function., Methods: SEB was apically administered to air-liquid interface (ALI) cultures of primary polyp and nasal epithelial cells of CRSwNP patients and healthy controls, respectively. Epithelial cell integrity and tight junction expression were evaluated. The involvement of Toll-like receptor 2 (TLR2) activation was studied in vitro with TLR2 monoclonal antibodies and in vivo in tlr2 -/- knockout mice., Results: SEB applied to ALI cultures of polyp epithelial cells decreased epithelial cell integrity by diminishing occludin and zonula occludens (ZO)-1 protein expression. Antagonizing TLR2 prevented SEB-induced barrier disruption. SEB applied in the nose of control mice increased mucosal permeability and decreased mRNA expression of occludin and ZO-1, whereas mucosal integrity and tight junction expression remained unaltered in tlr2 -/- mice. Furthermore, in vitro SEB stimulation resulted in epithelial production of IL-6 and IL-8, which was prevented by TLR2 antagonization., Conclusion & Clinical Relevance: SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S. aureus on inflammation in CRSwNP., (© 2020 John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socioeconomic burden. Monitoring of patient-reported outcomes by mobile technology offers the possibility to better understand real-life burden of CRS., Methods: This study reports on the cross-sectional evaluation of data of 626 users of mySinusitisCoach (mSC), a mobile application for CRS patients. Patient characteristics of mSC users were analysed as well as the level of disease control based on VAS global rhinosinusitis symptom score and adapted EPOS criteria., Results: The mSC cohort represents a heterogeneous group of CRS patients with a diverse pattern of major symptoms. Approximately half of patients reported nasal polyps. 47.3% of all CRS patients were uncontrolled based on evaluation of VAS global rhinosinusitis symptom score compared to 40.9% based on adapted EPOS criteria. The impact of CRS on sleep quality and daily life activities was significantly higher in uncontrolled versus well-controlled patients. Half of patients had a history of FESS (functional endoscopic sinus surgery) and reported lower symptom severity compared to patients without a history of FESS, except for patients with a history of more than 3 procedures. Patients with a history of FESS reported higher VAS levels for impaired smell., Conclusion: Real-life data confirm the high disease burden in uncontrolled CRS patients, clearly impacting quality of life. Sinus surgery improves patient-reported outcomes, but not in patients with a history of more than 3 procedures. Mobile technology opens a new era of real-life monitoring, supporting the evolution of care towards precision medicine., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Nasal hyperreactivity (NHR) is a common feature of various rhinitis subtypes and represents a novel phenotype of rhinitis. It is being reported in two-thirds of adult rhinitis patients irrespective of the atopic status. Data on the prevalence of NHR in patients with asthma are lacking, as well as the nature of evoking triggers., Methods: Postal questionnaires were distributed to an unselected group of asthmatic patients in Leuven (Belgium, n = 190) and completed by 114 patients. In Mexico City (Mexico) and Brasov (Romania), respectively, 97 out of 110 and 80 out of 100 asthmatic patients attending the outpatient clinic completed the questionnaire. Non-asthmatic volunteers were recruited amongst university and hospital co-workers in Leuven (n = 53). The presence of self-reported NHR, the type of triggers evoking nasal and bronchial symptoms, medication use, self-reported allergy, and environmental factors were evaluated., Results: Overall, 69% of asthma patients reported NHR, with 32% having more than 4 triggers evoking NHR. These triggers included mainly exposure to temperature and humidity changes, cigarette smoke, and strong odours. A higher prevalence of NHR was detected in allergic compared to non-allergic asthma patients (73% vs. 53% p < 0.01). The prevalence of NHR correlated with asthma severity, ranging from 63% (VAS ≤3) to 81% (VAS ≥7). BHR was found more frequently in patients with NHR compared to without NHR (89% vs. 53%, p < 0.0001)., Conclusion: NHR represents a clinical phenotype of upper airway disease affecting over two-thirds of asthma patients and correlates with asthma severity. Targeting NHR in patients with asthma is often overlooked and should be reinforced in the future to achieve better symptom control., Competing Interests: All authors state they have no conflict of interest in relation to this study and the results described in the manuscript., (© 2020 The Authors.)

Background: Increased epithelial permeability has been reported in allergic rhinitis, with histamine and type-2 inflammation being responsible for tight junction dysfunction. The impact of an epithelial barrier defect on allergic sensitization and mast cell (MC) degranulation remains speculative., Methods: Transepithelial passage of allergens was evaluated on primary human nasal epithelial cell cultures. Active sensitization was attempted by repeated intranasal ovalbumin (OVA) applications in Naïve mice. In a passive sensitization model, mice were injected with IgE to Dermatophagoides pteronyssinus (rDer p)2 and then exposed intranasally to the allergen. Chitosan was used to disrupt nasal epithelial integrity in vitro and in vivo., Results: Chitosan strongly reduced transepithelial electrical resistance and facilitated transepithelial allergen passage in cultured primary nasal epithelial cells. In vivo, intranasal chitosan affected occludin expression and facilitated allergen passage. After epithelial barrier disruption, intranasal OVA application induced higher OVA-specific IgG1 and total IgE in serum, and increased eosinophilia and interleukin-5 in bronchoalveolar lavage (BAL) compared to sham-OVA mice. Chitosan exposure, prior to rDer p2 allergen challenge in passively sensitized mice, resulted in increased β-hexosaminidase levels in serum and BAL compared to sham-rDer p2 mice. Intranasal treatment with the synthetic glucocorticoid fluticasone propionate prevented chitosan-induced barrier dysfunction, allergic sensitization, and MC degranulation., Conclusion: Epithelial barrier dysfunction facilitates transepithelial allergen passage, allergic sensitization, and allergen-induced MC degranulation even in the absence of inflammatory environment. These results emphasize the crucial role of an intact epithelial barrier in prevention of allergy., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2-targeting biologics such as anti-IgE, anti-IL4Rα, anti-IL5, and anti-IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma., (© 2019 The Authors Allergy Published by John Wiley & Sons Ltd.)

It is generally believed that the microbiome plays a role in the pathophysiology of chronic rhinosinusitis (CRS), though its exact contribution to disease development and severity remains unclear. Here, samples were collected from the anterior nares, nasopharynx, and maxillary and ethmoid sinuses of 190 CRS patients and from the anterior nares and nasopharynx of 100 controls. Microbial communities were analyzed by Illumina sequencing of the V4 region of 16S rRNA. The phenotype and patient characteristics were documented, and several serum inflammatory markers were measured. Our data indicate a rather strong continuity for the microbiome in the different upper respiratory tract (URT) niches in CRS patients, with the microbiome in the anterior nares being most similar to the sinus microbiome. Bacterial diversity was reduced in CRS patients without nasal polyps compared to that in the controls but not in CRS patients with nasal polyps. Statistically significant differences in the presence/absence or relative abundance of several taxa were found between the CRS patients and the healthy controls. Of these, Dolosigranulum pigrum was clearly more associated with URT samples from healthy subjects, while the Corynebacterium tuberculostearicum , Haemophilus influenzae/H. aegyptius , and Staphylococcus taxa were found to be potential pathobionts in CRS patients. However, CRS versus health as a predictor explained only 1 to 2% of the variance in the microbiome profiles in an adonis model. A history of functional endoscopic sinus surgery, age, and sex also showed a minor association. This study thus indicates that functional studies on the potential beneficial versus pathogenic activity of the different indicator taxa found here are needed to further understand the pathology of CRS and its different phenotypes. (This study has been registered at ClinicalTrials.gov under identifier NCT02933983.) IMPORTANCE There is a clear need to better understand the pathology and specific microbiome features in chronic rhinosinusitis patients, but little is known about the bacterial topography and continuity between the different niches of the upper respiratory tract. Our work showed that the anterior nares could be an important reservoir for potential sinus pathobionts. This has implications for the diagnosis, prevention, and treatment of CRS. In addition, we found a potential pathogenic role for the Corynebacterium tuberculostearicum , Haemophilus influenzae/H. aegyptius , and Staphylococcus taxa and a potential beneficial role for Dolosigranulum Finally, a decreased microbiome diversity was observed in patients with chronic rhinosinusitis without nasal polyps compared to that in healthy controls but not in chronic rhinosinusitis patients with nasal polyps. This suggests a potential role for the microbiome in disease development or progression of mainly this phenotype., (Copyright © 2019 De Boeck et al.)

Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The market of mobile health (mHealth) technology is rapidly evolving, making new mobile technologies potentially available for healthcare systems. Patient empowerment through self-monitoring of symptoms, shared decision making with the physician, and easily accessible education are important features extending the reach of mHealth technology beyond traditional care., Methods: Two digital distribution platforms (Apple App Store and Google Play Store) were searched for currently available mobile applications (apps) for patients with chronic respiratory diseases (CRDs). A new index (score ranging from 0 to 10) was developed to assess the potential of apps as a tool to empower patients through mobile technology (based on self-monitoring, personalized feedback, and patient education app features)., Results: One hundred and twelve apps were retained for analysis and could be classified in 5 categories: Asthma (n = 71), COPD (n = 15), Asthma and COPD (n = 15), Rhinitis and Asthma (n = 5), and Rhinosinusitis (n = 6). Eighty percent were developed by medical technology companies compared to 18% by medical doctors and 2% by pharmaceutical companies. Two-thirds of apps allow disease self-monitoring, whereas over half of apps provide patient feedback through graphs. Sixty percent of apps contain easily accessible patient education material. Only three percent of apps reach a score of ≥7 on the newly designed patient empowerment index., Conclusions: A variety of apps are available for patients with CRDs of which only few were developed by or jointly with medical doctors. The majority of these apps include self-monitoring tools, but only few also provide personalized feedback, which is needed to adopt these apps into daily care., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Purpose of Review: The current review describes the role of different types of innate lymphoid cells (ILCs) in the pathogenesis of asthma inflammatory phenotypes by linking findings from murine asthma models with human studies. Novel treatment options are needed for patients with steroid-insensitive asthma. Strategies targeting ILCs, or their upstream or downstream molecules are emerging and discussed in this review., Recent Findings: In eosinophilic asthma, ILCs, and especially type 2 ILCs (ILC2s), are activated by alarmins such as IL-33 upon allergen triggering of the airway epithelium. This initiates IL-5 and IL-13 production by ILC2, resulting in eosinophilic inflammation and airway hyperreactivity. Type 3 ILCs (ILC3s) have been shown to be implicated in obesity-induced asthma, via IL-1β production by macrophages, leading ILC3 and release of IL-17. ILC1s might play a role in severe asthma, but its role is currently less investigated., Summary: Several studies have revealed that ILC2s play a role in the induction of eosinophilic inflammation in allergic and nonallergic asthmatic patients mainly via IL-5, IL-13, IL-33 and thymic stromal lymphopoietin. Knowledge on the role of ILC3s and ILC1s in asthmatic patients is lagging behind. Further studies are needed to support the hypothesis that these other types of ILCs contribute to asthma pathogenesis, presumably in nonallergic asthma phenotypes.

Purpose of Review: Recent advances in both murine models and clinical research of neutrophilic asthma are improving our understanding on the etiology and pathophysiology of this enigmatic endotype of asthma. We here aim at providing an overview of our current and latest insights on the pathophysiology and treatment of neutrophilic asthma., Recent Findings: Activation of the NLRP3 inflammasome pathway with increased IL-1β has been demonstrated in various studies involving patients with asthma. It has been suggested that type 3 innate lymphoid cells are implicated in the inflammatory cascade leading to neutrophilic inflammation. The role of neutrophil extracellular traps is only at the start of being understood and might be an attractive novel therapeutic target. A diverse panel of nonallergic stimuli, such as cigarette smoke, intensive exercise, cold air or saturated fatty acids, have been linked with neutrophilic airway inflammation. Azithromycin treatment could reduce asthma exacerbations and quality of life in patients with persistent asthma., Summary: Research of the last few years has accelerated our insights in mechanisms underlying neutrophilic asthma. This is in stark contrast with the lack of efficacy of different therapies targeting neutrophil chemotaxis and/or signalling cascade, such as IL-17A or CXCR2. Macrolide therapy might be a useful add-on therapy for patients with persistent asthma.

The worldwide prevalence of allergic diseases has drastically increased in the past decades. Recent studies underline the importance of microbial exposure for the development of a balanced immune system. Consequently, probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. However, clinical probiotic intervention studies have so far yielded conflicting results. There is increasing awareness about the importance of host-associated factors that determine whether an individual will respond to a specific probiotic treatment, and it is therefore crucial to promote a knowledge-based instead of an empirical selection of promising probiotic strains and their administration regimen.In this Review, we summarize the insights from animal model studies of allergic disease, which reveal how host-related factors - such as genetic makeup, sex, age and microbiological status - can impact the outcomes of preventive or curative probiotic treatment. We explore why and how these factors can influence the results of probiotic studies and negatively impact the reproducibility in animal experiments. These same factors might profoundly influence the outcomes of human clinical trials, and can potentially explain the conflicting results from probiotic intervention studies. Therefore, we also link these host-related factors to human probiotic study outcomes in the context of airway allergies., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Physical exercise requires proper function of the upper and lower airways in order to meet exertional ventilatory requirements. Athletes performing frequent intensive exercise experience more sino-nasal symptoms and demonstrate objective decreases in sino-nasal function when compared with the general population. Sino-nasal dysfunction is known to interfere with sport performance. Nasal epithelial injury, neutrophilic influx, and decreased mucociliary clearance have been associated with intensive training. In this review, the authors provide a comprehensive overview of the prevalence of sino-nasal disease in athletes, the possible underlying pathophysiologic mechanisms, and a summary of diagnostic and treatment options., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Allergic rhinitis (AR) is characterized by mucosal inflammation, driven by activated immune cells. Mast cells and T H 2 cells might decrease epithelial barrier integrity in AR, maintaining a leaky epithelial barrier., Objective: We sought to investigate the role of histamine and T H 2 cells in driving epithelial barrier dysfunction in AR., Methods: Air-liquid interface cultures of primary nasal epithelial cells were used to measure transepithelial electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4 kDa, and mRNA expression of tight junctions. Nasal secretions were collected from healthy control subjects, AR patients, and idiopathic rhinitis patients and were tested in vitro. In addition, the effect of activated T H 1 and T H 2 cells, mast cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-γ, and TNF-α on mucosal permeability was tested in vivo., Results: Histamine as well as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1 antagonist, azelastine prevented the early effect of nasal secretions of AR patients on epithelial integrity. Supernatant of activated T H 1 and T H 2 cells impaired epithelial integrity, while treatment with anti-TNF-α or anti-IL-4Rα monoclonal antibodies restored the T H 1- and T H 2-induced epithelial barrier dysfunction, respectively. IL-4, IFN-γ, and TNF-α enhanced mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier disruption and tight junction downregulation in a mouse model of house dust mite allergic airway inflammation., Conclusions: Our data indicate a key role for allergic inflammatory mediators in modulating nasal epithelial barrier integrity in the pathophysiology in AR., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: There is a clear need for simple and reliable patient-reported outcome measures for chronic obstructive pulmonary disease (COPD) and asthma in daily practice. The purpose of this review is to facilitate the choice for clinicians of patient-reported outcomes which they can use in their daily practice., Recent Findings: More than 50 patient-reported outcome measures for asthma and COPD exist and clinicians are often left confused on which to use. Four tools (two for asthma and two for COPD) can be suggested based on validity/reliability, responsiveness, practicality and are particularly convenient in terms of time to measure., Summary: On the basis of ample evidence, the COPD assessment test and the clinical COPD questionnaire for COPD and asthma control questionnaire and the asthma control test for asthma can be recommended for use in both primary care and other clinical settings. A simple guide figured as smiley faces has been designed to assist physicians to easily select the appropriate measure. With the current direction of thinking into treatable traits, targeted measures that evaluate the upper airways like the control of allergic rhinitis and asthma test may also be more used in the future.

Rhinitis and rhinosinusitis are the two major clinical entities of chronic upper airway disease. Chronic rhinosinusitis (CRS) and allergic rhinitis (AR) affect respectively up to 10 and 30% of the total population, hence being associated with an important socio-economic burden. Different phenotypes of rhinitis and CRS have been described based on symptom severity and duration, atopy status, level of control, comorbidities and presence or absence of nasal polyps in CRS. The underlying pathophysiological mechanisms are diverse, with different, and sometimes overlapping, endotypes being recognized. Type 2 inflammation is well characterized in both AR and CRS with nasal polyps (CRSwNP), whereas type 1 inflammation is found in infectious rhinitis and CRS without nasal polyps (CRSsNP). The neurogenic endotype has been demonstrated in some forms of non-allergic rhinitis. Epithelial barrier dysfunction is shown in AR and CRSwNP. Emerging therapies are targeting one specific pathophysiological pathway or endotype. This endotype-driven treatment approach requires careful selection of the patient population who might benefit from a specific treatment. Personalized medicine is addressing the issue of providing targeted treatment for the right patient and should be seen as one aspect of the promising trend towards precision medicine. This review provides a comprehensive overview of the current state of endotypes, biomarkers and targeted treatments in chronic inflammatory conditions of the nose and paranasal sinuses.

Background: Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking., Methods: Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10 th /90 th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles., Results: Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13., Conclusion: We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

Purpose of Review: Airway inflammation is considered to be a cardinal feature of asthma. However, the type of airway inflammation is heterogeneous and airway inflammation may even be absent. Biomarkers may help to identify the inflammatory phenotype or endotype, especially now the time has come that targeted therapies enter daily practice., Recent Findings: Sputum biomarkers have increased our insights into the different inflammatory asthma phenotypes, their response to treatment and their association with progression of disease. New endotypes of type 2 driven inflammation were identified using a multidimensional approach. A specific mast cell subtype has been linked with type 2 driven inflammation and response to inhaled corticosteroids. Advances have been made with regard to sputum cytokine analysis and might also help to guide future treatment of severe asthma., Summary: Identifying the target population for biological therapies will not be possible without the use of biomarkers. Optimized, easy-to-apply, automated methods for sputum analysis (cellular content or soluble markers) need to be developed for implementation of sputum biomarkers in daily clinical practice.

In this consensus document we summarize the current knowledge on major asthma, rhinitis, and atopic dermatitis endotypes under the auspices of the PRACTALL collaboration platform. PRACTALL is an initiative of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology aiming to harmonize the European and American approaches to best allergy practice and science. Precision medicine is of broad relevance for the management of asthma, rhinitis, and atopic dermatitis in the context of a better selection of treatment responders, risk prediction, and design of disease-modifying strategies. Progress has been made in profiling the type 2 immune response-driven asthma. The endotype driven approach for non-type 2 immune response asthma, rhinitis, and atopic dermatitis is lagging behind. Validation and qualification of biomarkers are needed to facilitate their translation into pathway-specific diagnostic tests. Wide consensus between academia, governmental regulators, and industry for further development and application of precision medicine in management of allergic diseases is of utmost importance. Improved knowledge of disease pathogenesis together with defining validated and qualified biomarkers are key approaches to precision medicine., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR)., Objective: We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM-induced murine model of allergic airway disease., Methods: Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-γ, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo., Results: A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN-γ had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability., Conclusion: We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Several members of a swimming club complained of respiratory symptoms associated with attending a municipal indoor swimming pool. Trichloramine, a volatile chlorination by-product and a potent respiratory irritant, was the most probable culprit, but the exact cause for its presence in excessive concentrations remained elusive., Methods: Twenty-two competitive swimmers and six coaches were evaluated during the outbreak and nine swimmers and four coaches were re-evaluated one year later. Symptoms were recorded by non-standardized history taking; pulmonary function testing included spirometry, measurement of fraction of exhaled nitric oxide (FENO) and histamine provocation. Concentrations of trichloramine in air were measured repeatedly by the method of Héry., Results: The most commonly reported symptoms consisted of cough (n=16), dyspnoea (n=13), tearing eyes (n=10) and blocked or runny nose (n=6). Mean FEV1% predicted was 109.1%. Mean FENO level was 19.7 ppb (higher than 25 ppb in 3 subjects). Airway hyperreactivity to histamine (PC20 ≤ 8 mg/ml) was detected in 22/26 subjects. Measured trichloramine concentrations in air exceeded the maximal concentration (WHO) of 0.5mg/m(3) four times between May and October 2011 and four times between January and March 2012. Polyamine compounds, present in glue used for repairing pipework, were identified as a probable external source of nitrogen resulting in increasing trichloramine concentrations. After the removal of the presumed cause of the excessive trichloramine concentrations, most subjects improved clinically, but several subjects remained symptomatic and had bronchial hyperreactivity., Discussion: A high prevalence of airway hyperreactivity, accompanied by symptoms of upper and lower airways, was detected in swimmers who had been repeatedly exposed to high trichloramine concentrations. A glue containing polyamines, used to repair a pipework, was suspected to be the source of this excessive production of trichloramine., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Aims: Eighteen patients with asthma were evaluated during preparation to climb to extreme altitude in order to study the effects of low fractional inspired oxygen (FiO(2)), prolonged exposure to cold air and high altitude on lung function, asthma control and airway inflammation., Methods: Spirometry and airway inflammation (fractional exhaled nitric oxide (FeNO) and induced sputum) were studied under different test conditions: hypoxic (FiO(2)=11%) exercise test, 24-hour cold exposure (-5°C) and before, during and after an expedition that involved climbing the Aconcagua mountain (6965 m)., Results: Forced expiratory volume in 1 s (FEV(1)) and FeNO values were slightly lower (p<0.04) after 1 h of normobaric hypoxia. FEV(1) decreased (p=0.009) after 24-hour cold exposure, accompanied by increased sputum neutrophilia (p<0.01). During the expedition FEV(1) and forced vital capacity decreased (maximum FEV(1) decrease of 12.3% at 4300 m) and asthma symptoms slightly increased. After the expedition the Asthma Control Test score and prebronchodilator FEV(1) were reduced (p<0.02), sputum neutrophil count was increased (p=0.04) and sputum myeloperoxidase levels, sputum interleukin 17 mRNA, serum and sputum vascular endothelial growth factor A levels were significantly higher compared with baseline. Patients with asthma with the lowest oxygen saturation during the hypoxic exercise test were more prone to develop acute mountain sickness., Conclusions: Exposure to environmental conditions at high altitude (hypoxia, exercise, cold) was associated with a moderate loss of asthma control, increased airway obstruction and neutrophilic airway inflammation. The cold temperature is probably the most important contributing factor as 24-hour cold exposure by itself induced similar effects.