Publications by authors named "Peter Hellings"

158 Publications

Multidisciplinary Care for Severe or Uncontrolled Chronic Upper Airway Diseases.

Curr Allergy Asthma Rep 2021 Apr 1;21(4):27. Epub 2021 Apr 1.

Department of Otorhinolaryngology, University of Crete School of Medicine, Crete, Greece.

Purpose Of Review: A multidisciplinary approach is regarded as the best practice for many chronic diseases, such as cancer and asthma, with well-documented value. There is also evidence that it may be beneficial to patients with chronic rhinosinusitis (CRS) and/or allergic airway disease presenting to tertiary referral centres. We discuss here whether and how organizing this kind of healthcare transition into a more integrated care pathway would benefit severe chronic upper airways disease (SCUAD) management.

Recent Findings: Based on a recent related EUFOREA panel discussion, literature search, and review of the best overseas practices, an appropriate implementation strategy of multidisciplinary care and its potential results are presented. Organizational principles, hurdles, and challenges of the process, as well as envisaged solutions and results, are being reported. The efficiency of care and the quality control assessment are concepts that are currently gaining importance. At the same time, novel treatment options based on molecular and precision medicine advancements, such as biologics, are being increasingly prescribed. Appropriately organized multidisciplinary care teams can adapt to new demands, data, and discoveries to assure maximum benefit for both patients and healthcare professionals.
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http://dx.doi.org/10.1007/s11882-021-01004-zDOI Listing
April 2021

A TRiP Through the Roles of Transient Receptor Potential Cation Channels in Type 2 Upper Airway Inflammation.

Curr Allergy Asthma Rep 2021 Mar 18;21(3):20. Epub 2021 Mar 18.

Department of Otorhinolaryngology, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium.

Purpose Of Review: Despite their high prevalence, the pathophysiology of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) remains unclear. Recently, transient receptor potential (TRP) cation channels emerged as important players in type 2 upper airway inflammatory disorders. In this review, we aim to discuss known and yet to be explored roles of TRP channels in the pathophysiology of AR and CRS with nasal polyps.

Recent Findings: TRP channels participate in a plethora of cellular functions and are expressed on T cells, mast cells, respiratory epithelial cells, and sensory neurons of the upper airways. In chronic upper airway inflammation, TRP vanilloid 1 is mostly studied in relation to nasal hyperreactivity. Several other TRP channels such as TRP vanilloid 4, TRP ankyrin 1, TRP melastatin channels, and TRP canonical channels also have important functions, rendering them potential targets for therapy. The role of TRP channels in type 2 inflammatory upper airway diseases is steadily being uncovered and increasingly recognized. Modulation of TRP channels may offer therapeutic perspectives.
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http://dx.doi.org/10.1007/s11882-020-00981-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973410PMC
March 2021

Efficacy of dupilumab in patients with a history of prior sinus surgery for chronic rhinosinusitis with nasal polyps.

Int Forum Allergy Rhinol 2021 Feb 21. Epub 2021 Feb 21.

Sanofi Genzyme, Reading, UK.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease treated with sinus surgery when refractory to medical intervention. However, recurrence postsurgery is common. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor for interleukin 4 (IL-4) and IL-13, key and central drivers of type 2 inflammation. We report the efficacy of dupilumab in patients with CRSwNP from the SINUS-24/SINUS-52 trials (NCT02912468/NCT02898454), by number of prior surgeries and time since last surgery.

Methods: Patients were randomized to placebo or dupilumab 300 mg every 2 weeks. Post hoc subgroup analyses were performed for patients with 0, ≥1, 1/2, or ≥3 prior surgeries, and for patients who had surgery within <3, 3 to <5, 5 to <10, or ≥10 years. Efficacy outcomes at 24 weeks included co-primary endpoints nasal polyp score (NPS) and nasal congestion (NC), and Lund-Mackay (LMK), 22-item Sino-Nasal Outcome Test (SNOT-22), and smell scores.

Results: Of 724 patients randomized, 459 (63.4%) had ≥1 prior surgery. Baseline sinus disease (NPS, NC, LMK) and olfactory dysfunction (University of Pennsylvania Smell Identification Test [UPSIT] and loss of smell) scores were worse for patients with ≥3 prior surgeries vs no surgery. Baseline NPS and LMK were worse in patients with <3 years since last surgery than in patients with ≥5 years since last surgery. Dupilumab significantly improved all outcome measures vs placebo in all subgroups by number of surgeries and by time since last surgery. Improvements in NPS and LMK were greater in patients with <3 years since last surgery than patients with ≥5 years. Safety results were consistent with the known dupilumab safety profile.

Conclusion: Dupilumab improved CRSwNP outcomes irrespective of surgery history, with greater improvements in endoscopic outcomes in patients with shorter duration since last surgery.
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http://dx.doi.org/10.1002/alr.22780DOI Listing
February 2021

Indirect Treatment Comparison of Biologics in Chronic Rhinosinusitis with Nasal Polyps.

J Allergy Clin Immunol Pract 2021 Feb 4. Epub 2021 Feb 4.

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Background: Among patients with chronic rhinosinusitis with nasal polyps (CRSwNP), randomized clinical trials (RCTs) of biologics, such as anti-interleukin-4/interleukin-13 (dupilumab) and anti-immunoglobulin E (omalizumab), have demonstrated efficacy compared with intranasal corticosteroids (INCS). However, no head-to-head RCTs exist between biologics.

Objective: To perform an indirect treatment comparison (ITC) of the efficacy of biologics plus INCS versus placebo (INCS) as a common comparator.

Methods: Embase, MEDLINE, and Cochrane were searched for RCTs of biologics in CRSwNP. Bucher ITCs were performed for outcomes at week 24: nasal polyp score (NPS) (range, 0-8), nasal congestion (NC) (range, 0-3), loss of smell (range, 0-3), University of Pennsylvania Smell Identification Test (range, 0-40), total symptom score (range, 0-12), 22-item sinonasal outcome test (range, 0-110), and responder analyses based on NPS or NC improvement of one point or greater.

Results: Assessment of trial design, baseline characteristics, and outcome measures suggested that ITC was feasible with four phase 3 RCTs: dupilumab SINUS-24 and SINUS-52 (NCT02912468/NCT02898454) and omalizumab POLYP 1 and POLYP 2 (NCT03280550/NCT03280537). In the intent-to-treat population, dupilumab had significantly greater improvements from baseline to week 24 versus omalizumab across key outcomes: NPS (least squares mean difference [95% confidence interval], -1.04 [-1.63 to -0.44]), NC (-0.35 [-0.60 to -0.11]), loss of smell (-0.66 [-0.90 to -0.42]), University of Pennsylvania Smell Identification Test (6.70 [4.67-8.73]), and total symptom score (-1.18 [-1.95 to -0.41]). Improvement in the 22-item sinonasal outcome test was greater in dupilumab versus omalizumab but was not statistically significant. Dupilumab patients were significantly more likely to achieve one-point improvement or greater in NPS (odds ratio [95% CI] = 3.85 [1.82-7.04]) and NC (2.13 [1.12-4.04]) versus omalizumab.

Conclusions: Although ITCs have limitations, these results demonstrated that dupilumab had consistently greater improvements in key CRSwNP outcomes versus omalizumab at week 24.
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http://dx.doi.org/10.1016/j.jaip.2021.01.031DOI Listing
February 2021

Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma.

Ann Allergy Asthma Immunol 2021 Jan 16. Epub 2021 Jan 16.

Sanofi, Chilly-Mazarin, France.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and type 2 asthma share the same inflammatory pathophysiology and are frequent comorbidities. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin 4 and interleukin 13, which are key and central drivers of type 2 inflammation.

Objective: We report the effect of dupilumab vs placebo on outcome measures of the upper and lower airways and health-related quality of life (HRQoL) in the pooled population of patients with CRSwNP and comorbid asthma from the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies.

Methods: In these randomized, double-blind, placebo-controlled trials, patients received subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks on a background of mometasone furoate nasal spray. Changes from baseline at week 24 in the upper and lower airway outcome measures are reported.

Results: Of the 724 patients randomized, 428 (59.1%) had comorbid asthma. In patients with asthma at week 24, dupilumab vs placebo improved the nasal polyp score (-2.04), patient-reported nasal congestion score (-1.04), Lund-Mackay computed tomography scan score (-6.43), peak nasal inspiratory flow (46.15 L/min), and 22-item sinonasal outcome test score (-21.42; all P < .001). The forced expiratory volume in 1 second and 6-item asthma control questionnaire scores were also markedly improved with dupilumab vs placebo. The most common adverse events (nasopharyngitis, headache, injection-site erythema, worsening of nasal polyposis, and asthma) were more frequent with placebo than dupilumab.

Conclusion: Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated.

Trial Registration: ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).
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http://dx.doi.org/10.1016/j.anai.2021.01.012DOI Listing
January 2021

Brain activation after nasal histamine provocation in house dust mite allergic rhinitis patients.

Allergy 2020 Nov 29. Epub 2020 Nov 29.

KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, Leuven, Belgium.

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http://dx.doi.org/10.1111/all.14677DOI Listing
November 2020

International consensus statement on allergy and rhinology: rhinosinusitis 2021.

Int Forum Allergy Rhinol 2021 Mar;11(3):213-739

Capital Medical University, Beijing, China.

I.

Executive Summary: BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document.

Methods: ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary.

Results: ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided.

Conclusion: This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.
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http://dx.doi.org/10.1002/alr.22741DOI Listing
March 2021

The Role of Biologics in Chronic Rhinosinusitis with Nasal Polyps.

J Allergy Clin Immunol Pract 2021 Mar 20;9(3):1099-1106. Epub 2020 Nov 20.

Department of Medicine, Harvard Medical School, the Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass. Electronic address:

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease of the upper respiratory tract. This article provides expert opinion and points of view from both allergists and rhinologists who specialize in CRSwNP. Despite the potential value of biomarker-based endotyping to provide guidance regarding optimal care and treatment choices for patients with CRSwNP, current practice is largely not biomarker-based. In general, there is agreement that for patients with symptomatic CRSwNP who have failed a trial of a course of at least 3 months of intranasal steroids and a short course of oral corticosteroids, a surgical intervention will often be the next treatment of choice. Biologics may be considered before an initial surgery in patients with comorbid severe asthma and in those for whom surgery is less available, refused by the patient, or likely to be associated with a higher-than-average complication rate. Biologic use immediately following surgery may be considered in patients who have a history of nasal polyp recurrence within 12 months of a prior surgery. For many patients with recalcitrant disease, a combination of sinus surgery and use of a biologic that is targeted to their precise endotype may be the optimal treatment strategy, though which surgical approach and which biologics are best for each patient are debates that remain ongoing.
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http://dx.doi.org/10.1016/j.jaip.2020.11.017DOI Listing
March 2021

EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management.

J Allergy Clin Immunol 2021 Jan 20;147(1):29-36. Epub 2020 Nov 20.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. A rational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.
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http://dx.doi.org/10.1016/j.jaci.2020.11.013DOI Listing
January 2021

Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).

World Allergy Organ J 2020 Oct 5;13(10):100467. Epub 2020 Oct 5.

INSERM U 1168, VIMA: Ageing and Chronic Diseases Epidemiological and Public Health Approaches, Villejuif, France.

Air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (IAD) such as allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma, and chronic obstructive pulmonary disease (COPD). Oxidative stress in patients with IAD can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. We reviewed emerging data depicting the involvement of oxidative stress in IAD patients. We evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult.
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http://dx.doi.org/10.1016/j.waojou.2020.100467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534666PMC
October 2020

Surgery in Nasal Polyp Patients: Outcome After a Minimum Observation of 10 Years.

Am J Rhinol Allergy 2020 Oct 5:1945892420961964. Epub 2020 Oct 5.

Department of Otorhinolaryngology, University Hospital, Ghent, Belgium.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) often requires surgery, but recurrence even after surgery is common. Recurrence rates largely vary in literature and asthma seems to be a comorbid factor.

Objective: In this study, we aim to estimate disease recurrence during a long-term follow-up, together with the investigation of possible predicting and/or influencing parameters.

Methods: Out of 196 patients operated for CRSwNP between 01/2000 and 01/2006, 133 patients had a follow-up of at least 10 years and could be included. The inflammatory profile at surgery was determined on nasal tissue and sinonasal secretions, and included analysis of eosinophils, eosinophilic-rich mucus (ERM) typically containing Charcot-Leyden crystals (CLC), and fungal hyphae (FH). During follow-up, recurrence, received treatments and comorbidities were collected.

Results: Out of the 133 included patients, local eosinophilia was present in 81% and ERM in 60%. Recurrence during follow-up was observed in 62%, and was associated with local eosinophilia and ERM (both p < 0.001). Asthma was present in 28% at inclusion, and 17% developed asthma after surgery during follow-up. The presence of asthma, at inclusion as well as developed during follow-up, was significantly associated with recurrence of CRSwNP (p = 0.001 for group comparison).

Conclusion: Recurrence after CRSwNP surgery is common when a long-term follow-up is taken into account. ERM detected in sinonasal secretions at surgery seems to be a predictive factor for recurrence and need for revision surgery. Asthma is a frequently found comorbid factor in CRSwNP, develops even at higher age despite surgical treatment for CRSwNP, and is also associated with a higher recurrence rate. Sustained medical care after surgery is mandatory.
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http://dx.doi.org/10.1177/1945892420961964DOI Listing
October 2020

A 300 IR sublingual tablet is an effective, safe treatment for house dust mite-induced allergic rhinitis: An international, double-blind, placebo-controlled, randomized phase III clinical trial.

J Allergy Clin Immunol 2021 Mar 2;147(3):1020-1030.e10. Epub 2020 Sep 2.

Division of Allergy and Immunology, University of South Florida, Tampa, Fla.

Background: Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies.

Objective: We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus:Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate to severe HDM-induced allergic rhinitis.

Methods: In a phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period.

Results: A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P < .0001) than in the placebo group (4.35), with a relative least squares mean difference of -16.9% (95% CI, -24.0% to -9.2%). All prespecified secondary end points were consistently improved in the 300 IR group, relative to placebo. The 300 IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300 IR group and 14.9% in the placebo group.

Conclusions: The 300 IR sublingual HDM tablet is an effective, safe treatment for HDM-induced allergic rhinitis.
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http://dx.doi.org/10.1016/j.jaci.2020.07.036DOI Listing
March 2021

Role of Biologics in Chronic Rhinosinusitis With Nasal Polyposis: State of the Art Review.

Otolaryngol Head Neck Surg 2021 01 4;164(1):57-66. Epub 2020 Aug 4.

Department of Head & Neck Surgery, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA.

Objective: To review the current literature regarding the role of biologics in the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP).

Data Sources: PubMed/MEDLINE, EMBASE, Cochrane Review, ClinicalTrials.gov.

Review Methods: We conducted a comprehensive review of the literature on clinical studies investigating the efficacy of emerging biologics in CRSwNP, with a focus on randomized controlled trials.

Conclusions: There appears to be promising evidence to support the safety and efficacy of biologics in CRSwNP with and without asthma for select patients. However, additional large-scale randomized studies with longer follow-up are necessary to determine which patients would benefit the most from these novel systemic treatments.

Implications For Practice: Chronic rhinosinusitis with nasal polyposis refractory to medical and surgical therapy remains a challenging clinical problem for otolaryngologists. However, emerging biologic therapies may offer a new therapeutic option for such patients with recalcitrant disease.
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http://dx.doi.org/10.1177/0194599820939964DOI Listing
January 2021

Prevalence and triggers of self-reported nasal hyperreactivity in adults with asthma.

World Allergy Organ J 2020 Jun 1;13(6):100132. Epub 2020 Jul 1.

Department of Otorhinolaryngology-Head and Neck Surgery, University Hospitals Leuven, Belgium.

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.
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http://dx.doi.org/10.1016/j.waojou.2020.100132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334478PMC
June 2020

Epithelial barriers in allergy and asthma.

J Allergy Clin Immunol 2020 06;145(6):1499-1509

KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Unit, Leuven, Belgium; Department of Otorhinolaryngology, Head and Neck Surgery, University of Crete School of Medicine, Heraklion, Crete, Greece.

The respiratory epithelium provides a physical, functional, and immunologic barrier to protect the host from the potential harming effects of inhaled environmental particles and to guarantee maintenance of a healthy state of the host. When compromised, activation of immune/inflammatory responses against exogenous allergens, microbial substances, and pollutants might occur, rendering individuals prone to develop chronic inflammation as seen in allergic rhinitis, chronic rhinosinusitis, and asthma. The airway epithelium in asthma and upper airway diseases is dysfunctional due to disturbed tight junction formation. By putting the epithelial barrier to the forefront of the pathophysiology of airway inflammation, different approaches to diagnose and target epithelial barrier defects are currently being developed. Using single-cell transcriptomics, novel epithelial cell types are being unraveled that might play a role in chronicity of respiratory diseases. We here review and discuss the current understandings of epithelial barrier defects in type 2-driven chronic inflammation of the upper and lower airways, the estimated contribution of these novel identified epithelial cells to disease, and the current clinical challenges in relation to diagnosis and treatment of allergic rhinitis, chronic rhinosinusitis, and asthma.
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http://dx.doi.org/10.1016/j.jaci.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270816PMC
June 2020

Lactobacilli Have a Niche in the Human Nose.

Cell Rep 2020 05;31(8):107674

Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Electronic address:

Although an increasing number of beneficial microbiome members are characterized for the human gut and vagina, beneficial microbes are underexplored for the human upper respiratory tract (URT). In this study, we demonstrate that taxa from the beneficial Lactobacillus genus complex are more prevalent in the healthy URT than in patients with chronic rhinosinusitis (CRS). Several URT-specific isolates are cultured, characterized, and further explored for their genetic and functional properties related to adaptation to the URT. Catalase genes are found in the identified lactobacilli, which is a unique feature within this mostly facultative anaerobic genus. Moreover, one of our isolated strains, Lactobacillus casei AMBR2, contains fimbriae that enable strong adherence to URT epithelium, inhibit the growth and virulence of several URT pathogens, and successfully colonize nasal epithelium of healthy volunteers. This study thus demonstrates that specific lactobacilli are adapted to the URT and could have a beneficial keystone function in this habitat.
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http://dx.doi.org/10.1016/j.celrep.2020.107674DOI Listing
May 2020

Low-dose capsaicin (0.01 mM) nasal spray is equally effective as the current standard treatment for idiopathic rhinitis: A randomized, double-blind, placebo-controlled trial.

J Allergy Clin Immunol 2021 Jan 19;147(1):397-400.e4. Epub 2020 May 19.

Department of Otorhinolaryngology, Head & Neck Surgery, University Hospitals Leuven, Leuven, Belgium; Allergy and Clinical Immunology Research Unit, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Otorhinolaryngology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands; Laboratory of Upper Airways Research, Department of Otorhinolaryngology, University of Ghent, Ghent, Belgium.

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http://dx.doi.org/10.1016/j.jaci.2020.04.054DOI Listing
January 2021

Allergic respiratory disease care in the COVID-19 era: A EUFOREA statement.

World Allergy Organ J 2020 May 16;13(5):100124. Epub 2020 May 16.

Charite, Berlin, Germany.

Spring and Summer 2020 are unique in that the challenges of care for those suffering from pollen allergy coincide with the COVID-19 pandemic. Several considerations are important to allow optimal care of allergic rhinitis (AR) and asthma and hence prevention of coronavirus spread through sneezing, rhinorrhoea, and coughing. This compact overview of recommendations by the EUFOREA expert teams on allergic airway diseases and allergen-specific immunotherapy (AIT) is based on investigation of the current COVID-19 literature in association with the key words above and shared clinical experience of the experts involved. It deals with similarities and differences between AR and coronavirus infection, specific recommendations for allergic disease care in the COVID-19 era, including guidance on AIT.
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http://dx.doi.org/10.1016/j.waojou.2020.100124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229977PMC
May 2020

Real-life assessment of chronic rhinosinusitis patients using mobile technology: The mySinusitisCoach project by EUFOREA.

Allergy 2020 11 19;75(11):2867-2878. Epub 2020 Jun 19.

Department of Microbiology, Immunology & Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Belgium.

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.
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http://dx.doi.org/10.1111/all.14408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687134PMC
November 2020

Placebo effects in allergen immunotherapy-An EAACI Task Force Position Paper.

Allergy 2021 03;76(3):629-647

Department of Respiratory Medicine, Royal Sussex County Hospital, University of Sussex and University of Brighton, Brighton, UK.

The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
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http://dx.doi.org/10.1111/all.14331DOI Listing
March 2021

In-vivo diagnostic test allergens in Europe: A call to action and proposal for recovery plan-An EAACI position paper.

Allergy 2020 09;75(9):2161-2169

Allergy Section, Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
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http://dx.doi.org/10.1111/all.14329DOI Listing
September 2020

ARIA 2019, Allerjik Rinite Tedavi Yaklaşımı-Türkiye.

Turk Thorac J 2020 03 1;21(2):122-133. Epub 2020 Mar 1.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France.

Gerçek yaşamda, çevresel maruziyetlerin de etkilediği rinit ve astım mültimorbidite durumlarında, dijitalleşmiş ve kişiye odaklanan tedaviler için bütünleştirilmiş tedavi yollarının değerlendirilmesi önerilmektedir. Gerçek yaşamdaki bu durum mültisipliner bir yaklaşımla basamaklandırılıp, rehberilerinde ülkelerdeki gereksinimlere göre değiştilmesini gerektirebilir. Allerjik rinitte hem farmakoterapi hem immünoterapi açısından acil yeni yaklaşımlara ihtiyaç olduğu görülmüştür. 3. Aralık 2018'de Paris'te bir toplantı yapılmış ve iki ayrı belge hazırlanmıştır. Bu yayında bunlara ait bir özet sunulup, ülkeye ve sağlık sistemine uygun kullanımın çerçevesi oluşturulmak istenmiştir.
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http://dx.doi.org/10.5152/TurkThoracJ.2019.19084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089699PMC
March 2020

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico].

Rev Alerg Mex 2019 Oct-Dec;66(4):409-425

Universidad del Salvador, Facultad de Medicina, Buenos Aires, Argentina.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.
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http://dx.doi.org/10.29262/ram.v66i4.643DOI Listing
September 2020

Morphing as a Selection Tool in the Rhinoplasty Consult: A Cross-Sectional Study.

Facial Plast Surg 2020 Feb 24;36(1):112-119. Epub 2020 Feb 24.

Department of Otorhinolaryngology, Head and Neck Surgery, UZ Leuven Campus Gasthuisberg, Leuven, Belgium.

Despite the recognized value of morphing in the literature, this preoperative tool has never been studied in the context of selection process in rhinoplasty. The main purpose of this article is to identify the use of morphing as a filter for unsuitable patients, the attrition rate from the initial consultation to surgery, and whether patients' appreciation on morphing influence their decision-making process. Three-hundred thirty-four consecutive patients, seeking rhinoplasty, underwent two-dimensional computer imaging and completed a 14-question survey about their opinion on morphing. Based on the presence or absence of patient/physician consensus on the expected outcomes during simulation, patients were divided into accepted or rejected candidates for surgery. Accepted candidates were scheduled for rhinoplasty and subdivided into those who underwent surgery, those who postponed their surgery (static), and those who cancelled their procedure. Their responses to the survey were compared between different patients' categories. Forty-four patients (13.2%) were rejected for rhinoplasty since consensus was not achieved during morphing. From 290 accepted patients, 178 underwent their operation (53.3%), 74 patients (22.1%) postponed their rhinoplasty, and 38 (11.4%) cancelled their surgery. Fifty-seven percent of rejected patients and 42% of the static group were not satisfied with the proposed results of morphing, in contrast with 16% of the operated group. Sixty-four percent of rejected patients, and 47% of the static group were not reassured after morphing, compared with 26% of the operated group. Presence or absence of consensus during morphing can guide the surgeon regarding a given patients' suitability for surgery. Patient satisfaction and reassurance with the morphed images can be a good predictor of patients who will proceed to surgery, calling attention to the value of morphing as a selection tool for surgeons and patients alike.
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http://dx.doi.org/10.1055/s-0040-1701480DOI Listing
February 2020

Correlation between work impairment, scores of rhinitis severity and asthma using the MASK-air App.

Allergy 2020 07 22;75(7):1672-1688. Epub 2020 Mar 22.

ISGlobal, Barcelona, Spain.

Background: In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently.

Methods: All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated.

Results: A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures.

Conclusions: VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.
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http://dx.doi.org/10.1111/all.14204DOI Listing
July 2020

Prevalence and impact of nasal hyperreactivity in chronic rhinosinusitis.

Allergy 2020 07 15;75(7):1768-1771. Epub 2020 Feb 15.

Department of Microbiology & Immunology, Allergy and Clinical Immunology Research Unit, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1111/all.14199DOI Listing
July 2020

Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper.

Clin Transl Allergy 2020 3;10. Epub 2020 Jan 3.

3Upper Airway Research Laboratory, Dep. of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.

Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.
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http://dx.doi.org/10.1186/s13601-019-0303-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941282PMC
January 2020

Perspectives in allergen immunotherapy: 2019 and beyond.

Allergy 2019 12;74 Suppl 108:3-25

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Zurich, Switzerland.

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future.
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http://dx.doi.org/10.1111/all.14077DOI Listing
December 2019