Wytske J Fokkens

University of Amsterdam | UVA · Department of Otorhinolaryngology

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 to...

Background: Chronic rhinosinusitis, with or without nasal polyps, can have a major impact on a person's quality of life. Treatment is usually conservative and may include nasal saline, intranasal corticosteroids, antibiotics or systemic corticosteroids. If these treatments fail endoscopic sinus surgery can be considered. During surgery, visibility...

Nasal endoscopy is not only used for the diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP), but also for monitoring the response to therapy playing an important role in both daily practice and research. In contrast to patient-reported outcomes, endoscopic nasal polyp scoring by independent blinded readers is an objective measurement, n...

Plain English summary Patients with chronic rhinosinusitis (CRS) often have blocked or runny noses, and loss of sense of smell. They can also have sac-like growths in their nose called nasal polyps, which often require surgical removement. The symptoms of CRS with nasal polyps can affect quality of life. In a clinical study named SYNAPSE, a new tre...

MASK‐air®, a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK‐air® is a Good Practice of DG Santé on digitally‐enabled, patient‐centred care. It is...

Background: In clinical and epidemiological studies, cut-offs of Patient-Reported Outcome Measures (PROMs) can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cut-offs in MASK-air® have not been tested. Objective: To calculate cut-offs for VAS global, nasal, ocular, and asthma sy...

Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms....

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical...

Background Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on prevalence of uncontrolled CRS and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of effectiveness of marketed therapies including topical or...

Upper and lower airways diseases are very common, with population prevalence of 10% to 40%. The conditions are usually interlinked and referred to as "unified airway disease" or "the united airways." Especially in phenotypes with more severe disease, type 2 immunologic endotype is often noted. Comorbid upper and lower airway diseases are usually ca...

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differenc...

Chronic rhinosinusitis with nasal polyps (CRSwNP) associated with type 2 inflammation and non‐steroidal anti‐inflammatory drug (NSAID) ‐exacerbated respiratory disease (N‐ERD) can be difficult to control with standard medical therapy and sinus surgery. In this group, biologicals are potentially promising treatment options. The phase III clinical tr...

Background Several studies have suggested an impact of allergic rhinitis on academic productivity. However, large studies with real-world data (RWD) are not available. Objective To use RWD to assess the impact of allergic rhinitis on academic performance (measured through a visual analog scale – VAS education – and the WPAI+CIQ:AS questionnaire),...

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double-blind Phase III trial (NCT03085797) i...

Background Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and difference...

Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). Objective: To compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogu...

Objective Treatment for chronic rhinosinusitis with nasal polyps (CRSwNP) generally involves intranasal corticosteroids (INCS) and saline irrigation, followed by short courses of systemic corticosteroids (SCS) and/or surgery with postoperative medical therapy for patients who do not respond to INCS. However, both SCS use and surgery are associated...

Background: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. Objective: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual...

The European Position Paper on Rhinosinusitis and Nasal Polyps, EPOS, latest version EPOS2020 and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis, ICAR-RS, latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of m...

Background Non-allergic rhinitis (NAR) can be subdivided into several phenotypes: rhinorrhoea of the elderly, rhinitis medicamentosa, smokers’, occupational, hormonal, drug-induced, gustatory and idiopathic rhinitis. There are two pathophysiological endotypes of NAR: inflammatory and neurogenic. Phenotypes may serve as an indicator of an underlying...

Background Endoscopic sinus surgery (ESS) is a common operation for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) when medical therapy alone is insufficient. No randomised controlled trials on the efficacy of ESS have been published. We aimed to assess the efficacy of ESS plus medical therapy versus medical therapy alone in patien...

Objectives/hypothesis: Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, significantly improved outcomes for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-24 and SINUS-52 studies. This post hoc analysis evaluated dupilumab's effect on patient-reported sym...

Tight junction defects (TJ) have been associated with a defective epithelial barrier function in allergic rhinitis (AR). Intranasal corticosteroids are potent drugs frequently used to treat AR and are shown to restore epithelial integrity by acting on TJs and by reducing type 2 cytokine production. However, the effect of different classes of intran...

Patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) often suffer from chronic rhinosinusitis (CRS) with nasal polyps, a form of primary diffuse Type 2 CRS. Although this disease is also seen in NSAID-tolerant patients, CRS in N-ERD often is more severe and more treatment resistant; local nasal therapy...

Background MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. Methods Daily monitoring VAS data were assessed in MASK-...

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media (OM) characterized by eosinophilic accumulation in the middle ear mucosa and secretion. Associated sensorineural hearing loss can eventually lead to (functional) deafness. EOM is strongly associated with type 2 inflammation driven respiratory disease, i.e. asthma and chronic rhino...

Background : Recent data show uncontrolled disease in 35% of allergic rhinitis (AR) patients on medical treatment. The reasons for uncontrolled disease can arbitrarily be divided into disease-related, diagnosis-related, treatment-related, and patient-related factors. However, the relative importance of these factors in uncontrolled disease remains...

Allergen immunotherapy (AIT), the gradually increasing repeated administration of high doses of allergens to allergic patients, offers the potential for immune tolerance against reactions to the natural exposures to specific allergens. AIT may lead to the long-lasting remission of allergic symptoms and is the only disease-modifying intervention in...

Chronic rhinosinusitis (CRS) is a complex upper airway inflammatory disease with a broad spectrum of clinical variants. As our understanding of the disease pathophysiology evolves, so too does our philosophy towards the approach and management of CRS. Endotyping is gaining favour over phenotype‐based classifications, owing to its potential in progn...

EPOS2020 is the 4th and most recent version of the European Position Paper on Rhinosinusitis and Nasal Polyps which was f irst published in 2005. It aims to provide the most up to date scientifically robust information on the topic published in the literature which has been critically analysed by an international group of clinicians drawn from all...

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID‐19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID‐19 vaccines due to high risk of death. In very rare instances,the COVID‐19 vaccines can induce anaphylaxis, and the...

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID‐19 vaccines are expected to have similar positive impacts on health across the glob...

Background Chronic rhinosinusitis with nasal polyps affects approximately 2–4% of the general population, and long-term use of systemic corticosteroids is associated with adverse effects. The aim of this study was to assess the efficacy and safety of mepolizumab in adults with recurrent, refractory severe bilateral chronic rhinosinusitis with nasal...

Background Although there are many asymptomatic patients, one of the problems of COVID‐19 is early recognition of the disease. COVID‐19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID‐19 symptoms may be mistaken withthe common cold or allergic rhinitis. An ARIA‐EAACI study group attempted to differentiate upper r...

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared to the standard of care. Pubmed, EMBASE and Cochrane Library were searched for RCTs. Critical and important CRSwNP‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed u...

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared to the standard of care. Pubmed, EMBASE and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed u...

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the glob...

Group 2 innate lymphoid cells (ILC2s) orchestrate protective type 2 immunity and have been implicated in various immune disorders. In the mouse, circulatory inflammatory ILC2s (iILC2s) were identified as a major source of type 2 cytokines. The human equivalent of the iILC2 subset remains unknown. Here, we identify a human inflammatory ILC2 populati...

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10⁺ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1⁺ but not KLRG1– ILC2 produced IL-10 upon activation with IL-33 an...

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 conse...

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 updat...

[This corrects the article DOI: 10.1186/s13601-019-0303-6.].

Modern healthcare requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping and the development and application of reliable...

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 emergin...

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis.It strengthens the ARIA change management strategy in the prevention and manag...

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID‐19). This disease, caused by the severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2), has developed into a pandemic. To date it has resulted in ~6.5 million confirmed cases and caused almost 400,000 related deaths worldwide. Unequivocally, the C...

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...

The ARIA initiative was started during a World Health Organization workshop in 1999. The initial goals were to propose a new classification for allergic rhinitis, to promote the concept of multi-morbidity in asthma and rhinitis and to develop guidelines with stakeholders for worldwide use. ARIA is now focused on the implementation of emerging techn...

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date it has resulted in~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19...

Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease associated with a substantial personal and socio‐economic 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 use...

The development of biologics targeting various aspects of Type-2 inflammation for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) will provide clinicians with powerful tools to help treat these patients. However, other therapies are also available and positioning of biologics in a management algorithm will require comparative tri...

Correction to: Allergo J Int 2019 10.1007/s40629-019-00110-9 Affiliation and disclaimer have been misrepresented and are hereby corrected: Vera Mahler: Affiliation: Med. Faculty, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Germany. Disclaimer: The views expressed in this …

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...

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 measure...

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body: As an example...

Background: Non-allergic rhinitis is defined as dysfunction and non-infectious inflammation of the nasal mucosa that is caused by provoking agents other than allergens or microbes. It is common, with an estimated prevalence of around 10% to 20%. Patients experience symptoms of nasal obstruction, anterior rhinorrhoea/post-nasal drip and sneezing. S...

Die Anzahl der von Allergien betroffenen Patienten nimmt weltweit zu. Hiermit gehen erhebliche Kosten für die Gesundheits- und Sozialsysteme durch allergische Erkrankungen einher. Integrierte Versorgungskonzepte sind erforderlich, die innerhalb der nationalen Gesundheitssysteme eine umfassende Versorgung ermöglichen. Die ARIA-Initiative entwickelt...

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to i...

Background The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative de...

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key driv...

Smart devices and internet-based applications are largely used in allergic rhinitis and may help to address some unmet needs. However, these new tools need to first of all be tested for privacy rules, acceptability, usability and cost-effectiveness. Secondly, they should be evaluated in the frame of the digital transformation of health, their impac...