Publications by authors named "Hellings P"

Article Synopsis
  • In April 2024, the European Summit on chronic respiratory diseases (CRDs) was held in the European Parliament, organized by EUFOREA and hosted by MEPs Dorien Rookmaker and Mislav Kolakušić.
  • The Summit aimed to address the challenges faced by European patients with CRDs by fostering collaboration among various European and global health organizations.
  • Representatives from multiple societies and patient associations discussed strategies to improve respiratory care and prevention by sharing their visions and action plans.
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The introduction of biologics for the treatment of severe upper and lower (type 2) airway inflammation has been a gamechanger in the management of these diseases. Biologics are injectable medications targeting different molecules relevant in (type 2) inflammation in patients with severe (type 2) airway diseases, like asthma, eosinophilic chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS) and those who remain uncontrolled despite regular treatment (1-3). After the phase 3 trials, showing significant impact on symptoms, quality of life and interventions like surgery (for the upper airways) and exacerbations needing hospitalisation (for the lower airways), biologics are now used in daily practice in many parts of the world (4, 5).

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Remission has recently been proposed as the new goal of care in CRSwNP or Nasal Polyp Syndrome by the European Forum for Research and Education in Allergy and Airway Diseases / European Position Paper on Rhinosinusitis and Nasal Polyps (EUFOREA/EPOS) (1,2) as well as by global leaders in Rhinology (3). In CRSwNP, remission is defined as a prolonged state of control, without bothersome symptoms reported by the patient for at least 12 months, without the need for either oral corticosteroids or endoscopic sinus surgery (ESS), and without endoscopic signs of active disease (1). This new goal of care is to be encouraged by the ENT community and CRSwNP patients as persistent symptoms unalleviated by historical approaches (4,5) can be reduced by new therapies including biologics.

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Allergic rhinitis (AR), the most prevalent immunological disease, affects approximately 400 million individuals globally and can significantly impact quality of life (QoL). Despite nearly 25 years of guidelines, AR remains largely under- diagnosed, suboptimally treated and poorly controlled. In the light of new knowledge and treatment options, there is a necessity to update or revise fundamental AR definitions to facilitate communication across diverse specialties engaged in its treatment and to improve patient care.

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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a recurrent inflammatory disease associated with several comorbidities and a significant disease burden for patients. Treatments include corticosteroids and sinonasal surgery, but these can be associated with the risk of adverse events and nasal polyp recurrence. Biologic treatments such as mepolizumab can be used as an add-on treatment and are effective at reducing surgery and corticosteroid use.

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The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized the first European Biologic Training Course (EBTC) in Brussels on 1st March 2024. The aim of this hybrid EBTC including both face-to-face and web-based participation was to address the educational needs of physicians dealing with asthma and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) on the clinically relevant aspects of diagnosing and treatment with biologics. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities.

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Asthma is a common multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes and endotypes and the availability of targeted biologic treatment options, the disease remains uncontrolled in a substantial proportion of patients with risk of exacerbations, requiring systemic corticosteroids, and with progressive disease. Current international guidelines advocate a personalized management approach to patients with uncontrolled severe asthma.

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Chronic rhinosinusitis with nasal polyps (CRSwNP) often co-exists with asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), creating a more severe phenotype and an additional burden compared with CRSwNP disease alone. The relationship between these diseases in terms of shared immunological disbalance has been coined in the literature as "global airway disease" or "unified airway disease" and requires integrated treatment strategies. Our post hoc analysis of the Phase III randomised, double-blind, placebo-controlled, multicentre SYNAPSE study (GSK ID: 205687; NCT03085797) assessed the efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, in simultaneously improving both CRSwNP and asthma outcomes versus placebo.

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Purpose Of The Review: Thymic stromal lymphopoietin (TSLP) is increasingly recognized for its pivotal role in the pathogenesis of various epithelial-driven chronic inflammatory diseases. This review navigates the existing evidence on TSLP, with a particular focus on asthma, before delving into the current understanding of its role in chronic rhinosinusitis with nasal polyps (CRSwNP). We explore the role of TSLP in the pathogenesis of asthma and CRSwNP, two conditions often interconnected and collectively referred to as"Global Airway Disease".

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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma (SA) are 2 frequently coexisting conditions that are, in most cases, associated with eosinophilic inflammation. The concurrence of both diseases has a negative synergistic impact on disease severity and patients' health-related quality of life. Thus, a holistic, collaborative management of these patients is a critical unmet need.

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Article Synopsis
  • The SYNAPSE study found that mepolizumab, when combined with standard care, significantly reduced nasal polyp scores in patients suffering from chronic rhinosinusitis with nasal polyps compared to placebo.
  • Researchers aimed to examine the connection between nasal polyp scores, peak nasal inspiratory flow, and patient-reported outcomes.
  • Results indicated that patients who showed improvements in nasal polyp scores also experienced better peak nasal flow and symptom relief compared to those who did not improve.
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Article Synopsis
  • Interleukin-5 (IL-5) plays a crucial role in eosinophil behavior, which impacts various airway diseases through processes like maturation, activation, and survival of these cells.
  • Anti-IL-5 therapies were developed due to the cytokine's significant role in diseases associated with eosinophils, but recent findings show that the therapeutic effects may extend beyond just eosinophil depletion.
  • Emerging evidence indicates IL-5 influences a wider spectrum of immune cells—such as mast cells and T regulatory cells—suggesting that its role in type 2 inflammation and disease pathogenesis is more complex than previously understood.
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There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR.

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Background: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple outcomes of treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with dupilumab.

Objective: Our aim was to gain a better understanding of dynamics of the response to dupilumab over 52 weeks.

Methods: We used data from the SINUS-52 (ClinicalTrials.

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The European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual forum EUFOREUM in Berlin in November 2023. The aim of EUFOREUM 2023 was to highlight pediatric action plans for prevention and optimizing care for type 2 inflammatory conditions starting in childhood, with a focus on early-stage diagnosis, ensuring neither under- nor overdiagnosis, optimal care, and suggestions for improvement of care. EUFOREA is an international not-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic respiratory diseases through the implementation of optimal patient care via educational, research, and advocacy activities.

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The concept of pre-diabetes has led to provision of measures to reduce disease progression through identification of subjects at risk of diabetes. We previously considered the idea of pre-asthma in relation to allergic asthma and considered that, in addition to the need to improve population health via multiple measures, including reduction of exposure to allergens and pollutants and avoidance of obesity, there are several possible specific means to reduce asthma development in those most at risk (pre- asthma). The most obvious is allergen immunotherapy (AIT), which when given for allergic rhinitis (AR) has reasonable evidence to support asthma prevention in children (2) but also needs further study as primary prevention.

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Background: The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR).

Objective: We aimed to study basal cell subtypes in AR and healthy controls.

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Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinus cavities that significantly affects well-being and social function, particularly in young adults and middle-aged populations. CRSwNP is a common health condition in the Western world, with an estimated prevalence of 3%. Despite worldwide evidence-based treatment guidelines such as the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) chronic rhinosinusitis (CRS) pocket guide, a significant number of patients remain undiagnosed and/or uncontrolled with repeated oral corticosteroids (OCS) treatments and/or (multiple) endoscopic sinus surgeries (ESS).

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Objectives: To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement.

Methods: We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases.

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Article Synopsis
  • Nasal hyperreactivity (NHR) is common in chronic upper airway conditions like allergic rhinitis and chronic rhinosinusitis with nasal polyps, primarily driven by type 2 inflammation.
  • In a study involving 18 healthy controls and 45 patients, cold dry air provocation tests showed that NHR significantly reduced nasal airflow in patients, correlating subjective experiences with objective measurements.
  • Findings suggest that NHR varies in severity and is influenced by factors like neurogenic inflammation and increased histamine levels, indicating a spectrum of reactivity rather than a simple presence or absence.
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Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma.

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Background: House dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population.

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Impairment of nasal breathing is a highly prevalent and bothersome symptom that affects daily functioning and/or sleep quality. Those surgeons dealing with patients seeking rhinoplasty need to carefully analyze the preoperative nasal breathing capacity and predict the positive or even negative impact of rhino(septo)plasty on nasal breathing. Given the lack of correlation between the subjective feeling of suboptimal nasal breathing and the objective measurements of nasal flow and nasal resistance, a critical and mainly clinical evaluation of all anatomical, mucosal, and sensory mechanisms involved in nasal obstruction is mandatory.

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Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP.

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