Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery.

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.

IgA-producing B cells in lung homeostasis and disease.

Immunoglobulin A (IgA) is the most abundant Ig in mucosae where it plays key roles in host defense against pathogens and in mucosal immunoregulation. Whereas intense research has established the different roles of secretory IgA in the gut, its function has been much less studied in the lung. This review will first summarize the state-of-the-art knowledge on the distribution and phenotype of IgA+ B cells in the human lung in both homeostasis and disease. Second, it will analyze the studies looking at cellular and molecular mechanisms of homing and priming of IgA+ B cells in the lung, notably following immunization. Lastly, published data on observations related to IgA and IgA+ B cells in lung and airway disease such as asthma, cystic fibrosis, idiopathic pulmonary fibrosis, or chronic rhinosinusitis, will be discussed. Collectively it provides the state-of-the-art of our current understanding of the biology of IgA-producing cells in the airways and identifies gaps that future research should address in order to improve mucosal protection against lung infections and chronic inflammatory diseases.

European Academy of Allergy and Clinical Immunology position paper on endoscopic scoring of nasal polyposis.

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, not influenced by the placebo effect. It is safer and cheaper compared with computed tomography imaging and therefore, better suited for regular assessments of the extent of the disease. Since the early 90s, a variety of endoscopic staging methods have been proposed and used in clinical research, making it hard to compare results from different studies. This paper resulted from a task force with experts in the field of CRSwNP, originated by the Ear, Nose and Throat section of the European Academy of Allergy and Clinical Immunology and aims to provide a unified endoscopic NP scoring system that can serve as a reference standard for researchers, but also as a useful tool for practitioners involved in the management of CRSwNP.

Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology.

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.

The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

Chronic upper airway inflammation is amongst the most prevalent chronic disease entities in the Western world with prevalence around 30% (rhinitis) and 11% (rhinosinusitis). Chronic rhinitis and rhinosinusitis may severely impair the quality of life, leading to a significant socio-economic burden. It becomes more and more clear that the respiratory mucosa which forms a physiological as well as chemical barrier for inhaled particles, plays a key role in maintaining homeostasis and driving disease. In a healthy state, the mucosal immune system provides protection against pathogens as well as maintains a tolerance toward non-harmful commensal microbes and benign environmental substances such as allergens. One of the most important players of the mucosal immune system is immunoglobulin (Ig) A, which is well-studied in gut research where it has emerged as a key factor in creating tolerance to potential food allergens and maintaining a healthy microbiome. Although, it is very likely that IgA plays a similar role at the level of the respiratory epithelium, very little research has been performed on the role of this protein in the airways, especially in chronic upper airway diseases. This review summarizes what is known about IgA in upper airway homeostasis, as well as in rhinitis and rhinosinusitis, including current and possible new treatments that may interfere with the IgA system. By doing so, we identify unmet needs in exploring the different roles of IgA in the upper airways required to find new biomarkers or therapeutic options for treating chronic rhinitis and rhinosinusitis.

Perceptions of adolescents and young adults with allergy and/or asthma and their parents on EAACI guideline recommendations about transitional care: A European survey.

BACKGROUND: The European Academy of Allergy and Clinical Immunology has developed a guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of adolescents and young adults (AYA) with allergy and/or asthma. The goal of this work was to ensure that the draft recommendations are also important for patients. METHODS: We surveyed patients aged 11-25 years with allergy and/or asthma and their parents across Europe between 17 February and 16 March 2020. The multilingual survey was distributed through national allergy and asthma patient organizations in Europe as well as through social media. RESULTS: A total of 1210 responses from 24 European countries were collected. There were 415 (34.3%) AYA and 795 (65.7%) parents. The majority of AYA (72.3%) and parents (81.9%) were female. Patients had a history of asthma (61.1%), allergic rhinoconjunctivitis (54.1%), food allergy (53.8%), atopic eczema (42.6%) and anaphylaxis (28.8%). All recommendations achieved the median score of either 'important' or 'very important'. The least supported recommendations were the use of joint clinics with both paediatric and adult physicians attending and the use of web-based or mobile technologies for communication with the AYA. The most supported recommendation was checking that the AYA is knowledgeable and compliant with their prescribed medication. Qualitative analysis revealed conditional approval for some recommendations. CONCLUSIONS: There was agreement from patients and parents on the importance of the draft recommendations on transitional care for AYA with allergy and/or asthma and their parents. The recommendations now need to be implemented into clinical practice across Europe.

Multidisciplinary Care for Severe or Uncontrolled Chronic Upper Airway Diseases.

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.

Tackling nasal symptoms in athletes: Moving towards personalized medicine.

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.

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. METHOD: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. RESULTS: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. CONCLUSIONS: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.

Management of patients with chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position paper.

BACKGROUND: Chronic rhinosinusitis is regarded as a chronic airway disease. According to WHO recommendations, it may be a risk factor for COVID-19 patients. In most CRSwNP cases, the inflammatory changes affecting the nasal and paranasal mucous membranes are type-2 (T2) inflammation endotypes. METHODS: The current knowledge on COVID-19 and on treatment options for CRS was analyzed by a literature search in Medline, Pubmed, international guidelines, the Cochrane Library and the Internet. RESULTS: Based on international literature, on current recommendations by WHO and other international organizations as well as on previous experience, a panel of experts from EAACI and ARIA provided recommendations for the treatment of CRS during the COVID-19 pandemic. CONCLUSION: Intranasal corticosteroids remain the standard treatment for CRS in patients with SARS-CoV-2 infection. Surgical treatments should be reduced to a minimum and surgery preserved for patients with local complications and for those with no other treatment options. Systemic corticosteroids should be avoided. Treatment with biologics can be continued with careful monitoring in noninfected patients and should be temporarily interrupted during the course of the COVID-19 infection.

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

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

Current transition management of adolescents and young adults with allergy and asthma: a European survey.

BACKGROUND: Transition from parent-delivered to self-management is a vulnerable time for adolescents and young adults (AYA) with allergy and asthma. There is currently no European guideline available for healthcare professionals (HCPs) on transition of these patients and local/national protocols are also mostly lacking. METHODS: European HCPs working with AYA with allergy and asthma were invited to complete an online survey assessing challenges of working with these patients, current transition practices and access to specific healthcare resources. RESULTS: A total of 1179 responses from 41 European countries were collected. Most HCPs (86%) reported a lack of a transition guideline and a lack of a transition process (20% paediatric HCPs, 50% of adult HCPs, 56% HCP seeing all ages). Nearly half (48%) acknowledged a lack of an established feedback system between paediatric and adult medical services. Many respondents never routinely asked about mental health issues such as self-harm or depression and are not confident in asking about self-harm (66.6%), sexuality (64%) and depression (43.6%). The majority of HCPs (76%) had not received specific training in the care of AYA although 87% agreed that transition was important for AYA with allergy and asthma. CONCLUSION: Although there was agreement that transition is important for AYA with allergy and asthma, there are crucial limitations and variations in the current provision of transition services across Europe. Standardisation of AYA management and specific training are required. This should improve management and continuity of care during adolescence and into adulthood to achieve the best healthcare outcomes.

Occupational Rhinitis.

There is convincing evidence that tight relationships between the upper and lower airways also apply to the workplace context. Most patients with occupational asthma (OA) also suffer from occupational rhinitis (OR), although OR is 2 to 3 times more common than OA. OR most often precedes the development of OA, especially when high-molecular-weight protein agents are involved, and longitudinal cohort studies have confirmed that OR is associated with an increased risk for the development of OA. The level of exposure to sensitizing agents at the workplace is the most important determinant for the development of IgE-mediated sensitization and OR. Atopy is a risk factor for the development of IgE-mediated sensitization only to high-molecular-weight agents. In workers with work-related rhinitis symptoms, documentation of IgE-mediated sensitization to a workplace agent via skin prick testing or serum specific IgE confirms a diagnosis of probable OR, whereas specific nasal provocation testing in the laboratory remains the reference method to establish a definite diagnosis of OR. Complete avoidance of exposure to the causal agent is the most effective therapeutic option for controlling work-related nasal symptoms and preventing the development of OA. If complete elimination of exposure is expected to induce meaningful adverse socioeconomic consequences, reduction of exposure can be considered as an alternative approach, but it is important to consider the individual risk factors for the development of OA to implement a more personalized management of OR.

EAACI Guidelines on the effective transition of adolescents and young adults with allergy and asthma.

Adolescent and young adult (AYA) patients need additional support, while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process, which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multidisciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include the following: (a) starting transition early (11-13 years), (b) using a structured, multidisciplinary approach, (c) ensuring AYA fully understand their condition and have resources they can access, (d) active monitoring of adherence and (e) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (a) simplifying medication regimes and using reminders; (b) focusing on areas where AYA are not confident and involving peers in training AYA patients; (c) identifying and managing psychological and socio-economic issues impacting disease control and quality of life; (d) enrolling the family in assisting AYA to undertake self-management; and (e) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.

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

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.

The effectiveness of interventions to improve self-management for adolescents and young adults with allergic conditions: A systematic review.

BACKGROUND: This systematic review aimed to review the literature on interventions for improving self-management and well-being in adolescents and young adults (11-25 years) with asthma and allergic conditions. METHODS: A systematic literature search was undertaken across eight databases. References were checked by two reviewers for inclusion. Study data were extracted, and their quality was assessed in duplicate. A narrative synthesis was undertaken. RESULTS: A total of 30 papers reporting data from 27 studies were included. Interventions types were psychological (k = 9); e-health (k = 8); educational (k = 4); peer-led (k = 5); breathing re-training (k = 1). All interventions were for asthma. Psychological interventions resulted in significant improvements in the intervention group compared with the control group for self-esteem, quality of life, self-efficacy, coping strategies, mood and asthma symptoms. E-Health interventions reported significant improvements for inhaler technique, adherence and quality of life. General educational interventions demonstrated significantly improved quality of life, management of asthma symptoms, controller medication use, increased use of a written management plan and reduction in symptoms. The peer-led interventions included the Triple A (Adolescent Asthma Action) programme and a peer-led camp based on the Power Breathing Programme. Improvements were found for self-efficacy, school absenteeism and quality of life. CONCLUSION: Although significant improvements were seen for all intervention types, many were small feasibility or pilot studies, few studies reported effect sizes and no studies for allergic conditions other than asthma met the inclusion criteria. Research using large longitudinal interventional designs across the range of allergic conditions is required to strengthen the evidence base.

Understanding the challenges faced by adolescents and young adults with allergic conditions: A systematic review.

BACKGROUND: Adolescence represents a vulnerable time for individuals with asthma and allergic conditions. They suffer an unexpected degree of morbidity. This systematic review aimed to understand the challenges faced by adolescents and young adults with these conditions. METHODS: A systematic literature search was undertaken across eight databases. References were checked by two reviewers for inclusion. Study data were extracted, and their quality was assessed in duplicate. A narrative meta-synthesis was undertaken. RESULTS: A total of 108 papers describing 106 studies were retrieved, most focused on asthma. Five themes were identified across studies: (a) Health-related quality of life-impairment was associated with poor disease control, psychosocial issues, adolescent-onset allergic disease and female sex; (b) Psychological factors-asthma and food allergy were associated with anxiety and depression, atopic dermatitis was associated with suicidal ideation, and that parental emotional support may be protective; (c) Adherence-suboptimal adherence was associated with older age, barriers to medication usage, poor symptom perception and failure to take responsibility, and positive factors were routines, simpler treatment regimes, better knowledge and perceptions about medications; (d) Self-management-facilitated by education, knowledge and a positive attitude; and (e) Supportive relationships-families could modify barriers to adherence and foster positive views about self-management, adolescents suggested that their peers should be more involved in supporting them, and adolescents also wished to have support from nonjudgemental healthcare professionals. CONCLUSIONS: We have some understanding of the challenges faced by adolescents with asthma, less so for other allergic conditions. This knowledge will be used to support guidelines for managing adolescents.

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

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.

Key role of the epithelium in chronic upper airways diseases.

The respiratory epithelium of the upper airways is a first-line defence against inhaled irritants, pathogens and allergens. It ensures a physical barrier provided by apical junctions and mucociliary clearance to avoid excessive activation of the immune system. The epithelium also forms a chemical and immunological barrier, extensively equipped to protect the airways against external aggressions before the adaptive immune system is required. Under normal circumstances, the epithelium is capable of recovering rapidly after damage. This manuscript reviews these main properties of the upper airway epithelium as well as its reported impairments in chronic inflammatory diseases. The knowledge on normal epithelial functions and their dysregulation in upper airway diseases should help to design new epithelial-targeted treatments.

Exercise and Sinonasal Disease.

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.