Multimorbidities in Allergic Rhinitis-Current Evidence from Epidemiological Studies, Treatment Trials, and Molecular Data.

PURPOSE OF REVIEW: Given that allergic rhinitis (AR) commonly coexists with other diseases, the present narrative review attempts a brief presentation of current theories on multimorbidities in relation to phenotypes, genotypes, age, and treatment responses with the term "multimorbidities" indicating the uncertainty regarding the primary defect, organ, or pathophysiologic mechanism involved. RECENT FINDINGS: Though age-related manifestations allow for the generation of several hypotheses on AR's specific mechanisms, the various theories regarding the initiation or the aggravation of atopic disorders have yet to be proved. Multimorbid AR seems to have a different genetic basis from "stand-alone" AR as well a more severe phenotype. Most studies on the treatment of AR and its multimorbidities focus on allergen immunotherapy, which improves the atopic symptoms and may play a preventive role in the onset of new allergen sensitizations. The use of biological factors may also have a beneficial effect, even though it has currently been approved only for some comorbidities of AR, such as asthma. Employing the use of phenotypes and genotypes concerning multimorbidity broadens current knowledge, but further research is needed to develop diagnostic, stratificational, and predictive algorithms for single and multimorbid allergic diseases (Fig. 1). The real-time data obtained by mobile apps and the new insights on the pathophysiology of AR and its comorbidities will permit both timed preventive measures and better individualized and effective antiallergic treatment. Fig. 1 Current concepts and future trends in diagnosis and management of multimorbid allergic rhinitis.

Atopic children are more susceptible to viral respiratory infection at the age of 2-5 years old.

Background: The susceptibility of the atopic population to respiratory infections (RI) has not been fully elucidated. This susceptibility is attributed to the immune dysregulation that characterizes atopic diseases. Although, the exact mechanisms involved are not fully understood, there is evidence that shows that the maturation of innate immunity progresses differently in patients with atopy. Objective: The aim of the study was to evaluate the susceptibility to viral RIs (VRI) based on the number and duration of them in different age groups in subjects with atopy and subjects without atopy. Methods: Seventy-eight subjects (39 healthy and 39 with atopy) were included in the study. All the subjects were evaluated by a specialist and defined as being atopic if they had a clinical history and/or symptoms compatible with any allergic diseases and relevant sensitizations. Epidemiologic data were recorded based on a standardized questionnaire, which included recording habits, conditions, and living environment as well as the history of viral infections during the last year. Results: In our population, children with atopy were found to be more susceptible to viral RIs than children without atopy (p = 0.02), whereas there was no difference in susceptibility between healthy adults and adults with atopy (18-45 years old). More specifically, the atopic age group 2-5 years old showed the higher susceptibility to VRIs. Conclusion: This study provided evidence that children with atopy, especially at ages 2-5 years old, had more numerically and prolonged RIs than did the subjects without atopy. These clinical findings support the hypothesis of distracted maturation of innate immunity in subjects with atopy.

New concepts in pediatric rhinitis.

Rhinitis-and especially allergic rhinitis (AR)-remains the most frequent hypersensitivity condition, affecting up to a quarter of the population and impacting the quality of life of individual patients and the health economy. Data, especially with respect to underlying pathophysiologic mechanisms, mainly derive from studies on adults and are subsequently extrapolated to the pediatric population. Therapeutic algorithms for children with rhinitis are long based on the same principles as in adults. We explore and describe novel aspects of rhinitis, ranging from mechanisms to disease classification, phenotypes, diagnostic and monitoring tools, and the use of treatments, with a focus on the traits of pediatric age groups.

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.

Imaging in chronic rhinosinusitis: A systematic review of MRI and CT diagnostic accuracy and reliability in severity staging.

BACKGROUND: Computerized tomography (CT) severity scores are frequently used as an objective staging tool in chronic rhinosinusitis (CRS). Magnetic resonance imaging (MRI) has also been proposed as a valid option in CRS imaging. PURPOSE: The aim of this systematic review was to briefly present the recent developments on sinus imaging utilized in clinical practice with regard to diagnostic accuracy of imaging and severity staging in CRS according to evidence-based medicine (EBM) principles. MATERIAL AND METHODS: This review paper has been assembled following PRISMA guidelines. A PubMed and Scopus (EMBASE) search using CRS, "severity staging", "diagnostic accuracy "and "imaging "resulted with 80 results. Of these, only 12 (59%) contained original data, constituting the synthesis of best-quality available evidence. RESULTS: CT is the most commonly used imaging technique for the severity staging of CRS, but a question of higher cumulative radiation dose should be taken into consideration when repeating CT examinations in evaluating treatment efficacy. MRI may be a complementary diagnostic and staging tool, especially when repeated examinations are required, or when paediatric CRS patients are evaluated. The severity staging system may be improved to better correlate with subjective scores. CONCLUSIONS: MRI may be utilized as a staging tool with comparable diagnostic accuracy, using the same staging systems as with CT examinations.

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.

Local Allergic Rhinitis Revisited.

PURPOSE OF REVIEW: Local allergic rhinitis (LAR) represents a diagnostic and therapeutic challenge for clinicians. Even though it affects a considerable number of chronic rhinitis patients and a significant number of articles regarding prevalence, evolution, diagnosis, and treatment have been published, the condition remains still largely unrecognized and therefore misdiagnosed and mistreated. RECENT FINDINGS: LAR is a unique form of chronic rhinitis; it is neither classical allergic rhinitis (AR) nor non-allergic rhinitis (NAR). The symptoms, duration, severity, and complications of LAR are similar to those of AR and can affect adults and children. Thus, a portion of patients diagnosed with NAR or chronic rhinitis of unknown etiology may have LAR. The relationship between LAR inflammation and systemic allergic inflammation is unclear. Patients are frequently misdiagnosed with idiopathic NAR, and distinguishing between both entities is difficult without specific diagnostic tests. Underdiagnosis of LAR has implications on the management of these patients, as they are deprived of allergen immunotherapy (AIT) that has been demonstrated to modulate the immune mechanisms underlying allergic diseases. This review aims to comprehensively summarize the current knowledge on LAR and address unmet needs in the areas of disease diagnosis and treatment.

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study.

BACKGROUND: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: A total of 12 143 users were registered. A total of 6 949 users reported at least one VAS data recording. Among them, 1 887 users reported ≥7 VAS data. About 1 195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR ≥70% and PDC ≤1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.

Precision Medicine in Rhinosinusitis.

PURPOSE OF REVIEW: Our scope is the presentation of research and clinical progresses in relation to precision medicine that are expected to alter our clinical practice in relation to chronic rhinosinusitis (CRS). Current knowledge on phenotypes and endotypes, biomarkers, and clinical markers for diagnosis, medical and surgical therapy, and prognosis is presented as well as the role of precision medicine in United Airway Disease and SCUAD (severe-uncontrolled chronic upper airway inflammation). RECENT FINDINGS: Current technological progresses, mostly in relation to molecular biology and information technology, have permitted more detailed pathophysiological assessments and multidimensional approaches in airways diseases. Based on the concept of united airways diseases, new classification schemes, called endotypes, have been proposed for CRS. In addition, novel biological treatments that have been introduced for the treatment of asthma show great promise as well for severe uncontrolled cases of CRS with nasal polyps. Central to this approach are new biomarkers that are being examined in relation to complex bio-clinical traits of CRS. As this narrative review of the aforementioned precision medicine initiatives in relation to CRS advances, a modification of current practice is expected not only for severe chronic upper airways diseases in tertiary centers but also for milder and more common cases that are being encountered in the community.

Contemporary Use of Corticosteroids in Rhinology.

PURPOSE OF REVIEW: Exogenously administered corticosteroids are widely used today in the field of rhinology. Allergic rhinitis (AR), non-allergic rhinitis (NAR), acute rhinosinusitis (ARS), chronic rhinosinusitis with (CRSwNP) and without (CRSsNP) nasal polyps, and autoimmune disorders with nasal manifestations are common diseases treated effectively with intranasal and oral glucocorticoids. We focus on physiological pathways, therapeutic benefits, indications, contra-indications, and side effects of glucocorticoid utilization in the treatment of rhinologic disorders such as AR, NAR, ARS, CRSsNP, and CRSwNP. RECENT FINDINGS: Second-generation intranasal steroid (INS) agents have pharmacokinetic characteristics that minimize their systemic bioavailability, resulting in minimum risk for systemic adverse events. Several studies have demonstrated the symptomatic efficacy of both intranasal and oral corticosteroids in ARS. Moreover, intranasal and systemic steroid administration has been repeatedly proven beneficial in the conservative and perioperative management of CRSwNP. For patients with AR, there is no need for oral steroids, with the exception of severe cases, as there is lack of superiority to INS. SCUAD patients challenge currently available treatment schemes, underlining the importance of research in the field. Corticosteroids' effectiveness in the treatment of various rhinologic disorders is indisputable. However, their characteristics, and potential side effects, make a clear consensus for utilization difficult.

Pediatric Severe Chronic Upper Airway Disease (P-SCUAD).

The term SCUAD (severe chronic upper airway disease) has been previously introduced to describe cases with upper airway disorders and symptoms not adequately controlled despite correct diagnosis and management. It has been so far applied mainly in adults and no specific focus has been given on the pediatric population. When the term SCUAD is considered for children specifically, a series of issues may arise. These issues involve accurate definition, epidemiology, clinical characteristics, pathophysiology, and socioeconomic implications. These issues seem to clearly differentiate adult from pediatric SCUAD. We attempt to shed light on these issues in an effort to provide directions for future guideline development and research. In this context, P-SCUAD (pediatric severe chronic upper airway disease) is hereby introduced.

Evidence-based surgery for chronic rhinosinusitis with and without nasal polyps.

Meta-analysis of both large outcome studies as well as cohort studies support the safety and efficacy of Endoscopic Sinus Surgery for Chronic Rhinosinusitis. The efficacy of endoscopic sinus surgery is demonstrated in the improvement of both disease-specific and generic QOL as well as objective measures. However, this must be interpreted together with a well-recognized long-term 15-20 % revision rate, seen more often in patients with ASA trias and cystic fibrosis as well as osteitis and previous surgery. The effect of surgery is higher in managing nasal obstruction (effect size 1.7) and less so hyposmia (effect size 0.8). Allergy has an additive role on the symptomatology of CRS; however, its role if any on the outcome of ESS for CRS is unclear. The concurrent presence of aspiring sensitivity and asthma is associated with increased disease burden and more revision surgeries. Improved phenotyping of CRS may lead in the future to better tailoring of surgical treatments.

Intraoperative recurrent laryngeal nerve monitoring in revision thyroidectomy.

Recurrent laryngeal nerve (RLN) palsy is one of the most important complications after thyroid and parathyroid surgery. There is controversy in the literature regarding whether or not intraoperative nerve monitoring decreases the risk of injury. We report our experience using Nerve Integrity Monitoring (NIM) system in cases of revision thyroidectomy, providing clear indications for its use. A series of 97 patients who underwent revision thyroidectomy with and without intraoperative NIM alternately was evaluated. There were 121 RLN patients at risk. Use of NIM during revision thyroidectomy was not statistically significant compared to revision operation without monitoring (p value = 0.059). Furthermore, comparison of operative times either with or without NIM showed that use of NIM led to statistically significant prolonged operation time (p value <0.001). There is no strict indication to use RLN monitoring during thyroid surgery, especially as there is no statistical evidence that the use of this technique decreases the incidence of RLN palsy, although there is a trend especially in difficult revision cases.

Features of ENT Cases in the Emergency Department of a Tertiary Hospital in Greece: A Prospectively Driven Data Collection Study.

Primary healthcare is the pillar of a well-functioning healthcare system. General practitioners (GPs) should have a broad skillset to cope with the various conditions they encounter in everyday practice. Ear, nose, and throat (ENT) cases are some of the most common reasons for seeking care. The study aimed to define the frequency and type of ENT disorders seen in the emergency department of a tertiary hospital in Greece. All patients examined by an ENT specialist in the emergency department setting, within a year, were recorded, as well as all referrals from private practice or primary care facilities. From September to December 2021, data were collected from patients who agreed to complete a two-minute survey, namely, the Generalized Anxiety Disorder Scale (GAD-2) questionnaire. During the study year, 4542 cases were documented, from which the most common conditions listed were external otitis (6.9%/314), epistaxis (6.7%/305), and impacted earwax (5.7%/261). The diagnoses that led to hospitalization were 336 and the most common were peritonsillar abscess (16.4%/55), epistaxis (8.0%/27), and facial nerve paralysis (7.4%/25). Referrals from GPs working in the public sector represented more than the half of the total. There was a significant correlation between an increased number of hospital visits and an increased GAD-2 score, in the semester before the current visit (p < 0.001). Referrals to ENT specialists represent around 5% of all cases examined, and about 8% of all visits required hospitalization. Interdisciplinary clinical and research investment into GP training is compulsory to regulate ENT referrals by GPs.

Clinical Controversy Surrounding the Differential Diagnosis of Branchiogenic Carcinoma.

Clinical evaluation, differential diagnosis, and management of a neck mass constitute commonly encountered problems for the head and neck surgeon. An asymptomatic neck mass in adults may be the only clinical sign of head and neck cancer. A 50-year-old female patient presented with a painless, slowly enlarging, left lateral neck lump. Ultrasonography described a possible lymph node with cystic degeneration, and fine needle aspiration biopsy only detected atypical cells of squamous epithelium. An open biopsy under general anesthesia was performed. Histopathological findings suggested the diagnosis of lymph node infiltration by squamous cell carcinoma of an unknown primary site, but differential diagnosis also included branchiogenic carcinoma arising in a branchial cleft cyst. A diagnostic algorithm for metastatic squamous cell carcinoma of an unknown primary site was followed, including positron emission tomography with computed tomography. The patient underwent panendoscopy and bilateral tonsillectomy, and an ipsilateral p16 positive tonsillar squamous cell carcinoma was detected. Further appropriate management followed. The existence of true branchiogenic carcinoma is controversial. When such a diagnosis is contemplated, every effort should be made to detect a possible primary site. Branchiogenic carcinoma, if exists at all, remains a diagnosis of exclusion.

White Paper on European Patient Needs and Suggestions on Chronic Type 2 Inflammation of Airways and Skin by EUFOREA.

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 differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases. Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future. Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach. Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients. Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care.

Corrigendum on: White paper on European patient needs and suggestions on chronic type 2 inflammation of airways and skin by EUFOREA.

[This corrects the article DOI: 10.3389/falgy.2022.889221.].

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation.

BACKGROUND: Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation. METHODS: Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits. RESULTS: Sputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation. CONCLUSIONS: Only nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.