Pre-asthma: a useful concept? A EUFOREA paper. Part 2-late onset eosinophilic asthma.

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. In this second paper we explore the possibilities for similar actions in late onset eosinophilic asthma.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

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. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

The EUFOREA pocket guide for chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is known to affect around 5 % of the total population, with major impact on the quality of life of those severely affected (1). Despite a substantial burden on individuals, society and health economies, CRS often remains underdiagnosed, under-estimated and under-treated (2). International guidelines like the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) (3) and the International Consensus statement on Allergy and Rhinology: Rhinosinusitis 2021 (ICAR) (4) offer physicians insight into the recommended treatment options for CRS, with an overview of effective strategies and guidance of diagnosis and care throughout the disease journey of CRS.

Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1-allergic asthma.

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. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.

Delayed recovery from severe acute respiratory syndrome coronavirus-2 related anosmia predicts incomplete olfactory restoration.

OBJECTIVE: This study aimed to assess the olfactory recovery rates and patterns in a cohort of coronavirus disease 2019 positive patients, and to investigate the clinical predictors of poor long-term olfactory restoration. METHODS: An observational retrospective study was conducted on 146 patients between September 2020 and January 2021 at a tertiary referral hospital. Coronavirus disease 2019 positive patients with olfactory dysfunction were sent a modified version of the COVID-19 Anosmia Reporting Tool for Clinicians via e-mail. RESULTS: The difference in median recovery time between complete recovery and incomplete or no recovery was statistically significant. On multivariate analysis, the only significant factor associated with incomplete or no recovery was anosmia duration. CONCLUSION: After a mean time of 5.6 months from severe acute respiratory syndrome coronavirus-2 infection, persistent olfactory disorders were self-reported in 36.7 per cent of patients. Complete recovery was more likely to occur within 15 days. Given the high prevalence of coronavirus disease 2019, a large number of patients are expected to suffer from long-term olfactory morbidity.

Predisposing factors of rhinitis medicamentosa: what can influence drug discontinuation?

BACKGROUND: the primary end point of our study was to define risk factors and identify the underlying conditions that may have led to the abuse of vasoconstrictors in rhinitis medicamentosa. Moreover, we analysed factors that may influence the vasoconstrictors discontinuation. METHODOLOGY: this was a prospective case-control observational study. Cases and controls were evaluated at the baseline in order define factors that may have influenced onset of rhinitis medicamentosa. They were re-evaluated at 3 months to verify symptoms control and drug discontinuation. Finally, they underwent a phone call questionnaire after 12 months regarding drug discontinuation. A potential bias of our study is that evaluating discontinuation we included subjects treated differently according to the main diagnosis. RESULTS: patients with rhinitis medicamentosa were more frequently smokers than controls, they had higher mean HAMA scores and positive psychiatric diseases history. Additionally, we frequently detected a local inflammation at nasal cytology in patients with rhinitis medicamentosa. A significant improvement in all nasal symptoms scores was observed in cases and controls but 29.4% of cases did not discontinue the vasoconstrictors. Two major factors negatively influenced discontinuation: positive nasal cytology and pathological HAMA score. CONCLUSION: we observed that positive local inflammation, anxiety and smoking habit correlate positively with vasoconstrictors abuse. In addition, we demonstrated that anxiety and local inflammation were the most important factors impairing drug discontinuation.

Treatment-emergent central sleep apnoea after surgery for obstructive sleep apnoea.

Central sleep apnoea (CSA) is a lack of drive to breathe during sleep, which can occur in physiologic as well as in pathologic conditions. A particular type of CSA, defined treatment-emergent CSA (TECSA), may occur after the treatment of obstructive sleep apnoea syndrome (OSAS), either with CPAP or surgery. TECSA is transitory and seems to be related to the severity of OSAS. We describe a 51-year-old man affected by severe OSAS who developed severe, transient CSA immediately after upper airways surgery. We believe that CSA was triggered by the sudden variation in nocturnal arterial PCO2, which decreased from 52.3 mmHg before surgery to 42.0 mmHg after surgery. It is conceivable that, due to long-lasting severe OSAS, our patient lowered his chemosensitivity to PCO2. Consequently, the resolution of obstructive apnoeas and the restoration of normal nocturnal values of PCO2 may have reduced the nocturnal PCO2 to the point of being inadequate to stimulate ventilation.

IFN-γ and other serum cytokines in head and neck squamous cell carcinomas.

SUMMARY: Altered immune responses have been reported in head and neck cancer, and some of these responses have been associated with poor clinical outcomes. A multiple-array technology platform was used to simultaneously evaluate the levels of 25 cytokines. Pre-treatment serum levels were evaluated in 31 HNSCC patients and 6 healthy controls. The levels of 8 cytokines, specifically IL-1ra, IL-2, IL-5, IL-6, IL-8, IL-17, IFN-γ and IP-10, were significantly higher in patients than in controls. Among cancer patients we observed lower levels of IFN-γ and IL-7 in cases with nodal metastases compared to those with cN0 disease. We observed increases in the levels of some serum cytokines in HNSCC patients, as well as reductions in selected cytokines associated with regional progression. These findings provide an intriguing perspective on the development and validation of novel markers for follow-up evaluations and predictions of regional spreading in HNSCC patients.

Retrospective epidemiological study of mandibular rotational types in patients with orthodontical malocclusion.

SUMMARY: The primary aim of this study was to illustrate the prevalence of facial skeletal discrepancy in an Italian sample. Another aim was to evaluate the effectiveness of the sagittal skeletal discrepancy classification in order to establish a morphologic pattern of growth useful for diagnosis and prediction of therapeutic results. The authors considered a sample of 732 patients (426 females and 306 males) aged between 6 and 17 years old. Cephalometric parameters were evaluated in order to establish a relationship between sagittal skeletal discrepancy and the classification of facial rotations (Lavergne and Petrovic). Facial types with neutral mandibular growth direction were the most prevalent, and were most observed in classes I and II; the latter was more represented than others in our sample. Facial types with posterior mandibular growth direction were the most prevalent in class III. Sagittal skeletal discrepancy classification is not able to establish a specific facial type or predict an individual responsiveness to treatment.

Eagle's Syndrome, from clinical presentation to diagnosis and surgical treatment: a case report.

SUMMARY: Eagle's syndrome is a condition associated with the elongation of the styloid process or calcification of the stylohyoid ligament, clinically characterised by throat and neck pain, radiating into the ear. In this report, we describe the case of a 60-year-old woman who presented with a severe unilateral trigeminal and glossopharyngeal neuralgia. The patient was subjected to conservative therapy for four months and did not report improvement of the symptoms. After several consultations with different physicians, a diagnosis was accomplished by radiological investigation (multidetector computer tomography with multi-planar reconstructions and 3D volumetric reconstructions). Surgical styloidectomy was performed, with subsequent sudden remission of symptoms. Eagle's syndrome represents a commonly unrecognised nosological entity, clinically characterised by non-specific cranio-facial pain. Differential diagnosis includes glossopharyngeal and trigeminal neuralgia, temporal arteritis, migraine, myofascial pain dysfunction and cervical arthritis. Eagle's syndrome should always be suspected, mostly in adult women when the pain is unilateral and not responsive to painkillers.

Facial pain: sinus or not?

Facial pain remains a diagnostic and therapeutic challenge for both clinicians and patients. In clinical practice, patients suffering from facial pain generally undergo multiple repeated consultations with different specialists and receive various treatments, including surgery. Many patients, as well as their primary care physicians, mistakenly attribute their pain as being due to rhinosinusitis when this is not the case. It is important to exclude non-sinus-related causes of facial pain before considering sinus surgery to avoid inappropriate treatment. Unfortunately, a significant proportion of patients have persistent facial pain after endoscopic sinus surgery (ESS) due to erroneous considerations on aetiology of facial pain by physicians. It should be taken into account that neurological and sinus diseases may share overlapping symptoms, but they frequently co-exist as comorbidities. The aim of this review was to clarify the diagnostic criteria of facial pain in order to improve discrimination between sinogenic and non-sinogenic facial pain and provide some clinical and diagnostic criteria that may help clinicians in addressing differential diagnosis.

Septoplasty: is it possible to identify potential "predictors" of surgical success?

Septoplasty is one of the most frequent surgical procedures performed by otolaryngologists. Despite successful surgical correction, many patients are not satisfied with their outcomes. So far, in clinical practice there is no consensus of opinion about the reliability of objective measurements of nasal patency and the correlation between objective measurements and subjective nasal patency symptoms. This study aims to assess the reasons for patient dissatisfaction after septoplasty and optimise pre-operative diagnostic management to predict surgical outcomes. We analysed 494 patients undergoing septoplasties with turbinoplasty by subjective Nasal Obstruction Symptom Evaluation questionnaire (NOSE) and objective active anterior rhinomanometric measurements before surgery and after 6 months. In our series, 17% had postoperative septal re-displacement; all patients had an anterior deviations at baseline. We found that the type of septal deviation, anterior vs posterior, was a significant predictor of postoperative functional improvement, whereas demographic characteristics as age, gender and smoke habit were not. Our data suggest that the anterior segment of the nasal septum was the most critical area for nasal airway resistance and more difficult to manage because it is likely to re-displace vs the posterior one and for this reason it represents a negative predictor of postoperative satisfaction.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Salivary biomarkers and proteomics: future diagnostic and clinical utilities.

Saliva testing is a non-invasive and inexpensive test that can serve as a source of information useful for diagnosis of disease. As we enter the era of genomic technologies and -omic research, collection of saliva has increased. Recent proteomic platforms have analysed the human salivary proteome and characterised about 3000 differentially expressed proteins and peptides: in saliva, more than 90% of proteins in weight are derived from the secretion of three couples of "major" glands; all the other components are derived from minor glands, gingival crevicular fluid, mucosal exudates and oral microflora. The most common aim of proteomic analysis is to discriminate between physiological and pathological conditions. A proteomic protocol to analyze the whole saliva proteome is not currently available. It is possible distinguish two type of proteomic platforms: top-down proteomics investigates intact naturally-occurring structure of a protein under examination; bottom-up proteomics analyses peptide fragments after pre-digestion (typically with trypsin). Because of this heterogeneity, many different biomarkers may be proposed for the same pathology. The salivary proteome has been characterised in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease Sjögren's syndrome and other autoimmune disorders such as SAPHO, schizophrenia and bipolar disorder, and genetic diseases like Down's Syndrome and Wilson disease. The results of research reported herein suggest that in the near future human saliva will be a relevant diagnostic fluid for clinical diagnosis and prognosis.

Mathematical model for preoperative identification of obstructed nasal subsites.

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.

Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical-cytological grading: a precision medicine-based approach.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder that strongly impacts patients' quality of life. CRSwNP is still a challenge for ENT specialists due to its unknown pathogenesis, difficult control and frequent relapse. We tested the hypothesis that a new standardised therapeutic approach based on individual clinical-cytological grading (CCG), may improve control of the disease and prevent the needing for surgery. We analysed 204 patients suffering from bilateral CRSwNP, 145 patients of whom regularly assumed therapy, respecting the planned check-up, and were considered cases; 59 patients were not assuming therapy as indicated and were considered as controls. After five years of standardised treatment, 15 of 145 (10.5%) improved endoscopic staging, 61 of 145 (42%) did not change their endoscopic staging, and 69 of 145 (47.5%) were worse. In the control group, 49 of 59 (83%) were worse by at least two stages (p < 0.05). Patients and controls were stratified basing on clinical and cytological grading as mild, moderate and severe. After patient stratification, in the mild group (n = 27) 92% patients had a constant trend, with no worsening and no need for surgery over a 5-year period, whereas in the mild CCG control group 1 of 59 (1.6%) required surgery (p < 0.05). In moderate GCC (n = 83), 44% of patients did not modify or improve endoscopic staging and 3.6% needed surgery, compared to 13.6% of controls with moderate GCC (p < 0.05). In severe CCG (n = 35), even though no patients achieved significant amelioration of endoscopic grading, 40% of patients were considered as "clinically controlled" and 5.7% of patients underwent surgery, but the percentage was significantly higher (49%) in the control group significant (p = 0.0000). Finally, statistical analyses revealed a clear trend that polyp size increased at a faster rate in the control group than in the treatment group and for each subgroup (low, moderate and severe). The present study suggests a new approach in the management of CRS according to clinical cytological grading that allows defining the grade of CRSwNP severity and to adapt the intensity of treatment. This approach limited the use of systemic corticosteroids to only moderate-severe CRSwNP with a low corticosteroid dosage in comparison with those previously suggested. Our protocol seems to improve the adherence by patients, control of disease and the need for surgery in the long-term.

New olfactometric findings in Parkinson's disease.

OBJECTIVES: To investigate in Parkinson's disease-affected patients a correlation between hyposmia and gastrointestinal dysfunction and their possible identical etiopathogenesis. DESIGN: Retrospective cohort study. SETTING: ENT and neurology departments (Gemelli Hospital, Rome, Italy). PARTICIPANTS: A total of 78 patients with diagnosis of PD according to the UK Brain Bank criteria. INCLUSION CRITERIA: informed consent and olfactory testing executed; exclusion criteria: signs of dementia according to the DSM-IV criteria; Mini Mental State Examination score ≤26; head trauma; central neurological disorders, nasal or systemic diseases potentially affecting olfactory function. Motor condition was assessed by means of Hoehn and Yahr staging and by section III of the Unified PD Rating Scale, performed off and on medications. MAIN OUTCOME MEASURES: The patients underwent olfactory evaluation (TDI score), after rhinomanometry with nasal decongestion. A total of 25 non-motor symptoms were evaluated through an interview. RESULTS: Olfactory dysfunction was objectively found in 91.0% of patients, a percentage higher than the subjective hyposmia reported (55.1%) P = 0.0001. Seven patients (9.0%) were normosmic, 49 (62.8%) hyposmic and 22 (28.2%) anosmic. Subjective hyposmia, constipation, bloating and dyspepsia differed across groups, being higher in anosmic and hyposmic ones than in the normosmic group. P value was ≤0.05 for each symptom. Despite the original results, this study has the limitation of being based on subjective ratings by a relatively limited group of patients. CONCLUSIONS: Hyposmia and gastrointestinal symptoms are correlated, and this would support a possible common origin; the CNS could be reached through two different pathways, both starting in the peripheral nervous system.