Circulating calprotectin as a potential biomarker of persistent olfactory dysfunctions in Post-COVID-19 patients.

BACKGROUND: This longitudinal prospective study aims to investigate the potential of circulating calprotectin (cCLP) as a biomarker in persistent olfactory dysfunctions following COVID-19 infection. METHODS: Thirty-six patients with persistent hyposmia or anosmia post COVID-19 were enrolled (HT0) and re-evaluated after three months of olfactory training (HT1). Two control groups included 18 subjects without olfactory defects post COVID-19 (CG1) and 18 healthy individuals (CG2). Nasal brushing of the olfactory cleft and blood collection were performed to assess circulating calprotectin levels. RESULTS: Higher calprotectin levels were observed in serum and nasal supernatant of hyposmic patients (HT0) compared to control groups (CG1 and CG2). Post-olfactory training (HT1), olfactory function improved significantly, paralleled by decreased calprotectin levels in serum and nasal samples. Circulating calprotectin holds potential as a biomarker in persistent olfactory dysfunctions after COVID-19. The decrease in calprotectin levels post-olfactory training implies a role in monitoring and evaluating treatment responses. DISCUSSION AND CONCLUSIONS: These findings contribute to the growing literature on potential biomarkers in post-COVID-19 olfactory dysfunctions and underscore the importance of investigating novel biomarkers for personalized patient management. Nevertheless, further studies are needed to validate the application of calprotectin assay in nasal diseases and its correlation with nasal cytology.

Post-COVID-19 Hyposmia Does Not Exhibit Main Neurodegeneration Markers in the Olfactory Pathway.

The biological substrate of persistent post-COVID-19 hyposmia is still unclear. However, as many neurodegenerative diseases present with smell impairment at onset, it may theoretically reflect degeneration within the central olfactory circuits. However, no data still exist regarding the post-COVID-19 patients. As the olfactory neurons (ONs) mirror pathological changes in the brain, allowing for tracking the underlying molecular events, here, we performed a broad analysis of ONs from patients with persistent post-COVID-19 OD to identify traces of potential neurodegeneration. ONs were collected through the non-invasive brushing of the olfactory mucosa from ten patients with persistent post-COVID-19 hyposmia (lasting > 6 months after infection) and ten age/sex-matched controls. Immunofluorescence staining for protein quantification and RT-PCR for gene expression levels were combined to measure ONs markers of α-synuclein, amyloid-ß, and tau pathology, axonal injury, and mitochondrial network. Patients and controls had similar ONs levels of oligomeric α-synuclein, amyloid-ß peptide, tau protein, neurofilament light chain (NfL), cytochrome C oxidase subunit 3 (COX3), and the heat shock protein 60 (HSP60). Our findings thus did not provide evidence for synucleinopathy and amyloid-ß mismetabolism or gross traces of neuronal injury and mitochondrial dysfunction within the olfactory system in the early phase of persistent post-COVID-19 hyposmia.

Autoantibody profiles assessment in individuals with persistent olfactory impairment following SARS-CoV-2 infection.

BACKGROUND: Olfactory impairment, particularly hyposmia and anosmia, has emerged as a distinctive early symptom of SARS-CoV-2. Drawing on the historical association of autoimmune diseases with olfactory function, this study delves into the connections between COVID-19, autoimmunity, and persistent olfactory dysfunctions, focusing on individuals experiencing long-lasting smell disorders (3-18 months post-SARS-CoV-2 infection). METHODS: The study comprised 36 Long Covid patients with persistent olfactory dysfunctions, alongside two control groups. Olfactory functionality was assessed using the Sniffin' Sticks extended test. Non-invasive olfactory mucosa brushing and nasal secretions were processed for nasal samples, while serum samples were obtained through peripheral venous sampling. A panel of autoantibodies, including Immunocirculating Complexes, ANA, ENA, and AECA, was investigated in serum and brush supernatant samples. RESULTS: Contrary to expectations, the absence of traditional autoantibodies challenges the proposed autoimmune etiology of Long Covid-associated olfactory dysfunction. However, the presence and potential pathogenic role of AECA suggest viral cytopathic and inflammatory involvement in specific anatomical districts. One hypothesis explores the impact of inflammation and cytokine release induced by the viral infection, altering neuronal signaling and contributing to persistent hyposmia. CONCLUSION: This research contributes to our understanding of the complex relationships between autoimmunity, olfactory impairment, and COVID-19. The absence of classical autoantibodies challenges prevailing theories, while the prominence of AECA hints at unique viral-induced pathogenic mechanisms. By unraveling these complexities, this study enhances our comprehension of post-acute sequelae, offering valuable perspectives on immune-mediated responses in the aftermath of the pandemic.

Biologics in severe uncontrolled chronic rhinosinusitis with nasal polyps: A bicentric experience.

BACKGROUND AND AIM: The introduction of biologics in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP) has allowed new therapeutic options and Dupilumab represents the first approved biological agent. Aim of this paper is to provide a multicentric study in a real-life setting of treatment with Dupilumab for severe uncontrolled CRSwNP in Italy. METHODS: A retrospective data collection was performed from the departments of Otolaryngology of two major health institutions in Rome: San Camillo Forlanini Hospital and Tor Vergata University. Both centres contributed to the study providing information about patients affected by severe uncontrolled CRSwNP and treated with Dupilumab. RESULTS: A total of 83 patients were included in the study (43 males; 40 females; mean age: 55.8 years). Monitoring our patients, we observed improvement in reduction of nasal polyposis and nasal obstruction, respectively measured through NPS and PNIF. Concerning the CRSwNP symptoms and their impact on quality of life, we found an improvement in the olfaction, as measured respectively by SSIT-16 and SNOT-22. CONCLUSIONS: Dupilumab has demonstrated broad efficacy in CRSwNP management. Further studies are needed to confirm our results and to establish biomarkers to identify endotypes and predict response to biologics treatment in CRSwNP.

Correction: Guerrieri et al. Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection. Vaccines 2021, 9, 1499.

The authors wish to make the following corrections to this paper [...].

Local allergic rhinitis: considerations.

The term "local allergic rhinitis" has gained popularity as a clinical entity in recent years. Despite the apparent contradiction in the definitions of "nasal" and "local," we offer insights based on our extensive experience in the field. Local allergic rhinitis has been recognized and treated for many years, so it is not a new discovery. The nasal provocation test, which was introduced in the 1980s, was critical in identifying allergic rhinitis cases with suggestive symptoms but negative allergy tests. Our reflections aim to contribute to a precise terminological decision that is consistent with various points of view.

Rhinosinusitis: clinical-based phenotyping.

Rhinosinusitis (RS) is a common disease and is currently classified into two main types: acute RS (ARS) and chronic RS (CRS), which in turn includes CRS with or without nasal polyps. Different guidelines consider this classification. However, in clinical practice, other phenotypes exist. The current article would propose new clinical-based phenotyping of RS, including the following clinical phenotypes: simple catarrhal RS, Acute RS, acute bacterial RS, severe (complicated) acute RS, chronic RS, and recurrent chronic RS. Treatment strategy should be tailored considering the clinical phenotype and could include phytomedicines, intranasal non-pharmacological remedies, and local bacteriotherapy. In conclusion, RS requires thorough diagnostic work-up, and the therapeutic approach should be mainly based on appropriate management.

The impact of infections in the otolaryngologist's practice.

N/A.

Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection.

SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic. Approved mRNA COVID-19 vaccines are well known to induce a serum antibody responses against the spike protein and its RBD. Mucosal immunity plays a major role in the fight against COVID-19 directly at the site of virus entry; however, vaccine abilities to elicit mucosal immune responses have not been reported. We detected anti-SARS-CoV-2 IgA-S1 and IgG-RBD in three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection) on serum, saliva, and nasal secretions using two commercial immunoassays (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD). Our results show that the mRNA BNT162b2 vaccine Comirnaty (Pfizer/BioNTech, New York, NY, USA) determines the production of nasal and salivary IgA-S1 and IgG-RBD against SARS-CoV-2. This mucosal humoral immune response is stronger after the injection of the second vaccine dose compared to subjects recovered from COVID-19. Since there is a lack of validated assays on saliva and nasal secretions, this study shows that our pre-analytical and analytical procedures are consistent with the data. Our findings indicate that the mRNA COVID-19 vaccine elicits antigen-specific nasal and salivary immune responses, and that mucosal antibody assays could be used as candidates for non-invasive monitoring of vaccine-induced protection against viral infection.

Distortion Product Otoacoustic Emissions and Their Suppression as Predictors of Peripheral Auditory Damage in Migraine: A Case-Control Study.

Although several cochleo-vestibular symptoms are commonly associated with migraine, only a limited number of studies have been done in this regard. Some reported abnormalities in audiometry, auditory brainstem response and vestibular tests, considering these manifestations mainly related to central etiology. However, increasing evidence also suggests a peripheral involvement of the inner ear in migraine. The aim of this study was to investigate the peripheral auditory pathway in migraineurs using otoacoustic emissions (OAEs), to detect alteration of cochlear functioning and possible relationship with disease severity. Sixty-two migraineurs and sixty matched controls were enrolled in the study and underwent a routine neuro-otolaryngology examination; self-administered questionnaires were used to evaluate subjective perception of hearing disability. DPOAE and their suppression were lower in migraineurs compared to controls and significantly related to the disease duration. Altered DPOAE exposed migraineurs to the risk of affecting by migraine without aura, of presenting with ocular and/or auditory symptoms during attack and of using more painkillers. Concomitant dopaminergic symptoms and/or allodynia such as the acute non-consumption of triptans were significant determinants of decreased contralateral suppression of DPOAE among migraineurs. This potential subclinical cochlear impairment in migraine detected by OAEs may represent the earliest sign of sensorineural damage in these patients, providing a promising tool for the initial diagnosis and an opportunity to monitor disease course and treatment response over time.

An International Survey on the pragmatic management of epistaxis.

Epistaxis is one of the most common ear, nose and throat emergencies. The management of epistaxis has evolved significantly in recent years, including the use of nasal cautery and packs. However, a correct treatment requires the knowledge of nasal anatomy, potential risks, and complications of treatment. Epistaxis is often a simple and readily treatable condition, even though a significant bleed may have potentially severe consequences. At present, there are very few guidelines concerning this topic. The current Survey explored the pragmatic approach in managing epistaxis. A questionnaire, including 7 practical questions has been used. The current International Survey on epistaxis management reported a relevant prevalence (21.7%), mainly during childhood and senescence, an important hospitalization rate (11.8%), the common use of anterior packing and electrocoagulation, and the popular prescription of a vitamin supplement and intranasal creams.

The impact of allergic rhinitis in clinical practice: an Italian Survey.

Allergic rhinitis (AR) is a very common disorder. The current Survey was conducted on a sample of about 5,000 adult subjects in 5 Italian cities. A questionnaire, containing 15 questions, was administered on the road. AR affects about 20% of the general population. The most common diagnostic test was the skin prick test, but only 12% of patients performed an allergy test to confirm the diagnosis. About 50% of patients did not take any medicine. Even about 40% of treatments were suggested by friends or pharmacists. In conclusion, the current Survey demonstrated that AR is a common disorder in Italy, the diagnostic work-up is still incorrect, and the therapeutic approach does not adhere to the guidelines. Therefore, there is a need to implement adequate information on this topic in Italy.

Complications of adenotonsillectomy in pediatric age.

Although in recent years adenotonsillectomy procedures have shown an overall reduction in number, this surgery continues to be the most frequently performed in our speciality, especially in pediatric age. The progressive improvement in both surgical techniques and devices and anaesthesia has made adenotonsillectomy a less risky manoeuvre, but this does not mean that it is free from potential adverse events or even an easy, routine and risk-free procedure, as presented by some para scientific literature and mass media. Here we address issues related to the complications that can arise when performing this surgical procedure, which can be very serious.

HPV infection and clinical profiles in laryngeal diseases. A preliminary study.

PURPOSE: The study analysed the presence of HPV in samples tissue from laryngeal chronic hyperplastic inflammation, with and without pre-neoplastic potential, and from squamous cell carcinoma of the larynx. The aim of this analysis was to evaluate the presence/absence of different types of HPV and their relationship to the clinical profile of the patients studied (habit of smoking and drinking). METHODS: Sixty cases were randomly selected from patients undergoing surgical treatment of the larynx for inflammatory/ neoplastic lesions and of neck nodes. Patients underwent standard clinical workup, comprising medical history and physical examination, panendoscopy, whole-body CT scan (in cancer patients), diagnostic or therapeutic microlaryngoscopy with laryngeal biopsy, and HPV evaluation. RESULTS: The HPV analysis showed an increased risk for heavy smokers of HPV positivity, as well as precancer lesions and cancer. Type 6 and 16 seem to be prevalent in all types of laryngeal mucosa disease, but pre-neoplastic conditions versus cancer seem to show a wider variety of HPV infections while cancer patients are invariably affected by types 6 and 66. Heavy smoking is related to HPV infection likewise alcohol in association with smoking. Advanced T is more associated with HPV positivity. CONCLUSIONS: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours. KEY WORDS: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma.

Preventive nasal bacteriotherapy for the treatment of upper respiratory tract infections and sleep disordered breathing in children.

OBJECTIVES: The purpose of this prospective study was to assess the effectiveness and safety of Streptococcus salivarius 24SMBc administered as a nasal spray in children affected by recurring infections of the upper airways, adenotonsillar hypertrophy, and sleep disordered breathing (SDB). METHODS: Prospective study on 42 children with SDB. Anamnestic and general examination data were collected using the 'Sleep Clinical Record' (SCR) questionnaire during the first inspection and after three months of treatment with Streptococcus salivarius 24SMBc nasal spray. Quantitative variables were statistically compared. RESULTS: After three months, the enrolled patients showed lower SCR scores than during the first inspection (6.0 vs 7.5 p < 0.000), with a significant reduction of nasal obstruction (p = 0.001) and oral breathing (p = 0.04), and a positive Brouillette Score (p = 0.001). The children and parents did not declare any adverse reactions during the three months of treatment. CONCLUSIONS: This series confirms the effectiveness and safety of Streptococcus salivarius 24SMBc treatment in children affected by recurring upper respiratory tract infections, adenotonsillar hypertrophy, and sleep disordered breathing.

Influence of allergic rhinitis in children and adolescents with recurrent headache.

INTRODUCTION: Migraine and allergies are a common occurrence. The aim of this study was to investigate the relationship between respiratory allergy and migraine in childhood. MATERIALS AND METHODS: We screened 800 children for headache and its characteristics. After that we investigated the presence of allergy performing prick tests, rhinoscopy, endoscopy, rhinomanometry, cytology and mucociliary clearance tests. RESULTS: Out of 800 children screened, 96 suffered from headache. Among these, 67 suffered from both headache and allergy. We found a significant correlation between allergy and headache onset in the morning and headache onset in the evening in non-allergic subjects. The average duration of a headache attack was independent from the presence of allergy, as well as the frequency of the cephalalgy attacks, and location of the pain. Prodromal symptoms connected with headache were reported to be: dizziness, aura, sparkling scotoma, nausea and vomiting, and they were associated with absence of allergy. We also found a relationship between female gender and headache onset, but in teenagers only. Paracetamol or FANS were used in the majority of cases, but antihistamine therapy and/or topical nasal sprays were also reported. DISCUSSION: For an effective diagnostic and therapeutic approach to migraine, the pediatrician should take into account atopy and its related allergic manifestations requiring a consultation with an otorhinolaryngologist or allergist if necessary. Our findings also stress the potential role of medicines that are not usually administered in migraine attacks, such as antihistamines or topical decongestant nasal sprays.

Ear nose and throat (ENT) aspects of Obstructive Sleep Apnea Syndrome (OSAS) diagnosis and therapy. / Sindrome delle Apnee Ostruttive nel Sonno (OSAS): aspetti diagnostici e terapeutici otorinolaringoiatrici.

This article analyzes the role played by the ear, nose and throat (ENT) specialist in the diagnosis and treatment of the Obstructive Sleep Apnea Syndrome (OSAS). DIAGNOSIS: The instrumental methods of investigation of otolaryngology expertise are fiberoptic rhinolaryngoscopy and sleep endoscopy. To better define and treat OSAS it is essential to define location, extension and degree of obstruction. The major limitation of rhinolaryngoscopy is that it is conducted while the patient is awake. Sleep endoscopy was introduced to address this issue: it is an endoscopic examination conducted during pharmacologically induced sleep (midazolam, propofol). Surgical treatment: The applicability of surgical treatment is limited: it is not efficient for every patient and not to the same extent. Surgical therapy is based on the detection and correction of the site of obstruction, although in most cases the obstruction sites are located at different levels. The surgical approach usually follows a path characterized by "subsequent steps". According to Stanford University Powell-Riley Protocol the first phase includes: nasal surgery, palate surgery (UPPP, LAUP Laser Assisted uvulopalatoplasty, UvuloPalatalFlap UPF) and tongue base surgery (tongue suspension, genioglossus advancement, hyoid suspension) that could either be executed individually or associated. Four-six months after surgery a physical and polysomnography examination should be performed. In case of symptoms persistence, the surgeon could move on to phase II surgery as recovery therapy. The phase II surgery includes: maxillo-mandibular advancement, tongue base resection and tracheotomy. In selected cases a Phase II surgery could be planned at the beginning of treatment.

Surgical treatment of nasal septal perforations: SIR (Italian Society of Rhinology) experts opinion.

BACKGROUND AND AIM: The aim of our study has been to investigate the perception of aspects related to nasal perforation among experts in Rhinology and ENT surgeons. Our aim was reporting the situations in different Countries to improve the knowledge of colleagues interested in this topic. METHODS: A panel of experts prepared a 20-question questionnaire regarding nasal perforations and their surgical repair, that were emailed to all the members of SIR (Società Italiana di Rnologia - Italian Society of Rhinology). RESULTS: Data obtained from their answers showed that Cottle technique (64%) is the most common technique to perform septoplasty worldwide. 37% of the sample reported an occurrence of nasal septal perforation in less than 1% of patients and 75% attributed this occurrence to the skill of the surgeon, to infections, to drug use and to septal deformity. Trauma, pressure and Wegener's granulomatosis were also mentioned. The most common closure technique is the mucosal flap (75%), followed by the cartilage grafts (11%). Much less common were oral flaps, septal buttons and others. The majority agreed not to suggest septal perforation surgery in minimal (less than 3-4mm) perforations (73.5%), or limiting it to symptomatic patients (43.5%). The contraindications to repair surgery were reported to be: Wegener's granulomatosis, drug abuse, non-symptomatic perforation, its dimension and age of the patient. Septal deviation, atrophic rhinitis, smoke epistaxis and systemic diseases were also claimed. Failure in repair surgery has been observed to occur in less than 30% of cases. DISCUSSION AND CONCLUSIONS: Given the great difficulty to make random studies about controversial topics and obtain statistically significant data related to that, expert opinion shall be of great value (expert opinion, level of evidence 5).