Prefrontal dysfunction in post-COVID-19 hyposmia: an EEG/fNIRS study.

Introduction: Subtle cognitive dysfunction and mental fatigue are frequent after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, characterizing the so-called long COVID-19 syndrome. This study aimed to correlate cognitive, neurophysiological, and olfactory function in a group of subjects who experienced acute SARS-CoV-2 infection with persistent hyposmia at least 12 weeks before the observation. Methods: For each participant (32 post-COVID-19 patients and 16 controls), electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) data were acquired using an integrated EEG-fNIRS system during the execution of a P300 odd-ball task and a Stroop test. The Sniffin' Sticks test was conducted to assess subjects' olfactory performance. The Montreal Cognitive Assessment (MoCA) and the Frontal Assessment Battery (FAB) were also administered. Results: The post-COVID-19 group consisted of 32 individuals (20 women and 12 men) with an average education level of 12.9 ± 3.12 years, while the control group consisted of 16 individuals (10 women and 6 men) with an average education level of 14.9 ± 3.2 years. There were no significant differences in gender (X2 = 0, p = 1) or age between the two groups (age 44.81 ± 13.9 vs. 36.62 ± 11.4, p = 0.058). We identified a lower concentration of oxyhemoglobin (p < 0.05) at the prefrontal cortical level in post-COVID-19 subjects during the execution of the Stroop task, as well as a reduction in the amplitude of the P3a response. Moreover, we found that post-COVID-19 subjects performed worst at the MoCA screening test (p = 0.001), Sniffin's Sticks test (p < 0.001), and Stroop task response latency test (p < 0.001). Conclusions: This study showed that post-COVID-19 patients with persistent hyposmia present mild deficits in prefrontal function, even 4 months after the end of the infection. These deficits, although subtle, could have long-term implications for quality of life and cognitive wellbeing. It is essential to continue monitoring and evaluating these patients to better understand the extent and duration of cognitive impairments associated with long COVID-19.

Eosinophil-mast cell pattern of intraepithelial infiltration as a marker of severity in CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is defined as a Type 2 eosinophilic disease, while CRSsNP is considered a Type 1 neutrophilic disease. Since neutrophils are also activated in eosinophilic CRSwNP, the eosinophil-neutrophil dualism has been revaluated. Among the inflammatory cells infiltrating sinus-nasal tissues, the role of mast cells (MCs) is not already recognized, although Clinical-Cytological Grading, which defines the severity of CRSwNP, attributes to mixed eosinophil-MC forms of CRSwNP a greater risk of recurrence. We aimed to examine nasal polyps from both a cytological and histopathological point of view, to evaluate the presence and localization of MCs. Cytological and histological examination of 39 samples of nasal polyps were performed. Immunohistochemistry was used to evaluate the presence of Tryptase + CD117 + MCs, which were counted both in the epithelial layer and in the lamina propria. A statistically significant correlation was found between intraepithelial MCs and CRSwNP severity (p < 0.001) and between the total eosinophil count and the total mast cell count (p < 0.001). Cytological examination and immunohistochemistry were comparable in detecting the presence of intraepithelial MCs (p = 0.002). The histological cut-off of 6 intraepithelial MCs was identified to detect severe CRSwNP (p < 0.001). MCs have been shown to be located in the lamina propria of almost all eosinophilic nasal polyps without significantly affecting their severity. Intraepithelial MCs are associated with greater severity of CRSwNP. Histopathological criteria of the eosinophil-MC form of CRSwNP in addition to the eosinophilic one, should be defined to guarantee patients effective and tailored treatments.

Effects of benralizumab in a population of patients affected by severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a real life study.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe eosinophilic asthma (SEA), which may contribute to the loss of asthma control. CRSwNP and SEA share a T2-mediated mechanism and the use of some anti-asthma monoclonal antibodies has recently been extended to CRSwNP. Unlike dupilumab and omalizumab, benralizumab approval for CRSwNP is ongoing. We aimed to evaluate the efficacy of benralizumab efficacy on SEA and on CRSwNP in patients affected by both pathologies in a real life setting. METHODS: 17 patients affected by both SEA and CRSwNP participated to our study. At baseline (T0) and at one year after benralizumab initiation (T1), all participants underwent  spirometry, exhaled nitric oxide (FeNO), Asthma Control Test (ACT), nasal endoscopy with Nasal Polyp Score (NPS), nasal cytology and Sino-Nasal Outcome Test 22 (SNOT 22).The continuous oral corticosteroid therapy (OCS), the number of year exacerbations and the need for sinus surgery were also evaluated  for each patient. RESULTS: At T1, a marked reduction of SNOT-22, NPS, nasal eosinophils and neutrophils count were shown compared to T0. Moreover, at T1 ACT was significantly increased and FeNO, exacerbations/year and mean OCS dosage were significantly reduced compared to T0. CONCLUSIONS: Our real-life study demonstrates the efficacy of benralizumab not only on SEA but also on nasal cytology and on nasal polyposis, confirming that patients affected by both SEA and CRSwNP may receive a considerable benefit from anti-IL5 receptor, treating both the comorbidities at once.

Chronic rhinosinusitis with nasal polyps: how to identify eligible patients for biologics in clinical practice.

Objective: This study compared three severity measures for chronic rhinosinusitis with nasal polyps (CRSwNP). The outcome was to identify patients who are eligible for biological therapy. Methods: 330 adult patients with CRSwNP were examined. Nasal polyp score (NPS), sinonasal outcome test (SNOT-22) and clinical-cytological grading (CCG) were compared. Clinical history, past surgery and asthma control test were also considered. Results: Only 45 (13.6%) patients had a contextual positivity to the three severity measures. The concordance among tests was slight/fair. Patients with severe disease (all tests positive) had more impaired parameters. The mixed cytotype (OR = 4.07), nasal obstruction (OR = 10.06), post-nasal drip (OR = 1.98), embarrassment (OR = 2.53) and difficulty falling asleep (OR = 1.92) were significantly associated with severe CRSwNP. Conclusions: To identify candidates for biological therapy, the contextual use of NPS, SNOT-22 and CCG is preferable. In this way, global assessment of CRSwNP, including morphology, inflammation, comorbidity, symptoms and quality of life is possible.

COVID-19 lockdown and seasonal allergic rhinitis: our experience in 40 patients.

INTRODUCTION: The aim of this article was to study the course of seasonal allergic rhinitis during COVID-19 lockdown in order to understand if being quarantined at home for a long time can constitute a protective factor for allergic patients. MATERIALS AND METHODS: Telehealth consultations were performed by the departments of Otolaryngology of Foggia and Bari University Hospitals. Participants took part in a phone interview and were asked about their sinonasal symptoms during the COVID-19 lockdown, by answering the sinonasal outcome test (I-SNOT-22) questionnaire. Further data concerning the medications used to treat allergy and the number of days per month in which they were used were collected. The responses about the COVID-19 lockdown were compared to those obtained by the same patients in our clinics the previous year. The statistical analysis was executed by using the paired sample t-test and the Bartlett test considering as significant values with p values <0.05. RESULTS: Forty patients affected by cypress pollen allergy visited at Foggia and Bari University Hospitals were enrolled in this study. All I-SNOT-22 scores concerning the COVID-19 lockdown were lower than those of the previous year; moreover, 18 (81.8%) clinical parameters were statistically significant (p<0.05). Also, in regard to the treatment, results about COVID-19 lockdown were overall better than those of 2019, with 50% (n=3) of the investigated drugs, reporting statistical significance (p<0.05). CONCLUSIONS: The present study was able to evidence the fundamental role of primary prevention in Allergology. Paradoxically, the home quarantine ordered by the Italian Government appeared to be an effective measure not only in the fight against COVID-19 but also against pollen exposure.

ENT surgical emergencies during the COVID-19 outbreak.

INTRODUCTION: The restrictive measures adopted by the Italian Government during the COVID-19 outbreak caused dramatic changes in routine public health care. Surprisingly, emergency activity also registered a reduction in frequency. METHODS: This multicentre retrospective study aims to investigate eventual changes in ENT surgical emergencies in a highly populated area of southern Italy during the COVID-19 pandemic. Data concerning the period between the February 1 and the May 31, 2020 were collected from the main three hospitals in the district and compared with the same period of 2019. RESULTS: A substantial reduction was found in the number of ENT emergency interventions in 2020 compared to the same period of 2019, particularly in the main lockdown phase and in the tertiary referral centre. CONCLUSIONS: The reduction in the absolute number of emergency ENT interventions can be only partially explained by social distancing and home confinement. We have reason to believe that some of these patients may have not sought medical support due to fear of nosocomial SARS-CoV2 infection. This study could represent a trigger for further implementation of health system responses to emergencies in a period of transition that is likely to last for a prolonged period of time.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

COVID-19: When dust mites and lockdown create the perfect storm.

The aim of the present study was to understand if the course of the disease of patients suffering from dust mite allergy could have been negatively affected by the COVID-19 restrictions, which have been certainly important to fight the pandemic, but forced patients to stay at home for a long time.

Local allergic rhinitis: entopy or spontaneous response?

BACKGROUND: The existence of a local allergic rhintis was proposed on the basis of the detection of nasal IgE in the absence of a systemic sensitization. Nevertheless, the significance of this phenomenon remains still unclear. We assessed the presence of mucosal nasal IgE in patients with ascertained allergic rhinitis, nonallergic rhinitis with inflammation and in healthy controls. METHODS: Consecutive patients with a well ascertained diagnosis (clinical history, skin prick test, specific IgE assay, nasal endoscopy, nasal cytology) underwent an immunoenzymatic measurement of specific IgE to grass, cypress, parietaria and olive in nasal scrapings. RESULTS: Fifteen patients with allergic rhinitis, 12 with non allergic rhinitis and 14 healthy subjects were studied. The patients with allergic and nonallergic rhinitis had higher nasal symptoms as compared to control subjects. Systemic sensitizatition (assessed by skin test and CAP-RAST) was obviously more frequent in allergic rhinitis, than in the other two groups. Allergen-specific nasal IgE could be detected in all groups (86,7, 33,3, and 50 % positive, respectively), even more frequently in the control group than in nonallergic rhinitis patients. No difference among allergens was identified. Out of the 26 non-allergic patients (non allergic rhinitis + controls) nasal IgE were positive in 11(42 %). DISCUSSION: According to the results, the presence of nasal IgE against allergens seems to be a non-specific phenomenon, since they can be detected also in non allergic rhinitis and in healthy subjects. CONCLUSION: It can be hypothesized that the nasal IgE production represents a form of spontaneous immune response.

Allergic rhinitis phenotypes based on mono-allergy or poly-allergy.

BACKGROUND: Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. OBJECTIVE: The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. METHODS: 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. RESULTS: Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones (p = 0.0006) as well as they had more frequent sneezing (p < 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils (p = 0.0005) and mast cells (p = 0.0001), than mono-allergic patients. CONCLUSIONS: The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than mono-allergic ones.

Clinical characteristics associated with conjunctival inflammation in allergic rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis affects up to 30% of the general population worldwide and is increasing in prevalence. Among several comorbidities, conjunctivitis is probably the most common and occurs so frequently with allergic rhinitis that the term allergic rhinoconjunctivitis (ARC) has been coined. OBJECTIVES: The cytological characteristics of conjunctival inflammation in patients with ARC were assessed and then correlated to clinical characteristics. METHODS: Fifty-one patients with clinically diagnosed ARC (23 men; 32.4 ± 13.5 years old) underwent a detailed clinical history and standard diagnostic allergy workup as well as nasal and conjunctival scraping for cytological analysis. Patients were subdivided into 3 groups on the basis of cytological phenotype: (1) nasal and conjunctival inflammation, (2) nasal inflammation only, and (3) no mucosal inflammation. RESULTS: Group 1 patients reported significantly higher eye itching scores (5.8 ± 2.9 on a 0-10 scale) than did patients in group 2 (3.8 ± 2.8; P = .06) or 3 (2.6 ± 2.9; P = .018) and were mostly men (81.8%). Male sex (odds ratio, 8.4; P = .005) and eye itching (odds ratio, 1.3; P = .019) significantly correlated with conjunctival inflammation. The odds of exhibiting conjunctival inflammation, at multivariate analysis, increased 13-fold for men and 1.5-fold for each point on the eye itching scale. A cutoff value of 3 or more for eye itching effectively identified patients with conjunctival inflammation. CONCLUSIONS: Our study demonstrates that some clinical manifestations of ARC correlate well with conjunctival inflammation.

Does the type of rhinitis influence development of otitis media with effusion in children?

Otitis media with effusion (OME) is characterized by the presence of fluid in the middle ear cavity behind an intact eardrum and is considered a multifactorial condition with Eustachian tube dysfunction as the underlying pathophysiologic condition. One of the most debated causes of OME is allergy, in particular allergic rhinitis. The aim of this paper is to review the role of rhinitis in the development of OME and in particular the role of both allergic (AR) and non-allergic rhinitis (NAR). Most of the recent literature confirms the role of AR in the development of OME, while there are few reports on the role of NAR. In non-allergic children affected by obstructive adenoid hypertrophy, the presence of mast cells in the nasal smear was associated with a high risk of developing a chronic OME.

Quality of life after cholesteatoma surgery: intact-canal wall tympanoplasty versus canal wall-down tympanoplasty with mastoid obliteration.

OBJECTIVES: The aim of this study was to evaluate, by means of the Chronic Ear Survey (CES), the quality of life of patients who had undergone either intact-canal wall tympanoplasty (ICWT) or canal wall-down tympanoplasty (CWDT) with mastoid obliteration. METHODS: This was a retrospective case review study performed at a tertiary referral center. Among 379 patients affected by middle ear and mastoid cholesteatoma operated on between November 2000 and December 2009, 50 patients who underwent ICWT and 50 who underwent CWDT with mastoid obliteration were randomly selected. The CES scores were analyzed for both groups. RESULTS: The mean scores on the CES were 6.5 ± 2.1 in patients who underwent CWDT and 6.9 ± 2.2 in patients treated with ICWT (t = -0.93; p > 0.05). No significant differences between the two groups were found on the activity restriction, symptom, or medical resource subscales (p > 0.05). CONCLUSIONS: The results of this study demonstrate that CWDT with mastoid obliteration resulted in a quality of life comparable with that after ICWT. Postoperative hearing loss is the most frequently reported problem for both techniques.

A study of the role of different forms of chronic rhinitis in the development of otitis media with effusion in children affected by adenoid hypertrophy.

OBJECTIVE: The aim of the present study was to evaluate the role of the different forms of chronic rhinitis in the pathogenesis of otitis media with effusion in children affected by obstructive adenoid hypertrophy. METHODS: 81 patients, aged between 4 and 15 years (mean age of 6.9 years), affected by obstructive adenoid hypertrophy were evaluated. All patients underwent accurate history taking, physical examination with endoscopy of the nasopharynx, skin prick test, nasal cytology and hearing evaluation. RESULTS: Nasal citology showed that 21% of patients had a non-allergic rhinitis (NAR) subtype, 17.4% NAR overlapping with infectious rhinitis (IR), 29.6% IR, 4.9% allergic rhinitis (AR), 2.5% AR overlapping with IR and the remaining 24.6% a negative cytology. The presence of OME was positively correlated with neutrophils (p = 0.01) and mast cells (p = 0.022), while it was negatively correlated with the presence of eosinophils (p = 0.02) and bacteria (p = 0.02). CONCLUSIONS: A chronic rhinitis was present in more than 70% of children with AH and 60% of them showed OME. Nasal cytology together with SPT showed that AR was rarely present in this group of children, while the mast-cells and neutrophils positively correlated with OME.

Double-blind placebo-controlled randomized clinical trial on the efficacy of Aerosal in the treatment of sub-obstructive adenotonsillar hypertrophy and related diseases.

BACKGROUND: Adenotonsillar hypertrophy (ATH) is a frequent cause of upper airways obstructive syndromes associated to middle ear and paranasal sinuses disorders, swallowing and voice disorders, sleep quality disorders, and occasionally facial dysmorphisms. ATH treatment is essentially based on a number of medical-surgical aids including nasal irrigation with topical antibiotics and corticosteroids and/or treatment with systemic corticosteroids, immunoregulators, thermal treatments, adenotonsillectomy, etc. OBJECTIVES: The aim of the present study is to assess the efficacy of Aerosal halotherapy in the treatment of sub-obstructive adenotonsillar disease and correlated conditions compared to placebo treatment. METHODS: A total of 45 patients with sub-obstructive adenotonsillar hypertrophy were randomized to receive either Aerosal halotherapy or placebo for 10 treatment sessions. The main outcome was a reduction greater than or equal to 25% from the baseline of the degree of adenoid and/or tonsillar hypertrophy. RESULTS: In the intention-to-treat analysis, a reduction of the degree of adenoid and/or tonsillar hypertrophy ≥25% from baseline after 10 therapy sessions was found in 44.4% of the patients in the halotherapy arm and in 22.2% of the patients in the placebo arm (P=0.204). Among the secondary outcomes, the reduction of hearing loss after 10 treatment sessions in the halotherapy arm was higher than the placebo arm (P=0.018) as well as the time-dependent analysis showed significantly improved peak pressure in the Aerosal group (P=0.038). No side effects were reported during the trial. In addition, the therapy was well accepted by the young patients who considered it as a time for play rather than a therapy. CONCLUSIONS: Aerosal halotherapy can be considered a viable adjunct, albeit not a replacement, to conventional medical treatment of sub-obstructive adenotonsillar syndrome and related conditions. Further research is however needed to improve ATH treatment.

Intranasal sodium hyaluronate on the nasal cytology of patients with allergic and nonallergic rhinitis.

BACKGROUND: Rhinitis is an extremely common medical problem characterized by nasal congestion, clear rhinorrhea, sneezing, and itching. Hyaluronate is an endogenous compound that has an important role in mucociliary clearance by the epithelial surface of the nasal passages and in mucosal surface healing and repair. The objective of this work was to determine the effects of intranasal administration of sodium hyaluronate on nasal cytology in patients with allergic and nonallergic rhinitis. METHODS: In a single-center, randomized, blinded trial, 78 patients received intranasal mometasone and oral desloratadine plus either intranasal sodium hyaluronate or saline for 1 month. Nasal cytology was performed and the change from baseline in the numbers of neutrophils, eosinophils, mast cells, lymphocytes, and infective species was determined. Other outcomes included changes in symptoms and the endoscopic appearance of the nasal mucosa, and tolerability. RESULTS: Patients receiving sodium hyaluronate experienced a significant decrease in the median neutrophil count seen on nasal cytology compared with controls (p = 0.001). Sodium hyaluronate was associated with significant improvements in sneezing, rhinorrhea, and nasal congestion, and on exudate seen on endoscopy at 1 month compared with baseline. Intranasal sodium hyaluronate received better tolerability scores than saline over the 1-month treatment period. CONCLUSION: The addition of sodium hyaluronate to intranasal corticosteroid and systemic antihistamine reduced the neutrophil count seen on nasal cytology in patients with allergic and nonallergic rhinitis and improved several clinical and endoscopic parameters while being well tolerated. These data provide encouraging evidence of the efficacy of sodium hyaluronate in the treatment of this common disease.