RICHARD LOUIS VOEGELS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Otorrinolaringologia e Oftalmologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/32 - Laboratório de Otorrinolaringologia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/32 - Laboratório de Otorrinolaringologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis(2023) CARVALHO, Thiago; JR, Joao Ferreira de Mello; CALDINI, Elia Tamaso Espin Garcia; SALGADO, Daniel Calduro; CARVALHO, Nicole Mary Garcia de; DAMACENO-RODRIGUES, Nilsa Regina; VOEGELS, Richard LouisIntroduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis.Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR).Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate.Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score.Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.
- Upper Airway Mucociliary Clearance is Impaired in Dyspneic COVID-19 Patients(2023) PEZATO, Rogerio; DAVID, Andrea Goldwasser; BOGGI, Alexandre Coelho; MELO, Bruna; ROSALINO, Claudia Maria Valete; RODRIGUEZ, Athenea Pascual; THAMBOO, Andrew; VOEGELS, Richard LouisCovid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.
- Association of air pollution with olfactory identification performance of Sao Paulo residents: a cross-sectional study(2023) SCUSSIATTO, Henrique Ochoa; SILVA, Jose Lucas Barbosa Da; FIGUEIREDO, Alan Felipe; RAMOS, Rafael Antonio Matias Ribeiro; PINNA, Fabio De Rezende; VOEGELS, Richard Louis; PINTO, Jayant M. M.; FORNAZIERI, Marco AurelioObjectiveExposure to particulate matter of 10 mu m or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors.MethodsAdults from Sao Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects' zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT (R)). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell.ResultsAcute exposures to PM10 were related to worse UPSIT (R) scores, including 30- (beta = - 0.94, 95% Confidence Interval [CI] - 0.98, - 0.89), 60- (beta = - 1.09, 95% CI = - 1.13, - 1.04) and 90-day intervals (beta = - 1.06, 95% CI - 1.10, - 1.02) (reference for beta: 1 mu m/m(3) increase in PM10 exposure per point decrease in UPSIT (R) score). Chronic exposures were also associated with worse olfaction for both 180- (beta = - 1.06, 95% CI - 1.10, - 1.03) and 364-day (beta = - 0.87, 95% CI - 0.90, - 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance.ConclusionAcute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.
- Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study(2023) DAMIANO, Rodolfo Furlan; NETO, Deusdedit Brandao; OLIVEIRA, Joao Vitor Ribeiro; SANTOS, Jonatas Magalhaes; ALVES, Julia Vallin Rodrigues; GUEDES, Bruno F.; NITRINI, Ricardo; ARAUJO, Adriana Ladeira de; OLIVEIRA, Melaine; BRUNONI, Andre R.; VOEGELS, Richard Louis; BENTO, Ricardo Ferreira; BUSATTO, Geraldo; MIGUEL, Euripedes Constantino; FORLENZA, Orestes V.; PINNA, Fabio de RezendePreliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.
- Outcomes of Endoscopic Sinus Surgery for Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia(2023) PLANTIER, Diogo Barreto; PINNA, Fabio de Rezende; OLM, Mary Anne Kowal; ATHANAZIO, Rodrigo; PILAN, Renata Ribeiro de Mendonca; VOEGELS, Richard LouisIntroduction Primary ciliary dyskinesia (PCD) is a rare inherited disease associated with impairment of mucociliary transport and, consequently, with a high incidence of chronic rhinosinusitis. For patients with chronic rhinosinusitis who remain symptomatic despite medical treatment, endoscopic sinus surgery is a safe and effective therapeutic option. However, to date, no studies have been found evaluating the effect of surgery on the quality of life associated with the effect on olfaction and nasal endoscopy findings of patients with primary ciliary dyskinesia and chronic rhinosinusitis.Objective To describe the effect of endoscopic sinus surgery on the quality of life, on olfaction, and on nasal endoscopy findings of adults with PCD and chronic rhinosinusitis.Methods Four patients who underwent endoscopic sinus surgery were included. The Sinonasal Outcome Test-22 (SNOT-22) score, the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, and the Lund-Kennedy score were collected preoperatively and at 3 and 6 months postoperatively. The olfaction as assessed with the University of Pennsylvania Smell Identification Test (UPSIT), which was administered preoperatively and 3 months postoperatively.Results A total of 4 patients with a mean age of 39.3 years old (3 men and 1 woman) completed the study. All patients showed clinically significant improvement in the SNOT-22, NOSE, and Lund-Kennedy scores at 3 months postoperatively, and this improvement was sustained throughout the follow-up period. However, olfaction did not improve after surgery.Conclusion The endoscopic sinus surgery treatment of chronic rhinosinusitis in adults with PCD was associated with improvement in quality of life and endoscopic findings. However, no improvement in olfaction was demonstrated. Studies with a larger number of patients and control groups should help confirm these findings.
- Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth(2023) GOES, Hallyson Andre Nascimento de; SARAFAN, Masih; AMARAL, Jonatas Bussador do; ALMEIDA, Joyce dos Anjos; VOEGELS, Richard Louis; CRUZ, Leandro Ticlia de la; THAMBOO, Andrew; GOMES, Ligia Ferreira; PEZATO, RogerioIn chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48 h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of Sao Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of Sao Paulo (no CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.
- Computed Tomography Evaluation of the Paranasal Sinuses in Adults with Primary Ciliary Dyskinesia(2023) PLANTIER, Diogo Barreto; PILAN, Renata R. M.; ATHANAZIO, Rodrigo; OLM, Mary Anne K.; GEBRIM, Eloisa M. S.; VOEGELS, Richard LouisIntroduction Primary ciliary dyskinesia is a rare inherited disease that results in a malfunction of mucociliary clearance and sinonasal complaints. Aplasia/hypoplasia of the frontal and sphenoid sinuses has been described as more frequent in this population. However, to date, no studies have provided a detailed description of computed tomography findings in adult patients with a diagnosis of this condition. Objective To describe the computed tomography (CT) findings of adult patients with primary ciliary dyskinesia. Methods Retrospective observational study of adult patients with primary ciliary dyskinesia who underwent CT. Results Twenty-one adults were included in the study. Aplasia occurred in 38.1% of frontal sinuses and in 14.3% of sphenoid sinuses. Likewise, hypoplasia occurred in 47.6% of the frontal sinuses, in 54.8% of the sphenoid sinuses and in 40.5% of the maxillary sinuses. Furthermore, trabecular loss was identified in 61.9% ethmoidal sinuses. The mean Lund-Mackay score was 13.5. In addition, 9.5% of the patients had concha bullosa, 47.6% had marked bilateral inferior turbinate hypertrophy, 38.1% had marked middle turbinate hypertrophy, and 47.6% had marked septal deviation. Finally, we identified images suggestive of fungus ball, mucocele, osteoma, a possible antrochoanal polyp, and frontal bone erosions. Conclusion The present study provides a detailed description of CT findings in patients with primary ciliary dyskinesia. We also describe abnormalities that must be identified for safer surgical planning and that suggest a diagnosis of primary ciliary dyskinesia if found in patients with a consistent clinical picture.
- High prevalence of olfactory dysfunction detected in treatment-naive patients with head and neck cancer(2023) SILVA, Jose Lucas Barbosa da; ANZOLIN, Lucas Kanieski; NICACIO, Samuel Pissinati; DOTY, Richard L. L.; PINNA, Fabio de Rezende; VOEGELS, Richard Louis; FORNAZIERI, Marco AurelioBackgroundPrevious studies demonstrated the difficulty of patients with Head and Neck Cancer (HNC) in sensing food taste, a function in which olfaction has a significant role. However, neither study employed psychophysical tests or control groups to establish the veracity of such complaints.Aims/objectivesIn this study, we quantitatively tested the olfactory function of HNC individuals and compared their function to that of healthy controls.MethodsThirty-one HNC naive treatment patients and thirty-one controls, matched for sex, age, schooling, and smoking, were tested with the University of Pennsylvania Smell Identification Test (UPSIT).ResultsThe olfactory function was significantly worse among the patients diagnosed with head and neck cancer [UPSIT cancer = 22.9(CI 95%: 20.5-25.4) vs. UPSIT controls = 29.1(CI 95%: 26.9-31.3); p < .001]. Most patients with HNC had olfactory disorders (n = 29, 93.5%). The risk of olfactory loss was higher in the cancer group [OR: 10.5(CI 95%: 2.1-51.9; p = .001)].Conclusion and significanceOlfactory disorders can be detected in more than 90% of patients with head and neck cancer when evaluated using a well-validated olfactory test. Smell disorders may be a potential marker for early diagnosis of HNC.
- Olfaction in nasal polyp patients after Reboot surgery: an endotype-based prospective study(2023) GOMES, Sara Costa; DELEMARRE, Tim; HOLTAPPELS, Gabriele; ZELE, Thibaut Van; DERYCKE, Lara; BONNE, Ellen; EECKELS, Anne-Sophie; ZHANG, Nan; VOEGELS, Richard Louis; BACHERT, ClausPurpose To report biomarkers present in the olfactory mucosa in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison with nasal polyps and to nasal mucosal tissues from control patients. To evaluate the kinetics of smell over 6 months in patients who underwent Reboot surgery. Methods Cohort study from May 2021 to May 2022. We collected samples of olfactory mucosa and nasal polyps from 16 CRSwNP patients and inferior turbinate samples from 20 control subjects. The study was not randomized for surgical and/or medical treatment. Samples were analyzed by Luminex and Unicap 100 to measure biomarkers of inflammation (IL1-beta, IL4, IL5, IL6, IL17, CCL3, CCL4, G-CSF, SE-IgE, total IgE and ECP). 12 of the CRSwNP patients underwent Extended Sniffin'tests at timepoints 1-4 days pre-surgery, and 1, 3 and 6 months after Reboot surgery. Results Type-2 markers were significantly elevated in OM and polyp tissue in CRSwNP (n = 16) vs. controls (n = 20), P < 0.05. TDI scores improved already 1 month (P < 0.05) after surgery and remained stable for 6 months. Type-2 inflammation in nasal polyps was associated with decreased sense of smell and taste before surgery, but improved after surgery (P = 0.048). Type-3 inflammation was present in the olfactory mucosa and was associated with a better sense of smell before surgery, but a smaller improvement of smell afterward. Conclusions Type-2 inflammation is present in the olfactory mucosa in CRSwNP patients and is associated with smell loss. Reboot surgery, aiming to completely remove inflamed sinus mucosa, significantly improves the smell in this group of patients.
- Chemosensory Dysfunction 3-Months After COVID-19, Medications and Factors Associated with Complete Recovery(2023) FORNAZIERI, Marco Aurelio; SILVA, Jose Lucas Barbosa da; GAMEIRO, Juliana Gutschow; SCUSSIATO, Henrique Ochoa; RAMOS, Rafael Antonio Matias Ribeiro; CUNHA, Bruno Machado; FIGUEIREDO, Alan Felipe; TAKAHASHI, Eduardo Hideki; MARIN, Gabrielli Algazal; CAETANO, Igor Ruan de Araujo; MELI, Tainara Kawane; HIGUCHI, Diego Issamu; SANTOS, Rafael Rodrigues Pinheiro dos; RAMPAZZO, Ana Carla Mondek; PINNA, Fabio de Rezende; VOEGELS, Richard Louis; DOTY, Richard L.Objectives: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. Methods: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. Results: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. Conclusions: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants.