Inflammatory Profile of Chronic Rhinosinusitis With Nasal Polyp Patients in Brazil: Multicenter Study.

OBJECTIVES: To determine the inflammatory profile of CRSwNP in Brazil and characterize the subgroups of CRSwNP patients in this population through cluster analysis. STUDY DESIGN: Multicenter cross-sectional study involving 15 centers representing different regions of Brazil. SUBJECTS AND METHODS: Clinical data of 166 patients and 80 controls, aged 18 to 70 years old, number of surgeries for CRS, history of asthma and aspirin sensitivity, and Lund-Mackay scores on CT scans. During nasal endoscopy, we obtained the Lund-Kennedy scores and collected 2 samples of nasal polyps: one for eosinophil and neutrophil tissue counts and one to quantify different cytokines. RESULTS: 79.6% of our patients had 10 or more eosinophils/HPF. CRSwNP groups exhibited significantly lower concentrations of TNF-alpha and significantly higher concentrations of IFN-gamma, CCL11/Eotaxin, CCL24/Eotaxin-2/MPIF-2, and CCL26/Eotaxin-3 versus the control group (Kruskal-Wallis test). Comparison between CRSwNP groups (≥10 vs <10 eosinophils/HPF) showed no difference in cytokine concentration (Mann-Whitney test). Hierarchical clustering and PCA according to cytokine concentrations revealed 2 main Clusters, with a significantly higher concentration of all cytokines in Cluster 1 (n = 35) than in Cluster 2 (n = 121), except IL-6 and IL-33 (Mann-Whitney test). According to ROC curve analysis the best cut-off to differentiate the 2 clusters was 43 eosinophils/HPF. The group with ≥43 presented a higher prevalence of men and a higher Lund-Mackay score (Mann-Whitney test). CONCLUSIONS: CRSwNP patients in Brazil present mixed inflammation, with 2 distinct groups (high and low inflammatory pattern) that can be distinguished by tissue eosinophilia of ≥43 eosinophils/HPF cut-off in nasal polyps.

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update.

INTRODUCTION: Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. OBJECTIVES: The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. RESULTS: We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. CONCLUSIONS: This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

Brazilian guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps ‒ 2024 update

Abstract Introduction Biologics targeting type 2 inflammation have revolutionized the way we treat patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Particularly in severe and difficult-to-control cases, these drugs have provided a new reality for these patients, allowing for the effective and safe treatment of extensive diseases that were not completely managed with the typical strategy of surgery and topical medications. Objectives The experience achieved with the approval of these medications by ANVISA for use in CRSwNP and the knowledge obtained regarding outcomes, adverse effects, and the ideal patient profile prompted the update of the previously published guideline, with a detailed review of the most recent scientific literature, the personal experiences of experts, and the adaptation to the reality of the Brazilian healthcare system, both public and private. Results We proposed a new eligibility criterion for biologics in patients with CRSwNP based on four pillars of indication: the impact of the disease on the patient's life, whether in the presence of specific symptoms or in overall quality of life; the extent of sinonasal disease; the presence of type 2 comorbidities, considering other associated diseases that may also benefit from anti-T2 biologics, and the presence of biomarkers to define type 2 inflammation, especially those associated with worse disease prognoses. Conclusions This innovative and pioneering method has two major advantages. First, it ensures a comprehensive evaluation of patients; second, it is flexible, as advancements in our understanding of the disease and changes in cost-effectiveness can be addressed by simply adjusting the required score for indication, without the need to modify the entire evaluation scheme.

Which are the best murine models to study Eosinophilic Chronic Rhinosinusitis? A contemporary review.

OBJECTIVE: Mechanisms that lead to Eosinophilic Chronic Rhinosinusitis (ECRS) are not fully established in the literature. It is desirable to assess ECRS in a model that embraces most of the related events. This article reviewed the murine models for ECRS and compared them regarding eosinophilic polypoid formation. METHODS: The authors reviewed the articles that included the terms "chronic rhinosinusitis" OR "chronic sinusitis" AND "animal model". We analyzed articles in English that evaluated both the number of polyps and the number of eosinophils in the sinus mucosa of mouse models. RESULTS: We identified a total of 15 articles describing different models of ECRS that used BALB/c or C57BL/6 mice, and different triggers/stimulants such as Staphylococcus aureus Enterotoxin B (SEB) + Ovalbumin (OVA); House Dust Mite (HDM) ±â€¯Ovalbumin (OVA); and Aspergillus oryzae Protease (AP) + Ovalbumin (OVA). OVA associated with SEB was the commonest protocol to induce ECRS in both BALB/c and C57BL/6 mice, and it produced a robust response of eosinophilic nasal polyps in both. AP + OVA protocol also led to a good ECRS response. The other models were not considered adequate to produce eosinophilic polyps in mice. CONCLUSION: In conclusion, OVA associated with SEB seems to produce the most robust eosinophilic sinonasal inflammation.

Revisiting the orbital complications of acute rhinosinusitis.

OBJECTIVE: The present study revisited three classification systems of orbital complications of acute rhinosinusitis (ARS) (Chandler, Mortimore & Wormald, and Velasco e Cruz & Anselmo-Lima) and observed which of them presented the best clinical applicability. METHODS: Clinical data and CT scan findings of patients with orbital infection were retrospectively collected. To compare the three classification systems, we revised and graded all CT images accordingly, and divided the patients into four groups: Eyelid cellulitis (EC), orbital cellulitis (OC), subperiosteal abscess (SA), and orbital abscess (OA). The groups were compared regarding the presence of sinus opacification, the need for hospitalization and/or surgical treatment, and the presence of further complications/sequelae. RESULTS: 143 patients were included. The median number of sinuses involved in patients in the OC, SA, and OA groups was 2.0. ARS was rarely associated with signs of EC (present in both Chandler's and Mortimore & Wormald's classifications. The hospitalization rate was significantly lower in the EC group compared to the other three groups. Surgery was performed in all cases in the OA group, in 58.1% in the SA group, 19.4% in the OC group, and 12.5% in the EC group (p-value < 0.0001). Complications were present at higher rates in the OA group compared to the other three groups. CONCLUSIONS: ARS was rarely associated with Eyelid Cellulitis. The stratification in the other three groups showed to be clinically relevant. Velasco e Cruz & Anselmo-Lima's classification system proved valid, simple, and effective for categorizing orbital complications of ARS.

Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

OBJECTIVES: Successful recovery from chronic rhinosinusitis (CRS) following endoscopic sinus surgery (ESS) can be characterized by minimal presence of symptoms and absence of disease on endoscopy. However, molecular markers of surgical success remain to be characterized. These could allow for better tailoring of perioperative therapy. This study aims to identify novel molecular markers associated with surgery responsive patient. STUDY DESIGN: Prospective cohort study. SETTING: Single academic hospital center. METHOD: One hundred eighteen consecutive patients with CRS at high risk of recurrence after surgery were followed prospectively following ESS in an academic medical center. Symptomatic and endoscopic outcomes were assessed at 4 months, with success rigorously defined subjectively as minimal or no symptoms (no symptom greater than 1 on an ordinal scale of 0-3) and objectively by the absence of nasal polyposis on sinus cavity endoscopy and Lund-Kennedy endoscopic edema score no greater than 1. Samples were obtained at the time of surgery and at 4-month postoperatively. Changes associated with surgery were determined by gene expression profiling using Affymetrix's Clariom S Human HT arrays. RESULTS: Successful ESS was characterized by a mild upregulation in Type 1 inflammation, upregulation of cell cycle progression, and epithelial barrier and proliferation-associated genes and pathways. ESS failure was associated to very high levels of Type 1 inflammation along with downregulation of epithelial barrier function and regeneration genes and pathways. CONCLUSION: Successful recovery from ESS involves restoration of epithelial function and regulated activation of Type 1 inflammation. Excessively elevated Type 1 inflammation is associated with epithelial barrier dysfunction.

Effect of rapid maxillary expansion on masticatory and swallowing functions in children with posterior crossbite.

OBJECTIVE: Investigate the influence of posterior crossbite on masticatory and swallowing functions by videofluoroscopy examination and to analyze the effects of Rapid Maxillary Expansion (RME) on the same functions. METHODS: A prospective longitudinal study was conducted on 32 children, 21 of them with posterior crossbite (10 girls and 11 boys, mean age 9.2 years, study group) and 11 children with no occlusal changes (6 girls and 5 boys, mean age 9.3 years, control group). The children were evaluated by an orthodontist for diagnosis, group characterization and occlusal treatment, by the otorhinolaryngology team for the assessment of respiratory symptoms, and by a speech therapist for videofluoroscopic evaluation of masticatory and swallowing parameters. The children with posterior crossbite were treated orthodontic ally using the Haas disjunctor for approximately six months and re-evaluated 5-months after removal of the appliance. Data were analyzed statistically by the Studentt-test for independent samples for comparison of the crossbite and control groups before and after treatment. RESULTS: There was no significant difference in oral preparatory and oral transit times, nor in cycles and masticatory frequency, between the pre and post orthodontic treatment groups and the control group. CONCLUSION: Rapid maxillary expansion did not influence the masticatory and swallowing variables studied by videofluoroscopy. However, the data require caution in interpretation.

Azithromycin Mechanisms of Action in CRS Include Epithelial Barrier Restoration and Type 1 Inflammation Reduction.

OBJECTIVE: Previous in vitro transcriptomic profiling suggests azithromycin exerts its effects in patients with chronic rhinosinusitis (CRS) via modulation of type 1 inflammation and restoration of epithelial barrier function. We wished to verify these postulated effects using in vitro models of epithelial repair and in vivo transcriptional profiling. STUDY DESIGN: Functional effects of azithromycin in CRS were verified using in vitro models of wounding. The mechanism of the effect of azithromycin was assessed in vivo using transcriptomic profiling. SETTING: Academic medical center. METHODS: Effects of azithromycin on the speed of epithelial repair were verified in a wounding model using primary nasal epithelial cells (pNEC) from CRS patients. Nasal brushings collected pre-and posttreatment during a placebo-controlled trial of azithromycin for CRS patients unresponsive to surgery underwent transcriptomic profiling to identify implicated pathways. RESULTS: Administration of azithromycin improved the wound healing rates in CRS pNECs and prevented the negative effect of Staphylococcus aureus on epithelial repair. In vivo, response to azithromycin was associated with downregulation in pathways of type 1 inflammation, and upregulation of pathways implicated in the restoration of the cell cycle. CONCLUSION: Restoration of healthy epithelial function may represent a major mode of action of azithromycin in CRS. In vitro models show enhanced epithelial repair, while in vivo transcriptomics shows downregulation of pathways type 1 inflammation accompanied by upregulation of DNA repair and cell-cycle pathways. The maximal effect in patients with high levels of type 1-enhanced inflammation suggests that azithromycin may represent a novel therapeutic option for surgery-unresponsive CRS patients.

Which are the best murine models to study Eosinophilic Chronic Rhinosinusitis? A contemporary review

Abstract Objective: Mechanisms that lead to Eosinophilic Chronic Rhinosinusitis (ECRS) are not fully established in the literature. It is desirable to assess ECRS in a model that embraces most of the related events. This article reviewed the murine models for ECRS and compared them regarding eosinophilic polypoid formation. Methods: The authors reviewed the articles that included the terms "chronic rhinosinusitis" OR "chronic sinusitis" AND "animal model". We analyzed articles in English that evaluated both the number of polyps and the number of eosinophils in the sinus mucosa of mouse models. Results: We identified a total of 15 articles describing different models of ECRS that used BALB/c or C57BL/6 mice, and different triggers/stimulants such as Staphylococcus aureus Enterotoxin B (SEB) + Ovalbumin (OVA); House Dust Mite (HDM) ± Ovalbumin (OVA); and Aspergillus oryzae Protease (AP) + Ovalbumin (OVA). OVA associated with SEB was the commonest protocol to induce ECRS in both BALB/c and C57BL/6 mice, and it produced a robust response of eosinophilic nasal polyps in both. AP + OVA protocol also led to a good ECRS response. The other models were not considered adequate to produce eosinophilic polyps in mice. Conclusion: In conclusion, OVA associated with SEB seems to produce the most robust eosinophilic sinonasal inflammation.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil / Validação do teste de olfato de Connecticut (CCCRC) adaptado para o Brasil

Abstract Introduction Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p < 0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC = 0.65) and excellent in the right nostril (ICC = 0.77) in the combined score. Conclusion The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Resumo Introdução Alterações olfativas são bastante comuns na população, causam significativo impacto na qualidade de vida. A documentação da função olfatória é fundamental para o diagnóstico, tratamento e seguimento de pacientes que cursam com doenças inflamatórias das vias aéreas superiores, neurodegenerativas ou infecções virais. Entre os diferentes testes de olfato existentes, o teste do Connecticut Chemosensory Clinical Research Center (CCCRC) é barato, de fácil aplicação, mas que ainda não foi avaliado em grande escala para a população brasileira. Objetivo Validar o teste de olfato CCCRC com adaptação para a população brasileira, avaliar o desempenho de voluntários saudáveis e a estabilidade do teste em retestes. Método Neste estudo fizemos adaptação cultural do teste CCCRC para o Brasil. Para validação e determinação dos escores de normalidade, aplicamos o teste em 334 voluntários saudáveis, com mais de 18 anos. O reteste foi ainda feito em até quatro semanas em 34 voluntários adicionais para avaliar concordância dos resultados. Resultados Avaliando o desempenho dos participantes, valores de normosmia e hiposmia leve foram obtidos em mais de 95% deles. Mulheres (58,4%) apresentaram melhor acurácia em relação aos homens (41,6%), p< 0,02; e indivíduos acima dos 60 anos apresentaram pior desempenho (mediana: 6; percentil 75: 6,5; percentil 25: 5). O teste e reteste dos 34 voluntários demonstrou que houve concordância (coeficiente de correlação intraclasse, CCI) considerada boa em narina esquerda (CCI = 0,65) e excelente em narina direita (CCI = 0,77) no escore combinado. Conclusão O teste CCCRC adaptado para o Brasil apresentou valores de normalidade semelhantes ao teste originalmente descrito e a validações em outros países, com alta taxa de reprodutibilidade. Considerando a relação custo-benefício altamente favorável, o CCCRC adaptado é uma ferramenta muito útil para mensuração da função olfatória na população brasileira.

Association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone / Relação entre a influência da gravidade da apneia obstrutiva do sono e alterações craniofaciais e do posicionamento do osso hioide

Abstract Introduction The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. Objective To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. Methods 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. Results Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p < 0.05). Between the two obstructive sleep apnea subgroups, patients with moderate or severe disease showed significantly shorter horizontal distance between the hyoid bone and the posterior pharyngeal wall (p < 0.05), when compared to the groups with mild obstructive sleep apnea. We also observed a significant positive correlation between obstructive apnea and hypopnea index and the distance from the hyoid to the mandibular plane (p < 0.05) as well as a significant negative association between obstructive apnea and hypopnea index and the horizontal distance from the hyoid to the posterior pharyngeal wall (p < 0.01). Conclusion We did not observe any association between obstructive sleep apnea and linear lateral alterations of the face. In contrast, there is a direct association between obstructive sleep apnea severity and the inferior and posterior position of the hyoid bone in children aged 7 to 10 years old.

Resumo Introdução A relação entre a intensidade da apneia obstrutiva do sono e alterações esqueléticas da face e do hioide em crianças é pouco explorada na literatura. Objetivo Avaliar se a intensidade da apneia obstrutiva do sono correlaciona-se às alterações craniofaciais e ao posicionamento do osso hioide em crianças em fase de dentição mista. Método Foram submetidas 76 crianças entre 7 e 10 anos à avaliação otorrinolaringológica, polissonografia e avaliação ortodôntica, inclusive cefalometria. Os participantes foram divididos em 3 grupos: grupo 1 com ronco primário, grupo 2 com apneia obstrutiva do sono leve e grupo 3 com apneia obstrutiva do sono moderada/grave. Foram analisadas medidas cefalométricas da face e do osso hioide. Essas medidas foram comparadas entre si dentro dos diferentes grupos por teste t de Student não pareado. Além disso, essas medidas foram correlacionadas com a variável índice de apneias obstrutivas e hipopneias do paciente através do teste de correlação de Pearson. Resultados Das 76 crianças, 14 constituíram o grupo 1, ronco primário; 46 o grupo 2, apneia obstrutiva do sono leve; e 16 o grupo 3, apneia obstrutiva do sono moderada/grave. Não se observou diferença significante entre os grupos para as variáveis craniofaciais. Observou-se maior distância do osso hioide ao plano mandibular nos dois grupos com apneia obstrutiva do sono quando comparado ao ronco primário (p < 0,05). Entre os dois subgrupos da apneia obstrutiva do sono, os pacientes com doença moderada ou grave apresentaram distância horizontal entre o hioide e a parede posterior da faringe significantemente menor (p < 0,05), quando comparados aos grupos com apneia obstrutiva do sono leve. Observamos ainda correlação significantemente positiva entre índice de apneias obstrutivas e hipopneias e a distância do hioide ao plano mandibular (p < 0,05) e significantemente negativa entre índice de apneias obstrutivas e hipopneias e distância horizontal do hioide com a parede posterior da faringe (p < 0,01). Conclusão Não observamos relação da apneia obstrutiva do sono com alterações lineares laterais da face. Em contraste, existe relação direta entre a gravidade da apneia obstrutiva do sono e a posição inferior e posterior do osso hioide em crianças entre 7 e 10 anos.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil / Diretriz para o uso dos imunobiológicos em rinossinusite crônica com pólipo nasal (RSCcPN) no Brasil

Abstract Introduction Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. Objective To review the current status of biologic treatment indications in chronic rhinosinusitis. Methods The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. Results Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. Conclusion The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Resumo Introdução A rinossinusite crônica com pólipos nasais grave não controlada impacta negativamente na qualidade de vida do indivíduo. Para esses casos, novos imunobiológicos têm surgido, para uso em fenótipos específicos da rinossinusite crônica, e mudaram os paradigmas de seu tratamento. Objetivo Revisar o estado atual das indicações de imunobiológicos em rinossinusite crônica. Método A Academia Brasileira de Rinologia reuniu diferentes especialistas para sugerir uma conduta que considerasse suas particularidades e seus aspectos relacionados à realidade nacional. Resultados De particular interesse para a tomada de decisão serão a identificação dos subgrupos de pacientes refratários às opções de tratamento pré-existentes e a construção de uma estratégia que realmente melhore a qualidade de vida deles, dentro da melhor relação custo-benefício. Conclusão O uso de imunobiológicos é uma opção válida para tratamento em casos mais graves. Essa estratégia deve ser mais bem compreendida e aprimorada no futuro, com mais estudos e maior experiência clínica.

Guideline for the use of immunobiologicals in chronic rhinosinusitis with nasal polyps (CRSwNP) in Brazil.

INTRODUCTION: Severe uncontrolled chronic rhinosinusitis with nasal polyps has a negative impact on an individual's quality of life. Therefore, new biologics have emerged for use in specific phenotypes of chronic rhinosinusitis, changing the paradigms of its treatment. OBJECTIVE: To review the current status of biologic treatment indications in chronic rhinosinusitis. METHODS: The Brazilian Academy of Rhinology brought together different specialists to suggest a course of action, considering its particularities and aspects related to the national reality. RESULTS: Of particular interest for decision making will be the identification of subgroups of patients refractory to pre-existing treatment options and the construction of a strategy that improves their quality of life, with the best cost-benefit ratio. CONCLUSION: The use of biologics is a valid option for treatment in more severe cases. This strategy must be better understood and improved in the future, with more studies and greater clinical experience.

Can drug-induced sleep endoscopy (DISE) predict compliance with positive airway pressure therapy? A pilot study.

PURPOSE: Drug-induced sleep endoscopy (DISE) has been poorly explored as an examination to assess positive airway pressure (PAP) therapy in patients with obstructive sleep apnea (OSA). The present study aimed to identify by DISE possible characteristics related to low compliance with PAP therapy due to respiratory complaints. METHODS: Patients using PAP for OSA underwent DISE in two conditions: (1) baseline (without PAP) and (2) PAP (with the same mask and airway pressure used at home). We compared patients reporting low compliance to PAP due to respiratory complaints to those well-adapted to therapy. VOTE classification (assessment of velopharynx, oropharynx, tongue base, and epiglottis) and TOTAL VOTE score (the sum of VOTE scores at each anatomical site) were assessed. ROC curve analyzed the accuracy of TOTAL VOTE to predict low compliance due to persistent pharyngeal obstruction in both conditions. RESULTS: Of 19 patients enrolled, all presented multilevel pharyngeal obstruction at baseline condition, with no difference between groups at this study point. When PAP was added, the median VOTE value was higher in the epiglottis (P value=0.02) and tended to be higher at the velum and tongue base in the poorly adapted group; TOTAL VOTE score was also significantly increased in patients with low compliance (P value<0.001). ROC curve demonstrated that patients with TOTAL VOTE scored 2.5 or more during DISE with PAP presented a 4.6-fold higher risk for low compliance with PAP therapy due to pharyngeal obstruction (AUC: 0.88±0.07; P value<0.01; sensitivity: 77%; specificity: 83%). CONCLUSIONS: Adding PAP during a DISE examination may help to predict persistent pharyngeal obstruction during PAP therapy.

Association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone.

INTRODUCTION: The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. OBJECTIVE: To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. METHODS: 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. RESULTS: Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p<0.05). Between the two obstructive sleep apnea subgroups, patients with moderate or severe disease showed significantly shorter horizontal distance between the hyoid bone and the posterior pharyngeal wall (p<0.05), when compared to the groups with mild obstructive sleep apnea. We also observed a significant positive correlation between obstructive apnea and hypopnea index and the distance from the hyoid to the mandibular plane (p<0.05) as well as a significant negative association between obstructive apnea and hypopnea index and the horizontal distance from the hyoid to the posterior pharyngeal wall (p<0.01). CONCLUSION: We did not observe any association between obstructive sleep apnea and linear lateral alterations of the face. In contrast, there is a direct association between obstructive sleep apnea severity and the inferior and posterior position of the hyoid bone in children aged 7 to 10 years old.

Validation of the Connecticut olfactory test (CCCRC) adapted to Brazil.

INTRODUCTION: Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. OBJECTIVE: To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. METHODS: In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. RESULTS: When evaluating the participants' performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p<0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC=0.65) and excellent in the right nostril (ICC=0.77) in the combined score. CONCLUSION: The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Does ibuprofen, prednisolone, or amoxicillin reduce post-tonsillectomy pain in children? A prospective randomized controlled trial.

OBJECTIVE: To evaluate whether the use of anti-inflammatory or antibiotic in the postoperative period modifies pain in children undergoing tonsillectomy. METHODS: 225 children who underwent cold knife tonsillectomy ± adenoidectomy were randomized into five groups, receiving #1 metamizole/acetaminophen, #2 amoxicillin, #3 ibuprofen, #4 prednisolone, or #5 amoxicillin plus prednisolone. All groups received oral analgesics (metamizole/acetaminophen) to use as needed. Pain was monitored during the 7 days following surgery using the Parents' Postoperative Pain Measurement (PPPM) and the Faces Pain Scale - Revised (FPS-R). Pain was also indirectly evaluated by the dose of analgesics administered on each day and by the time needed to return to a solid diet. RESULTS: After losses (24%), 170 individuals were submitted for analysis. Multiple comparisons demonstrated that the evolution of pain between the different groups, as matched day-per-day, was not significantly different by either PPPM or FPS-R (p > 0.05). The instances of analgesic intake were also similar in all the groups (p > 0.05), as was the return to solid food ingestion (p = 0.41). All groups presented a similar standard of clinical improvement at intervals of 2 days (p < 0.01). Independent of postoperative pain management, patients developed significant pain up to the day 4 following surgery. CONCLUSION: The addition of amoxicillin, ibuprofen, prednisolone, or amoxicillin and prednisolone does not modify postoperative pain in children undergoing cold-knife tonsillectomy. Special pain control should be performed on the first 4 days following tonsillectomy in children.

HPV genotype is a prognosticator for recurrence of respiratory papillomatosis in children.

OBJECTIVES: This study aimed to compare the prognosis according to age, genotype or human papillomavirus (HPV) variant in patients with recurrent respiratory papillomatosis (RRP). DESIGN: Non-concurrent cohort. PARTICIPANTS: Forty one patients with RRP. SETTING: Tertiary referral hospital. MAIN OUTCOME MEASURES: Disease severity was defined by the number of surgeries performed, and Derkay score at surgeries, obtained from medical records. HPV was detected and genotyped, and HPV-6 variants were also assessed. RESULTS: Fifteen (36.58%) individuals belonged to the juvenile RRP group (JoRRP, less than 18 years), while 26 patients (63.41%) were allocated at the adult group (AoRRP, equal or more than 18 years). JoRRP patients needed, in average, a higher number of surgeries to control the disease than AoRRP patients (mean difference: 3.36). Also, JoRRP patients showed a higher Derkay score at each surgery (mean difference: 3.76). There was no significant difference in the number of surgeries when we compared patients infected with HPV-6 or HPV-11, neither in accordance to HPV-6 variants. Patients with HPV-11 presented a higher mean Derkay score at surgery than those with HPV-6 (mean difference: 4.39); when co-variated by age, we observed that this difference occurred only among JoRRP patients (mean difference: 6.15). CONCLUSIONS: Age of onset of RRP has an important impact on number of surgeries to control disease. Patients with JoRRP and HPV-11 tend to present worse Derkay score at each surgery. HPV genotype among adults and HPV-6 variants had no impact on the outcome of the disease.

Silent Infection of B and CD8+ T Lymphocytes by Influenza A Virus in Children with Tonsillar Hypertrophy.

Influenza A viruses (IAVs) cause more than 2 million annual episodes of seasonal acute respiratory infections (ARI) and approximately 500,000 deaths worldwide. Depending on virus strain and host immune status, acute infections by IAV may reach sites other than the respiratory tract. In the present study, IAV RNA and antigens were searched for in tissues of palatine tonsils and adenoids removed from patients without ARI symptoms. A real-time reverse transcriptase PCR (RT-PCR) screening revealed that 8 tissue samples from 7 patients out of 103 were positive for IAV. Positive samples were subjected to next-generation sequencing (NGS) and 3 of 8 tissues yielded complete IAV pH1N1 genomes, whereas in 5 samples, the PB1 gene was not fully assembled. Phylogenetic analysis placed tonsil-derived IAV in clusters clearly segregated from contemporaneous Brazilian viruses. Flow cytometry of dispersed tissue fragments and serial immunohistochemistry of paraffin-embedded sections of naturally infected biopsies indicated that CD20+ B lymphocytes, CD8+ T lymphocytes, and CD11c+ cells are susceptible to IAV infection. We sought to investigate whether these lymphoid tissues could be sites of viral replication and sources of viable virus particles. MDCK cells were inoculated with tissue lysates, enabling recovery of one IAV isolate confirmed by immunofluorescence, reverse transcriptase quantitative PCR (RT-qPCR), and NGS. The data indicate that lymphoid tissues not only harbor expression of IAV proteins but also contain infectious virus. Asymptomatic long-term infection raises the possibility of IAV shedding from tonsils, which may have an impact on host-to-host transmission.IMPORTANCE Influenza A virus (IAV) infections are important threats to human health worldwide. Although extensively studied, some aspects of virus pathogenesis and tissue tropism remain unclear. Here, by different strategies, we describe the asymptomatic infection of human lymphoid organs by IAV in children. Our results indicate that IAV was not only detected and isolated from human tonsils but displayed unique genetic features in comparison with those of contemporaneous IAVs circulating in Brazil and detected in swabs and nasal washes. Inside the tissue microenvironment, immune cells were shown to be carrying IAV antigens, especially B and T CD8+ lymphocytes. Taken together, these results suggest that human lymphoid tissues can be sites of silent IAV infections with possible impact on virus shedding to the population.