Introdução: A rinossinusite crônica (RSC), doença multifatorial, na qual podem estar envolvidos fatores genéticos e ambientais, ainda tem muitos aspectos obscuros na sua patogênese. A genética tem se mostrado promissora na elucidação dessa complexa doença. Alguns estudos apontam que a expressão de interleucina (IL) 22 se apresenta reduzida em pacientes com RSC, podendo resultar também na redução da barreira epitelial e diminuição da produção de citocinas pró-inflamatórias Th1. Objetivos: Pesquisar a frequência dos polimorfismos no gene IL22RA1 (receptor subunidade alfa um da interleucina 22) em pacientes portadores de RSC com e sem pólipos nasais e em indivíduos normais, utilizando a técnica de sequenciamento, pelo método de Sanger, para análise de mutações; comparar as frequências dos polimorfismos encontrados no gene IL22RA1 entre os grupos e com a literatura médica e também comparar a técnica de Sanger com outras técnicas convencionais descritas na literatura. Casuística e Métodos: Foram avaliados 247 pacientes, no período de maio de 2011 a fevereiro de 2016, subdivididos em três grupos: 122 pacientes portadores de RSC com pólipos nasais (RSCcPN), 21 casos de RSC sem pólipos nasais (RSCsPN) e 104 voluntários sem sintomatologia nasal. Foram colhidas amostras de sangue venoso periférico de todos os casos e controles, e realizada a extração de DNA, com posterior análise das mesmas. Após a exclusão das perdas, restaram 70 casos de RSCcPN, 14 de RSCsPN e 68 controles. Resultados: O sequenciamento apontou 10 polimorfismos no gene IL22RA1, nos exon 2 (rs10903022, c.113_114insA/Q26Pfs*11, c.74T>A e c.141C>A), exon 4 (rs17852649), exon 5 (rs16829204), exon 6 (rs142356961) e exon 7 (rs17852648, rs34967816 e rs3795299). Os polimorfismos encontrados nos exons 2 (em homozigose), 5 e 6 foram exclusivos do grupo das patologias analisadas (RSC com e sem PN), sendo as duas últimas consideradas variáveis não sinônimas, ou seja, com capacidade de alterar a estrutura da proteína, podendo produzir impacto na patogênese da RSC. A alteração do exon 6 foi a única variante encontrada, com frequência do alelo menor (MAF) inferior a 0,01, exclusiva do grupo RSCcPN. Conclusões: Foram detectados três polimorfismos no gene IL22RA1, que até o momento não estão descritos na literatura, sendo a inserção c.113_114insA/Q26Pfs*11, possivelmente patogênica, com frequência maior nos grupos com RSC. O polimorfismo rs17852649 em heterozigose no exon 4, foi o único com diferença estatística, com predominância do alelo mutado no grupo controle, podendo conferir proteção contra o fenótipo. Também se destaca o polimorfismo rs142356961, no exon 6, do tipo não sinônimo, ou seja, capaz de alterar a estrutura final da proteína, com índice MAF<0,01, sendo exclusiva de pacientes negros portadores de RSCcPN. Estudos de replicação e com maiores coortes serão necessários para determinar se os achados do presente estudo se deram ao acaso. / Introduction: Chronic rhinosinusitis (CRS), a multifactorial disease, with genetic and environmental factors that may be involved, still have many aspects of its pathogenesis unknown. Genetics has shown itself promising in the elucidation of this complex disease. Some studies have indicated that the expression of IL-22 is reduced in patients with CRS, which may result in reduction of the epithelial barrier and decrease in the production of Th1 proinflammatory cytokines. Objectives: To investigate the frequency of polymorphisms in the IL22RA1 gene in patients with chronic rhinosinusitis with and without nasal polyps and in individuals without these pathologies, using the Sanger sequencing technique for mutation analysis; to compare the frequencies of the polymorphisms found in the IL22RA1 gene between the groups and the medical literature and also to compare the Sanger technique with other conventional techniques in the medical literature. Casuistic and Methods: From May 2011 to February 2016, 247 patients were evaluated, subdivided into three groups: 122 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), 21 cases of chronic rhinosinusitis without nasal polyps (CRSsNP) and 104 volunteers without nasal symptoms. Samples of peripheral venous blood were collected from all cases and controls, and DNA extraction was performed, with subsequent analysis at the Molecular Genetics Laboratory - Ribeirão Preto Medical School Blood Center - USP. After the loss exclusion, there were 70 cases of CRSwNP, 14 CRSsNP and 68 controls. Results: Sequencing indicated 10 polymorphisms in the IL22RA1 gene, exon 2 (rs10903022, c.113_114insA / Q26Pfs * 11, c.74T> A and c.141C> A), exon 4 (rs17852649), exon 5 (rs16829204), exon 6 (rs142356961) and exon 7 (rs17852648, rs34967816 and rs3795299). Polymorphisms in exons 2 (in homozygosis), 5 and 6 were exclusive from the analyzed pathologies group (RSC with and without NP), the latter two being considered non-synonymous variables, that is, with capacity to alter the protein structure, being able to produce impact on the pathogenesis of CRS. The exon 6 alteration was the only variant found, with the minor allele frequency (MAF) under 0.01, exclusive of the RSCcPN group. Conclusions: Three polymorphisms were detected in the IL22RA1 gene, which until now are not described in the literature, and the possibly pathogenic insert c.113_114insA / Q26Pfs * 11, with a higher frequency in the groups with CRS. The polymorphism rs17852649 in heterozygosis in exon 4 was the only one with a statistical difference, with predominance of the mutated allele in the control group, which could confer protection against the phenotype. Also notable is the polymorphism rs142356961, in exon 6, of the non-synonymous type, that is, capable of altering the final structure of the protein, with MAF index <0.01, being exclusive in black patients with chronic rhinosinusitis with nasal polyps. Replication studies and larger cohorts are necessary to rule out the findings at random.

No description available.

In der vorliegenden Arbeit wurde Gewebe aus den Nasennebenhöhlen von Patienten mit Nasenpolypen untersucht. Außerdem wurden Zusammenhänge zwischen den Zellpopulationen und den Angaben zu allergischen Erkrankungen und wiederholtem Auftreten der Polypen analysiert. Es fand sich eine interindividuell unterschiedlich starke Infiltration mit eosinophilen Granulozyten. Es konnten keine Unterschiede in der prozentualen Verteilung von eosinophilen Granulozyten im Polypengewebe bei allergischen/ nichtallergischen Patienten oder Patienten mit/ ohne Rezidiv nachgewiesen werden. Die Untersuchungen erfolgten mit dem Laser Scanning Zytometer (LSC), das mit der Standardmethode, der Begutachtung mittels Lichtmikroskop, verglichen wurde. Mit der beschriebenen Methode erfolgte die Untersuchung von Polypengewebe nach einem speziell für diese Anwendung entwickelten Protokoll. Die Ergebnisse korrelierten gut mit den Ergebnissen der Lichtmikroskopie. Aufgrund der Weiterentwicklung des LSC und der ständig wachsenden Anzahl der Nachweismöglichkeiten der an der Polyposis nasi beteiligten Zytokine stellt das LSC eine ideale Methode für die Erforschung der Pathogenese von chronischen Entzündungen der Nasennebenhöhlen dar.

In der vorliegenden Arbeit wurde Gewebe aus den Nasennebenhöhlen von Patienten mit Nasenpolypen untersucht. Außerdem wurden Zusammenhänge zwischen den Zellpopulationen und den Angaben zu allergischen Erkrankungen und wiederholtem Auftreten der Polypen analysiert. Es fand sich eine interindividuell unterschiedlich starke Infiltration mit eosinophilen Granulozyten. Es konnten keine Unterschiede in der prozentualen Verteilung von eosinophilen Granulozyten im Polypengewebe bei allergischen/ nichtallergischen Patienten oder Patienten mit/ ohne Rezidiv nachgewiesen werden. Die Untersuchungen erfolgten mit dem Laser Scanning Zytometer (LSC), das mit der Standardmethode, der Begutachtung mittels Lichtmikroskop, verglichen wurde. Mit der beschriebenen Methode erfolgte die Untersuchung von Polypengewebe nach einem speziell für diese Anwendung entwickelten Protokoll. Die Ergebnisse korrelierten gut mit den Ergebnissen der Lichtmikroskopie. Aufgrund der Weiterentwicklung des LSC und der ständig wachsenden Anzahl der Nachweismöglichkeiten der an der Polyposis nasi beteiligten Zytokine stellt das LSC eine ideale Methode für die Erforschung der Pathogenese von chronischen Entzündungen der Nasennebenhöhlen dar.

Objective: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC). - Methods: A total of 75 individuals participated (age 19–78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin’ Sticks test battery. Trigeminal sensitivity was assessed with CO₂ detection thresholds.Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO₂) stimuli using high-precision air-dilution olfactometry. - Results: In comparison to HC, AR patients had lower CO₂ thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC. - Conclusion: AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups.

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Results: Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r(2) = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r(2) = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-gamma signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, T(H)1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045). Conclusions: A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

Rinossinusite crônica (RSC), com ou sem pólipo nasal é uma inflamação crônica da mucosa nasal e seios paranasais, cujo tratamento muitas vezes pode ser a cirurgia. Vários vírus respiratórios são detectados em biópsias de pólipo nasal, concha média e mucosa do seio maxilar de pacientes com a doença, mas seu papel no desencadeamento dessa inflamação não é claro. O Objetivo do presente estudo teve como objetivo localizar e caracterizar in situ sítios de infecção por rinovírus (HRV), metapneumovírus (HMPV) e vírus sincicial respiratório (HRSV), detectar se há replicação dos mesmos, caracterizar as células, em tecidos de pólipo nasal, concha média e mucosa do seio maxilar removidas cirurgicamente de pacientes com rinossinusite crônica. Tecidos de 17 pacientes positivos por qPCR foram utilizados para identificar a localização e caracterização dos sítios de infecção, além de avaliar a atividade replicativa, onde proteínas de capsídeo viral foram detectadas por imunohistoquimica (IHQ). Para identificação das células infectadas pelos vírus estudados, foi realizada a técnica de SIMPLE. Os resultados revelaram positividade em 7 de 11 amostras positivas para HRV analisadas por PCR em tempo real, sendo encontrada a proteína viral em 5 amostras de pólipo nasal, uma amostras da mucosa do seio maxilar e uma em concha média. Cinco amostras tiveram seu genoma detectado no PCR em tempo real para HMPV, sendo que 3 delas tiveram marcação da proteína por IHQ, uma amostra positiva em cada tecido estudado. Em um total de 4 amostras, houve detecção da proteína F de HRSV em 3 delas, sendo 2 em pólipo nasal e uma concha média. Em todas as reações de IHQ foram incluídos controles positivos e negativos adequados. Depois da detecção das proteínas desses vírus respiratórios, as amostras tiveram seus fenótipos testados, células produtoras de muco e epiteliais ciliadas, mastócitos, células dendríticas, eosinófilos e linfócitos através da técnica SIMPLE. Foi demonstrado que há evidência de replicação de rinovírus, metapneumovírus e vírus sincicial respiratório no epitélio e no estroma tecidual de pólipo nasal, concha média e mucosa do seio maxilar. Foram detectadas células CD4+ e CD123+ infectadas por HRSV, evidenciadas pela marcação da proteína estrutural viral F. Adicionalmente, observamos células CD4+, CD14+ e CD20+, além de células residentes em glândulas produtoras de muco, infectadas com HRV utilizando anticorpo anti-VP1 viral. Para HMPV a infecção se limitou ao epitélio superficial dos tecidos e glândulas produtoras de muco. Esses dados revelam uma possível persistência de HRV, HRSV e HMPV em tecidos de pacientes com rinossinusite crônica, que podem assim serem reservatórios de vírus na ausência de sintomas de infecção aguda. / Chronic rhinosinusitis (CRS) with or without nasal polyp is a chronic inflammation of the nasal mucosa and paranasal sinuses, whose treatment can often be surgery. Several respiratory viruses are detected in biopsies of nasal polyp, middle shell and maxillary sinus mucosa of patients with the disease, but their role in triggering this inflammation is unclear. The objective of the present study was to locate and characterize in situ sites of infection by rhinovirus (HRV), metapneumovirus (HMPV) and respiratory syncytial virus (HRSV), to detect if there is replication of the same, to characterize the cells in nasal polyp tissues , middle shell and maxillary sinus mucosa surgically removed from patients with chronic rhinosinusitis. Tissues from 17 patients positive for qPCR were used to identify the location and characterization of infection sites, and to evaluate the replicative activity, where viral capsid proteins were detected by immunohistochemistry (IHC). To identify the cells infected by the viruses studied, the SIMPLE technique was performed. The results revealed positivity in 7 of 11 HRV positive samples analyzed by real-time PCR. Viral protein was found in 5 nasal polyp samples, one in the maxillary sinus mucosa and one in the middle shell. Five samples had their genome detected in the realtime PCR for HMPV, 3 of them had protein marking by IHC, a positive sample in each tissue studied. In a total of 4 samples, HRSV F protein was detected in 3 of them, 2 in nasal polyp and 1 medium concha. All positive and negative controls were included in all IHC reactions. After the detection of the proteins of these respiratory viruses, the samples had their tested phenotypes, mucus-producing cells and ciliated epithelial cells, mast cells, dendritic cells, eosinophils and lymphocytes through the SIMPLE technique. It has been demonstrated that there is evidence of rhinovirus, metapneumovirus and respiratory syncytial virus replication in the epithelium and in the tissue stroma of the nasal polyp, middle concha and maxillary sinus mucosa. CD4 +, CD14 + and CD20 + cells were detected, as well as cells residing in mucus-producing glands, infected with HRV using anti-viral VP1 antibody. For HMPV the infection was limited to the superficial epithelium of the tissues and mucus producing glands. These data reveal a possible persistence of HRV, HRSV and HMPV in tissues of patients with chronic rhinosinusitis, who may thus be virus reservoirs in the absence of symptoms of acute infection.

Introdução: Várias controvérsias e diversos questionamentos existem sobre a fisiopatogenia e o melhor tratamento para a doença Rinossinusite Crônica (RSC). Alguns estudos apontam que a dosagem de Óxido Nítrico (ON) do ar expirado pelas narinas pode contribuir no diagnóstico e seguimento desta afecção. Objetivos: Determinar se há diferença na dosagem de ON expirado pelas narinas de pacientes com RSC e indivíduos sem RSC e estabelecer correlação entre os achados clínicos, exames complementares e a quantidade de ON encontrada nos pacientes. Casuística e Método: Estudo retrospectivo com 104 pacientes com RSC e 35 indivíduos sem RSC, atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, entre os anos de 2013 e 2016. Foram realizadas dosagens de ON do ar expirado pelas narinas dos pacientes e controles. Posteriormente, realizou-se correlação entre os achados clínicos e exames complementares dos pacientes e a quantidade de ON obtida. Resultados: As dosagens de ON nos pacientes com RSC foram significativamente menores em relação aos controles. Também se observou relação entre dosagem de ON e intensidade de sintomas, queixas clínicas, achados endoscópicos e tomográficos, e o número de seios acometidos, quando realizada a cirurgia. Conclusão: Diante dos resultados obtidos, o que mais chama atenção é a possibilidade de avaliação dos pacientes portadores de RSC com ou sem pólipo nasal por um método aqui padronizado, de fácil manuseio pelos técnicos e pacientes, de baixo custo, não invasivo e que permite também comparar resultados antes e após o tratamento. / Introduction: Chronic rhinosinusitis (CRS) is a disease of the upper respiratory tract with great questions regarding its clinical management. Nitric Oxide (NO) dosing by the air expiratory by the nostrils, can contribute to the diagnosis and follow-up of this affection. Objectives: To determine if there is a difference in the NO expiratory dose in the nostrils of people with CRS and people who do not have CRS, and to establish a clinical correlation between the findings and the amount of NO found in the patients. Casuistic and Method: Retrospective study conducted in 104 patients with CRS and 35 individuals without CRS at Hospital of Clínics of Ribeirão Preto Medical School, University of São Paulo. Between the years of 2013 and 2016. NO dosages were performed by expiratory air from the nostrils of people with and without CRS, and, later an analysis of the clinical findings of the patients with the amount of NO obtained was performed. Results: The NO dosages of patients with CRS were significantly lower in relation to those without CRS. We also found a relationship between the NO dosage, and the intensity of the symptoms, clinical complaints, endoscopic and tomographic findings, and the number of sinuses involved in the surgery. Conclusions: In view of the results obtained, what is most striking is the possibility of evaluating patients with CRS with or without PN, using a low-cost, noninvasive method that is easy to handle by technicians and patients. before and after treatment.

Abstract: The role of bacterial biofilms in patients with persistent CRS is of growing concern. The limited efficacy of some medical and surgical treatments for CRS illustrates the need for further progress in this area. The current treatments of chronic rhinosinusitis are concentrated on medical +/- surgical therapy. In this thesis, we consider two methods performed in chronic rhinosinusitis, endoscopic sinus surgery and long term low-dose macrolide therapy, and consider how they can affect bacterial biofilms. The effect of endoscopic sinus surgery on bacterial biofilms and the clinical impact of this condition on CRS patients may be far more profound than we can currently understand. To understand the impact of ESS on bacterial biofilms, we have performed the first prospective study to evaluate the effect of ESS on bacterial biofilms in patients with CRS and patients’ clinical outcomes after 3 months follow-up. We have shown that ESS results in a statistically significant improvement in QoL, subjective and objective outcome measures. In terms of bacterial biofilms, the mean OD630nm of isolates was significantly reduced after 3 months follow-up (p=0.043). No correlations between the reduction of bacterial biofilms with any of the objective, subjective and QoL outcomes were seen in our study. Macrolides have demonstrated their anti-inflamatory effects in the treatment of diffuse panbronchiolitis, asthma, cystis fibrosis and chronic rhinosinusitis. In recent years, there are a number of in vitro studies supporting the anti-biofilm effects of macrolide antibiotics, especially at sub-MICs level. These have shown that macrolides alter the outer membrane, lipopolysaccharide of biomass and inhibit the expression of other bacterial virulence factors which may disrupt the adherence of bacteria to form biofilms. Long term low dose macrolide therapy, therefore, may transform bacterial biofilms from the protected organized form into the plantonic form. In this thesis, we also report the first in vivo efficacy of long term low dose macrolides on bacterial biofilms in patients with CRS. Patients receiving oral macrolide showed significant improvements in subjective, objective and QoL scores following a 12 week course. Nasal swabs were taken from CRS patients at the first visit and 3 months after macrolide therapy. Using the microtiter biofilm assay, these swabs showed a reduction in the mean OD630nm of isolates in 8/12 patients. While it is well-known that bacterial biofilms are established in CRS patients, the relationship between the improvement of clinical symptoms and the severity of bacterial biofilm is less clear.

Abstract Acute rhinosinusitis (ARS) is a common condition often treated with antibiotics, even though the cause is usually viral. Despite the commonness of ARS, there is limited evidence on the development and diagnosis of bacterial cases. So far, we lack prospective studies where the bacterial cause would have been confirmed with a bacterial culture of the paranasal sinus aspirate. The purpose of the study was to investigate the course of ARS with a prospective inception cohort study among young adults with ARS, using sequential and standardized methods. To differentiate viral and bacterial ARS, maxillary sinus aspiration and a bacterial culture were used as a reference standard for bacterial ARS. Fifty conscripts with ARS were recruited between February and April 2012. Eight patients (16%) had a positive culture from the maxillary sinus aspirate at 9–10 days and thus, had bacterial ARS. Viral and bacterial coinfection resulted in extensive paranasal mucosal abnormalities and increased symptoms during the episode. The paranasal mucosal abnormalities developed rapidly and remained relatively constant during the episode in both bacterial and non-bacterial ARS. A change in inflammatory biomarker levels indicated both local and systemic inflammatory responses, which were strongest at the onset of symptoms. Symptoms or their changes were of little use in diagnosing bacterial ARS, but secretion seen in the nasal cavity, posterior pharynx or middle meatus predicted bacterial ARS quite well. These results suggest that bacterial infection may modify symptoms and paranasal abnormalities already at the beginning of an ARS episode, although the spread of paranasal abnormalities may not be an etiological factor in the development of bacterial ARS. ARS involves local and systemic inflammatory responses, which are strongest at the beginning of the episode. Examination of the nose and throat is recommended for diagnosing bacterial ARS. / Tiivistelmä Nenän äkillinen sivuontelotulehdus on tavallinen tauti, jonka hoitoon käytetään paljon antibiootteja, vaikka sen aiheuttaja on useimmiten virus. Bakteerin aiheuttaman tautimuodon kehittymisestä ja diagnostiikasta ei ole julkaistu tutkimuksia, joissa potilaita olisi seurattu taudin alusta lähtien ja bakteerin olemassaolo olisi varmistettu nenän sivuontelosta otetulla bakteerinäytteellä. Tämän väitöskirjatyön tarkoituksena oli selvittää nenän äkillisen sivuontelotulehduksen kulkua käyttämällä toistuvia, standardisoituja menetelmiä. Bakteerin aiheuttama tauti todettiin poskiontelopistolla ja bakteeriviljelyllä. Tutkimukseen osallistui viisikymmentä (50) äkilliseen ylähengitystieinfektioon sairastunutta varusmiestä keväällä 2012. Kahdeksalla (16 %) potilaalla todettiin bakteerin aiheuttama tauti poskiontelopiston avulla 9–10 päivää oireiden alkamisen jälkeen. Viruksen ja bakteerin sekainfektio aiheutti laajemmat sivuonteloiden tulehduslöydökset ja voimakkaammat oireet kuin pelkän viruksen aiheuttama tauti. Sivuonteloiden tulehduslöydökset kehittyivät nopeasti ja pysyivät sekä bakteerin että viruksen aiheuttamassa taudissa varsin muuttumattomina. Tulehdusmerkkiaineiden muutokset osoittivat sekä paikallisen, että yleisen tulehdusreaktion, jotka olivat voimakkaimmillaan taudin alussa. Oireet tai niissä taudin aikana tapahtuneet muutokset eivät osoittautuneet hyviksi merkeiksi bakteerin aiheuttaman taudin toteamiseksi, mutta eritteen näkyminen nenässä, nielussa tai keskikäytävässä ennakoi hyvin bakteerin aiheuttaman sivuontelotulehduksen toteamista. Bakteeri saattaa vaikuttaa oireisiin ja sivuonteloiden tulehduslöydöksiin jo nenän äkillisen sivuontelotulehduksen alussa, mutta tulehduslöydösten laajuus ei välttämättä liity bakteerin aiheuttaman taudin kehittymiseen. Nenän äkilliseen sivuontelotulehdukseen liittyy paikallinen ja yleinen tulehdusreaktio, jotka ovat voimakkaimmillaan taudin alussa. Potilaan nenän ja nielun tutkiminen on tärkeää bakteerin aiheuttaman nenän sivuontelotulehduksen toteamiseksi.