Twenty publications are submitted. All deal with the issues of control of two ends of the spectrum of immune-mediated respiratory disorders in children, namely atopic (asthma and allergic rhinitis) and HIV-related lung disease. This submission summarises the research by the author into this spectrum of lung diseases of children in South Africa, highlighting the diversity of conditions that are not only clinically important, but also common. Understanding of all conditions is required to improve the health of children in this region. Management of chronic conditions requires two major end points - adequate and timely diagnosis and - management to control the condition. The author has a passion for improving the quality of life of children and firmly believes that the research findings will, and have, led to transformation in management of both these common disorders. This document follows the progression of the authors research work and highlights how interesting and important is the scope of two disorders which could be thought to have a central origin, namely in the T-cell. T-cells form the basis of cellular immunity and an excess of T-helper 2 cell activity promotes atopy, whilst the human immunodeficiency (HI) virus infects T-helper cells and promotes cellular immune deficiency and its attendant clinical disorders. The author’s research work is not based on the immunological basis of these conditions but does deal with the clinical implications and especially aspects relating to control of these two extremes of a clinical spectrum of disorders. To take the clarity of two diseases at the end of a spectrum to its natural conclusion these extremes are defined in aetiology or pathophysiological differences (excess versus suppression of the immune system), occurring in the affluent and poor alike versus just the poor, control being required to improve quality of life versus to save lives and finally that management requires anti-inflammatory therapy versus antibiotic and anti-infective therapy. For the eight publications based on atopic respiratory disease in children the themes are firstly that children with asthma and chronic rhinitis are diagnosed late, that most individuals with these conditions are not well controlled and finally that the reasons for lack of control are becoming obvious. For the first time, the significant lack of asthma and allergic rhinitis control in South Africa is documented. These studies suggest that, like surveys from the rest of the world, asthma control is seriously under-estimated and neglected in all asthmatics in South Africa, in both the privileged and the under-privileged. The research also defines reasons for poor asthma and allergic rhinitis control in this region. As in many studies published from around the world it is now evident that poor asthma and allergic rhinitis control cannot be blamed on any one source. A multitude of reasons underlie this phenomenon and each of the subsequent papers in this section illustrates attempts at defining these principles. The three most important reasons for poor control are probably that most asthmatics are managed in the wrong hands (by doctors who don’t understand adequate control and who aren’t empowered to use the correct therapy), that control may actually be a pipe dream and practically difficult to do or even impossible to achieve and lastly that the allergic basis of asthma is over emphasised and may not in fact determine all asthma. The subsequent papers summarise research work in the field of HV infection in children and exposes the opposite end of a spectrum of Paediatric respiratory disease and highlight research into the conditions common in HIV-infected children. Eleven papers are presented. For the diseases associated with the HI virus the major complications of inadequate diagnosis and prevention in children are acute pneumonia (especially severe pneumonia) and bronchiectasis. Bronchiolitis is not common in HIV infected children, despite epidemics of this condition in non-infected children. Passive smoking does not aggrevate or worsen disease progression in children. The complications of HIV related diseases in children require the same principles of adequate diagnosis and control as would apply to the chronic atopic conditions. Once the author delved into the disorders at the other end of the clinical spectrum, namely those associated with immune deficiency secondary to HIVinfection he faced the question of a possible relationship between the conditions. One submission explores that relationship. This research has a unique perspective, conferred by the fact that these two conditions do not occur to the same extent anywhere else in the world. Atopic respiratory conditions and HIV-related lung diseases occur side by side in abundance in this region. This perspective has created a clarity for research to address the two most important aims in clinical medicine, namely to diagnose correctly and then to manage the condition so that control is achieved. These must be universal principles of the successful practice of medicine. / Thesis (DSc)--University of Pretoria, 2013. / gm2013 / Paediatrics and Child Health / unrestricted

Background. Seasonal allergic rhinitis (SAR) is a chronic disease affecting about 23% of the European population with increasing prevalence rates. Beside classical symptoms (i.e. sneezing, nasal congestion), patients frequently complain about subjective impairments in cognitive functioning during periods of acute allergic inflammation. However, objective evidence for such deficits or the role of potential modulators and underlying mechanisms is limited. The present study aimed to investigate the effect of SAR on attention-related cognitive processes. In addition, relationships between attention performance, sleep and mood disturbances as well as specific disease characteristics as potential modulators of this link were explored. Method. SAR patients (n = 41) and non-allergic healthy controls (n = 42) completed a set of attention tasks during a symptomatic allergy period and during a non-symptomatic period. Influences of sleep, mood, total immunoglobulin E (IgE) levels and individual allergy characteristics on cognitive performance were evaluated. Results. Compared to healthy controls, SAR patients had a slower processing speed during both symptomatic and nonsymptomatic allergy periods. Additionally, they showed a more flexible adjustment in attention control, which may serve as a compensatory strategy. Reduction in processing speed was positively associated with total IgE levels whereas flexible adjustment of attention was linked with anxious mood. No association was found between SAR-related attention deficits and allergy characteristics or sleep. Conclusions. SAR represents a state that is crucially linked to impairments in information processing and changes in attentional control adjustments. These cognitive alterations are more likely to be influenced by mood and basal inflammatory processes than sleep impairments or subjective symptom severity.

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: Allergic sensitization is the most important risk factor for asthma and rhinitis among children, adolescents and young adults. Less is known about the incidence and remission of allergic sensitization, particularly in older adults. Furthermore, it is not clear if the earlier documented increase in prevalence of allergic sensitization continues. This thesis is focused on prevalence, incidence and remission of allergic sensitization to airborne allergens among adolescents and adults as well as on time trends in prevalence among adults. Furthermore, associated risk factors and the relation of allergic sensitization to asthma and rhinitis were assessed. Methods: In the study of children and adolescents, incidence, remission and prevalence of allergic sensitization were assessed in a cohort study of schoolchildren, aged 7-8 years (y) at baseline. In the studies of adults, incidence and remission of allergic sensitization were assessed in a randomly selected adult population sample in 1994 (n=664) aged 20-69 y, which was followed up in 2004 (n=555). Trends in prevalence of allergic sensitization were assessed by comparing two cross-sectional studies; the cohort from 1994 and another randomly selsected population sample examined in 2009 (n=737). The relation of allergic sensitization to asthma and rhinitis was determined in the adult cohort in 2009. Allergic sensitization was assessed by skin prick test (SPT) with ten common airborne allergens at ages 7-8, 11-12 and 19 y in the cohort of children and in the participants ≤ 60 y in the adult cohorts. Specific IgE to nine airborne allergens was analyzed in the adult cohorts in 2004 and 2009. Risk factors for allergic sensitization and variables defining respiratory disease and symptoms were assessed by questionnaires in the cohort of children and by structured interviews in the adult cohorts. Results: The 10-year cumulative incidence of allergic sensitization among the adults from 1994 to 2004 was 5%, while remission was 32%. In both adult cohorts, the prevalence of allergic sensitization was highest among young adults, aged 20-29 y, 55% and 61% and decreased significantly with increasing age. Among children and adolescents, both incidence and persistence of allergic sensitization were high, and the prevalence of allergic sensitization increased by age from 21% at age 7-8 y to 42% at age 19 y. Multisensitization at age 19 y was strongly associated with early onset of sensitization. The prevalence of sensitization to the major specific allergens birch, timothy, cat and dog as well as multisensitization (from 40% in 1994 to 56% in 2009, p=0.002) increased significantly from 1994 to 2009 among the adults. Sensitization to any allergen increased from 35% to 39%, however not significantly (p=0.13). A family history of allergic rhinitis was strongly and consistently associated with allergic sensitization in all ages. Male sex and urban living were significantly positively and birth order and furry animals at home in childhood were negatively associated with onset of sensitization before the age of 7-8 y, but not with onset of sensitization from 11-12y to 19 y. Young adult age and urban living were significant factors associated with allergic sensitization in adult age. Sensitization to any animal was significantly positively associated with current asthma (OR4.80 (95% CI 2.68-8.60)), whereas both sensitization to any pollen (OR 4.25 (2.55-7.06)) and any animal (OR 3.90 (95% CI 2.31-6.58)) were associated with current allergic rhinitis. The association between allergic sensitization and allergic rhinitis was strongest in young adult age and decreased with increasing age, while asthma was similarly associated with sensitization to any animal across all adult ages. Among asthmatics, the prevalence of allergic sensitization decreased with increasing age of asthma onset. Conclusion: Both incidence and persistence of allergic sensitization were high among children and adolescents explaining the increase in prevalence by increasing age. An inverse pattern with low incidence and high remission of allergic sensitization was seen among adults. The decrease in prevalence of allergic sensitization by increasing adult age might at least partly be explained by normal ageing and not only by an effect of year of birth (cohort effect). The significant increase in prevalence of sensitization to the specific allergens explained the significant increase in multisensitization over 15 years. A family history of allergy was the strongest and the only consistent risk factor for allergic sensitization in all ages. The prevalence of allergic sensitization decreased with increasing age of asthma onset among adult asthmatics.

Genome-scale ordered RNA structure (GORS) was first identified in 2004. It refers to the presence of secondary structure throughout the length of the RNA genomes of certain genera of RNA virus families, as predicted by bioinformatic analysis. It was also observed that the viruses containing GORS were able to establish persistent infections in their natural hosts, raising the possibility that the presence of GORS could play a role in viral avoidance of the innate immune system. This thesis describes the first study of GORS and its possible role in persistence. Two GORS viruses have been studied, equine rhinitis A virus (ERAV) and murine norovirus (MNV). A 55% seroprevalence of ERAV has been determined in a cohort of Scottish horses indicating a wide exposure to the virus. Equine faecal samples were screened for ERAV by PCR with the intention of identifying a virus, possibly from a persistently infected animal, which would not have undergone any cell culture adaptations as laboratory strains have. Newly identified viruses would then be sequenced, their secondary structures predicted and further studies carried out. Unfortunately, none of the 50 faecal samples screened were positive and clinical isolates of ERAV provided by the Animal Health Trust were sequenced but were identical to laboratory strains, so the study then focussed on MNV. Prevalence of MNV in laboratory mice was determined by PCR of faecal samples to be 67%. MNV was also discovered in the faeces of a pet shop mouse and a wild wood mouse (Apodemus sylvaticus). The complete genomes of 4 laboratory mouse MNVs, the pet shop mouse and wood mouse MNVs were sequenced. Phylogenetic analysis showed the wood mouse MNV had a p distance of 23% from other MNVs, although the laboratory mice and pet shop mouse were closely related to other MNVs. Structural analysis of the genomes of 6 sequenced MNVs, including the wood mouse virus, showed all were GORS viruses. A laboratory strain of MNV, MNV-3, was serially passaged in RAW 264.7 cells to test the hypothesis that in an animal with an intact immune system, there is a pressure for GORS viruses to maintain their genomic RNA structure as a means of immune avoidance, and that cell culture adaptation would attenuate the degree of secondary structure. The complete genome of passage 33 was sequenced, which revealed 7 base mutations, a mutation rate of 0.1 %, which was not considered significant enough to have affected the degree of secondary structure. In order to assess if structured and unstructured RNA behaved differently in cells, replication deficient RNA transcripts were made from the infectious clones of a panel of GORS and non-GORS viruses. These transcripts were electroporated into cells and their rate of decay measured, but there was no difference between the GORS and non-GORS transcripts. The full length and 4 kilobase transcripts were transfected into NIH3T3 cells and the degree of interferon-β induction measured by quantitative PCR and a luciferase reporter assay. The IFN-β response differed across the panel of viruses, and although none of the GORS viruses induced strongly, the non-GORS viruses were variable in their ability to induce an IFN-β response, some inducing strongly, other not at all. This result indicates that during exposure of viral genomes in the cytoplasm during infection, GORS-virus RNAs are unlikely to induce an interferon response, possibly contributing to their ability to persist. It is unclear why some non-GORS-viruses failed to induce IFN and there are likely to be other contributory factors.

Introdução: surtos de asma, por poeira da soja, têm sido relatados, havendo casos fatais. Objetivo: correlacionar exposição, sensibilização e alergia respiratória a esta, no Brasil. Métodos: 590 voluntários (testes de punctura e dosagem de IgE específica). Resultados: operários da indústria apresentaram 15% de. sensibilização à soja. Caminhoneiros 22%. Moradores no entorno da indústria 22% enquanto aqueles que residem distantes 6%. .Na região agrícola distante das plantações 13% e em meio à soja 28% com 5% de sensibilizados somente à soja. O percentual de IgE positivas para soja foi 16%. Houve marcante sensibilização aos fungos. Conclusão: A prevalência de sensibilização à soja demonstra o impacto desse tipo de poluição. A sensibilização aos fungos que colonizam a soja estocada não deve ser subestimada / Background: Asthma outbreaks, by soybean dust inhalation, have been reported fatal cases.. Objective: To correlate exposure and sensitization to soybean dust in Brazil.. Methods: 590 volunteers exposed to soy dust. Prick skin tests were performed and specific IgE were measured in sera.. Results: the workers from the oil refinery had sensitization to soy (15%). Truck drivers 22%. Industry neighborhood 22%. and people who live far from this place presented only 6%. People from agricultural area far from the soy plantations 13% and in the middle of the soy 28%.with 5% sensitized only by soybean . Positive IgE was 16 %. Conclusion: a high prevalence of sensitivity to soybean hull demonstrates the impact of this kind of pollution. The sensitization to the fungi which colonize soybean storage can not be underestimated

Diferentes estudos têm demonstrado uma maior prevalência de rinite alérgica nas áreas urbanas, sugerindo um efeito decorrente da exposição à poluentes. Por esta razão, resolvemos estudar a relação da poluição atmosférica com os achados do citológico nasal em 11 pacientes com rinite alérgica nas quatro estações do ano e compará-los a 12 indivíduos normais. No verão, observamos um aumento significante de eosinófilos no grupo alérgico (p = 0,007) e um predomínio de células ciliadas no grupo controle (p = 0,021). No outono, houve um predomínio de neutrófilos no grupo controle (p = 0,027). No inverno, ocorreu um aumento de neutrófilos (p = 0,015) no grupo controle. Houve um aumento das células caliciformes (p = 0,019) no grupo alérgico. Na primavera, ocorreu um aumento dos neutrófilos (p = 0,025) no grupo controle / Different studies have demonstrated an increase in the prevalence of allergic rhinitis in urban areas, suggesting an effect resulting from exposure to pollutants. Therefore, we studied the relationship between atmospheric pollution and nasal cytological findings in 11 patients with allergic rhinitis during the four seasons of the year compared to 12 normal individuals. In summer, a significant increase in eosinophils was observed in the allergic group (p = 0.007) and there was a predominance of ciliated cells in the control group (p = 0.021). In autumn, neutrophils predominated in the control group (p = 0.027), and an increase in neutrophils (p = 0.015) was observed in winter. An increase in goblet cells (p = 0.019) was observed in the allergic group. In spring, there was an increase of neutrophils (p = 0.025) in the control group

INTRODUÇÃO: O conhecimento da prevalência das doenças alérgicas é de fundamental importância para a instituição de medidas para sua prevenção. Vários métodos têm sido utilizados para este fim, sendo que recentemente o questionário padronizado ISAAC (International Study of Asthma and Allergies in Childhood) tem permitido a comparação dos dados epidemiológicos em várias regiões. Os OBJETIVOS deste estudo foram: avaliar a prevalência da asma, rinite e eczema atópicos e sintomas relacionados, entre escolares de 6 a 7 anos, da região oeste da cidade de São Paulo, utilizando-se o questionário escrito ISAAC e comparar os dados encontrados com aqueles obtidos na fase I do Estudo ISAAC em São Paulo, examinando tendências temporais na prevalência das doenças alérgicas. MÉTODOS: Entre junho e outubro de 2002 foi aplicado questionário escrito ISAAC em 3.312 alunos. As diferenças entre proporções foram avaliadas pelo Teste do Qui-quadrado e quando necessário o Teste Exato de Fisher, sendo também calculados a Razão das Chances (Odds Ratio OR) e intervalo de confiança 95% (IC 95%) entre os sexos e na associação das doenças alérgicas. Os valores de p < 0,05 foram considerados de significância estatística. Após obtenção dos resultados, procedeu-se a nova análise, convocando-se uma amostra dos alunos que não haviam devolvido o questionário, sendo estes novos resultados considerados na análise final. RESULTADOS: As prevalências encontradas foram: asma de 24,4%, diagnóstico médico de asma 5,7%, diagnóstico de asma provável 21,5%, rinite de 25,7%, rinoconjuntivite de 11,3% , diagnóstico médico de rinite 20%, eczema atópico de 9,2% e o diagnóstico pelo critério combinado de 5,7%. Houve associação entre asma, rinite e eczema atópico em 3,8% dos escolares. O sexo masculino foi predominante para sintomas de asma e rinite, não havendo diferença para eczema. Comparando-se os dados da fase I aos dados atuais, observou-se prevalência mais elevada dos sintomas e gravidade de asma e valores menores para sintomas de rinite e eczema. CONCLUSÕES: As prevalências de asma e rinite neste estudo mostraram valores elevados em comparação ao diagnóstico médico. A prevalência de eczema atópico foi maior que aquela avaliada pelo critério combinado. Houve predomínio do sexo masculino nas respostas positivas para asma e rinite. As associações mais freqüentes foram entre asma e rinite e entre asma e eczema, havendo associação das três doenças em pequeno número de alunos. Em comparação aos dados da Fase I na região centro-sul de São Paulo, observou-se que na região oeste houve maior prevalência dos sintomas e gravidade da asma e menor prevalência de rinite e eczema. / INTRODUCTION: The knowledge about the prevalence of allergic diseases is important to introduce prevention strategies. The written questionnaire standardized by \"International Study of Asthma and Allergies in Childhood\" - ISAAC, has been used to compare epidemiological data from different regions. The aims of the present study were: to evaluate the prevalence of asthma, rhinitis and allergic eczema and related symptoms, among students from 6 to 7 years in the west area of São Paulo city, through the written questionnaire from the ISAAC study, to compare this data with those obtained in ISAAC Phase I in São Paulo identifying temporal trends in the allergic diseases prevalence. METHODS: In the period from June to October/2002 written questionnaire were applied to 3312 students. The proportion differences were estimated by Qui-square or Fisher exact test. Odds Ratio (OR) and 95% confidence interval (IC95%) between gender and the allergic diseases were evaluated. Values of p < 0,05 were considered statistically significant. RESULTS: The prevalence found were: asthma 24,4%, medical diagnosis of asthma 5,7%, probable asthma 21,5%, rhinitis 25,7%, rhino conjunctivitis 11,3%, medical diagnosis of rhinitis 20%, atopic eczema 9,2% and the medical diagnosis by the combined criterion of eczema 5,7%. There was association among asthma, rhinitis and atopic eczema in 3,8% of the schoolchildren. Male sex was prevalent in all of the subjects regarding asthma and rhinitis, but there was no difference about gender for atopic eczema. In comparison with data from ISAAC phase I, in this study it was observed higher prevalence and severity of asthma and lower values for rhinitis and eczema symptoms. CONCLUSIONS: This study demonstrated high prevalence of asthma and rhinitis when compared to their medical diagnosis. The prevalence of atopic eczema was higher than combined criterion. The male gender predominates in all positive responses regarding asthma and rhinitis. The more frequent association was observed between asthma and rhinitis, asthma and eczema, and a low number of schoolchildren presented the three allergic diseases. Comparing with phase carried out at the south area of São Paulo city, in the west region there were higher prevalence of symptoms and severity of asthma, lower prevalence of rhinitis and eczema.

Introdução: As afecções nasais e sinonasais em cães possuem causas variadas, e algumas vezes cursam com sinusites, sendo raros os casos que não há doença nasal pré-existente. O diagnóstico presuntivo é baseado nas manifestações clínicas como secreção nasal uni ou bilateral anormais, esternutações, esternutações reversas paroxísticas, respiração estertorosa, engasgos, halitose, epistaxes, rinorragia, tosse, distrição respiratória, dor e deformação facial. Para concluir o diagnóstico, são indicados exames de imagem, rinoscopia, culturas, citologia e histopatológico. Objetivo: O presente estudo observacional teve como objetivo avaliar a contribuição ao diagnóstico das afecções da cavidade nasal e seios paranasais de cães, da radiografia, tomografia computadorizada e rinoscopia, realizando-se a comparação dos métodos diagnósticos mediante ao escore comparativo idealizado para este fim. Materiais e métodos: Foram utilizados 20 cães atendidos do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, com manifestações clínicas compatíveis com afecção nasal e submetidos a exame radiográfico, tomográfico e rinoscópico. A biópsia foi realizada, em 18 cães, por meio da rinoscopia, nos casos em que visibilizou-se proliferação tecidual, úlcera ou alteração na mucosa nasal sendo encaminhadas para estudo histológico. Resultados: Foram observados resultados estatisticamente significativos, baseados pelo escore, a radiografia em conjunto com a tomografia computadorizada, a rinoscopia associada à tomografia computadorizada e, também, a rinoscopia isoladamente, como métodos diagnósticos mais específicos na diferenciação de lesão maligna. A rinoscopia demonstrou como vantagem a visibilização direta diferenciando a presença ou não de inflamação ou proliferação tecidual, alteração anatômica, corpo estranho e placa fúngica. Conclusão: Os resultados do presente estudo indicam que embora possuam especifidade diferentes a utilização da radiografia, tomografia computadorizada e rinoscopia se complementaram como métodos diagnósticos nas afecções nasais e sinonasais dos cães avaliados. Nos casos de proliferação tecidual o estudo histológico demonstrou ser mais útil para conclusão diagnóstica em comparação aos exames de imagem e a rinoscopia. / Introduction: The nasal and sinus disorders in dogs have various causes, and sometimes go with sinusitis that there is no pre-existing nasal disease. The presumptive diagnosis is based on clinical manifestations as nasal discharge, sneezing, reverse sneezing, gagging, stertor, halitosis, epistaxis, cough, open-mouth breathing, pain and facial deformation. To complete the diagnosis, image examinations, rhinoscopy, cultures, cytology and histopathological fidings. Objectives: This observational study aimed to evaluate the contribution to the diagnosis of disorders of the nasal cavity and paranasal in dogs, radiography, computed tomography and rhinoscopy, performing comparison of diagnostic methods through the comparative score conceived for this purpose. Materials and methods: This study used 20 dogs of Veterinary Hospital of the Faculty of Veterinary Medicine and Zootechny of the University of São Paulo, with clinical signs compatible with nasal disorder and undergone radiographic examination, computed tomography and rhinoscopy. The biopsy was performed on 18 dogs through rhinoscopy, where is tissue proliferation, ulcer or change in the nasal mucosa histology study being forwarded to. Results: Significant results were observed by the score with radiography, computed tomography, rhinoscopy associated with computed tomography, and also, separately, as rhinoscopy diagnostic methods more specific differentiation of malignant lesion. The rhinoscopy demonstrated how advantage to visualize directly differentiating presence or not of inflammation or tissue proliferation, alteration, foreign body and fungal plaques. Conclusion: The results of this study indicate that although having different specific utilization, radiography, computed tomography and rhinoscopy as diagnostic methods arranged in nasal disorders of dogs and evaluated. In cases of tissue proliferation, histological study proved most useful in final diagnostic compared to the image exams and rhinoscopy.

Conclusions. SBL showed its efficacy in treating the animal model of allergic rhinitis. Its mechanisms may be related to its suppressive action on PCA reaction, the production of TXB2 and the expression of eNOS, as well as its modulation of cytokines, including IL-4, IL-6, IL-8, GM-CSF and TNF-alpha, release from mast cells. The clinical trial showed that SBL had more beneficial action on the quality of life, in comparison to the placebo, in the domains of RE and BP. Some symptoms evaluations of PAR patients, including GF, NB and SF were more markedly improved in the SBL group when compared with the placebo group. Furthermore, the use of SBL, with the study dose and treatment period, was safe. However, the accurate efficacy and mechanisms of SBL are largely unknown and need further investigation. (Abstract shortened by UMI.) / Introduction. Although great progress in treatment of allergic rhinitis have made in recent years, remarkably increasing prevalence and cost in epidemiology studies strongly suggest the difficulties in the management of allergic rhinitis. Shi-Bi-Lin (SBL) is a formula modified from the traditional Chinese herbal formula Cang-Er-Zi-San (CEZS) and a classic European formula SinupretRTM. CEZS has been used for the treatment of allergic rhinitis for several centuries in East Asia communities, and SinupretRTM has been used in treating paranasal sinusitis and rhinitis widely in Europe for decades. However, its therapeutic mechanisms remain unclear. We examined the efficacy and the possible mechanism of SBL in an animal model of allergic rhinitis and in cell culture study using Human Mast Cell Line (HMC-1) and Peripheral Blood Mononuclear Cells (PBMC). In addition, a clinical trial was conducted to examine its clinical efficacy and safety. / Results. In the animal study, SBL showed a potent effect in relieving the symptoms of nasal obstruction, sneezing and nasal scratching (P&lt;0.05 or P&lt;0.01), but had no convincing effect in decreasing the nasal discharge (P>0.05). In PCA test, IgG1 increased in a modest manner in the SBL-treated group when compared with the sham group (P&lt;0.05 or P&lt;0.01). Eosinophil infiltration and the expression of eNOS in nasal mucosa, but not iNOS, were obviously lower in the SBL treated group (P&lt;0.05 or P&lt;0.01) in comparison to the sham group. The levels of thromboxane B (TXB)2 in the nasal lavage fluid, but not histamine and peptide leukotrienes (p-LTs), showed significantly lower than that of the sham group (P&lt;0.05). In vitro study showed that SBL modulated the cytokines, including interleukin (IL)-4, IL-6, IL-8, Granulocyte/Macrophage Colony-Stimulating Factor (GM-CSF) and tumor necrosis factor (TNF)-alpha, release from human mast cell line (HMC-1). However, the mRNA expressions of these cytokines were not significantly altered. As the controls, dexamethasone, desloratadine and budesonide had more potently inhibitory effects on cytokines release from HMC-1. The component herbs generally had stimulatory effects on the cytokine release from HMC-1 and variable effects on PBMC. In the clinical trial, a total of 84 patients were recruited in the clinical trial and 77 of them completed the trial. Although no significant differences of each domain between the SBL and placebo groups were detected, findings supported the efficacy of SBL were obtained. / by Zhao Yu. / "July 2005." / Advisers: C. A. Van Hasselt; Ping-Chung Leung; Kong-Sang Woo. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0172. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.