Dissertations / Theses on the topic 'Bakers asthma; allergic diseases'

Background: Recent studies have suggested that aside from the inhalational route, skin exposure may also play an important role in the sensitization to allergens, resulting in adverse allergic respiratory outcomes including asthma in workers exposed to these agents. This appears to be reported more commonly for low molecular weight agents such as isocyanates and some cleaning agents. This study investigated whether skin symptoms, in the presence or absence of allergic sensitization, can predict the development of allergic respiratory outcomes and asthma in bakery workers. Methods: A cohort study investigated 263 bakery workers using a modified ECRHS questionnaire; immunological tests including skin prick tests for common local aeroallergens (ALK-Abello´ A/S, Horsholm, Denmark), Phadiatop and serum-specific IgE to bakery allergens (wheat, rye and fungal α-amylase); and pulmonological tests including spirometry, non-specific bronchial hyperresponsiveness, and fractional exhaled nitric oxide (FeNO), after a 4 year period. Results: Workers’ median age was 32 years (IQR: 26-38), 50% were female, 54% were ever smokers and 32% were atopic. At baseline, 26% of workers were sensitized to bakery allergens, skin symptoms were present in 22% and 11% reported work-related skin symptoms (WRSS). 3 While the incidence of general upper (19%) and lower (22%) respiratory symptoms over the follow-up period were very similar, work-related upper (29%) respiratory symptoms were higher than lower (20%) respiratory symptoms. However, the incidence of allergic sensitization to bakery allergens was only 8% and a new asthma diagnosis present in 4% over this period. In multivariate adjusted (gender, atopy and smoking status) regression models, having a history of skin symptoms was associated with an increased risk of developing work-related lower respiratory symptoms - WRLRS (RR=2.2, 95% CI: 1.03-4.83), while having clinically significant symptoms of eczema or urticaria was associated with an increased risk of reporting general upper respiratory symptoms (RR=5.5, 95% CI: 1.30-24.20) as well as WRLRS (RR= 4.8, 95% CI: 1.60-14.40). Furthermore, WRSS was associated with an increased risk of general upper respiratory symptoms (RR=5.1, 95% CI: 1.31-19.81), WRLRS (RR=4.1, 95% CI: 1.43-11.85) and elevated FeNO levels (FeNO>25ppb: RR=2.9, 95% CI: 1.19-7.28). The association between clinically significant skin symptoms or WRSS and new onset upper or lower respiratory symptoms were modified by use of dermal personal protective equipment. Infrequent or absent glove usage was associated with a higher risk (RR=5.3, 95% CI: 1.54-18.43) of having new onset WRLRS. Conclusion: Skin symptoms, more so if work-related, appear to be associated with future development of general and work-related upper and lower respiratory symptoms and inflammatory markers suggestive of asthma in bakery workers.

This study showed a strong association between asthma, hay fever, and eczema in the same child. The presence of pets outdoors but not indoors appeared to be associated with an increased incidence of wheezing in children. Use of the traditional Gulf incense also appeared to be a precipitating factor for asthma in this study. There were also statistically significant relationships between asthma and exposure to dust at home from air conditioner blasts, which is consistent with studies elsewhere. Moreover, in this study, passive exposure to tobacco smoking at home did not appear to have any significant relationship with asthma. There was, however, a statistically significant relationship between asthma and exposure to pollen from indoor plants, which is also consistent with studies elsewhere. Parental asthma but not parental atopy was a significant risk factor for asthma in offspring, a finding which agrees with other studies that have shown that parental atopy may enhance the likelihood of the expression of asthma, but does not, on its own, impact as a risk factor in the same way as parental asthma. There was a statistically significant difference in the prevalence of asthma and the symptoms of asthma between different areas across the United Arab Emirates, but not for eczema or hay fever. This is most likely attributable to the impact of radically different environmental conditions on the development of allergies in two genetically homogenous populations of United Arab Emirates nationals. Asthma, wheeze, dyspnoea and nocturnal cough were more prevalent in coastal humid Dubai, compared to dry inland Al-Ain. However, there was no statistically significant difference in the prevalence of eczema and hay fever between coastal and inland areas in the United Arab Emirates. An environmental survey carried out in Dubai and Al-Ain to study the effect of air pollution among asthmatic children showed that overall air quality in both Dubai and in Al-Ain is good, except during adverse weather conditions, strong winds and dust storms, in summer time, where the level of Respirable Particulates (PM10) is occasionally high in Dubai. However, a previous study of seasonal trends in hospital admissions for asthmatic children in Dubai showed that the highest numbers of admissions for asthmatic children occurred between the months of October and February. These are the coldest months of the year in the United Arab Emirates. Therefore air pollution from dust storms was not the cause of the high prevalence of asthma in Dubai. Although the prevalence of asthma and wheezing was lower in the United Arab Emirates than in some developed countries, it was still higher than other chronic diseases. This study demonstrated that symptoms suggestive of asthma are quite common and constitute a major health problem in the United Arab Emirates. High rates of consanguineous marriage, a buoyant economy, rapid industrialization, development of the agricultural sector, an increase in the domestication of animals and dairy farms, combined with an emphasis on 'greening' the environment, may have resulted in an increase of the prevalence of asthma. World-wide trends have been in this direction. Therefore, a concentrated effort should be made to implement therapeutic and non-therapeutic programmes for the management of asthma by parents, teachers and physicians.

Background: It is unclear how far the superior efficacy of omalizumab, established in randomized controlled clinical trials of patients with severe allergic asthma (SAA), translates into routine practice and when compared to matched controls. Methods: New-onset omalizumab-treated (OT) patients with SAA (n = 53) were compared to a matched control group of usual-care (UC) patients (n = 53). Treatment and procedures were naturalistic. Subsequent to a baseline assessment, patients were followed up over at least 6 months with at least two follow-up assessments. Primary clinical outcomes were the number of asthma attacks, persistence of asthma symptoms and degree of control [asthma control test (ACT), Global Initiative for Asthma]. Secondary outcome criteria were quality of life (Euro-Qol 5D) and number of medications. For each outcome we compared within-group effects from baseline to 6-month follow-up as well as between-group effects. Results: OT patients showed significant improvements in number [effect size (ES) = 0.03] and frequency (ES = 0.04) of asthma attacks as well as asthma control (ES = 0.09), whereas controls revealed no significant improvements in these measures. Further improvements in the OT group were found for ‘perceived control always’ (ACT, p = 0.006), no impairment (ACT, p = 0.02), reduction of sickness days (p = 0.002) and number of medications needed (p = 0.001). Conclusions: Substantial beneficial effects of omalizumab, similar to those observed in controlled trials and after marketing studies, were confirmed, particularly with regard to the reduction of asthma attacks, persistence of symptoms, asthma control and reduction of concomitant asthma medications. This study provides a tougher test and generalizable evidence for the effectiveness of omalizumab in routine care.

Chronic respiratory diseases (CRDs) include chronic diseases involving the airways and other structures of the lung. In the current circumstance of Vietnam, people are exposed to numerous risk factors of CRD, such as heavy smoking, high frequency of pulmonary tuberculosis, chronic helminthiasis, allergic factors, migration and urbanization (the last associated with traffic-related pollution). The phenotype diagnoses should take into account the risk factors of each individual besides the clinical features, while the differential diagnoses mostly depend on the available techniques in each healthcare center. Our aim was to improve the differential diagnoses of the 3 most frequent CRDs: chronic obstructive pulmonary disease (COPD), asthma and COPD – asthma overlap syndrome (ACOS), in Vietnam. In the first part, we evaluated the prevalence of the allergen sensitization among patients with CRD, in regard to the urban and rural area in the South of Vietnam. House dust mites and cockroach droppings were the most frequent sensitizer. Compared with participants born in the urban setting, those born in the rural environment were less frequently sensitized and this protective effect disappeared in the case of migration from rural to urban areas. In the second part, we evaluated skin prick test as a method to screen dust mite sensitization in CRD in southern Vietnam. The data suggested that, in the present circumstance, skin prick test can be used to screen mite sensitization. In the third part, we evaluated the risk of mite sensitization in the native and migrant population, in regard to several environmental factors. Consistently with the hygiene hypothesis, compared to urban, exposure to high endotoxin concentration in rural was a protective factor against allergic sensitization. We reported for the first time that this effect was reversible among the migrants from rural to urban setting in association with lower endotoxin exposure. In the fourth part, we have defined asthma, COPD and ACOS based on clinical symptoms, cumulative smoking and airway expiratory flow with reversibility, on one side, and the age-related of the different phenotypes, on the other side. We hypothesized that the cumulative exposure to noxious particles should increase the age-related prevalence of COPD, while due to the immunosenescence process, the prevalence of IgE-mediated asthma should decrease with age, and ACOS prevalence being not related to age due to the combined mechanisms.  In conclusion, we showed in the South of Vietnam that:1) mites and cockroach allergens were the most frequent sensitizer in chronic respiratory diseases;2) the skin prick test to mite has been validated to screen mite sensitization;3) associated with a reduced level of endotoxin level, migration from rural to the urban setting was a risk factor of mite sensitization in chronic respiratory diseases;4) based on the clinical symptoms, spirometric values, and cumulative smoking, the diagnosis of asthma, COPD and ACOS have been made and their prevalence were 25, 42 and 33%, respectively.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished

Les allergies représentent un problème de santé majeur avec une prévalence en nette augmentation et pour lesquelles il n’existe pas de thérapie à longue durée. L’IL-4, l’IL-13 et l'IgE jouent un rôle clé dans les réactions allergiques. Ces cibles thérapeutiques ont été validées en clinique, grâce aux anticorps monoclonaux. Néanmoins, leur utilisation reste contraignante de par leur coût excessif et la nécessité de réinjections fréquentes. L’objectif de cette thèse a été de développer des vaccins contre l’IL-4, l’IL-13 et l’IgE, appelés kinoïdes, et d’apporter la preuve de concept de l’efficacité dans des modèles d’asthme et de choc allergique. Nous avons démontré qu’une vaccination combinée contre l’IL-4 et l’IL-13 permet de réduire les taux d’IgE, l’hyperréactivité bronchique, l’éosinophilie et la production de mucus dans un modèle murin d’asthme chronique. De plus, nous avons montré qu’une vaccination avec des kinoïdes IL-4/IL-13 humains induit des anticorps neutralisants anti-IL-4 et IL-13 humaines et et réduit les niveaux d’IgE dans des souris humanisées pour l’IL-4, l’IL-13 et IL-4Ra. Nous avons également développé un vaccin conjugué contre l’IgE humaine. Nous avons montré que ce vaccin induit une forte production d’anticorps neutralisant anti-IgE humains, dans une nouvelle souche de souris humanisée pour l’IgE et le récepteur FceRI. Une vaccination des souris humanisées IgE/FceRI avec le kinoïde IgE humain réduit fortement les taux d’IgE et protège contre un choc anaphylactique induit par les IgE. L’ensemble de ces études démontre qu’une vaccination contre l’IL-4, l’IL-13 ou l’IgE pourrait représenter une solution thérapeutique contre les maladies allergiques
Allergies represent major public health problems of increasing prevalence and for which there is still no efficient long-term therapy. IL-4 and IL-13, and IgE play key roles in allergic reactions, and therefore represent good therapeutic targets. These targets have been clinically validated with approved monoclonal antibodies (mAb). However, use of mAb is limited by high cost and the need to perform repeated injections. Therefore, there is a clear need to improve current strategies in order to reach long term effects. The objective of this thesis was to develop anti-IL-4, anti-IL-13 and anti-IgE vaccines called kinoids, and provide a proof-of-concept of their safety and efficacy. We developed conjugate vaccines against IL-4 and IL-13, and demonstrated their prophylactic and therapeutic efficacy in reducing IgE levels, airway hyperresponsiveness, eosinophilia and mucus production in a house dust mite-induced mouse model of asthma without any detectable adverse effect. The human version of the IL-4/IL-13 kinoid was also efficient at neutralizing human IL-4 and IL-13, and reducing IgE levels in mice humanized for IL-4, IL-13 and their common receptor subunit IL-4Ra. In addition, we also developed a conjugate vaccine against human IgE. We showed that this anti-IgE vaccine induces long-term production of anti-human IgE neutralizing antibodies in a novel mouse strain we characterized and which is humanized for IgE and its high-affinity receptor FceRI. Anti-human IgE vaccination reduced hIgE, and fully protected against IgE-mediated anaphylaxis. Altogether, our results showed that vaccination against IL-4, IL-13 and IgE could be a valuable strategy to target allergic disorders

Background: Childhood asthma has increased worldwide, although recent studies report a prevalence plateau in some western countries. Aims: To investigate the prevalence of asthma and the associated risk factor patterns from ages 7-8 to 11-12 with special emphasis on the hereditary component, and further to study prevalence trends at age 7-8 from 1996 to 2006 and the possible determinants of these trends. Methods: The studies involved two cohorts from Kiruna, Luleå and Piteå: one previously identified cohort of 3430 children age 7-8 followed by yearly questionnaires until age 11-12 with 97% yearly participation. Skin-prick tests for allergic sensitisation were performed at ages 7-8 and 11-12 in subsets of 2148 and 2155 children respectively (88% of invited). In 2006 a new cohort of 7-8-year-olds was identified and examined identically. 2585 (96% of invited) and 1700 (90% of invited) participated in the questionnaire and skin-prick tests, respectively. The questionnaire included questions about symptoms of asthma, allergic rhinitis and eczema, and possible risk factors. Results: In the 1996 cohort, from age 7-8 to 11-12 the prevalence of physician-diagnosed asthma increased (5.7%-7.7%, P<0.01) while current wheeze decreased (11.7%-9.4%, P<0.01), and 34.7% reported ever wheee at ≥one occasion. Remission was 10% of which half relapsed during the study. Remission was significantly lower among sensitised children. The strongest risk factors for current asthma at ages 7-8 and 11-12 were allergic sensitisation (OR 5) and family history of asthma (OR 3). Several other significant risk factors, e.g. respiratory infections, damp house and low birth weight, had lost importance at age 11-12. At age 7-8, parental asthma was a stronger risk factor (OR 3-4) than parental rhinitis or eczema (OR 1.5-2). Sibling asthma had no independent effect. Biparental asthma had a multiplicative effect (OR 10). Maternal and paternal asthma was equally important, regardless of the child’s sex and sensitisation status. From 1996 to 2006 the prevalence of current wheeze and asthma at age 7-8 did not increase (P=0.13, P=0.18), while lifetime prevalence of ever wheeze and physician-diagnosed asthma increased (P<0.01, P=0.01). Symptoms of rhinitis and eczema were unchanged, despite 45% increase (P<0.01) in allergic sensitisation. For current asthma the adjusted population attributable fractions of sensitisation and parental asthma increased (35%-41%, 27%-45%). This was however balanced by decreased exposure to infections, maternal smoking and home dampness, resulting in stable asthma prevalence. Stratification by sex revealed that current wheeze increased in boys (P<0.01) but tended to decrease in girls (P=0.37), seemingly due to symptom persistence in males. Several asthma indices followed this pattern. The boy-to-girl ratio in exposure to all studied risk factors increased, which may explain the sex-specific prevalence trends in wheeze. Conclusions: The prevalence of current asthma and wheeze did not increase statistically significantly. However, the risk factor pattern has changed considerably since 1996, which will presumably affect the clinical features of childhood wheeze in this region. Sex-specific trends in wheeze can be explained by changes in exposure, and trends in risk factors should be explored parallel to prevalence trends.

Background: It is unclear how far the superior efficacy of omalizumab, established in randomized controlled clinical trials of patients with severe allergic asthma (SAA), translates into routine practice and when compared to matched controls. Methods: New-onset omalizumab-treated (OT) patients with SAA (n = 53) were compared to a matched control group of usual-care (UC) patients (n = 53). Treatment and procedures were naturalistic. Subsequent to a baseline assessment, patients were followed up over at least 6 months with at least two follow-up assessments. Primary clinical outcomes were the number of asthma attacks, persistence of asthma symptoms and degree of control [asthma control test (ACT), Global Initiative for Asthma]. Secondary outcome criteria were quality of life (Euro-Qol 5D) and number of medications. For each outcome we compared within-group effects from baseline to 6-month follow-up as well as between-group effects. Results: OT patients showed significant improvements in number [effect size (ES) = 0.03] and frequency (ES = 0.04) of asthma attacks as well as asthma control (ES = 0.09), whereas controls revealed no significant improvements in these measures. Further improvements in the OT group were found for ‘perceived control always’ (ACT, p = 0.006), no impairment (ACT, p = 0.02), reduction of sickness days (p = 0.002) and number of medications needed (p = 0.001). Conclusions: Substantial beneficial effects of omalizumab, similar to those observed in controlled trials and after marketing studies, were confirmed, particularly with regard to the reduction of asthma attacks, persistence of symptoms, asthma control and reduction of concomitant asthma medications. This study provides a tougher test and generalizable evidence for the effectiveness of omalizumab in routine care.

Aspergillus fumigatus is an opportunistic fungal pathogen that causes lethal invasive pulmonary disease in immunocompromised hosts and allergic asthma in sensitized individuals. This dissertation explores how eosinophils may protect hosts from acute infection while driving asthma pathogenesis by co-producing IL-23 and IL-17 in both contexts. In an acute model of pulmonary aspergillosis, eosinophils were observed to associate with and kill A. fumigatus spores in vivo. In addition, eosinopenia was correlated with higher mortality rates, decreased recruitment of inflammatory monocytes to the lungs, and decreased expansion of lung macrophages. As IL-17 signaling must occur on a local level to elicit its stereotypical response, such as the up-regulation of antimicrobial peptides and specific chemokines from stromal cells, eosinophils were discovered to be a significant source of pulmonary IL-17 as well as one of its upstream inducers, IL-23. In the context of asthma, this discovery opens a new paradigm whereby eosinophils might be driving asthma pathogenesis.

INTRODUÇÃO: Há evidências consistentes a partir de estudos epidemiológicos de que os profissionais de limpeza têm um risco elevado de desenvolver asma. Os determinantes deste risco não são totalmente conhecidos. Esses trabalhadores estão expostos a agentes ocupacionais de baixo e alto peso molecular, tanto a agentes sensibilizantes, como a irritantes. É importante produzir evidências de que este risco está relacionado ao trabalho e não às condições sociais ou outros fatores concorrentes, conhecer a anormalidade patológica subjacente, e investigar os possíveis agentes. O acúmulo deste conhecimento permitirá a proposição de medidas para substituição ou controle do uso dos agentes envolvidos e prevenção da ocorrência de novos casos desnecessariamente. Além disso, o uso de novas técnicas não invasivas, como a citologia do escarro e A FeNO, poderá facilitar o diagnóstico precoce dos casos. Desta maneira, este estudo pretende avaliar se o ambiente de trabalho induz inflamação pulmonar em trabalhadores assintomáticos, antes da alteração das provas funcionais e a eficácia do escarro induzido e da FeNO NO como marcadores de inflamação pulmonar precoce entre trabalhadores de limpeza profissional não doméstica. MÉTODO: Os trabalhadores foram avaliados através da comparação da citologia do escarro, valores da FeNO, espirometria e PFE, realizados durante o período de trabalho e após as férias. A amostra foi caracterizada através do questionário de triagem do estudo de saúde respiratória da Comunidade Européia, questionário de sintomas respiratórios e a pontuação no ISAAC. RESULTADOS: Em nosso estudo, encontramos um aumento significativo dos valores do VEF1 após o período de férias, (pré 2,76 ± 0,57 e pós 2,94 ± 0,61; p < 0,05) apesar de estar dentro da normalidade, em ambos os períodos. A média das medidas do PFE também mostrou-se maior durante o período de férias em comparação ao período de trabalho, embora não estatisticamente significante (pré 366,6 ± 54,1 e pós 386,4 ± 62,9 e p > 0,05). Encontramos uma redução dos valores da medida da FeNO após as férias (pré 16,3 ± 9,7 e pós 13,8 ± 7,8 p < 0,05) e redução de eosinófilos (pré 0,019 ± 0,05 e pós 0,003 ± 0,01 p < 0,05), linfócitos (pré 0,16 ± 0,35 e pós 0,01 ± 0,09 p < 0,05) e macrófagos (pré 0,421 ± 0,47 e pós 0,235 ± 0,30 p < 0,05) na citologia do escarro induzido, realizada após o período de férias. CONCLUSÃO: Demonstramos que o ambiente ocupacional ao qual são expostos os trabalhadores de limpeza profissional não doméstica provoca inflamação nas vias aéreas de trabalhadores assintomáticos. Esta inflamação pode ser aferida por métodos não invasivos como escarro induzido e FeNo, antes do aparecimento de alterações nas provas funcionais, embora estes métodos ainda necessitem de padronização. São necessários novos estudos para quantificar a exposição ao cloro e sua relação com inflamação, assim como para padronizar o uso do escarro induzido e da FeNO no diagnóstico de doenças ocupacionais entre trabalhadores de limpeza, além de medidas preventivas e educativas nesta população
There is consistent evidence from epidemiological studies that the cleaning professionals have a high risk of developing asthma. The determinants of this risk are not fully known. These workers are exposed to occupational agents of low and high molecular weight, both the sensitizing agents, such as irritant. It is important to produce evidence that this risk is related to work and not social conditions or other competitive factors, know the underlying pathological abnormality, and investigate possible agents. The accumulation of this knowledge will allow proposing measures to replace or control the use of the agents involved and preventing the occurrence of new cases unnecessarily. In addition, the use of new non-invasive techniques, such as sputum cytology and the FeNO may facilitate early diagnosis of cases. Thus, this study aims to assess if the work environment induces lung inflammation in asymptomatic workers, before the change of functional tests and the effectiveness of induced sputum and exhaled NO as early lung inflammation markers between professional cleaning workers. METHOD: Workers were evaluated by comparing the sputum cytology, FeNO values, spirometry and PEF, made during the work period and after the holidays. The sample was characterized by screening questionnaire of respiratory health study of the European Community, questionnaire of respiratory symptoms and a score in ISAAC. RESULTS: In our study, we found a significant increase in FEV1 values after the vacational period, (pre 2.76 ± 0.57 and 2.94 ± 0.61; post; p < 0.05) despite of being within the normal range in both periods. The average peak flow measurements also was higher during the vacational period compared to the period of work, although not statistically significant (366.6 ± 54.1 pre and post 386.4 ± 62.9; p > 0.05). We found a reduction of the exhaled measured values of NO after the holidays (pre and post 16.3 ± 9.7, 13.8 ± 7.8; p < 0.05), reduction of eosinophils (pre and post 0.05 ± 0.019, 0.003 ± 0.01; p < 0.05), lymphocytes (pre and post 0.16 ± 0.35, 0.01 ± 0.09; p < 0.05) and macrophages (pre and post 0.421 ± 0.47 0.235 ± 0 30 p < 0.05) in induced sputum cytology, performed after the holiday period. CONCLUSION: We demonstrate that the occupational environment to which professional cleaning non-domestic workers are exposed causes inflammation in the airways of asymptomatic workers. This inflammation can be measured by non-invasive methods such as induced sputum and FeNo, before the onset of changes in functional tests, although these methods still require standardization. Further studies are needed to quantify the exposure to chlorine and its relation to inflammation, as well as to standardize the use of induced sputum and exhaled nitric oxide in the diagnosis of occupational diseases among cleaning workers, and preventive and educational measures in this population

Sy, Hing Yee.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2011.
Includes bibliographical references (leaves lxxiv-xciv).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese; appendixes I-III in Chinese.

Indiana University-Purdue University Indianapolis (IUPUI)
Rationale: Tissue remodeling and complement activation are asthma hallmarks. Type V collagen [col(V)], a cryptic antigen, becomes exposed during lung remodeling. IL-17 is key to anti-col(V) immunity, and regulates complement activation. We have reported that col(V)-induced tolerance down regulates IL-17 and prevents immune-mediated lung diseases. Objectives: Determine a role for anti-col(V) immunity in asthma. Methods: Serum anti-col(V) antibodies were measured in asthma patients, and immunohistochemistry utilized to detect interstitial col(V) in fatal asthma. Balb/c mice were tolerized with col(V) prior to sensitization with ovalbumin (OVA), and subsequent OVA intranasal challenge. Airway hyper-responsiveness (AHR) to methacholine was measured; and RT-PCR utilized to determine local Il17 transcripts. Bronchoalveolar lavage levels of C3a¸ C5a and OVA-specific IgE were measured; and immunohistochemistry utilized to detect expression of complement regulatory proteins, expression, CD46/Crry and CD55, in lung tissue. Results: Compared to normal subjects, anti-col(V) antibodies were increased in asthmatics; and interstitial col(V) was over expressed in fatal asthma. OVA-induced AHR up regulated anti-col(V) antibodies systemically, and increased OVA-specific IgE and C3a in BAL, and parenchymal Il17 transcripts. Col(V)-induced tolerance abrogated AHR, down regulated OVA-induced T cell proliferation, as well as total and OVA-specific IgE, C3a, IL-17 expression and tracheal smooth muscle contraction. Crry/CD46 and CD55, key to preventing complement activation, were down regulated on goblet cells in murine allergic airway disease. Conclusions: Anti-col(V) immunity correlates with asthma pathogenesis, and col(V)-induced tolerance may be a novel therapeutic for asthma. Decreased expression of Crry/CD46 and CD55 on goblet cells may in part account for complement activation in asthma.

Wang, Shuxin.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2013.
Includes bibliographical references (leaves 191-212).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts also in Chinese; appendixes includes Chinese.

碩士
中山醫學院
毒理學研究所
88
Atopic disorder（including asthma and allergic rhinitis）is one of the worldwide chronic diseases, has been seen an exponential increase in childhood. The raised prevalence of the atopic disorder may be dued to the strong environmental factor, but hereditary factor is also the important factor. To identify genetic factors for susceptibility to atopy asthma and allergic diseases in childhood, 258 subjects were identified, mainly from Taichung in Taiwan, of whom 41 were unrelated controls, 41 were asthma cases, 31 were allergic rhinitis cases, 92 were both asthma and allergic rhinitis cases, and 53 other allergic disease cases. All the subjects were characterized for lung function（FEV1, forced expiratory volume in the first second）, eosinophil counts , total serum IgE and specific IgE reactivity to common aeroallergens. Asthma or allergic disease was defined as FEV1 ＜85% and/or increased IgE levels. Several candidate genes was investigated, and genome-wide linkage analysis was been initiated. Increased total serum IgE levels, reduced FEV1 and eosinophil counts have been detected in both control and allergic disorders. The regions of interest were amplified from genomic DNA using polymerase chain reaction（PCR）, while restriction enzyme digestion was used for genotyping individuals for the candidate gene polymorphisms. An analysis was then performed on 41 unrelated controls, 41 asthmatic , 31 allergic rhinitis , 92 both asthmatic and allergic rhinitis , and 53 other allergic disease children for each polymorphism. The LT-α, IL-4Rα（R576）and FcεRⅠ（intron 2、exon 7）polymorphisms were not associated with allergic diseases, but the TNF-α and FcεRⅠ（E237G）polymorphisms were associated with allergic rhinitis. The increased total serum IgE levels was found to be linked to each polymorphism. FcεRⅠ（exon 7）positive subjects had a significantly elevated eosinophil counts to both asthma and allergic rhinitis. TNF-α、LT-α、IL-4Rα（R576）及FcεRⅠ（intron 2）positive subjects had a significantly elevated eosinophil counts to both asthma and allergic rhinitis, and other allergic diseases. FcεRⅠ（E237G）positive subjects had a significantly elevated eosinophil counts to asthma, both asthma and allergic rhinitis, and other allergic diseases. Among the six polymorphisms, TNF-α, LT-α, IL-4Rα（R576）and FcεRⅠ（intron 2）demonstrated an association with a significantly reduced FEV1 to both asthma and allergic rhinitis, and other allergic disease. FcεRⅠ（E237G）positive subjects had a significantly reduced FEV1 to both asthma and allergic rhinitis. FcεRⅠ（exon 7）showed no association with reduced FEV1 to atopic disorder. We also examined the relative contributions of four environmental factors to the development of atopic disorders. Smoking and incensing in house were associated with allergic rhinitis, both asthma and allergic rhinitis, and other allergic disease. These results suggest that the TNF-α, LT-α, IL-4Rα（R576）and FcεRⅠ（E237G, intron 2 and exon 7）polymorphisms were not associated with asthma and the other allergic diseases, but TNF-αand FcεRⅠ（E237G）polymorphisms were associated with allergic rhinitis.

no
Background  Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human β-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. Objectives  To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. Methods  hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. Results  Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL−1 of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. Conclusions  Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing – thus indicative for contact of the epidermis with serum components.

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

Indiana University-Purdue University Indianapolis (IUPUI)
IL-17-producing T cells are critical to the development of pathogen and tumor immunity, but also contribute to the pathology of autoimmune diseases and allergic inflammation. CD8+ (Tc17) and CD4+ (Th17) IL-17-secreting T cells develop in response to a cytokine environment that activates Signal Transducer and Activator of Transcription (STAT) proteins, though the mechanisms underlying Tc17/Th17 development and stability are still unclear. In vivo, Tc17 cells clear vaccinia virus infection and acquire cytotoxic potential, that is independent of IL-17 production and the acquisition of IFN-γ-secreting potential, but partially dependent on Fas ligand, suggesting that Tc17-mediated vaccinia virus clearance is through cell killing independent of an acquired Tc1 phenotype. In contrast, memory Th cells and NKT cells display STAT4-dependent IL-23-induced IL-17 production that correlates with Il23r expression. IL-23 does not activate STAT4 nor do other STAT4-activating cytokines induce Il23r expression in these populations, suggesting a T cell-extrinsic role for STAT4 in mediating IL-23 responsiveness. Although IL-23 is important for the maintenance of IL-17-secreting T cells, it also promotes their instability, often resulting in a pathogenic Th1-like phenotype in vitro and in vivo. In vitro-derived Th17 cells are also flexible when cultured under polarizing conditions that promote Th2 or Th9 differentiation, adopting the respective effector programs, and decreasing IL-17 production. However, in models of allergic airway disease, Th17 cells do not secrete alternative cytokines nor adopt other effector programs, and remain stable IL-17-secretors. In contrast to Th1-biased pro-inflammatory environments that induce Th17 instability in vivo, during allergic inflammatory disease, Th17 cells are comparatively stable, and retain the potential to produce IL-17. Together these data document that the inflammatory environment has distinct effects on the stability of IL-17-secreting T cells in vivo.