Thesis (M Nutr)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Background Adverse reactions to food are frequently suspected in daily clinical practice yet the knowledge of health care workers regarding correct diagnosis and management remains limited. This is compounded by few allergy consultants and may contribute to patient dissatisfaction and self‐diagnoses. The primary treatment modality for food hypersensitivity remains strict but nutritionally adequate elimination of offending food allergens based on accurate diagnosis. Nutritional misconceptions and incorrect diagnosis may lead to inappropriate dietary restriction resulting in nutritional deficiencies, malnutrition, growth retardation, and feeding difficulties in children. Elimination diets thus require supervision and monitoring similar to drug treatments, being reviewed regularly for possible food re‐challenges. There is limited research to assess knowledge and management approaches of food allergies by medical doctors and no research of this nature exists for Dietitians. There is also limited information as to whether current approaches conform to the most recent evidence‐based recommendations, particularly with regard to dietary intervention and allergy prevention strategies. Aim The aim of this survey was to determine aspects of food allergy related knowledge and practices of Medical Doctors and Dietitians. Methodology This was an analytical cross sectional study with participants randomly selected from the three largest provinces in South Africa, Gauteng, Western Cape and Kwazulu Natal (N=660). A quantitative questionnaire was compiled to explore aspects of food allergy diagnosis and management. Participants were currently working in South Africa and were selected according to three categories, General Practitioners, Dietitians and Medical Specialists. Ethics approval was obtained from the University of Stellenbosch, Faculty of Health Sciences Committee of Human Research. Results Even though valuable insights were obtained, poor response from all three groups (N=82) compromised the strength of significant findings. There was limited knowledge regarding appropriate diagnosis, dietary intervention and allergy prevention strategies. 98% of respondents believed they needed more education and training in management of allergies. Approximately 50% reported use of complementary therapy by patients prior to and while using conventional medicine. Dietitians weren't consulted for nutritional management by 72% General Practitioners and 45% Specialists. For allergy prevention, over 50% of health professionals advised extensive food avoidance for the first year in high risk infants. Dietitians recommended multiple food avoidance for the longest period of time per food in infants, pregnant and lactating women to prevent allergy. Advice for infant feeding and introduction of solid foods was not evidence‐based. Goat's milk, soya formula and breast milk with maternal dietary avoidance were advised for allergy prevention. 54% of medical doctors and 31% of Dietitians provided no guidance for implementing an elimination diet. Only 15% of respondents did growth assessment of allergic patients. 99% of all participants recognised a need for South African specific 'best practice' guidelines. Conclusion The study highlighted a need in South Africa, at undergraduate and post graduate levels, for better education and training of food allergy, in particular diagnosis, dietary management and prevention strategies. This will create a platform for the achievement of minimum levels of competency in allergy care. It should also provide motivation for the establishment of South African specific guidelines, allergy support networks and better public awareness. / AFRIKAANSE OPSOMMING: Agtergrond Afwykende reaksies tot voedsel word dikwels by gesondheidsorg instellings verdag. Nieteenstaande, bestaan daar steeds beperkte kennis oor allergië. Die tekort aan allergie konsultante vererger sake en het dikwels ontevrede pasiënte en self‐diagnose tot gevolg. Die primêre modaliteit van behandeling van voedsel hipersensitiwiteit behels doelmatige verwydering van die oorsaaklike voedsel allergene deur middel van 'n streng dog voedingswaardige dieet. Ontoepaslike bestuur van, en die verkeerde implementering van die uitskakelings dieet mag egter lei tot komplikasies by kinders soos hongersnood, groei vertraging en voedings probleme. Daar is tans beperkte navorsing om die peil van kennis van voedsel allergië en die bestuur van die probleem te meet. Geen sodanige navorsing ten opsigte van dieëtkundiges is al gedoen nie. Slegs beperkte inligting is beskikbaar tot welke mate huidige behandelings praktyk konformeer met die mees onlangse bewys‐gebaseerde aanbevelings, veral met betrekking tot allergie voorkomende strategië. Doelstelling Die doelstelling van hierdie opname was om die kundigheid en bestuur van voedsel verwante allergië deur medici en dieëtkundiges te bepaal. Metodologie Dwarsprofiel analiese was gedoen met respondente wat onwillekeurig gekies was uit profesionele mediese en dieëtkundige praktisyns uit die drie grootste provinsies in Suid Afrika, Gauteng, Wes‐Kaap en Kwazulu Natal (N=660). Deelnemers was versoek om vraelyste met 'n samestelling van aspekte van voedsel allergie diagnose en bestuur te voltooi. Deelnemers is huidiglik werksaam in Suid Afrika en was verteenwoordigend van drie kategorië, naamlik Algemene Praktisyns, Dieetkundiges en Mediese Spesialiste. Etiese goedkeuring was bekom van die Universiteit Stellenbosch se Fakulteit Gesondheidswetenskappe Navorsingsetiek komitee. Bevindinge Desnieteenstaande insiggewende inligting is die bevindinge gekompromitteer deur beperkte respons (N=82). Kennis met betrekking tot diagnose, dieëtkundige intervensie en allergie voorkomings strategië, is beperk. 88% van respondente versoek meer opleiding in die bestuur van allergië. 53% beweer dat pasiënte komplementêre terapie aanwend voor en gelyktydig met die gebruik van konvensionele medikasie. Interdisiplinêre konsultasie is beperk. Dieëtkundiges word nie geraadpleeg deur 72% van algemene praktisyns en 54% mediese spesialiste nie. Meer as 50% gesondheidsorg praktisyns beveel algemene voedsel ontwyking aan by hoë risiko kleuters gedurende die eerste lewensjaar. Dieëtkundiges se allergie voorkomings aanbevelings aan kleuters, swanger en lakterende vrouens was vir die langste periode. Advies vir kleuter voeding was nie bewys‐gebaseerd nie. Bokmelk, soya formule en borsmelk van moeders met dieëtkundige beperkinge word aanbeveel vir die voorkoming van allergië by kleuters. 54% mediese en 31% dieëtkundiges voorsien geen voorkomings dieët riglyne nie. Slegs 15% respondente takseer kleuter groei van allergie pasiënte. 99% van al die respondente ondersteun die vestiging van spesifieke 'beste praktyk' riglyne vir Suid Afrika. Gevolgtrekking Die bevindinge van die studie beklemtoon die behoefte in Suid Afrika vir verbeterde en doelgerigte voedsel allergie onderrig en opleiding, vir voorgraadse en nagraadse onderrig. Meer doeltreffende diagnose, dieëtkundige bestuur en allergie voorkomings strategië word aanbeveel. Daar word 'n doelwit geskep vir die bereiking van minimum vaardigheids vlakke vir allergie versorging. Die inligting motiveer ook die vestiging van doelgerigte Suid‐Afrikaanse riglyne, allergie ondersteunings bronne en beter, openbare bewuswording van allergië.

Measurement error is common in epidemiologic studies and can lead to biased statistical inference. It is well known, for example, that regression analyses involving measurement error in predictors often produce biased model coefficient estimates. The work in this dissertation adds to the existing vast literature on measurement error by proposing a missing data treatment of measurement error through general location models. The focus is on the case in which information about the measurement error model is not obtained from a subsample of the main study data but from separate, external information, namely the external calibration. Methods for handling measurement error in the setting of external calibration are in need with the increase in the availability of external data sources and the popularity of data integration in epidemiologic studies. General location models are well suited for the joint analysis of continuous and discrete variables. They offer direct relationships with the linear and logistic regression models and can be readily implemented using frequentist and Bayesian approaches. We use the general location models to correct for measurement error and misclassification in the context of three practical problems. The first problem concerns measurement error in a continuous variable from a dataset containing both continuous and categorical variables. In the second problem, measurement error in the continuous variable is further complicated by the limit of detection (LOD) of the measurement instrument, resulting in some measures of the error-prone continuous variable undetectable if they are below LOD. The third problem deals with misclassification in a binary treatment variable. We implement the proposed methods using Bayesian approaches for the first two problems and using the Expectation-maximization algorithm for the third problem. For the first problem we propose a Bayesian approach, based on the general location model, to correct measurement error of a continuous variable in a data set with both continuous and categorical variables. We consider the external calibration setting where in addition to the main study data of interest, calibration data are available and provide information on the measurement error but not on the error-free variables. The proposed method uses observed data from both the calibration and main study samples and incorporates relationships among all variables in measurement error adjustment, unlike existing methods that only use the calibration data for model estimation. We assume by strong nondifferential measurement error (sNDME) that the measurement error is independent of all the error-free variables given the true value of the error-prone variable. The sNDME assumption allows us to identify our model parameters. We show through simulations that the proposed method yields reduced bias, smaller mean squared error, and interval coverage closer to the nominal level compared to existing methods in regression settings. Furthermore, this improvement is pronounced with increased measurement error, higher correlation between covariates, and stronger covariate effects. We apply the new method to the New York City Neighborhood Asthma and Allergy Study to examine the association between indoor allergen concentrations and asthma morbidity among urban asthmatic children. The simultaneous occurrence of measurement error and LOD is common particularly in environmental exposures such as measurements of the indoor allergen concentrations mentioned in the first problem. Statistical analyses that do not address these two problems simultaneously could lead to wrong scientific conclusions. To address this second problem, we extend the Bayesian general location models for measurement error adjustment to handle both measurement error and values below LOD in a continuous environmental exposure in a regression setting with mixed continuous and discrete variables. We treat values below LOD as censored. Simulations show that our method yields smaller bias and root mean squared error and the posterior credible interval of our method has coverage closer to the nominal level compared to alternative methods, even when the proportion of data below LOD is moderate. We revisit data from the New York City Neighborhood Asthma and Allergy Study and quantify the effect of indoor allergen concentrations on childhood asthma when over 50% of the measured concentrations are below LOD. We finally look at the third problem of group mean comparison when treatment groups are misclassified. Our motivation comes from the Frequent User Services Engagement (FUSE) study. Researchers wish to compare quantitative health and social outcome measures for frequent jail-and-shelter users who were assigned housing and those who were not housed, and misclassification occurs as a result of noncompliance. The recommended intent-to-treat analysis which is based on initial group assignment is known to underestimate group mean differences. We use the general location model to estimate differences in group means after adjusting for misclassification in the binary grouping variable. Information on the misclassification is available through the sensitivity and specificity. We assume nondifferential misclassification so that misclassification does not depend on the outcome. We use the expectation-maximization algorithm to obtain estimates of the general location model parameters and the group means difference. Simulations show the bias reduction in the estimates of group means difference.

Chapter 1. Background: Asthma is the most common chronic childhood disease and is characterized by recurrent airway obstruction, bronchial hyper-responsiveness, and airway inflammation. Asthma is the leading cause of childhood hospitalization and school absenteeism in the United States. The associations between adverse respiratory effects and exposure to indoor nitrogen dioxide (NO2) and other byproducts of combustion such as particulate matter (PM) in particular ultrafine particulates (UFP), Ozone (O3) and Sulfur Dioxide (SO2), have been the focus of many epidemiological studies in recent years. Indoor exposure to NO2 and other pollutants from combustion may increase the risk of acute and chronic respiratory disease, reduce lung function, initiate and exacerbate asthma in children. The levels of exposure to NO2 indoors are of public health concern because children spend nearly 70% of their time indoors at home. According to the 2010 US Census report, approximately 39% of US households use natural gas for cooking, and the primary source of residential NO2 is a gas-fuel cooking appliance. Indoor levels of NO2 where NO2 sources are present can be much higher than outdoors, where the primary source of NO2 is vehicular traffic. Epidemiological studies in developed countries suggest that gas stoves used for cooking and/or heat are associated with an increased risk of asthma and respiratory symptoms in children. While there are numerous, epidemiological studies supporting an association between increased NO2 levels and gas stoves and asthma symptom severity in children, there are other studies that have examined the relationship in homes that did not observe significant associations. A better understanding of how NO2 and other indoor environmental (e.g., environmental tobacco smoke (ETS), allergens) exposures contribute to asthma morbidity in inner city preschool children will allow interventions to more effectively designed and implemented. To date, there are conflicting results on the role of exposure to indoor NO2 and its association with new-onset asthma in young inner-city children. The recent studies assessing the effects of indoor NO2 on asthma morbidity were limited to inner-city children, largely older, who were diagnosed with asthma. A gap in knowledge remains regarding the role indoor NO2 plays on the development of asthma in children not previously diagnosed. The scientific and public health rationale for conducting this dissertation was to describe the association of exposure to indoor NO2 and primary sources with the initiation and exacerbation of asthma symptoms among pre-school children with and without diagnosed asthma. The data analyzed in the current research come from a larger study of Endotoxin, Obesity, and Asthma (EOA) in the New York City Head Start Program, funded in the summer of 2002. The primary research objective of that study was to identify modifiable risk factors associated with asthma and asthma persistence among preschool children from low-income families living in select New York City neighborhoods with high pediatric asthma hospitalization rates. We conducted a cross-sectional analysis of data collected from the study questionnaire and home visit sampling at study enrollment. The analyses were performed in two phases: the first phases used data collected at study enrollment and the second phase used data collected 12-months after study baseline. Henceforth, the dissertation will refer to the first analyses as the baseline study and the second as the follow-up study. The research evaluated the association of NO2 exposure with asthma status among New York City Head Start children with and without asthma at study enrollment and with respiratory symptoms among children with asthma at 12-month follow-up. Chapter 2. Baseline Study: We conducted a cross-sectional analysis of data collected from the study questionnaire and home visit sampling at study enrollment. Specifically, the research sought to evaluate the association of NO2 exposure with asthma status among New York City Head Start children with and without asthma at study enrollment and with respiratory symptoms among children with asthma at enrollment. A total of 503 children were included in the baseline study. A total of 105 children (20.9%) met the criteria for both asthma and allergy, and 67 (13.3%) met the criteria for asthma alone. Girls made up 51.7% and boys, 48.3% of the 503 study participants. Descriptive analyses suggested that asthma/allergy status was associated with: male gender, non-Mexican ethnicity/national origin, presence of a smoker in the child’s home, number of smokers in the child’s home, self-reported parental history of asthma, mother’s education level and sensitization to one or more of the four allergens. Logistic regression models were used to investigate the magnitude and direction (as well as trend) of the association between childhood asthma and indoor NO2 sources in the child’s home. Chapter 3. Follow-up Study: Our follow-up study involved the analysis of the 12-month follow-up data from the study of Endotoxin, Obesity, and Asthma in the New York City Head Start Program funded in the summer of 2002. We focused on assessing the magnitude and direction of the associations of exposure to indoor NO2 levels (based on baseline NO2 measurements) with children’s asthma status and with symptom severity among asthmatics at 1-year follow-up. For the follow-up study, we categorized children by whether their asthma status had changed since baseline. Descriptive analyses were performed looking at key characteristics by “change in asthma status.” Children’s asthma status at baseline and at follow-up, were based on responses to the questionnaire. We analyzed indoor NO2 level measurements at baseline in relation to asthma outcomes on follow-up. We did not have enough data on NO2 levels at follow-up to analyze them in relation to asthma status on follow-up. Unless the family had relocated since baseline and/or reported changes since baseline in the use of gas appliances or the number of smokers in the home, we assumed that baseline NO2 levels in the participating children’s homes were reasonable proxies for current exposures. We looked at the number of children who moved since baseline and whether the move (for example, looking at gas stove status, age of new building) may have impacted indoor NO2 levels. Of the 503 children who were included in the baseline analyses, 47.3% had data on asthma status on follow-up. A total of 238 children (111 male, 127 female) were grouped into the four mutually exclusive outcome categories: 122 (51.3%) did not have asthma at baseline or on follow-up, 34 (14.3%) had asthma on follow-up but not at baseline, 65 (27.3%) had asthma at baseline but not on follow-up, and 17 (7.1%) had asthma at baseline and on follow-up. The mean age at 1-year follow-up was 59.5 months (6.95), and neither age nor gender was associated with asthma. The distribution of ethnicity/national origin among the 238 children remained the same as at baseline; no one ethnicity group experienced disproportionate loss to follow-up, and asthma status remained associated with non-Mexican ethnicity/national origin, although 44.1% with new-onset asthma were of Mexican background. Asthma was also associated with self-reported parental history of asthma and allergy in children, but nearly 80% of children with new-onset asthma had no such parental history of asthma. More parents of children with new-onset (35.3%) or persistent asthma (23.5%) than of other children reported making efforts to reduce risk factors or triggers for asthma exacerbations in the past 12 months. Chapter 4. Dissertation Conclusion : The primary objective of the dissertation research was the examination of the relationship between asthma and asthma severity and exposure to gas cooking and residential NO2. In both our baseline and 12-month follow-up studies, exposure to indoor NO2 was represented by the baseline measurement of NO2 and the NO2 surrogate, gas stove. Asthma status of children was based on parental responses on the questionnaire regarding asthma symptoms and urgent care visits due to respiratory distress over the course of each 12-month period prior to the conducting study questionnaires. For both studies, we did not find an association between exposure to NO2 levels at baseline and asthma status or severity. Our findings contradict the results of most recent studies of both NO2 levels and residential sources of NO2 and their effects on asthma symptoms in very young children. However, it remains difficult to compare our results we those of previous published studies because those studies primarily focused on children who were diagnosed with asthma, whereas our research included preschool aged children with and without asthma. Based on our findings and the fact they conflict with other epidemiological studies, of which there were also conflicting results, we feel that the relationship between asthma symptoms and NO2 exposures remains ambiguous. The lack of consistent results of epidemiological research raises questions that should be the focus of future epidemiological studies. What are the roles of co-pollutants and co-risk factors? Does NO2 work alone or in concert with other indoor pollutants? There exists a real lack of understanding on the possible synergistic effects of exposure to NO2 and other combustion byproducts. Important to furthering our knowledge of the role of exposure to indoor NO2 and asthma is determining whether NO2 acts as a surrogate for co-pollutants that are considered risk factors for asthma and other respiratory conditions. Another focus of future indoor pollution studies should be the development of effective methods and technologies for measuring the constituents of the complex mixture of pollutants in indoor air; these methods and technologies can then be applied in personal monitoring of exposure to indoor pollutants in epidemiological studies that would help to determine with much more accuracy the effects of individual indoor pollutants on asthma and other respiratory symptoms. This knowledge would help in the development of more effective public health and environment policies towards reducing the burden of childhood asthma.

published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Medical Sciences

Diabetes mellitus Typ 1 und Allergien vom Soforttyp gehören zu den häufigsten chronischen Erkrankungen des Kindes- und Jugendalters. Diabetes mellitus Typ 1 wird verursacht durch eine autoimmune Zerstörung der Beta-Zellen des Pankreas. Aus immunologischer Sicht wird dieser Prozess durch TH1-Zellen dominiert. Im Gegensatz dazu wird vermutet, dass Allergien vom Soforttyp, wie die allergische Rhinitis, das allergische Asthma und die allergische Urtikaria mit TH2-Zellen assoziiert seien. Die Hypothese, dass TH1- und TH2-Zellen sich gegenseitig in ihrer Aktivität hemmen, ist immer noch gültig. Ziel unserer Fall-Kontroll-Studie war es, die Assoziation zwischen Typ 1 Diabetes und IgE-vermittelten Allergien zu untersuchen. Zur Prüfung unserer Forschungshypothese wurden ein standardisierter, evaluierter Fragebogen sowie verschiedene Laboranalysen herangezogen. Es konnte gezeigt werden, dass Diabetes mellitus Typ 1 mit einem erhöhten Risiko für das gleichzeitige anamnestische Vorliegen IgE-vermittelter allergischer Symptome assoziiert sein könnte. Somit konnten wir bestätigen, dass die noch heute weit verbreitete TH1/TH2-Hypothese eine Vereinfachung tatsächlich viel komplizierterer immunologischer Vorgänge darstellt. Um diese Assoziation im Detail zu prüfen, bedarf es jedoch weiteren populationsbasierten epidemiologischen Studien.:I. Bibliographische Beschreibung 7 II. Abkürzungsverzeichnis 9 1. Einführung 11 1.1 Epidemiologie und Pathogenese des Diabetes mellitus Typ 1 11 1.2 Epidemiologie und Pathogenese von Allergien vom Soforttyp 13 1.3 Aktueller Forschungsstand zum Thema 14 2. Das Promotionsprojekt 17 2.1 Forschungshypothese und Fragestellung 17 2.2 Patienten und Methoden 17 2.3 Statistische Datenauswertung 19 2.4 Ergebnisse 20 2.5 Einordnung in den aktuellen wissenschaftlichen Diskurs 23 3. Publikationsmanuskript 29 4. Zusammenfassung der Arbeit 43 5. Literaturverzeichnis 47 III. Erklärung über die eigenständige Abfassung der Arbeit 55 IV. Curriculum Vitae 57 V. Liste der Veröffentlichungen 59 VI. Danksagung 61