THE STUDY OF OCCUPATIONAL RISK FACTORS AND INTERVENTIONS FOR BAKER’S ALLERGY AND ASTHMA AMONG SUPERMARKET BAKERY WORKERS By Roslynn Baatjies Thesis presented for the degree of Doctor of Philosophy in the School of Public Health and Family Medicine University of Cape Town August 2013 n w The copyright of this thesis vests in othe author. No T quotation from it or information derived from it is to be e published without full acknowledgement of the source. p The thesis is to be used fora private study or non- C commercial research purposes only. f o Published by the Universyity of Cape Town (UCT) in terms t of the non-exclusive liciense granted to UCT by the author. s r e v i n U THE STUDY OF OCCUPATIONAL RISK FACTORS AND INTERVENTIONS FOR BAKER’S ALLERGY AND ASTHMA AMONG SUPERMARKET BAKERY WORKERS By Roslynn Baatjies Thesis presented for the degree of Doctor of Philosophy in the School of Public Health and Family Medicine University of Cape Town August 2013 Supervisor: Professor Mohamed Fareed Jeebhay Co-supervisors: Professor Dick Heederik and Dr Tim Meijster This thesis is presented in fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) in the School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town. The work on which this thesis is based is original research and has not, in whole or in part, been submitted for another degree at this or any other university. The contents of this thesis are entirely the work of the candidate, or in the case of multi-authored published papers, constitutes work for which the candidate was the lead author. The contribution of the candidate to included multi- authored papers is further delineated in the preface to the thesis and in the introduction to each included paper as appropriate. ____________________________ Roslynn Baatjies August 2013 ABSTRACT Background: Baker’s asthma is the most serious manifestation of occupational allergy among bakery workers. It is caused by IgE-mediated sensitisation and subsequent allergic reaction in the airways to specific occupational airborne allergens in flour or baking ingredients. Major aims of this study were to: characterise asthma phenotypes and environmental exposure to flour allergens among bakers and modifying factors; study associations between phenotype and environmental exposure and identify potential modifying factors of this association; determine the effectiveness of specific interventions in reducing exposure and the risk of sensitisation or allergic respiratory disease. Methods: A cross-sectional study was conducted among 517 bakery workers employed in 31 supermarkets. Health outcomes were assessed using a standardized questionnaire, immunological tests (sIgE, sIgG), methacholine challenge test and fractional exhaled nitric oxide (FeNO). Exposure assessment conducted pre- and post-intervention entailed determination of inhalable concentration of particulate mass and specific allergen levels. The intervention employed a group-randomised design to evaluate dust control measures. Results: Prevalence of probable occupational asthma (POA, 13%) was higher than atopic (AA, 6%), non-atopic (NAA, 6%) and work-aggravated asthma (WAA, 3%). Sensitisation to flour allergens was a major determinant of elevated FeNO among bakers. Bread bakers had the highest dust particulate (mean = 1.33 mg/m3) and allergen exposures. Exposure- response relationships followed a bell-shaped curve, with the prevalence of IgE- sensitisation, allergic symptoms and POA, increasing up to 10-15 µg/m3 of airborne wheat allergen concentrations before declining. The association for IgE sensitization was not modified by IgG4 to wheat. The overall effect of the intervention revealed a 50% decrease in mean flour dust, wheat allergen and rye exposures in bakeries. Conclusion: Occupational asthma is the most common phenotype among supermarket bakery workers, with sensitisation to cereal flour allergens being the main determinant of allergic airway inflammation. The bell-shaped exposure response relationship is not modified by the presence of blocking antibodies and is probably due to a healthy worker effect. The multi-pronged intervention strategy was effective in reducing airborne flour dust and allergen levels. It is recommended that further studies investigate the long term health impact of these interventions in reducing the disease burden. ACKNOWLEDGEMENTS I would like to express my sincere thanks and acknowledge the following people who have contributed to successful completion of this thesis: My supervisor, Prof Mohamed Fareed Jeebhay and co-supervisors, Professor Dick Heederik and Dr Tim Meijster (University of Utrecht, Netherlands), for their insights, guidance, patience and support Research assistant, Ms Nadia Viljoen and Sisters Leonie Ritchie, Faieza Omar, Sister Dawn Venter, Sister Shiela Parrot, Sharief Abrahams in conducting the fieldwork, including the data coding and management Ms Verne Barnard, Alta Olckers and technologists from the Department of Respiratory Medicine and Lung Institute of the University of Cape Town for the pulmonary function and methacholine challenge testing Prof Rodney Ehrlich and Jonny Myers and support staff, Sharon Ferguson, Faranaaz Bennett of the Centre for Occupational and Environmental Health Research Unit in the School of Public Health and Family Medicine at the University of Cape Town Dr Shahieda Adams, my friend and colleague for encouragement, support and comments Emmanuel Rusford and Shafiek Hassan from the Department of Environmental and Occupational Studies at the Cape Peninsula University of Technology for assistance with the collection and analysis of the environmental samples Ms Jhurien van Niekerk for data entry and management and Mr Rauf Sayed and Prof Francesca Little, from the Departments of Public Health and Statistical Sciences at the University of Cape Town and Professor Hans Kromhout (University of Utrecht, Netherlands) for statistical advice and support SACCAWU, their Shopstewards' Committees and members and specifically Mr Faghmi Benn who sat on the coordinating committee of the project The bakery staff of Pick and Pay in the Western Cape that participated in the project, including Sisters Tessa van der Walt, Ricardo DuPreez, who sat on the coordinating committee of the project. A special thanks to Mr Louis De Beer, head of the national bakery division for his support Funding support provided by the research grants from the Medical Research Council of South Africa, National Research Foundation, THRIPP, Fogarty International Centre and Pick and Pay Bakery division I want to thank my mom for always encouraging me, believing in me and supporting me emotionally through this journey. Finally, I wish to thank my partner, and best friend, Troy Jermaine Neethling, for his unconditional love, unwavering support and encouragement. PREFACE This thesis includes published papers, as per general provision 6.7 in the General Rules for the Degree of Doctor of Philosophy (PhD) of the University of Cape Town, and with the approval in 2013 of the University Doctoral Degrees Board. The following five papers are formally included as part of the thesis: 1. Baatjies R, Lopata AL, Sander I, Raulf-Heimsoth M, Bateman E, Meijster T, Heederik D, Robins TG, Jeebhay MF. Determinants of asthma phenotypes among supermarket bakery workers. European Respiratory Journal 2009; 34(4):825-833. 2. Baatjies R, Meijster T, Lopata AL, Sander I, Raulf-Heimsoth M, Heederik D, Jeebhay MF. Exposure to flour dust in South African supermarket bakeries: Modeling of baseline measurements of an intervention study. Ann. Occup. Hyg 2010; 54(3): 309–318 3. Baatjies R, Jeebhay MF. Sensitisation to wheat is a major determinant of elevated exhaled nitric oxide in bakers. Occup Environ Med, 2013;70(5):310-316 4. Baatjies R, Meijster T, Heederik D, Jeebhay MF. Exposure-response relationships for wheat allergen exposure and asthma. Submitted to Occupational and Environmental Medicine 5. Baatjies R, Meijster T, Heederik D, Sander I, Jeebhay MF. Effectiveness of interventions to reduce flour dust exposure in supermarket bakeries. Submitted to Allergy The contribution of the candidate to each paper is outlined in the introduction to each paper. The candidate was the lead author for each paper, prepared all datasets for the analyses, conducted all the analyses and drafted all versions of the manuscripts. The candidate was responsible for circulating the manuscripts to co-authors, reviewing co-author comments and suggestions before integrating them into the manuscript as appropriate. All co-authors critically reviewed and approved the submitted manuscripts prior to submission. TABLE OF CONTENTS DECLARATION ABSTRACT ACKNOWLEDGEMENTS Page CHAPTER 1: INTRODUCTION 1.1 Introduction 2 1.2 Study aim 3 1.3 Objectives of the study 4 1.4 Structure of the thesis 4 1.5 REFERENCES 8 CHAPTER 2: LITERATURE REVIEW 2.1 Background and review of the literature on bakery workers 10 2.2 The baking process and high risk environmental exposure 10 settings 2.3 Constituents of flour dust and potential allergen and their 11 sources 2.4 Epidemiology of allergic sensitisation and asthma 13 associated with flour dust 2.5 Exposure assessment strategies for characterising 18 exposure to flour dust 2.6 Environmental risk factors and exposure-response 32 relationships for flour dust and baker’s asthma 2.7 Host-associated risk factors for allergic sensitisation and 33 asthma associated with flour dust 2.8 Prevention strategies for reducing flour dust exposure and 35 baker's asthma
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