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FACULTY OF HEALTH SCIENCES
UNIVERSITY OF CAPE TOWN
Recent developments in occupational asthma research in the
Western Cape
Prof Mohamed F Jeebhay
Occupational Medicine Division and
Centre for Environmental & Occupational Health Research
School of Public Health and Family Medicine, University of Cape Town
SASOM Western Cape AGM and Conference, Nov 2018
Classification of work-related asthma and rhinitis
(Lemiere and Vandenplas, 2017)
University of Cape Town Faculty of Health Sciences
The occupational setting offers a convenient opportunity to study the
complex relationships between allergen exposures, their interaction
with other co-exposures and the risk of developing asthma
• Major workplace allergens are well characterized and allergen exposure
can be estimated, either through immunological techniques or careful
recording of stereotyped job tasks
• Large workplace populations are easily enumerated, readily accessible and
assembled, allowing for efficient study of representative populations
• Prior sensitisation to workplace allergens among new employees is rare
and early immunogenesis can be examined following initial exposure
• Incidence of IgE antibody sensitization, allergy and asthma can be high,
developing in most instances within just 2 years of initial exposure
• Highly specific asthma phenotypes can be established
• The majority of workers remain healthy, allowing for the examination of
early responses that may lead to immune tolerance
(Jones, 2008)
University of Cape Town Faculty of Health Sciences
Incidence of OA in LMIC countries appears to be as low as in HIC countries -
under-detection, under-reporting or low risk populations?
Occupational asthma in Europe,
Incidence rate ratio relative to
2007 (Mathius, 2017)
Occupational asthma in the
developing and industrialised
world (Jeebhay, IJTLD, 2007)
(Lemiere and Vandenplas, 2017)
University of Cape Town Faculty of Health Sciences
Work-related asthma in a sanitary
production plant worker
Investigators: Knight D, Lopata A, Nieuwenhuizen N, Jeebhay MF
University of Cape Town Faculty of Health Sciences
OASYS Graph of a worker
handling cellulose fibre:
• >20% variability in
PEF measurements
• Work effect Index
(WEI) = 3.8
(Cut off = <2.5)(http://www.occupationalasthma.com/oasys.aspx)
AWAY FROM WORK
Serial PEF in a worker with work-related asthma symptoms in a
sanitary pad production plant (Knight, et al, AJIM, 2018)
Occupational asthma due to cellulose dust confirmed using a specific
bronchial challenge test
SBT and continuous dust
monitoring in a sanitary
pad production worker
(ACGIH TLV: 10mg/m3)
(Knight, et al, AJIM, 2018)
FEV1- cellulose
challengeCellulose dust
University of Cape Town Faculty of Health Sciences
BAKER’S ALLERGY AND ASTHMA
Investigators: Baatjies R, Meijster T, Heederik D, Sander I,
Al-Badri F, Jeebhay MF
University of Cape Town Faculty of Health Sciences
Average current wheat exposure g/m3
0 10 20 30 40 50
Pre
va
len
ce
0.0
0.1
0.2
0.3
0.4
0.5
0.6
Sensitisation to wheat
Allergic chest symptoms
Probable occupational asthma
Allergic ocular-nasal symptoms
Exposure-response relationships for wheat allergen exposure
and asthma (Baatjies et al, OEM, 2015)
Sensitisation to wheat
Allergic ocular-nasal symptoms
Probable occupational asthma
Inhalable dust
~ 0.5 mg/m3
= ACGIH limit
Atopy is an effect modifier for wheat sensitisation among bakers
(Baatjies et al, OEM, 2015)
ATOPIC
NON-ATOPIC
Average current wheat exposure g/m3
0 10 20 30 40 50
Pre
vale
nce (
%)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Sensitisation in atopics
Sensitisation in non-atopics
Sensitisation in all workers
Relationship between wheat sensitisation and wheat allergen concentration among supermarket bakery workers, stratified by atopic status
Atopic
Non-atopic
Group randomised interventionstudy of supermarket bakeries (n=31)
Effectiveness of interventions to reduce flour dust exposures in
supermarket bakeries (Baatjies et al, OEM, 2014)
A multi-faceted focused intervention yields the greatest
reduction in flour dust and allergen levels in bakeries (Baatjies et al, OEM, 2014)
University of Cape Town Faculty of Health Sciences
Relative decline in allergic respiratory health outcomes in supermarket bakery
workers (n=337) one year post-intervention
(Al Badri et al, 2018 In preparation)
Health outcome Intervention Grp
(n=244)
Control Grp
(n=93)
Work-related ocular nasal symptoms 37 (40%) 17 (50%)
Work-related chest symptoms 24 (39%) 5 (36%)
Asthma attack in the last 12 months 6 (62%) 2 (40%)
Cereal flour sensitisation
(IgE >0.35kU/L)
14 (21%) 1 (6%)
FeNO (group mean ± SD), ppb 2.2 ± 23.0 1.7 ± 14.5
- FeNO >25ppb group 16.9 ± 35.2 7.7 ± 24.2
- FeNO >50ppb group 26.1±45.5 11.5±39.3
>10% decline in FeNO from baseline 125 (51%) 40 (43%)
University of Cape Town Faculty of Health Sciences
Determinants of 10% or greater decline in FeNO among
supermarket bakery workers in multivariate models(Al Badri et al. In preparation)
Predictor Crude odds ratio (CI) Work-related ocular-nasal symptoms present
Work-related ocular-nasal symptoms absent
OR 95% CI p-value OR 95% CI p-value OR 95% CI p-
value
Intervention vs Control Group
1.62 0.93 - 2.81 0.088 3.73 1.22 - 11.42 0.021 1.62 0.56 - 2.25 0.747
Current smoker 0.92 0.56 - 1.52 0.749 0.99 0.42 - 2.39 0.995 1.00 0.52 - 1.92 0.996
Cereal flour
sensitisation
(IgE≥ 0.35 kU/L)
0.45 0.25 - 0.81 0.008 0.43 0.16 - 1.17 0.099 0.69 0.31 - 1.53 0.357
Baseline FeNO>25ppb 3.57 1.94 - 6.59 <0.001 5.03 1.79 - 14.16 0.002 3.03 1.35 - 6.77 0.007
University of Cape Town Faculty of Health Sciences
WORK-RELATED ASTHMA IN SPICE
MILL WORKERS
Investigators: van der Walt A, Baatjies R, Singh T, Jeebhay MF
Environmental factors associated with work-related serial changes in
exhaled nitric oxide - FeNO (ln) in spice mill workers
PREDICTORS Baseline FeNO
(>50ppb) pre-shift
FeNO increase
(>12%) across
8-hour shift
FeNO increase
(>12%) across
24-hour period
Particulate mass concentration (mg/m³)
- Med vs Low 0.22 (0.02-2.49) 2.12 (0.51-8.82) 3.77 (1.01-14.24)
- High vs Low 0.91 (0.20-4.19) 2.35 (0.75-7.31) 2.27 (0.75-6.90)
Chili pepper concentration (μg/m³)
- Med vs Low 0.23 (0.03-1.63) 1.50 (0.37-6.14) 2.57 (0.68-9.72)
- High vs Low 0.72 (0.15-3.56) 2.11 (0.63-7.03) 2.08 (0.63-6.82)
Garlic allergen concentration (μg/m³)
- Med vs Low 0.51 (0.04-6.80) 1.64 (0.31-8.63) 1.05 (0.21-5.18)
- High vs Low 1.31 (0.31-5.53) 1.89 (0.71-5.05) 1.21 (0.50-2.91)
Logistic regression model adjusted for gender, atopy, smoking, recent green vegetable intake
Particulate mass concentration (mg/m³) tertiles: high>3.78; medium>1.18<3.78; low<1.18
Chilli pepper allergen concentration (mg/m³) tertiles: high>0.92; medium>0.09<0.92; low<0.09
Garlic allergen concentration (mg/m³) tertiles: high>0.235; medium>0.066<0.235; low<0.066
(van der Walt et al, OEM, 2016)
University of Cape Town Faculty of Health Sciences
WORK-RELATED ASTHMA IN POULTRY
FARMERS
Investigators: Ngajilo D, Singh T, Ratshikopa E, Dayal P,
Baatjies R, Jeebhay MF
Allergic sensitisation and work related asthma in poultry
workers (Ngajilo et al., AJIM, 2018)
Each OR represents a separate model adjusted for gender and atopy
Outcome Casual versus
permanent work
<2 yrs vs >6yrs
employment
Episode of high
GDF exposures
causing asthma
symptoms
Work-related ocular-nasal
symptoms
0.15 (0.02-1.24) 1.05 (0.45-2.46) 2.73 (1.58-4.73)
Work related chest
symptoms
- 0.95 (0.32-2.82) 4.73 (2.35-9.54)
Sensitization to at least one
poultry work related
allergen
0.99 (0.24-4.06) 2.60 (1.01-7.34) 1.04 (0.56-1.93)
Sensitization to chicken
specific allergens
3.68 (0.83-16.41) 1.36 (0.22-8.41) 0.68 (0.25-1.84)
Bronchial reversibility 10.85 (1.95-60.26) 2.60 (0.41-16.49) 0.90 (0.29-2.78)
Atopic asthma** - 0.61 (0.09-4.17) 1.98 (0.55-7.13)
Non-atopic asthma** - 0.38 (0.08-1.82) 3.65 (1.13-11.76)
Each OR represents a separate model adjusted for age, gender and smoking
University of Cape Town Faculty of Health Sciences
WORK-RELATED ASTHMA SEAFOOD
PROCESSORS
Investigators: Jeebhay MF, Baatjies R, Lopata AL
University of Cape Town Faculty of Health Sciences
Allergic (IgE) and non-allergic inflammation in
seafood exposed workers
(Jeebhay and Bang, in preparation)
Exposures >30 ng/m3 (fishmeal, canning) associated with
2-fold increased asthma risk (OR =2.25, CI:1.06-4.75)
Cumulative pilchard antigen conc. (ng/m3-yr)
(Models: linear *p<0.05 spline *p<0.10)
Current pilchard antigen conc. (ng/m3)
(Models: linear *p<0.05 spline *p<0.10)
100 ng/m3
Sensitisation
NSBH**
airway hyperresponsiveness
Work-related asthma
symptoms (WRAS)*
NSBH*
WRAS*
Sensitisation*
Exposure-response relationships for work-related asthma and
airborne fish antigen exposures (current vs cumulative exposure)
among fish processors in the Western Cape (Jeebhay et al, iFISH 2018)
University of Cape Town Faculty of Health Sciences
WORK-RELATED ASTHMA IN HEALTH
WORKERS
Investigators: Mwanga H, Singh T, Ratshikopa E, Baatjies R,
Jeebhay MF
Allergic sensitisation profiles of health care workers at Groote Schuur
hospital – new agents causing asthma (n=339)
(Mwanga et al. EAACI 2016)
Peroxidase: 19 (6%); OPA: ortho-phthalaldehyde; *Sensitisation to at least one occupational allergen (OPA,
Chlorhexidine or Latex) and peroxidase negative (in relation to latex)
47
4
1 1 1
6
0
5
10
15
20
25
30
35
40
45
50
Atopy (Phadiatop
test)
OPA Chlorhexidine Latex Hev b5 Latex Hev b6.02 Sensitisation to at
least one
occupational
allergen
Pe
rce
nta
ge
(%
)
Latex allergy prevalence in
previous studies of tertiary
hospitals:
TBH - 20.8% (De Beer, 1999)
GSH – 9.2% (Potter, 2001)
RXH – 5% (Braithwaite, 2001
RESEARCH FOCUS ON ALLERGENS AND ASTHMA
Theme 1Risk factors for allergy
and asthma prevention
Theme 2Identification,
characterisation and development of
allergens
Theme 3Improved surveillance,
diagnosis and treatment
Environmental exposure
characterisation of workplaces
Allergy and asthma profile in working
populations
Risk factors (host, environment) characterisation and
interaction
Intervention tools (primary, secondary,
tertiary levels)
Identification of risk allergens
Molecular characterisation of
allergens
Diagnostic and therapeutic allergen
development
Allergen detectionand monitoring
Component resolved IgE profiling
Early immunological, inflammatory, pulmonary
and genetic markers
Focused risk allergen test battery development
IgE pattern identification, marker allergens and
epitope profilesIntegration of risk assessment,
surveillance, diagnostic, treatment and preventive tools
ALLERGY AND ASTHMA PREVENTION
University of Cape Town Faculty of Health Sciences
THANK YOU