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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