Supplementary materials - European Respiratory Journal

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Title: Application of a prediction model for work-related sensitization in bakery
workers
Authors: E.Meijer1, E. Suarthana1,2, J. Rooijackers1,4, D.E. Grobbee5 , J.H. Jacobs1, T.
Meijster1 , J.G.R. de Monchy3, E. van Otterloo1, G.B.G.J..van Rooy 1,4, J.J.G. Spithoven1,
V.A.C. Zaat4, D.J.J. Heederik1,5.
Affiliations: Institute for Risk Assessment Sciences, Division Environmental Epidemiology,
Utrecht University, Utrecht, The Netherlands1, Community Medicine Department, Faculty of
Medicine, University of Indonesia, Jakarta, Indonesia2, Department of Allergology,
University Medical Center Groningen, Groningen, the Netherlands3, Netherlands Expertise
Centre for Occupational Respiratory Disorders, Division Heart and Lungs, University
Medical Center Utrecht, Utrecht, the Netherlands4, Julius Center for Health Sciences and
Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands5
Development of the prediction model.
Data from a cross sectional study among 390 Dutch bakery workers were used to derive a
prediction model for IgE sensitization to wheat and or α-amylase allergens.[1] Workers were
asked to complete a self-administered questionnaire which was derived from the IUATLD [2]
and the MRC-ECCS [3]. The questionnaire consisted of employment (job, tasks) data, history
of lower and upper respiratory symptoms, allergic symptoms due to common allergens,
symptoms suggesting bronchial hyperresponsiveness, work-related upper and lower
respiratory symptoms, skin symptoms, absenteeism, medication use, changes in tasks or jobs,
and smoking habits. Informed consent was obtained from all participating workers. Venous
blood was drawn to identify specific IgE antibodies against wheat and α-amylase allergens.
IgE serology was measured with a commercial immunoassay (Pharmacia Unicap system,
Pharmacia Diagnostics, Sweden). Class II positive IgE serology was used in the analyses. The
final predictors in the model were established after backward stepwise selection and a
bootstrapping procedure to adjust for optimism as described by Harrell.[4,5] The final
diagnostic model consisted of four predictors (Table S1). The model showed good calibration
(H-L test p-value=0.748) and reasonable discrimination (ROC area 0.73 (CI: 0.67-0.79)). For
practical application the model, based on questionnaire information, was transformed into a
score chart to calculate sum scores. (Sum scores = (asthma attacks*2) + (rhinitis
symptoms*2) + (conjunctivitis symptoms*1) + (during work symptoms*1.5). Each symptom is
valued as 1 when present and 0 when absent.
Table S1. Score chart
Predictors
Answer
Score
“Have you ever had asthma in the past 12 months?”
If yes
2
“Have you ever had allergic rhinitis including hay-fever?”
If yes
2
“Have you ever had itchy and/or red eyes in the past 12 months?”
If yes
1
“Do you experience more of the following symptoms during work:
shortness of breath, chest tightness, itchy eyes, itchy nose, or
sneezing ?”
If yes
1.5
Sum scores
Max
6.5
Sum score
0
1
2
3.5
4.5
5.5
6.5
Predicted probability (%)
9
14
20
31
42
53
64
The predicted probability of flour sensitization:
= 1 / (1 + EXP( - ( - 2.32 + 0.92 *asthma + 0.90 *rhinitis + 0.46* conjunctivitis + .62 * during work symptoms)))
1
Risk categories
The sum scores were categorized according to the cut-off points: 0 to 1: low risk; 1.5 to 3.0:
intermediate risk; 3.5 or higher: high risk of being sensitized. The cut-off point of 1.5
corresponds to an overall sensitization rate of 20% and classified individuals below this score
into the low score group. A cut off point of ≥ 3.5 was used to classify workers in the high
score group.
The short screening questionnaire
A short self-administered questionnaire was developed by incorporating the four predictors
from the diagnostic model with additional questions on respiratory symptoms, allergy, and
bronchial hyper responsiveness invariably associated with the outcome (sensitization to wheat
and/or α-amylase). The questionnaire was also enriched with questions on absenteeism,
medication use, doctor’s visit, change in job title due to allergic symptoms, and smoking
habit. The questionnaire was produced in a 2-pages scan-able form. The first page contained
basic information and job history (job title, task, percentage of time spent as bread baker, date
start working in the current job, total weekly working hours, and shifts). The second page
consisted of the above mentioned 19 questions.
Evaluation of the results
Performance of the model was evaluated in 674 traditional and industrial bakers who
participated both in the health surveillance program (n= 5,325) as in a validation study. This
validation study comprised of 890 individuals from 340 randomly selected traditional and 28
industrial bakeries.[6] All workers were asked to complete a long questionnaire that matched
closely the original questionnaire used to develop the model. Blood for IgE serology
(common and specific allergens) was drawn from 867 individuals. So, scores (predicted
probabilities for flour sensitization) from the screening questionnaire were available for every
2
individual and were used to evaluate questionnaire responses and IgE serology derived from
the validation study.
For clinical evaluation no specific challenge testing with flour allergens was carried out. The
diagnosis of work-related asthma was based on the American College of Chest Physicians
(ACCP) consensus statement [7]. Work-related asthma was excluded if non specific bronchial
hyperresponsiveness (NSBHR) with histamine was absent while the baker was at work.
All workers with NSBH when at work performed serial peak expiratory flow rate (SPEFR)
measurements during 2 weeks at work and 2 weeks away from work after which histamine
challenge with assessment of NSBH was repeated. A change of one doubling dose increase in
PD20 was regarded as significant. SPEFR measurements were interpreted using direct visual
analysis by a panel of two experienced physicians. A diurnal variation in PEFRs of > 20%
was considered as diagnostic criterion [8].
The medical diagnosis of OA was based on four criteria according to the ACCP, and was
considered present when there was a history of work-related asthmatic symptoms,
sensitisation to a workplace allergen, NSBHR at work and serial PEFR showing a workrelated pattern and/or at least one doubling dose increase in PD20 comparing work and away
from work[8]. Work-exacerbated asthma was defined as workers not fulfilling the criteria for
OA and known to have pre-existing asthma in which symptoms worsened during work and
diminished away from work
Work-related allergy was considered present if there was a history of work related upper
respiratory or eye symptoms that disappeared or diminished after work in the presence of
flour sensitization.
Serology
Specific IgE antibodies against wheat and α-amylase allergens were measured with an earlier
developed and modified enzyme immunoassay.[8] An optical density (OD) of 492 exceeding
3
the OD +0.1 of the reagent blank (no serum control) was considered as a positive IgE
serology to wheat or α-amylase allergens.
For the clinical evaluation, a commercial immunoassay (Pharmacia UniCAP assay, Pharmacia
Diagnostics, Sweden) was used to detect IgE antibodies against wheat flour, α-amylase, and
five common inhalant allergens. Individuals with levels of class 1 (> 0.35 kU/L) or higher
were considered positive. The EIA has been compared earlier to the CAP assay for fungal amylase and wheat allergens. For -amylase, the agreement was good across the
measurement range. For wheat, the sensitivity was lower, especially at lower titres, but the
specificity was high. The overall agreement was satisfactory, and good at higher titres.[8]
References
1. Oostenbrink JH TJ, Tempels Z, Heide S, Steketee HA, Kerkhof M, Monchy JGR.
Aard en omvang van beroepsgebonden klachten bij werknemers in bakkerijen,
meelfabrieken en grondstoffenindustrie. Groningen: Academisch Ziekenhuis
Groningen, 2002.
2. Burney PG, Laitinen LA, Perdrizet S, et al. Validity and repeatability of the
IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison.
Eur Respir J 1989;2(10):940-5.
3. van der Lende R, Orie NG. The MRC-ECCS questionnaire on respiratory
symptoms (use in epidemiology). Scand J Respir Dis 1972;53(4):218-26.
4. Harrell FE, Jr., Lee KL, Mark DB. Multivariable prognostic models: issues in
developing models, evaluating assumptions and adequacy, and measuring and
reducing errors. Stat Med 1996;15(4):361-87.
5. Suarthana E, Vergouwe Y, Moons C, de Monchy J, Grobbee D, Heederik D,
Meijer E. A diagnostic model for the detection of sensitization to wheat allergens
was developed and validated in bakery workers. J Clin Epidemiol 2010; In Press.
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6. Jacobs JH, Meijster T, Meijer E, Suarthana E, Heederik D. Wheat allergen
exposure and the prevalence of work-related sensitization and allergy in bakery
workers. Allergy. 2008;63(12):1597-604.
7. Tarlo SM, Balmes J, Balkissoon R, Beach J, Beckett W, Bernstein D,Blanc PD,
Brooks SM, Cowl CT, Daroowalla F, Harber P, Lemiere C, Liss GM, Pacheco
KA, Redlich CA, Rowe B, Heitzer J. Diagnosis and management of work-related
asthma: American College Of Chest Physicians Consensus Statement. Chest.
2008;134:1S-41S.
8. Cote J, Kennedy S, ChanYeung M, Sensitivity And Specificity Of PC20 And Peak
Expiratory Flow Rate In Cedar Asthma. J Allergy Clin Immunol 1990; 85 : 592598.
9. Doekes G, Douwes J, Wouters I, de Wind S, Houba R, Hollander A. Enzyme
immunoassays for total and allergen specific IgE in population studies. Occup
Environ Med 1996;53(1):63-70.
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