Appendix by Levone


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Title: Application of a prediction model for work-related sensitization in bakery


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 Netherlands 1, Community Medicine Department, Faculty of

Medicine, University of Indonesia, Jakarta, Indonesia 2, 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 Netherlands 5

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                If yes                 1.5
sneezing ?”

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)))

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

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 work-

related 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.


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

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]


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