Int Arch Occup Environ Health (2003) 76: 167–170
DOI 10.1007/s00420-002-0396-3
SH O RT CO MM U N IC A T IO N
Jonas Brisman Æ Linnéa Lillienberg Æ Lars Belin
Mats Åhman Æ Bengt Järvholm
Sensitisation to occupational allergens in bakers’ asthma
and rhinitis: a case – referent study
Received: 20 November 2001 / Accepted: 9 September 2002 / Published online: 1 November 2002
Springer-Verlag 2002
Abstract Objectives: To study the importance of sensitisation to occupational allergens for the occurrence of
asthma and rhinitis in bakers. Methods: This is a nested
clinical case–referent study of bakers based on a cohort
of Swedish former bakery students. Cases were asthmatic (n=25) or rhinitic bakers (n=20). Randomly
selected bakers (n=44) were referents. All subjects
underwent skin prick tests (SPTs) with common allergens, flours, fungal a-amylase and the storage mite
L. destructor. Indices of airway inflammation were
assessed in serum and the nose. Results: Seven of the
asthmatics and eight of the rhinitics reported onset of
disease during bakery work. Flour SPTs were positive in
43% of the asthmatics or rhinitics vs 16% of referents.
The corresponding figures for a-amylase were 29%,
25%, and 7%. The odds ratio, adjusted for atopy, for an
SPT positive to flour or a-amylase for asthmatics with
onset during bakery work was 5.8 (95% confidence
interval 1.1–32), and 2.6 (0.4–16) for the corresponding
rhinitics. The positive predictive value of sensitisation
to flour or a-amylase in relation to a clinical diagnosis of
asthma or rhinitis was 71%. Sensitisation to L. destructor
Mats Åhman has died since this article was written
J. Brisman (&) Æ L. Lillienberg
Occupational Medicine, Department of Internal Medicine,
Sahlgrenska University Hospital, S:t Sigfridsgatan 85,
412 66 Gothenburg, Sweden
E-mail: jonas.brisman@ymk.gu.se
Tel.: +46-31-3438100
Fax: +46-31-409728
J. Brisman Æ L. Belin
Department of Respiratory Medicine and Allergology,
Sahlgrenska University Hospital, Gothenburg, Sweden
M. Åhman
Department of Occupational Health,
Karolinska Hospital, Stockholm, Sweden
B. Järvholm
Occupational Medicine,
Department of Public Health and Clinical Medicine,
Umeå University, Umeå, Sweden
was rare. The indices of airway inflammation were
similar in cases and in referents. Conclusions: Bakers’
asthma is associated with sensitisation to flour and/or aamylase, atopy taken into account. A similar association
was suggested in bakers’ rhinitis. Indices of airway inflammation were of low predictive value for detecting
bakers’ asthma or rhinitis in this study.
Keywords Bakers Æ Sensitisation Æ Asthma Æ Rhinitis
Introduction
Asthma and rhinitis among bakers are regarded as
some of the most common occupational respiratory
diseases. Occupational asthma is reported to affect
2%–5 %, and rhinitis 3%–21% of bakers, as reviewed
by Houba et al. [10]. It is assumed that a substantial
proportion of the respiratory morbidity is caused by
IgE-mediated sensitisation to flour proteins or fungal aamylase [2, 13, 15]. Cross-sectional studies have revealed that 5%–28% of bakers are sensitised to flours
and 2%–16% to fungal a-amylase [10]. However, not
all bakers reporting respiratory symptoms are sensitised
to occupational allergens. Houba [9] reported that only
about one-third of bakers with work-related respiratory
symptoms were sensitised to bakery allergens. It is not
clear whether this is due to non-allergic mechanisms or
because of methodological shortcomings of cross-sectional studies.
We have previously reported the findings from a
retrospective cohort questionnaire study in bakers,
showing approximately doubled risks for asthma in
men and for rhinitis in bakers of both genders [5, 7].
The objective of this clinical case–referent study was to
evaluate the importance of sensitisation to occupational
sensitisers for asthma and rhinitis in bakers. The study
is based on the previously reported questionnaire study
[5, 7].
168
Methods
Subjects
Cases and referents were selected from a cohort comprising persons
who had completed the bakery programme of a trade school from
1961 to 1989 as previously reported [7]. In a mailed questionnaire
2,226 persons answered (response rate 76%) and 1,644 reported
working as a baker after graduating. For practical reasons the
study base was restricted to persons living in Gothenburg and
Stockholm (n=717). All asthmatics (n=31), a random sample of
rhinitics (n=25) and a random sample of all questionnaire responders (referents, n=50) were invited to participate. Hence, cases
could also be selected as referents, as they represented the study
base rather than ‘‘healthy’’ persons [14].
Asthma in the questionnaire study was defined as having
asthma diagnosed by a doctor. Rhinitis was defined as having a
blocked or runny nose and/or attacks of sneezes without having a
cold or hay fever.
Five of the asthmatics, four rhinitics and six referents abstained
from participating. Thus, there were 26 asthmatics, 21 rhinitics,
and 44 referents participating.
Clinical examinations
Skin prick tests (SPTs) were performed with a standard battery of
common allergens including pollens, house-dust mites, moulds, cat
and dog dander; and positive and negative controls. SPTs were also
carried out with a bakery series with the storage mite L. destructor
(1,000 NU/ml, Diephuis, The Netherlands), flour of wheat, rye and
barley, and hops (1:2 w/v); two fungal a-amylase (10 mg/ml)
products (Novo Industries, Bagsvaerd, and Grindsted Products,
Braband, Denmark); flours of commercial soy and malt, and
malted wheat and rye (1:20 w/v), diluted in 0.9% saline with 50%
glycerol and 0.5% phenol. A wheal reaction greater or equal to
one-quarter of the positive control was regarded as positive [1].
Atopy was defined as an SPT positive to at least one common
allergen and sensitisation to flour as an SPT positive to at least one
flour extract.
Whole blood was analysed for eosinophil cationic protein
(ECP) according to the manufacturer’s instructions (Pharmacia &
Upjohn Diagnostics, Uppsala, Sweden).
All 25 asthmatic bakers (one baker with self-reported asthma was
excluded because asthma was clinically unlikely) and 22 randomly
selected referents underwent spirometry with a Vitalograph, which
was calibrated regularly. Three technically acceptable trials (maximum variation 5%) were performed, and the largest value for the
vital capacity (VC) and the forced expiratory volume in one second
(FEV1) was compared with predicted values [3]. A methacholine
challenge test (MCT) was performed according to Thorn et al. [16].
All 20 rhinitic bakers and 15 randomly selected referents had
nasal examinations performed (one referent was excluded due to an
upper airway infection). Nasal peak expiratory flow (nasal PEF),
nasal mucociliary clearance function, and nasal lavage (NAL) were
performed [6]. The NAL fluid was analysed for ECP, myeloperoxidase (MPO) and hyaluronic acid (HA) according to the manufacturer’s instructions (Pharmacia & Upjohn Diagnostics, Uppsala,
Sweden).
Clinical definitions of asthma and rhinitis
All participants were interviewed by a structured questionnaire by
one of the authors (J.B. or M.Å.). Clinical asthma was defined
according to criteria modified after Hopp et al. [8]. Definite asthma
included (1) occasions of shortness of breath or wheeze and (2)
normal breathing in-between and (3) a physician’s diagnosis of
asthma or having been hospitalised with asthma. Probable asthma
included (1) and (2). Possible asthma included (1) or cough with
wheeze together with (3) or medication because of asthma, or
shortness of breath, wheeze or cough when exposed to cold air,
exertion, pollen, furred pets or dust at home or at work.
Clinical definite rhinitis included (1) a blocked or runny nose or
attacks of sneezes without having a cold but (2) elicited by exposure
to pollen, furred pets or dust at home or at work, (3) having seen a
doctor and (4) received medication because of the nasal symptoms.
Probable rhinitis included (1) and (2). Possible rhinitis included (1).
In the analysis of sensitisation asthmatics and rhinitics with a
definite, probable or a possible clinical diagnosis were included. All
referents were included, as they should reflect the occurrence of the
determinants in the study base, i.e. among all bakers.
Statistical analyses
Comparisons of proportions were performed with the chi-square
test, and comparisons of continuous variables with Students
t-test. Variables without a normal distribution were transformed
logarithmically. Odds ratios (ORs) were calculated by MantelHaenszel procedures with test-based 95% confidence intervals (95%
CI) [11, 12].
Results
Clinical vs questionnaire diagnosis
One each of the asthmatics and rhinitics, according to
the questionnaire, did not fulfil the clinical criteria of
asthma or rhinitis, respectively. The referents, as a random sample of all bakers, contained one baker included
among the selected asthmatics and two bakers also included among the selected rhinitics. There were four
cases of clinical asthma and 27 cases of clinical rhinitis in
the referents.
The asthmatics had a significantly lower mean FEV1
than the referents (91% vs 101% of predicted, P=
0.0018) but no significant difference in VC (94% vs 97%,
P=0.42). A significantly higher proportion of the asthmatics had a positive MCT (18 out of 25), compared
with the referents (5/22, P=0.001).
Markers of airway inflammation, and nasal examination
Serum concentrations of ECP were generally low, and
the means were similar in all groups (Table 1). There
Table 1 Age, ECP in serum (geometric mean), and prevalence of
SPTs positive to common or bakery allergens. The asthmatics and
rhinitics with onset during bakery work are in separate columns
(‘‘as baker’’)
Characteristic
Age (mean)
ECP (lg/l)
Sensitisation
% (n)
SPT
Common
allergens
Any flour
Amylase
Asthma
Rhinitis
Referents
All
n=25
As baker All
n=7
n=20
As baker
n=8
n=44
31
7.7
36
6.7
35
7.1
32
6.8
33
7.4
64 (16) 71 (5)
79 (11) 71 (5)
32 (14)
40 (10) 43 (3)
24 (6) 29 (2)
30 (6)
10 (2)
16 (7)
7 (3)
43 (3)
25 (2)
169
Table 2 Prevalence of SPTs positive to any flour, and a-amylase,
in relation to atopy in bakers with a clinical diagnosis of asthma or
rhinitis, and in referents
Category
Atopics
Asthma
Rhinitis
Referents
Non-atopics
Asthma
Rhinitis
Referents
Number
Any flour
Amylase
%
(n)
%
(n)
16
14
14
50
43
21
(8)
(6)
(3)
38
14
0
(6)
(2)
(0)
9
6
30
22
0
13
(2)
(0)
(4)
0
0
10
(0)
(0)
(3)
were no differences in nasal PEF, the mucociliary function or concentrations of MPO, ECP and HA between
rhinitics and referents (data not shown).
Sensitisation
Atopy or sensitisation to flour or a-amylase was more
common among persons with asthma or rhinitis than
among referents (Table 1). An SPT positive to L. Destructor was rare and similarly distributed among asthmatics, rhinitics and referents (n=2, n=2 and n=4,
respectively).
Approximately half of the atopic bakers with asthma
or rhinitis were SPT positive to flour, twice as many as
among the atopic referents (Table 2). Seven of the
asthmatics and eight of the rhinitics reported onset of
disease during bakery work (Table 1). In the case–referent analysis, the crude OR for sensitisation to flour or
a-amylase was 7.0 (95% CI 1.5–34) among the asthmatics with onset during bakery work and 3.2 (0.6–16)
among the eight rhinitics. The corresponding ORs adjusted for atopy were 5.8 (1.1–32) and 2.6 (0.4–16).
Discussion
It is indicated that the asthma questionnaire diagnosis
had a relatively high predictive value in this group of
bakers. Only 1/26 asthmatics, according to the questionnaire, was clinically unlikely to have that diagnosis.
Differences in spirometry and bronchial hyper-reactivity
between asthmatics and referents also supported the
clinical and questionnaire diagnoses. Torén et al. reviewed the validity of questionnaires to diagnose asthma
[17]. The sensitivity varied between 48%–100%, but the
specificity was high, especially for the question on
‘‘physician-diagnosed asthma’’ (specificity ‡ 99%). Since
we examined only a small sample of referents, the sensitivity of our study was only 32% and the specificity
99.8%, after we had corrected for the sampling fractions.
The clinical diagnosis of rhinitis strongly depends on
the history, and the occurrence may vary over time. The
clinical examinations in this study did not improve the
diagnostic accuracy.
The number of examined persons was low, making the
estimates less precise. Few bakers were lost to follow-up
(12%–16%), and the loss probably does not influence the
results considerably. Both sensitisation and symptoms of
asthma or rhinitis may vary over time, and an examination at the time of diagnosis would have been preferable.
Our results, however, based on rather small material,
indicate that sensitisation to flour or a-amylase is an
important mechanism in bakers’ asthma. There was a
similar tendency among the rhinitics with onset during
bakery work. Flour was a more common sensitiser than
a-amylase – all bakers but one sensitised to a-amylase
were also sensitised to flour. Our sensitisation rates of
16% to flour and 7% to a-amylase are similar to those
found in cross-sectional studies [10]. The relation between sensitisation rates of flour and a-amylase may
differ between studies because of differences in exposure.
Sensitisation to L. Destructor seemed to be of very little
or no clinical importance in Swedish bakers. Other
studies have also indicated that storage mites are not to
be regarded as occupational allergens in bakers [10].
The positive predictive value (PPV) of sensitisation to
flour or a-amylase in relation to a clinical diagnosis of
asthma or rhinitis was estimated in the referents, as a
random sample of all bakers. Seven bakers were sensitised to flour or a-amylase, five had either clinical asthma or rhinitis. The PPV was thus 71% (5/7). (One of the
two without a clinical diagnosis had not worked as a
baker for 17 years, and past symptoms might have been
forgotten. The other was sensitised only to soy flour.)
ECP in serum or inflammatory markers in NAL
seems to be of low sensitivity in detecting asthma and
rhinitis in bakers. Neither seems to contribute to diagnosis. The result of the nasal examinations was similar in
cases and in referents, indicating that those tests have
low predictive value for diagnosing rhinitis.
In conclusion, sensitisation to an occupational allergen, especially flour, is an important, but not the only,
mechanism in bakers’ asthma. There was a suggestion
for a similar importance in bakers’ rhinitis. Sensitisation
to L. Destructor seemed to be of very little or no clinical
importance in Swedish bakers. The indices of airway
inflammation seemed to be of low predictive value in
detecting bakers’ asthma or rhinitis in this study.
Acknowledgements The study was supported by the Swedish
Council for Work Life Research, by the Swedish Asthma and Allergy Foundation and the Vårdal Foundation. The authors thank
Gerd Granung, Birgitta Olofsson, Kristina Wass, Kerstin Bergemalm-Rynell, Eva Thunberg and Lars Persson for skilful data
collection. The Committee of Ethics of Gothenburg University
approved the study.
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