00 r
Andri;ja Stampar School of Public Health
4 Rocicefellerova
41000 Zagreb, Yugoslavia
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FINAL PROGRESS REPORT
Project title:
HEALTH EFFECTS OF INDUSTRIAL AEROSOLS
In collaboration with:
Environmental Protection Agency, USA
Principal investigator:
;2u2kiri^ M.D. , D.Sci.
Duration of the report:
June 1981 - May 1986
U.S. Environmental Protection Agency
Library, Room 3404 PM-211-A
401 M Street, S.W.
Washington, DC 20460 .......:-.:-.;.v.Vi'!
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CONTENT
FIRST YEAR
1, STUDY ON THE EFFECT OF COFFEE DUST
2. STUDY ON THE EFFECT OF COTTON BRACT
II SECOND YEAR
1. EPIDEMIC-LOGICAL STUDY ON THE EFFECT OF TEA DUST
a) Respiratory function in tea workers
b) Immunological changes in tea workers
2. EXPERIMENTAL STUDY ON THE EFFECT OF TEXTILE DUST
EXTRACTS
a) Inhalation studies in healthy subjects with
different textile dust extracts
b) Inhalation studies with cotton bract extract
and methacholine in healthy subjests
3. EXPERIMENTAL STUDY ON THE EFFECT OF COFFEE DUST
EXTRACTS
a) Experiments with green and roasted coffee dust
extract on isolated guinea pig trachea
4. EPIDEMIOLOGICAL STUDY OF IMMUNOLOGICAL STATUS IN
WORKERS EXPOSED TO FOOD AEROSOLS
III THIRD YEAR
1. The pharmacological characterization of aqueous
extracts of vegetable dusts
2. Characterisation of textile dust extracts: II.
Bronchoconstriction in man
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3. Effect of green coffee dust on lung function
in guinea pigs
IV FORTH YEAR
1. AIRWAY REACTIVITY AND COTTON BRACT-INDUCED
BRONCHIAL OBSTRUCTION
2. BRONCHIAL REACTIVITY IN GREEN COFFEE EXPOSURE
3. fiESPIRATORY FUNCTION IN TEA WORKERS
FIFTH YEAR
1. IMMUNOLOGICAL AND RESPIRATORY CHANGES IN
TEA WORKERS
2. EFFECT OF FOOD ADDITIVES ON RESPIRATORY
FUNCTION IN EXPOSED WORKERS
3. RESPIRATORY CHANGES IN FURRIERS
4. AIRWAY RESPONSIVENESS IN WORKERS PROCESSING
POLYESTER RESINS
5. RESPIRATORY FUNCTION IN RUBBER WORKERS
VI FINANCIAL REPORT
VII LIST OF PUBLICATIONS
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FIRST YEAR
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r o
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1. STUDY ON THE EFFECT OF COFFEE DUST
Study has shown that exposure to green or roasted
coffee might contribute to the development of chronic
respiratory symptoms and lung function changes in expo-
sed workers. Prevalence of almost all chronic respirato-
ry symptoms was significantly higher in coffee workers
than in controls* During Monday work: shift there was a
significant mean acute decrease in MEF50% and in MEF25%-
Acute reductions in FEV, were considerably smaller. Acute
decreases in flow rates at low lung volumes suggest that
the bronchoconstrictor effect of the dust acts mostly on
smaller airways. Administration of Intal before work: shift
considerably diminshed acute reductions in flow rates. A
comparison of ventilatory function values in exposed and
matched control workers demonstrated a significantly
lower values in coffee workers than in controls. Positive
skin reactivity to green coffee beans was considerably
more pronounced than to roasted coffee. Such data indicate
that occupational exposure to dust of green or roasted
coffee may lead in more sensitive subjects to persistent
loss of pulmonary function.
O
x - ^-
en
2. STUDY ON THE EFFECT OF COTTON BRACT
Decrease in pulmonary function following cotton
bract dust can be reproduced in the laboratory in healthy
subjects never previously exposed to textile dust after
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1. EPIDEMIOLOGICAL STUDY OK THE EFFECT OF TEA DUST
Respiratory function and immunologies! status
were studied in tea Workers occupationally exposed to
different types of tea. The highest prevalence of almost
all chronic respiratory symptoms was found in workers
processing dog-rose, followed by sage and gruzyan tea.
During Monday work shift there was a significant mean
acute decrease in MEF50% and at MEF25%. Pre-shift admini-
stration of Intal significantly diminished acute reductions
in flow rates except in workers processing indian tea*
Comparison of ventilatory capacity in tea workers with
those in controls vindicate that exposure to tea dust in
/
some workers-may lead to chronic respiratory impairment.
Skin tests ,with tea allergens demonstrated the
)••
highest percentage of positive skin, reactions to sage,
gruzyan :tea, mentha and dog-rose. Serum levels '£of total
IgE were increased in considerably larger number of tea
than in control workers. Prevalence of almost all chronic
respiratory symptoms was higher in tea workers with posi-
tive skin tests than in those with negative skin tests to
tea allergens.
•
2. EXPERIMENTAL STUDY ON THE EFFECT OF TEXTILE DUST
EXTRACT
Inhalation of cotton tracts extract induced bron-
choconstriction in normal healthy subjects. Pulmonary
function changes occured in both central and peripheral
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airways. Flow rates on the partial expiratory flow-volume
curves were the most sensitive indicators of positive
inhalation tests. When bracts extract was freeze dried
and reconstituted in deionized water the biological acti-
vity was unchanged. Double strength of bracts extract
induced a significantly greater bronchospastn than single
strength bracts. Dialysis of the extract shows that the
active component(s) had of small molecular size since we
measured approximately 65% of the original biological
activity in the dialysate while the dialysed material was
biologically inert. We showed that the active substance(s)
is stable to moderate heat, acid or alkin conditions. The
bronchoconstrictor agent is readily soluble in water; a
single extraction of bracts removes all biologically active
material.
Some responders to cotton bract extract exhibit
greater airway reactivity than nonresponders. Differences
may exist between methacholine and histamine response among
these groups or alternatively there may be subgroups of
individuals among responders with hyperreactive airways.
3- EXPERIMENTAL STUDY ON THE EFFECT OP COFFEE DUST EXTEACTS
Green coffee extracts induced concentration depen-
dent contraction, but the maximal tension were never excee-
ded 76.3 - 5*2 of a maximal histamine contraction. One
gram of green coffee dust had a biological activity equi-
valent to 1.23 - 0.1 mg of histamine. The potency of green
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coffee was unaffected by taepyramine maleate while that
of histaraine was reduced 500 fold. Tissues contracted
with histaraine were not significantly relaxed by green
coffee extracts. In contrast, roasted coffee extracts
induced concentration dependent relaxation uncontracted
and histamine contracted tissues. Tissues contracted
with green coffee extracts were also completely relaxed
by roasted coffee extracts. Our results show that coffee
dust extracts have considerable biological activity which
changes from a contractile to a relaxant action as a
consequence of processing. The greater incidence of adver-
se reactions to green coffee dust(s) in coffee workers may
be related to the contractile activity present in green
coffee dust.
4. EPIDENIOLOGICAL STUDY OF IMMUHOLOGICAL STATUS IN
WORKERS EXPOSED TO POOD AEROSOLS
Our data indicate that sensitive persons could
develop immunological changes in occupational exposure
to food dusts. Such persons might eventually develop
symptoms of allergic diseases. Skin testing demonstrated
the highest specificity for ooffee allergen, followed by
tea and food additives. IgE above normal level was found
in 24# of coffee, 23# of tea and 30# of food additives
workers.
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III THIRD YEAR
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1. THE PHARMACOLOGICAL CHARACTERIZATION OF AQUEOUS
EXTRACTS OP VEGETABLE DUSTS
All extracts reduced both basal tone and histamine-
'induced tone in tracheal spirals. The relaxation of tracheal
spirals by theophylline was concentration dependent and it
also reduced basal tone. Thus, the total relaxation as a
percentage of induced tone is greater than 100#. Efficasy
of the extracts varied.
2. CHARACTERIZATION OP TEXTILE DUST EXTRACTS: II BRONCHO-
CONSTRICTION IN MAN
In this study we have developed an assay system that
mimics the acute byssinotic response. Inhalation of an
aqueous.extract of cotton bracts causes a gradually incre-
asing bronchoconstriction that takes upu to one hour to
.reach its peak; Conductance changes, which also occur,
reflect constriction in large and central airways. Our
data show that the agent(s) is highly water soluble.
Steaming of cotton bales has resulted in reduced biologi-
t . -,r. ..,
*. ,'*••: '*
cal activity, and pur results suggest that a vigorous
washing of cotton bales bafore processing might be a
simple arid effective way to control the acute symptoms of
byssinosis.
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3. EFFECT OF GREEN COFFEE DUST ON LUNG FUNCTION
IN GUINEA PIGS
Experimental studies with green coffee dust
in guinea pigs indicate that there are variations in
sensitivity of exposed animals to green coffee dust.
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IV FORTH YEAR
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1. AIRWAY REACTIVITY AND COTTON BRACT-INDUCED
BRONCHIAL OBSTRUCTION
Most semingly healthy persons challenged with
an aerosol of cotton bract extract develop some degree
of bronchospasm. The role of nonspecific reactivity of
the airways in this reaction to cotton bract extract is
undefined* Some responders to cotton bract extract exhi-
bit greater reactivity of the airways than nonresponders.
2. BRONCHIAL REACTIVITY IN GI
COFFEE EXPOSURE
Exposure to dust in coffee processing is likely to
cause the development of chronic respiratory symptoms and
changes in lung function in coffee workers. A significan-
tly higher prevalence of chronic respiratory symptoms was
found in exposed than in control workers. Provocative inha-
lation of green coffee allergen caused immediate broncho-
constriction in four out of nine tested subjects. The
effect of coffee allergen in our workers was mostly pro-
nounced in flow rates at low lung volumes. All workers with
positive bronchial provocation test had positive skin reac-
tion to green coffe. Such results indicate a great speci-
ficity of skin reactions to green coffee allergen in detec-
ting workers sensitive to green coffee.
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3. RESPIRATORY FUNCTION IN TEA WORKERS
The prevalence of almost all chronic respiratory
symptoms was significantly higher in workers processing
dog-rose, sage, and gruzyan tea than in control workers.
During Monday ahift there was a significant mean acute
decrease in ventilatory capacity. Preshift administration
of Intal significantly diminished acute reductions in
flow rates. Exposure to tea dust may, in some worters,
lead to chronic respiratory impairment.
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V FIFTH TEAR
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1. IKMUNOLOGICAL AND RESPIRATORY CHANGES IK TEA WORKERS
Skin tests with tea allergens demonstrated the
highest percentage of positive reaction to sage, gruzyan,
mentha and dog rose. Serum levels of IgE were increased
in 2?# of the tea workers and in 7% of the control subjects.
Prevalence of almost all chronic respiratory symptoms was
higher in tea workers with positive skin tests than in
those with negative skin tests to tea allergen.
OP FOOD ADDITIVES ON RESPIEATORY FUNCTION
WORKERS:.
The same subjects were tested after period of 10
years. There was a decrease in the prevalence of acute
and chronic respiratory symptoms in 1985 in comparison
to 1976, although the differences were not statistically
significant. -There was a statistically significant acute
mean decrease in all measured ventilatory capacity para-
meters. Comparison of the mean measured annual decrease
for FVC, FEV^ and MEF50# with the expected mean annual
decrease demonstrated considerably larger mean annual
decrease in exposed workers. Preshift administration of
Intal considerably diminished acute reductions of venti-
latory capacity over work shift in comparison to placebo.
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3. RESPIRATORY CHANGES IN FURRIERS
The highest prevalence of chronic respiratory
symptoms among furriers was recorded for sinusitis,
followed by nasal catarrh, dyspnea and chronic cough.
A considerably larger number of workers complained of
acute symptoms during working hours. The largest mean
relative acute reductions in ventilatory capacity were
recorded for MEF50# indicating obstructive changes mostly
in smaller airways. The measured values of ventilatory
capacity were significantly smaller than normal values
for PVC and MEP25%. A relatively small number of workers
demonstrated positive stein reactions. Furriers mostly
reacted to lamb hair and to marten.
4. AIRWAY RESPONSIVENESS IN WORKERS PROCESSING
£ POLYESTER RESINS
A relatively large number of workers complained
of acute or chronic respiratory symptoms. A higher preva-
lence of chronic respiratory symptoms was found among men
than among women. Atropine significantly prevented the
acute reductions in flow rates while propranolol potenti-
ated the acute reductions in relation to a placebo. These
results indicate that the autonomic nervous system is
important in determining the lunges response to polyester
resin.
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5. RESPIRATORY FUNCTION IN RUBBER WORKERS
We found significantly higher prevalence of
chronic respiratory symptoms in rubber workers than in
adequate controls. Exposure to different noxious agents
in rubber industry causes significant acute reductions
in ventilatory capacity. In comparison to control preshift
data, rubber workers had considerably lower preshift valu-
es than control workers. In relation to the duration of
exposure, smokers and nonsmolcers exposed for more than
20 years had considerably lower preshift values of all
tests than expected normal values(80$). A mean annual
decrease of FEY^ in rubber workers was significantly
greater than in control workers. Our study suggest that
exposure in rubber processing might effect pulmonary
function. Reductions of exposure and further longitudinal
studies are recommended especially in regard to those most
heavily exposed.
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VI FINANCIAL REPORT
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SUMMAHY BUDGET
ATTACHMENT A
BUDGET CATEGORIES
A. Salaries
& Wa/ros
Professional Staff
Supporting Staff
Consultants
B. Materials, Supplies
and Services
C. Travel
Expenses
I
D. Equip-
ment
Travel Within
;he Country
Travel Outside
the Country
General
Purpose
Special
Purpose
B. Other Direct Costa
F, Audit . .
SUB-TOTAL
G. Consultative Travel of
Project Officer and ;
U. S. Consultants
£ Waiting final report ,
Computing services
Yugoslav consultants
GRAND TOTAL
1981-1986 YKAR. (five^vrsi
.
KD
1.497-665
3.452.255.
1.760.400
467.000
150.000
42.500
2.458.200
9.828.000
500.000
250.000
10.578.000
USg
3.540
3.540
3.540
-
x Since Project Officer Dr. David L. Coffin did not come during the last
year of the project, the amount of 250.000- ND has been used to cover
expenses of writing the final report, for computing services and for
Yugoslav consultants service.
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VII LIST OF PUBLICATIONS
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1. Zu§kin, E., Valid, F., and Stairid, "B.: Respiratory
function in coffee workers, Brit. J. industr. Med.
36:117-122, 1979.
2. ZuSkin, E., Valid, F., and Kancelja, B.: Immunologi-
cal and respiratory changes in coffee workers.
Thorax 36:9-13, 1981.
3. Schachter, E.N., Zustein, E., Buck:, A. and Bouhuys, A.:
The effect of mediator modifyng drugs in cotton
bract-induced bronchospasm. Chest 79:73-77* 1981.
4. Schachter, E.N., Brown, S., Zuskin, E., Buck:, M.,
Kolack, B. and Bouhuys, A*: Airway reactivity in cotton
bract-induced bronchospasm. Amer. Rev. Resp. Dig.
123:273-276, 1981.
5. ZuSkin, E., Duncan, P.6. and Douglas, J.S.: Pharmaco-
logical characterization of coffee extracts. XI Intern.
Congress of Allergology and Clinical Immunology*
London, 1982. Abstract no. 454*
6. JCanceljafc-Macan, B« and ZuSlcin; E.: Immunological
status in workers occupationally exposed to different
food allergens. XI Intern* Congress of Allergology and
Clinical Immunology. London, 1982,.Abstract no. 454.
7* zVs'lti.n, E. and Skuric, Z.: Respiratory function in
tea workers. Brit. J. industr. Med. 41:88, 1984.
8. £u§kin, E., Duncan, P.G. and Douglas, J.S.: Pharmaco-
logical characterization of extracts of coffee dusts.
Brit. J. industr. Med. 40:193, 1983.
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9« Schachter, E.N., ZuSkin, E., Buck:, M.G., Wite'c, T.J.,
Beck, G.J. and Tyler, D.: The relation of sensitivity
to cotton bract extract and raethacholine. Amer. Rev.
Heap. Dis. 12?:156, 1983-
10. ZuSteLn, E., Duncan, P.G., and Douglas, J.S.: Characte-
rization of tectile dust extracts. Bronchoconstriction
in man. Brit. J. industr. Med., in press.
11. Z\i5kin, E., Duncan, P.G. and Douglas, J.S.: The
pharmacological characterization of aqueous extracts
of vegetable dusts* Lung 161:301, 1983.
12. 2uSkin, E., Duncan, P.G. and Douglas, J.S.: Airway
responses to different cotton bracts extracts in man.
XXIX Congress of The International Union of Physio-
logical Sciences, Sydney, 1983*
/•
13* 2u£lti.ii, E., Duncan, F.G. and Douglas, J.S.: Characte-
rization of textile dust extracts* II Bronchoconstric-
tion in man. Brit. J. industr. Med. 41:70, 1984.
14. Zufiicin, E., Kanceljak, B., Skruric, Z., Ivan>covi6, D,:
fiespiratory function in tea workers. Third Internatio-
nal Meeting on Occupational Health, Lisboa, May 14-18,
1984, pp. 55
15* Zuikin, E., Slcuric, Z., Ivantcovic, D.: A ten-year
follow-up study in cotton workers. XXI International
Congress on Occupational Health, Dublin, 9-14 September,
1984, pp. I??
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16. Kanceljak, B. , Zu§kin, E. : Airway responses to coffee
dust. International Symposium on Prevention of Allergic
Diseases, Florence, June 24-27, 1984.
1?. ZuSkin, E. and Sfcuric, Z. : Respiratory function in
tea workers. Brit. J. industr. Med. 41:88, 1984.
18. Schachter, E.N. , ZuSfcin, E. , Bucfc, M.G. , Witelc, T.J.,
Beck, G.J. , Tyler, D, : Airway reactivity and cotton
bract-induced bronchial obstruction, Chest 87:51-55,1985-
19. Zugfcin, E. , Kanceljafc, B. , Steurid, Z., Butfcovic, D. :
Bronchial reactivity in green coffee exposure. Brit.
J. industr. Med. 42:415, 1985-
20. Sugfcin, E. , Kanceljak, B. , Sfcuric, Z., Ivankovic, D. :
Itamunological and respiratory changes in tea workers.
Arch. Occup. Environ. Health 56:57* 1985.
21. ZuSkin, E., Kanceljak, B. , Skuric, Z. , Sari 6, M. :
Respiratory and immunological responses to polyester
resins in industrial workers. Occupational Lung
Diseases (Eds. J.B.L. Gee, W.K.C. Morgan, S.M.Brooks),
Haven Press, New York, 1984, pp. 189
22. Zugkin, E., Kanceljak, B., Ivankovic, D.: Comparison
of airway reactivity in bronchoprovocation testing
with green coffee allergen and Methacholine. 19th
Annual C ongress of the European Society to Clinical
Respiratory Physiology (SEPCR), Hague, June, 1985,pp. 22
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23. Zugfcin, E, f Kaneel3ate,B., Schachter, E.N., Bronchial
reactivity in exposure to organic aerosols. 1985
Adriatic Meeting on the Regulation of Breathing.
Dubrovnifc, September, 1985, pp. 13
24. Kan eel jak, B. , Zus"teLn, £. , Svorigcec, B. , PaviSic, P.:
Airway response to exercise in patients with chronic
obstructive pulmonary disease. 1985 Adriatic Meeting
on. the fiegulation of Breathing. Dubrovnifc, September,
1985, pp. 13
25. ZuSkin, E., Slcuric, Z., Kancel;ja!c, B., §ari6, K. :
Effect of coffee and tea dust in industrial workers.
Sixth International Symposium on Inhaled Particles.
Cambridge, September, 1985* PP. 154
26. &aSldn, E. , Kanceljalc, B. , Schachter, E.N. , Ivan(covi6, P,
Airway reactivity to green coffee allergen. XII Inter-
national Congress of Allergology and Clinical Immuno-
* /Washington, October, 1985 » PP* 264
Principal investigator:
Eugenia Zuslcin, M.D., D.Sci.
Zagreb, March, 1986
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