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* From the Centre for Agricultural Medicine (Drs. Dosman and Senthilselvan, and Ms. Kirychuk), the College of Agriculture (Dr. Barber), the Veterinary Infectious Disease Organization (Dr. Willson), and the Division of Respiratory Medicine of the Department of Medicine (Mr. Hurst), University of Saskatchewan, Saskatoon, Saskatchewan, Canada; the Prairie Swine Centre Inc (Dr. Lemay), Saskatoon, Saskatchewan; and the Centre de Pneumologie (Dr. Cormier), University of Laval, Ste-Foy, Québec, Canada.
Correspondence to: James A. Dosman, MD, FCCP, Centre for Agricultural Medicine, P.O. Box 120, Royal University Hospital, 103 Hospital Dr, Saskatoon S7N 0W8, Canada; e-mail: dosman{at}sask.usask.ca
| Abstract |
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Design: A crossover trial design was used in the study.
Setting: The study was carried out at the research facilities of the Centre for Agricultural Medicine, the Royal University Hospital, and the Prairie Swine Centre Inc, Saskatoon, Saskatchewan, Canada.
Participants: Twenty-one nonsmoking healthy male subjects with no previous swine barn exposure participated in the study.
Interventions: The subjects participated in a laboratory session (baseline day), a 4-h exposure in a traditional swine room wearing the respirator (intervention day), and a 4-hour exposure in a traditional swine room without a respirator (nonintervention day).
Measurements: Lung function, methacholine challenge tests, blood counts, nasal lavage, and cytokines in serum and nasal lavage fluid.
Results: Mean (± SE) shift change in FEV1, from preexposure to postexposure, was highest on nonintervention day (-8.1 ± 1.01%) and was significantly different from intervention day (0.32 ± 0.62%; p < 0.0001) and baseline day (1.57 ± 0.51%; p < 0.0001). Similar patterns were observed in the mean values of the provocative concentration of a substance (methacholine) causing a 20% fall in FEV1 (nonintervention day, 130.4 ± 36.9 mg/mL; intervention day, 242.0 ± 38.0 mg/mL; and baseline day, 328.0 mg/mL ± 34.1 mg/mL). Significant increases in serum neutrophil levels and nasal cell counts were observed on the nonintervention day in comparison to the baseline and intervention days. Significant increases also were found in the levels of cytokines interleukin (IL)-6 and IL-8 in nasal lavage fluid and in the levels of IL-6 in serum for the nonintervention day in comparison to the other 2 days.
Conclusions: The results demonstrate that an N-95 disposable respirator can help to significantly reduce acute negative health effects in subjects not previously exposed to a swine barn environment.
Key Words: blood counts bronchial responsiveness cytokines intervention lung function naive subjects nasal lavage respirator swine confinement
| Introduction |
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High levels of dusts and gases can be found in the indoor environment of swine confinement buildings.14 15 16 Several cross-sectional studies have shown that dust and gases in the indoor environment are related to the respiratory health of the swine confinement workers.17 18 19 Recent cross-sectional and longitudinal studies have shown that endotoxin is related to respiratory symptoms, lower lung function levels, and lung function decline in swine confinement workers.20 21
A crossover trial22 was conducted to examine the human health effects of sprinkling canola oil in a swine barn to control dust. In this trial, 20 naive healthy subjects were exposed to a traditional swine confinement room and a room sprinkled with canola oil. The oil treatment significantly reduced dust levels and resulted in lower mean shift changes in pulmonary function, lower WBC counts, lower total cells in nasal lavage fluid, and increased mean provocative concentrations of a substance (methacholine) causing a 20% fall in FEV1 (PC20).22
In a 1993 study,23 only 30% of swine confinement workers reported the use of dust masks when working inside a barn. Attitudes toward wearing masks improved in an intervention study designed to examine the effects of improving knowledge, attitudes, and behaviors related to respiratory health in swine workers.24 In an industrial hygiene experiment, the degree of dust protection offered by respiratory masks was assessed. Masks were mounted on glass funnels and dust was sampled with filters that were kept inside the funnel. Respiratory protection limited total dust exposures to < 25% of the nonmasked values with two-tie masks and to < 50% with one-tie masks. The number of respirable particles was reduced to < 58% by using two-tie masks.25
In this article, we report the results of a crossover trial conducted to examine the human health effects of wearing an N-95 disposable respirator in a swine barn. In addition to the technician-administered questionnaire, pulmonary function tests, nasal lavage, methacholine challenge tests, and blood sampling were conducted on 21 male, nonsmoking volunteers who were naive to the swine barn environment.
| Materials and Methods |
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Recruitment
Through postings, lifetime nonsmoking male subjects, aged 18 to
35 years, were recruited for the study. Female subjects were not
included in the study as a larger sample size would have then been
required to control for sex in statistical analysis and to have
adequate statistical power to detect differences in the outcomes
between the 2 exposure days.
Prescreening
The prescreening included signing an informed consent
form, a questionnaire to assess previous hog barn exposure, medical,
smoking and allergy histories, as well as skin prick tests were
performed for aeroallergens including the following: animals (cat, dog,
cattle, horse, feathers, and hog dander); trees (box elder, birch,
polar, willow, and mixed allergens); ragweed, mixed grasses, and mixed
weeds; foods (eggs, milk, peanuts, and shell fish); dusts (house,
grain, and wheat); house dust mites; molds (Aspergillus, Alternaria,
Cladosporium, and Helmiathosporium species); and histamine. A
positive result of a skin test was indicated by a wheal that was
3
mm. From this prescreening, 22 lifetime nonsmoking male subjects who
were 18 to 35 years old were selected for the study.
Exclusions
Subjects with previous swine barn exposure, a history of
smoking, a history of asthma, an adverse medical history, or a positive
result of a skin prick test to any of the substances except histamine
were excluded from the study.
Training Day
The 22 subjects selected for the study from the prescreening
attended a training day prior to baseline assessment. A questionnaire
that retrieved information on previous occupational exposures,
respiratory symptoms, past illnesses including allergy, asthma, and
other respiratory conditions, and an informed consent form were
completed at that time. In an attempt to decrease the "learning
effect" of performing repetitive pulmonary function
tests,26
nasal lavage, and mask donning, subjects
practiced these procedures during the training session. Subjects also
were educated on the appropriate protocol for barn entry procedures at
the Prairie Swine Centre Inc.
Baseline Day
Baseline assessments were conducted at the Centre for
Agricultural Medicine and the Royal University Hospital. Subjects
arrived at 7:00 AM for pulmonary function tests and
returned at 11:00 AM for repeat pulmonary function tests,
nasal lavage, and blood samples. Subjects returned to the Royal
University Hospital at 4:00 PM for methacholine challenge
tests. After baseline assessment, one subject was excluded from the
study, because the methacholine PC20 was 32
mg/mL, whereas other subjects went up to the maximum methacholine
concentration of 256 mg/mL. Twenty-one subjects participated in the
remainder of the study. The minimum duration between training day,
baseline day, and each of the exposure days was at least 7 days.
Crossover Design
Four subjects were assigned to the animal room each day. A
randomization list was prepared for designating the subjects to
intervention or nonintervention. Two subjects were randomly chosen to
wear a respirator (intervention), whereas the other two subjects did
not wear a respirator (nonintervention). After a minimum of at least 7
days, the subjects who wore respirators were assigned to the same
animal room without a respirator. Similarly, the two subjects who did
not wear a respirator were instructed to wear a respirator and were
assigned to the same animal room. The days on which the subjects wore
respirators hereafter will be referred to as intervention days, and the
days on which the subjects did not wear respirators will be referred to
as nonintervention days.
Exposure Day 1
Subjects arrived at the swine barn at 7:00 AM for
pulmonary function measurements. Personal air samplers were attached to
each subject, and subjects wearing respiratory protection had a
quantitative fit test of the respirator prior to entering the barn.
Subjects left the exposure room after 2 h for a 15-min period to
perform pulmonary function tests and for those subjects wearing a
respirator to have a fit test on a new respirator. These measurements
were conducted in a room adjacent to the exposure room. To simulate the
usual workload in a swine barn, subjects rode a stationary bike for 3
km at 18-km/h for each hour they spent in the barn. When subjects were
not riding the bike, they were allowed to read quietly without
disturbing the pigs. Subjects recorded severity of cough, nasal
congestion, eye irritation, shortness of breath, chills, phlegm,
headache, and chest tightness every hour (7 AM to 10
PM) using a Likert scale ranging from 0 to 5 (0, no
symptoms; 5, severe symptoms). At the end of exposure (11:30
AM), pulmonary function was measured, nasal lavage
performed, and blood was drawn. Subjects returned to the Royal
University Hospital at 4:00 PM for methacholine challenge
tests.
Exposure Day 2
After a minimum interval of at least 7 days after exposure day
1, subjects who wore respiratory protection on the first exposure day
were assigned to the same animal room without respiratory protection on
exposure day 2. Similarly, the subjects who did not wear respiratory
protection on exposure day 1 wore respiratory protection on exposure
day 2. Identical methods were used on exposure day 1 and exposure day
2.
Animal Facilities and Management
The exposure study was conducted in a swine grower/finisher room
at the Prairie Swine Centre Inc. The room measured
14.3 x 11.0 x 3.0 m. The pen floor was partially slatted (30% of
the pen area). A 0.6-m deep manure collection channel was located
beneath the slatted portion of the floor. Interior walls had plywood
sheathing on both sides of a stud wall frame. A bank of propeller fans
(total air delivery capacity, 6,500 L/s at 20 Pa) exhausted air from
one wall of the room. Unit block air inlets were located in the
ceiling. Fresh air entered the attic through screened soffit openings.
Heat was supplied by an unvented natural gas unit heater. An electronic
controller regulated the sequencing and speed of exhaust fans, the
opening area of supply inlet modules, and the operation of the heaters
using a proportional control algorithm.
A total of 132 pigs was housed in the room. The average mass of the animals was 95 kg (SD, 12 kg) at the completion of the experiment. Pellet feed was filled daily to a single-space dry feeder in each of 12 pens. The management of the room and the production methods conformed to those commonly used in the swine industry in Saskatchewan. Over the course of the 2.5-week experiment, the alleyway floor of the room was not swept or cleaned.
Respiratory Protection and Fit Test
The National Institute for Occupational Safety and
Health-approved N-95 disposable particulate respirators with two straps
and metal nose clips (model 8210; 3M Canada Inc; London, ON, Canada)
were utilized. Subjects were clean shaven for experiment days in the
barn. A quantitative fit test was performed prior to subjects entering
the barn and after 2 h in the barn environment. A new respirator
was donned for each testing. The quantitative fit test was performed
using a Porta-Count Plus (TSI Inc; St. Paul, MN), an N-95
Companion (TSI Inc), and a particle generator (TSI Inc) to assess
particle levels inside and outside the respirator. A sampling probe
(TSI Inc) was inserted in the respirator breathing zone prior to the
subjects donning the respirator. During the quantitative fit test,
subjects performed six exercises (normal breathing, deep breathing,
head side to side, head up and down, talking out loud, and normal
breathing) for 90 s each. A fit factor was calculated from all
exercises and is an expression of the ratio of the mean concentration
of ambient particles outside the respirators to the concentration of
particles inside the respirator. A fit factor of > 100 was required
to assume that the respirator was well fit. After completing the fit
test, a plastic Luer lock cap was applied to the open end of the probe
on the subjects respirator to prevent any air leakage, and subjects
then entered the barn environment. Respirators were not removed while
in the barn environment.
Lung Function
A volume displacement spirometer (SensorMedics; Anaheim,
CA) was used for pulmonary function measurements. Measurements were
performed according to American Thoracic Society
standards.27
Each subject performed the pulmonary function
tests in the sitting position. The variables, FVC,
FEV1, FEV1/FVC ratio, and
maximal mid-expiratory flow rate were measured. The percentage changes
in pulmonary function from the first measurement to the last
measurement from each day were determined and were referred to as the
shift change in pulmonary function for that day.
Methacholine Challenge Tests
Methacholine challenge studies were performed with the
inhalation of a diluent followed by the inhalation of increasing doses
of methacholine, starting at 1 mg/mL, with each increment representing
a doubling of the dose to a maximum final concentration of 256
mg/mL.28
Bronchial challenges were performed with a
nebulizer (Bennett Twin Jet; Puritan Bennett Corp; Carlsbad, CA) at a
driving pressure of 50 lb per square inch, which produced an output of
0.13 mg/mL. The subjects in sitting position inhaled the nebulized
solution through a mask held close, but not tightly applied, to the
face and breathed the mist quietly at tidal volume for 2 min. The
FEV1 was measured at 30 and 90 s after the
2-min inhalation of methacholine, with doses of methacholine
administered at 5-min intervals. A clinical pulmonary function
spirometer (MCG; Medigraphics Corp; St. Paul, MN) was used to measure
FEV1. The PC20 was
interpolated from the log concentration-response curve or was
extrapolated from the last two responses to 256 mg/mL.
PC20 was used as an indicator of airway
responsiveness.
Nasal Lavage Procedure and Analysis
The nasal lavage procedure was adapted from Naclerio et
al29
The subjects extended their necks approximately 30°
from the horizontal while in sitting position. Five milliliters of room
temperature normal saline solution (0.9%) was instilled into each
nostril. Subjects did not breathe or swallow while obstructing the
oropharynx with their tongue, and, after a minimum of 10 s and a
maximum of 2 min, subjects flexed their necks forward, allowing the
mixture of mucus and saline solution to be passively expelled into a
sterile specimen container, which was stored on ice until analysis. For
analysis, the total sample volume of the nasal lavage fluid was
recorded. The sample then was centrifuged (RT600B Refrigerated
Centrifuge; Sorvall; Newtown, CT) at 400 rotations per minute (rpm) for
10 min at 4°C. The supernatant (2-mL aliquot) was removed and was
stored in plastic tubes, which then were frozen at -70°C for later
cytokine analysis. The sediment was gently resuspended and washed once
with phosphate-buffered saline solution, the supernatant was removed by
vacuum suction, and the sediment was gently resuspended to a volume of
0.5 or 1 mL, depending on a visual estimation of cellularity. The cell
count was performed on a Neubauer hemocytometer
(Bright-Line; Americas Optical; Buffalo, NY). The cell count was
calculated on the hemocytometer using the number of cells divided by
the original fluid volume to give the number of cells per milliliter. A
direct smear of the sediment was made for staining with Wright-Giemsa
stain (Diff Quik; Jade Diagnostics; Aguada, Puerto Rico), and another
direct smear of the sediment was made for esterase staining. A cytospin
preparation (Cytospin 2; Shandon Southern Instruments; Sewickley, PA)
of the sediment was performed at 500 rpm for 10 min at room
temperature. The cytospin serves as a gentle centrifuge to concentrate
cell-poor fluids for microscopic examination.29
WBC Methodology
The methodology for counting WBCs utilized the impotence
principle with the use of a cell counter (Coulter Counter, model STKS;
Coulter Electronics; Hialeah, FL). Analysis and classification of WBCs
were based on the Coulter method of leukocyte differential counting
using the following three measurements: individual cell volume, high
frequency conductivity, and laser light scatter. The well-clotted blood
sample was centrifuged at room temperature at a speed of 1,500 rpm for
10 min, which separated the serum from the cells. The serum then was
divided into 1-mL aliquots and was placed into a polypropylene
container. The sample was then frozen at -70°C for later cytokine
analysis.
Nasal and Serum Cytokines
Proinflammatory cytokines interleukin (IL)-6 and IL-8 were
measured in cell-free nasal wash supernatant and in sera by
commercially available immunoassay kits for IL-8 (Perseptive
Diagnostics; Cambridge, MA) and (high-sensitivity) for IL-6 (R&D
Systems; Minneapolis, MN). These cytokines were chosen to examine
acute-phase response and to confirm the previous finding that acute
reactions to swine dust might be mediated by the cytokine
IL-6.22
Environmental Dust Measurements
Dust mass was collected using personal aerosol samplers (Dupont
Air Sampler; Canada Safety Supply; Saskatoon, SK, Canada) that were
carried by the subjects. The samplers ran over the 4-h exposure period
at a flow rate of 2.0 L/min with a preweighed, binder-free glass fiber
filter (SKC; Edmonton, AB, Canada) inline. The cassette was attached at
the shoulder near the subjects breathing zone. Filters were
desiccated before and after sampling. Area samples for dust
concentration were also collected (Aircon2; Gilian Instrument Corp;
Caldwell, NJ). The sample was drawn through a 37-mm binder-free glass
fiber filter (SKC). After weighing, filters were placed in 50-mL
polypropylene centrifuge tubes and were stored at 4°C until endotoxin
analysis. Particle counts were performed using a laser particle counter
(MetOne Inc; Grants Pass, OR), which was placed on a table that was
1.0 m above the floor and near the study subjects. The particle
counter provided the following four particle-size (in optical diameter)
ranges: 0.3 to 0.49 µm (diminutive dust); 0.5 to 0.99 µm; 1.0 to
4.99 µm (modified respirable dust); and > 0.5 µm (modified
inhalable dust). Counts were taken four times per day and lasted 1 min
per measurement. The mean of the four dust particle counts then were
calculated.
Endotoxin Analysis
Endotoxin analysis was performed in laboratories of the
Veterinary Infectious Disease Organization. The binder-free glass fiber
filters with collected dust were extracted individually in the
centrifuge tubes with 10 mL sterile nonpyrogenic water for injection
USP (DIN 00624721; Astra Pharma Inc; Mississagua, ON, Canada) and were
incubated for 1 h at room temperature in a sonicating water bath.
The extracts were decanted, and serial twofold dilutions of the
supernatant fluids were analyzed for Gram-negative bacterial endotoxin
using an end-point assay (model QCL-1000; BioWhitaker; Walkersville,
MD). The extracts were stored at 4°C for < 24 h before being tested
for endotoxin content. The endotoxin standard that was supplied with
the assay (Escherichia coli O111:B4, lot No. 6 L2110;
BioWhitaker) in duplicate at four concentrations from 0.1 to 1.0
endotoxin units (EU)/mL was assayed simultaneously to generate the
standard curve. Linear regression determined the formula for the
calculation of EU in the extracted dust samples from optical density
readings that were within the range that resulted from the assay of the
endotoxin standard. Hence, the lower detection limit is 0.1 EU/mL,
which is equivalent to 1.0 EU per filter. The sampling time and flow
rate were used to calculate the concentration of endotoxin in air
(EU/m3).
Ammonia and Carbon Dioxide Measurements
Gas levels were measured during each exposure day. An air sample
was collected continuously into a Tedlar bag
(Cole-Parmer; Anjou, Quebec, Canada), and
diffusion tubes were used to measure the daily mean ammonia
(Matheson Gas Products; Edmonton, AB, Canada) and carbon dioxide
(Matheson Gas Products) levels. Three tubes were used for each air
sample, and a mean value was obtained from the three readings.
Temperature Measurements
Room temperature and relative humidity were measured and
recorded four times per day using a wet-bulb psychrometer
(Cole-Parmer). Outdoor temperature was monitored once per day at 10:30
AM using a probe connected to the barns communications
and ventilation control system (OMNI 4000; Phasou; Winnipeg, MB,
Canada).
Statistical Methods
Paired t tests were used to test the significant
differences in dust and endotoxin concentrations, and symptom scores
were used to test differences between intervention and nonintervention
days. Overall differences between the baseline day and two experimental
days in pulmonary function measurements, methacholine challenge
results, WBC counts and differential, nasal lavage and serum cytokine
levels were tested using an F statistic based on Pillai test for
multivariate repeated-measures analysis of variance.30
If
the Pillai tests indicated a significant overall difference, paired
t tests then were used to test the differences between any 2
days.31
Since the pair-wise comparisons were preplanned, p
values were not corrected for multiple comparisons.
| Results |
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Dust, Gas, and Endotoxin Concentrations
Mean particle counts and measurements of ammonia and carbon
dioxide concentrations over the 12-day study period are shown in
Table 1 . Table 2
outlines the results of dust and endotoxin measurements, and personal
sampler assessments. These results indicate that no significant
differences were observed for mean dust and endotoxin concentrations
during the 4-h swine barn exposure between intervention and
nonintervention days.
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Symptom Scores
The mean self-reported symptom scores on intervention and
nonintervention days are shown in Figure 1
. The mean scores related to cough, chest tightness, and phlegm were
significantly greater on the intervention day than those on the
nonintervention day. No significant differences were observed in scores
related to headache and nasal irritation.
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Proinflammatory Cytokines
In comparison to the baseline day, significant increases were
observed in the proinflammatory cytokines IL-8 and IL-6 in nasal lavage
fluid on intervention and nonintervention days (Table 5
). The mean values of IL-8 and IL-6 on nonintervention day were three to
six times greater than those observed on intervention day. Only IL-6
was detectable in the blood serum on all three occasions, and the mean
IL-6 concentration was significantly greater on nonintervention day
than those observed on intervention and baseline days (Table 5)
. The
difference in levels of IL-6 between intervention and baseline days was
not statistically significant.
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| Discussion |
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In our study, we detected IL-6 and IL-8 in nasal lavage fluid and IL-6 in serum. The inability to detect IL-8 in serum might be related to interference of the IL-1 receptor antagonist in the acute reaction.32 33 These findings indicate that IL-6 may be an important regulatory cytokine in the inflammatory response to a swine barn environment. Although there was a significant decrease in the mean PC20 on the intervention day compared to the baseline day, the dose levels were 242.0 and 328.0 mg/mL, respectively, indicating that neither day produced any clinically important bronchial responsiveness. Whereas on the nonintervention day, a mean PC20 of 130.4 mg/mL indicates that the wearing of a respirator reduced bronchial responsiveness.
In describing these findings, we have confirmed and extended our previous observations that environmental control measures in swine facilities using sprinkled canola oil result in reductions in acute shift changes in FEV1 that are similar to those that we herein reported with the use of disposable respirators.22 We also have extended previous work by ourselves and others on the efficacy of respiratory personal protection in swine confinement facilities. In our previous work, we reported that swine producers who used respirators for preventive purposes had better lung function than did those who did not use respirators or those who used respirators because of respiratory symptoms.23 Further, it has been demonstrated that educational intervention can increase the use of respiratory personal protection.24
Industrial hygiene experiments have indicated the potential capability of paper masks to reduce particulate concentrations.25 Popendorf et al34 measured work protection factors (WPFs) for three classes of respirators (fully disposable, reusable half-mask with valve, and powered air-purifying helmet) by measuring dust and endotoxin levels collected inside and outside these masks during agricultural exposures (swine, poultry, and grains).34 They demonstrated that, while the disposable paper mask had a WPF of only 16, vs 19 and 30 for the reusable half-mask and powered air-purifying helmets, respectively, the disposable paper masks were favored by workers for weight and convenience.34 While we did not evaluate the WPF, we did show that a properly fitted disposable half-mask (metal nose clip and two straps) can afford apparent extensive protection, at least in naive, previously unexposed, nonallergic volunteers.
Our previous work,12 20 and that of others,21 35 36 has shown that of the various exposures inside animal confinement facilities, including dusts, endotoxins and ammonia are the principal substances associated with acute changes. We have previously demonstrated that by simultaneously reducing dust and endotoxin concentrations in swine confinement facilities by sprinkling canola oil, we could effect marked reductions in both the respiratory and systemic effects of exposure.22 As the use of a disposable respirator in these experiments achieved reductions in both respiratory and systemic effects of exposure in the naive volunteers that were similar to those seen with dust and endotoxin control with sprinkled canola oil, it seems reasonable to assume that reductions of within-mask concentrations of the substances occurs, and that endotoxins, which are present on dust particles, can be controlled with either dust control with canola oil or with filtering by means of a respiratory personal protective device.
What are the mechanisms of the dramatic reductions in response to
exposures in these naive volunteers? Previous work clearly has
demonstrated that swine barn exposures in naive volunteers are
associated with short-term shift changes,22
increases in
airways responsiveness,22
evidence of inflammatory
response,7
and production of immunologic mediators tumor
necrosis factor-
, IL-6, and IL-8, 22
37
38
whether by
mouth or nose breathing.39
All of the foregoing effects of
exposures in naive, previously unexposed volunteers could be evidence
of a nonspecific response to acute exposures that may or may not be
relevant in the genesis of suspected dysfunction that has been
described previously in chronically exposed workers in the swine
industry.1
2
3
4
5
35
36
Our previous work has demonstrated that reductions in contaminant concentrations result in marked amelioration of the effects in volunteers.22 The work reported herein demonstrates that use of personal protection has similar effects. Although unproven, it seems reasonable to suggest that both the reduction of exposures through dust control and the use of personal protection should result in similar beneficial long-term effects, at least in most exposed workers. While personal protection is useful to assist workers in short-term high-dose exposures, we believe that long-term prevention of dysfunction requires the development of control technologies and production technologies that allow workers to function within a healthful environment. In the meantime, many workers, especially those with asthma or other symptoms, who are exposed may benefit from appropriate respiratory protection,40 as would workers exposed to short-term high-dose exposures that may be difficult to control by currently available technologies. Further work to develop economically and technologically feasible control technologies that would allow for appropriate advice for these workers and their employers is required.
| Acknowledgements |
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| Footnotes |
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Received for publication November 4, 1999. Accepted for publication February 8, 2000.
| References |
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