AMERICAN JOURNAL OF INDUSTRIAL MEDICINE

Respiratory Morbidity in a Coffee Processing
Workplace With Sentinel Obliterative
Bronchiolitis Cases
Rachel L. Bailey, DO, MPH,1Ã Jean M. Cox-Ganser, PhD,1 Matthew G. Duling, MS,1
Ryan F. LeBouf, PhD,1 Stephen B. Martin Jr., PhD,1 Toni A. Bledsoe, MS,2
Brett J. Green, PhD,2 and Kathleen Kreiss, MD1

Rationale Obliterative bronchiolitis in former coffee workers prompted a cross-sectional
study of current workers. Diacetyl and 2,3-pentanedione levels were highest in areas for
flavoring and grinding/packaging unflavored coffee.
Methods We interviewed 75 (88%) workers, measured lung function, and created
exposure groups based on work history. We calculated standardized morbidity ratios
(SMRs) for symptoms and spirometric abnormalities. We examined health outcomes by
exposure groups.
Results SMRs were elevated 1.6-fold for dyspnea and 2.7-fold for obstruction. The exposure
group working in both coffee flavoring and grinding/packaging of unflavored coffee areas
had significantly lower mean ratio of forced expiratory volume in 1 s to forced vital capacity
and percent predicted mid-expiratory flow than workers without such exposure.
Conclusion Current workers have occupational lung morbidity associated with high
diacetyl and 2,3-pentanedione exposures, which were not limited to flavoring areas.
Am. J. Ind. Med. Published 2015. This article is a U.S. Government work and is in the
public domain in the USA.
KEY WORDS: obliterative bronchiolitis; diacetyl; 2,3-pentanedione; flavorings;
coffee; asthma

INTRODUCTION
In the last 15 years, occupational obliterative bronchiolitis with indolent onset has been recognized in workers
manufacturing microwave popcorn [Kanwal et al., 2006],
cookie dough [Cavalcanti et al., 2012], and butter and other

1
Centers for Disease Control and Prevention (CDC), National Institute for Occupational Safety and Health (NIOSH), Respiratory Health Division, Field Studies Branch, Morgantown, WV
2
CDC, NIOSH, Health Effects Laboratory Division, Allergy and Clinical Immunology
Branch, Morgantown, WV
Ã
Correspondence to: Rachel L. Bailey, DO, MPH, Field Studies Branch, Respiratory
Health Division, National Institute for Occupational Safety and Health, 1095 Willowdale
Road, MS H2800, Morgantown, WV 26505. E-mail: feu2@cdc.gov

Accepted 27 August 2015
DOI 10.1002/ajim.22533. Published online in Wiley Online Library
(wileyonlinelibrary.com).

flavorings used in such food manufacture [NIOSH, 2011]. A
common exposure across these industries has been diacetyl
(2,3-butanedione). Given concerns about diacetyl’s respiratory toxicity, manufacturers have sought out diacetyl
substitutes, often similar alpha-diketones, such as 2,3pentanedione [Day et al., 2011; Cummings et al., 2014].
However, animal studies indicate that 2,3-pentanedione also
is toxic to the respiratory epithelium [Hubbs et al., 2012;
Morgan et al., 2012].
Recently, two cases of biopsy-proven obliterative
bronchiolitis occurred in former workers of a coffee
processing facility [CDC, 2013]. Three additional cases in
former workers who had worked in the flavoring room
subsequently were diagnosed on the basis of clinical
presentation and results of non-invasive testing.
This paper describes the respiratory morbidity of current
workers in this coffee plant, derived from a 2012 public

Published 2015.This article is a U.S. Government work and is in the public domain in the USA.

 2

Bailey et al.

health investigation conducted by the National Institute
for Occupational Safety and Health (NIOSH), in response
to employee concerns about respiratory symptoms, lung
disease, and eye irritation related to substances used in the
manufacturing of coffee products, including ingredients
mixed in the flavoring process. Our specific aim was to
identify whether the sentinel case patients reflected a risk of
occupational lung disease among current workers and to
identify possible risk factors to guide intervention priorities,
including alpha-diketone exposure–response relations.
Given the occurrence of lung disease cases who had
worked in the flavoring room, we expected high exposures
in that area. However, many fermentation and pyrolysis
products also generate diacetyl exposures as in the
manufacture of beer, wine, dairy products, and roasted
coffee [Akiyama et al., 2003; Daglia et al., 2007; HSDB,
2007]. Even the tobacco in cigarettes generates diacetyl
during combustion [Polzin et al., 2007]. Thus, we
recognized that flavoring chemical exposures and lung
disease risk might not be limited to the flavoring room.
Furthermore, the coffee industry has a known risk of
occupational asthma in relation to green and roasted coffee
dusts [Karr et al., 1978; Zuskin et al., 1979, 1985; Jones
et al., 1982; Thomas et al., 1991] and castor bean dusts
from contaminated shipping bags [Figley and Rawling,
1950; Thomas et al., 1991]. We therefore considered workrelated asthma, in addition to flavoring-related lung disease,
as a possible health outcome.

Workforce, Facility, and Exposures
In September 2012, the plant had approximately 85
employees, producing flavored and unflavored whole bean
and ground roasted coffee and packaging some tea, largely
for commercial consumers. The current facility, occupied in
2003, consisted of a one-story steel industrial-style building
that contained the production operations, directly attached to
a two-story office space. Trucks delivered green coffee beans
in burlap bags to the facility. Workers known as greens
unloaders used forklifts to transfer the bags onto pallets
stacked in the greens warehouse. Material handlers moved
the pallets to dumping stations for each roasting line.
Workers known as greens dumpers emptied the burlap bags
of green coffee beans into hoppers in the floor. The beans
were automatically fed into a gas-fired coffee roaster.
Workers known as roasters monitored the process and took
samples of roasted coffee beans to the quality control room to
evaluate the color of the roasted coffee. After the roasting
process, the beans were cooled and then transferred by a
bucket elevator system to hoppers on a mezzanine above
the packaging lines in the grinding/packaging room. In
the grinding/packaging room, unflavored whole bean coffee
was packaged or ground and then packaged. Grinding

and packaging machine operators frequently ascended the
mezzanine stairs to inspect hopper material levels and
dislodge material. Packers and helpers placed cardboard
boxes at the end of the packaging lines to catch bags from
the conveyer belt and taped full cardboard boxes and
stacked them on pallets which were transported by material
handlers to the finished products warehouse. For small
batches, hand packers manually filled and labeled bags
with roasted whole bean or ground coffee. Hand packers
also performed rework, where coffee with faulty packaging
was manually redirected into the packaging process. Coffee
designated for flavoring was transported from the roasting
room mezzanine level by elevators to hoppers in the
flavoring room. Workers known as flavoring specialists
and mixers flavored ground or whole bean coffee as
described in Duling et al. [in clearance for submission].
Flavored coffee was packaged in the flavoring room.
Quality control technicians performed quality checks
throughout the production process.
Many unflavored coffee production areas (warehouse,
roasting room, grinding/packaging room, hold room,
production support corridor) were not completely isolated,
as the walls did not reach to the ceiling, and large curtained
openings between the spaces existed to facilitate forklift
traffic. The flavoring room was isolated with walls to the
ceiling and had a strip curtain door separating it from
unflavored coffee production. The flavoring room was kept
under negative air pressure with respect to the other
production areas, to prevent contamination of unflavored
coffee with flavorings. Respiratory protection had not been
commonly used in the facility prior to NIOSH involvement
in August 2012 and then was introduced in the flavoring
room.
The facility had requested diacetyl-free flavorings
beginning in the fall of 2011, and quantitative measurements
by NIOSH of alpha-diketones in headspace of bulk samples
of flavorings being used in July/August 2012 suggested that
2,3-pentanedione may have been substituted for diacetyl in
several flavorings [Duling et al., in clearance for submission]. The highest mean area concentrations of diacetyl and
2,3-pentanedione occurred in the grinding/packaging room
and flavoring room (Fig. 1). Similarly, the highest personal
sample concentrations, averaged over job titles within a
location, were highest for workers in the grinding/packaging
room and flavoring room. The sum of the means of the
two alpha-diketones for grinders in grinding/packaging
room was 283 ppb, similar to the sum for mixers of
227 ppb and packer/helpers of 244 ppb in the flavoring
room (Fig. 2). A 15-min air sample collected at the open
hatch of a grinding/packaging room mezzanine hopper
holding unflavored ground coffee above an active packaging
line measured concentrations of 14,300 ppb diacetyl and
18,400 ppb 2,3-pentanedione; workers opening these hatches
momentarily to monitor coffee levels in the hoppers

 Coffee Processing Respiratory Morbidity

3

FIGURE1. Mean 2,3-pentanedione and diacetyl air sampling results (OSHA method 1012) by location at coffee processing facility,
NIOSH industrial hygiene survey, November 2012. Offices-nonproduction includes reception area; warehouse includes the green coffee
warehouse and finished goods warehouse; offices-production category also includes corridor, break room, and maintenance room air
samples; grinding/packaging room category also includes the tea machine and hold room air samples; all-over includes material
handlers and maintenance technicians. LEV, local exhaust ventilation; ppb, parts per billion.

throughout their shifts would be exposed to such levels. The
roasting room was unique in having higher total inhalable
particulate concentrations than other areas, with a mean of
0.78 milligrams per cubic meter (mg/m3), ranging up to
1.24 mg/m3, for the 17 out of 20 samples with detectable
results.

METHODS
Participants
We invited all 85 current employees, including on-site
temporary workers, to participate in the medical survey at the

FIGURE 2. Mean 2,3-pentanedione and diacetyl personal air sampling results (OSHA method 1012) by job title at coffee processing
facility, NIOSH industrial hygiene survey, November 2012. Note: PACK, grinding/packaging room; FLAV, flavoring room; ppb, parts per
billion.

 4

Bailey et al.

workplace, after written informed consent approved by the
NIOSH Institutional Review Board. We consented and tested
the five sentinel former workers with physician-diagnosed
obliterative bronchiolitis off-site, as well as eight other
former workers with chest symptoms. The intervieweradministered computerized medical and work history
questionnaire had questions derived from the European
Community Respiratory Health Survey (ECRHS) [Grassi
et al., 2003], the American Thoracic Society (ATS) adult
respiratory questionnaire (ATS-DLD-78) [Ferris, 1978], and
the Third National Health and Nutrition Examination Survey
(NHANES III) questionnaire [CDC, 1996], supplemented
with questions on respiratory, dermatological, and systemic
symptoms and current and past work areas and jobs.
On the basis of industrial hygiene monitoring [Duling
et al., in clearance for submission], we classified workers
who worked in both the grinding/packaging area for
unflavored coffee and the flavoring area to be the highest
alpha-diketone-exposed group, and compared them to the
remainder of employees, as well as to workers who worked in
neither of these high exposure areas. Most workers had
intermittent duties apart from the department area to which
they were assigned, precluding estimation of quantitative
individual alpha-diketone exposure based on job title.

Spirometry
We used a volume spirometer, ATS criteria for
acceptability and repeatability [Miller et al., 2005], and
equations for predicted values and lower limits of normal
(LLN) derived from NHANES III data to define abnormal
spirometry [Hankinson et al., 1999]. We defined obstruction
as a forced expiratory volume in one second (FEV1)/forced
vital capacity (FVC) and FEV1 less than the LLN; restrictive
pattern as an FVC less than the LLN; and mixed obstruction
and restrictive pattern as having FEV1, FVC, and FEV1/
FVC all less than the LLN. We used the FEV1 percent
predicted to categorize abnormalities as mild, moderate,
moderately severe, severe, or very severe [Pellegrino et al.,
2005]. In participants with these abnormal spirometric
measurements, we tested for reversibility of at least 12% and
200 milliliters (ml) for either FEV1 or FVC with albuterol as
bronchodilator. We defined abnormal mid-expiratory flow
(FEF25–75) as less than the LLN.

Diffusing Capacity and Alveolar Volume
We used the single breath technique with helium as the
tracer gas to measure diffusing capacity of the lung for
carbon monoxide (DLCO) and alveolar volume, ATS criteria
for acceptability and repeatability [MacIntyre et al., 2005],
and reference values for the LLN generated from a stratified

random sample of the general population of an entire state
[Miller et al., 1983]. From the same test, we estimated total
lung capacity using the calculated alveolar volume.

Mannitol Challenge Test for Bronchial
Hyperresponsiveness
In workers with normal spirometry, we measured the
FEV1 following successive doses of mannitol (0, 5, 10, 20,
40, 80, 160, 160, 160 milligrams [mg]). The maximum
cumulative dose of mannitol was 635 mg. Airways hyperreactivity was defined as a 15% fall in FEV1 from baseline
(0 mg dose) or a 10% fall in FEV1 between two successive
doses [Porsbjerg et al., 2009].

Total and Specific Immunoglobulin
E and G
We tested participants’ serum to determine if they had
immunoglobulin G (IgG) and/or immunoglobulin E (IgE)
antibodies that reacted to coffee (Rf221), green coffee beans
(k70), or castor beans (k71) allergens, as well as total IgE
by fluoroenzymeimmunoassay using the ImmunoCAP100
(Phadia AB, Uppsala, Sweden). We defined atopy as having
total IgE serum levels equal to or greater than 100 kilounits
per liter (kU/L). Sensitivity to a specific allergen was
considered positive when IgE titers exceeded 0.35 kUA/L.
Exposure to a specific antigen was considered present when
antigen-specific IgG was 0.02 milligrams per liter (mg/L) or
higher.

Lung Disease Case Definitions
Suspect obliterative bronchiolitis was defined as:
shortness of breath on exertion (a report of shortness of
breath walking with people of his/her own age on level
ground; of having to stop for breath when walking at his/her
own pace on level ground; or having to stop for breath after
walking about 100 yards or after a few minutes); cough; chest
wheeze/whistling; regular trouble with breathing; abnormal
spirometry; decreased diffusing capacity; and/or decreased
alveolar volume. Thus, suspect obliterative bronchiolitis
could be based solely on reported chest symptoms, as lung
function can be normal or have abnormalities in any pattern
in biopsy-proven cases of this disease [Markopoulou et al.,
2002; Ghanei et al., 2008; King et al., 2011]. However, we
did not require symptoms, as pulmonary function abnormalities consistent with obliterative bronchiolitis may occur in
asymptomatic flavoring-exposed workers [Kreiss et al.,
2002]. We accepted physician diagnosis of obliterative
bronchiolitis in the former worker sentinel cases.

 Coffee Processing Respiratory Morbidity

Suspect asthma was defined as any of the following:
awoken by an attack of shortness of breath or a feeling of
tightness in the chest in the past 12 months; cough; chest
wheeze/whistling in the past 12 months; and regular trouble
with breathing. Probable asthma was defined as the presence
of asthma symptoms and either obstruction on spirometry
with a bronchodilator response or positive response to
mannitol. We defined suspect occupational asthma as that
arising during employment and probable occupational
asthma as having a positive IgE response to coffee, green
coffee beans, or castor bean allergens. We defined physiciandiagnosed pre-employment asthma with symptoms that
improved when away from work as work-exacerbated
asthma.

Statistical Analysis
Using indirect standardization, we calculated standardized morbidity ratios (SMRs) by comparing the observed
numbers of participants with symptoms and spirometric
obstructive and restrictive abnormalities and abnormal
FEF25-75 to the expected numbers calculated using gender,
race (black, Hispanic, white), age ( 39 years and !40
years), and smoking (ever/never) specific prevalences from a
sample of the general population reflected in the NHANES
III [CDC 1996]. For restrictive pattern on spirometry, we
also included body mass index (BMI: <25, >25, and <30;
>30 kilograms per meter squared) specific prevalences in the
calculation of expected values. We derived 95% confidence
intervals for a SMR assuming that the observed data were
from a Poisson distribution.
We conducted analyses using SAS version 9.3 (SAS
Institute, Cary, North Carolina). We ran linear regressions
using the GLM procedure on percent predicted FEV1, FVC,
FEF25-75, DLCO, and alveolar volume, and on the FEV1/
FVC ratio in relation to currently and ever having any work
time in the grinding/packaging room and flavoring room
(high exposure areas), as well as for currently and ever
having any work time in the roasting room (higher particulate
exposure). We used logistic regression models to evaluate
prevalence of upper and lower respiratory symptoms, sinus
symptoms, systemic symptoms, and eye irritation in relation
to currently having worked in the grinding/packaging room
and/or flavoring room, and currently having worked in the
roasting room. The comparison group for having work time
in the grinding/packaging room or flavoring room was
composed of participants who did not have work time in
either. We used two comparison groups for having work time
in both the grinding/packaging room and flavoring room:
participants who did not have work time in both; and
participants who did not have work time in either. The
comparison group for working in the roasting room was
those who did not have work time in the roasting room. The

5

models for symptoms and the FEV1/FVC ratio were adjusted
for age and smoking pack-years, while the percent predicted
lung function parameter models were adjusted for smoking
pack-years only. We chose a probability of less than or equal
to 0.05 as a criterion for statistical significance. In view of
the small size of the worker population and the curtailed
distribution of exposure indices, we report a probability
>0.05 and <0.1 as marginally significant.

RESULTS
Former Workers
We tested 13 former workers, five of whom reported
physician-diagnosed obliterative bronchiolitis. At the time of
our testing, the five ranged in age from 25 to 42 years. All
five reported post-hire onset of lower respiratory symptoms
and had abnormal spirometry (FEV1 range: 22.4–41.9% of
predicted; FVC range: 73.1–88.3% of predicted; FEV1/FVC
ratio range: 25.9–43.6%; FEF25-75 range: 6.1–12.3% of
predicted). Two had obstructive abnormalities, and three had
mixed abnormalities with reduction in FEV1/FVC ratio,
FEV1, and FVC. None had reversibility with bronchodilator.
The two participants with the lowest percent predicted
FEV1s (22.4% and 31.9%) had low alveolar volumes.
All five who reported physician-diagnosed obliterative
bronchiolitis had worked in the flavoring room (as a mixer,
flavor specialist, hand packer/helper, packaging machine
operator, and/or grinder); four reported working in the
grinding/packaging room (as a helper, packaging machine
operator, and/or grinder). Some reported that in addition to
their primary job, they sometimes had secondary duties
helping out in other areas including grinding coffee or
performing re-works in the flavoring room. Two of the five
had high levels of total IgE; none of the five had specific IgE
to coffee, green coffee beans, or castor beans. Only one of
five had ever smoked, although an age less than 40 years
indicated that smoking was not an etiology for the severe
spirometric abnormality.
The remaining eight former workers tested reported
chest symptoms and ranged in age from 22 to 51 years. One
had mild restriction on spirometry without bronchodilator
response, and the remainder had normal spirometry and other
lung function tests. Another had probable occupational
asthma with specific IgE to green coffee, coffee, and castor
bean allergens, as well as an elevated total IgE. Two others
also had high total IgE.

Current Workers
Of 75 current employee participants (88% response
rate), the majority were male (68%), Hispanic (69%), and

 6

Bailey et al.

current (31%) or ex-smokers (23%), with an average age
of 35 years (range 18–67 years). The mean duration of
employment at the current facility was 2.9 years, with a
median of 1.3 years, and a range of 0.04-9.3 years. Forty-one
percent of participants had worked one year or less. Of
the 75 employees, 12 had also worked at the previous coffee
processing facility. Mean years employed at the current and
the previous plant was 4.3 years and ranged to 25.0 years.
At the time of the survey, 67% of the 75 participants
reported currently spending work time in the grinding/
packaging room (n ¼ 50) and a similar percentage reported
work time in the flavoring room (n ¼ 50). The number
currently spending work time in either area was 63 (84%).
The number spending work time in both areas was 37
(49.3%). During their tenure at the current facility, 58
(77.3%) participants had ever spent work time in the
grinding/packaging room, and 54 (72%) had ever spent work
time in the flavoring room, with 66 (88%) having ever spent
work time in one or the other high alpha-diketone exposure
areas, and 46 (61.3%) having ever concurrently spent work
time in both high alpha-diketone exposure areas. The number
of workers reporting currently spending work time in the
roasting area was 33 (44%), and 43 (57.3%) reported ever
spending work time in the roasting area during their tenure.

Medical Tests
Of 69 participants with spirometry results, five had
obstructive abnormalities (four mild and one moderate); two
had restrictive abnormalities; and eight had low FEF25-75
(Table I). The five with obstructive abnormalities constituted
a statistically significant 2.7-fold SMR (95% confidence
interval [CI]: 1.2–6.4) in comparison to the general U.S.
population sample. The SMRs for abnormal restrictive
spirometry (0.4; CI: 0.1–1.6) and FEF25-75 (1.1; CI: 0.6–
2.2) were not elevated. Of three participants with mild
TABLE I. Results of Lung FunctionTesting for Current Coffee Processing
Workers, September 2012
Spirometry (n ¼ 69)
FEV1% predicted, mean (range)
FVC % predicted, mean (range)
FEV1/FVC %, mean (range)
FEF25^75% predicted, mean (range)
Abnormally low FEF25^75, n (%)
Obstruction, n (%)
Restriction, n (%)

97.6 (55.4^130.9)
99.9 (60.8^136.9)
80.5 (51.1^91.6)
94.4 (27.1^163.0)
8 (11.6%)
5 (7.2%)
2 (2.9%)

FEV1, forced expiratory volume in one second; FVC, forced vital capacity;
FEF25-75, forced expiratory flow between 25% and 75% of exhaled volume
(forced mid-expiratory flow).

obstruction, one met the definition of reversibility with
bronchodilator, and the others were not administered
bronchodilator. All five participants with obstruction had
normal diffusing capacity and alveolar volumes. The two
with a restrictive pattern on spirometry had a low DLCO
and/or alveolar volume. Four other participants with low
DLCO and/or alveolar volume had normal spirometry.
Of the 45 participants who completed the mannitol
challenge test, five had abnormal tests reflecting bronchial
hyperreactivity. All five had normal spirometry, diffusing
capacity, and alveolar volume. Two of those with abnormal
mannitol tests reported no respiratory symptoms, excluding a
diagnosis of clinical asthma. Four of the five with an
abnormal mannitol challenge test participated in the blood
draw, and three had elevated total IgE reflecting atopy, but
none had detectable levels of specific IgE to allergens from
green coffee beans, coffee, or castor bean.
Of 60 current worker participants with ImmunoCAP
blood tests, all had evidence of having been exposed to
green coffee beans by their IgG levels (mean 1.54 mg/L).
The great majority also had evidence of exposure to coffee
(n ¼ 57, 95%, mean 0.95 mg/L) and castor beans (n ¼ 52,
87%, mean 0.60 mg/L). Of the 60 participants, 22 (36.6%)
had high levels of total IgE; however, no current worker
had specific IgE to coffee or green coffee beans. One
participant had specific IgE to castor beans. This participant
reported no physician-diagnosed asthma; he/she reported
waking up with chest tightness in the past 12 months but
not in the previous 4 weeks. The participant’s spirometry
was normal; the participant did not complete the mannitol
challenge test.

Lung Function by Work Area
When we ran models on the spirometry data for all 69
participants (Table II), we found that participants currently
spending time in both high exposure areas had significantly
lower mean FEV1/FVC ratios compared to those who did
not currently spend time in both areas (77.9% vs. 82.9%,
P ¼ 0.0004). Participants who currently spent work time
in either the grinding/packaging room or the flavoring room
had marginally significantly lower FEV1/FVC ratio compared to participants who currently did not spend work time
in either area (80.0% vs. 83.4%, P ¼ 0.08). Participants
currently spending time in both high exposure areas had
significantly lower percent predicted FEF25-75 than those
who did not currently spend time in both areas (83.1%
vs. 104.1%, P ¼ 0.002). A logistic regression of abnormal
FEF25-75 indicated a marginally significant effect of
currently spending time in both high exposure areas (OR
8.8, CI ¼ 0.98–79.7, P ¼ 0.052).
No other lung function parameter was associated with
major work area or with time spent in these two high alpha-

 Coffee Processing Respiratory Morbidity

7

TABLE II. Adjusted Means of Lung Function ParametersVersus Work in High Alpha-Diketone Areas Currently or Ever DuringTenure, From Regression
Models, Coffee Processing Facility, 2012
Work Area
Currently in Grinding/Packaging or Flavoring
Yes (n ¼ 57)
No (n ¼12)
Currently in Grinding/Packaging and Flavoring
Yes (n ¼ 32)
No (n ¼ 37)c
Currently in Grinding/Packaging and Flavoringd
Yes (n ¼ 32)
No (n ¼12)e
Ever in Grinding/Packaging and Flavoringc
Yes (n ¼ 40)
No (n ¼ 29)

% predicted FEV1a

% predicted FVCa

FEV1/FVC %b

% predicted FEF25^75a

97.9
96.5

100.8
95.5

80.0Ã
83.4

93.3
99.8

94.9
100.0

100.2
99.7

77.9ÃÃ
82.9

83.1ÃÃ
104.1

94.4
95.9

100.1
95.5

77.3ÃÃ
82.7

81.9Ã
98.3

96.1
99.7

100.3
99.3

79.0ÃÃ
82.7

87.1ÃÃ
104.4

Ã

0.05 < P 0.1.
P 0.05.
a
Models adjusted for smoking pack-years.
b
Models adjusted for age and smoking pack-years.
c
Model with different comparison group from above.
d
Comparison group are those not spending work time in both grinding/packaging and flavoring areas; this includes workers spending work time in one or the other of
these areas.
e
Comparison group are those not spending work time in either grinding/packaging or flavoring areas.
ÃÃ

diketone exposure areas. No lung function parameter was
associated with spending work time (either currently or ever)
in the roasting room.

Symptoms and Diagnoses
Of the 75 participants, 21 (28%) reported shortness of
breath hurrying on level ground or walking up a slight hill,
which represented a SMR of 1.6 in comparison to the U.S.
population sample (95%CI: 1.0–2.4). Of these 21 participants, nine reported being short of breath walking with
people of his or her own age on level ground, and
five reported having to stop for breath after walking about
100 yards or after a few minutes on level ground. Of the
12 who provided a start date for onset of shortness of
breath, half reported that their onset was after or the same
month as hire date. The only other symptom that approached
a statistically significant SMR was wheeze (SMR 1.5,
95%CI: 0.9–2.5).
Mucous membrane irritation of eyes, nose, or sinuses
was common, and the majority reported that such symptoms
were better away from work or that something at work
caused or aggravated the symptoms (data not shown). At the
time of the survey, 26% (20/75) of participants reported one
or more of the following symptoms in the past 12 months:
wheezing or whistling in their chest, waking up with chest
tightness, or awakening by an attack of shortness of breath.
Of the 20, one reported current asthma with physician

diagnosis after hire, and one reported a past physician
diagnosis of asthma with diagnosis after hire. No current
workers reported a diagnosis of emphysema, bronchiolitis
obliterans, interstitial lung disease, hypersensitivity pneumonitis, or chemical pneumonitis. No current employee
participants reported having changed job duties because of
breathing difficulties.

Symptoms by Work Area
In comparison to working in other areas, currently
spending work time in the roasting room was significantly
associated with the following symptoms in the last
12 months: having trouble with breathing (OR 3.8,
CI ¼ 1.0–14.0, P ¼ 0.044); wheeze (OR 3.4, CI ¼ 1.0–
11.3, P ¼ 0.047); sinus symptoms (OR 4.2, CI ¼ 1.2–14.6,
P ¼ 0.025); burning eyes (OR 4.4, CI ¼ 1.3–15.2, P ¼ 0.020),
and flu-like achiness or achy joints (OR 4.9, CI ¼ 1.6–15.6,
P ¼ 0.007). There were no significant associations between
any symptoms and currently spending work time in the
flavoring and/or grinding/packaging rooms (Table III).

Suspect Work-Related Lung Disease
Six participants, who had spent part of their tenure in the
flavoring room or the grinding/packaging room, met our
criteria for suspect obliterative bronchiolitis, of whom five

 8

Bailey et al.

TABLE III. Prevalence of Health Conditions Reported by Participants During the Previous12 Months, Coffee Processing Facility, September 2012
Currently in
grinding/packaging
or flavoring
Symptom in the last12 months
Stuffy, itchy, or runny nose
Stinging, burning, irritated nose
Watery, itchy eyes
Stinging, burning, irritated eyes
Sinusitis or sinus problems
Usual Cough
Awoke with chest tightness
Awoke with shortness of breath
Breathing trouble
Shortness of breath on level ground or walking up a slight hill
Shortness of breath walking with people of own age on level or
worsea
Chest wheezing or whistling
Flu-like achiness or achy joints
Fever or chills
Usual tiredness or fatigue
Skin rash or skin problems

Currently in
grinding/packaging
and flavoring

Currently in roasting

Yes (%)
n ¼ 63

No (%)
n ¼12

Yes (%)
n ¼ 37

No (%)
n ¼ 38

Yes (%)
n ¼ 33

No (%)
n ¼ 42

42.9
11.1
38.1
23.8
27.0
17.5
11.1
12.7
15.9
28.6
14.3

58.3
16.7
41.7
8.3
16.7
8.3
8.3
0.0
25.0
25.0
16.7

43.2
13.5
40.5
21.6
32.4
16.2
8.1
8.1
16.2
27.0
16.2

47.4
10.5
36.8
21.1
18.4
15.8
13.2
13.2
18.4
29.0
13.2

54.6
12.1
42.2
33.3
36.4
18.2
15.2
9.1
27.3
36.4
18.2

38.1
11.9
35.7
11.9ÃÃ
16.7ÃÃ
14.3
7.1
11.9
9.5ÃÃ
21.4
11.9

17.5
25.4
12.7
27.0
26.6

33.3
33.3
25.0
41.7
8.3

16.2
35.1
13.5
29.7
21.6

23.7
18.4
15.8
29.0
15.8

30.3
42.4
15.2
33.3
21.2

11.9ÃÃ
14.3ÃÃ
14.3
26.2
16.7

ÃÃ

P 0.05.
Threeparticipantsanswered‘‘yes’’tothemainquestion(shortnessofbreathonlevelgroundorwalkingupaslighthill)andthethirdsub-question(Stopforbreathafterwalking
about a100 yards or a few minutes) but ‘‘no’’ to one or both of the first two sub-questions.

a

had shortness of breath on exertion. Three of the five reported
post-hire onset of the shortness of breath, and the other two
did not give a date of onset. Four of the six reported other
lower respiratory symptoms. Three of the six had spirometric
obstructive, restrictive, or mixed abnormalities. Four of the
six had never smoked, and two had a minor smoking history
of less than one pack-year. One of the six reported a
diagnosis of walking pneumonia that did not respond to
antibiotics, and one had a post-hire diagnosis of asthma but
did not report current asthma.
In addition to the worker mentioned above with suspect
obliterative bronchiolitis and a post-hire diagnosis of asthma,
five other workers met our criteria for suspect work-related
asthma, including two with probable or suspect occupational
asthma. One had specific IgE to castor beans; the second had
mild obstruction and post-hire diagnosis of asthma. Three
participants had suspect work-exacerbated asthma based on
asthma symptoms that improved away from work. One had
pre-hire onset of symptoms; two were mannitol-sensitive and
had elevated total IgE.
In summary, eleven current employees had medical
test abnormalities or symptoms consistent with suspect
occupational lung disease, either obliterative bronchiolitis or
work-related asthma.

DISCUSSION
The current workforce of a coffee plant had evidence of
occupational respiratory health effects in addition to the
five sentinel cases of physician-diagnosed obliterative
bronchiolitis and probable case of occupational asthma
among former workers. Our findings consistent with this
conclusion follow. (1) A statistically significant 2.7-fold
excess of measured spirometric obstruction and a 1.6-fold
excess of shortness of breath (when hurrying on level
ground or walking up a slight hill) existed in the current
coffee plant workers compared to the U.S. noninstitutionalized population of the same age, race/ethnic, sex, and
cigarette smoking distribution. (2) Several workers had a
severe degree of exertional shortness of breath (without
diagnoses), which is unusual in working populations.
(3) Participants currently spending work time in both
grinding/packaging and flavoring rooms (the two high
alpha-diketone exposure areas) had a 5.4 percentage
point decrease in mean FEV1/FVC ratio in comparison to
workers that had not worked in either area, adjusted for
age and smoking. (4) Workers currently spending work
time in both of the high alpha-diketone exposure areas
had a mean FEF25–75% predicted that was 21 percentage

 Coffee Processing Respiratory Morbidity

points lower than workers without such exposure. (5) We
identified six workers with production area alpha-diketone
exposures whose shortness of breath and/or abnormalities
on the battery of medical tests suggested undiagnosed
obliterative bronchiolitis and were unlikely to be explained
by cigarette smoking. In addition, we identified five current
workers with suspect work-related asthma, of whom two had
likely occupational asthma.
The current worker participants had a 2.7-fold excess
of obstructive spirometry. The five former workers with
physician-diagnosed obliterative bronchiolitis had marked
obstructive or mixed obstructive and restrictive spirometric
abnormalities on our testing, consistent with their physician
diagnoses. We found no current workers with that degree
of impairment on spirometry, although five current workers
reported comparable degrees of severe shortness of breath
with exertion. One purpose of spirometric measurement is
to identify workers with mild or moderate impairment
so that they can be prevented from developing severe
impairment, precluding their employment and many
activities of daily living, as in those former workers with
diagnoses. Three biopsied case series of obliterative
bronchiolitis have shown that cases can have any pattern
of spirometric abnormality or even normal spirometry
[Markopoulou et al., 2002, Ghanei et al., 2008, King et al.,
2011]. For that reason, in addition to those with abnormal
spirometry, we suggest exposure cessation and/or diagnostic testing based on the cardinal symptom, exertional
shortness of breath, particularly in workers from workforces with sentinel cases.
We found that workers currently assigned to or spending
time in both grinding and flavoring areas with high exposure
to diacetyl and 2,3-pentanedione had a 5.4 percentage points
lower average FEV1/FVC ratio, compared to other workers.
This finding suggests that there may be a subclinical effect
on spirometry in this group, which accounts for nearly half
of the current production population. Our finding of a
21 percentage point difference in the mean FEF25–75%
predicted in the high exposure group compared to all other
workers is consistent with a small airways effect in
employees who spent time in both high exposure areas,
as was striking in the sentinel former worker obliterative
bronchiolitis cases whose FEF25–75 measurements were all
less than 12.3% predicted. Medical surveillance programs
for alpha-diketone exposed workers, whether in flavoring
production or food production that involves flavoring or
pyrolizing exposures, as in roasting coffee, can identify
workers who have excessive declines in FEV1 and FEV1/
FVC ratio that, if continued, will result in their developing
abnormal spirometry. Identifying such workers allows
prevention of occupational lung disease through counseling
regarding risks, engineering interventions to lower exposure,
possible reassignment to lower exposure jobs, and motivating better adherence to respiratory protection.

9

We found that spending time in the roasting room was
associated with sinus trouble, burning eyes, wheezing, and
having trouble with breathing in the last 12 months, despite
the comparison group that included those with high alphadiketone exposures in grinding/packaging and/or flavoring
areas. Mucous membrane irritation of eyes, nose, or sinuses
was attributed by some participants to the burlap bags, green
or roasted coffee dust, smoke, pallet dust/debris, or roasting
room heat. However, irritant symptoms related to dust and
smoke are more likely attributed to the workplace than the
chronic exertional dyspnea associated with obliterative
bronchiolitis which is not temporally related to work shift
or employment cessation.
Twenty current worker participants had symptoms of
wheezing or whistling in their chest, waking up with chest
tightness, or awakening by an attack of shortness of breath,
but only five current workers reported a physician diagnosis
of asthma. Asthma symptoms have been reported among
diagnosed cases of obliterative bronchiolitis [Akpinar-Elci
et al., 2004; Modi et al., 2008; Cavalcanti et al., 2012]. A
previous case series concentrating on occupational asthma
has documented a worker in coffee processing with shortness
of breath and fixed pulmonary function abnormality who
may have been unrecognized case of obliterative bronchiolitis [Karr et al., 1978]. The absence of physician diagnosis
of asthma or objective tests consistent with asthma are
worrisome in the presence of excess exertional shortness of
breath, which is the predominant symptom of obliterative
bronchiolitis.
This study had several limitations. The first is that the
workforce was small, and the second is that there was not
an optimal internal unexposed group with which we could
compare the alpha-diketone exposed workers. We had
initially planned to compare flavoring workers with other
production workers. However, the environmental data
collected by NIOSH showed that alpha-diketone exposures
were similar for workers in the flavoring room and workers
in the grinding and packaging area of unflavored coffee.
Furthermore, the questionnaire responses indicated that
workers from a number of different departments spent at
least some time in the high exposure areas, although we did
not have sufficient information to estimate the proportion of
work time spent in different locations. We contend that the
human body cannot differentiate between chemicals that
are created by roasting green coffee and grinding roasted
unflavored coffee (so-called natural chemicals) and the same
chemicals that are present in chemical flavors added to
coffee. Both diacetyl and 2,3-pentanedione have comparable
toxicity to the airway epithelium in animals exposed to the
chemicals [Hubbs et al., 2012; Morgan et al., 2012], and
NIOSH’s draft recommendation is for similar exposure
limits for both (5 ppb and 9.3 ppb, respectively) [NIOSH,
2011]. Apart from the adverse effect of working in the two
high alpha-diketone exposure areas on FEV1/FVC ratio and

 10

Bailey et al.

percent predicted FEF25-75, our inability to show other
exposure–response relationships for alpha-diketone exposure associated with adverse respiratory outcomes is likely
explained by most employees’ (including those in production
offices adjacent to the grinding/packaging room) having
similar exposures at some time during their work tenure.
With little range in exposures, it is possible that nearly the
entire workforce had some exposures sufficient to have
affected them to some degree. This is consistent with the
comparison to national data which showed that the current
workforce as a whole had excess abnormalities in obstruction
and shortness of breath.
A third limitation was that historical alpha-diketone
measurements did not exist when the five sentinel cases
became ill enough to seek medical attention. One change that
may have affected chemical exposures in the flavoring room
was the substitution of diacetyl-containing flavorings with
flavorings containing 2,3-pentanedione. However, since
2,3-pentanedione is no safer than diacetyl, this change is
unlikely to have lowered risk to workers. Another change
that may have lowered average levels of exposure to
flavoring chemicals was the engineering controls introduced in the flavoring room, including exhaust hoods,
ventilated storage cabinets, and changes in the process of
flavoring coffee. Respiratory protection for volatile
chemicals was not introduced until after our initial visit
and increased in the flavoring room after the NIOSH
medical survey. In any case, even powered air-purifying
respirators with an assigned protection factor of 1,000
might be inadequate to lower the peak exposure risk of
many thousands of ppb diacetyl and 2,3-pentanedione for a
few seconds that were measured on the mezzanine over
bins of unflavored ground coffee stored for off-gassing.
Peak exposures appeared to be risk factors for obstructive
spirometry in the microwave popcorn industry [Kreiss
et al., 2002; Kanwal et al., 2006].
Despite its limitations, our study of the current coffee
processing workforce strengthens the previous sentinel case
reports by epidemiologically establishing unexpected respiratory morbidity in a new industry related to chemicals also
present in butter and nut flavorings. Our finding of high
diacetyl and 2,3-pentanedione exposures in the grinding of
unflavored coffee beans merits consideration by clinicians
seeing patients working in the coffee industry, whether
flavored or unflavored, as well as further systematic study of
coffee processing workforces and their exposures.

AUTHORS’ CONTRIBUTION
All authors made substantial contributions to the
conception or design of the paper; or the acquisition,
analysis, or interpretation of data for the paper. All authors
drafted the paper or revised it critically for important

intellectual content. All authors provided final approval of
the version to be published. All authors agree be accountable
for all aspects of the paper in ensuring that questions related
to the accuracy or integrity of any part of the paper are
appropriately investigated and resolved.

ACKNOWLEDGMENTS
We thank the worker participants and management of
the coffee facility, as well as the NIOSH medical and
environmental field teams who administered tests, translated
study materials into Spanish, and/or assisted with data
analyses, including Chris Piacitelli, Nicole Edwards,
Diana Freeland, Mike Beaty, Elizabeth Garza, Diana Cale,
Cammie Chaumont Men endez, PhD and Drs. Kristin
Cummings, Anna-Binney McCague, and Walter A. Alarcon.
Don Beezhold, PhD, contributed to discussions with the
laboratory co-authors regarding allergen study design and
serum results.
Disclosure Statement: The authors report no conflicts of
interest. This paper has been reviewed and approved at
NIOSH as a work product conducted by the authors as part of
their employment without external funding.
Written informed consent approved by the NIOSH
Institutional Review Board was obtained from all the
participants.

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Disclosure Statement: The authors report no conflicts of interests.