Granath and colleagues take issue with our update of a cohort of
acrylamide (AMD) workers from three U.S. plants[1] claiming that "it
exemplifies the shortcomings of studies of this type to detect moderate
influences of specific causative factors on cancer mortality or
incidence." To support their contention that we overlooked a small but
"unacceptable" increase in cancer risk, they performed a crude
q...
Granath and colleagues take issue with our update of a cohort of
acrylamide (AMD) workers from three U.S. plants[1] claiming that "it
exemplifies the shortcomings of studies of this type to detect moderate
influences of specific causative factors on cancer mortality or
incidence." To support their contention that we overlooked a small but
"unacceptable" increase in cancer risk, they performed a crude
quantitative risk assessment. Granath et al. suggested that we perform a
within cohort dose-response analysis with all malignant neoplasms as the
endpoint as a means of attaining greater statistical power. They further
contend that a priori focus on specific cancer sites implicated in
previous experimental animal studies is mostly a consequence of the
pattern of background incidences in the animal strain used. While choosing
a generic health outcome such as all cancer sites combined will certainly
increase statistical power, it also greatly reduces the ability to
evaluate the all important specificity of an exposure-response
relationship. It is unlikely that even the most potent carcinogenic agent
will increase the risks of all cancer sites to a level that can be
detected with epidemiological methods.
We were fully justified in using cancer site-specific findings as the
focus of our epidemiological investigation. The use of cancer site-
specific findings from experimental animal studies to formulate a priori
testable etiologic hypotheses for human studies is an effective, accepted
method commonly employed in occupational epidemiological research. Animal
studies can be particularly helpful when investigators are faced with a
paucity of extant epidemiological evidence such as in the case of AMD.
This practice does not preclude, however, the exploratory investigation of
other non-implicated sites as long as the related findings are interpreted
in light of their hypothesis generating nature.
We agree that for many of the a priori cancer sites examined in our
study, the statistical power to detect a moderate mortality excess (1.5 to
twofold or greater) was low, a point addressed in the discussion section
of our paper. However, the power of our study to detect a twofold or
greater excess in lung cancer, the endpoint of primary concern, at the one
-sided 5% significance level was in the excellent range (0.87), as would
be the power to detect a similar excess of pancreatic cancer in a future
update of this cohort.
Granath et al. overlook a fundamental point - occupational cohort
studies of the type we used to evaluate cancer mortality risks among AMD
exposed workers are neither designed nor necessarily well suited for
quantitative risk assessment purposes. Occupational cohort studies are
purposely not designed to detect small excesses in the range of 5-15%
deemed by Granath et al. as unacceptable. The primary reason for this is
that excesses of this magnitude could easily be due, at least in part, to
one or more confounding factors. Observational epidemiological studies
usually cannot discriminate among such small mixed effects, and are
generally most useful for detecting increases in risk that exceed 50-100%
as these are unlikely to be due to uncontrolled confounding. Statistical
power considerations notwithstanding, the fact remains that our study is
the largest and most comprehensive study of AMD exposure conducted to
date, and will continue to provide useful epidemiological Information
through future updates and analysis.
Gary M. Marsh
Ada O. Youk
Lorraine J. Lucas
Laura C. Schall
1. Marsh GM, Lucas L, Youk AO, Schall LC: Mortality Patterns among
Workers
Exposed to Acrylamide: 1994 Follow-Up. Occup Environ Med 1999;56:181-190.
In their 1999 study of workers exposed to acrylamide, Marsh et al
conducted an SMR analysis and fit several relative risk regression models
to the data.[1] In each analysis, they found risk of pancreatic cancer
elevated by about twofold for workers in the highest cumulative exposure
group, but risk of pancreatic cancer did not increase monotonically with
cumulative exposure in any of their analyses. Dur...
In their 1999 study of workers exposed to acrylamide, Marsh et al
conducted an SMR analysis and fit several relative risk regression models
to the data.[1] In each analysis, they found risk of pancreatic cancer
elevated by about twofold for workers in the highest cumulative exposure
group, but risk of pancreatic cancer did not increase monotonically with
cumulative exposure in any of their analyses. Duration of exposure was
monotonically related and mean intensity showed a nearly monotonic
relationship with pancreatic cancer risk.
The cut points Marsh et al chose for the cumulative exposure groups
are based on multiples of current and proposed regulated levels of
exposure intensity.[1] [2] Because these cut points resulted in small
numbers of expected deaths in the low and intermediate exposure groups,
1.08 and 2.74 respectively, we have regrouped the data to attempt to
obtain more stable SMRs. These results are presented in Table 1 and
indicate a monotonic dose-response pattern with the SMRs increasing from
0.80 to 1.31 to 2.26.
Table 1. Observed deaths, expected deaths, and SMRs for cancer of
the
pancreas, all US workers, 1950-94, local county comparisons, two
lowest exposure groups combined.
Cumulative Exposure (mg/m3.y)
Obs
Exp
SMR
95% CI
30
37.50
0.80
0.54-1.14
0.001-0.29
5
3.82
1.31
0.35-3.05
>0.30
9
3.98
2.26
1.03-4.29
In part based on the absence of a pattern of monotonically increasing
risk with increased cumulative exposure, Marsh et al. argue that, "our
findings for cancer of the pancreas should be interpreted with caution, in
the context of an exploratory analysis to generate hypotheses."[1]
Nevertheless, given the sufficient evidence in experimental animals for
the carcinogenicity of acrylamide.[3] this study plays an important role
in the evaluation of safety for occupational exposures to acrylamide.
When data are sparse, it is not always clear how best to choose cut
points; the grouping we have shown results in a finding that is more
compatible with the findings for duration and for intensity of exposure.
It would be interesting to see if a regrouping of the exposure categories
alters the results of the analyses based on internal comparisons.
MR. Schulz
I Hertz-Picciotto
E van Wijngaarden
J Calderon Hernandez
Department of Epidemiology,
University of North Carolina at Chapel Hill
LM. Ball
Department of Environmental Sciences and Engineering,
University of North Carolina at Chapel Hill
1. Marsh GM, Lucas LJ, Youk AO, et al. Mortality patterns among
workers exposed to acrylamide: 1994 follow up. Occup Environ Med
1999;56:181-90.
2. Collins JJ, Swaen GH, Marsh GM, et al. Mortality patterns among workers
exposed to acrylamide. J Occup Med 1989;31:614-17.
3. International Agency for Research on Cancer. Acrylamide In IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans; Some
Industrial Chemicals Volume 60. Lyon, France 1994.
We thanks Barratt and colleagues for their comments. We agree that
"care should be taken to validate model estimates with empirical
measurements wherever possible". Barratt and colleagues cite two stations
from the European Environment Agency database as located in the Railway
Ring and they report increasing NO2 concentrations from 2001 to 2005.
However, one station (IT0953A) is actually located i...
We thanks Barratt and colleagues for their comments. We agree that
"care should be taken to validate model estimates with empirical
measurements wherever possible". Barratt and colleagues cite two stations
from the European Environment Agency database as located in the Railway
Ring and they report increasing NO2 concentrations from 2001 to 2005.
However, one station (IT0953A) is actually located in the middle of a
large park within the Railway Ring, and thus reflecting urban background
concentrations, while the other station is not located in the Railway
Ring, making a direct validation nearly impossible. The correct code of
another traffic station located within the Railway Ring is IT0828A and the
annual mean NO2 concentration went from 80 ?g/m3 in 2001 to 68 ?g/m3 in
2005, which is a clear decrease supporting our work.
Moreover, official data from the Regional Environmental Agency
document that in Rome there was a decrease in nitrogen dioxide (NO2)
concentrations in most of the fixed monitoring stations from 2001 to
2005.[1] Moreover, Cattani et al. have documented a decrease in both NO2
and PM concentrations, especially in sites located near traffic, over a
longer period.[2]
That NOx emission standards of the different EURO vehicle classes are
much smaller than initially anticipated when the policy was formulated is
discovered very recently, and was not known at the time of this study.
Modelling studies are hampered by assumptions about for example emission
factors which may not be correct. Policy evaluation by measurements will
encounter difficulties as well, particularly by other developments
unrelated to the policy (for example an increase in the proportion of
diesel vehicles in the London congestion charging zone). Apart from
traffic other sources of air pollution on both the local and regional
scale, coupled with varying meteorological conditions could all confuse
air pollution trends. Therefore, multiple time windows surrounding the
policy and inclusion of sites not affected by the policy should be
evaluated in a proper empirical evaluation. Since this data was not
readily available at the time of this study, we performed a modelling
approach, reflecting real word conditions as close as possible.
2. Cattani G, Di Menno di Bucchianico A, Dina D, et al. Evaluation of
the temporal variation of air quality in Rome, Italy, from 1999 to 2008.
Ann Ist Super Sanita. 2010;46:242-53.
In their reply to me (Weill et al, 2005), I stand reproved for
ignorance and partisanship ("...more interested in the "adversarial
spectrum than the science!"). Modesty precludes me from protesting the
first, but I affirm that I have never been funded by industry or by unions
to write opinions or conduct research on their behalf, nor have I been
paid to assist them in litigation or to support or conte...
In their reply to me (Weill et al, 2005), I stand reproved for
ignorance and partisanship ("...more interested in the "adversarial
spectrum than the science!"). Modesty precludes me from protesting the
first, but I affirm that I have never been funded by industry or by unions
to write opinions or conduct research on their behalf, nor have I been
paid to assist them in litigation or to support or contest proposals to
alter an asbestos hygiene standard.
I would take issue on their interpretation of Wagner's inhalation
experiments, which are not so clear cut and dried in relation to the
development of malignant mesothelioma. In fact, Wagner was persuaded by
his early experimental studies in South Africa, that crocidolite and
Amosite should be considered as hazardous as chrysotile. In later years he
certainly became more kindly disposed towards chrysotile and testified
accordingly at conferences and in depositions on behalf of industry.
Defenders of chrysotile contend that it must be safer than
amphiboles, pleading the alternative that the shape of its fibres renders
it less respirable, and that anyway it is rapidly cleared from the lung
parenchyma (though what this has to do with disease of the pleura is not
apparent). For all this, chrysotile fibres are found in the lung
parenchyma in Man in substantial quantities, long after exposure has
ceased, and after mixed asbestos dust exposure chrysotile is commonly
found juxtapleurally in cases of malignant mesothelioma. The insistence of
chrysotile's protagonists that it is the amphibole in the parenchyma that
is the causal agent rather than the chrysotile near the tumour site, is
that an example of Weill et al's "adversarial spectrum" or "science"?
Weill et al speak of asbestos associated cancers as "...a problem
that with proper control of exposure, will slowly disappear...". In 1906
and at regular intervals subsequently, proper control of exposure was
deemed to to have been exerted so that future generations of physicians
would never see a case of asbestosis. Well regrettably they have , lots
of them as well as lots of bronchial carcinomas and malignant
mesotheliomas. WHO, IPCS, and EU among others, are not persuaded that the
phrase, "the safe use of asbestos" is other than an oxymoron when employed
in Developed Countries let alone in the Third World.
The authors ask despairingly, "..if there will ever come a time when
any good news about asbestos related health effects is welcomed by all who
profess to have worker health as their primary motivation". In the past
good news about asbestos related health effects has ncluded: assurance
from government and industry that Canada's miners and millers were in
robust good health well into their 70s ; that asbestos exposure protected
against pulmonary tuberculosis; that Richard Doll's claim for a causal
association between lung cancer excess and asbestos exposure could not be
corroborated; that asbestos diseases were relegated to history. The World
Trade Organization, Commissioners, who have never been perceived to be
antipathetic to the interests of commerce, have not opposed an EU
Directive that on health grounds will apply a virtual total ban on the use
of chrysotile. For now, the resultant surplus chrysotile mined is being
marketed freely in the Third World, but the United Nations Environment
Programme's Rotterdam Convention may yet require Prior Informed Consent
for this. By all means discount the opinions of hypocrites who profess to
have worker health as their primary motivation, but do the decisions of
IPCS, WTO, and UN, represent good or bad news?
Burns et al.[1] report a significant excess of deaths due to amyotrophic lateral sclerosis (ALS) in a cohort of Dow employees potentially exposed to the herbicide 2,4-Dichlorophenoxyacetic (2,4-D), but then argue against the plausibility of a causal association, concluding that the association "is not consistent with previous human or animal studies".
This conclusion and the authors' characterisatio...
Burns et al.[1] report a significant excess of deaths due to amyotrophic lateral sclerosis (ALS) in a cohort of Dow employees potentially exposed to the herbicide 2,4-Dichlorophenoxyacetic (2,4-D), but then argue against the plausibility of a causal association, concluding that the association "is not consistent with previous human or animal studies".
This conclusion and the authors' characterisation of the relevant epidemiologic studies appear to rely entirely upon statistical significance, which downplays the importance of their finding. Firstly, the authors state that "cohort studies of people with exposure to 2,4-D (have not) reported
increased rates of ALS," citing two studies,[2] [3] both of which have limited power to detect the risk of ALS. One of the two studies assessed risk in a cohort that was quite young with a relatively short follow up,[2] and would therefore be unlikely to detect an increased risk for a
disease such as ALS, which has a much older median age at onset. Burns et al then go on to state that "exposure to pesticides and agricultural chemicals have shown no significant association in several studies"(emphasis added).[1]
In each of the three case-control studies cited, however, ALS was positively associated with pesticides or agricultural chemicals, with reported ORs of 1.4,[4] 2.0,[5]
and 3.0,[6] although the associations do not reach statistical significance. Finally, Burns et al refer to a case-control study,[7] which found a significant association between ALS and pesticides, but, they emphasise, "did not find a significant association of exposure to
herbicides".[1] The association between ALS and herbicide exposure was increased, however, and the lack of statistical significance reflected, at least in part, small numbers.
None of this is meant to say that the finding of a significant association between ALS and 2,4-D is conclusive.
The finding is, however, consistent with several previous studies and, instead of being played down, warrants serious attention in future studies.
D M Freedman
National Cancer Institute
Division of Cancer Epidemiology and Genetics
USA
1. Burns CJ, Beard KK, Cartmill JB. Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945-94: an update. Occup Environ Med 2001;58:24-30.
2. Zahm SH. Mortality study of pesticide applicators and other employees of a lawn care service company. J Occup Environ Med 1997;39:1055-67.
3. Coggon D, Pannett B, Winter P. Mortality and incidence of cancer at four factories making phenoxy herbicides. Br J Ind Med 1991;48:173-8.
4. Chancellor AM, Slattery JM, Fraser H, et al. Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 1993;56:1200-6.
5. Deapen DM, Henderson BE. A case-control study of amyotrophic lateral sclerosis. Am J Epidemiol 1986;123:790-9.
6. Saviettieri G, Salemi G, Arcara A, et al. A case-control study of amyotrophic lateral sclerosis. Neuroepidemiology 1991;10:242-5.
7.McGuire V, Longstreth WT Jr, Nelson LM, et al. Occupational exposures and amyotrophic lateral sclerosis.
Am J Epidem 1997;145:1076-88.
In the article, "Parkinson’s disease and other basal ganglia or
movement disorders in a large nationwide cohort of Swedish welders,"1 the
authors conclude:
"This nationwide record linkage study offers no support for a relation between welding and Parkinson’s disease or other specific basal ganglia and movement disorders."
They argue that there is a need for their study, a 29 year stu...
In the article, "Parkinson’s disease and other basal ganglia or
movement disorders in a large nationwide cohort of Swedish welders,"1 the
authors conclude:
"This nationwide record linkage study offers no support for a relation between welding and Parkinson’s disease or other specific basal ganglia and movement disorders."
They argue that there is a need for their study, a 29 year study with
a large number of welders, because other studies have conjectured that low
grade exposure to manganese fumes may increase the risk for Parkinson’s
disease and other basal ganglia and movement disorders. They point out
that, unlike their study, these other studies were neither long term nor
did they include a large number of welders.
In the referenced studies cited to support their argument manganese
exposure levels were not measured. But they were measured in the subject
study and the exposure levels were at a relatively low level. According to
Table 2 of the study, the average median exposure level was roughly
0.21mg/m3 for 1974-1975 (assumed to be a representative year). This is
very close to the guidelines of the Agency for Toxic Substances and
Disease Registry - Toxicological Profile for the Manganese air quality
guideline for 2000 of 0.15 mg/m3(Recommended Air Quality Guideline for
Europe: annual average).2
Other credible studies do find a linkage where the exposure levels
are significant. A case study of 8 welders entitled, "Neurologic
manifestations in welders with pallidal MRI T1 hyperintensity" concluded
that welding without proper protection was associated with syndromes of
Parkinsonism where the welding was done with inadequate ventilation. The
symptoms included hand and postural tremor and unsteady gate.3
Neither the conclusion nor the abstract mention this qualification.
Only by reading the full article would the reader know that the airborne
manganese levels were kept at such a low level. The public often relies on
medical journal articles and the danger of misconstruing
the meaning of this article is a significant one. A report
published in the Welding Information and Knowledge Base4
interpreted the Swedish article to say:
"Study of Almost 50,000 Swedish Welders is Most Powerful To Date; Offering Support That Welders Are Not at Increased Risk for Movement Disorders."
Although the subject study is a valuable addition to the
literature of the risks of exposure to airborne manganese, the conclusion
reached is easily subject to misinterpretation. In this case,
misinterpretation poses a significant health risk.
Robert Eli
References
1. Fored CM, Fryzek JP, Brandt L, et al. Parkinson's disease and
other basal ganglia or movement disorders in a large nationwide cohort of
Swedish welders. Occupational
and Environmental Medicine 2006; 63; 135-140.
2. Agency for Toxic Substances and Disease Registry.2000.
Toxicological profile for Manganese. U.S. Department of Health and Human
Services Public Health Service
Available at:
http://www.atsdr.cdc.gov/toxprofiles/tp151.html
3. Josephs KA, Ahlskog JE, Klos KJ, et al. Neurologic manifestations
in welders with pallidal MRI T1 hyperintensity. Neurology 2005; 64:2033-2039.
We appreciate the interest taken in our study by Dr. Freedman.[1] At the heart of the discussion are the interpretation of statistical significance in our study,[2] and the lack of statistical significance in others. A critical point in valuing causation is the weight of the evidence to be placed upon the nonsignificant increase of nonspecific exposures observed in human studies of amyotrophic lateral sclerosis (ALS) compare...
We appreciate the interest taken in our study by Dr. Freedman.[1] At the heart of the discussion are the interpretation of statistical significance in our study,[2] and the lack of statistical significance in others. A critical point in valuing causation is the weight of the evidence to be placed upon the nonsignificant increase of nonspecific exposures observed in human studies of amyotrophic lateral sclerosis (ALS) compared to the
weight placed upon controlled animal studies specific to the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D).
I agree with Dr. Freedman that undue reliance upon statistical significance is ill advised. He is correct that the case-control studies cited in our paper showed elevated odds ratios,[3][4][5][6] but there is no evidence that any subjects were actually exposed to 2,4-D since the exposures were limited to "pesticides" and "agricultural chemicals" and "herbicides". The cohort studies examined workers who were definitely exposed to 2,4-D and thus provide a more valid assessment of risk even though they are less powerful than the case-control studies.[7][8] The cohort studies of 2,4-D do not consistently show increased risk of ALS.
The associations observed in the case-control studies are clearly unsupported by the experimental studies that have been conducted on 2,4-D. Environmental causes of ALS remain unknown. If future epidemiological studies investigate the neurotoxicity of herbicides such as 2,4-D, the researchers must improve upon the status quo of surrogate exposure
information used in case-control studies or perform further studies of the 2,4-D workers. Epidemiologist must make a commitment to quality exposure assessment of individual pesticides, perhaps coupled with biomonitoring, to address the putative health concerns associated with pesticides.
CJ Burns
1 Freeman DM. Mortality in chemical workers potentially
exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945 – 94: an update. Occup Environ Med 2001.
2 Burns CJ, Beard KKI, Cartmill JB. Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid 1945-94: an update. Occup Environ Med 2001;58:24-30.
3 Chancellor AM, Slattery JM, Fraser H, et al. Risk factors for motor neuron disease: a case-control study based on patients from the Scottish Motor Neuron Disease Register. J Neurol Neurosurg Psychiatry 1993;56:1200-
6.
4 Deapen DM, Henderson BE. A case-control study of amyotrophic lateral sclerosis. Am J Epidemiol 1986;123:790-9.
5 Saviettieri G, Salemi G, Arcara A, et al. A case-control study of amyotrophic lateral sclerosis. Neuroepidemiology 1991;10:242-5.
6 McGuire V, Longstreth WT Jr, Nelson LM, et al. Occupational exposures and amyotrophic lateral sclerosis. Am J Epidemiol 1997;145:1076-88.
7 Zahm SH. Mortality study of pesticide applicators and other employees of a lawn care service company. J Occup Environ Med 1997;39:1055-67.
8 Coggon D, Pannett B, Winter P. Mortality and incidence of cancer at four factories making phenoxy herbicides. Br J Ind Med 1991;48:173-8.
We read with interest the article by Alamgir et al (1) regarding the
use of hospital discharge records in occupational health in the April
issue of Occupational and Environmental Medicine. The paper adds to the
evidence that these records represent an alternative and independent
source of information for serious work-related injuries. In their
introduction, the authors also make the point that, to...
We read with interest the article by Alamgir et al (1) regarding the
use of hospital discharge records in occupational health in the April
issue of Occupational and Environmental Medicine. The paper adds to the
evidence that these records represent an alternative and independent
source of information for serious work-related injuries. In their
introduction, the authors also make the point that, to their knowledge,
studies in Canada using this data source have not validated its use
against other available indicators.
We would like to bring to the attention of readers a previous
Canadian study conducted by us (2) in which we attempted to confirm the
diagnoses in the hospital records. In an initial study (3), we examined
the association of pneumoconiosis and cor pulmonale in Ontario using
hospital discharge data available from the Hospital Medical Records
Institute (HMRI, now the Canadian Institute for Health Information) and
the Ontario Ministry of Health (3). In the follow-up report (2), we
attempted to confirm the validity of the coding of the diagnoses of a
subset of the hospital discharges from the original study, and to identify
work exposure (occupation and industry) information available in hospital
records. We wrote to hospitals providing abstraction forms to be
completed for 521 subjects hospitalized for pneumoconiosis, cor pulmonale
or both requesting information regarding diagnoses, occupation and
industry data. We received completed abstraction forms from 151 (76%) of
the hospitals contacted, representing 720 (76%) of the 944 discharges and
421 (81%) of the 521 patients. The HMRI diagnoses were confirmed for 97%
of those with silicosis and for 96% of those with asbestosis, and there
was very good agreement between the two sources for the presence or
absence of these conditions (kappa of 0.84 and 0.86, respectively). We
also examined occupation and industry information available in the charts
for which silicosis was a diagnosis. Of the 242 charts with silicosis,
122 had occupation/ industry information that could be classified
regarding exposure to a specific dust type, and of these 89 (73%) were
classified as consistent with silica exposure.
Furthermore, as a check against a second available indicator, of 34
individuals in this data set known from the Ontario Ministry of Labour’s
Chest Clinic x-ray surveillance program of miners to have silicosis, 33
(97%) were diagnosed by the hospitals as having pneumoconiosis, and all
but two were silicosis. These findings indicated that at least for
pneumocioses (conditions that are pathognomonic of occupation), we could
confirm the diagnoses and the hospital records frequently contained
information about the responsible exposures.
Gary M Liss, MD, MS, FRCPC,
Robert A. Kusiak, MSc,
Ontario Ministry of Labour,
Toronto, ON, Canada
References
1. Alamgir H, Koehorn M, Ostry A, Tompa E, Demers P. An
evaluation of hospital discharge records as a tool for serious work
related injury surveillance. Occup Environ Med 2006; 63:290-296.
2. Liss GM, Kusiak RA, Gailitis MM. Hospital records: an
underutilized source of information regarding occupational diseases and
exposures. Am J Ind Med 1997; 31:100-106.
3. Kusiak RA, Liss GM, Gailitis MM. Cor pulmonale and
pneumoconiotic lung disease: An investigation using hospital discharge
data. Am J Ind Med 1993; 24:161-173.
Dr Burge and his coworkers raise a very important issue in terms of the physiological criteria on which a diagnosis of occupational asthma should be based, and in particular, the clinical significance of small work related declines in peak expiratory flow. We fully accept that a lack of an increase in diurnal variation does not exclude a diagnosis of occupational asthma. The pattern of peak flow measurements...
Dr Burge and his coworkers raise a very important issue in terms of the physiological criteria on which a diagnosis of occupational asthma should be based, and in particular, the clinical significance of small work related declines in peak expiratory flow. We fully accept that a lack of an increase in diurnal variation does not exclude a diagnosis of occupational asthma. The pattern of peak flow measurements in occupational asthma quite frequently reveals a marked difference in the mean peak flow on working days compared to days away from work without any increase in
diurnal variation.
Dr Burge and his colleagues refer to the phenomenon of small work related changes and raise the question as to whether this represents asthma or other lung pathology.[1] At that time, their opinion was that the significance of these small changes was unclear. The example that they gave showed that taking the lowest peak flow recording during the working week and the highest peak flow recording on days away from work, a variation in peak flow in excess of 20% which we would accept as compatible with asthma and from the pattern
illustrated probable occupational asthma. The small group of workers that we studied had diurnal variations in peak flow ranging between 5.7% and 9.8% and taking the worst working day peak flow and the best day off work peak flows, a variation between 11% and 13.5% (our peak flow recordings
were linearised). This degree of variation does not satisfy the BTS criteria for a diagnosis of bronchial asthma, neither do they satisfy a positive challenge response in bronchial challenge study. We have seen similar
patterns of peak flow recordings in textile workers exposed to dust, both with and without, significant contamination with endotoxin.
We took the view that the small peak flow changes were due to an irritant effect and postulate the same mechanism in this group exposed to glutaraldehyde. The
clinical histories provided by these workers does not suggest increasing
respiratory symptoms with continued exposure. While it is possible that
the changes that we have reported may represent a very mild form of
occupational asthma, the clinical picture and the small physiological
variation in peak flow, in our opinion is more consistent with
an irritant airway response than the development of occupational asthma.
Our paper is not intended to suggest that glutaraldehyde is not capable of inducing occupational asthma, for which there is convincing published evidence, in addition to our own personal experience. Our paper reports the findings of an epidemiological survey of a large population of
currently exposed endoscopy nurses and has demonstrated that while respiratory symptoms occur in this group, that the lung physiology and the immunology has not supported a suggestion of a high prevalence of occupational asthma
at current exposure levels.
The current research paper by Fransen et al. (2006) contributes
interesting and useful data to the emerging research area examining the
potential risk of extended working hours, unusual work patterns, and the
occurrence of a work related injury.
I am concerned, however, that readers may conclude that working
permanent night shifts carries no increased risk of work injury, despite
contrary evidence as they cited...
The current research paper by Fransen et al. (2006) contributes
interesting and useful data to the emerging research area examining the
potential risk of extended working hours, unusual work patterns, and the
occurrence of a work related injury.
I am concerned, however, that readers may conclude that working
permanent night shifts carries no increased risk of work injury, despite
contrary evidence as they cited. Highlighted in their report (including
the Abstract and Main Messages) was their conclusion that “Permanent night
work is not associated with increased risk of work injury after adjusting
for these other risk factors.”
In Table 4, the reported point estimate (RR) and 95% confidence
interval (CI) for permanent night shift was 1.38 (0.95-2.00). I would
argue that this “mutually adjusted result” suggests a fairly strong
association between working permanent night shifts and the risk of a work
injury; however, since the number of injured cases in this cell was small
(n=69), this result is a potential Type II error and possibly
statistically underpowered result (Freiman, J.A., T.C. Chalmers, H. Smith
et al., 1978). Thus, it should have been interpreted with caution rather
than suggesting with certainty that there is no association.
Additionally, it would be of interest to see the adjusted results
when using working hours as a continuous variable, rather than a single
cut point of 40 hours, which may or may not reflect long working hours.
Again, I am grateful to the authors for publishing these important
results.
Fransen M, Wilsmore B, Winstanley J, Woodward M, Grunstein R,
Ameratunga S, Norton R Shift work and work injury in the New Zealand
Blood Donors' Health Study. Occup Environ Med 2006 May; 63(5) :352-8.
Freiman, J.A., T.C. Chalmers, H. Smith et al. The importance of beta,
the type II error and sample size in the design and interpretation of the
randomized control trial. New England Journal of Medicine 299:690-694,
1978.
Editor,
Granath and colleagues take issue with our update of a cohort of acrylamide (AMD) workers from three U.S. plants[1] claiming that "it exemplifies the shortcomings of studies of this type to detect moderate influences of specific causative factors on cancer mortality or incidence." To support their contention that we overlooked a small but "unacceptable" increase in cancer risk, they performed a crude q...
Editor,
In their 1999 study of workers exposed to acrylamide, Marsh et al conducted an SMR analysis and fit several relative risk regression models to the data.[1] In each analysis, they found risk of pancreatic cancer elevated by about twofold for workers in the highest cumulative exposure group, but risk of pancreatic cancer did not increase monotonically with cumulative exposure in any of their analyses. Dur...
Dear Editor,
We thanks Barratt and colleagues for their comments. We agree that "care should be taken to validate model estimates with empirical measurements wherever possible". Barratt and colleagues cite two stations from the European Environment Agency database as located in the Railway Ring and they report increasing NO2 concentrations from 2001 to 2005. However, one station (IT0953A) is actually located i...
Dear Editor,
In their reply to me (Weill et al, 2005), I stand reproved for ignorance and partisanship ("...more interested in the "adversarial spectrum than the science!"). Modesty precludes me from protesting the first, but I affirm that I have never been funded by industry or by unions to write opinions or conduct research on their behalf, nor have I been paid to assist them in litigation or to support or conte...
Editor
Burns et al.[1] report a significant excess of deaths due to amyotrophic lateral sclerosis (ALS) in a cohort of Dow employees potentially exposed to the herbicide 2,4-Dichlorophenoxyacetic (2,4-D), but then argue against the plausibility of a causal association, concluding that the association "is not consistent with previous human or animal studies".
This conclusion and the authors' characterisatio...
Dear Editor,
In the article, "Parkinson’s disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders,"1 the authors conclude:
"This nationwide record linkage study offers no support for a relation between welding and Parkinson’s disease or other specific basal ganglia and movement disorders."
They argue that there is a need for their study, a 29 year stu...
We appreciate the interest taken in our study by Dr. Freedman.[1] At the heart of the discussion are the interpretation of statistical significance in our study,[2] and the lack of statistical significance in others. A critical point in valuing causation is the weight of the evidence to be placed upon the nonsignificant increase of nonspecific exposures observed in human studies of amyotrophic lateral sclerosis (ALS) compare...
Dear Editor:
We read with interest the article by Alamgir et al (1) regarding the use of hospital discharge records in occupational health in the April issue of Occupational and Environmental Medicine. The paper adds to the evidence that these records represent an alternative and independent source of information for serious work-related injuries. In their introduction, the authors also make the point that, to...
Editor
Dr Burge and his coworkers raise a very important issue in terms of the physiological criteria on which a diagnosis of occupational asthma should be based, and in particular, the clinical significance of small work related declines in peak expiratory flow. We fully accept that a lack of an increase in diurnal variation does not exclude a diagnosis of occupational asthma. The pattern of peak flow measurements...
The current research paper by Fransen et al. (2006) contributes interesting and useful data to the emerging research area examining the potential risk of extended working hours, unusual work patterns, and the occurrence of a work related injury.
I am concerned, however, that readers may conclude that working permanent night shifts carries no increased risk of work injury, despite contrary evidence as they cited...
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