Letter to the editor:
We appreciate the opportunity to comment on the article by Thomsen RW et al. Risk of asbestos, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. We believe there are many problems in methodology and we disagree with author’s interpretations and conclusions especially in relation to asbestos and mesothelioma in vehicle mechanics in this article.
The epidemiology analysis described by Thomsen et al lacks asbestos exposure data and uses cross-sectional occupation data as surrogates for longitudinal use. Occupational categories are not equal to exposure. Especially for asbestos it has been clear that obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease. Without longitudinal individual exposure histories in the Thomson et al study, there is undoubtably significant misclassification of exposure in both the motor vehicle mechanic group (unexposed considered exposed) and even more problematic in the control group (exposed classified as unexposed). This double likelihood of exposure misclassification creates unreliable analytics which result in an epidemiologic bias towards the null. 1
Thomsen et al used cross-sectional data at variable dates to place workers in their two study cohorts based on reported current occupation and industry. The occupation on the 1970 census or when first...
Letter to the editor:
We appreciate the opportunity to comment on the article by Thomsen RW et al. Risk of asbestos, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. We believe there are many problems in methodology and we disagree with author’s interpretations and conclusions especially in relation to asbestos and mesothelioma in vehicle mechanics in this article.
The epidemiology analysis described by Thomsen et al lacks asbestos exposure data and uses cross-sectional occupation data as surrogates for longitudinal use. Occupational categories are not equal to exposure. Especially for asbestos it has been clear that obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease. Without longitudinal individual exposure histories in the Thomson et al study, there is undoubtably significant misclassification of exposure in both the motor vehicle mechanic group (unexposed considered exposed) and even more problematic in the control group (exposed classified as unexposed). This double likelihood of exposure misclassification creates unreliable analytics which result in an epidemiologic bias towards the null. 1
Thomsen et al used cross-sectional data at variable dates to place workers in their two study cohorts based on reported current occupation and industry. The occupation on the 1970 census or when first mentioned for individuals on later registrations was used to assign vehicle mechanic occupation with the assumption that asbestos exposure had occurred. The selected occupation categories for the “comparison” cohort assumed non-asbestos exposed occupations throughout their working lifetime. Other than looking for the vehicle mechanic category, apparently no search was made in subsequent registries to see if they had switched to another occupation with asbestos exposure likelihood. The authors do mention that about one half of the 21,102 1970 census vehicle mechanic individuals were in the same category in the 1996-1999 registry. However, was the work they performed the same? The cohort was very young at entrance at any of the time intervals (median age 25) and the median follow-up was 20 years. The age at which mesothelioma occurs is usually in the 70+ age group. Latency for mesothelioma can be as high as 50 years or more. Over 70% of the cohort were first enrolled after 1986 when asbestos use in Danish vehicle brakes was disappearing, exposure standards in place and the likelihood of high exposure for those just entering the cohort reduced. Only 23% of the cohort was deceased and the vast majority had not reached the age group where mesotheliomas or asbestosis would occur, given their long latent period.
The overall finding of Thomsen et al was that asbestosis was elevated in motor vehicle mechanics, but not mesothelioma. A clinical diagnosis of asbestosis requires a history of asbestos exposure while at autopsy a tissue diagnosis may be made when no exposure history is found. What is striking is that there were 313 comparator cases of asbestosis in the morbidity data and 108 in mortality. This information supports the case for exposure misclassification in the comparison group. Similarly, the occurrence of 553 mesothelioma/pleural cancer mortality cases among the comparators and 628 cases in the morbidity files also suggests misclassification among the “non-asbestos exposed” as an explanation for the lack of statistical differences between the cohorts.
The high number of asbestosis cases and deaths among the comparison group and the statistical excess among the vehicle mechanics but not an excess of mesothelioma/pleural cancer is puzzling as a higher dose of asbestos exposure is needed for asbestosis than for mesothelioma.2 An explanation may be that the years of follow-up in the Thomsen et al study may not have been long enough for the peak mesothelioma risk but sufficient for clinical detection of asbestosis/pleural abnormalities. Supporting this is that Thomsen et al found the highest association with mesothelioma in the 1970 census cohort, which had the longest follow-up.
Thomsen et al. states that asbestos use in brakes is now phased out in most countries. Unfortunately, this is not true. Chrysotile asbestos is currently being widely used in Brazil, Russia, China, India, Thailand, Malaysia and elsewhere and is being used in the manufacture of brakes. (2-5) Since there is potential exposure to toxic chrysotile asbestos fibers of various sizes in the dusty environment of motor vehicle mechanics, which is continuing in several countries around the world, precaution should point to policies that concentrate on industrial hygiene measures that limit worker dust exposure.
Marty S Kanarek, PhD1, Henry A Anderson, MD1
1 Department of Population Health Sciences and in the Nelson Institute for Environmental Studies, University of Wisconsin-Madison, Madison, Wisconsin, USA
Correspondence to Professor Marty Kanarek, Department of Population Health Sciences, School of Medicine and Public Health, 610 N. Walnut Street, University of Wisconsin-Madison, 53726; mkanarek@wisc.edu
Contributors MSK was the lead author. HAA was co-author, reviewing the original response and contributing original content in addition to editing. Final version was approved by both authors.
Funding None
Competing interests Both Kanarek and Anderson have served as consultants to government and international agencies on asbestos health effects, and have been consultants and witnesses on plaintiff’s litigation concerning asbestos and disease.
References
1. Checkoway H, Pearce N, Kriebel D. Research methods in occupational epidemiology. Monographs in Epidemiology, 2nd Ed. 2004, Oxford U Press.
2. Kanarek, MS, Anderson HA. Mesothelioma from asbestos exposure in brake mechanics: epidemiology in context. Epidemiology: Open Access 2018;8:2. DOI. 10.4172/2161-1165.1000340.
3. Kunpeuk W, Sataporn J, Mathudara P1, Jeerapa S1, et al
A scoping review on occupational exposure of silica and asbestos among
industrial workers in Thailand. Outbreak, Surveillance Investigation and Response OSIR Journal , 2021, Volume 14, Issue 2:.41-51.
4. Chen T, Xiao-Ming S, Wu L. High time for complete ban on asbestos use
in developing countries. JAMA Oncology 2019; May 23 E1-E2.
5. Omar A, Lamin F , Mohamed N. Comparative study of brake pads in Malaysian
automotive aftermarket. International Journal of Crashworthiness 2016; http://dx.doi.org/10.1080/13588265.2016.1221372.
We appreciate the thoughtful letter from Drs. Kanarek and Anderson. Our study does not address the well-established fact that asbestos exposure is the main causal factor of mesothelioma. The objective of our study was to investigate the risk of mesothelioma (and other asbestos related diseases) in motor vehicle mechanics. The key finding is that Danish motor vehicle mechanics do not on average have an elevated risk of mesothelioma during the studied up to 45 years of follow-up. This does not exclude the possibility that some subpopulations of motor vehicle mechanics with more extreme exposure/latency time are at increased risk – but this occupation as a group is not.
We agree that exposure misclassification is a potential problem in epidemiology studies based on occupation and industry titles. We also agree that lifetime asbestos exposure histories, if they could be obtained, might reduce exposure misclassification. However, asbestos exposure is often not recognized or recalled by workers, and workers often do not recall jobs in the distant past. Also, experts may misclassify self-reported jobs regarding asbestos exposure, particularly with respect to asbestos fiber type. Thus, while Drs. Kanarek and Anderson claim “obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease” they offer no practical advice on how reliable asbestos exposure histories can be obtained. They also...
We appreciate the thoughtful letter from Drs. Kanarek and Anderson. Our study does not address the well-established fact that asbestos exposure is the main causal factor of mesothelioma. The objective of our study was to investigate the risk of mesothelioma (and other asbestos related diseases) in motor vehicle mechanics. The key finding is that Danish motor vehicle mechanics do not on average have an elevated risk of mesothelioma during the studied up to 45 years of follow-up. This does not exclude the possibility that some subpopulations of motor vehicle mechanics with more extreme exposure/latency time are at increased risk – but this occupation as a group is not.
We agree that exposure misclassification is a potential problem in epidemiology studies based on occupation and industry titles. We also agree that lifetime asbestos exposure histories, if they could be obtained, might reduce exposure misclassification. However, asbestos exposure is often not recognized or recalled by workers, and workers often do not recall jobs in the distant past. Also, experts may misclassify self-reported jobs regarding asbestos exposure, particularly with respect to asbestos fiber type. Thus, while Drs. Kanarek and Anderson claim “obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease” they offer no practical advice on how reliable asbestos exposure histories can be obtained. They also provide no evidence that such histories can differentiate between chrysotile and amphibole fibers, and provide no evidence that exposure misclassification from such histories would be less than from the methods we used.
We note that Dr. Anderson and colleagues recently published a study of mesothelioma incidence and mortality in Wisconsin (1) that identified asbestos-exposed occupations based on the self-reported “longest held job reported at the time of diagnosis” or the “usual industry and occupation” recorded on death certificates for mesothelioma cases. It was noted in that paper, that the authors were unable “to determine occupational exposure to asbestos that may have occurred from other work periods” and could not “identify nonoccupational exposure to asbestos.” Dr. Anderson acknowledged that “we would expect any bias introduced to be toward the null and lead to more conservative estimates of effect.” We believe that occupational histories in our study, which were based on historic, written employment records gathered in independent, population-based registers, were far more reliable than the self-reported usual occupations in Dr. Anderson et al.’s study.
There are now over 30 published studies of mesothelioma risks among automobile mechanics, only one of which found increased risk of mesothelioma in which the 95% confidence interval excluded the null, and which otherwise show no increased risk of mesothelioma among automobile mechanics. The consistency of these results observed by different persons, in different places, circumstances, and times (2) (some of which had lifetime occupational and environmental asbestos exposure histories) is a strong argument against the premise that exposure misclassification substantially biased the results.
Dr. Kanarek recently published a review paper in which he reported “There have not been definitive epidemiology studies of brake mechanics because of the nature of the workforce. It is generally nonunionized and spread out in car repair shops” and “Exposure to asbestos from brakes can occur to automobile or truck mechanics anywhere in a vehicle repair shop and the workers are highly transient and not documented.” Dr. Kanarek also noted there have not been “any prospective cohort studies conducted on a group of automobile mechanics.” (3). We believe our study, which is a prospective cohort study based on documented work in vehicle repair shops, answers many of his concerns.
Drs. Kanarek and Anderson point out that over 70% of our cohort of vehicle mechanics were first enrolled after 1986 when asbestos use in Danish vehicle brakes was disappearing. While this statement is correct, it ignores that 21,102 of our subjects were enrolled as mechanics in the 1970 nationwide census and that they were followed through 2015. Moreover, many of them were mechanics prior to the 1970 census. This is substantial number of people followed for a long time, regardless of whether they made up a small proportion of our entire study population. Selikoff’s landmark study of insulators (4) included only 17,800 workers, the majority of whom had yet to achieve 20 years from first exposure at the start of the study, and who were followed for only 10 years. Our population exceeded all these metrics: it was adequate to detect a substantial risk increase of mesothelioma, had there been one. Kanarek and Anderson recognize that our study was adequate to report a significant excess of asbestosis, even though there were fewer asbestosis deaths (19) than there were mesothelioma deaths (48) and the same numbers of incident cases of asbestosis cases (47) as mesotheliomas (47). This is again evidence that our study was adequate to find excess risks of both asbestosis and mesothelioma when they existed.
Drs. Kanarek and Anderson suggest that observing 313 cases of asbestosis in comparators supports the case for exposure misclassification in the comparison group. While it is possible that a small proportion of the 845,480 comparators (who functioned as 1,385,590 comparators after matching with replacement) may have had asbestos exposure at some point in their lives, the more appropriate conclusion is that the comparators were extremely unlikely to be diagnosed with asbestosis (incidence rate 1.19 per 100,000 person-years) or die of asbestosis (mortality rate 0.42 per 100,000 person years), and that not all cases of asbestosis (or mesothelioma) are caused by known exposure to asbestos. We believe a strength of our study was the choice of comparator occupations: we chose those that would be unlikely to have occupational asbestos exposure and that would have no overlapping skills with typical asbestos exposed jobs (such as in shipyards, construction, insulators, plumbing, etc.)
We acknowledge that asbestos is still used in several countries and that that these exposures should be eliminated. The findings in our paper cannot and should not be taken as an argument not to pursue this goal. We thank Drs. Anderson and Kanarek for facilitating a more thorough discussion of these issues.
References cited
1) Tomasallo CD, Christensen KY, Raymond M, Creswell PD, Anderson HA, Meiman JG. An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin. J Occup Environ Med. 2018;60(12):1143-9.
2) Hill AB. The environment and disease: association or causation. Proceedings of the Royal Society of Medicine. 1965;58:295-300.
3) Kanarek MS, Anderson HA. Mesothelioma from Asbestos Exposure in Brake Mechanics: Epidemiology in Context. Epidemiology (Sunnyvale). 2018;8(1):12.
4) Selikoff IJ, Hammond EC, Seidman H. Latency of asbestos disease among insulation workers in the United States and Canada. Cancer. 1980;46:2736-40.
Thomsen et al’s. (2021)1 suggestion that “asbestosis occurs at cumulative chrysotile exposure levels where mesotheliomas are rare or none were observed…”.to explain the increased risk of asbestosis in the absence of an increased risk of mesothelioma among vehicle mechanics appears implausible for many reasons:
a. Scientific literature shows that when there is a risk of asbestosis there is also an increased risk of pleural mesothelioma2;
b. Cumulative exposures to chrysotile asbestos sustained by career vehicle mechanics are far below the cumulative asbestos exposures traditionally associated with asbestosis (25 fibre/cc-years) as cited by Thomsen et al.1,3;
c. That chrysotile asbestos, with much shorter biopersistence than amphibole asbestos, is more fibrogenic is biologically implausible, and inconsistent with the studies that show that the degree of lung fibrosis/asbestosis correlates with retained amphibole asbestos content, not chrysotile 3,4.
d. Fibre counts amongst vehicle mechanics with mesothelioma have been found to be either within control reference limits or show increased commercial amphibole asbestos, unrelated to friction exposures 2.
e. Animal studies do not report asbestosis or mesothelioma following high-dose inhalation exposures to brake dust with and without added chrysotile 5.
We consider, as Thomsen et al 1 did, that the most plausible explanation is diagnostic bias based on control selection.
In Thomsen et al...
Thomsen et al’s. (2021)1 suggestion that “asbestosis occurs at cumulative chrysotile exposure levels where mesotheliomas are rare or none were observed…”.to explain the increased risk of asbestosis in the absence of an increased risk of mesothelioma among vehicle mechanics appears implausible for many reasons:
a. Scientific literature shows that when there is a risk of asbestosis there is also an increased risk of pleural mesothelioma2;
b. Cumulative exposures to chrysotile asbestos sustained by career vehicle mechanics are far below the cumulative asbestos exposures traditionally associated with asbestosis (25 fibre/cc-years) as cited by Thomsen et al.1,3;
c. That chrysotile asbestos, with much shorter biopersistence than amphibole asbestos, is more fibrogenic is biologically implausible, and inconsistent with the studies that show that the degree of lung fibrosis/asbestosis correlates with retained amphibole asbestos content, not chrysotile 3,4.
d. Fibre counts amongst vehicle mechanics with mesothelioma have been found to be either within control reference limits or show increased commercial amphibole asbestos, unrelated to friction exposures 2.
e. Animal studies do not report asbestosis or mesothelioma following high-dose inhalation exposures to brake dust with and without added chrysotile 5.
We consider, as Thomsen et al 1 did, that the most plausible explanation is diagnostic bias based on control selection.
In Thomsen et al 1, the selection of controls ‘with no occupational asbestos exposures’ essentially minimises the identification of any asbestosis cases in this group. Central to a diagnosis of asbestosis is an evaluation of appropriate exposure. Because vehicle mechanics are considered to be exposed to chrysotile asbestos from friction products, clinicians would be more inclined to assign a label of asbestosis than another cause for interstitial lung fibrosis, in a vehicle mechanic than in a subject with no known occupational asbestos.
The choice of control subjects from occupations known not to be exposed to asbestos raises another quite distinct issue. Ideally, both the study and control groups should have equal probabilities of exposure to asbestos from sources other than friction products. A control group selected to include only occupations known not to be exposed to asbestos is appropriate only if the vehicle mechanics in the study group were not exposed to asbestos in another occupation. Because vehicle mechanics have technical skills to allow their engagement in occupations with asbestos this is unlikely. The choice of control group in the Thomsen et al.1 study could lead to an upward bias in the estimates of the risks of asbestos-associated diseases among vehicle mechanics; this increased risk could not be attributed to asbestos exposure sustained during work as a vehicle mechanic. However, the bias, if any, in this study appears small because it confirms no increased mesothelioma risk in vehicle mechanics.
It would be ideal to have complete occupational histories in both the vehicle mechanic and control group; these occupational histories could then be controlled in statistical analyses. Such ideal data are rarely available so what may be done with the available data. Here are our suggestions:
1.The authors should give a clear description of how the definition of asbestosis has changed over the period of the study and, in particular, how the level of exposure required for labelling interstitial fibrosis as asbestosis has evolved over the period of the study.
2.Because the risks of ‘lung disease due to external agents’ is the same in the study and controls, it would be of interest to investigate the reported risks of interstitial fibroses other than asbestosis in the two groups. An increased reported risk in the control group would support the conclusion that diagnostic bias explains the increased reported risk of asbestosis among vehicle mechanics.
This paper raises two fundamental questions with respect to the diagnoses of pulmonary fibrosis and of asbestosis specifically. First, were cases of fibrosis preferentially diagnosed in either the study group or the controls? Second, was asbestosis preferentially diagnosed in one of the two groups? These questions could be addressed if appropriate clinical records were available for the study subjects. A random sample of these clinical records with occupational history expunged could be evaluated by a panel of experts blinded to the group allocation, whether vehicle mechanic or control, from which the records were sourced. This panel of experts could independently determine 1. whether or not the individual had interstitial fibrosis and 2. whether or not it could be diagnosed as asbestosis.
REFERENCES
1. Thomsen RW, Riis AH, Flachs EM, Garabrant DH, et al. Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. Thorax 2021 Jul 8; 10.1136/thoraxjnl-2020-215041.
2. Roggli VL, Sharma A: Analysis of tissue mineral fiber content, Ch. 11, In: Pathology of Asbestos Associated Diseases, 3rd Ed. (Oury TD, Sporn TA, Roggli VL eds.) Springer: New York, 2014, 253-292.
3. Roggli VL, Gibbs AR, Attanoos R, Churg A, Popper H, Cagle P, Corrin B, Franks T, Galateau-Sallé F, Galvin J, Hasleton P, Henderson D, Honma K: Pathology of Asbestosis: An Update of the Diagnostic Criteria. Report of the Asbestosis Committee of the College of American Pathologists and Pulmonary Pathology Society. Arch. Pathol. Lab. Med. 134: 462-480, 2010.
4. Green FH, Harley R, Vallyathan V, Althouse R, Fick G, Dement J, Mitha R, Pooley F. Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers. Occup Environ Med. 1997 Aug;54(8):549-59.
5. Bernstein, D. M., B. Toth, R. A. Rogers, P. Kunzendorf, J. I. Phillips, and D. Schaudien. Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity. Toxicol Appl Pharmacol 2021; 424:115-598.
We agree with Drs. Moolgavkar and Attanoos that our observation of increased risk of asbestosis unaccompanied by increased risk of mesothelioma among motor vehicle mechanics (Thomsen, 2021) is inconsistent with other studies of chrysotile exposed populations. As we discussed in our paper, mesothelioma ascertainment is highly reliable in Denmark and our mesothelioma findings are consistent with previous studies (DeBono, 2021; Garabrant, 2016; Hessel, 2021; Tomasallo, 2018; Van den Borre, 2015). Thus, we believe our findings are reliable. Conversely, the asbestosis findings raise important questions. A diagnosis of asbestosis can only be made when a clinician believes the patient has been exposed to asbestos. Pulmonary fibrosis in a vehicle mechanic might readily be diagnosed as asbestosis if the clinician was aware of the occupational history and possible presence of asbestos in brakes, clutches, gaskets, or other vehicle parts. Since our comparison subjects held jobs that did not involve obvious asbestos exposure, it is less likely that pulmonary fibrosis would be diagnosed as asbestosis in this group. Moolgavkar and Attanoos suggest that our comparison selection could have led to diagnostic bias if the vehicle mechanics and the comparisons did not have equal probabilities of exposure to asbestos from sources other than friction products. We agree - we reported that the abrupt increase in outpatient clinic diagnosed asbestosis beginning in the mid-2000s is consistent with...
We agree with Drs. Moolgavkar and Attanoos that our observation of increased risk of asbestosis unaccompanied by increased risk of mesothelioma among motor vehicle mechanics (Thomsen, 2021) is inconsistent with other studies of chrysotile exposed populations. As we discussed in our paper, mesothelioma ascertainment is highly reliable in Denmark and our mesothelioma findings are consistent with previous studies (DeBono, 2021; Garabrant, 2016; Hessel, 2021; Tomasallo, 2018; Van den Borre, 2015). Thus, we believe our findings are reliable. Conversely, the asbestosis findings raise important questions. A diagnosis of asbestosis can only be made when a clinician believes the patient has been exposed to asbestos. Pulmonary fibrosis in a vehicle mechanic might readily be diagnosed as asbestosis if the clinician was aware of the occupational history and possible presence of asbestos in brakes, clutches, gaskets, or other vehicle parts. Since our comparison subjects held jobs that did not involve obvious asbestos exposure, it is less likely that pulmonary fibrosis would be diagnosed as asbestosis in this group. Moolgavkar and Attanoos suggest that our comparison selection could have led to diagnostic bias if the vehicle mechanics and the comparisons did not have equal probabilities of exposure to asbestos from sources other than friction products. We agree - we reported that the abrupt increase in outpatient clinic diagnosed asbestosis beginning in the mid-2000s is consistent with diagnostic bias.
Moolgavkar and Attanoos suggest that we could clarify our results if we had complete occupational histories in the vehicle mechanic and comparison groups. Unfortunately, we do not have these histories, nor do we believe we could reliably estimate asbestos exposure in every historic job segment if we had them. They also suggest that we should give a clear description of how the definition of asbestosis has changed over the period of the study and how the level of exposure required for labeling interstitial fibrosis as asbestosis has evolved. We do not believe this is feasible because the diagnosis of asbestosis is not centralized to a few hospitals in Denmark and we are not aware of any resource that describes how the definition of asbestosis has changed over time. Their final suggestion, that we examine the risks of interstitial lung disease in the vehicle mechanics and the comparisons to see whether the risk of interstitial fibrosis other than asbestosis differs between the groups, is a good idea that might indicate whether one group was preferentially diagnosed with asbestosis. We will explore the feasibility of doing this.
References
1. DeBono NL, Warden H, Logar-Henderson C, Shakik S, Dakouo M, MacLeod J, et al. Incidence of mesothelioma and asbestosis by occupation in a diverse workforce. Am J Ind Med. 2021;64(6):476-87. Epub 2021/04/10.
2. Garabrant DH, Alexander DD, Miller PE, Fryzek JP, Boffetta P, Teta MJ, et al. Mesothelioma among Motor Vehicle Mechanics: An Updated Review and Meta-analysis. AnnOccupHyg. 2016;60(1):8-28.
3. Hessel PA. Mesothelioma among vehicle mechanics: a controversy? Thorax. 2021. Epub 20211105.
4. Thomsen RW, Riis AH, Flachs EM, Garabrant DH, Bonde JPE, Toft Sorensen H. Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. Thorax. 2021. Epub 2021/07/11.
5. Tomasallo CD, Christensen KY, Raymond M, Creswell PD, Anderson HA, Meiman JG. An Occupational Legacy: Malignant Mesothelioma Incidence and Mortality in Wisconsin. J Occup Environ Med. 2018;60(12):1143-9.
6. Van den Borre L, Deboosere P. Enduring health effects of asbestos use in Belgian industries: a record-linked cohort study of cause-specific mortality (2001-2009). BMJ Open. 2015;5(6):e007384-e.
The AERATOR study (Hamilton et al) compares and quantifies the risk of aerosol generation in both healthy patients and those infected with COVID-19 in a variety of contexts, including normal respiration, speaking and coughing, and the same activities whilst receiving therapy with continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO), and also whilst wearing a fluid-resistant surgical mask (FSRM)1. This study is particularly welcome as it is an area where data are scarce, yet the theoretical risks have major implications for both patients and health care professionals and influence recommendations that guide patient care, such as the use of side rooms and personal protective equipment, both of which are limited resources2. However, we have some questions about the study design.
Hamilton et al demonstrated that the size of aerosols generated by healthy individuals and those infected with COVID-19 were comparable, thereby validating the use of healthy volunteers for aerosol characterisation, though the sample sizes involved within the COVID-19 cohort were relatively small (n=6). Furthermore, the study highlights that aerosolisation was lower in healthy volunteers with non-humidified CPAP, whilst it was increased in those receiving HFNO (though it was shown to originate mostly from the device), compared to baseline for breathing, speaking, and coughing. Given the study also mentions a considerable degree of inter- and intra-individual variability...
The AERATOR study (Hamilton et al) compares and quantifies the risk of aerosol generation in both healthy patients and those infected with COVID-19 in a variety of contexts, including normal respiration, speaking and coughing, and the same activities whilst receiving therapy with continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO), and also whilst wearing a fluid-resistant surgical mask (FSRM)1. This study is particularly welcome as it is an area where data are scarce, yet the theoretical risks have major implications for both patients and health care professionals and influence recommendations that guide patient care, such as the use of side rooms and personal protective equipment, both of which are limited resources2. However, we have some questions about the study design.
Hamilton et al demonstrated that the size of aerosols generated by healthy individuals and those infected with COVID-19 were comparable, thereby validating the use of healthy volunteers for aerosol characterisation, though the sample sizes involved within the COVID-19 cohort were relatively small (n=6). Furthermore, the study highlights that aerosolisation was lower in healthy volunteers with non-humidified CPAP, whilst it was increased in those receiving HFNO (though it was shown to originate mostly from the device), compared to baseline for breathing, speaking, and coughing. Given the study also mentions a considerable degree of inter- and intra-individual variability in aerosol generation, information on sample size calculation may be relevant especially in the COVID-19 group which included only six participants³.
COVID-19 patients included in the study were either on low-flow oxygen or room air suggesting that these patients were suffering a non-severe form of the disease. COVID-19 patients requiring CPAP/HFNO tend to manifest with more respiratory symptoms4, and it is not known if these patients would also yield the same outcome as those with milder illness. Would including patients across the disease severity spectrum strengthen the evidence in order to reappraise current infection control practices?
Furthermore, six healthy volunteers underwent further studies to check reproducibility of aerosol number concentration generated at an interval of one month which showed a better correlation for breathing and only a modest value for speaking and coughing. It is unclear if the given number is sufficient to study the reproducibility of aerosol generation. In addition, the study shows the technical challenges in reliably measuring aerosol number concentration for Covid-19 patients due to background aerosols. So aerosol measurement was possible only during coughing, but not breathing or speaking. Therefore better measuring devices/methods with optimisation for background aerosol concentration to test COVID-19 patients would also be useful.
References :
1.Hamilton FW, Gregson FK, Arnold DT et al. Aerosol emission from the respiratory tract:an analysis of aerosol generation from oxygen delivery systems. Thorax 2021.DOI: 10.1136/thoraxjnl-2021-217577
1.Hamilton FW, Gregson FK, Arnold DT,et al. Aerosol emission from the respiratory tract: an analysis of aerosol generation from oxygen delivery systems. Thorax 2021-217577 Google Scholar Pub Med
2. Public Health England. COVID-19: personal protective equipment use for aerosol generating procedures, 2020. Available: https://www.gov.uk/government/publications/covid-19-personal-protective-... [Accessed 24 Jun 2021].
3. Faber J, Fonseca LM. How sample size influences research outcomes. Dental Press J Orthod. 2014;19(4):27-9 Google Scholar Pub Med
4. Klompas M, Baker MA, Rhee C. Airborne transmission of SARS-CoV-2: theoretical considerations and available evidence. JAMA 2020; 324:441–2. Google Scholar Pub Med
We thank Nimmo et al for their comments on our paper, and for recognising that this work
addresses an important gap in high quality data on aerosol generation and also the technical
challenges associated with measuring aerosol from the respiratory tract.
We agree that interparticipant variability in aerosol emission is significant (spanning several orders
of magnitude) and acknowledge in the paper that interpretation of the data on patients with COVID-
19 is limited due to the small cohort size. The AERATOR study was the first group to collect detailed
aerosol measures from patients with active SARS-CoV-2, the aim of this exploratory sub group
analysis was to consider if active infection had a meaningful impact on the use of healthy controls as
proxies in the main analysis.
Measuring aerosol emission from patients with COVID-19 is very challenging in the acute clinical
setting because of both the very low aerosol background concentration required to make a
measurement and infection control precautions. We therefore chose to report the raw data while
acknowledging the difficulties in interpretation.
In this analysis, we did not perform a sample size calculation; as we were limited by both
epidemiological (level of COVID-19 infection in the community) and practical challenges, detailed
below.
Future studies could consider the collection of detailed aerosol measures from patients a...
We thank Nimmo et al for their comments on our paper, and for recognising that this work
addresses an important gap in high quality data on aerosol generation and also the technical
challenges associated with measuring aerosol from the respiratory tract.
We agree that interparticipant variability in aerosol emission is significant (spanning several orders
of magnitude) and acknowledge in the paper that interpretation of the data on patients with COVID-
19 is limited due to the small cohort size. The AERATOR study was the first group to collect detailed
aerosol measures from patients with active SARS-CoV-2, the aim of this exploratory sub group
analysis was to consider if active infection had a meaningful impact on the use of healthy controls as
proxies in the main analysis.
Measuring aerosol emission from patients with COVID-19 is very challenging in the acute clinical
setting because of both the very low aerosol background concentration required to make a
measurement and infection control precautions. We therefore chose to report the raw data while
acknowledging the difficulties in interpretation.
In this analysis, we did not perform a sample size calculation; as we were limited by both
epidemiological (level of COVID-19 infection in the community) and practical challenges, detailed
below.
Future studies could consider the collection of detailed aerosol measures from patients at various
stages of infection (early and late) and respiratory support , but there are technical and practical
challenges which are currently largely insurmountable (patients receiving these therapies are cared
for in acute clinical settings such as shared multiple bedded bays with background aerosol
concentrations too high to obtain an informative measurement). As far as we are aware, no-one has
published data on patients with COVID-19 receiving any form of non-invasive ventilation or HFNO.
However, given that we did not find any aerosol generation during CPAP (a finding consistent with
other, recent papers 1,2 ), the sum of evidence does not suggest that non-invasive respiratory support
increases aerosol emission, independent of other factors.
As both our data and Wilson et al have shown, aerosol emission is, however, related to respiratory
activity, in particular cough. Therefore we have argued exposure to patients acutely unwell with
COVID-19 is the main driver of risk of nosocomial transmission within healthcare settings, rather
than exposure to patients receiving a given form of respiratory support. 3
Our limited data set does suggest that individuals consistently generate similar amounts of aerosol
while performing the same activity. These data are consistent with some very preliminary published
measurements. 4 Further research, which is being undertaken through the UKRI-funded PERFORM
study will clarify what factors influence aerosol emission on an individual and population level.
1. Wilson NM, Marks GB, Eckhardt A, et al. The effect of respiratory activity, non-invasive
respiratory support and facemasks on aerosol generation and its relevance to COVID-19.
Anaesthesia [Internet] 2021;Available from: http://dx.doi.org/10.1111/anae.15475
2. Gaeckle NT, Lee J, Park Y, Kreykes G, Evans MD, Hogan CJ Jr. Aerosol Generation from the
Respiratory Tract with Various Modes of Oxygen Delivery. Am J Respir Crit Care Med
2020;202(8):1115–24.
3. Hamilton F, Arnold D, Bzdek BR, et al. Aerosol generating procedures: are they of relevance for
transmission of SARS-CoV-2? Lancet Respir Med 2021;9(7):687–9.
4. Asadi S, Wexler AS, Cappa CD, Barreda S, Bouvier NM, Ristenpart WD. Aerosol emission and
superemission during human speech increase with voice loudness. Sci Rep 2019;9(1):2348.
Intravenous interleukin-5 antagonist has great potential and studies
have shown that it may be beneficial in chronic asthmatics for 3 to 6
months.
Now the understanding of cytokines and their beneficial and harmful
effects are well known but still cure of bronchial asthma appears to be a
remote possibility. Non-compliance in patients is very high and once they
feel better they take medicines irre...
Intravenous interleukin-5 antagonist has great potential and studies
have shown that it may be beneficial in chronic asthmatics for 3 to 6
months.
Now the understanding of cytokines and their beneficial and harmful
effects are well known but still cure of bronchial asthma appears to be a
remote possibility. Non-compliance in patients is very high and once they
feel better they take medicines irregularly.
Effort should be made to make use of usefull cytokines and to raise
their level in asthmatics.
Obstructive sleep apnea is an increasingly well-recognized disease
characterized by periodic collapse of the upper airway during sleep. This
leads to either complete or partial obstruction of the airway, resulting
in apneas, hypopneas, or both.
Interest in oral applicance therapy for snoring and sleep apnea has
increased recently. Johson et al. Examined the effect of mandibular
protrusio...
Obstructive sleep apnea is an increasingly well-recognized disease
characterized by periodic collapse of the upper airway during sleep. This
leads to either complete or partial obstruction of the airway, resulting
in apneas, hypopneas, or both.
Interest in oral applicance therapy for snoring and sleep apnea has
increased recently. Johson et al. Examined the effect of mandibular
protrusion in 10 patients with documented sleep apnea [1]. They found that
their patients were able to move their mandibles anteriorly an average of
6.9 mm. That led to an increase in posterior airway space (PAS) from the
base of the tongue to the posterior pharyngeal wall of 56%.
Mandibular advancement appliances, appear to have a somewhat
different effect on airway dimension than voluntary forward movement of
the mandible. One explanation is that it is possible that mandibular
advancement devices both advance the mandible and may produce downward
rotation of the mandible to varying degrees, opening up the vertical
dimension.
Oral appliance have many side effects [2](Box 1).
Box 1 : Side effects of oral appliances.
Excessive salivation
Drynes of the mouth
Transient discomfort may prevent early acceptance of the appliance
TMJ or jaw discomfort (Long-term problems)
Movement of the teeth
However, oral appliances appear to be effective in patients with mild
to moderate disease and
are generally accepted more easily than nasal CPAP.
Sincerely
Dr. Murat Enoz
References
1- Johnson LM, Arnett GW, Tamborello JA, Binder A. Airway changes in
relationship to mandibular posturing. Otolaryngol Head Neck Surg. 1992
Feb;106(2):143-8.
2- Schmidt-Nowara WW, Lowe A, Wiegand L, et al: Oral appliances fort
the treatment of snoring and obstructive sleep apnea: A review. Sleep 1995
;18:501-510.
Obstructive sleep apnea (OSA) is a common disorder associated with an
increased risk of cardiovascular disease and stroke. As it is strongly
associated with known cardiovascular risk factors, including obesity,
insulin resistance, and dyslipidemia, OSA is an independent risk factor
for hypertension and has also been implicated in the pathogenesis of
congestive cardiac failure, pulmonary hypertension...
Obstructive sleep apnea (OSA) is a common disorder associated with an
increased risk of cardiovascular disease and stroke. As it is strongly
associated with known cardiovascular risk factors, including obesity,
insulin resistance, and dyslipidemia, OSA is an independent risk factor
for hypertension and has also been implicated in the pathogenesis of
congestive cardiac failure, pulmonary hypertension, arrhythmias, and
atherosclerosis [1].
Obstructive sleep apnea is part of a spectrum of sleep-related
breathing disorders that includes snoring, upper airway resistance
syndrome (increased respiratory effort without apnea or hypopnea), and
central sleep apnea (CSA) (apnea without respiratory effort). The OSA
syndrome is the combination of obstructive apneas with daytime tiredness
or recurrent awakenings or gasping episodes [1].
Clinical suspicion of OSA is usually raised by complaints of snoring
and daytime tiredness, despite an adequate duration of sleep. Mainly, OSA
patients are managed clinically by sleep physicians with a background in
respiratory medicine or neurology. Atypical presentations are not
uncommon, however, and result in OSA patients presenting to a variety of
medical specialists.
Obstructive sleep apnea is now recognized to be an independent risk
factor for daytime hypertension. An association between OSA and
hypertension was suggested by a series of population and cohort studies,
observational studies in patients attending hypertension clinics and sleep
clinics [2,3]. Increased variability of blood pressure and loss of the
nocturnal blood pressure dip were also reported [4]. A recent
prospective, randomized, placebo-controlled comparison between therapeutic
and subtherapeutic CPAP reported a reduction in blood pressure,
particularly in those with more severe OSA [5].
Patients with OSA have many features in common with the “metabolic
syndrome,” including systemic hypertension, central obesity [6], and
insulin resistance [7]. The AHI correlates with BMI, waist-to-hip ratio,
hypertension, and diabetes, whereas trends toward lower high-density
lipoprotein and elevated triglycerides are reported for OSA subjects
<_65 years="years" old="old" _8.="_8." p="p"/> The role of sleep-disordered breathing in arrhythmias in heart
failure is still being defined. In a study of 81 males with stable heart
failure, incidences of atrial fibrillation and ventricular tachycardia
were significantly higher in sleep apnea subjects (AHI The risk of experiencing angina or an acute coronary syndrome is
increased in the hours after waking from sleep. In OSA, cyclical
variations in heart rate and blood pressure are dramatic [12], more so
than many hemodynamic stresses in daily life, and occur during sleep, a
time when in normal subjects blood pressure and heart rate are the lowest
and least variable. In OSA, increased peripheral sympathetic nerve
activity during sleep persists during wakefulness at approximately twice
the normal levels [13] and may affect acute coronary events in the early
hours of the day.
Patients with heart failure can have a combination of CSA and OSA,
which can vary during sleep or over time. In one study, within-night
changes were documented with progression from predominantly OSA early in
the night to CSA, presumably due to the fall in the arterial pCO2 level to
below the apneic threshold [14].
Positive airway pressure has been known to help acute cardiogenic
pulmonary edema for decades. The beneficial effects are thought to operate
via an increased intrathoracic pressure and reduced left ventricular
transmural pressure gradient, increased lung volume, assistance to
inspiratory respiratory muscles and stabilisation of the upper airway.
Cardiac work is reduced as a result [15].
In patients with established congestive heart failure is likely to be
a marker of advanced disease, via the mechanisms of impaired cardiac
output and elevated sympathetic activity, hyperventilation, reduced lung
volume and circulatory delay. Importantly, such patients who have not
responded to maximal medical therapy might be responsive to positive
airway pressure.
Sincerely
Dr. Murat Enoz
References
1- The report of an American Academy of Sleep Medicine Task Force.
Sleep-related breathing disorders in adults: recommendations for syndrome
definition and measurement techniques in clinical research. Sleep
1999;22:667–89.
2- Gislason T, Almqvist M. Somatic diseases and sleep complaints: an
epidemiological study of 3,201 Swedish men. Acta Med Scand
1987;221:475–81.
3- Worsnop CJ, Naughton MT, Barter CE, Morgan TO, Anderson AI, Pierce
RJ. The prevalence of obstructive sleep apnea in hypertensives. Am J
Respir Crit Care Med 1998;157:111–5.
4- Wilcox I, Grunstein RR, Collins FL, Doyle JM, Kelly DT, Sullivan
CE. Circadian rhythm of blood pressure in patients with obstructive sleep
apnea. Blood Press 1992;1:219–22.
5- Pepperell JCT, Ramdassingh-Dow S, Crosthawaite N, et al.
Ambulatory blood pressure after therapeutic and subtherapeutic nasal
positive airway pressure for obstructive sleep apnoea: a randomised
parallel trial. Lancet 2001;359:204–10.
6- Grunstein R, Wilcox I, Yang TS, Gould Y, Hedner J. Snoring and
sleep apnoea in men: association with central obesity and hypertension.
Int J Obes Relat Metab Disord 1993;17:533–40.
7- Elmasry A, Lindberg E, Berne C, et al. Sleep-disordered breathing
and glucose metabolism in hypertensive men: a population-based study. J
Intern Med 2001;249:153–61.
8- Newman AB, Nieto FJ, Guidry U, et al. Relation of sleep-disordered
breathing to cardiovascular disease risk factors: the Sleep Heart Health
Study. Am J Epidemiol 2001;154:50–9.
9- Javaheri S, Parker TJ, Liming JD, et al. Sleep apnea in 81
ambulatory male patients with stable heart failure: types and their
prevalences, consequences, and presentations. Circulation 1998;97:2154–9.
10- Javaheri S. Effects of continuous positive airway pressure on
sleep apnea and ventricular irritability in patients with heart failure.
Circulation 2000;101:392–7.
11- Garrigue S, Bordier P, Jais P, et al. Benefit of atrial pacing in
sleep apnea syndrome. N Engl J Med 2002;346:404–12.
12- Mayer J, Becker H, Brandenburg U, Penzel T, Peter JH, von Wichert
P. Blood pressure and sleep apnea: results of long-term nasal continuous
positive airway pressure therapy. Cardiology 1991;79:84–92.
13- Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG.
Augmented resting sympathetic activity in awake patients with obstructive
sleep apnea. Chest 1993;103:1763–8.
14- Tkacova R, Niroumand M, Lorenzi-Filho G, Bradley TD. Overnight
shift from obstructive to central apneas in patients with heart failure:
role of PCO2 and circulatory delay. Circulation 2001;103:238–43.
Positive-pressure ventilation may be associated with adverse
cardiovascular effects, particularly when using large tidal volumes and /
or high PEEP. The increased intra-thoracic pressure decreases venous
return to the heart with subsequent reduction of cardiac filling, cardiac
output and blood pressure. On the other hand, positive-pressure
ventilation may have beneficial hemodynamic effects. If the pos...
Positive-pressure ventilation may be associated with adverse
cardiovascular effects, particularly when using large tidal volumes and /
or high PEEP. The increased intra-thoracic pressure decreases venous
return to the heart with subsequent reduction of cardiac filling, cardiac
output and blood pressure. On the other hand, positive-pressure
ventilation may have beneficial hemodynamic effects. If the positive
airway pressure is timed to occur during systole and the airway pressure
is released during diastole, cardiac output can sometimes be increased and
the mechanical ventilator can actually function as a partial ventricular
assist device ( as if the ventilator is squeezing the heart when the intra
-thoracic pressure is increased during systole) . Based on clinical
observation, many patients with decompensated heart failure (who were
intubated and ventilated because of acute pulmonary oedema) improved
significantly several hours after mechanical ventilation. Compensatory
tachycardia, ventricular ectopics and gallop rhythm decreased and many
patients showed much better diuretic response. In addition, some patients
with underlying Coronary artery disease - CAD - demonstrated ECG evidence
of improved myocardial ischemia after initiation of positive- pressure
ventilation (nitrates and calcium antagonists were not given to those
patients with borderline B.P for fear of exaggerated ventilator - induced
hypotension). It should be remembered that ventilator-induced hypotension
is a potential complication in volume-depleted patients rather than the
fluid-overloaded patients with heart failure. We can assume that
mechanical ventilator may be particularly useful to patients with
decompensated heart failure as it may augment ventricular contraction,
improve arterial oxygenation and hence myocardial O2 supply and reduce
preload (as a result of increased intra-thoracic pressure and reduced
venous return). Preload reduction not only reduces pulmonary congestive
symptoms but also decreases left ventricular end-diastolic diameter (
L.V.EDD ), L.V wall tension and therefore cardiac work and myocardial O2
demand (the same mode of action of nitrates that may explain the ECG
evidence of improved ischemia in some patients with CAD shortly after
intubation. It is to be remembered that L.V wall tension depends on
L.V.EDD - determined by preload - and intra-ventricular pressure -
determined by after load. Positive - pressure ventilation may also be
beneficial in the clinical setting of acute pulmonary oedema in which up
to 40 – 50 % of the cardiac output may be taken up by the overacting
respiratory muscles of the severely distressed patients. After intubation,
ventilation and sedation (with or without muscle paralysis), mechanical
ventilator provides "rest" to the overacting respiratory muscles and
allows redistribution of the cardiac output from the respiratory muscles
to the heart, brain and kidneys. This may lead to improved coronary blood
flow and myocardial O2 supply which may further enhance myocardial
contractility and reduce myocardial ischemia. In addition, renal blood
flow may also be increased which may explain the enhanced diuretic
response in heart failure patients after intubation and mechanical
ventilation. In conclusion, positive-pressure ventilation may have several
beneficial effects in patients with decompensated heart failure who are
intubated because of acute pulmonary oedema and hypoxemic respiratory
failure. This may include increased cardiac output, improved myocardial
ischemia (due to increased O2 supply and reduced O2 demand) and increased
renal perfusion and diuretic response. Finally, this issue needs more
evaluation using echocardiography (to assess L.V function and regional
wall motion), invasive hemodynamic monitoring (to measure cardiac output,
PCWP and pulmonary artery pressure) as well as biochemical markers of
heart failure such as the recently available B-type natriuretic peptide
that may be of value in assessing the severity of heart failure.
References
1. Pinsky HR. Cardiovascular effects of ventilatory support and withdrawal. Anaesth. Analg 1994; 79: 567 – 576
2. Veisprille A. The pulmonary circulation during mechanical ventilation. Acta Anesthesiol Scand 1990; 34 (Suppl):51-62.
Letter to the editor:
We appreciate the opportunity to comment on the article by Thomsen RW et al. Risk of asbestos, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. We believe there are many problems in methodology and we disagree with author’s interpretations and conclusions especially in relation to asbestos and mesothelioma in vehicle mechanics in this article.
The epidemiology analysis described by Thomsen et al lacks asbestos exposure data and uses cross-sectional occupation data as surrogates for longitudinal use. Occupational categories are not equal to exposure. Especially for asbestos it has been clear that obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease. Without longitudinal individual exposure histories in the Thomson et al study, there is undoubtably significant misclassification of exposure in both the motor vehicle mechanic group (unexposed considered exposed) and even more problematic in the control group (exposed classified as unexposed). This double likelihood of exposure misclassification creates unreliable analytics which result in an epidemiologic bias towards the null. 1
Thomsen et al used cross-sectional data at variable dates to place workers in their two study cohorts based on reported current occupation and industry. The occupation on the 1970 census or when first...
Show MoreWe appreciate the thoughtful letter from Drs. Kanarek and Anderson. Our study does not address the well-established fact that asbestos exposure is the main causal factor of mesothelioma. The objective of our study was to investigate the risk of mesothelioma (and other asbestos related diseases) in motor vehicle mechanics. The key finding is that Danish motor vehicle mechanics do not on average have an elevated risk of mesothelioma during the studied up to 45 years of follow-up. This does not exclude the possibility that some subpopulations of motor vehicle mechanics with more extreme exposure/latency time are at increased risk – but this occupation as a group is not.
We agree that exposure misclassification is a potential problem in epidemiology studies based on occupation and industry titles. We also agree that lifetime asbestos exposure histories, if they could be obtained, might reduce exposure misclassification. However, asbestos exposure is often not recognized or recalled by workers, and workers often do not recall jobs in the distant past. Also, experts may misclassify self-reported jobs regarding asbestos exposure, particularly with respect to asbestos fiber type. Thus, while Drs. Kanarek and Anderson claim “obtaining an individual lifetime occupational and environmental exposure history is crucial to understanding individual work-related causes of disease” they offer no practical advice on how reliable asbestos exposure histories can be obtained. They also...
Show MoreThomsen et al’s. (2021)1 suggestion that “asbestosis occurs at cumulative chrysotile exposure levels where mesotheliomas are rare or none were observed…”.to explain the increased risk of asbestosis in the absence of an increased risk of mesothelioma among vehicle mechanics appears implausible for many reasons:
Show Morea. Scientific literature shows that when there is a risk of asbestosis there is also an increased risk of pleural mesothelioma2;
b. Cumulative exposures to chrysotile asbestos sustained by career vehicle mechanics are far below the cumulative asbestos exposures traditionally associated with asbestosis (25 fibre/cc-years) as cited by Thomsen et al.1,3;
c. That chrysotile asbestos, with much shorter biopersistence than amphibole asbestos, is more fibrogenic is biologically implausible, and inconsistent with the studies that show that the degree of lung fibrosis/asbestosis correlates with retained amphibole asbestos content, not chrysotile 3,4.
d. Fibre counts amongst vehicle mechanics with mesothelioma have been found to be either within control reference limits or show increased commercial amphibole asbestos, unrelated to friction exposures 2.
e. Animal studies do not report asbestosis or mesothelioma following high-dose inhalation exposures to brake dust with and without added chrysotile 5.
We consider, as Thomsen et al 1 did, that the most plausible explanation is diagnostic bias based on control selection.
In Thomsen et al...
We agree with Drs. Moolgavkar and Attanoos that our observation of increased risk of asbestosis unaccompanied by increased risk of mesothelioma among motor vehicle mechanics (Thomsen, 2021) is inconsistent with other studies of chrysotile exposed populations. As we discussed in our paper, mesothelioma ascertainment is highly reliable in Denmark and our mesothelioma findings are consistent with previous studies (DeBono, 2021; Garabrant, 2016; Hessel, 2021; Tomasallo, 2018; Van den Borre, 2015). Thus, we believe our findings are reliable. Conversely, the asbestosis findings raise important questions. A diagnosis of asbestosis can only be made when a clinician believes the patient has been exposed to asbestos. Pulmonary fibrosis in a vehicle mechanic might readily be diagnosed as asbestosis if the clinician was aware of the occupational history and possible presence of asbestos in brakes, clutches, gaskets, or other vehicle parts. Since our comparison subjects held jobs that did not involve obvious asbestos exposure, it is less likely that pulmonary fibrosis would be diagnosed as asbestosis in this group. Moolgavkar and Attanoos suggest that our comparison selection could have led to diagnostic bias if the vehicle mechanics and the comparisons did not have equal probabilities of exposure to asbestos from sources other than friction products. We agree - we reported that the abrupt increase in outpatient clinic diagnosed asbestosis beginning in the mid-2000s is consistent with...
Show MoreThe AERATOR study (Hamilton et al) compares and quantifies the risk of aerosol generation in both healthy patients and those infected with COVID-19 in a variety of contexts, including normal respiration, speaking and coughing, and the same activities whilst receiving therapy with continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO), and also whilst wearing a fluid-resistant surgical mask (FSRM)1. This study is particularly welcome as it is an area where data are scarce, yet the theoretical risks have major implications for both patients and health care professionals and influence recommendations that guide patient care, such as the use of side rooms and personal protective equipment, both of which are limited resources2. However, we have some questions about the study design.
Hamilton et al demonstrated that the size of aerosols generated by healthy individuals and those infected with COVID-19 were comparable, thereby validating the use of healthy volunteers for aerosol characterisation, though the sample sizes involved within the COVID-19 cohort were relatively small (n=6). Furthermore, the study highlights that aerosolisation was lower in healthy volunteers with non-humidified CPAP, whilst it was increased in those receiving HFNO (though it was shown to originate mostly from the device), compared to baseline for breathing, speaking, and coughing. Given the study also mentions a considerable degree of inter- and intra-individual variability...
Show MoreWe thank Nimmo et al for their comments on our paper, and for recognising that this work
Show Moreaddresses an important gap in high quality data on aerosol generation and also the technical
challenges associated with measuring aerosol from the respiratory tract.
We agree that interparticipant variability in aerosol emission is significant (spanning several orders
of magnitude) and acknowledge in the paper that interpretation of the data on patients with COVID-
19 is limited due to the small cohort size. The AERATOR study was the first group to collect detailed
aerosol measures from patients with active SARS-CoV-2, the aim of this exploratory sub group
analysis was to consider if active infection had a meaningful impact on the use of healthy controls as
proxies in the main analysis.
Measuring aerosol emission from patients with COVID-19 is very challenging in the acute clinical
setting because of both the very low aerosol background concentration required to make a
measurement and infection control precautions. We therefore chose to report the raw data while
acknowledging the difficulties in interpretation.
In this analysis, we did not perform a sample size calculation; as we were limited by both
epidemiological (level of COVID-19 infection in the community) and practical challenges, detailed
below.
Future studies could consider the collection of detailed aerosol measures from patients a...
Intravenous interleukin-5 antagonist has great potential and studies have shown that it may be beneficial in chronic asthmatics for 3 to 6 months.
Now the understanding of cytokines and their beneficial and harmful effects are well known but still cure of bronchial asthma appears to be a remote possibility. Non-compliance in patients is very high and once they feel better they take medicines irre...
Dear Editor,
Obstructive sleep apnea is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both.
Interest in oral applicance therapy for snoring and sleep apnea has increased recently. Johson et al. Examined the effect of mandibular protrusio...
Dear Editor,
Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension...
Dear Editor
Positive-pressure ventilation may be associated with adverse cardiovascular effects, particularly when using large tidal volumes and / or high PEEP. The increased intra-thoracic pressure decreases venous return to the heart with subsequent reduction of cardiac filling, cardiac output and blood pressure. On the other hand, positive-pressure ventilation may have beneficial hemodynamic effects. If the pos...
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