Hessel(1) published an editorial concerning mesothelioma among vehicle mechanics and concluded that ‘with nearly two dozen studies of mesothelioma among vehicle mechanics and no evidence of increased risk, it would appear obvious that vehicle mechanics as an occupational group, are not at increased risk of mesothelioma.’ In my opinion Hessel relies too heavily upon epidemiology for his conclusions. Epidemiology is important if studies reliably address the question at issue, but published epidemiologic studies are generally not helpful to the evaluation of risk among vehicle mechanics. Few were designed to be studies of mesothelioma in mechanics. Most are general studies of the disease Mesothelioma in which some of the subjects happened to be mechanics. Since they were not designed to be studies of vehicle mechanics, none of the information necessary for a study of risk, such as the numbers of brake jobs performed, the use of compressed air, sanding or grinding, was collected. Not a single one of the studies had information adequate to compute a quantitative exposure estimate for any of the subjects. Misclassification of exposures will mask risk among those truly exposed(2,3).
Hessel suggests that the paper in Thorax by Thomsen (4) supports his opinion. The aim of that paper was to compare risk among men in a cohort of vehicle mechanics with a comparison cohort of men not occupationally exposed to asbestos. When studying risk in a population exposed to a toxic subs...
Hessel(1) published an editorial concerning mesothelioma among vehicle mechanics and concluded that ‘with nearly two dozen studies of mesothelioma among vehicle mechanics and no evidence of increased risk, it would appear obvious that vehicle mechanics as an occupational group, are not at increased risk of mesothelioma.’ In my opinion Hessel relies too heavily upon epidemiology for his conclusions. Epidemiology is important if studies reliably address the question at issue, but published epidemiologic studies are generally not helpful to the evaluation of risk among vehicle mechanics. Few were designed to be studies of mesothelioma in mechanics. Most are general studies of the disease Mesothelioma in which some of the subjects happened to be mechanics. Since they were not designed to be studies of vehicle mechanics, none of the information necessary for a study of risk, such as the numbers of brake jobs performed, the use of compressed air, sanding or grinding, was collected. Not a single one of the studies had information adequate to compute a quantitative exposure estimate for any of the subjects. Misclassification of exposures will mask risk among those truly exposed(2,3).
Hessel suggests that the paper in Thorax by Thomsen (4) supports his opinion. The aim of that paper was to compare risk among men in a cohort of vehicle mechanics with a comparison cohort of men not occupationally exposed to asbestos. When studying risk in a population exposed to a toxic substance one could ask: (1) How does the disease risk in this population compare to the disease risk in another population also exposed to this toxic substance? Or, (2) How does the risk in this population compare with the risk in an unexposed population? Thomsen wrote “the IR of mesothelioma in our comparison workers was 2.39 per 100 000 person-years, 31% of the IR among Danish men of the same median age, suggesting that our controls were less likely to have been exposed to asbestos than the general population of Danish men.” Thomsen thus addressed question (1) “How does the disease risk among vehicle mechanics compare to the disease risk in another population also exposed to asbestos?” They showed that the risk of mesothelioma among mechanics was less than the risk of mesothelioma in a population of subjects with asbestos exposure sufficient to cause asbestosis in some one in 2500 subjects. They have not demonstrated absence of risk in comparison to the unexposed.
Reference List
1. Hessel PA. Mesothelioma among vehicle mechanics: a controversy? Thorax. 2021.
2. Teschke K. Thinking about Occupation-Response and Exposure-Response Relationships: Vehicle Mechanics, Chrysotile, and Mesothelioma. Ann Occup Hyg. 2016;60:528-530.
3. Van den Borre L, Deboosere P. Asbestos in Belgium: an underestimated health risk. The evolution of mesothelioma mortality rates (1969-2009). Int J Occup Environ Health. 2014;20:134-140.
4. Thomsen RW, Riis AH, Flachs EM, Garabrant DH, Bonde JPE, Sorensen HT. Risk of asbestosis, mesothelioma, other lung disease or death among motor vehicle mechanics: a 45-year Danish cohort study. Thorax. 2021.
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.
We thank James R Camp for his response and interest in our study. To answer the question posed directly, we did not use blood eosinophils as a covariate in the model, since leukocyte differential count is not routinely made at every outpatient visit for COPD patients in Denmark.
The relation between blood eosinophils in COPD and pulmonary infections is not a trivial one. As mentioned by James R Camp, mouse models indicate that eosinophils have antibacterial properties in vitro (1). However, few clinical studies have included blood eosinophil counts as a risk factor of pneumonia in COPD, mostly showing either a weak or no association (2,3).
Eosinophils from human blood have been demonstrated to have bactericidal effects against S. aureus and E. coli, but noteworthy, this effect was not as potent as the neutrophils (4). Additionally, severe acute bacterial infection like sepsis almost uniformly causes eosinopenia (5,6) and experimental lipopolysaccharide injection in healthy humans and diabetic humans cause profound and long-lasting eosinopenia (7). This is not easily comprehensible if the eosinophils are a needed part of the innate host immune response to bacterial infection.
An alternative explanation for a possible association could be that eosinophils and neutrophils act in bacterial infection in a complex interplay, while regulating and adjusting the response of each other. To support this, it has been demonstrated that integrin β chain-2 (CD18),...
We thank James R Camp for his response and interest in our study. To answer the question posed directly, we did not use blood eosinophils as a covariate in the model, since leukocyte differential count is not routinely made at every outpatient visit for COPD patients in Denmark.
The relation between blood eosinophils in COPD and pulmonary infections is not a trivial one. As mentioned by James R Camp, mouse models indicate that eosinophils have antibacterial properties in vitro (1). However, few clinical studies have included blood eosinophil counts as a risk factor of pneumonia in COPD, mostly showing either a weak or no association (2,3).
Eosinophils from human blood have been demonstrated to have bactericidal effects against S. aureus and E. coli, but noteworthy, this effect was not as potent as the neutrophils (4). Additionally, severe acute bacterial infection like sepsis almost uniformly causes eosinopenia (5,6) and experimental lipopolysaccharide injection in healthy humans and diabetic humans cause profound and long-lasting eosinopenia (7). This is not easily comprehensible if the eosinophils are a needed part of the innate host immune response to bacterial infection.
An alternative explanation for a possible association could be that eosinophils and neutrophils act in bacterial infection in a complex interplay, while regulating and adjusting the response of each other. To support this, it has been demonstrated that integrin β chain-2 (CD18), an important component in the cellular adhesion and cell-surface signalling in bacterial infection, can downregulate eosinophil chemotaxis (8).
Human data from randomised controlled trials are necessary to help unravel this. We did, in fact, at an earlier occasion, conduct a large scale randomised controlled trial, the CORTICO-COP trial (9), in which COPD-patients with severe acute exacerbation, were randomly allocated to either a corticosteroid sparing regimen, or a standard regimen with a 5-day-course of oral corticosteroids. This resulted in approximately 60% lower use of corticosteroids, and the eosinophil suppression in this study differed between the two groups: median (IQR); 0.06 (0.09-0.21) vs. 0.10 (0.14-0.34), p<0.0001). Thus, if eosinophils had an important role in the bacterial host immune response, we would have expected patients in the “low eosinophil group” to have a worse clinical course. This was not the case, since no difference in any clinical outcomes was observed. Moreover, there were no significant association between bacterial infection and treatment group or eosinophil count. Similarly, a large randomised controlled trial of hospitalised patients with community-aquired pneumonia has reported significantly shorter time to clinical stability and shorter hospital stay with adjunct prednisone treatment compared to placebo (10), despite the expected corticosteroid-induced eosinophil suppression in the intervention group.
To summarise, there are so far no solid clinical data supporting an important antibacterial effect of eosinophils, although some laboratory data support this. To return to the point of John R. Camp, we find it unlikely that adjusting our data for eosinophil counts would alter the signal of our study.
1. Linch SN, Kelly AM, Danielson ET, Pero R, Lee JJ, Gold JA. Mouse eosinophils possess potent antibacterial properties in vivo. Infection and immunity. 2009;77(11):4976-82.
2. Pascoe S, Barnes N, Brusselle G, Compton C, Criner GJ, Dransfield MT, Halpin DMG, Han MK, Hartley B, Lange P, Lettis S, Lipson DA, Lomas DA, Martinez FJ, Papi A, Roche N, van der Valk RJP, Wise R, Singh D. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial. Lancet Respir Med. 2019 Sep;7(9):745-756. doi: 10.1016/S2213-2600(19)30190-0. Epub 2019 Jul 4. PMID: 31281061.
3. Pavord ID, Lettis S, Anzueto A, Barnes N. Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis. Lancet Respir Med. 2016 Sep;4(9):731-741.
4. Yazdanbakhsh M, Eckmann CM, Bot AA, Roos D. Bactericidal action of eosinophils from normal human blood. Infect Immun. 1986 Jul;53(1):192-8.
5. Bass DA. Behavior of eosinophil leukocytes in acute inflammation. II. Eosinophil dynamics during acute inflammation. J Clin Invest. 1975 Oct;56(4):870-9.
7. Gilbert HS, Rayfield EJ, Smith H Jr, Keusch GT. Effects of acute endotoxemia and glucose administration on circulating leukocyte populations in normal and diabetic subjects. Metabolism. 1978 Aug;27(8):889-99.
8. Nagata M, Sedgwick JB, Busse WW. Differential effects of granulocyte-macrophage colony-stimulating factor on eosinophil and neutrophil superoxide anion generation. J Immunol. 1995 Nov 15;155(10):4948-54.
9. Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, Eklöf J, Holm FS, Armbruster K, Sivapalan P, Mosbech C, Ali AKM, Seersholm N, Wilcke JT, Brøndum E, Sonne TP, Rønholt F, Andreassen HF, Ulrik CS, Vestbo J, Jensen JS. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8):699-709.
10. Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, Arici B, Urwyler SA, Refardt J, Tarr P, Wirz S, Thomann R, Baumgartner C, Duplain H, Burki D, Zimmerli W, Rodondi N, Mueller B, Christ-Crain M. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Apr 18;385(9977):1511-8.
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 recently read the recent publication by Elköf and colleagues in the recent issue of Thorax titled ‘Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease’(1) with great interest. The paper highlights an important clinical observation in a well-defined cohort.
We were interested that Elköf and colleagues, tentatively discuss that biological mechanisms resulting from ICS alterations on the immune system may be an explanation for a change in the microbial composition in the airways(1). As the authors discussed, eosinophilic inflammation in COPD identifies a group of patients with ICS responsiveness(2). In the mouse model, there are data examining that eosinophils have anti-microbial properties(3). Access to eosinophil counts from this cohort may be invaluable in unravelling the relationship of eosinophils and COPD and could provide insight into the impact of steroids in bacterial infection. Did the authors investigate the peripheral blood eosinophil count as a covariate in their main analyses?
References
1. Eklöf J, Ingebrigtsen TS, Sørensen R, Saeed MI, Alispahic IA, Sivapalan P, et al. Use of inhaled corticosteroids and risk of acquiring <em>Pseudomonas aeruginosa</em> in patients with chronic obstructive pulmonary disease. Thorax. 2021:thoraxjnl-2021-217160.
2. Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, et al....
We recently read the recent publication by Elköf and colleagues in the recent issue of Thorax titled ‘Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease’(1) with great interest. The paper highlights an important clinical observation in a well-defined cohort.
We were interested that Elköf and colleagues, tentatively discuss that biological mechanisms resulting from ICS alterations on the immune system may be an explanation for a change in the microbial composition in the airways(1). As the authors discussed, eosinophilic inflammation in COPD identifies a group of patients with ICS responsiveness(2). In the mouse model, there are data examining that eosinophils have anti-microbial properties(3). Access to eosinophil counts from this cohort may be invaluable in unravelling the relationship of eosinophils and COPD and could provide insight into the impact of steroids in bacterial infection. Did the authors investigate the peripheral blood eosinophil count as a covariate in their main analyses?
References
1. Eklöf J, Ingebrigtsen TS, Sørensen R, Saeed MI, Alispahic IA, Sivapalan P, et al. Use of inhaled corticosteroids and risk of acquiring <em>Pseudomonas aeruginosa</em> in patients with chronic obstructive pulmonary disease. Thorax. 2021:thoraxjnl-2021-217160.
2. Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, et al. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018;6(2):117-26.
3. Linch SN, Kelly AM, Danielson ET, Pero R, Lee JJ, Gold JA. Mouse eosinophils possess potent antibacterial properties in vivo. Infection and immunity. 2009;77(11):4976-82.
We thank N. Hürsoy and colleagues for their interest in our study of patients four months after severe COVID-19 [1]. We agree that there needs to be continued development of terms describing the radiographic appearance of post-COVID fibrotic-like patterns. We acknowledge that without the benefit of histopathology or serial imaging, our ability to define pulmonary fibrosis is limited.
The authors posit that parenchymal bands, irregular densities, and ground glass opacities, may be considered fibrotic-like patterns. We have included irregular densities, characterized as reticulations or traction bronchiectasis, as fibrotic-like changes. We did not include parenchymal bands [2], as these can be associated with atelectasis, which is common in COVID and can disappear over time [3]. Similarly, we did not include isolated ground glass opacities as fibrotic-like changes, as these have been found to decrease over time in CT lung cancer screening cohorts [4] and in other post COVID-19 cohorts [5, 6].
A priori, we evaluated for both previously established interstitial lung abnormality categories [7], as well as categories of radiographic abnormalities reported in Acute Respiratory Distress Syndrome (ARDS) survivors using an established scoring system [8]. This inclusive approach should facilitate meta-analyses and comparisons with future studies of COVID-19 survivors, interstitial lung disease studies, and studies of non-COVID ARDS survivors. Fu...
We thank N. Hürsoy and colleagues for their interest in our study of patients four months after severe COVID-19 [1]. We agree that there needs to be continued development of terms describing the radiographic appearance of post-COVID fibrotic-like patterns. We acknowledge that without the benefit of histopathology or serial imaging, our ability to define pulmonary fibrosis is limited.
The authors posit that parenchymal bands, irregular densities, and ground glass opacities, may be considered fibrotic-like patterns. We have included irregular densities, characterized as reticulations or traction bronchiectasis, as fibrotic-like changes. We did not include parenchymal bands [2], as these can be associated with atelectasis, which is common in COVID and can disappear over time [3]. Similarly, we did not include isolated ground glass opacities as fibrotic-like changes, as these have been found to decrease over time in CT lung cancer screening cohorts [4] and in other post COVID-19 cohorts [5, 6].
A priori, we evaluated for both previously established interstitial lung abnormality categories [7], as well as categories of radiographic abnormalities reported in Acute Respiratory Distress Syndrome (ARDS) survivors using an established scoring system [8]. This inclusive approach should facilitate meta-analyses and comparisons with future studies of COVID-19 survivors, interstitial lung disease studies, and studies of non-COVID ARDS survivors. Furthermore, it allows for future post-hoc analyses if alternate definitions of fibrotic-like patterns in COVID-19 survivors are established. Additionally, we showed that objective quantitative analyses closely agreed with visual assessments (Figure S2). These types of quantitative imaging analyses may facilitate the convergence of data from multiple centers if imaging protocols become more standardized [9].
Efforts are underway to characterize pulmonary impairments and radiographic abnormalities in our cohort over time in order to assess longitudinal evolution. We acknowledge that our findings do not exclude the possibility of pre-existing lung disease and we therefore look forward to reviewing independent studies, such as the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) [10] project, which will provide better understanding of radiographic changes by comparing chest imaging studies before and after SARS-CoV-2 infection.
1. McGroder, C.F., et al., Pulmonary fibrosis 4 months after COVID-19 is associated with severity of illness and blood leucocyte telomere length. Thorax, 2021.
2. Pulmonary Parenchymal Band. Available from: https://www.ncbi.nlm.nih.gov/medgen/978776.
3. Kong, M., et al., Evolution of chest CT manifestations of COVID-19: a longitudinal study. J Thorac Dis, 2020. 12(9): p. 4892-4907.
4. Jin, G.Y., et al., Interstitial lung abnormalities in a CT lung cancer screening population: prevalence and progression rate. Radiology, 2013. 268(2): p. 563-71.
5. Nagpal, P., et al., Case Studies in Physiology: Temporal Variations of the Lung Parenchyma and Vasculature in Asymptomatic COVID-19 Pneumonia: A Multi-Spectral CT Assessment. J Appl Physiol (1985), 2021.
6. Liu, D., et al., The pulmonary sequalae in discharged patients with COVID-19: a short-term observational study. Respir Res, 2020. 21(1): p. 125.
7. Hatabu, H., et al., Interstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society. Lancet Respir Med, 2020. 8(7): p. 726-737.
8. Burnham, E.L., et al., Chest CT features are associated with poorer quality of life in acute lung injury survivors. Crit Care Med, 2013. 41(2): p. 445-56.
9. Nagpal, P., et al., Quantitative CT imaging and advanced visualization methods: potential application in novel coronavirus disease 2019 (COVID-19) pneumonia. BJR Open, 2021. 3(1): p. 20200043.
10. Collaborative Cohort of Cohorts for COVID-19 Research. Available from: https://c4r-nih.org/content/overview.
We have read with great interest the article investigating the relationship between computed tomography (CT) findings of the patients with fibrotic-like patterns and telomere length after four months of acute COVID-19 infection. According to the literature and our experience, post-COVID interstitial lung disease is a potential public health problem. Thus, we aimed to share our concerns about the fibrotic-like patterns in this group of patients.
Post-COVID fibrosis is not as the same as the other interstitial lung diseases. In the article, the authors describe CT findings of fibrotic-like patterns as limited to reticulation, honeycomb cysts, and traction bronchiectasis. However, post-COVID fibrosis CT findings were shown to be more varied and may include parenchymal bands, irregular densities, and ground-glass areas (1–3). As we move towards the future, all of us need to create a common language, a lingua franca in the definition of post-COVID fibrosis. To achieve this, we need brainstorming and close cooperation.
It will also be helpful to elaborate the characteristics of the non-fibrotic pattern in the table. The clinical importance of the ground glass areas, which persist four months after active infection but not defined as fibrotic, is unknown. We consider that these patterns cannot be separated from fibrotic-like patterns precisely. Additionally, we can also classify parenchymal bands as fibrosis-like appearance. In our experience...
We have read with great interest the article investigating the relationship between computed tomography (CT) findings of the patients with fibrotic-like patterns and telomere length after four months of acute COVID-19 infection. According to the literature and our experience, post-COVID interstitial lung disease is a potential public health problem. Thus, we aimed to share our concerns about the fibrotic-like patterns in this group of patients.
Post-COVID fibrosis is not as the same as the other interstitial lung diseases. In the article, the authors describe CT findings of fibrotic-like patterns as limited to reticulation, honeycomb cysts, and traction bronchiectasis. However, post-COVID fibrosis CT findings were shown to be more varied and may include parenchymal bands, irregular densities, and ground-glass areas (1–3). As we move towards the future, all of us need to create a common language, a lingua franca in the definition of post-COVID fibrosis. To achieve this, we need brainstorming and close cooperation.
It will also be helpful to elaborate the characteristics of the non-fibrotic pattern in the table. The clinical importance of the ground glass areas, which persist four months after active infection but not defined as fibrotic, is unknown. We consider that these patterns cannot be separated from fibrotic-like patterns precisely. Additionally, we can also classify parenchymal bands as fibrosis-like appearance. In our experience, subpleural parenchymal bands are not uncommon. Furthermore, respiratory symptoms may persist in patients with parenchymal bands. So, this pattern should be considered as a part of fibrotic-like pattern.
Another challenge is the lack of proof regarding fibrosis development due to COVID-19 infection. For example, honeycomb cysts are an indicator of irreversible fibrosis, and it is uncertain whether they are present in the previous CT images or not. A similar condition may apply to irregular reticulation and traction bronchiectasis. The development of fibrotic patterns may also differ from the images during the active infection (4). It may be instructive to examine the process by which signs of active involvement evolve into fibrosis, as well as the development of a fibrotic-like pattern.
We need a more precise interpretation of the development of fibrotic-like patterns. Therefore, we suggest analysing subtypes of post-COVID fibrosis, compare present findings on CT with long-term follow-up images. Also, it might be beneficial to show, if possible, that there is no fibrotic pattern in the CTs before acute Covid 19 infection.
References
1. Huang W, Wu Q, Chen Z, Xiong Z, Wang K, Tian J, et al. The potential indicators for pulmonary fibrosis in survivors of severe COVID-19. Vol. 82, Journal of Infection. 2021.
2. Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, et al. Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Ann Am Thorac Soc. 2021;18(5).
3. Shah AS, Wong AW, Hague CJ, Murphy DT, Johnston JC, Ryerson CJ, et al. A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations. Vol. 76, Thorax. 2021.
4. Guan CS, Wei LG, Xie RM, Lv Z Bin, Yan S, Zhang ZX, et al. CT findings of COVID-19 in follow-up: Comparison between progression and recovery. Diagnostic Interv Radiol. 2020;26(4):301–7.
We thank Dr Abdulqawi for interest in our work (1). He comments that the referral, uptake and completion rates for pulmonary rehabilitation in the current study were lower than in a previous study by Jones and colleagues (2). We would caution against retrospective comparison with unmatched historical controls due to confounding factors such as differences in patient characteristics and practice pathways that may contribute to inaccurate point estimates.
We hypothesised that the COPD discharge bundle would impact on referral rates. Strengths of the current work include the prospective real-world nature of the study, with the research team having no involvement in treatment allocation. The clinical team delivering the bundle were blinded to the study objectives, thus minimising any Hawthorne effect.
Dr Abdulqawi raises the point that pulmonary rehabilitation completion rates were low in the current study (albeit based on a low denominator). The reasons for non-completion of PR are often complex and multi-factorial (3) and may not be directly related to referral source. However, what is clear is that without a referral for pulmonary rehabilitation, uptake and completion rates are zero.
1. Barker RE BL, Maddocks M, Nolan CM, Patel S, Walsh JA, Polgar O, Wenneberg J, Kon SSC, Wedzicha JA, Man WDC, Farquhar M. Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the M...
We thank Dr Abdulqawi for interest in our work (1). He comments that the referral, uptake and completion rates for pulmonary rehabilitation in the current study were lower than in a previous study by Jones and colleagues (2). We would caution against retrospective comparison with unmatched historical controls due to confounding factors such as differences in patient characteristics and practice pathways that may contribute to inaccurate point estimates.
We hypothesised that the COPD discharge bundle would impact on referral rates. Strengths of the current work include the prospective real-world nature of the study, with the research team having no involvement in treatment allocation. The clinical team delivering the bundle were blinded to the study objectives, thus minimising any Hawthorne effect.
Dr Abdulqawi raises the point that pulmonary rehabilitation completion rates were low in the current study (albeit based on a low denominator). The reasons for non-completion of PR are often complex and multi-factorial (3) and may not be directly related to referral source. However, what is clear is that without a referral for pulmonary rehabilitation, uptake and completion rates are zero.
1. Barker RE BL, Maddocks M, Nolan CM, Patel S, Walsh JA, Polgar O, Wenneberg J, Kon SSC, Wedzicha JA, Man WDC, Farquhar M. Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the Model Using Accelerated Experience-Based Co-Design. Int J Chron Obstruct Pulmon Dis. 2021;16:1035-49.
2. Jones SE, Green SA, Clark AL, Dickson MJ, Nolan AM, Moloney C, et al. Pulmonary rehabilitation following hospitalisation for acute exacerbation of COPD: Referrals, uptake and adherence. Thorax. 2014;69(2):181-2.
3. Jones SE, Barker RE, Nolan CM, Patel S, Maddocks M, Man WD. Pulmonary rehabilitation in patients with an acute exacerbation of chronic obstructive pulmonary disease. J Thorac Dis. 2018;1(1):S1390-S9.
The idea that smoking might have a protective effect against COVID-19 is an intriguing, man bites dog type of story, which gives it a certain attraction. Happily, it appears to be false and the assumption of harm has turned out to be correct[1-5].
Our data show clearly that in the 2.4 million Zoe COVID Symptom Study App users, people who smoked were at increased risk of symptomatic COVID-19[2] and were at risk of more severe disease, which is consistent with a systematic review of patients hospitalized with COVID-19[4]. Our findings are also consistent with The UCL COVID-19 Social Study3 which found increased risk of test confirmed COVID-19 (OR=2.14 (1.49–3.08)) and with the COVIDENCE study where smokers had an OR of1.42 (0.99-2.05) for test-confirmed COVID-19[1].
The OpenSafely dataset based on data from the primary care records of 17.3 million adults in the UK found that, adjusted for age and sex, also identifies smoking as a risk factor - current smoking was associated with a hazard ratio for COVID-19-related death of 1.14 (1.05–1.23)5. The apparently protective effect in the “fully adjusted” model is due to over-correction producing collider bias.
Since any protective effect of smoking in COVID-19 appears to be illusory, pursuing a mechanism for it is unlikely to be productive.
References
1 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021:2021.2003...
The idea that smoking might have a protective effect against COVID-19 is an intriguing, man bites dog type of story, which gives it a certain attraction. Happily, it appears to be false and the assumption of harm has turned out to be correct[1-5].
Our data show clearly that in the 2.4 million Zoe COVID Symptom Study App users, people who smoked were at increased risk of symptomatic COVID-19[2] and were at risk of more severe disease, which is consistent with a systematic review of patients hospitalized with COVID-19[4]. Our findings are also consistent with The UCL COVID-19 Social Study3 which found increased risk of test confirmed COVID-19 (OR=2.14 (1.49–3.08)) and with the COVIDENCE study where smokers had an OR of1.42 (0.99-2.05) for test-confirmed COVID-19[1].
The OpenSafely dataset based on data from the primary care records of 17.3 million adults in the UK found that, adjusted for age and sex, also identifies smoking as a risk factor - current smoking was associated with a hazard ratio for COVID-19-related death of 1.14 (1.05–1.23)5. The apparently protective effect in the “fully adjusted” model is due to over-correction producing collider bias.
Since any protective effect of smoking in COVID-19 appears to be illusory, pursuing a mechanism for it is unlikely to be productive.
References
1 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021:2021.2003.2027.21254452
2 Hopkinson NS, Rossi N, El-Sayed Moustafa J, et al. Current smoking and COVID-19 risk: results from a population symptom app in over 2.4 million people. Thorax 2021 https://pubmed.ncbi.nlm.nih.gov/33402392/
3 Jackson SE, Brown J, Shahab L, et al. COVID-19, smoking and inequalities: a study of 53 002 adults in the UK. Tobacco Control 2020:tobaccocontrol-2020-055933
4 Reddy RK, Charles WN, Sklavounos A, et al. The effect of smoking on COVID-19 severity: A systematic review and meta-analysis. Journal of medical virology 2021; 93:1045-1056
5 Williamson EJ, Walker AJ, Bhaskaran K, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature 2020; 584:430-436
We have read the paper by Barker et al. (1) with interest. We congratulate the authors for conducting and publishing their prospective cohort study evaluating the effect of COPD discharge bundle on pulmonary rehabilitation (PR) referral and uptake following hospitalisation for acute exacerbation of COPD (AECOPD).
The authors have shown that the COPD discharge bundle had a positive effect on PR referral compared with a no bundle (17.5% (40 of 228) referral rate vs 0%(0 of 63)). This figure is lower than the expected 30% referral rate to PR following AECOPD (2). However, the paper offers no potential reasons for the lower referral rate.
The study had two bundle groups:
• COPD discharge bundle delivered by a current PR practitioner
• COPD discharge bundle delivered by a practitioner with no involvement in PR
Compared to delivery by a practitioner with no PR involvement, completion of the bundle delivery by a current PR practitioner resulted in higher referral and pick-up rates (60% vs 12% and 40% vs 32%, respectively). These results support the concept of integrating PR and hospital services.
Unfortunately, the completion rate (number of subjects who completed PR divided by the number of referrals) was disappointingly low. Also, there was no difference between the two bundle groups (13% (2 of 15) vs 12% (3 of 25)), as stated in the supplementary data.
It seems that patients' willingness or ability to complete PR is not af...
We have read the paper by Barker et al. (1) with interest. We congratulate the authors for conducting and publishing their prospective cohort study evaluating the effect of COPD discharge bundle on pulmonary rehabilitation (PR) referral and uptake following hospitalisation for acute exacerbation of COPD (AECOPD).
The authors have shown that the COPD discharge bundle had a positive effect on PR referral compared with a no bundle (17.5% (40 of 228) referral rate vs 0%(0 of 63)). This figure is lower than the expected 30% referral rate to PR following AECOPD (2). However, the paper offers no potential reasons for the lower referral rate.
The study had two bundle groups:
• COPD discharge bundle delivered by a current PR practitioner
• COPD discharge bundle delivered by a practitioner with no involvement in PR
Compared to delivery by a practitioner with no PR involvement, completion of the bundle delivery by a current PR practitioner resulted in higher referral and pick-up rates (60% vs 12% and 40% vs 32%, respectively). These results support the concept of integrating PR and hospital services.
Unfortunately, the completion rate (number of subjects who completed PR divided by the number of referrals) was disappointingly low. Also, there was no difference between the two bundle groups (13% (2 of 15) vs 12% (3 of 25)), as stated in the supplementary data.
It seems that patients' willingness or ability to complete PR is not affected by the referral source, i.e. whether the referral was received by a practitioner involved in PR or not. A previous publication has demonstrated a 47% completion rate for PR referrals following AECOPD, with a 72% completion rate for those who started the programme (2).
We are curious whether the authors have explored the potential reasons for the lower completion rate in their study. Causes could include dissatisfaction with the provided programme, a patient’s anxiety, and lack of perceived benefit from PR participation.
References
1. Barker RE, Kon SS, Clarke SF, et alCOPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPDThorax Published Online First: 02 March 2021. doi: 10.1136/thoraxjnl-2020-215464
2. Jones SE, Green SA, Clark AL, et alPulmonary rehabilitation following hospitalisation for acute exacerbation of COPD: referrals, uptake and adherenceThorax 2014;69:181-182.
Hessel(1) published an editorial concerning mesothelioma among vehicle mechanics and concluded that ‘with nearly two dozen studies of mesothelioma among vehicle mechanics and no evidence of increased risk, it would appear obvious that vehicle mechanics as an occupational group, are not at increased risk of mesothelioma.’ In my opinion Hessel relies too heavily upon epidemiology for his conclusions. Epidemiology is important if studies reliably address the question at issue, but published epidemiologic studies are generally not helpful to the evaluation of risk among vehicle mechanics. Few were designed to be studies of mesothelioma in mechanics. Most are general studies of the disease Mesothelioma in which some of the subjects happened to be mechanics. Since they were not designed to be studies of vehicle mechanics, none of the information necessary for a study of risk, such as the numbers of brake jobs performed, the use of compressed air, sanding or grinding, was collected. Not a single one of the studies had information adequate to compute a quantitative exposure estimate for any of the subjects. Misclassification of exposures will mask risk among those truly exposed(2,3).
Show MoreHessel suggests that the paper in Thorax by Thomsen (4) supports his opinion. The aim of that paper was to compare risk among men in a cohort of vehicle mechanics with a comparison cohort of men not occupationally exposed to asbestos. When studying risk in a population exposed to a toxic subs...
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...
Show MoreWe thank James R Camp for his response and interest in our study. To answer the question posed directly, we did not use blood eosinophils as a covariate in the model, since leukocyte differential count is not routinely made at every outpatient visit for COPD patients in Denmark.
The relation between blood eosinophils in COPD and pulmonary infections is not a trivial one. As mentioned by James R Camp, mouse models indicate that eosinophils have antibacterial properties in vitro (1). However, few clinical studies have included blood eosinophil counts as a risk factor of pneumonia in COPD, mostly showing either a weak or no association (2,3).
Eosinophils from human blood have been demonstrated to have bactericidal effects against S. aureus and E. coli, but noteworthy, this effect was not as potent as the neutrophils (4). Additionally, severe acute bacterial infection like sepsis almost uniformly causes eosinopenia (5,6) and experimental lipopolysaccharide injection in healthy humans and diabetic humans cause profound and long-lasting eosinopenia (7). This is not easily comprehensible if the eosinophils are a needed part of the innate host immune response to bacterial infection.
An alternative explanation for a possible association could be that eosinophils and neutrophils act in bacterial infection in a complex interplay, while regulating and adjusting the response of each other. To support this, it has been demonstrated that integrin β chain-2 (CD18),...
Show MoreLetter 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 recently read the recent publication by Elköf and colleagues in the recent issue of Thorax titled ‘Use of inhaled corticosteroids and risk of acquiring Pseudomonas aeruginosa in patients with chronic obstructive pulmonary disease’(1) with great interest. The paper highlights an important clinical observation in a well-defined cohort.
We were interested that Elköf and colleagues, tentatively discuss that biological mechanisms resulting from ICS alterations on the immune system may be an explanation for a change in the microbial composition in the airways(1). As the authors discussed, eosinophilic inflammation in COPD identifies a group of patients with ICS responsiveness(2). In the mouse model, there are data examining that eosinophils have anti-microbial properties(3). Access to eosinophil counts from this cohort may be invaluable in unravelling the relationship of eosinophils and COPD and could provide insight into the impact of steroids in bacterial infection. Did the authors investigate the peripheral blood eosinophil count as a covariate in their main analyses?
References
1. Eklöf J, Ingebrigtsen TS, Sørensen R, Saeed MI, Alispahic IA, Sivapalan P, et al. Use of inhaled corticosteroids and risk of acquiring <em>Pseudomonas aeruginosa</em> in patients with chronic obstructive pulmonary disease. Thorax. 2021:thoraxjnl-2021-217160.
Show More2. Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, et al....
To the editor,
We thank N. Hürsoy and colleagues for their interest in our study of patients four months after severe COVID-19 [1]. We agree that there needs to be continued development of terms describing the radiographic appearance of post-COVID fibrotic-like patterns. We acknowledge that without the benefit of histopathology or serial imaging, our ability to define pulmonary fibrosis is limited.
The authors posit that parenchymal bands, irregular densities, and ground glass opacities, may be considered fibrotic-like patterns. We have included irregular densities, characterized as reticulations or traction bronchiectasis, as fibrotic-like changes. We did not include parenchymal bands [2], as these can be associated with atelectasis, which is common in COVID and can disappear over time [3]. Similarly, we did not include isolated ground glass opacities as fibrotic-like changes, as these have been found to decrease over time in CT lung cancer screening cohorts [4] and in other post COVID-19 cohorts [5, 6].
A priori, we evaluated for both previously established interstitial lung abnormality categories [7], as well as categories of radiographic abnormalities reported in Acute Respiratory Distress Syndrome (ARDS) survivors using an established scoring system [8]. This inclusive approach should facilitate meta-analyses and comparisons with future studies of COVID-19 survivors, interstitial lung disease studies, and studies of non-COVID ARDS survivors. Fu...
Show MoreDear Editor,
We have read with great interest the article investigating the relationship between computed tomography (CT) findings of the patients with fibrotic-like patterns and telomere length after four months of acute COVID-19 infection. According to the literature and our experience, post-COVID interstitial lung disease is a potential public health problem. Thus, we aimed to share our concerns about the fibrotic-like patterns in this group of patients.
Post-COVID fibrosis is not as the same as the other interstitial lung diseases. In the article, the authors describe CT findings of fibrotic-like patterns as limited to reticulation, honeycomb cysts, and traction bronchiectasis. However, post-COVID fibrosis CT findings were shown to be more varied and may include parenchymal bands, irregular densities, and ground-glass areas (1–3). As we move towards the future, all of us need to create a common language, a lingua franca in the definition of post-COVID fibrosis. To achieve this, we need brainstorming and close cooperation.
It will also be helpful to elaborate the characteristics of the non-fibrotic pattern in the table. The clinical importance of the ground glass areas, which persist four months after active infection but not defined as fibrotic, is unknown. We consider that these patterns cannot be separated from fibrotic-like patterns precisely. Additionally, we can also classify parenchymal bands as fibrosis-like appearance. In our experience...
Show MoreWe thank Dr Abdulqawi for interest in our work (1). He comments that the referral, uptake and completion rates for pulmonary rehabilitation in the current study were lower than in a previous study by Jones and colleagues (2). We would caution against retrospective comparison with unmatched historical controls due to confounding factors such as differences in patient characteristics and practice pathways that may contribute to inaccurate point estimates.
We hypothesised that the COPD discharge bundle would impact on referral rates. Strengths of the current work include the prospective real-world nature of the study, with the research team having no involvement in treatment allocation. The clinical team delivering the bundle were blinded to the study objectives, thus minimising any Hawthorne effect.
Dr Abdulqawi raises the point that pulmonary rehabilitation completion rates were low in the current study (albeit based on a low denominator). The reasons for non-completion of PR are often complex and multi-factorial (3) and may not be directly related to referral source. However, what is clear is that without a referral for pulmonary rehabilitation, uptake and completion rates are zero.
1. Barker RE BL, Maddocks M, Nolan CM, Patel S, Walsh JA, Polgar O, Wenneberg J, Kon SSC, Wedzicha JA, Man WDC, Farquhar M. Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the M...
Show MoreThe idea that smoking might have a protective effect against COVID-19 is an intriguing, man bites dog type of story, which gives it a certain attraction. Happily, it appears to be false and the assumption of harm has turned out to be correct[1-5].
Our data show clearly that in the 2.4 million Zoe COVID Symptom Study App users, people who smoked were at increased risk of symptomatic COVID-19[2] and were at risk of more severe disease, which is consistent with a systematic review of patients hospitalized with COVID-19[4]. Our findings are also consistent with The UCL COVID-19 Social Study3 which found increased risk of test confirmed COVID-19 (OR=2.14 (1.49–3.08)) and with the COVIDENCE study where smokers had an OR of1.42 (0.99-2.05) for test-confirmed COVID-19[1].
The OpenSafely dataset based on data from the primary care records of 17.3 million adults in the UK found that, adjusted for age and sex, also identifies smoking as a risk factor - current smoking was associated with a hazard ratio for COVID-19-related death of 1.14 (1.05–1.23)5. The apparently protective effect in the “fully adjusted” model is due to over-correction producing collider bias.
Since any protective effect of smoking in COVID-19 appears to be illusory, pursuing a mechanism for it is unlikely to be productive.
References
Show More1 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021:2021.2003...
We have read the paper by Barker et al. (1) with interest. We congratulate the authors for conducting and publishing their prospective cohort study evaluating the effect of COPD discharge bundle on pulmonary rehabilitation (PR) referral and uptake following hospitalisation for acute exacerbation of COPD (AECOPD).
The authors have shown that the COPD discharge bundle had a positive effect on PR referral compared with a no bundle (17.5% (40 of 228) referral rate vs 0%(0 of 63)). This figure is lower than the expected 30% referral rate to PR following AECOPD (2). However, the paper offers no potential reasons for the lower referral rate.
The study had two bundle groups:
• COPD discharge bundle delivered by a current PR practitioner
• COPD discharge bundle delivered by a practitioner with no involvement in PR
Compared to delivery by a practitioner with no PR involvement, completion of the bundle delivery by a current PR practitioner resulted in higher referral and pick-up rates (60% vs 12% and 40% vs 32%, respectively). These results support the concept of integrating PR and hospital services.
Unfortunately, the completion rate (number of subjects who completed PR divided by the number of referrals) was disappointingly low. Also, there was no difference between the two bundle groups (13% (2 of 15) vs 12% (3 of 25)), as stated in the supplementary data.
It seems that patients' willingness or ability to complete PR is not af...
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