336 e-Letters

  • Malignant Mesothelioma Among Vehicle Mechanics

    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...

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  • Response to: Letter to the Editor of Thorax by Drs. Marty S. Kanarek and Henry A. Anderson RE: Risk of asbestosis, mesothelioma, other lung diseases or death among motor vehicle mechanics: a 45-year Danish cohort study

    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...

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  • Author response: Eosinophils as covariates

    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),...

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  • Letter to the Editor

    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...

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  • Eosinophils as covariates

    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?


    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....

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  • Response to Hursoy and colleagues

    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...

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  • Different Views About Post-Covid Fibrotic-Like Patterns

    Dear 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...

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  • Reply to: Referral to pulmonary rehabilitation (PR) by a current PR practitioner has no effect on PR completion rate

    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...

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  • Dog bites man - COVID-19 and smoking.

    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.

    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...

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  • Referral to pulmonary rehabilitation (PR) by a current PR practitioner has no effect on PR completion rate

    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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