69 e-Letters

published between 2019 and 2022

  • Response to Priyadarshi

    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
    Future studies could consider the collection of detailed aerosol measures from patients a...

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    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...

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  • View from South East Asia on Post-COVID Fibrotic Lung Disease

    Dear Editor,

    We read with interest McGroder et al’s study on the radiographic findings of patients four months after severe COVID-19 and the associated risk factors. Hürsoy and colleagues’ comment (1) on the paper was equally thought-provoking. We would like to further this discussion by contributing some of our observations from the pulmonology clinic at a major academic medical center in South East Asia.

    It has been tremendously challenging globally to achieve precision in the diagnosis of Interstitial Lung Disease (ILD) post-COVID as invasive testing such as lung biopsies are performed sparingly. Histopathological pulmonary findings have largely remained inaccessible since COVID survivors are hypoxic so biopsies pose a high risk for the patient, and healthcare personnels are reluctant to perform such high-risk procedures. Hence, we are left to derive our diagnosis from radiological data and pulmonary function tests (PFTs) of the patient.

    We propose that a consensus definition be reached for the diagnosis of post-COVID ILD, one that incorporates well-accepted radiological terms (used to represent any interstitial lung disease). We recommend that lung fibrosis only be classified as ILD if the lung parenchymal abnormalities persist for a minimum of six months after the COVID infection has resolved. Post-COVID ILD should then be further subclassified based on distinct radiological patterns. In our retrospective cohort study, four patterns of post-COV...

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  • 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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