65 e-Letters

published between 2016 and 2019

  • The effect of living at high altitude and living in urban settings on lung function decline

    We read with interest the findings of Miele et al. on the relationship between environmental exposures and decline in lung function (1). The authors reported that living in urban settings and living at high altitude were associated with accelerated decline in pre-bronchodilator FEV1 and FVC. Investigating the effects at area level is important from a public health perspective and extra analysis on this valuable dataset as suggested below will help to untangle these links further.
    Study participants were recruited from four settings in Peru: Lima, Tumbles, urban Puno and rural Puno (1). Urban living and high-altitude dwelling (as binary variables) were defined based on these four settings. The authors compared the effect of urban living (Lima and urban Puno) with rural living (Tumbes and rural Puno); and the effect of high-altitude dwelling (urban Puno and rural Puno) with low-altitude dwelling (Lima and Tumbes). It is possible that the observed independent effects found by the authors of urban living and high-altitude dwelling may be driven by the urban Puno group (high altitude and urban living). In other words, there may be an interaction between urban living and high-altitude dwelling and investigating this potential interaction would be informative.
    As discussed by the authors, the adverse effect of high-altitude dwelling on lung function decline may partly be related to hypoxia and adverse effects from living in urban settings may be related to outdoor air...

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  • Lung volumes measurement for risk stratification in smokers without COPD

    We appreciate the points raised by the commentator about our study (Zeng et al.)[1] published in June 2018 issue of Thorax that (1) the prevalence of abnormal residual volume to total lung capacity ratio (RV:TLC) in our study of ever-smokers with preserved spirometry is substantially higher than that observed in the commentator’s past studies,[2-4] and (2) an assumption by the commentator that stringent exclusion of those with abnormally low TLC and those with diagnosis codes of interstitial lung diseases (ILD) in their electronic health records (EHR) may have resulted in overestimation of the prevalence of abnormally high RV:TLC among smokers with preserved spirometry.

    We would like to draw the attention of commentator and readers to the following points:

    1- The studies referenced by the commentator used pulmonary function tests (PFT) data collected from 708 patients in 2013 across 5 clinical sites associated with University of Minnesota Medical Center with inclusion criteria of patients 18 years of age or older with or without history of smoking.[2] They included about 50% women and 3 African Americans. Our study was performed on PFT data obtained from 1985 through 2017 through the United States Veterans Affairs (VA) nationwide EHR from 7,479 patients across 37 VA medical centers in the United States with inclusion criteria of patients 40 years of age or older with an EHR diagnosis code of smoking, which likely suggests heavy smoking for VA patients. Our st...

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  • Should lung volumes measurement accompany every spirometry?

    Should lung volumes measurement accompany every spirometry?
    Spyridon Fortis MD1
    1Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa Hospital and Clinics, Iowa City, IA, USA

    Corresponding Author:
    Spyridon Fortis, MD
    UIHC – Internal Medicine
    200 Hawkins Drive – C33 GH
    Iowa City, IA 52242
    Email: spyridon-fortis@uiowa.edu
    Word Count:
    Author Disclosures: Authors declare that there is no conflict of interest regarding the publication of this paper.
    Running Head: Lung volumes with every spirometry
    Key Words: COPD, diagnosis, lung volumes, RV/TLC, preserved lung function.

    In their study published in the June 2018 issue of Thorax, Zeng et al showed that RV/TLC ratio in smokers with preserved lung function is associated with clinical diagnosis of COPD, higher rates of respiratory medications prescriptions, emergency room visits, hospitalizations, and all cause-mortality[1]. The findings strongly support that patients with respiratory symptoms and normal spirometry who have air trapping in lung volume measurements have worse outcomes than those with no air trapping. Those patients at risk for COPD may suffer early obstructive lung disease which has not yet met the spirometric criteria for COPD diagnosis.
    I congratulate the authors for their study as they address a very clinically relevant topic. Further studies are neede...

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  • Response to “Prospective randomised controlled trial: fixed 1-year screening interval group versus a tailored intervals group,” letter response by Silva et al

    We thank the authors of the letter in response to our paper for their interest and positive appraisal of our model. Likewise, we appreciate the design of the Multicenter Italian Lung Detection (MILD) trial which, despite its small sample size, demonstrates that annual intervals are unnecessary for the majority of screenees. Once more European data is available to perform cost-effectiveness analyses, we hypothesize that personalised screening intervals will prove to be the preferred design. Furthermore, it is estimated that most inclusion criteria used to select high-risk participants encompass only 70% of all lung cancer cases in the population; reassessing risk and tailoring interval groups after the baseline scan may enable the inclusion of persons of lower risk. As Silva et al mentioned, there is no reason to set the upper limit of follow-up intervals at 2-years. We also agree that volumetric nodule measurements are better suited for determining follow-up procedures than (perpendicular) diameter, and hope to be able to implement this into a future model. Moreover, risk scores may be calculated autonomously by computers in the future, with only a select few dubious cases requiring radiologist attention.

  • The EPICC trial, is it possible to perform intensive rehabilitation in the current framework of intensive care?

    The EPICC trial addresses the rarely investigated topic of rehabilitation in the critical care setting [1]. We note with interest that no improvement was found in outcomes in the rehabilitation group compared to the standard treatment group. Some of the reasons are clearly highlighted by Schaller et al. in their response to the paper including the time to starting intervention, therapy times and also sample size. Only 41% of the participants in the intervention group and 35% of the standard treatment group contributed data throughout the study period. In addition to this, only 8% of the intervention group managed over half the target therapy time and the EPICC trial showed that ‘an extra 10 minutes of physical therapy per day does not make a difference [2]’
    This study triggered an audit within our own 16 bedded mixed surgical and medical intensive care department assessing the number of sessions carried out over a 2 week period compared to those attempted. We investigated the actual duration of sessions achieved as compared to a target of 45 minutes rehabilitation each day during the working week (Monday-Friday). On average, 23.3 (standard deviation 20.19 minutes) minutes of rehabilitation per day was achieved and only 35% of attempted physical therapy sessions were completed. These figures are similar to those cited within the EPICC trial and highlight some of the difficulties of achieving longer therapy times within a busy intensive care department. Some of the fac...

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  • Prospective randomised controlled trial: fixed 1-year screening interval group versus a tailored intervals group

    In 2011, the National Lung Cancer Screening Trial (NLST) showed that annual low-dose computed tomography (LDCT) improved overall survival (1). More recently, longer interval between LDCT rounds was advocated to improve screening efficiency after baseline (2).
    Schreuder et al reported a comprehensive model for optimization of LDCT by biennial rounds for subjects at lower 2-year risk of lung cancer (3). They built a promising polynomial model including both patient characteristics and nodule descriptors. The retrospective simulation on NLST data provided enough power to test Schreuder’s model (3) as well as other models for selection of subjects to be forwarded to biennial screening (2, 4). We appreciate this approach to parsimonious LDCT administration as we are strongly convinced that annual screening should be tailored to subjects with remarkably high risk of lung cancer. The authors refer that prospective randomized controlled trial with tailored screening intervals would be hardly feasible, however we would like to remind that some experience was already reported in the literature.
    Since 2005, the Multicenter Italian Lung Detection (MILD) trial conducted a prospective comparison between annual (LDCT1 = 1,152 screenees) and biennial LDCT (LDCT2 = 1,151 screenees) (5). The LDCT2 screenees were shifted to annual screening in case of solid nodule > 60 mm^3 and/or subsolid nodules. In other words, the MILD trial prospectively tested a risk model for tailored s...

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  • Comparison of ICS doses

    We are grateful to Dr. Duerden and Dr. Levy for their comments on our paper which highlight the difficulty of comparing doses of ICS steroids when there is no gold standard comparator. Our aim in compiling Table 1 was to point out that the NICE table does not allow for the greater potency of HFA FP compared to HFA BDP. We were concerned that this was a significant safety issue especially in children [1]. In our efforts to simplify this message, we had not fully explained or allowed for some of the other variables.

    1. Dr. Levy is correct to point out that the original GINA table (used by NICE) of “Low, medium and high daily doses of inhaled corticosteroid for children 6-11 years” has a statement below indicating that the table is not a table of “dose equivalency”, the term we used in Table 1, but of “estimated clinical comparability”.

    2. The GINA table (but not NICE) also has a footnote explaining the inclusion of beclometasone dipropionate CFC (BDP CFC) as a comparison with older literature. CFCs (chlorofluorocarbons), as propellants in metered dose inhalers, were phased out under the Montreal Protocol and were replaced by HFAs (hydrofluorolakanes). However, CFC BDP is still often used as the reference standard when comparing ICS in terms of their potency.

    3. Most newer HFA ICSs have been formulated to be equipotent with the CFC ICS they were replacing. As one example, the BTS/SIGN table includes the proprietary HFA BPD, Clenil modulite, commonly us...

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  • Contact screening in TB: is it time to re-brand?

    We welcome the letter by Anna Humphreys and colleagues highlighting the secondary benefits of screening contacts of extra pulmonary tuberculosis for LTBI in areas where active cases are predominantly amongst the non-UK born (1). 
    We share the view that novel approaches are needed to identify and offer testing to those at risk of LTBI, and that contact tracing provides a unique opportunity to reach those who may be eligible.  

    Early results from the London Borough of Newham, the pilot site for the national latent TB screening programme highlight that uptake of LTBI screening amongst recent migrants is only 40 percent (2). Efforts are being made to improve awareness including animated health promotion tools (https://youtu.be/tKwAHJ7JeV0) and TB Alert’s Latent TB Handbook (https://www.tbalert.org/health-professionals/ltbi-toolkit/) and novel interventions to improve LTBI screening and treatment uptake are being implemented across the country. We are currently investigating the efficacy of managing LTBI entirely within primary care (https://clinicaltrials.gov/ct2/show/NCT03069807). Recent work has also identified that opportunistic LTBI screening in non-health settings is acceptable to recent migrants (3).
    In areas where the majority of active cases are amongst those...

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  • What does the EPICC trial really tell us?

    We have read with great interest the multi-centred EPICC trial that randomized over 300 patients [1]. While the delivery of a complex physical rehabilitation intervention in clinical trials is difficult, we believe that several aspects of the trial may have resulted in the inability to detect a difference between the control and intervention groups. These factors include the delayed time to start the intervention, inadequate delivery of the intervention and the large loss to follow-up for the primary outcome measure. In our opinion, these three factors limit the interpretation of the results of the study. While the authors have mentioned some of these concerns in their discussion, and Connolly et al. raised some of these points already [2], we hope to learn some important lessons from the authors to better understand these limitations and how they can be minimized in future studies.
    The number of randomized controlled trials evaluating early physical rehabilitation in ICUs is increasing [3]. Positive effects on primary outcomes were only found in studies in which physical rehabilitation was started within 72 hours of ICU admission [4-6]. Studies, which did not meet this criterion of early onset of physical rehabilitation, did not demonstrate benefit of the intervention [7]. Therefore, this time frame has been defined in rehabilitation guidelines [8]. Based on this evidence, we are not surprised that the authors of the EPICC trial were unable to demonstrate beneficial...

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  • Smoking duration, smoke intensity or pack-years: what is the best method for exposure ascertainment?

    The article of Bhatt et al addresses an important topic (1). The authors assessed the relative contribution of intensity and duration of tobacco smoke exposure to the development of chronic obstructive pulmonary disease (COPD). They concluded that smoking duration alone provides stronger risk than the composite index of pack years. In other words, the effect of long and low intensity exposure has a stronger association with COPD than short exposures of high intensities. The article of Marks consents this finding, concluding that pack years are a suboptimal index of exposure (2).

    A major limitation of the study of Bhatt, which surprisingly is not stated as such, is the use of a cross-sectional design that does not allow drawing causal conclusions. The conclusions drawn therefore might be flawed.

    Selection bias due the healthy ‘survivor’ effect might have occurred. The duration of smoking could have been influenced by the deleterious effects a person experiences from the exposure to smoke. Those with a long smoke duration are more likely not to experience (or experience less) health issues due to smoking, and might therefore have less severe (or no) COPD than those with a short smoke duration. In line with this, selective ‘drop-out’ of the more diseased persons may have biased the results.

    Furthermore, the authors use retrospective data, while this often leads to recall bias. Participants often do not precisely remember the numbers of cigarettes smoked...

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