258 e-Letters

  • Effect of inhaled corticosteroid dose on blood eosinophils

    Lommatzsch et al1 report significant falls in blood eosinophils in 11 asthma patients (mean FEV1 87%) in response to increasing the dose of inhaled corticosteroid from 1000ug to 2000ug/day (beclometasone equivalent dose ) ,with a median difference of 240 cells/ul . Jabbal et al 2 reported in 217 asthma patients (FEV1 85%) a mean fall of 71 cells/ul (95%CI 38-105) comparing 200ug verses 800ug belcometasone equivalent dose ,along with a 14.5ppb (95%CI 7.9-22.1) fall in FeNO. The patients reported by Lommatzsch et al had a higher baseline level of eosinophils with a median value of 560 cells/ul as compared to a mean value 356 cells/ul for Jabbal et al . Nonetheless we agree with the conclusion that the prevailing inhaled corticosteroid dose should be taken into consideration when making decisions to initiate treatment with biologics such as anti-IL5 and anti-IL4α, where the response is determined by levels of blood eosinophils .


    1. Lommatzsch M, Klein M, Stoll P, Virchow JC. Impact of an increase in the inhaled corticosteroid dose on blood eosinophils in asthma. Thorax 2018. doi:10.1136/thoraxjnl-2018-212233
    2. Jabbal S, Lipworth BJ. Blood eosinophils: The forgotten man of inhaled steroid dose titration. Clin Exp Allergy 2018; 48:93-5.

  • Science is the great antidote to the poison of enthusiasm and superstition

    To the Editor

    Science is the great antidote to the poison of enthusiasm and superstition

    We thank Langer and colleagues for their interest in our editorial. In many ways the title they have chosen for their response confirms our thesis. ‘Absence of evidence’ may not be ‘Evidence of absence’ but it is ……………….. Absence of evidence . Our contention overall is that the relentless search for benefit despite the recently reported negative trials is driven by emotion rather than data.
    Whilst physiological arguments are of interest to physiologists, there remains no convincing evidence in our view either that respiratory muscle fatigue is present in patients with COPD, or that it contributes to exercise limitation. The various suggestions they make in the hope of eliciting a ‘positive result’ for IMT (e.g. changing outcome measure, patient selection) are credible research suggestions and we would not oppose interested investigators pursuing research in this arena, but this does not alter our contention that IMT has no place in current clinical practice.
    Clinically their argument is that IMT alone is beneficial in COPD. We think this argument is specious (irrespective of whether it is correct); pulmonary rehabilitation, in part thanks to the Leuven group, has one of the strongest evidence bases for any therapy in COPD. Therefore the idea that one might drop PR in order to do IMT instead is not one we believe should be taken into the clinical arena....

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  • The importance of experimental conditions in the assessment of products relevant to human consumption

    Although electronic cigarettes (ECs) are a much less harmful alternative to tobacco cigarettes, there is concern as to whether long-term ECs use may cause risks to human health. There are reasonable concerns and should be elucidated as soon as possible to learn how to best employ these products, causing the least possible damage to users.
    Scott and colleagues aimed at define whether e-cig vapors have a negative impact on human alveolar macrophages (AMs) viability and function (1). They tested human AMs from lung resection specimens from healthy donors by exposing these cells to the electronic cigarette vapour condensate (ECVC).
    First of all, the authors dedicated a detailed explanation to the method used to condensate the vapour, but the protocol used to generate vapour is quite ambiguous, omitting to indicate puff volume, puff number, and in particular if the pump used to aspirate the vapors were able to generate the correct puff profile (2). This is a crucial step in the validation process of an exposure method, because if the vapours are generated with incorrect regimes, they can lead to the production of inaccurate ECVC and thus to distorted results invalidating all the conclusions of the study. We think the author could detail the regimen employed for vapour generation.
    Furthermore, airway macrophages are resident in the connective tissue and not exposed directly to the liquid-air interface, therefore the method used for the exposition of these cells...

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  • Additional differentitation

    The differentiation between an empyema and a peripheral lung abscess is really difficult. The authors have summarized most points on differentiation. We had of a similar case, which looked like an Abscess on Chest Xray and had Acute angulation with lungs on Chest Ct, but due to the smooth inner walls and enhancement of pleura, we treated the case like an Empyema. Interestingly the initial CT showed some volume loss with ribs appearing crowded and this feature was more pronounced in the subsequent CT done after 2 weeks. Thus, associated volume loss with rib crowding could also be an additional point in the differentiation favoring Empyema and this volume loss might appear fairly early as well.

    ****can provide CT films of the same****

  • Cost-effectiveness and tuberculosis elimination: never the twain shall meet

    The National Institute for Health and Care Excellence (NICE) 2016 Tuberculosis (TB) guidelines no longer recommend screening contacts of adults with extra-pulmonary TB (ETB). However, no new evidence since the previous published guidelines was provided to support this policy change. Moreover, despite the guidance, some regional TB multidisciplinary teams and services continue to screen ETB contacts.(1)

    In their original article in Thorax, Cavany et al estimated the cost-effectiveness of screening ETB contacts in London.(2) The authors’ findings suggest that screening of such contacts is unlikely to be cost-effective at the threshold of £30,000/QALY - the “willingness to pay” threshold commonly used by NICE.(3) The authors’ findings are tempered by the data being London-specific and not generalizable to the rest of England, and the lack of robust available evidence on either transmission rates or index cases’ pre-diagnosis symptom duration. Nevertheless, the authors recognise these limitations and their sensitivity analysis suggests that, even with assumptions of higher rates of transmission or prolonged symptom duration, their principal findings would not change.

    The findings of this strong, well-designed study are important and provide much needed evidence for national debate around strategies for TB contact screening. Resources for TB services across England, especially those allocated to tracing contacts of TB patients, are becoming increasingly constrain...

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  • Impact of electronic cigarette on our health

    According to recent study published by Sebastian et al., (1) electronic cigarette vapor impairs the activity of alveolar macrophages, which engulf and remove dust particles, bacteria, and allergens that have evaded the other mechanical defenses of the respiratory tract. This study finding is important and it shows that the long term health impact of e-cigarettes use may be more harmful than we know (2).

    Meanwhile, industry, tobacco research community and the online information are promoting electronic cigarette as a less harmful tobacco cessation tool. However, before more leeway to advertise the harm-reduction benefits of vaping products, we believe that the first step would be to establish whether vaping products are indeed safer tobacco cessation device or harm reduction tool (3). Moreover, currently available evidence (including clinical guidelines and position statements of credible medical organizations) based information need to ensure that people are protected from commercial interests and are able to make informed decisions based on current best evidence on electronic cigarette and its long term health effects (3). It is our moral obligation that we should not be promoted electronic cigarette to our children and people those who never wanted to smoke tobacco. At the same time, it is important to promote the proven non-tobacco nicotine products such as Nicotine Replacement Therapy (gum or inhalators) to smokers those who are sincerely wanted to quit.

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  • Absence of evidence is not evidence of absence! Lessons from recent trials of adjunctive IMT in COPD and recommendations for further research: careful selection of candidates, controlling interventions and choosing the most adequate outcomes.

    We support the view of Drs. Polkey and Ambrosino that recommendations for clinical practice should not be based on either positive or negative preoccupation concerning the potential effectiveness of a treatment but rather on an impartial evaluation of the available data. In their editorial entitled ‘Inspiratory Muscle Training in COPD: can data finally beat emotion’ they unfortunately provide a fairly one-sided evaluation of this treatment, based on an incomplete and largely outdated review of the available evidence1. It is unfortunate that they neglect a major part of available data, which could contribute to a more balanced and fair discussion about this intervention. We therefore deemed it necessary to add this missing evidence along with our own interpretation of recent findings to the discussion.
    Complexity of studying add-on interventions to pulmonary rehabilitation
    Based on the results from three recent multicentre trials2-4, Polkey and Ambrosino exclude a role for adjunctive IMT in the rehabilitation of patients with COPD. As emphasized in a previous opinion piece by Dr. Ambrosino5, it is important to distinguish between studies that evaluate the effects of inspiratory muscle training (IMT) as a standalone intervention (i.e. in comparison to no intervention or a sham control intervention) and studies on the effects of IMT added to a pulmonary rehabilitation program (PRP).
    Concerning the first comparison, there is a large amount of data available s...

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  • 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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