305 e-Letters

  • AIRWAY Reflux in IPF

    We read with interest this article by Dutta et al evaluating the feasibility of proton pump inhibitor (PPI) therapy in Idiopathic Pulmonary Fibrosis (IPF). We congratulate the authors for successfully conducting this first ever double blind, randomised, placebo-controlled pilot trial of PPI in IPF despite the challenges to the recruitment in this disease with high prevalence of gastroesophageal reflux. Furthermore, we agree with the authors that cough is a neglected but important outcome measure in IPF trials and they should be praised for pursuing this.
    The role of gastro-oesophageal reflux in IPF has long been debated and its prevalence has been evaluated in a number of studies (1,2). However, the value of anti-acid therapy in relation to clinically meaningful outcomes has lacked true prospective randomised and controlled evaluation in previous trials/analyses. Furthermore, a pooled analysis (3) of 3 randomised controlled trials (RCTs) of Pirfenidone in IPF showed no clinical benefit of antacid use in terms of disease progression, mortality or markers of functional assessment with a signal towards increased infection rate in those with advanced disease and receiving antacids.
    Though airway reflux has been implicated in the exacerbation and pathophysiology of chronic cough in IPF, the aspect of oesophageal dysmotility/ non-acid reflux has largely been ignored. Dutta and colleagues had a small fraction of patients completing oesophageal manometry in the trial (...

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  • Lung Health Check Pilot and Implications for Population Screening

    We read the extremely important paper by Crosbie et al1 with interest as it has potential implications for population screening for lung cancer. However, the paper contains some ambiguities and inconsistencies and it would be very helpful to obtain clarification from the authors in order to interpret their findings in a population screening context.

    Firstly, in the methods section, it is stated that ever smokers aged 50 to 74 years registered at participating general practices were invited to a community based lung health check (LHC). It is not stated whether every individual registered as an ever smoker was invited. However, assuming this was the case it appears from the flow chart that a total of 16,402 invitation letters were sent out, but if the aim was to send these only to individuals registered as ever smokers it is not clear why 6,476 letters were sent to never smokers.

    In any event, the flow chart indicates that letters were sent to 9,926 smokers and that 2,613 attended the LHC. Thus the uptake of the first filter was 26.3% which does not resonate with the first statement in the results section i.e. “Demand was extremely high”.

    There are also two apparent inconsistencies in the data presented; in table 1 the number of attendees is stated as 2,541 yet in the flow chart it is 2,613. In addition, in the legend for the flow chart it is indicated that the overall numbers are based on General Practitioner recorded smoking status for 15,072 individua...

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  • COPD patients should take Vitamin D supplements

    In the systematic review by Jolliffe et al. patients with Vitamin D deficiency benefitted most from supplementation. The hypothesis is put forward that exacerbations in the Vitamin D deficient groups are driven largely by Vitamin D deficiency. It may be that strategies aimed at reducing the prevalence of Vitamin D deficiency in the COPD population are the most effective. A population health perspective may be sensible. The Scientific Advisory Committee on Nutrition recommends a daily Vitamin D dietary intake of 10 micrograms for everyone 4 years and over. A pragmatic change to our practice could be to encourage, advocate and remind these patients to take a dietary supplement bought from their pharmacy. This advice can be imparted by clinicians during routine reviews and exacerbations both in Primary and Secondary care.

    1. Jolliffe DA, Greenberg L, Hooper RL, et al, Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax 2019;74:337-345.
    2. Vitamin D and Health Report, Scientific Advisory Committee on Nutrition , 2016

  • Cost-effectiveness and tuberculosis elimination: a détente?

    We would like to thank Dr. Wingfield et al. for their thoughtful response on our cost-effectiveness analysis of tuberculosis contact tracing in London(1). The authors provide a number of insights which complement and expand upon our results and highlight the many complexities of TB interventions, both currently and as we head towards elimination.

    Wingfield et al. raise important points regarding heterogeneity on contact tracing yield, something we touched upon in the discussion of our paper. As they mention, such heterogeneity is likely to increase as countries such as the UK near elimination. We found that the yield of active cases around non-pulmonary cases needed to be very high – in our analyses, the incremental cost-effectiveness ratio (ICER) for screening such contacts was below £30,000 per quality-adjusted life year (QALY) when the yield of contacts reached about 0.1 active cases found per index case, i.e. when 4% of contacts screened are positive. However, this ignores synergistic effects caused by those infectious contacts potentially being more infectious and infectious for longer, due to their being part of a high-risk group, and so the actual threshold may be lower.

    We also agree with Wingfield et al. that careful thought must be given to the interpretation of the ICER in the context of TB elimination, as in any context. Rather than treating the willingness-to-pay threshold as a strict and universal cut-off value, the ICER should be considered alo...

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  • First study on effect and impact of mechanical ventilation in myotonic dystrophy type 1

    We thank Dr. Seijger and colleagues for their analysis. These queries are legitimate and most of the answers are in the online repository. Indeed, in order to comply with the guidelines for letters to Thorax (no more than 1000 words and 2 tables / figures), we could not include all our descriptive and univariate analysis.

    We agree that the analysis of survival of patients with type 1 myotonic dystrophy is complex. Our results in Figure 1 and Table R1 demonstrated that patients who refused to initiate NIV, or who delayed NIV initiation, had both a more severe respiratory function and a higher risk for severe event (invasive ventilation or death). Independently from determining whether these severe complications were due to the severity of the initial respiratory function, the lack of compliance to treatment or both, we believe that it was important to underline the presence of this triptych, which is not observed with other neuromuscular groups, such as Duchenne muscular dystrophy where the acceptance of NIV increases with the respiratory dysfunction severity.

    Our suggestion that failure to adhere to home mechanical ventilation was associated with increased mortality (tracheostomy excluded), was based on a Cox model analysing predictors of 10-year mortality among NIV users (Table 1). The Cox model was used to evaluate death risk ratios associated with NIV adherence category and was adjusted for other risk factors described in the literature. The covariates i...

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  • Reply to ‘effect and impact of mechanical ventilation in myotonic dystrophy type 1: a prospective cohort study.’

    To the editor,

    We read with great interest the paper of Boussaïd et al.1. They showed that Myotonic Dystrophy type 1 (DM1) patients who refused or delayed non-invasive ventilation were at higher risk for severe events, the latter defined as invasive ventilation or death. In the NIV users, risk of death was associated with orthopnoea and adherence to therapy. The investigators concluded that non-use or poor adherence of home mechanical ventilation (HMV) may be associated with increased mortality. Despite the importance of these findings several comments can be made.

    First, survival analyses in DM1 patients are complex due to heterogeneity and several other factors which have to be taken into account if the effects of HMV are assessed. For example not only the variance of reduced pulmonary function but also neuromuscular deficits, apathy, cardiac conduction disturbances, presence of obstructive or central sleep apnea do all influence the clinical condition and prognosis of these patients2. In addition, there remains the possibility that hypercapnia might not always be a result of ventilatory pump failure and that HMV might not be effective3. Correction for these confounders is needed to investigate the real effect of HMV. Moreover, both groups differ in vital capacity and presence of hypercapnia at baseline. So, we are not sure whether the risk of a severe event is really higher in the l/noNIV group than in the other groups. Therefore the presented difference...

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    The global increase in air travel, with over 3.97 billion people traveling by air each year, and the ageing population, increase the number of those with an illness who wish to travel (1). Even more, in countries like Greece with hundreds of islands, health professionals are frequently asked to assess a patient’s fitness to fly. Doctors can receive advice and guidance mainly from two sources: the IATA passenger medical clearance guidelines (2) and the Aerospace Medical Association in which the British Thoracic Society’s recommendations for air travel (3) are suggested.
    Many respiratory conditions can affect a passenger’s fitness to fly with pulmonary embolism being the most debatable (3). A major question that respiratory physicians frequently have to answer, mostly with visitors from overseas who need to be repatriated following diagnosis of pulmonary embolism, is about the right time to “fly with a clot”. The British Thoracic Society guidelines recommend against airline travel during the first four weeks following pulmonary embolism (3). On the other hand, in the IATA medical guidelines published in 2018 it is suggested that patients can fly 5 days after an acute pulmonary embolism episode, if they receive anticoagulation and their PaO2 is normal on room air (2). Although there is little scientific evidence to support the above mentioned recommendations, the huge difference in the suggested period can really confuse healthcare professionals. Moreover, asking patie...

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  • 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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