69 e-Letters

published between 2019 and 2022

  • Carbon footprint, environmental impact, and patient outcomes in inhalation therapy: No simple solution to the complex challenges

    It was with great interest and not a little concern that we read the recent Brief Communication by Janson and colleagues [1] into the impact of pressurised metered dose inhalers (pMDIs) on the global warming potential (GWP) of respiratory care. We note the tenacity of one of the authors who has succeeded in publishing a second paper [2] based on a similar, flawed logic just two weeks later. The sense of proportion that is missing in both reports has, thankfully, been identified in the press this week.[3] However, we feel it essential to scrutinise the current contribution scientifically.

    The authors report the carbon footprints of a range of devices marketed by GlaxoSmithKline (GSK) following analysis undertaken by the Carbon Trust (a UK not-for dividend company). Subsequently, calculations were undertaken aimed to determine how the carbon footprint of inhalation therapy in the UK’s National Health Service (NHS) might be reduced by altering the prescribing patterns of UK physicians (where more pMDIs are prescribed than dry powder inhalers (DPIs)) to resemble those of Swedish physicians (where the converse holds). While we acknowledge the authors’ declaration that their data are potentially flawed by the fact that their calculations are based on extrapolating the carbon footprints of just three device formats manufactured by one company to predict the effects of total DPI and pMDI usage in the UK when the carbon footprints of most other devices are unknown, we wou...

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  • Patient engagement is vital

    This paper provides welcome reassurance that switching of inhalers can be carried out not only without risk of deterioration but that improvements in disease control may be seen. My supposition is that this is due to the interaction between clinician and patient to discuss the switch that stimulates increased engagement in the patient leading to better outcomes. Whatever the mechanism this paper is timely with the BBC just today featuring an article on the environmental impact of inhalers and the need to reduce the NHS carbon footprint by choosing more environmentally friendly options.
    The latest BTS/SIGN national asthma guideline includes new information on this and highlights opportunities to recycle pMDIs where possible.
    However, a word of caution on inhaler switching may be in order. Although only anecdotal evidence from my lengthy clinical practice I have on several occasions met patients from different surgeries who have had their regular inhaled therapies repeat prescription changed without discussion, never mind agreement - usually on cost saving rather than environmental reasons - leading at best to loss of confidence in their local surgery and at worst loss of control of their asthma such that an attack was precipitated leading to hospital admission. This was not only a significant risk for the individual but far more costly than the anticipated s...

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  • To the Editor and to the Authors

    To The Editor and to The Authors.

    I wish to congratulate the authors. I find their review on RSV-induced severe disease attractive in all respects. It impressively presents research ranging from epidemiology to molecular immunology, and includes promising treatment opportunities. My perhaps peripheral comments relate to the authors’ conclusion that “much remains to be discovered regarding the host response to RSV infection”.

    Loss of epithelial cells and pathogenic roles of exaggerated epithelial regeneration.
    I’d like to dwell somewhat on RSV-induced epithelial cell loss, which is mentioned in passing in the review. Bodies constituted of many epithelial cells clumped together in airway lumen material have been named Creola bodies by Naylor (1) who demonstrated numerous Creola bodies in association with exacerbations of asthma. However, Creola bodies, as a sign of widespread patches of epithelial shedding, may also be a prominent feature of RSV infection. Indeed, in RSV-infected infants Creola bodies in aspirates seem to be a requisite for the infection to be followed by development of asthma (2,3). This is of interest because epithelial regeneration processes alone, rather than the reputed increased permeability to inhaled material (which is not observed in vivo in asthma (4)) are causative regarding several facets of airway inflammation and remodelling (5,6).

    Lethal RSV infections in children are associated with extensive and patchy loss of bron...

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  • Variants of VEGF in Congenital Diaphragmatic Hernia and Pulmonary Hypertension

    We have read this vital article, and after reading we would like to agree with the findings of the authors but we would like to suggest a complementary study for future directions. The VEGF gene encodes angiogenic protein and it is located at chromosome 6p21.1. Numerous SNPs in the promoter, 5'-, and 3'- untranslated regions (UTR) VEGF have been reported. Some of the more frequent SNPs involved in major solid tumour are well reported inclusive of rs2025039 (1), rs1570360 (2), rs699947 and rs2010963 (3), rs1570360 and rs8333061 (4). There is a serious need to study the role of these SNPs in congenital diaphragmatic hernia and pulmonary hypertension.


    1. Krippl P, Langsenlehner U, Renner W, et al.A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk. International Journal of Cancer2003;106:468–71. doi:10.1002/ijc.11238

    2. Howell WM, Rose-Zerilli MJ. Cytokine Gene Polymorphisms, Cancer Susceptibility, and Prognosis. The Journal of Nutrition2007;137. doi:10.1093/jn/137.1.194s

    3. Jin Q. Vascular Endothelial Growth Factor Polymorphisms in Relation to Breast Cancer Development and Prognosis. Clinical Cancer Research2005;11:3647–53. doi:10.1158/1078-0432.ccr-04-1803

    4. Gupta D, Gupta V, Singh V, et al.Vascular endothelial growth factor gene polymorphisms and association with age related macular degeneration in Indian patients. Meta Gene2016;9:249–53. doi:10....

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  • 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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