66 e-Letters

published between 2018 and 2021

  • Response to correspondence (Jackson et al. Thorax 2021)

    The influence of obesity on both asthma and T2 biomarkers remains poorly understood and we fully agree this requires further investigation, as does the relationship between obesity, depression and persistent symptoms of breathlessness. However, the data correlating obesity and FeNO is conflicting and the reported weak positive associations have often not been adjusted for corticosteroid dose and may simply reflect higher doses of corticosteroid therapy in more breathless obese patients than by those of normal weight, rather than a specific mechanistic relationship.
    Moreover, the UKSAR population appears very different from the cohorts described in some of these reports. For example, the average FeNO was only 25ppb in the Komakula study, whilst in the study by Lugogo subjects were predominantly T2-low across all BMI categories: the upper quartile value of blood eosinophils in both lean and obese groups was <300 cells/µL, whilst the upper quartile of FeNO in both lean and obese groups was <30ppb. In contrast, even in the UKSAR T2 high cohort, the mean BMI was in the obese range.
    The nature and veracity of the ‘T2-low’ phenotype remains unclear, particularly in severe asthma. What is increasingly apparent is that patients are frequently prescribed high dose inhaled and systemic corticosteroids for respiratory symptoms, which suppresses T2 inflammation in the process. In the context of obesity and other co-morbidities known to be associated with increased re...

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  • Erector spinae muscle area is not associated with mortality in the COPDGene cohort

    We thank Tanimura and colleagues for their thoughtful commentary on our recent manuscript, “Respiratory exacerbations are associated with muscle loss in current and former smokers” and read their analysis of erector spinae muscle area (ESMA) with interest (1). In their commentary, they note that muscle loss can occur heterogeneously, with the greatest expected impact on the muscles of ambulation. They suggest that erector spinae muscles, due to their fiber composition and anti-gravity role, are a better reflection of inactivity-related muscle loss and posit that changes in pectoralis muscle area (PMA) may only reflect changes in nutrition (as measured by body mass index, BMI).

    We agree that muscle loss is unlikely to be uniform; however, a disconnect has been reported between the postural muscles of the trunk and ambulatory muscle (e.g. quadriceps) weakness, despite similar fiber types (2). Few studies measure both groups of muscles simultaneously, but there is evidence that inspiratory force is more affected than peripheral muscle force in patients with COPD; implying that deconditioning is not the sole driver of muscle dysfunction (3). While the pectoralis muscle potentially underestimates inactivity-related atrophy, these studies suggest its role as an accessory muscle of inspiration makes it a reasonable target for capturing any underlying systemic process.

    In contrast to Tanimura et al’s findings, in the COPDGene participants (n=8,603) BMI was more stro...

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  • Letter to the editors

    We read with interest the recent paper from DJ Jackson et al, “Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era” [1], and share their concerns regarding the risk of excessive corticosteroid exposure in T2-low individuals. We congratulate the authors for gathering such an extensive range of data in this large cohort of people with severe asthma, enabling meaningful comparisons, particularly between biologic and non-biologic populations. We echo the call for further work to identify and validate pragmatic T2-low endotype-specific biomarkers through clearer understanding of this inflammatory cascade. This cohort of patients continues to be under-served, made all the more evident by the paucity of novel therapies in this era of precision medicine.
    We note the authors’ comments on T2-biomarker increase with corticosteroid dose reduction, and the presence of a historic T2-high profile in some individuals from the T2-low group. Whilst the postulated explanation reported by the authors, one of corticosteroid-induced T2-biomarker suppression, is undoubtedly a key factor (and indeed supported by the significant difference in corticosteroids between the groups), we would suggest another important factor that may be relevant to the understanding of the T2-low pathway.
    The authors report a significant difference in BMI between T2-high and T2-low groups (30.2kg/m2 and 32.1kg/m2 respectively, P-value = <0.001). Whilst the...

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  • Frequent exacerbations of COPD can contribute to accelerated loss of antigravity muscles rather than pectoralis muscles

    To the editor,

    We read the interesting report by Mason et al, “Respiratory exacerbations are associated with muscle loss in current and former smokers”.[1] In this study, the authors demonstrated that exacerbations are associated with accelerated loss of pectoralis muscles (PMs) in two large observational cohorts and quantified the impact of each annual exacerbation as the equivalent of 6 months of age-expected decline.
    Skeletal muscle loss is one of the major systemic manifestations associated with mortality in patients with COPD. Not only systemic muscle loss but also loss of specific muscle groups are associated with clinical outcomes such as exacerbations and mortality in patients with COPD.[2, 3] Moreover, muscle loss can occur heterogeneously.[4] This may be partially because each muscle group has its physiological function or biological characteristics such as muscle fiber composition. This supports that loss of specific muscle groups may have different implications in the clinical course of COPD.
    We previously analyzed the cross-sectional area of erector spinae muscles (ESMCSA) and that of PMs (PMCSA) in male patients with COPD using chest CT.[3] ESMs are ones of antigravity muscles which are involved in maintaining an upright posture. PMs play an important role in the movement of upper limbs. Both muscles also act as accessory inspiratory muscles. ESMs are composed of 60% type 1 fibers and 40% of type 2 fibers and PMs are composed in the reverse...

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  • Current smoking as a risk for COVID-19

    We thank the authors for their letter in response to our paper(1). We disagree however that the data among the tested subgroup are more informative than our other findings. This is because the small subgroup (1.1% of app users - 0.7% negative, 0.3% positive, 0.1% result unknown) who reported that they had undergone testing for COVID-19 at this relatively early stage in the pandemic (the month from 24th March 2020) were heavily selected. Testing policies focused on healthcare workers and others interacting with healthcare - in particular, patients tested who may have been attending healthcare settings for other, non-COVID-19 related, conditions. As numerous health conditions are smoking-related this would tend to increase the exposure of smokers without COVID-19 to testing. For these reasons, as discussed in the paper, the finding that smoking rates were lower in those testing positive is likely to be due to sampling bias. Rather than being “more relevant”, extrapolation from this subgroup to population risk is entirely inappropriate.
    The letter does appear to misunderstand the groups presented – the “standard user” group were not asymptomatic during the study. Rather, as set out in the first paragraph of the results, they were individuals who at the point of registration with the Zoe COVID Symptom Study App did not think that they already had COVID-19. Among this group of “standard users” current smokers were more likely to report the onset of new symptoms suggesting...

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  • Understanding the differences in impact of public health measures on hospital admissions for COPD exacerbations during the COVID-19 pandemic

    We thank Brennan et al, for sharing their experiences. In contrast to our observed reduction of more than 50% in AECOPD hospital admissions over a 6-month period, Brennan and colleagues observed a reduction of only 18% over a 4-month period. In addition, while we saw a significant and sustained decrease, Brennan et al. observed a decrease only in the first month following lockdown. At the fundamental level, respiratory viruses can spread either via contact, droplet or aerosols[1] and thus in theory mask wearing, social distancing and increased personal respiratory etiquette and community hygiene would reduce transmission and contribute to reduced incidence of AECOPD. The use of masks has been shown to reduce exposure to acute respiratory viruses by 46%[2].

    We hypothesise that these differences could potentially be due to variations in the degree of adherence to mask wearing/social distancing, as well as nuances in public health measures introduced in various countries during the COVID-19 pandemic.
    For instance, Singapore had mandated face-mask wearing in April 2020. The observations reported by Brennan et al terminated in June 2020 while Ireland only mandated face-mask wearing in August 2020. and hence may not have captured the impact of compulsory mask wearing. The difference in timing of implementation and enforcement of government policies during the COVID-19 pandemic possibly contributed to a different experience in Ireland.

    Aside from early impleme...

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  • ‘Better safe than sorry’

    With great interest we have read the study by Deshayes et al. The authors present two cases of silvernitrate (AgNO3) aspiration in laryngectomized patients.
    1) In both cases the applicator tip broke off.
    2) The authors conclude that treatment should comprise oral antibiotics and one should refrain from bronchial washing with sodium chloride solution.
    With this response we would like to reply to both points addressed above.
    Five years ago we were confronted with the aspiration of an AgNO3 applicator tip in a laryngectomized patient. After the incident we analyzed the case to prevent future AgNO3 applicator tip aspiration. The AgNO3 pencil, used in both our case and the cases in the current article, is specifically designed to treat dermal lesions like verruca which requires repeated use. The pencil therefore contains a relatively large volume of AgNO3. AgNO3 is a brittle substance. When the pencil is used with a little too much pressure there is risk for the tip to break, and when used in a tracheostomy, there is risk for aspiration.
    Our case led us to immediately stop using the AgNO3 pencils for treatment of granulation tissue in a tracheostomy. We strongly recommend the use of disposable AgNO3 cutaneous sticks for the treatment of granulation tissue around a tracheostomy. The disposable sticks contains less volume of AgNO3. Moreover, the stick is easier to use in narrow spaces like a tracheostomy.
    Aspiration of AgNO3 i...

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  • Reduction in hospital admissions for Acute Exacerbations of COPD during COVID-19- A Different Experience

    We read with interest the recent study by our colleagues Tan et al (1) which reported the introduction of public health measures during the pandemic, such as social distancing and universal mask wearing, were observed to coincide with a marked reduction in transmission of other circulating respiratory viral infections. They reported a reduction in hospital admissions with acute exacerbation of COPD (AECOPD) by over 50% during the six month period of the pandemic from February to June 2020. They supported this observation with microbiological data showing a significant reduction in PCR-positive respiratory viral infections compared to the pre-pandemic era.

    Ireland has the highest rate of hospitalisations for AECOPD in all OECD Countries (2). The first case of COVID-19 in the Republic of Ireland was reported on 29/02/2020 and stringent public health measures were introduced in mid-March to combat the spread (3).
    We wish to describe our experiences of hospital admission with AECOPD during the first wave of the pandemic in a tertiary referral hospital in the West of Ireland. In our clinical practice, we noticed a reduction in patients admitted with COPD exacerbations at the beginning of the pandemic. We aimed to evaluate the impact of these infection control measures on our COPD population.

    We conducted a retrospective cohort study of electronic health care records of patients who were hospitalised with a primary diagnosis of AECOPD over the four-month per...

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  • Symptom app data are consistent with smokers having increased risk of COVID-19-like symptoms, but a decreased risk of actual SARS-CoV-2 infection

    The paper by Hopkinson et al (1) provides unique and important data on smoking prevalence and COVID-19 symptoms, but their conclusion does not reflect the data well. The authors conclude “these data are consistent with people who smoke being at an increased risk of developing symptomatic COVID-19”. The study includes over 150,000 people with self-reported COVID-19 symptoms and over two million without such symptoms. It also includes data on over 25,000 people who were tested for SARS-CoV-2 and their test results. Based on our analysis of these more relevant data, we interpret the study differently. Our conclusion would be “these data are consistent with smokers having an increased risk of symptoms such as cough and breathlessness, but a decreased risk of having SARS-CoV-2 infection”.

    The difficulty in interpreting these results is that both symptoms and testing are likely colliders in a causal model of smoking and COVID-19. The data reported on SARS-CoV-2 test results make it possible to compare smoking prevalence by age-group and sex in three groups: those who tested positive for SARS-CoV-2 (n=7,123); those who tested negative (n=16,765); and untested asymptomatic users (n=2,221,088, called “standard users” by the authors). Overall smoking prevalence was less in those tested (8.9%) than in all users of the app (11.0%). This might be thought of as a surprising finding – smoking-related symptoms should lead to testing – but can probably be explained by most asymptom...

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  • Improving the quality of life in asthmatic patients supplemented with vitamin D: variability in the studies and discrepancy in the results.

    Vitamin D could have potentiating effects on the innate and adaptive immune system (1). This would explain a potential defense effect against respiratory infections. Based on this, this vitamin has been linked to respiratory diseases such as COPD, asthma, respiratory infections and even lung cancer (2). In November 2020, our work team published the ACVID randomized clinical trial, and we have received a letter from Dr. Nobuyuki Horita asking us two questions about our results. In the first place, he lists a series of studies that show a great discrepancy in the results on quality of life, requesting our opinion on this discrepancy. Second, he asks for our opinion on the results of our work in terms of improving quality of life without an increase in lung function.
    The authors continue to maintain that “some beneficial association was observed in the group of patients receiving vitamin D compared to the placebo group” in the studies analyzed in our article. In fact, in the VIDA research (3) the authors describe a small but significant association with the decrease in the dose of ciclesonide required to maintain asthma control in the vitamin D group. It is true that in this study the quality improvement Life is better in the control group, but this is a secondary objective. In the ViDiAs study (4) the authors found no significant differences in the reduction of asthma attacks or upper airway infections (coprimary outcomes), but, although they did not find clinical impr...

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