309 e-Letters

  • Reply to: Referral to pulmonary rehabilitation (PR) by a current PR practitioner has no effect on PR completion rate

    We thank Dr Abdulqawi for interest in our work (1). He comments that the referral, uptake and completion rates for pulmonary rehabilitation in the current study were lower than in a previous study by Jones and colleagues (2). We would caution against retrospective comparison with unmatched historical controls due to confounding factors such as differences in patient characteristics and practice pathways that may contribute to inaccurate point estimates.

    We hypothesised that the COPD discharge bundle would impact on referral rates. Strengths of the current work include the prospective real-world nature of the study, with the research team having no involvement in treatment allocation. The clinical team delivering the bundle were blinded to the study objectives, thus minimising any Hawthorne effect.

    Dr Abdulqawi raises the point that pulmonary rehabilitation completion rates were low in the current study (albeit based on a low denominator). The reasons for non-completion of PR are often complex and multi-factorial (3) and may not be directly related to referral source. However, what is clear is that without a referral for pulmonary rehabilitation, uptake and completion rates are zero.

    1. Barker RE BL, Maddocks M, Nolan CM, Patel S, Walsh JA, Polgar O, Wenneberg J, Kon SSC, Wedzicha JA, Man WDC, Farquhar M. Integrating Home-Based Exercise Training with a Hospital at Home Service for Patients Hospitalised with Acute Exacerbations of COPD: Developing the M...

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  • Dog bites man - COVID-19 and smoking.

    The idea that smoking might have a protective effect against COVID-19 is an intriguing, man bites dog type of story, which gives it a certain attraction. Happily, it appears to be false and the assumption of harm has turned out to be correct[1-5].
    Our data show clearly that in the 2.4 million Zoe COVID Symptom Study App users, people who smoked were at increased risk of symptomatic COVID-19[2] and were at risk of more severe disease, which is consistent with a systematic review of patients hospitalized with COVID-19[4]. Our findings are also consistent with The UCL COVID-19 Social Study3 which found increased risk of test confirmed COVID-19 (OR=2.14 (1.49–3.08)) and with the COVIDENCE study where smokers had an OR of1.42 (0.99-2.05) for test-confirmed COVID-19[1].
    The OpenSafely dataset based on data from the primary care records of 17.3 million adults in the UK found that, adjusted for age and sex, also identifies smoking as a risk factor - current smoking was associated with a hazard ratio for COVID-19-related death of 1.14 (1.05–1.23)5. The apparently protective effect in the “fully adjusted” model is due to over-correction producing collider bias.
    Since any protective effect of smoking in COVID-19 appears to be illusory, pursuing a mechanism for it is unlikely to be productive.

    1 Holt H, Talaei M, Greenig M, et al. Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK). medRxiv 2021:2021.2003...

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  • Referral to pulmonary rehabilitation (PR) by a current PR practitioner has no effect on PR completion rate

    We have read the paper by Barker et al. (1) with interest. We congratulate the authors for conducting and publishing their prospective cohort study evaluating the effect of COPD discharge bundle on pulmonary rehabilitation (PR) referral and uptake following hospitalisation for acute exacerbation of COPD (AECOPD).

    The authors have shown that the COPD discharge bundle had a positive effect on PR referral compared with a no bundle (17.5% (40 of 228) referral rate vs 0%(0 of 63)). This figure is lower than the expected 30% referral rate to PR following AECOPD (2). However, the paper offers no potential reasons for the lower referral rate.

    The study had two bundle groups:
    • COPD discharge bundle delivered by a current PR practitioner
    • COPD discharge bundle delivered by a practitioner with no involvement in PR

    Compared to delivery by a practitioner with no PR involvement, completion of the bundle delivery by a current PR practitioner resulted in higher referral and pick-up rates (60% vs 12% and 40% vs 32%, respectively). These results support the concept of integrating PR and hospital services.

    Unfortunately, the completion rate (number of subjects who completed PR divided by the number of referrals) was disappointingly low. Also, there was no difference between the two bundle groups (13% (2 of 15) vs 12% (3 of 25)), as stated in the supplementary data.

    It seems that patients' willingness or ability to complete PR is not af...

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  • Current smoking as a risk factor for COVID-19

    There is no question that the harms of smoking hugely outweigh any potential health benefits. Many people, ourselves included, assumed at the beginning of the pandemic that greater susceptibility to COVID-19 would be another harm of tobacco smoking to be added to the long list. Surprisingly, most of the epidemiological data published over the last year do not support this claim. Indeed whereas ex-smokers are consistently found to be at increased risk of both SARS-CoV-2 infection and severe COVID-19, current smokers are consistently at lower risk than ex-smokers and in many studies they appear to be at a lower risk than never smokers. The lower infection rate in smokers compared to non-smokers and ex-smokers has been found across 62 studies (1, 2), including now a full cohort with a dose-response pattern (3).

    The authors’ response does not counter the observation that among nearly 27,000 individuals who had a SARS-CoV-2 test in their study, smoking prevalence was lower in those who tested positive than in those who tested negative.

    In the OpenSAFELY study (4) too, the direction of the association between smoking and death from COVID-19 depends critically on what adjustments are made. The primary analysis appears to be based on a fully adjusted Cox regression model in which the hazard ratio for current smokers relative to never smokers was 0.89 (95% CI 0.82-0.97). The value (1.14; 1.05-1.23) cited by Hopkinson and colleagues is after adjusting for age and sex...

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  • 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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