313 e-Letters

  • Does vitamin D supplementation in patients with vitamin D deficiency improve quality of life?

    Asthma and chronic obstructive pulmonary disease (COPD) are two major obstructive lung diseases. Many epidemiological and genetic research including ours suggested possible association between vitamin D (VitD) and these diseases.[1 2] A meta-analysis by Jolliffe in 2019 demonstrated that VitD supplementation surely reduced the frequency of exacerbations in COPD patients who had VitD deficiency.[3] Vitamin D is an attractive option especially in developing countries because some of currently used medications such as bronchodilators and biologics are pricy. Given such background, VitD supplementation has been expected to be a new strategy for asthmatic patients with VitD deficiency. Thus, we read a report by Dr. Andújar-Espinosa et al. with a great interest.[4] The ACVID trial, a well-designed triple-blind randomized controlled trial (RCT), indicated greater improvement of quality of life (QOL) measured by Asthma Control Test (ACT) score as the primary endpoint, in the calcifediol arm compared to the placebo arm. Nonetheless, we have two concerns for this trial.
    First, there was a considerable discrepancy about the efficacy with previous reports. Inconsistency is a reason to degrade the quality of evidence.[5] Authors mentioned that "some beneficial association was observed in the group of patients receiving VitD compared with the placebo group" in all previous studies.[4] However, very limited data support the QOL improvement observed in ACVID trial. Dr. And...

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  • Accounting for regression to the mean

    We would like to thank Dr. Rosenthal for his comment on our research. Dr. Rosenthal highlights that a change in FEV will inevitably be negatively correlated with the initial value; otherwise known as regression to the mean. One important distinction with our work is that we calculated the conditional change score based on z-scores and thus demonstrate the changes that are greater than that predicted by regression to the mean. By calculating the conditional change using z-scores we change the scale which is used and account for this fallacy. Reporting the differences using Bland-Alman is an alternative approach but will be limited to analysis of fixed time-intervals and if the variability is constant across age and time.

  • Reply to: Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.

    To the Editor

    We thank Dr. Bhakta and colleagues for their interest in our article on the use of extracorporeal CO2 removal (ECCO2R) in patients with stable COPD and chronic hypercapnia (1).
    Bhakta et al. pointed out the role of non invasive ventilation (NIV) to treat chronic hypercapnic respiratory failure by improving alveolar ventilation. The Authors additionally argued that, in evaluating the efficacy of ECCO2R in hypercapnic COPD stable patients who have failed NIV therapy, we only concentrated on the hypercapnic rather than the hypoxic aspects, pointing out that in this population symptomatic relief and long-term CO2 reduction cannot occur without improved oxygenation.
    These points of discussion give us the opportunity to better explain the ECCO2R functioning and consequently the methodology of our study.
    ECCO2R refers to an extracorporeal circuit that is able to selectively extract carbon dioxide from blood with little to no effect on oxygenation. Various ECCO2R systems are now available. In addition to PaCO2 baseline level, the ability of different ECCO2R devices to eliminate CO2 is dependent upon two important determinants: 1) the surface area available for gas exchange and 2) the blood flow rate (2). Moreover, the partial pressure gradient of the gas across the membrane can be obtained by using oxygen or air as sweep gas, according to Fick’s law of diffusion. Because in minimally invasive veno-venous ECCO 2 R systems the ratio of catheter...

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  • Paediatric reproducibility limits for the forced expiratory volume in 1 s

    I was surprised to see figure 2 in the paper by Stanojevic et al (1) on assessing paediatric FEV1 reproducibility as, on the face of it, the authors may have fallen into a notorious statistical trap. A change in any variable (FEV1, blood pressure etc) is ALWAYS negatively correlated with the initial value because if x is initial value then y-x is the change, so inevitably related. If as an example one uses two separate sets of 100 normally distributed random numbers, each set with mean 100 and standard deviation 12 to mimic percent FEV1 and plot the first set as X against the difference between the two sets (Y-X) it will show an entirely spurious negative correlation (r = -0.7) with typically around 50% of the ‘variance’ explained. Altman(2) instead has recommended plotting a change against their average as an improved way of assessing the true relationship and using identical values, the spurious correlation disappears.

    1. Stanojevic S, Filipow N, Ratjen F. Paediatric reproducibility limits for the forced expiratory volume in 1 s. Thorax 2020;75:891-896.

    2. Altman DG. From: Practical statistics for medical research. Chapman and Hall, Boca Raton, USA. 1999:282-285.

  • Is the use of the Herder score valid in these guidelines?

    Dear Editors,
    This journal published the BTS guidelines for the management of pulmonary nodules in August 2015 (1), leading to widespread evidence-based management of this common clinical problem. The use of the Herder score (2) to estimate or predict the likelihood of malignancy has since become routine in lung cancer MDMs around the country.
    We therefore wish to highlight that the Herder prediction model was developed using the intensity of FDG uptake (absent, faint, moderate or intense) from the uncorrected PET images. However, as far as we are aware, lung cancer MDMs routinely assess the intensity of FDG uptake from the corrected images which is not in accordance with the original Herder model.
    The use of uncorrected images in the original Herder study (2) to distinguish between uptake categories potentially alters the perceived evidence base of the recommendations in the BTS guidelines (1) to distinguish between faint and moderate uptake according to mediastinal blood pool given that this scale of uptake was not used in the original score, has not been validated and could mean we are not using the correct category in the risk model.
    Furthermore, when considering the widespread use of the Herder score, it should be appreciated that it was formulated from patients scanned between 1997 and 2001. The Herder paper describes that “emission scans were acquired in a two-dimensional mode … and were reconstructed using ordered subset expectation maximisa...

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  • Congenital pulmonary airway malformations: what's new?

    We have read with interest the article by Taylor et al. concerning "the mechanism of lung development in the etiology of congenital malformations of the pulmonary airways in adults". The authors discussed the etiology of congenital malformations of the pulmonary airways, suggesting a partial modification of lung development with a potential risk of malignancy.

    Although we generally agree with their assessment, there are some weaknesses in their work that we would like to highlight as well as some points on which we would like to propose an alternative point of view. Different transcription factors known to be involved in lung development have already been studied in CPAM. Two of them, SOX2 and SOX9 are described as important in the spatiotemporal branching development since the pseudoglandular stage [1, 2]. In CPAM, SOX2 is present in both CPAM types (1 and 2), but their expression differs between them [3]. In addition, previously published papers have shown persistent SOX2 expression in healthy lung, which is not the case in this paper. Unfortunately, Talyor et al present "adult" samples and not adjacent healthy. However, this is not sufficient to explain these differences and classical tissues from children should have been included to demonstrate this point. Moreover, a difference in the cells forming the two types of CPAM has already been described by immunohistochemistry and proteomic results. Nevertheless these points are not addressed in t...

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  • Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.

    Title: Extracorporeal CO2 removal (ECCO2R) in patients with stable COPD with chronic hypercapnia: applying the concept.
    Pradipta Bhakta, Antonio M. Esquinas, Brian O’Brien.
    1. Dr. Pradipta Bhakta (MD, MNAMS, FCAI, EDRA, EDIC)
    Department of Anaesthesia and Intensive Care,
    University Hospital Kerry, Tralee, Kerry, Ireland.
    Phone: 00353894137596.
    Email: bhaktadr@hotmail.com
    2. Dr. Antonio M. Esquinas (PhD, MD)
    Department of Intensive Care,
    Hospital Morales Meseguer,
    Murcia, Spain.
    Phone: 0034609321966
    Email: antmesquinas@gmail.com
    3. Dr. Brian O’Brien [FCARCSI, FJFICMI, FCICM (ANZ)]
    Consultant and Chair,
    Department of Anaesthesia and Intensive Care,
    Cork University Hospital, Cork, Ireland.
    Mobile: 00353877931656
    Email: drbobrien@hotmail.com
    Authors and their role:
    1. Dr. Pradipta Bhakta: Was involved analysis of the article, writing and editing the letter.
    2. Dr. Antonio M. Esquinas: Was involved analysis of the article, writing and editing the letter.
    3. Dr. Brian O’Brien: Was involved analysis of the article, writing and editing the letter.
    Corresponding Author: Dr. Pradipta Bhakta,

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  • Sneeze is unrealistic

    The sneeze is depicted as horizontal, presumably for the camera. In a real sneeze, the head first tends to first tilt back, but during the actual sneeze, tends to point downwards. This means that large droplets tend to move toward the floor. Would have been nice to see a P2/N95 mask. Apart from that, a useful paper.

  • When to test for alpha-1 antitryspin deficiency in patients with bronchiectasis

    Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.

    The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.

    Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of t...

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  • Awake Prone Positioning in COVID-19 pneumonia: A useful strategy in patients not suitable for mechanical ventilation

    We read with interest the article by Koeckerling et al. (1) regarding ‘Awake Prone
    Positioning in COVID’. The authors have discussed the pros and cons of an
    intervention that is being widely used during the COVID-19 pandemic. Although
    we broadly agree with their assessment, there are some inaccuracies we would
    like to point out as well as a few issues where we would like to offer an
    alternative viewpoint:
    1. Koeckerling and colleagues (1) quote that 78% of patients with severe
    ARDS from a study by Ding et al (2) needed intubation. The original study
    was performed prior to COVID-19 pandemic and reported that 55% of
    patients with moderate to severe ARDS undergoing awake prone
    positioning in conjunction with high flow nasal oxygen (HFNO) /non-
    invasive ventilation (NIV) avoided intubation. All clinicians would agree that
    invasive mechanical ventilation should not be delayed in the face of a
    failing non-invasive intervention. The monitoring of the response to any
    treatment is key to determining the appropriate management plan.
    2. Koeckerling and colleagues report that CT scanning is essential to identify
    which patients would benefit from awake prone positioning but this may not
    be possible in view of the large numbers of patients. Gattinoni et al. do
    describe different phenotypes based on CT appearances, but this is to
    explain the pathophysiology of in different ph...

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