336 e-Letters

  • 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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  • Response to eLetter “What is the mechanism of pneumomediastinum?”.

    Dear Editor,

    We would like to thank Dr. Klepikov for his interest in our article [1], despite his dispute of the pathophysiology we presented. As it may be clearly understood from the article, our purpose was to present a relatively rare clinical case represented by a tension pneumomediastinum and not to evaluate its underlying pathophysiological mechanism. In our experience, this clinical scenario is extremely rare to face in a general thoracic surgery unit, but it has become more frequent in the last year due to SARS-CoV2 pandemic and the frequent use of high volume invasive ventilation in these patients [2,3]. The article [1] focuses on the most important aspects of the clinical case from the mechanical ventilation to the surgical therapy briefly mentioning the most likely mechanism of the origin of pneumomediastinum according to the peer-reviewed literature at hand [3,4]. As one can imagine an extensive and in-depth analysis of the pathophysiology of pneumomediastinum would be a difficult task to undertake in an article with a 500-word limit which aims to present our treatment of the condition.
    According to literature [2,3,4], different hypotheses have been proposed to explain the pathophysiology underlying spontaneous pneumomediastinum, but the most accepted one has been described by Macklin and Macklin [5]. The presence of a pressure gradient between the alveoli and the lung interstitium results in alveolar rupture and, if the pressure gradient is mainta...

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  • What is the mechanism of pneumomediastinum?

    Short comment to the article:
    Campisi A, Poletti V, Ciarrocchi AP, et al. (2020). Tension pneumomediastinum in patients with COVID-19. Thorax 2020; 75:1130-1131.
    Igor Klepikov*
    The authors describe a relatively rare complication that usually accompanies various diseases of the respiratory system and can significantly worsen the condition of patients. The fact that this complication occurs not only in patients with lung ventilation problems, but even in women in labor (1) suggests that an important trigger factor for this phenomenon is sudden attacks of increased intra-bronchial pressure. Such a sudden increase in air pressure in a confined space, according to Pascal's law (2), spreads evenly in all directions and can create an air flow to the surrounding tissues, damaging the weakest or previously damaged tissues.
    However, free air in the mediastinum has a clear anatomical localization, and its appearance is due to tissue damage in the area that has a common anatomical space and a free communication with the Central intra-thoracic space. In this regard, the mechanism of air penetration into the mediastinal fiber, which is described by the authors (3), automatically borrowing it from the assumptions of other researchers (4), looks, from my point of view, fantastic, far from real conditions.
    First of all, there is no objective evidence that air enters the mediastinum through the perivascular spaces as a result of damage...

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  • 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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