231 e-Letters

  • MRI is promising but not yet ready for routine use

    Magnetic resonance imaging (MRI) of the lung is an exciting field that is currently undergoing a period of rapid advancement. With its ability to measure lung function as well as structure, MRI stands to greatly improve our understanding of cystic fibrosis (CF) pathophysiology in children. However, there are still a number of significant hurdles to overcome if MRI is to become a tool for routine monitoring of paediatric CF lung disease.

    Compared to other commonly used modalities such as computed tomography (CT), spirometry, and multiple breath washout (MBW), MRI is considerably more expensive and, due to high demand, generally has long wait times for access. In addition, the cost of Helium for inhalation as a contrast agent is substantial, and due to diminishing reserves, access is likely to be more problematic in the future. The use of hyperpolarised gas requires expensive equipment that is not available in all centres, such as specially tuned radiofrequency coils and a gas hyperpolariser, as well as the expertise to run them [1]. The significant cost to set up and maintain such a system presents a huge barrier to entry for many CF centres, compared to the nearly universal presence of CT and lung function testing facilities.

    Standardisation of MRI between centres is challenging. Many sequences are protected under intellectual property law resulting in vendor-specific protocols, hampering comparisons between platforms [2]. Magnetic field inhomogeneity can lea...

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  • Diabetes control status and TB treatment response: confounded by treatment adherence?

    The paper by Yoon et al [1] addressees an important subject - diabetes mellitus (DM) probably increases the risk of TB by a factor of three [2]. The authors present data showing an association of poorer diabetes control status with both the characteristics of pulmonary TB at presentation, and the response to treatment. Compared to patients with no or controlled DM, those with uncontrolled DM reported worse symptoms at presentation, were more likely to be sputum smear positive, and had more substantial radiographic changes. Patients with uncontrolled DM were also more likely to remain sputum culture positive at two months, and either fail treatment or die.

    Although these observations are entirely consistent with a biologically plausible explanation that hyperglycaemia itself influences the development of TB and its response to treatment, there is an important confounding factor which may not have been fully accounted for: treatment adherence, and the wider general use of health care.

    Patients with uncontrolled diabetes, by definition, are less well treated than those with controlled diabetes. Part of the reason for this will be treatment adherence. Such patients may also be less well engaged with health services. Hence a reason for more advanced TB disease at diagnosis in those with uncontrolled DM compared to controlled or no DM might be due to later presentation to health services. Indeed, a recent study in China reported that patients with hyperglycaemia a...

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  • Response to Dr Aiello and others regarding the PEARL score

    We are grateful to the authors for their comments on the PEARL paper, especially those supporting our decision to assess outcome over 90 days. In regard to CODEX, most, but not all, patients had been hospitalised and, more importantly, death or readmission was not the primary outcome.1 Developed tools tend to be optimal for their primary outcome; a tool specifically designed to predict readmission/ death without readmission is likely to be a better predictor of this outcome than one that was not developed primarily for this purpose. This may, at least in part, explain the observed difference in performance. Prognostic tools should also undergo external validation. However, we acknowledge that the brevity of the abstract makes this unclear. At the editor’s discretion, we suggest the abstract could be amended to state: “no tool has been developed and externally validated…”

    We agree that data about mortality alone is relevant, and highlight that this is included in table E3 in the online supplement. The optimal predictors of death and readmission are not identical, although there is overlap. The reasons for including readmission or death without readmission as a combined outcome are: 1) they are competing risks, and assessing readmission alone would mean that death without readmission would be categorised as a favourable outcome; 2) a patient who would otherwise have died at home may be readmitted if they are identified as high risk and appropriate services are put in...

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  • Occupational pesticide exposure and respiratory health

    We read with great interest the recent study by Negatu et al. which illustrated significantly increased risks for respiratory troubles such as chronic cough and breath shortness and decreased lung functions in farm workers exposed to pesticide as compared to unexposed workers 1. However, the authors have not controlled for farming practices of both exposed and unexposed groups; did they use diesel-powered or gasoline-powered vehicles to plow their fields? Diesel exhaust may exacerbate, in particular, allergic airway inflammation 2 and thus could account for increased risk of adverse respiratory health. Also, pesticide could contribute to asthma exacerbation 3. Therefore, there might existed synergistic effects of pesticide and diesel exhaust particles on impaired respiratory health in exposed subjects as compared to unexposed ones (in particular, office workers) in their studies, which raise the possibility to exaggerate the results.

  • Response to 'Extracellular Vesicles Research in Lipopolysaccharide-induced Acute Lung Injury Model'

    Dear Editors

    We thank Dr Zhang and colleagues for their comments on our paper1. We certainly agree that in this emerging field of extracellular vesicle (EV) research, it is vital that identification and characterisation of different EV populations are as robust as possible. To this end, we very much welcome detailed discussions on methodologies used for each study, to enhance and improve the quality of EV-related work within the lung research community.

    In our paper, we specifically chose to examine the role of microvesicles (MVs) in acute lung injury (ALI), and the roles of apoptotic bodies and exosomes are beyond the scope of the study. We do not exclude the presence of apoptotic bodies or surfactant micelles in our in vivo samples, or indeed single or clustered MVs larger than 1µm, however our surface marker analysis of MV subpopulations by flow cytometry was deliberately conservative and limited to only events below the conventional size cut off of 1µm. Hence figure 3 of our paper shows effectively only one EV population, i.e. MVs. For our isolation of MVs for functional studies, we used differential centrifugation to enrich MVs but these technical matters were discussed in some detail in the published manuscript.

    Dr Zhang and colleagues have concerns about the dose of LPS (20µg) used in our in vivo ALI model. However, intratracheal (i.t.) instillation of high dose LPS (20µg or more per mouse) is a clinically-relevant, well established model of AL...

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  • Time to consider modifiable (especially motivational) determinants of physical activity among COPD patients? A commentary on Arbillaga-Etxarri et al. (2017)

    I read with interest the article published by Arbillaga-Etxarri et al.[1] titled “Socioenvironmental correlates of physical activity in patients with chronic obstructive pulmonary disease (COPD)”. In the introduction section, the authors stated that the current interventions (e.g., pharmacological treatment, rehabilitation, self-management) aiming to change physical activity behavior in COPD patients lack effectiveness, particularly in the long-term. The authors argue that this absence of effectiveness could be due to a lack of knowledge of physical activity determinants in this population. To address this issue, Arbillaga-Etxarri et al.[1] examined the socio-ecological determinants of active behaviours in 400 COPD patients and found that, after controlling potential confounders, having a dog and grandparenting were positively associated with physical activity; effects sizes were small, β = .19 and very small β = .08 for dog walking and grandparenting, respectively. The authors concluded that these two socio-environmental characteristics should be considered to promote physical activity both at the clinical level and in future research. This study is important because there is a lack of knowledge regarding the determinants of physical activity in this population.[2]

    Nonetheless, there are some reservations regarding the clinical utility of physical activity socio-environmental correlates to design physical activity programs. Socioenvironmental correlates of physica...

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  • Pearl score and death or readmission after hospialization for COPD.

    We commend Dr. Echevarria et al. for their excellent article, published in Thorax online (February 2017), concerning a new index (PEARL score) to predict the 90-day risk of death or readmission after hospitalization for an acute exacerbation of COPD (AECOPD). I agree with the authors on the relevance of 3 months’ prognosis after a hospitalization for AECOPD. Although policymakers usually consider 30-day readmissions as the marker of quality of care, only 36% of readmissions in COPD patients in this period are for a relapse, incomplete recovery, or a new COPD exacerbation. (1) The rest of readmissions in COPD patients are related with the deleterious complications associated with any hospitalization (post-hospital syndrome), especially in an aged population, with frequent comorbidities and often physical frailty. (2) In this sense, a 90-day time frame can probably better capture not only hospital and ambulatory quality of care, but also risk variables associated with readmissions in COPD patients. However, we believe that the article deserves some reflection.
    First, the authors stated that no tool has previously been developed in COPD to predict short-term readmission or death. This is only partially true. As they themselves note later, the CODEX index was specifically developed and validated to evaluate the risk of mortality, readmission, and their combination in the short- (3 months) or medium-term (1-year) after hospital discharge for AECOPD. (3)
    Second, the...

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  • Change in NEWS from emergency department to medical ward in patients with COPD

    We read the article by Hodgson LE, et al with interest. The authors examined the performance of National Early Warning Score (NEWS) for patients with an acute exacerbation of COPD. A limitation to this study was that the electronic scores (ward-based) were used as first NEWS - as the (paper) observations within the emergency department (ED) could not be included. We have reviewed data from our Hospital Trust of patients admitted with exacerbation of COPD (n=111), to determine whether NEWS scores from the ED department (paper records) differed from the first observation recorded on subsequent transfer to the acute medical wards (Electronic Patient Records). Admissions direct to ICU or HDU were excluded. Wilcoxon rank test was used to compare NEWS scores from ED to ward. Results are median (IQR).
    NEWS in ED fell from 6 (4-8) to 4 (3-6) on the acute medical ward (P<0.0001) over a mean time interval of 377 (sd 182) mins. The change in NEWS was due to a reduction in scores for respiratory rate and heart rate. Improvement in score for oxygen saturations was offset by scoring for use of oxygen.
    Not including the NEWS at presentation could underestimate risk of mortality, and hence contribute to the reduced sensitivity of NEWS that was observed in patients with COPD. Alternatively, utilising the NEWS at presentation to ED may lead to lower specificity in a patient with rapidly improving physiology.
    Harmonisation of data collection between ED and the hospital...

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  • A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation - Author response

    We thank Cardwell et al for their thoughtful comments on our paper.[1] The two alternative scoring systems did not demonstrate improved discrimination or calibration in our large dataset of AECOPD admissions. The authors suggest employing the Salford-NEWS only in patients ‘at risk’ of hypercapnic respiratory failure however, this introduces a subjective element that may negate the benefits of an objective physiological scoring system. As we emphasised in what we believe was a balanced discussion, patients with COPD should be managed in the right place by specialists and on-going education is crucial to avoid potential harms associated with misinterpretation of the NEWS alluded to by Cardwell and colleagues. Our article adds evidence that suggested RCP thresholds would indeed lead to unnecessary callouts in such patients. However, as we proposed, rather than abandon a scoring system that provides the significant advantages of standardisation and familiarity, it is possible to individualise patient management. For example, lowering observation frequency in a patient who is clinically ‘stable’, not increasing oxygen delivery if the prescribed target saturation is achieved, or taking into account prior/baseline physiology when deciding observation frequency and whether a senior review is required. Indeed a senior review may be appropriate to interpret whether the patient is at risk of hypercapnic respiratory failure and be able to advise on appropriate targets and level of mon...

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  • Extracellular Vesicles Research in Lipopolysaccharide-induced Acute Lung Injury Model

    Dear Editors,
    We are writing to comment on the work entitled “Alveolar macrophage-derived microvesicles mediate acute lung injury” published by Dr. Soni et al on Thorax 2016; 71:1020-1029[1].

    Our group focuses on lung extracellular vesicle (EV) research and also studied the inhaled LPS-induced EVs in mouse models. Based on our experience, we raise the following comments to the work done by Dr. Soni et al and wish to draw attentions to future EV researchers. EV research is a novel field and carries a promising potential for the development of diagnostic and therapeutic agents. However, given the early stage of EV research, particular in the field of lung injury, the consistency of results relies largely on the precise techniques used in the isolation and characterization of these vesicles.

    Briefly, EV is currently classified into three major categories per the definition of Society of extracellular vesicle research [2]. Apoptotic bodies (ABs) are the largest sizes of EVs usually larger than 1 µm and often resulted from cell death. Microvesicles (MVs) are the middle sized EVs (200 nm-1 µm) and are generated via plasma membrane budding. Exosomes (Exos) are the smallest EVs (less than 200 nm) and often generated from IVB-ER-Golgi system. Due to the different mechanisms of generation, MVs and Exos usually favor different compositions and subsequently may carry differential downstream biological functions[3 4]. For example, Exos have been reported to carry t...

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