263 e-Letters

  • Changing the way we diagnose UIP: it’s all about probabilities

    I read with great interest the article “The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia”, by Brownell and colleagues [1]. The study has great methodological strength, and I applaud the authors for such an elegant work. But what really caught my attention was the clear use of pre-test probability and likelihood ratio to establish the diagnosis of usual interstitial pneumonia (UIP) in patients with suspected UIP. I believe this article should change the way we care for those patients.

    The study included patients with “possible UIP" and “inconsistent with UIP” patterns on high-resolution computed tomography (HRCT) of the chest. Those patients represent a diagnostic dilemma we commonly face in interstitial lung diseases clinical practice. Three different radiologists (two in the derivation and one in the validation cohort) reviewed the HRCT scans, and most importantly: they were blinded to clinical information and pathology results. All patients had the reference standard surgical lung biopsy, which were prospectively evaluated by expert pathologists.

    The likelihood ratio for male patients, with ≥ 60 years-old, and possible UIP with traction bronchiectasis score ≥ 4 was as high as 47 in the derivation cohort. Since likelihood ratios are a ratio of two likelihoods (the likelihood of a test results in disease / the likelihood of the same test result in no disease [2]), the further away from on...

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  • 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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  • Recovery needs friends!

    I have read the paper by McDowell et al with great interest. While the trial showed no significant improvement in the main outcome measure it is crucial to understand why. The intervention group had 30 patients who were recruited from 6 hospitals over a period of 3 years or in other words hospitals recruited 1-2 patients per year who had personalised (lonely) exercise sessions. Outcomes from rehabilitation of COPD are thought to be driven by a multi-disciplinary approach [1] and peer-support from fellow patients [2]. The latter is likely to improve resilience [3] and impact on overall self-reported quality of life.
    [1] Griffiths TL, Burr ML, Campbell IA, Lewis-Jenkins V, Mullins J, Shiels K, Turner-Lawlor PJ, Payne N, Newcombe RG, Ionescu AA, Thomas J, Tunbridge J. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial. Lancet. 2000 Jan 29;355(9201):362-8.
    [2] Poureslami I, Camp P, Shum J, Afshar R, Tang T, FitzGerald JM. Using Exploratory Focus Groups to Inform the Development of a Peer-Supported Pulmonary Rehabilitation Program: DIRECTIONS FOR FURTHER RESEARCH. J Cardiopulm Rehabil Prev. 2017 Jan;37(1):57-64.
    [3] Bradley-Roberts EM, Subbe CP. Role of Psychological Resilience on Health-Outcomes in Hospitalized Patients with Acute Illness: A Scoping Review. Acute Med. 2017;16(1):10-15.

  • 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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