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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...
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 are more likely to delay presenting to health services with symptoms of pulmonary TB [3].
And at least part of the reason for delayed sputum culture conversion in uncontrolled DM in the current study could be poorer adherence to TB treatment. Although this was not entirely borne out by the data, there was a suggestion of poorer treatment compliance in patients who remained culture positive at two months compared to those who did not (Table 3; p=0.22). It is not clear from the paper how TB treatment compliance was associated with DM control status. Neither is it clear precisely what methods were employed by the TB nurse in the study to assess treatment adherence.
So although the findings of Yoon et al support a direct effect of diabetes control status on TB presentation and treatment response, further work is required to exclude the potential confounding effects of delayed presentation of TB and adherence to treatment. Health records could be used to assess level of engagement with health services prior to the TB diagnosis, and directly-observed TB treatment in all study subjects could address potential compliance issues.
References:
1. Yoon YS, Jung JW, Jeon EJ et al. The effect of diabetes control status on treatment response in pulmonary tuberculosis: A prospective study. Thorax. 2017; 72: 263–70.
2. Jeon CY, Murray MB. Diabetes mellitus increases the risk of active tuberculosis: A systematic review of 13 observational studies. PLoS Med. 2008; 5: e152.
3. Wang Q, Ma A, Han X et al. Hyperglycemia is associated with increased risk of patient delay in pulmonary tuberculosis in rural areas. J Diabetes. 2017; 9: 648–655.
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.
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...
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 place; and 3) hospital admission may prevent death. One way to analyse readmissions alone without including death as a favourable outcome would be to exclude those that died. However, this would bias the population by excluding those at higher risk of readmission. We plan to separately publish data on long-term predictors of death.
We acknowledge the difficulties diagnosing heart failure with preserved ejection fraction, previously termed diastolic heart failure, and its prevalence in this population. However, this does not carry the same mortality risk as left ventricular dysfunction. We separately assessed heart failure as a clinical diagnosis alone (without the need for evidence of reduced left ventricular function on echocardiography); this did not have the same predictive power as left ventricular failure. Consequently, left ventricular failure based on echocardiogram results was appropriately selected. We also highlight the European Society of Cardiology position: “Echocardiography is the most useful, widely available test in patients with suspected HF to establish the diagnosis.”2
The Charlson Index comprises of 19 indices and is a component of CODEX and LACE. The PEARL index includes only two measures of co-morbidity (individually shown to be strong predictors of outcome), and was superior to LACE in all three cohorts, and to CODEX in two of three cohorts. It is clear that the PEARL score is more parsimonious than scores containing the Charlson index, and therefore it is easier to score. Furthermore, it can be recalled and calculated at the bedside. Whilst we agree that ideally a full medical history should be performed in all patients, the more indices that appear in a score, the more likely that there will be missing data leading to biased estimates.
1. Almagro P, Soriano JB, Cabrera FJ, et al. Short- and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index. Chest 2014; 145(5): 972-80.
2. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016; 18(8): 891-975.
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.
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...
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 ALI, used very widely by investigators in ALI research including ourselves2-5. Dr Zhang stated that large doses of LPS often result in release of apoptotic bodies but few MVs from alveolar macrophages, but we wonder if this statement is based on in vitro experiments using non-primary cells, rather than in vivo ALI models? Dr Zhang’s group recently showed6 the production of apoptotic bodies with 1µg LPS treatment, but their results were obtained using an immortalised cell line (MH-S alveolar macrophages) in vitro, rather than primary alveolar macrophages in vivo. Interestingly, they observed that apoptotic body production peaked later (at 6 hours) when primary cells (bone marrow derived macrophages) were treated with LPS in vitro, highlighting a clear difference between primary cells and immortalised cell lines (such as RAW cells, THP-1 and MH-S cells)6. While we cannot entirely exclude the possibility that some apoptotic bodies were produced within our model, it has been shown that i.t. LPS in vivo does not initiate apoptosis of alveolar macrophages until much later time points7,8. Taken together, we believe that concerns regarding apoptotic bodies influencing our conclusions are unsubstantiated for the acute responses investigated in our model. This is of course not to say that the release of apoptotic bodies or other EVs does not play an important role during subsequent phases of ALI pathophysiology.
Sanooj Soni, Michael R Wilson, Kieran P O’Dea, Masao Takata
Section of Anaesthetics, Pain Medicine & Intensive Care, Imperial College London, UK
1. Soni S, Wilson MR, O'dea KP, et al. Alveolar macrophage-derived microvesicles mediate acute lung injury. Thorax 2016;71(11):1020-29.
2. Woods SJ, Waite AA, O'Dea KP, et al. Kinetic profiling of in vivo lung cellular inflammatory responses to mechanical ventilation. American Journal of Physiology-Lung Cellular and Molecular Physiology 2015;308(9):L912-L21.
3. Gong J, Wu Zy, Qi H, et al. Maresin 1 mitigates LPS‐induced acute lung injury in mice. British journal of pharmacology 2014;171(14):3539-50.
4. Islam MN, Das SR, Emin MT, et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature medicine 2012;18(5):759-65.
5. Dorr AD, Wilson MR, Wakabayashi K, et al. Sources of alveolar soluble TNF receptors during acute lung injury of different etiologies. Journal of Applied Physiology 2011;111(1):177-84.
6. Zhu Z, Zhang D, Lee H, et al. Macrophage-derived apoptotic bodies promote the proliferation of the recipient cells via shuttling microRNA-221/222. Journal of Leukocyte Biology 2017:jlb. 3A1116-483R.
7. Vernooy JH, Dentener MA, Van Suylen RJ, et al. Intratracheal instillation of lipopolysaccharide in mice induces apoptosis in bronchial epithelial cells: no role for tumor necrosis factor-α and infiltrating neutrophils. American journal of respiratory cell and molecular biology 2001;24(5):569-76.
8. Kearns MT, Barthel L, Bednarek JM, et al. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation. American Journal of Physiology-Lung Cellular and Molecular Physiology 2014;307(1):L62-L70.
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...
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 physical activity are often largely beyond participants’ control and thus non-modifiable during an intervention for a clinician, such as the ‘walkability’ of the environment. For example, in the current study, only 18 % of the sample had a dog and 12% of the participants reported walking it. The authors explained that patients could have concerns about dogs such as difficulties with controlling the animal, which could explain the lack of dog owners in the study. It could also be hypothesized that patients have a dog because they are already active and feel capable of owning a dog. Nevertheless, it could be difficult to use this leverage during a physical activity counseling intervention.
Physical activity is a complex behavior that may depend from many different factors, such as socio-environmental variables (e.g. age, family support), biological functions (e.g. functional capacity), or environmental factors (e.g. climatic conditions; ‘walkability’ of the environment). Among these potential predictors of physical activity there is an urgent need to identify factors that could be modifiable during an intervention. In this regard, the concept of motivation is an important target.
Motivation could be operationalized through different theoretical constructs, which have received different levels of empirical support regarding their associations with physical activity behaviour depending on the context [3]. These constructs could be clustered into (1) intentional processes (the development of objectives and intentions to be active), (2) affective judgments (feelings about physical activity) (3) self-perception of capability and opportunity (confidences in one’s capacity to be active) (4) self-regulation processes ( strategies used to maintain motivation and dealing with barriers) and (5) automatic or unconscious processes (physical activity habits driven by feelings about physical activity). Methodologically, these processes are often measured through either self-reported questionnaires [4] or computerized reaction-time tests.[5] To date, research dealing with motivational processes toward physical activity for patients with chronic respiratory disease are scarce. Selzler et al [6] found that stronger physical activity-specific self-efficacy was positively associated with exercise attendance, as well as 6-minute walk test improvement during pulmonary rehabilitation. Chevance et al [7] highlighted that unconscious feelings (measuring with computerized test) about physical activity prospectively predict self-reported physical activity at 6 months after pulmonary rehabilitation. These preliminary results are important because identifying modifiable determinants of physical activity could help (i) to motivate patient to integrate a program, or identify patient at risk to failing physical activity after an intervention and (ii) to design more effective evidence-based interventions regarding physical activity in COPD patients. In conclusion, future studies should consider the motivational determinants of physical activity as well as interventions to specifically enhance motivation.
Acknowledgments : I sincerely thank Anne-Marie Selzler for their comments
References
1. Arbillaga-Etxarri A, Gimeno-Santos E, Barberan-Garcia A, et al. Socio-environmental correlates of physical activity in patients with chronic obstructive pulmonary disease (COPD). Thorax, forthcoming. doi: 10.1136/thoraxjnl-2016-209209.
2. Gimeno-Santos E, Frei A, Steurer-Stey C, et al. Determinants and outcomes of physical activity in patients with COPD: a systematic review. Thorax, 2014;69: 731-39. doi: 10.1136/thoraxjnl-2013-204763.
3. Rhodes R. The Evolving Understanding of Physical Activity Behavior: A Multiprocess Action Control Approach. Advances in Motivation Science, 2017;4:171-205. doi: 10.1016/bs.adms.2016.11.001.
4. Rodgers W, Wilson P, Hall C, et al. Evidence for a Multidimensional Self-Efficacy for Exercise Scale. Res Q Exerc Sport, 2008;79:222-34. doi:10.1080/02701367.2008.10599485.
5. Chevance G, Heraud N, Guerrieri A, et al. Measuring implicit attitudes toward physical activity and sedentary behavior: Test-retest reliability of three scoring algorithms of the Implicit Association Test and Single Category-Implicit Association Test. Psychology of Sport and Exercise, 2017;31:70-8. doi: 10.1016/j.psychsport.2017.04.007.
6. Selzler A, Rodgers W, Berry T, et al. The importance of exercise selfefficacy for clinical outcomes in pulmonary rehabilitation. Rehabil Psychol, 2016;61:380-8. doi: 10.1037/rep0000106
7. Chevance G, Héraud N, Varray A, et al. Change in Explicit and Implicit Motivation toward Physical Activity and Sedentary Behavior in Pulmonary Rehabilitation and Associations with Postrehabilitation Behaviors. Rehabil Psychol, forthcoming. doi: 10.1037/rep0000137.
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...
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 authors only analyse the combination of death or readmission. Clearly both are relevant events for the patients, but their impact is obviously different, and no data about mortality are detailed in the article. In our opinion, it would be more illustrative to analyse PEARL score separately for deaths, readmissions (excluding deceased patients without readmissions), and the combined variable. This is especially important in the follow-up at 1 year, represented in Figure3B of the article.
Third, the authors based the diagnosis of left ventricular failure (LVF) on echocardiographic results. However, heart failure is a clinical syndrome and not an echocardiographic diagnosis. This is especially important in heart failure with preserved ejection fraction, the most frequent cause of heart failure in aged patients with comorbidities. In these patients, echocardiographic evaluation is more difficult and less reliable. (4) The diagnosis of LVF based exclusively on echocardiographic results can exclude patients with heart failure without previous echocardiogram or with indeterminate results. This would explain the low prevalence of left ventricular failure observed in the present study compared with previous publications. (3,5)
Finally, the authors point out as a limitation of the CODEX and LACE indexes the requirement to calculate the Charlson index. We have doubts with this statement. The Charlson index is the most widely recognized prognostic index of comorbidity. It is easy and quick to calculate and in fact the variables included (previous chronic diseases) must be collected in any medical history.
1.-Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360:1418-28.
2.-Krumholz HM. Post-hospital syndrome--an acquired, transient condition of generalized risk. N Engl J Med. 2013;368(2):100-2.
3.- Almagro P, Soriano JB, Cabrera FJ, et al. Short- and medium-term prognosis in patients hospitalized for COPD exacerbation: the CODEX index. Chest. 2014;145:972-80.
4.- Ponikowski P, Voors AA, Anker SD, et al.2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 ;18:891-975.
5.-Roversi S, Fabbri LM, Sin DD, Hawkins NM, Agustí A. Chronic obstructive pulmonary disease and cardiac diseases. An urgent need for integrated care. Am J Respir Crit Care Med. 2016;194:1319-1336.
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...
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 ward is needed so that these questions may be addressed.
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...
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 monitoring for the individual with subsequent avoidance of alarm fatigue.
1. Hodgson LE, Dimitrov BD, Congleton J, Venn R, Forni LG, Roderick PJ. A validation of the National Early Warning Score to predict outcome in patients with COPD exacerbation. Thorax 2017;72(1):23-30 doi: 10.1136/thoraxjnl-2016-208436.
2. Prytherch DR, Smith GB, Schmidt PE, Featherstone PI. ViEWS--Towards a national early warning score for detecting adult inpatient deterioration. Resuscitation 2010;81(8):932-7 doi: 10.1016/j.resuscitation.2010.04.014.
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...
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 the very minimal amount of popular microRNAs (miRNAs). Even for those most promising miRNA markers, less than 1 copy of miRNA can be found in each Exo[5]. This is part of the reason why the classification of EVs may be important.
In the work presented by Dr. Soni et al, a very large dose of LPS (20 μg per mouse) has been delivered to mice via intratracheal instillation. Certainly, different batch of LPS may carry different levels of potency. However, we found that the larger dose of LPS often quickly resulted in the release of ABs but rather than MVs by alveolar macrophages. In our experiences, as little as 1 μg LPS (Sigma-Aldrich, cat #L2630, St. Louis, MO, USA) resulted in the robust amount of MVs (about 50% in total EVs). However, a fair amount of Exos (about 25% in total EVs) is still mixed in the LPS-induced EVs. Additionally, the FACS analysis presented in figure 3 shows only one population of vesicles. This could be due to the overly too large dose of LPS and the detected EVs fall mainly on the range of ABs. In our experience, using a smaller dose of LPS, we often clearly observe two different population of EVs, one belongs to the larger size of ABs, and the other belongs to the smaller MVs.
We recognize that the variability of results could result from different technique, detecting apparatus, different batch of LPS and also different size/age/strain of mice. However, we would like to discuss our findings on this emerging novel topic and our comments may be found interesting and useful by other audience.
Thank you for your time and attention!
REFERENCES
1. Soni S, Wilson MR, O'Dea KP, et al. Alveolar macrophage-derived microvesicles mediate acute lung injury. Thorax 2016;71(11):1020-29. doi: 10.1136/thoraxjnl-2015-208032
2. Gyorgy B, Szabo TG, Pasztoi M, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 2011;68(16):2667-88. doi: 10.1007/s00018-011-0689-3
3. Yanez-Mo M, Siljander PRM, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 2015;4 doi: ARTN 27066
10.3402/jev.v4.27066
4. Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013;200(4):373-83. doi: 10.1083/jcb.201211138
5. Alexander M, Hu RZ, Runtsch MC, et al. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun 2015;6 doi: ARTN 7321
10.1038/ncomms8321
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...
Show MoreI 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.
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...
Show MoreWe 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.
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...
Show MoreI 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...
Show MoreWe 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.
Show MoreFirst, 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...
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).
Show MoreNEWS 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...
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...
Show MoreDear 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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