Publications by authors named "Mark W Elliott"

32 Publications

The NIV Outcomes (NIVO) Score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

Eur Respir J 2021 Jan 28. Epub 2021 Jan 28.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Introduction: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used.

Methods: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally non-invasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD recommendations.

Results: Derivation cohort, n=489, in-hospital mortality 25.4%; validation cohort, n=733, in-hospital mortality 20.1%. Using 6 simple categorised variables; extended Medical Research Council Dyspnoea score (eMRCD)1-4/5a/5b, time from admission to acidaemia >12 h, pH<7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant NIVO score had area under the receiver operated curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort.

Discussion: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism, and comparing risk-adjusted outcomes across centres.
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http://dx.doi.org/10.1183/13993003.04042-2020DOI Listing
January 2021

European Respiratory Society statement on sleep apnoea, sleepiness and driving risk.

Eur Respir J 2021 Feb 25;57(2). Epub 2021 Feb 25.

School of Medicine, University College Dublin, Dept of Respiratory and Sleep Medicine, St Vincent's University Hospital, Dublin, Ireland

Obstructive sleep apnoea (OSA) is highly prevalent and is a recognised risk factor for motor vehicle accidents (MVA). Effective treatment with continuous positive airway pressure has been associated with a normalisation of this increased accident risk. Thus, many jurisdictions have introduced regulations restricting the ability of OSA patients from driving until effectively treated. However, uncertainty prevails regarding the relative importance of OSA severity determined by the apnoea-hypopnoea frequency per hour and the degree of sleepiness in determining accident risk. Furthermore, the identification of subjects at risk of OSA and/or accident risk remains elusive. The introduction of official European regulations regarding fitness to drive prompted the European Respiratory Society to establish a task force to address the topic of sleep apnoea, sleepiness and driving with a view to providing an overview to clinicians involved in treating patients with the disorder. The present report evaluates the epidemiology of MVA in patients with OSA; the mechanisms involved in this association; the role of screening questionnaires, driving simulators and other techniques to evaluate sleepiness and/or impaired vigilance; the impact of treatment on MVA risk in affected drivers; and highlights the evidence gaps regarding the identification of OSA patients at risk of MVA.
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http://dx.doi.org/10.1183/13993003.01272-2020DOI Listing
February 2021

Assessment of Sleepiness in Drivers: Current Methodology and Future Possibilities.

Sleep Med Clin 2019 Dec 27;14(4):441-451. Epub 2019 Sep 27.

Department of Respiratory Medicine, Sleep and Non-invasive Ventilation Service, St. James's University Hospital, Beckett Street, Leeds, West Yorkshire LS9 7TF, UK. Electronic address:

Many patients with obstructive sleep apnea syndrome (OSAS) drive a vehicle both for pleasure and as part of their employment. Some, but not all, patients with OSAS are at increased risk of being involved in road traffic accidents. Clinicians are often asked to make recommendations about an individual's fitness to drive, and these are likely to be inconsistent in the absence of objective criteria. This article discusses the current practice of the assessment of individuals' sleepiness with respect to driving, the limitations of available techniques, and future possibilities.
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http://dx.doi.org/10.1016/j.jsmc.2019.08.003DOI Listing
December 2019

Acute non-invasive ventilation - getting it right on the acute medical take.

Clin Med (Lond) 2019 05;19(3):237-242

St James's University Hospital, Leeds, UK.

Non-invasive ventilation (NIV) given to the right patient, in the right setting, in the right way and at the right time improves outcomes. However, national audits reveal poor practice in patient selection, clinical judgement, treatment initiation and availability of trained staff. NIV is indicated for persistent acute hypercapnic respiratory failure (AHRF) with acidosis after usual medical management in chronic obstructive pulmonary disease (COPD) exacerbation and even without acidosis in neuromuscular disorders or other restrictive conditions eg obesity hypoventilation or kyphoscoliosis. Having trained staff in a suitable environment with adequate equipment are keys to its success, along with close monitoring. A plan should be put in place at the time of initiating NIV about the ceiling of care, eg escalation to intubation or palliation, if the patient is not improving with NIV. Early NIV failure is most likely due to technical issues, such as inadequate pressures or mask leak, while late failure is usually the consequence of advanced disease. Any presentation with AHRF is a poor prognostic indicator and outpatient respiratory follow-up is indicated following discharge. For selected patients with COPD who remain hypercapnic 2 weeks after an exacerbation, domiciliary NIV can reduce admissions and improve survival. For patients with neuromuscular disorders or kyphoscoliosis a presentation with AHRF almost always indicates the need for domiciliary NIV.
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http://dx.doi.org/10.7861/clinmedicine.19-3-237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542238PMC
May 2019

Beyond the guidelines for non-invasive ventilation in acute respiratory failure: implications for practice.

Lancet Respir Med 2018 12;6(12):935-947

Department of Respiratory Medicine, St James' University Hospital, Leeds, UK. Electronic address:

Non-invasive ventilation is standard therapy in the management of both hypoxaemic and hypercapnic respiratory failure of various causes. The evidence base for its use and when and how it should be used has been reviewed in two recent guidelines. In this Series paper, we look beyond the guidelines to what is happening in everyday clinical practice in the real world, how patient selection can be refined to maximise the chances of a successful outcome, and emerging alternative therapies. Real-world application of non-invasive ventilation diverges from guideline recommendations, particularly with regard to patient selection and timing of initiation. To improve patient outcomes education programmes need to stress these issues and the effectiveness of non-invasive ventilation that is delivered needs to be monitored by regular audit.
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http://dx.doi.org/10.1016/S2213-2600(18)30388-6DOI Listing
December 2018

Non-invasive ventilation: Essential requirements and clinical skills for successful practice.

Authors:
Mark W Elliott

Respirology 2019 12 23;24(12):1156-1164. Epub 2018 Nov 23.

Department of Respiratory Medicine, St James's University Hospital, Leeds, UK.

Audits and case reviews of the acute delivery of non-invasive ventilation (NIV) have shown that the results achieved in real life often fall short of those achieved in research trials. Factors include inappropriate selection of patients for NIV and failure to apply NIV correctly. This highlights the need for proper training of all involved individuals. This article addresses the different skills needed in a team to provide an effective NIV service. Some detail is given in each of the key areas but it is not comprehensive and should stimulate further learning (reading, attendance on courses, e-learning, etc.), determined by the needs of the individual.
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http://dx.doi.org/10.1111/resp.13445DOI Listing
December 2019

Looking under the bonnet of patient-ventilator asynchrony during noninvasive ventilation: does it add value?

ERJ Open Res 2017 Oct 14;3(4). Epub 2017 Dec 14.

St James's University Hospital, Leeds, UK.

http://ow.ly/rXoA30gCm8O.
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http://dx.doi.org/10.1183/23120541.00136-2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731773PMC
October 2017

A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice.

Cancer Immunol Immunother 2018 02 24;67(2):247-259. Epub 2017 Oct 24.

Oncology Research and Development Pfizer Inc., La Jolla, CA, USA.

Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. However, this approach has not been validated in solid tumors. PF-06671008 is a dual-affinity retargeting (DART)-bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex in the presence of solid tumors expressing P-cadherin. This bispecific molecule elicited potent P-cadherin expression-dependent cytotoxic T cell activity across a range of tumor indications in vitro, and in vivo in tumor-bearing mice. Regression of established tumors in vivo was observed in both cell line and patient-derived xenograft models engrafted with circulating human T lymphocytes. Measurement of in vivo pharmacodynamic markers demonstrates PF-06671008-mediated T cell activation, infiltration and killing as the mechanism of tumor inhibition.
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http://dx.doi.org/10.1007/s00262-017-2081-0DOI Listing
February 2018

Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure.

Eur Respir J 2017 08 31;50(2). Epub 2017 Aug 31.

Pulmonary and Critical Care Medicine, Lenox Hill Hospital, New York, NY, USA.

Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema, hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
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http://dx.doi.org/10.1183/13993003.02426-2016DOI Listing
August 2017

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial.

JAMA 2017 06;317(21):2177-2186

Lane Fox Unit, Guy's and St Thomas' NHS Foundation Trust, London, England2Asthma, Allergy, and Lung Biology, King's College London, London, England.

Importance: Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death.

Objective: To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation.

Design, Setting, And Participants: A randomized clinical trial of patients with persistent hypercapnia (Paco2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible.

Interventions: There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute.

Main Outcomes And Measures: Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI.

Results: A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] Paco2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group.

Conclusions And Relevance: Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months.

Trial Registration: clinicaltrials.gov Identifier: NCT00990132.
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http://dx.doi.org/10.1001/jama.2017.4451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710342PMC
June 2017

Factors that affect simulated driving in patients with obstructive sleep apnoea.

ERJ Open Res 2015 Oct 7;1(2). Epub 2015 Dec 7.

Dept of Respiratory Medicine, St James' University Hospital, Leeds, UK.

http://ow.ly/TWPgm.
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http://dx.doi.org/10.1183/23120541.00074-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005126PMC
October 2015

Diaphragm pacing and motor neurone disease: lessons for all?

Authors:
Mark W Elliott

ERJ Open Res 2015 Oct 5;1(2). Epub 2015 Nov 5.

Consultant Respiratory Physician, Dept of Respiratory Medicine, Sleep and Non-invasive Ventilation Service, St James University Hospital, Leeds, UK.

http://ow.ly/TIxe5.
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http://dx.doi.org/10.1183/23120541.00073-2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005125PMC
October 2015

Prevalence of and treatment outcomes for patients with obstructive sleep apnoea identified by preoperative screening compared with clinician referrals.

Eur Respir J 2016 07 30;48(1):151-7. Epub 2016 Mar 30.

St. James's University Hospital, Leeds, UK

Obstructive sleep apnoea (OSA) has implications perioperatively. We compared the prevalence of OSA and outcome with continuous positive airway pressure (CPAP) in patients diagnosed through preoperative screening and following referrals from other clinicians.Among 1412 patients (62% males) the prevalence of OSA, Epworth Sleepiness Score (ESS), the number referred for CPAP, and short and longer term use of CPAP were compared between the two groups.The prevalence of OSA was similar (62% versus 58%). There were differences in mean±sd age (61±16 versus 55±13 years; p<0.0001), ESS (11±6 versus 8±5; p<0.0001) and oxygen desaturation index (22±20 versus 19±17; p=0.039). Clinician-referred patients were more likely to be offered CPAP (p<0.0001; OR 2.84). Pre-assessment patients with mild OSA were less likely to continue CPAP long term (p=0.002; OR 6.8). No difference was seen between moderate and severe OSA patients.The prevalence of OSA was similar in both groups but pre-assessment patients were younger and less symptomatic. Preoperative screening of patients is worthwhile, independent of any effect of CPAP upon surgical outcomes; younger and less symptomatic patients are identified earlier. Pre-assessment patients with mild OSA were less likely to use CPAP; this should be considered when offering CPAP to these patients prior to surgery.
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http://dx.doi.org/10.1183/13993003.01503-2015DOI Listing
July 2016

Domiciliary Non-invasive Ventilation in COPD: An International Survey of Indications and Practices.

COPD 2016 08 8;13(4):483-90. Epub 2016 Jan 8.

j Alma Mater University, Department of Clinical, Integrated and Experimental Medicine (DIMES) , Respiratory and Critical Care Unit , S. Orsola-Malpighi Hospital, Bologna , Italy.

Despite the fact that metanalyses and clinical guidelines do not recommend the routine use of domiciliary non-invasive ventilation (NIV) for patients diagnosed with severe stable Chronic Obstructive Pulmonary Disease (COPD) and with chronic respiratory failure, it is common practice in some countries. We conducted an international web-survey of physicians involved in provision of long-term NIV to examine patterns of domiciliary NIV use in patients diagnosed with COPD. The response rate was 41.6%. A reduction of hospital admissions, improvements in quality of life and dyspnea relief were considered as the main expected benefits for patients. Nocturnal oxygen saturation assessment was the principal procedure performed before NIV prescription. Recurrent exacerbations (>3) requiring NIV and failed weaning from in hospital NIV were the most important reasons for starting domiciliary NIV. Pressure support ventilation (PSV) was the most common mode, with "low" intensity settings (PSV-low) the most popular (44.4 ± 30.1%) compared with "high" intensity (PSV-high) strategies (26.9 ± 25.9%), with different geographical preferences. COPD is confirmed to be a common indication for domiciliary NIV. Recurrent exacerbations and failed weaning from in-hospital NIV were the main reasons for its prescription.
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http://dx.doi.org/10.3109/15412555.2015.1108960DOI Listing
August 2016

PET imaging to non-invasively study immune activation leading to antitumor responses with a 4-1BB agonistic antibody.

J Immunother Cancer 2013 27;1:14. Epub 2013 Aug 27.

Department of Medicine (Division of Hematology-Oncology) at David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, USA ; Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, USA ; Jonsson Comprehensive Cancer Center (JCCC), Los Angeles, USA ; Department of Medicine, Division of Hematology-Oncology, 11-934 Factor Building, Jonsson Comprehensive Cancer Center at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1782, USA.

Background: Molecular imaging with positron emission tomography (PET) may allow the non-invasive study of the pharmacodynamic effects of agonistic monoclonal antibodies (mAb) to 4-1BB (CD137). 4-1BB is a member of the tumor necrosis factor family expressed on activated T cells and other immune cells, and activating 4-1BB antibodies are being tested for the treatment of patients with advanced cancers.

Methods: We studied the antitumor activity of 4-1BB mAb therapy using [(18) F]-labeled fluoro-2-deoxy-2-D-glucose ([(18) F]FDG) microPET scanning in a mouse model of colon cancer. Results of microPET imaging were correlated with morphological changes in tumors, draining lymph nodes as well as cell subset uptake of the metabolic PET tracer in vitro.

Results: The administration of 4-1BB mAb to Balb/c mice induced reproducible CT26 tumor regressions and improved survival; complete tumor shrinkage was achieved in the majority of mice. There was markedly increased [(18) F]FDG signal at the tumor site and draining lymph nodes. In a metabolic probe in vitro uptake assay, there was an 8-fold increase in uptake of [(3)H]DDG in leukocytes extracted from tumors and draining lymph nodes of mice treated with 4-1BB mAb compared to untreated mice, supporting the in vivo PET data.

Conclusion: Increased uptake of [(18) F]FDG by PET scans visualizes 4-1BB agonistic antibody-induced antitumor immune responses and can be used as a pharmacodynamic readout to guide the development of this class of antibodies in the clinic.
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http://dx.doi.org/10.1186/2051-1426-1-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019904PMC
May 2014

Identifying poor compliance with CPAP in obstructive sleep apnoea: a simple prediction equation using data after a two week trial.

Respir Med 2013 Jun 10;107(6):936-42. Epub 2012 Nov 10.

Department of Respiratory Medicine, St. James's University Hospital, Leeds, UK.

Introduction: It is important to identify those patients with OSA who are likely to benefit from long term CPAP, not only for symptomatic relief, but also potentially to reduce vascular morbidity and mortality, but are unlikely to adhere to treatment. We have validated a model which we developed previously for predicting long term compliance with CPAP using data after a 2 week trial.

Methods: The model was applied retrospectively to patients undergoing a trial of CPAP. Predicted outcomes were compared with the actual outcomes.

Results: Prediction equation was applied to 448 patients [77% males, Age 53 ± 11 years, ESS 14 ± 4, AHI 37 ± 24]. Of 407 patients included in the study 333 were issued a CPAP and 74 declined long term CPAP. At one year, 81% patients were using CPAP at least 2 h and 70% > 4 h. A score >50% from the equation was associated with a high probability of CPAP usage at one year. 295 patients had a probability score of >50% and of them 84% were using CPAP satisfactorily at 1 year. The sensitivity in identifying compliers was 91%. Of the 112 patients with a score ≤50%, 38 opted to accept CPAP and 60% of them were still using it at 1 year.

Conclusions: This simple equation has now been validated to be highly sensitive in identifying long term compliers and it also identifies those with worse compliance. This group could be targeted for a more intensive follow up regime with the aim of improving their compliance.
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http://dx.doi.org/10.1016/j.rmed.2012.10.008DOI Listing
June 2013

Noninvasive positive pressure ventilation for acute respiratory failure in delirious patients: understudied, underreported, or underappreciated? A systematic review and meta-analysis.

Lung 2012 Dec 11;190(6):597-603. Epub 2012 Jul 11.

Academic Unit of Psychiatry and Behavioural Sciences, Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.

Background: We performed a systematic review and meta-analysis of the literature to determine the prevalence of delirium in patients receiving noninvasive positive pressure ventilation (NPPV) for acute respiratory failure and to quantify the prognostic impact of delirium with respect to NPPV failure.

Method: We searched the databases EMBASE (1996 to present), MEDLINE (1996 to present), PsycINFO(®) (2002 to present) and CINAHL (1992 to present). A Google™ search and hand searching of bibliographies or relevant articles were also performed. We searched for prospective observational studies conducted in a setting where patients with acute respiratory failure receiving NPPV were screened for delirium. All authors independently assessed references for inclusion and extracted data. Information was collated regarding study design, baseline characteristics of included patients, and the prevalence of delirium. Where prognostic information regarding NPPV failure was reported, a risk ratio for the association between delirium and NPPV failure was derived. These values were pooled in the meta-analysis.

Results: Three articles were retrieved by the search strategy. These included 239 patients receiving noninvasive ventilation who were assessed for delirium. The prevalence of delirium was recorded at between 33 and 38 % with a pooled prevalence of 37 %. Two studies reported prognostic data and the risk ratios for noninvasive ventilation failure in delirium were calculated as 1.79 (95 % CI 1.09-2.94) and 3.28 (95 % CI 1.60-6.73). A meta-analysis was performed and the pooled risk ratio was found to be 2.12 (95 % CI 1.41-3.18).

Conclusions: The data in this context was scarce and of low quality. A diagnosis of delirium was made in 9 patients and inferred in 80. Despite the current lack of high-quality data and studies, the high reported prevalence of delirium and the association with noninvasive ventilation failure lends support for more awareness amongst health-care professionals and more routine screening. More focused primary research is necessary in this area. Adherence to NICE guidelines regarding delirium in these patients should be a standard of care.
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http://dx.doi.org/10.1007/s00408-012-9403-yDOI Listing
December 2012

Continuous measures of driving performance on an advanced office-based driving simulator can be used to predict simulator task failure in patients with obstructive sleep apnoea syndrome.

Thorax 2012 Sep 5;67(9):815-21. Epub 2012 May 5.

Department of Respiratory Medicine, St James' University Hospital, Beckett Street, Leeds LS9 7TF, UK.

Introduction: Some patients with obstructive sleep apnoea syndrome are at higher risk of being involved in road traffic accidents. It has not been possible to identify this group from clinical and polysomnographic information or using simple simulators. We explore the possibility of identifying this group from variables generated in an advanced PC-based driving simulator.

Methods: All patients performed a 90 km motorway driving simulation. Two events were programmed to trigger evasive actions, one subtle and an alert driver should not crash, while for the other, even a fully alert driver might crash. Simulator parameters including standard deviation of lane position (SDLP) and reaction times at the veer event (VeerRT) were recorded. There were three possible outcomes: 'fail', 'indeterminate' and 'pass'. An exploratory study identified the simulator parameters predicting a 'fail' by regression analysis and this was then validated prospectively.

Results: 72 patients were included in the exploratory phase and 133 patients in the validation phase. 65 (32%) patients completed the run without any incidents, 45 (22%) failed, 95 (46%) were indeterminate. Prediction models using SDLP and VeerRT could predict 'fails' with a sensitivity of 82% and specificity of 96%. The models were subsequently confirmed in the validation phase.

Conclusions: Using continuously measured variables it has been possible to identify, with a high degree of accuracy, a subset of patients with obstructive sleep apnoea syndrome who fail a simulated driving test. This has the potential to identify at-risk drivers and improve the reliability of a clinician's decision-making.
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http://dx.doi.org/10.1136/thoraxjnl-2011-200699DOI Listing
September 2012

Validation of the English Severe Respiratory Insufficiency Questionnaire.

Eur Respir J 2012 Aug 19;40(2):408-15. Epub 2011 Dec 19.

Dept of Respiratory Medicine, St James's University Hospital, Leeds, UK.

Assessment of health-related quality of life in patients with respiratory failure on home ventilation requires appropriate and highly specific measurement tools. We attempt to validate the English version of the Severe Respiratory Insufficiency Questionnaire (SRI). Psychometric properties of the SRI in 152 patients established on home ventilation were assessed. Cronbach's alpha ranged between 0.77 and 0.89 for the seven subscales and and was 0.93 for the summary scale. Principal components analysis revealed a one-factor solution for four and two factors for three subscales. Confirmatory factor analysis revealed a two-factor solution for six subscales, but these factors were dependent on each other. One factor was extracted out of the subscales confirming one summary scale accounting for 70% of the total variance. Correlation analysis between scales of the SRI and the Medical Outcome Study 36-item short-form health survey demonstrated highest correlations between comparable subscales. Chronic obstructive pulmonary disease patients had lower summary scale scores than patients with restrictive chest wall diseases, neuromuscular disorders and obesity hypoventilation syndrome. The English SRI has high internal consistency reliability, clearly established construct and concurrent validity, and is capable of differentiating between different diseases. It is now validated for use in research involving patients receiving home ventilation.
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http://dx.doi.org/10.1183/09031936.00152411DOI Listing
August 2012

Quantification of lung surface area using computed tomography.

Respir Res 2010 Oct 31;11:153. Epub 2010 Oct 31.

University of British Columbia James Hogg Research Centre and the Heart and Lung Institute, St. Paul’s Hospital, Burrard Street, Vancouver, Canada.

Objective: To refine the CT prediction of emphysema by comparing histology and CT for specific regions of lung. To incorporate both regional lung density measured by CT and cluster analysis of low attenuation areas for comparison with histological measurement of surface area per unit lung volume.

Methods: The histological surface area per unit lung volume was estimated for 140 samples taken from resected lung specimens of fourteen subjects. The region of the lung sampled for histology was located on the pre-operative CT scan; the regional CT median lung density and emphysematous lesion size were calculated using the X-ray attenuation values and a low attenuation cluster analysis. Linear mixed models were used to examine the relationships between histological surface area per unit lung volume and CT measures.

Results: The median CT lung density, low attenuation cluster analysis, and the combination of both were important predictors of surface area per unit lung volume measured by histology (p < 0.0001). Akaike's information criterion showed the model incorporating both parameters provided the most accurate prediction of emphysema.

Conclusion: Combining CT measures of lung density and emphysematous lesion size provides a more accurate estimate of lung surface area per unit lung volume than either measure alone.
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http://dx.doi.org/10.1186/1465-9921-11-153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976969PMC
October 2010

Non-invasive ventilation during sleep: time to define new tools in the systematic evaluation of the technique.

Authors:
Mark W Elliott

Thorax 2011 Jan 20;66(1):82-4. Epub 2010 Aug 20.

Department of Respiratory Medicine, St James's University Hospital, Leeds, UK.

Non-invasive ventilation (NIV) has been remarkably effective in the management of chronic respiratory failure, despite initially rudimentary equipment and limited understanding of what was actually happening, minute by minute when ventilation was applied. Modern ventilators, controlled by complex algorithms, and with integrated monitoring allow for sophisticated customisation of ventilatory support to an individual. However, if problems with ventilation are not recognised, and their significance understood, they cannot be fixed. Experience of monitoring during sleep from patients predominantly with sleep apnoea can be transferred and extended to patients receiving NIV. This article, the first in a series, explores the rationale for NIV and how its application to an individual patient can be monitored using simple tools and, when problems are identified, the causes can be identified using sophisticated interpretation of more detailed monitoring. This requires a detailed understanding of how different modes of ventilation work and some knowledge of the algorithms that control each machine. These themes are explored in this article and developed in subsequent articles in the series.
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http://dx.doi.org/10.1136/thx.2010.142117DOI Listing
January 2011

Nitric oxide synthase isoenzyme expression and activity in peripheral lung tissue of patients with chronic obstructive pulmonary disease.

Am J Respir Crit Care Med 2010 Jan 24;181(1):21-30. Epub 2009 Sep 24.

National Heart and Lung Institute, Imperial College London, UK.

Rationale: Nitric oxide (NO) is increased in the lung periphery of patients with chronic obstructive pulmonary disease (COPD). However, expression of the NO synthase(s) responsible for elevated NO has not been identified in the peripheral lung tissue of patients with COPD of varying severity.

Objectives:

Methods: Protein and mRNA expression of nitric oxide synthase type I (neuronal NOS [nNOS]), type II (inducible NOS [iNOS]), and type III (endothelial NOS [eNOS]) were quantified by Western blotting and reverse transcription-polymerase chain reaction, respectively, in specimens of surgically resected lung tissue from nonsmoker control subjects, patients with COPD of varying severity, and smokers without COPD, and in a lung epithelial cell line (A549). The effects of nitrative/oxidative stress on NOS expression and activity were also evaluated in vitro in A549 cells. nNOS nitration was quantified by immunoprecipitation and dimerization of nNOS was detected by low-temperature SDS-PAGE/Western blot in the presence of the peroxynitrite generator, 3-morpholinosydnonimine-N-ethylcarbamide (SIN1), in vitro and in vivo.

Measurements And Main Results: Lung tissue from patients with severe and very severe COPD had graded increases in nNOS (mRNA and protein) compared with nonsmokers and normal smokers. Hydrogen peroxide (H(2)O(2)) and SIN1 as well as the cytokine mixture (IFN-gamma, IL-1beta, and tumor necrosis factor-alpha) increased mRNA expression and activity of nNOS in A549 cells in a concentration-dependent manner compared with nontreated cells. Tyrosine nitration resulted in an increase in nNOS activity in vitro, but did not affect its dimerization.

Conclusions: Patients with COPD have a significant increase in nNOS expression and activity that reflects the severity of the disease and may be secondary to oxidative stress.
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http://dx.doi.org/10.1164/rccm.200904-0493OCDOI Listing
January 2010

Acceptance, effectiveness and safety of continuous positive airway pressure in acute stroke: a pilot study.

Respir Med 2009 Jan 18;103(1):59-66. Epub 2008 Sep 18.

Unità Operativa di Pneumologia, Endoscopia Toracica e UTSIR, Ospedale San Donato ASL8, Via Pietro Nenni, 20, 52100, Arezzo, Italy.

Objectives: To evaluate the acceptance, effectiveness in preventing upper airways obstruction, and haemodynamic effects of continuous positive airway pressure (CPAP) in acute stroke.

Methods: Twelve patients (4 M, and 8 F; mean (SD), 75.2 (5.5) years) within 48 h of acute stroke onset underwent: (1) sleep studies (1st night: auto-CPAP mode; 2nd night: diagnostic); (2) nocturnal non-invasive blood pressure studies (1st night during CPAP; 2nd night during spontaneous breathing (SB)); and (3) daytime cerebral blood flow velocity measurement in middle cerebral artery (FV) with transcranial Doppler during SB and with CPAP (5, 10, 15 cm H(2)O).

Results: Ninety percent, 60% and 50% of stroke patients had a respiratory disturbance index (RDI) of >or=5, >or=10 and >or=15 events per hour, respectively (18.2 (11.3)). CPAP acceptance was 84%; 42% used CPAP more than 6h and 42% between 1-3h with a mean use of CPAP of 5.2h (4.0). Compared to SB, CPAP reduced, though not significantly, RDI, time with SaO(2)<90%, mean blood pressure and mean blood pressure dips (10 mm Hg)/h. Compared with SB, any level of CPAP progressively and significantly reduced systolic and mean FV; drop in diastolic FV was significant at CPAP10 and CPAP15. The partial pressure of end-tidal CO(2) was significantly lowered by all levels of CPAP.

Conclusions: According to this pilot study, CPAP is reasonably well tolerated by patients with acute stroke for at least one night. Despite its possible beneficial effect on obstructive sleep-disordered breathing and blood pressure variability, CPAP use in acute stroke should be still considered with caution due to possible harmful haemodynamic effects at higher pressures.
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http://dx.doi.org/10.1016/j.rmed.2008.08.002DOI Listing
January 2009

An unusual exacerbation of chronic obstructive pulmonary disease (COPD) with herpes simplex tracheitis: case report.

J Med Case Rep 2007 Sep 19;1:91. Epub 2007 Sep 19.

Department of respiratory medicine, St James's university hospital, Leeds, UK.

Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity in the UK and is increasingly seen in elderly patients, often requiring multiple courses of steroids. We present a case of a 72 year old lady with repeated exacerbations of COPD which did not respond to conventional treatment. Herpes simplex virus (HSV1) tracheobronchitis was diagnosed following a rigid bronchoscopy and her symptoms improved with intravenous acyclovir. This is the first published case of HSV tracheitis in a non immunosuppressed individual with chronic lung disease.
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http://dx.doi.org/10.1186/1752-1947-1-91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2089074PMC
September 2007

The effect of mouth leak and humidification during nasal non-invasive ventilation.

Respir Med 2007 Sep 29;101(9):1874-9. Epub 2007 Jun 29.

Department of Respiratory Medicine, Airedale General Hospital, Skipton Road, Keighley BD20 6TD, UK.

Background: Poor mask fit and mouth leak are associated with nasal symptoms and poor sleep quality in patients receiving domiciliary non-invasive ventilation (NIV) through a nasal mask. Normal subjects receiving continuous positive airways pressure demonstrate increased nasal resistance following periods of mouth leak. This study explores the effect of mouth leak during pressure-targeted nasal NIV, and whether this results in increased nasal resistance and consequently a reduction in effective ventilatory support.

Methods: A randomised crossover study of 16 normal subjects was performed on separate days. Comparison was made of the effect of 5 min of mouth leak during daytime nasal NIV with and without heated humidification. Expired tidal volume (V(T)), nasal resistance (R(N)), and patient comfort were measured.

Results: Mean change (Delta) in V(T) and R(N) were significantly less following mouth leak with heated humidification compared to the without (DeltaV(T) -36+/-65 ml vs. -88+/-50 ml, p<0.001; DeltaR(N) +0.9+/-0.4 vs. +2.0+/-0.7 cm H(2)O l s(-1), p<0.001). Baseline comfort was worse without humidification (5.3+/-0.4 vs. 6.2+/-0.4, p<0.01), and only deteriorated following mouth leak without humidification.

Conclusions: In normal subjects, heated humidification during nasal NIV attenuates the adverse effects of mouth leak on effective tidal volume, nasal resistance and improves overall comfort. Heated humidification should be considered as part of an approach to patients who are troubled with nasal symptoms, once leak has been minimised.
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http://dx.doi.org/10.1016/j.rmed.2007.05.005DOI Listing
September 2007

Daytime variability in carotid baroreflex function in healthy human subjects.

Clin Auton Res 2007 Feb 30;17(1):26-32. Epub 2007 Jan 30.

Institute for Cardiovascular Research, University of Leeds, Leeds, UK.

Variability of blood pressure is limited by arterial baroreceptors, yet blood pressure still shows circadian changes. This study was undertaken to examine if the responses to the carotid baroreflex also change throughout the day. Responses of cardiac interval (RR), mean arterial pressure (MAP) and vascular resistance (VR) to carotid baroreflex stimulation and inhibition using pressures and suction applied to a neck chamber, were measured in 14 healthy, normotensive subjects. Studies were carried out at three hourly intervals between 09:00 and 21:00 hours. Stimulus-response curves were defined and the first differential of the curve was calculated to establish reflex sensitivity (maximal slope) and "operating" point (estimated carotid sinus pressure at point of maximum slope, OP). The principal findings are: (1) baroreflex sensitivity for the control of VR was at its highest at 09:00 (-3.4 +/- 0.6 units) compared to 12:00 (-1.9 +/- 0.4 units), 15:00 (-2.0 +/- 0.4 units) and 18:00 (-1.9 +/- 0.3 units) (all P < 0.05); (2) baroreflex OP for the control of MAP was at its lowest at 09:00 (P < 0.01); (3) baroreflex sensitivity for control of VR was significantly correlated with prevailing mean pressure (P < 0.05) and OP for the control of MAP (P < 0.02); (4) OP for control of RR, MAP and VR are all highly correlated to prevailing MAP (P < 0.0001). Our results suggest that baroreflex function varies throughout the day and this favors higher sensitivity and lower blood pressure in the mornings. We speculate that this may be of importance in long-term blood pressure regulation.
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http://dx.doi.org/10.1007/s10286-006-0390-zDOI Listing
February 2007

Titration of non-invasive positive pressure ventilation in chronic respiratory failure.

Respir Med 2006 Jul 28;100(7):1262-9. Epub 2005 Nov 28.

Department of Respiratory Medicine, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

Non-invasive ventilation (NIV) is widely used for acute and chronic respiratory failure. If arterial blood gas tensions do not improve, the level of support can be increased. However, there may be a limit above which increasing ventilatory support leads only to greater interface leak with no improvement in ventilation. The aim of this study was to establish whether there is such a limit. During a daytime study in 24 ventilated stable patients (10 with chronic obstructive pulmonary disease (COPD), 14 with chest wall deformity, CWD), inspiratory pressures up to 20 cm H(2)O and set tidal volumes up to 10 ml kg(-1) were associated with mask leak of <5 l min(-1). Although leak increased with higher levels of support, there was still an increase in minute ventilation. The mean (2 sd) tolerated pressure was 24 cm H(2)O (8-40) in both groups, and set tidal volume 12.7 ml kg(-1) (5.0-20.4) in CWD and 9.6 ml kg(-1) (3.9-14.8) in COPD. Measures of respiratory effort were significantly reduced at all levels with both forms of ventilatory support. There is debate about whether the therapeutic aim of NIV should be to reduce respiratory muscle effort, or to reverse nocturnal hypoventilation. We conclude that if the primary aim is to improve arterial blood gas tensions and this is not achieved, higher levels of ventilation can be obtained using greater pressure or volume, despite additional interface leak. If the aim is to abolish muscle effort completely, there is little to be gained by increasing the level of inspiratory pressure above 20 (CWD) or 25 (COPD) cm H(2)O.
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http://dx.doi.org/10.1016/j.rmed.2005.10.012DOI Listing
July 2006

Co-morbidity and acute decompensations of COPD requiring non-invasive positive-pressure ventilation.

Intensive Care Med 2004 Sep 17;30(9):1747-54. Epub 2004 Jul 17.

U.O. Pneumologia, USL8, Ospedale S. Donato, Via Nenni 20, 52100 Arezzo, Italy.

Objective: To assess the prevalence and the impact of chronic and/or acute non-respiratory co-morbidity on short and longer-term outcome of non-invasive positive pressure ventilation (NIPPV) in acute decompensations of chronic obstructive pulmonary disease (COPD) with acute hypercapnic respiratory failure (AHRF).

Design And Setting: An observational study in a three-bed respiratory monitoring unit in a respiratory ward of a non-university hospital.

Patients: We grouped 120 consecutive COPD patients requiring NIPPV for AHRF (pH 7.28+/-0.05, PaO2/FIO2 ratio 192+/-63, PaCO2 78.3+/-12.3 mmHg) according to whether NIPPV succeeded (n=98) or failed (n=22) in avoiding the need for endotracheal intubation and whether alive (n=77) or dead (n=42) at 6 months.

Measurements And Results: The prevalence of chronic and acute co-morbidity was, respectively, 20% and 41.7%; most of the cases were cardiovascular. In-hospital NIPPV failure was greater in patients with than in those without chronic (33.3% vs. 14.6%) or acute co-morbidity (32% vs. 8.6%). Six-month mortality was worse in patients with than in those without chronic (54.2% vs. 30.5%) or more than one acute co-morbidity (66.7% vs. 30.8%). Multiple regression analysis predicted in-hospital NIPPV failure by acute co-morbidity and forced expiratory volume in 1 s, while death at 6 months was predicted by having more than one acute co-morbidity, non-cardiovascular chronic co-morbidity and Activities of Daily Living score.

Conclusions: Chronic and acute co-morbidities are common in COPD patients with AHRF needing NIPPV and their presence influences short and longer-term outcome.
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http://dx.doi.org/10.1007/s00134-004-2368-4DOI Listing
September 2004

Effect of upper airway obstruction on blood pressure variability after stroke.

Clin Sci (Lond) 2004 Jul;107(1):75-9

Department of Respiratory Medicine, The Leeds Teaching Hospitals NHS Trust, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

Approx. 60% of acute stroke patients have periods of significant UAO (upper airway obstruction) and this is associated with a worse outcome. UAO is associated with repeated fluctuation in BP (blood pressure) and increased BP variability is also associated with a poor outcome in patients with acute stroke. UAO-induced changes in BP, at a time when regional cerebral perfusion is pressure-dependent in areas of critically ischaemic brain, could explain the detrimental effect of UAO on outcome in these patients. The aim of the present study was to examine the relationship between UAO and BP variability in patients with acute stroke. Twelve acute stroke patients and 12 age-, sex- and BMI (body mass index)-matched controls underwent a sleep study with non-invasive continuous monitoring of BP to assess the impact of UAO on BP control after stroke. Stroke patients had significantly more 15 mmHg dips in BP/h than the controls (51 compared with 6.7 respectively; P<0.004). Stroke patients also demonstrated significantly higher BP variability than the controls (26.8 compared with 14.4 mmHg; P<0.001). There were significantly more 15 mmHg dips in BP/h in stroke patients who had significant UAO than those who did not (85.7 compared with 29.5 respectively; P<0.032). Furthermore, stroke patients without UAO (RDI <10, where RDI is respiratory disturbance index) had significantly more 15 mmHg dips in BP/h than the controls (29.5 compared with 6.7 respectively; P<0.037). There was a positive correlation between the severity of UAO (RDI) and 15 mmHg dips in BP/h (r=0.574, P<0.005) in stroke patients. Our results suggest that UAO alone does not explain BP variation post-stroke, but it does play an important role, particularly in determining the severity of the BP fluctuation.
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http://dx.doi.org/10.1042/CS20030404DOI Listing
July 2004