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1.
Eur Respir J ; 58(2)2021 08.
Article in English | MEDLINE | ID: mdl-33479109

ABSTRACT

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 noninvasive 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 (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 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 Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating 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.


Subject(s)
Noninvasive Ventilation , Pulmonary Disease, Chronic Obstructive , Disease Progression , Hospital Mortality , Humans , Prospective Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Respiration, Artificial
2.
Eur Respir J ; 57(2)2021 02.
Article in English | MEDLINE | ID: mdl-33008939

ABSTRACT

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.


Subject(s)
Automobile Driving , Sleep Apnea, Obstructive , Accidents, Traffic/prevention & control , Continuous Positive Airway Pressure , Humans , Risk Factors , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Sleepiness
3.
Respirology ; 24(12): 1156-1164, 2019 12.
Article in English | MEDLINE | ID: mdl-30468277

ABSTRACT

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.


Subject(s)
Clinical Competence , Needs Assessment , Noninvasive Ventilation , Respiratory Insufficiency/therapy , Humans , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/methods , Noninvasive Ventilation/standards , Quality Improvement , Treatment Failure
4.
Cancer Immunol Immunother ; 67(2): 247-259, 2018 02.
Article in English | MEDLINE | ID: mdl-29067496

ABSTRACT

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.


Subject(s)
Antibodies, Bispecific/immunology , Antibodies, Bispecific/pharmacology , Cadherins/immunology , Immunotherapy/methods , Neoplasms/immunology , Neoplasms/therapy , T-Lymphocytes/immunology , Animals , CD3 Complex/immunology , Cell Line, Tumor , Cricetinae , Cricetulus , Female , HCT116 Cells , HT29 Cells , Humans , Mice , Xenograft Model Antitumor Assays
5.
Eur Respir J ; 50(2)2017 08.
Article in English | MEDLINE | ID: mdl-28860265

ABSTRACT

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, de novo 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.


Subject(s)
Noninvasive Ventilation/methods , Respiratory Insufficiency , Acute Disease , Critical Care/methods , Diagnosis, Differential , Humans , Practice Guidelines as Topic , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
6.
JAMA ; 317(21): 2177-2186, 2017 06 06.
Article in English | MEDLINE | ID: mdl-28528348

ABSTRACT

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.


Subject(s)
Noninvasive Ventilation , Oxygen Inhalation Therapy , Patient Readmission/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/therapy , Aged , Combined Modality Therapy , Female , Forced Expiratory Volume , Home Care Services , Humans , Hypercapnia/etiology , Hypercapnia/therapy , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/mortality , Quality of Life , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Risk , Time Factors
7.
Eur Respir J ; 48(1): 151-7, 2016 07.
Article in English | MEDLINE | ID: mdl-27030678

ABSTRACT

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.


Subject(s)
Continuous Positive Airway Pressure , Oxygen/blood , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/therapy , Adult , Aged , Databases, Factual , Female , Humans , Male , Middle Aged , Preoperative Period , Referral and Consultation , Retrospective Studies , Severity of Illness Index , Sleep Stages , Treatment Outcome , United Kingdom/epidemiology
8.
COPD ; 13(4): 483-90, 2016 08.
Article in English | MEDLINE | ID: mdl-26744042

ABSTRACT

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.


Subject(s)
Dyspnea/therapy , Home Care Services , Noninvasive Ventilation/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/therapy , Disease Progression , Dyspnea/etiology , Europe , Hospitalization/statistics & numerical data , Humans , Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive/complications , Pulmonologists , Quality of Life , Surveys and Questionnaires , Ventilator Weaning
9.
Respir Med ; 222: 107513, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38159781

ABSTRACT

BACKGROUND: Traditionally continuous positive airways pressure (CPAP) trials for obstructive sleep apnoea (OSA) are through face to face (F2F) set up. During Covid-19 pandemic CPAP was classed as aerosol-generating hence Leeds sleep service moved to a virtual service. Patients received equipment by post followed by virtual reviews (VR). We evaluated the adherence and symptomatic benefit of postal compared to F2F method. METHODS: Observational data were collected from databases monitoring CPAP loans. F2F patients met a sleep technician for hands on setup in 2019, and in 2020 postal patients received equipment, written guides, and links to custom made YouTube videos. All (F2F and postal) patients had a telephone and VR appointment to discuss symptoms, and CPAP machine (AirSense 10, ResMed Inc., San Diego, USA) data including data on usage and treatment apnoea-hypopnoea index (AHI). Data was analysed using unpaired T-tests, Mann-Whitney U tests, and chi-square tests to examine differences in means, medians, and proportions, respectively of the F2F and postal groups. RESULTS: Both groups (n = 1,221, 656 F2F, 53.7%) were similar in all categories except length of CPAP trial (postal 33 vs F2F 84 days,p < 0.0001), change in AHI (postal 22.4/Hr vs F2F 25.1/Hr,p = 0.04), and trial average use (postal 4.9 vs F2F 5.2 h,p = 0.04). There was no significant difference in the proportion of patients continuing with CPAP (postal 64%, F2F 66%, p = 0.71), the improvement in Epworth Sleepiness Score (ESS) (postal 6.9/24, F2F 7.1/24, p = 0.31) or the patient's subjective rating on whether they felt much better, better, the same or worse on CPAP (p = 0.27). Logistic regression showed factors which affected odds ratios of continuing CPAP were diagnostic AHI, treatment AHI, treatment ESS and how they felt on CPAP. Trial type did not affect the odds ratios of continuing CPAP. CONCLUSIONS: Postal CPAP trial patients had similar odds of continuing CPAP therapy compared to patients with F2F trials and achieved similar levels of ESS improvement and reporting feeling better on CPAP. This provides support for postal trials as a viable option post-pandemic.


Subject(s)
Pandemics , Sleep Apnea, Obstructive , Humans , Continuous Positive Airway Pressure/methods , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/therapy , Sleep
10.
Thorax ; 67(9): 815-21, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22561529

ABSTRACT

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.


Subject(s)
Automobile Driving , Sleep Apnea, Obstructive/physiopathology , Accidents, Traffic/prevention & control , Accidents, Traffic/statistics & numerical data , Adult , Computer Simulation , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC Curve , Regression Analysis , Task Performance and Analysis
11.
Eur Respir J ; 40(2): 408-15, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22183492

ABSTRACT

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.


Subject(s)
Psychometrics/methods , Respiratory Insufficiency/diagnosis , Surveys and Questionnaires , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Humans , Language , Male , Models, Statistical , Principal Component Analysis , Quality of Life , Reproducibility of Results , Respiration, Artificial , United Kingdom
12.
Lung ; 190(6): 597-603, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22782122

ABSTRACT

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.


Subject(s)
Delirium/complications , Noninvasive Ventilation , Positive-Pressure Respiration , Respiratory Insufficiency/therapy , Delirium/diagnosis , Humans , Respiratory Insufficiency/complications
13.
Thorax ; 66(1): 82-4, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20729234

ABSTRACT

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.


Subject(s)
Respiration, Artificial/methods , Respiratory Insufficiency/therapy , Sleep , Humans , Monitoring, Physiologic/methods , Respiratory Insufficiency/physiopathology , Technology Assessment, Biomedical/methods
14.
Am J Respir Crit Care Med ; 181(1): 21-30, 2010 Jan 01.
Article in English | MEDLINE | ID: mdl-19797159

ABSTRACT

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. 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.


Subject(s)
Nitric Oxide Synthase Type II/metabolism , Pulmonary Disease, Chronic Obstructive/enzymology , Up-Regulation , Adult , Aged , Breath Tests , Case-Control Studies , Cell Line , Disease Progression , Epithelial Cells , Female , Forced Expiratory Volume , Humans , Isoenzymes/metabolism , Male , Middle Aged , Oxidative Stress , Registries , Smoking
15.
Respir Res ; 11: 153, 2010 Oct 31.
Article in English | MEDLINE | ID: mdl-21040527

ABSTRACT

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.


Subject(s)
Lung/diagnostic imaging , Lung/pathology , Tomography, X-Ray Computed/standards , Aged , Female , Humans , Male , Middle Aged , Organ Size , Tomography, X-Ray Computed/methods
16.
Sleep Med Clin ; 14(4): 441-451, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31640872

ABSTRACT

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.


Subject(s)
Accidents, Traffic , Automobile Driving , Sleep Apnea, Obstructive/physiopathology , Sleepiness , Humans
17.
Clin Med (Lond) ; 19(3): 237-242, 2019 05.
Article in English | MEDLINE | ID: mdl-31092518

ABSTRACT

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.


Subject(s)
Noninvasive Ventilation , Acute Disease , Humans , Respiratory Insufficiency/therapy
18.
Lancet Respir Med ; 6(12): 935-947, 2018 12.
Article in English | MEDLINE | ID: mdl-30629932

ABSTRACT

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.


Subject(s)
Noninvasive Ventilation/methods , Oxygen Inhalation Therapy/methods , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Humans , Hypoxia/therapy , Intubation, Intratracheal/adverse effects , Noninvasive Ventilation/adverse effects , Noninvasive Ventilation/mortality , Patient Selection , Practice Guidelines as Topic , Severity of Illness Index
19.
Respir Med ; 101(9): 1874-9, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17601720

ABSTRACT

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.


Subject(s)
Masks , Respiration, Artificial/instrumentation , Airway Resistance , Cross-Over Studies , Heating , Humans , Humidity , Mouth , Nasal Cavity , Respiration, Artificial/methods , Tidal Volume
20.
ERJ Open Res ; 3(4)2017 Oct.
Article in English | MEDLINE | ID: mdl-29255721

ABSTRACT

During noninvasive ventilation it is reasonable to try to abolish clinically apparent patient-ventilator asynchronies but the use of more invasive tests to detect subtle asynchronies cannot be justified http://ow.ly/rXoA30gCm8O.

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