James W. Dodd

Cognitive function in COPD

In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function. Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD. Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function.

The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study

Background The COPD (chronic obstructive pulmonary disease) assessment test (CAT) is a recently introduced, simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD. It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation (PR) programmes or what the minimum clinically important difference is. Methods The introduction of the CAT score as an outcome measure was prospectively studied by PR programmes across London. It was used alongside other measures including the St Georges Respiratory Questionnaire, the Chronic Respiratory Disease Questionnaire, the Clinical COPD Questionnaire, the Hospital Anxiety and Depression score, the Medical Research Council (MRC) dyspnoea score and a range of different walking tests. Patients completed a 5-point anchor question used to assess overall response to PR from ‘I feel much better’ to ‘I feel much worse’. Results Data were available for 261 patients with COPD participating in seven programmes: mean (SD) age 69.0 (9.0) years, forced expiratory volume in 1 s (FEV1) 51.1 (18.7) % predicted, MRC score 3.2 (1.0). Mean change in CAT score after PR was 2.9 (5.6) points, improving by 3.8 (6.1) points in those scoring ‘much better’ (n=162), and by 1.3(4.5) in those who felt ‘a little better’ (n=88) (p=0.002). Only eight individuals reported no difference after PR and three reported feeling ‘a little worse’, so comparison with these smaller groups was not possible. Conclusion The CAT score is simple to implement as an outcome measure, it improves in response to PR and can distinguish categories of response.

Brain structure and function in chronic obstructive pulmonary disease: a multimodal cranial magnetic resonance imaging study.

RATIONALE Brain pathology is a poorly understood systemic manifestation of chronic obstructive pulmonary disease (COPD). Imaging techniques using magnetic resonance (MR) diffusion tensor imaging (DTI) and resting state functional MR imaging (rfMRI) provide measures of white matter microstructure and gray functional activation, respectively. OBJECTIVES We hypothesized that patients with COPD would have reduced white matter integrity and that functional communication between gray matter resting-state networks would be significantly different to control subjects. In addition, we tested whether observed differences related to disease severity, cerebrovascular comorbidity, and cognitive dysfunction. METHODS DTI and rfMRI were acquired in stable nonhypoxemic patients with COPD (n = 25) and compared with age-matched control subjects (n = 25). Demographic, disease severity, stroke risk, and neuropsychologic assessments were made. MEASUREMENTS AND MAIN RESULTS Patients with COPD (mean age, 68; FEV(1) 53 ± 21% predicted) had widespread reduction in white matter integrity (46% of white matter tracts; P < 0.01). Six of the seven resting-state networks showed increased functional gray matter activation in COPD (P < 0.01). Differences in DTI, but not rfMRI, remained significant after controlling for stroke risk and smoking (P < 0.05). White matter integrity and gray matter activation seemed to account for difference in cognitive performance between patients with COPD and control subjects. CONCLUSIONS In stable nonhypoxemic COPD there is reduced white matter integrity throughout the brain and widespread disturbance in functional activation of gray matter, which may contribute to cognitive dysfunction. White matter microstructural integrity but not gray matter functional activation is independent of smoking and cerebrovascular comorbidity. The mechanisms remain unclear, but may include cerebral small vessel disease caused by COPD.

BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults

### Principles of mechanical ventilation #### Modes of mechanical ventilation Recommendation 1. Pressure-targeted ventilators are the devices of choice for acute NIV (Grade B). Good practice points #### Choice of interface for NIV Recommendation 2. A full face mask (FFM) should usually be the first type of interface used (Grade D). Good practice points #### Indications for and contra-indications to NIV in AHRF Recommendation 3. The presence of adverse features increase the risk of NIV failure and should prompt consideration of placement in high dependency unit (HDU)/intensive care unit (ICU) (Grade C). Good practice points #### Monitoring during NIV Good practice points #### Supplemental oxygen therapy with NIV Recommendations 4. Oxygen enrichment should be adjusted to achieve SaO2 88–92% in all causes of acute hypercapnic respiratory failure (AHRF) treated by NIV (Grade A). 5. Oxygen should be entrained as close to the patient as possible (Grade C). Good practice points

British Thoracic Society/Intensive Care Society Guideline for the ventilatory management of acute hypercapnic respiratory failure in adults

The British Thoracic Society (BTS) published the guideline ‘The use of non-invasive ventilation in acute respiratory failure’ in 2002.1 This was in response to trials that had demonstrated that non-invasive ventilation (NIV) was an alternative to invasive mechanical ventilation (IMV) in life-threatening respiratory acidosis due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). It drew attention to evidence that, when NIV was used in the less severely unwell patient, it also limited progression to more severe respiratory failure.2 The trial also demonstrated the feasibility, of delivering NIV on general medical or admission wards that had enhanced support and when staff were provided with ongoing training. In subsequent years, NIV has been shown to deliver better rather than equivalent outcomes to invasive ventilation in AECOPD and better evidence has accumulated for the use of NIV in non-COPD disease in the intervening years. Repeated national audits have, however, raised concerns that expected patient benefit is not being delivered and have pointed to a number of process deficiencies.3–5 There is also the risk, in the absence of justifying trial evidence, that the preferred use of NIV in AECOPD might be extended to all hypercapnic patients, irrespective of circumstance or underlying disease process. That this is a real risk might be inferred from the BTS audits where the indication for NIV was not COPD in over 30% of cases.3 ,4 NIV development in the UK has been largely outside the organisational ‘umbrella’ of critical care. This may have adversely affected resource allocation and contributed to a lack of integration in NIV and IMV patient pathways. Other unintended consequences might be a restriction on access to invasive ventilation and delay in the development of extended applications of NIV, such as accelerating extubation and its use in the management of …

Remote pulmonary function testing using a depth sensor

We propose a remote non-invasive approach to Pulmonary Function Testing using a time-of-flight depth sensor (Microsoft Kinect V2), and correlate our results to clinical-standard spirometry results. Given point clouds, we approximate 3D models of the subjects chest, estimate the volume throughout a sequence and construct volume-time and flow-time curves for two prevalent spirometry tests: Forced Vital Capacity and Slow Vital Capacity. From these, we compute clinical measures, such as FVC, FEV1, VC and IC. We correlate automatically extracted measures with clinical spirometry tests on 40 patients in an outpatient hospital setting. These demonstrate high within-test correlations.

Executive Function, Survival, and Hospitalization in Chronic Obstructive Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment Trial (NETT)

RATIONALE Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. OBJECTIVES We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. METHODS This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. MEASUREMENTS AND MAIN RESULTS The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. Georges Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B-A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. CONCLUSIONS In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and there was a possible modest association with survival. It is plausible that cerebrovascular comorbidities explain previously described cognitive pathology in COPD.

Chronic breathlessness: re-thinking the symptom

We wholly applaud the move by Johnson et al. [1] to improve awareness of breathlessness and to raise its profile as a subject for focussed clinical research. We consider their research and the ensuing proposal to recognise breathlessness via a new medical term, “chronic breathlessness syndrome”, as important and justified. We share their goal, which is to direct attention to this neglected, undertreated and under-researched symptom. People with breathlessness should be involved in renaming their condition as their experience can be influenced by clinical language http://ow.ly/ZKNj30hzUUM

Toward Respiratory Assessment Using Depth Measurements from a Time-of-Flight Sensor

Introduction: There is increasing interest in technologies that may enable remote monitoring of respiratory disease. Traditional methods for assessing respiratory function such as spirometry can be expensive and require specialist training to perform and interpret. Remote, non-contact tracking of chest wall movement has been explored in the past using structured light, accelerometers and impedance pneumography, but these have often been costly and clinical utility remains to be defined. We present data from a 3-Dimensional time-of-flight camera (found in gaming consoles) used to estimate chest volume during routine spirometry maneuvres. Methods: Patients were recruited from a general respiratory physiology laboratory. Spirometry was performed according to international standards using an unmodified spirometer. A Microsoft Kinect V2 time-of-flight depth sensor was used to reconstruct 3-dimensional models of the subjects thorax to estimate volume-time and flow-time curves following the introduction of a scaling factor to transform measurements to volume estimates. The Bland-Altman method was used to assess agreement of model estimation with simultaneous recordings from the spirometer. Patient characteristics were used to assess predictors of error using regression analysis and to further explore the scaling factors. Results: The chest volume change estimated by the Kinect camera during spirometry tracked respiratory rate accurately and estimated forced vital capacity (FVC) and vital capacity to within ± <1%. Forced expiratory volume estimation did not demonstrate acceptable limits of agreement, with 61.9% of readings showing >150 ml difference. Linear regression including age, gender, height, weight, and pack years of smoking explained 37.0% of the variance in the scaling factor for volume estimation. This technique had a positive predictive value of 0.833 to detect obstructive spirometry. Conclusion: These data illustrate the potential of 3D time-of-flight cameras to remotely monitor respiratory rate. This is not a replacement for conventional spirometry and needs further refinement. Further algorithms are being developed to allow its independence from spirometry. Benefits include simplicity of set-up, no specialist training, and cost. This technique warrants further refinement and validation in larger cohorts.

White matter lesions characterise brain involvement in moderate to severe chronic obstructive pulmonary disease, but cerebral atrophy does not.

BackgroundBrain pathology is relatively unexplored in chronic obstructive pulmonary disease (COPD). This study is a comprehensive investigation of grey matter (GM) and white matter (WM) changes and how these relate to disease severity and cognitive function.MethodsT1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV1 52.1% pred., PaO2 10.1 kPa) and 24 age, gender-matched controls. T1-weighted images were segmented into GM, WM and cerebrospinal fluid (CSF) tissue classes using a semi-automated procedure optimised for use with this cohort. This procedure allows, cohort-specific anatomical features to be captured, white matter lesions (WMLs) to be identified and includes a tissue repair step to correct for misclassification caused by WMLs. Tissue volumes and cortical thickness were calculated from the resulting segmentations. Additionally, a fully-automated pipeline was used to calculate localised cortical surface and gyrification. WM and GM tissue volumes, the tissue volume ratio (indicator of atrophy), average cortical thickness, and the number, size, and volume of white matter lesions (WMLs) were analysed across the whole-brain and regionally – for each anatomical lobe and the deep-GM. The hippocampus was investigated as a region-of-interest. Localised (voxel-wise and vertex-wise) variations in cortical gyrification, GM density and cortical thickness, were also investigated. Statistical models controlling for age and gender were used to test for between-group differences and within-group correlations. Robust statistical approaches ensured the family-wise error rate was controlled in regional and local analyses.ResultsThere were no significant differences in global, regional, or local measures of GM between patients and controls, however, patients had an increased volume (p = 0.02) and size (p = 0.04) of WMLs. In patients, greater normalised hippocampal volume positively correlated with exacerbation frequency (p = 0.04), and greater WML volume was associated with worse episodic memory (p = 0.05). A negative relationship between WML and FEV1 % pred. approached significance (p = 0.06).ConclusionsThere was no evidence of cerebral atrophy within this cohort of stable COPD patients, with moderate airflow obstruction. However, there were indications of WM damage consistent with an ischaemic pathology. It cannot be concluded whether this represents a specific COPD, or smoking-related, effect.