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.
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 George's 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'.
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 (FEV(1)) 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.
The CAT score is simple to implement as an outcome measure, it improves in response to PR and can distinguish categories of response.
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.
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.
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.
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.
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.
Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV
) <80% predicted and FEV
/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms ...and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities.
We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed.
22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (r
) between PRISm and spirometric COPD (r
=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (r
=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits.
This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene
), rs9431040 (
), rs62018863 (
) and rs185937162 (
), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.
Background
Several biological treatments have become available for management of severe asthma. There is a significant overlap in the indication of these treatments with lack of consensus on the ...first‐line biologic choice and switching practice in event of treatment failure.
Aims
To evaluate outcomes of biologic treatments through analysis of the UK Severe Asthma Registry (UKSAR), and survey of the UK severe asthma specialists' opinion.
Methods
Patients registered in the UKSAR database and treated with biologics for severe asthma in the period between January 2014 and August 2021, were studied to explore biologic treatments practice. This was complemented by survey of opinion of severe asthma specialists.
Results
A total of 2490 patients from 10 severe asthma centres were included in the study (mean age 51.3 years, 61.1% female, mean BMI 30.9 kg/m2). Biologics use included mepolizumab 1115 (44.8%), benralizumab 925 (37.1%), omalizumab 432 (17.3%), dupilumab 13 (0.5%) and reslizumab 5 (0.2%). Patients on omalizumab were younger and had earlier age of onset asthma than those prescribed mepolizumab or benralizumab. Patients prescribed mepolizumab and benralizumab had similar clinical characteristics. Those on benralizumab were more likely to continue treatment at approximately one year follow‐up (93.9%), than those on mepolizumab (80%), or omalizumab (69.6%). The first‐choice biologic differed between centres and changed over the study time period. Experts' opinion also diverged in terms of biologic initiation choice and switching practice.
Conclusion
We observed significant variation and divergence in the prescribing practices of biologics in severe asthma that necessitates further research and standardization.
Exercise induces signaling networks to improve muscle function and confer health benefits. To identify divergent and common signaling networks during and after different exercise modalities, we ...performed a phosphoproteomic analysis of human skeletal muscle from a cross-over intervention of endurance, sprint, and resistance exercise. This identified 5,486 phosphosites regulated during or after at least one type of exercise modality and only 420 core phosphosites common to all exercise. One of these core phosphosites was S67 on the uncharacterized protein C18ORF25, which we validated as an AMPK substrate. Mice lacking C18ORF25 have reduced skeletal muscle fiber size, exercise capacity, and muscle contractile function, and this was associated with reduced phosphorylation of contractile and Ca
handling proteins. Expression of C18ORF25 S66/67D phospho-mimetic reversed the decreased muscle force production. This work defines the divergent and canonical exercise phosphoproteome across different modalities and identifies C18ORF25 as a regulator of exercise signaling and muscle function.
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.
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 subject's 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.
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.
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.
Brain 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.
T1-weighted and fluid-attenuated inversion recovery images were acquired for 31 stable COPD patients (FEV
52.1% pred., PaO
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.
There 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 FEV
% pred. approached significance (p = 0.06).
There 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.
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