Sub-clinical left and right ventricular dysfunction in patients with COPD

SummaryBackgroundCardiovascular manifestations in COPD include increased arterial stiffness, ischaemic heart disease, chronic heart failure and cor pulmonale. We hypothesised that sub-clinical right (RV) and left ventricular (LV) dysfunction occurs in patients with COPD, related to the severity of airflow obstruction, arterial stiffness and systemic inflammation.MethodsThirty six patients and 14 controls, all free of overt cardiovascular disease underwent tissue Doppler echocardiography, spirometry, measurement of aortic pulse wave velocity (PWV) and venous sampling for inflammatory markers.ResultsMean LV myocardial strain and strain rate were less in patients than controls, p<0.05. LV isovolumic relaxation time (IVRT) was prolonged in patients (125±15.2ms) compared with controls (98.2±21.1ms), p<0.01, indicating LV diastolic dysfunction. The RV free wall strain and strain rate were less in patients than controls, both p<0.05, indicating RV systolic dysfunction. Patients had sub-clinical pulmonary arterial hypertension with a greater RV myocardial relaxation time and Tei index, both p<0.01. Patients with mild airways obstruction had LV and RV dysfunction and evidence of increased RV afterload compared with controls. In multivariate analyses aortic PWV predicted LV IVRT, p<0.01, while FEV1 predicted RV Tei index and myocardial relaxation time, both p<0.01.ConclusionsPatients with COPD have sub-clinical left ventricular dysfunction related to arterial stiffness, and right ventricular dysfunction related to airways obstruction. Both right and left ventricular dysfunction are present in patients with mild airways obstruction suggesting that cardiac co-morbidities commence early in the development of COPD

The development and validation of the major life changing decision profile (MLCDP)

Background Chronic diseases may influence patients taking major life changing decisions (MLCDs) concerning for example education, career, relationships, having children and retirement. A validated measure is needed to evaluate the impact of chronic diseases on MLCDs, improving assessment of their life-long burden. The aims of this study were to develop a validated questionnaire, the “Major Life Changing Decision Profile” (MLCDP) and to evaluate its psychometric properties. Methods 50 interviews with dermatology patients and 258 questionnaires, completed by cardiology, rheumatology, nephrology, diabetes and respiratory disorder patients, were analysed for qualitative data using Nvivo8 software. Content validation was carried out by a panel of experts. The first version of the MLCDP was completed by 210 patients and an iterative process of multiple Exploratory Factor Analyses and item prevalence was used to guide item reduction. Face validity and practicability was assessed by patients. Results 48 MLCDs were selected from analysis of the transcripts and questionnaires for the first version of the MLCDP, and reduced to 45 by combination of similar themes. There was a high intraclass correlation coefficient (0.7) between the 13 members of the content validation panel. Four more items were deleted leaving a 41-item MLCDP that was completed by 210 patients. The most frequently recorded MLCDs were decisions to change eating habits (71.4%), to change smoking/drinking alcohol habits (58.5%) and not to travel or go for holidays abroad (50.9%). Factor analysis suggested item number reduction from 41 to 34, to 29, then 23 items. However after taking into account item prevalence data as well as factor analysis results, 32 items were retained. The 32-item MLCDP has five domains education (3 items), job/career (9), family/relationships (5), social (10) and physical (5). The MLCDP score is expressed as the absolute number of decisions that have been affected. Conclusions The 32-item (5 domains) MLCDP has been developed as an easy to complete generic tool for use in clinical practice and for quality of life and epidemiological research. Further validation is required

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular events and osteoporosis. Increased arterial stiffness is an independent predictor of cardiovascular disease. Objectives: We tested the hypothesis that patients with COPD would have increased arterial stiffness, which would be associated with osteoporosis and systemic inflammation. Methods: We studied 75 clinically stable patients with a range of severity of airway obstruction and 42 healthy smoker or ex-smoker control subjects, free of cardiovascular disease. All subjects underwent spirometry, measurement of aortic pulse wave velocity (PWV) and augmentation index, dual-energy X-ray absorptiometry, and blood sampling for inflammatory mediators. Measurements and Main Results: Mean (SD) aortic PWV was greater in patients, 11.4 (2.7) m/s, than in control subjects, 8.95 (1.7) m/s, p < 0.0001. Inflammatory mediators and augmentation index were also greater in patients. Patients with osteoporosis at the hip had a greater aortic PWV, 13.1 (1.8) m/s, than those without, 11.2 (2.7) m/s, p < 0.05. In patients, aortic PWV was related to age (r = 0.63, p < 0.0001) and log10 IL-6 (r = 0.31, p < 0.01), and inversely to FEV1 (r = –0.34, p < 0.01). The strongest predictors of aortic PWV in all subjects were age (p < 0.0001), percent predicted FEV1 (p < 0.05), mean arterial pressure (p < 0.05), and log10 IL-6 (p < 0.05). Conclusions: Increased arterial stiffness was related to the severity of airflow obstruction and may be a factor in the excess risk for cardiovascular disease in COPD. The increased aortic PWV in patients with osteoporosis and the association with systemic inflammation suggest that age-related bone and vascular changes occur prematurely in COPD

COPD: what is the unmet need?

Chronic obstructive pulmonary disease (COPD) is now recognized as a major source of ill health around the world with an important impact on both developed and developing economies. The emphasis in research has shifted from a purely physiological focus that mainly considered how airway smooth muscle tone can be modulated to improve lung emptying. Although long-acting inhaled β-agonist and antimuscarinic antagonists have improved clinical management for many symptomatic patents, there is increasing attention being paid to the inflammatory component of COPD in the airways and lung parenchyma and to its close association with other diseases, which cannot simply be attributed to their having a common risk factor such as tobacco smoking. This clinical review is intended to identify not only those areas where pharmacological treatment has been successful or has offered particular insights into COPD but also to consider where existing treatment is falling short and new opportunities exist to conduct original investigations. A picture of considerable complexity emerges with a range of clinical patterns leading to several common end points such as exacerbations, exercise impairment and mortality. Defining subsets of patients responsive to more specific interventions is the major challenge for the next decade in this field