Almost 40 million people currently live with dementia but this is estimated to double over the next 20 years; despite this, research identifying modifiable risk factors is scarce. There is increasing ...evidence that cognitive impairment is more frequent in those with chronic lung disease than those without. Chronic obstructive pulmonary disease affects 210 million people, with cognitive impairment present in 60% of certain populations. Co-morbid cognitive dysfunction also appears to impact on important outcomes such as quality of life, hospitalisation and survival. This review summarises the evidence of an association between cognition, impaired lung function and obstructive lung disease. It goes on to examine the contribution of neuro-imaging to our understanding of the underlying pathophysiology. While the mechanisms of brain pathology and cognitive impairment are likely to be complex and multi-factorial, there is evidence to suggest a key role for occult cerebrovascular damage independent of traditional vascular risk factors, including smoking.
Preserved ratio impaired spirometry (PRISm) is defined as a FEV
of less than 80% predicted and a FEV
/forced vital capacity (FVC) ratio of 0·70 or higher. Previous research has indicated that PRISm ...is associated with respiratory symptoms and is a precursor of chronic obstructive pulmonary disease (COPD). However, these findings are based on relatively small selective cohorts with short follow-up. We aimed to determine the prevalence, risk factors, clinical implications, and mortality of PRISm in a large adult general population.
For this cohort analysis, we used data from the UKBiobank to assess PRISm prevalence, risk factors and associated symptoms, and associated comorbidities in a large adult population. Participants with spirometry deemed acceptable by an investigator (best measure FEV
and FVC values) at baseline were included. Participants were excluded if they did not have acceptable spirometry or were missing data on body-mass index or smoking status. Control spirometry was defined as a FEV
of 80% or more predicted and a FEV
/FVC ratio of 0·70 or higher. Airflow obstruction was defined as a FEV
/FVC ratio of less than 0·70. We used multivariable regression to determine risk factors for PRISm and associated comorbidities. Individuals who lived within close proximity to an assessment centre were invited for follow-up, with repeat spirometry. Only participants who had been included at baseline were examined in follow-up. This allowed for a longitudinal analysis of PRISm over time and risk factors for transition to airflow obstruction. We also did the survival analysis for a 12-year period.
Participants were recruited by UK Biobank between Dec 19, 2006, and Oct 10, 2010. We included 351 874 UK Biobank participants (189 247 women and 162 627 men) in our study, with a median follow-up of 9·0 years (IQR 8·0-10·0). 38 639 (11·0%) of 351 874 participants had PRISm at baseline. After adjustment, PRISm was strongly associated with obesity (odds ratio OR 2·40 2·26-2·55, p<0·0001), current smoking (1·48 1·36-1·62, p<0·0001), and patient reported doctor-diagnosed asthma (1·76 1·66-1·88, p<0·0001). Other risk factors identified included female sex, being overweight, trunk fat mass, and trunk fat percentage. PRISm was strongly associated with symptoms and comorbidity including increased risk of breathlessness (adjusted OR 2·0 95% CI 1·91-2·14, p<0·0001) and cardiovascular disease (adjusted OR 1·71 1·64-1·83, p<0·0001 for heart attack). Longitudinal analysis showed that 241 (12·2%) of 1973 participants who had PRISm at baseline had transitioned to airflow obstruction consistent with COPD. PRISm was associated with increased all-cause mortality (adjusted hazard ratio 1·61 95% CI 1·53-1·69, p<0·0001) versus control participants.
PRISm was associated with breathlessness, multimorbidity, and increased risk of death, which does not seem to be explained by smoking, obesity, or existing lung disease. Although for many patients PRISm is transient, it is important to understand which individuals are at risk of progressive lung function abnormalities. Further research into the genetic, structural and functional pathophysiology of PRISm is warranted.
UK Medical Research Council and University of Bristol.
Observational studies suggest an association between reduced lung function and risk of coronary artery disease and ischaemic stroke, independent of shared cardiovascular risk factors such as ...cigarette smoking. We use the latest genetic epidemiological methods to determine whether impaired lung function is causally associated with an increased risk of cardiovascular disease.
Mendelian randomisation uses genetic variants as instrumental variables to investigate causation. Preliminary analysis used two-sample Mendelian randomisation with lung function single nucleotide polymorphisms. To avoid collider bias, the main analysis used single nucleotide polymorphisms for lung function identified from UKBiobank in a multivariable Mendelian randomisation model conditioning for height, body mass index and smoking.Multivariable Mendelian randomisation shows strong evidence that reduced forced vital capacity (FVC) causes increased risk of coronary artery disease (OR 1.32, 95% CI 1.19-1.46 per standard deviation). Reduced forced expiratory volume in 1 s (FEV
) is unlikely to cause increased risk of coronary artery disease, as evidence of its effect becomes weak after conditioning for height (OR 1.08, 95% CI 0.89-1.30). There is weak evidence that reduced lung function increases risk of ischaemic stroke.
There is strong evidence that reduced FVC is independently and causally associated with coronary artery disease. Although the mechanism remains unclear, FVC could be taken into consideration when assessing cardiovascular risk and considered a potential target for reducing cardiovascular events. FEV
and airflow obstruction do not appear to cause increased cardiovascular events; confounding and collider bias may explain previous findings of a causal association.
Background Cognitive impairment is one of the least well-studied COPD comorbidities. It is known to occur in hypoxemic patients, but its presence during acute exacerbation is not established. ...Objectives The purpose of this study was to assess neuropsychological performance in patients with COPD who were awaiting discharge from hospital following acute exacerbation and recovery and to compare them with stable outpatients with COPD and with healthy control subjects. Methods We recruited 110 participants to the study: 30 inpatients with COPD who were awaiting discharge following an exacerbation, 50 outpatients with stable COPD, and 30 control subjects. Neuropsychological tests measured episodic memory, executive function, visuospatial function, working memory, processing speed, and an estimate of premorbid abilities. Follow-up cognitive assessments for patients who were stable and those with COPD exacerbation were completed at 3 months. Results Patients with COPD exacerbation were significantly worse ( P < .05) than stable patients over a range of measures of cognitive function, independent of hypoxemia, disease severity, cerebrovascular risk, or pack-years smoked. Of the patients with COPD exacerbation, up to 57% were in the impaired range and 20% were considered to have suffered a pathologic loss in processing speed. Impaired cognition was associated with worse St. George's Respiratory Questionnaire score ( r = −0.40-0.62, P ≤ .02) and longer length of stay ( r = 0.42, P = .02). There was no improvement in any aspect of cognition at recovery 3 months later. Conclusions In patients hospitalized with an acute COPD exacerbation, impaired cognitive function is associated with worse health status and longer hospital length of stay. A significant proportion of patients are discharged home with unrecognized mild to severe cognitive impairment, which may not improve with recovery.
Core outcome sets (COS) represent the minimum health outcomes to be measured for a given health condition. Interest is growing in using COS within routine care to support delivery of patient-focused ...care. This review aims to systematically map COS developed for routine care to understand their scope, stakeholder involvement, and development methods.
Medline (Ovid), Scopus, and Web of Science Core collection were searched for studies reporting development of COS for routine care. Data on scope, methods, and stakeholder groups were analyzed in subgroups defined by setting.
Screening 25,301 records identified 262 COS: 164 for routine care only and 98 for routine care and research. Nearly half of the COS (112/254, 44%) were developed with patients, alongside input from experts in registries, insurance, legal, outcomes measurement, and performance management. Research publications were often searched to generate an initial list of outcomes (115/198, 58%) with few searching routine health records (47/198, 24%).
An increasing number of COS is being developed for routine care. Although involvement of patient stakeholders has increased in recent years, further improvements are needed. Methodology and scope are broadly similar to COS for research but implementation of the final set is a greater consideration during development.
Mild cognitive impairment is a common systemic manifestation of chronic obstructive pulmonary disease (COPD). However, its pathophysiological origins are not understood. Since, cognitive function ...relies on efficient communication between distributed cortical and subcortical regions, we investigated whether people with COPD have disruption in white matter connectivity.
Structural networks were constructed for 30 COPD patients (aged 54-84 years, 57% male, FEV1 52.5% pred.) and 23 controls (aged 51-81 years, 48% Male). Networks comprised 90 grey matter regions (nodes) interconnected by white mater fibre tracts traced using deterministic tractography (edges). Edges were weighted by the number of streamlines adjusted for a) streamline length and b) end-node volume. White matter connectivity was quantified using global and nodal graph metrics which characterised the networks connection density, connection strength, segregation, integration, nodal influence and small-worldness. Between-group differences in white matter connectivity and within-group associations with cognitive function and disease severity were tested.
COPD patients' brain networks had significantly lower global connection strength (p = 0.03) and connection density (p = 0.04). There was a trend towards COPD patients having a reduction in nodal connection density and connection strength across the majority of network nodes but this only reached significance for connection density in the right superior temporal gyrus (p = 0.02) and did not survive correction for end-node volume. There were no other significant global or nodal network differences or within-group associations with disease severity or cognitive function.
COPD brain networks show evidence of damage compared to controls with a reduced number and strength of connections. This loss of connectivity was not sufficient to disrupt the overall efficiency of network organisation, suggesting that it has redundant capacity that makes it resilient to damage, which may explain why cognitive dysfunction is not severe. This might also explain why no direct relationships could be found with cognitive measures. Smoking and hypertension are known to have deleterious effects on the brain. These confounding effects could not be excluded.
The Severe Asthma Questionnaire (SAQ) is a health related quality of life (HRQoL) questionnaire validated for use in severe asthma. It is scored using the mean value of 16 items (SAQ score) in ...addition to a single item global rating of HRQoL (SAQ-global). The aim was to validate clinically relevant subscales using exploratory factor analysis (EFA).
The SAQ was completed, along with measures of asthma control and EQ5D-5L by patients attending six UK severe asthma centres. Clinical data were included in the analysis. EFA using principal axis factoring and oblimin rotation was used to achieve simple structure of data.
460 patients with severe asthma participated, 65% women, mean age 51 (16-83) years. A three factor solution achieved best fit and showed that the SAQ items formed three distinct but inter-correlated groups of items where items were grouped in a way that was consistent with item content. The three subscales were differentially associated with clinically relevant variables (lung function and mood). Males and females interpreted the question of night disturbance in different ways.
This paper provides a template for best practice in the use of EFA when validating HRQoL subscales. The SAQ can be scored as three subscales with content reflecting three different constructs people with severe asthma use when making judgements about their lives. The subscale 'My Life' assesses the impact of severe asthma on different life activities, 'My Mind' assesses the perceived emotional impact and 'My Body' the impact of extra-pulmonary symptoms and side effects.
Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and ...consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort.
This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline.
18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria.
18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.
Observational studies show an association between reduced lung function and impaired cognition. Cognitive dysfunction influences important health outcomes and is a precursor to dementia, but ...treatments options are currently very limited. Attention has therefore focused on identifying modifiable risk factors to prevent cognitive decline and preserve cognition. Our objective was to determine if lung function or risk of COPD causes reduced cognitive function using Mendelian randomization (MR).
Single nucleotide polymorphisms from genome wide association studies of lung function and COPD were used as exposures. We examined their effect on general cognitive function in a sample of 132,452 individuals. We then performed multivariable MR (MVMR), examining the effect of lung function before and after conditioning for covariates.
We found only weak evidence that reduced lung function (Beta - 0.002 (SE 0.02), p-value 0.86) or increased liability to COPD (- 0.008 (0.008), p-value 0.35) causes lower cognitive function. MVMR found both reduced FEV
and FVC do cause lower cognitive function, but that after conditioning for height (- 0.03 (0.03), p-value 0.29 and - 0.01 (0.03) p-value 0.62, for FEV1 and FVC respectively) and educational attainment (- 0.03 (0.03) p-value 0.33 and - 0.01 (0.02), p-value 0.35) the evidence became weak.
We did not find evidence that reduced lung function or COPD causes reduced cognitive function. Previous observational studies are probably affected by residual confounding. Research efforts should focus on shared risk factors for reduced lung function and cognition, rather than lung function alone as a modifiable risk factor.
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