No association between exacerbation frequency and stroke in patients with COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of stroke than the general population. Chronic inflammation associated with COPD is thought to contribute to this risk. Exacerbations of COPD are associated with a rise in inflammation, suggesting that there may be an association between exacerbation frequency and the risk of stroke. This study examined that association. METHODS: Using the UK Clinical Practice Research Datalink, COPD patients with a first stroke between January 2004 and December 2013 were identified as cases and matched on age, sex, and general practice to controls with COPD but without a stroke (6,441 cases and 19,323 controls). Frequent exacerbators (FEs) were defined as COPD patients with ≥2 exacerbations, and infrequent exacerbators (IEs) have ≤1 exacerbation in the year prior to their stroke. Conditional logistic regression was used to estimate the association between exacerbation frequency and stroke overall, and by stroke subtype (hemorrhagic, ischemic, or transient ischemic attack). Exacerbations were also categorized into 0, 1, 2, or ≥3 exacerbations in the year prior to stroke. RESULTS: There was no evidence that FE had an increased odds of stroke compared to IE (OR [odds ratio] =0.95, 95% CI [confidence interval] =0.89-1.01). There was strong evidence that the risk of stroke decreased with each exacerbation of COPD experienced per year (P trend =0.003). In the subgroup analysis investigating stroke subtype, FE had 33% lower odds of hemorrhagic stroke than IE (OR =0.67, 95% CI =0.51-0.88, P=0.003). No association was found within other stroke types. CONCLUSION: This study found no evidence of a difference in the odds of stroke between IE and FE, suggesting that exacerbation frequency is unlikely to be the reason for increased stroke risk among COPD patients. Further research is needed to explore the association through investigation of stroke risk and the severity, duration, treatment of exacerbations, and concurrent treatment of cardiovascular risk factors

Diagnosis of acute kidney injury and its association with in-hospital mortality in patients with infective exacerbations of bronchiectasis: cohort study from a UK nationwide database.

BACKGROUND: Many patients with bronchiectasis have recurrent hospitalisations for infective exacerbations. Acute kidney injury (AKI) is known to be associated with increased in-hospital mortality. This study examined the frequency of AKI, associated risk-factors, and the association of AKI with in-hospital mortality among patients with bronchiectasis. METHODS: Anonymised data of patients with non-cystic fibrosis bronchiectasis from the UK Clinical Practice Research Datalink, linked to Hospital Episode Statistics, were used to identify hospitalisations with a primary diagnosis of lower respiratory tract infection (LRTI), from 2004 to 2013. After estimating the proportion of AKI diagnoses, a multivariable logistic regression model was constructed to investigate which background factors were associated with AKI. In-hospital mortality was compared between hospitalisations with and without an AKI diagnosis, with subsequent logistic regression analyses carried out for the association between AKI and in-hospital mortality. RESULTS: Of 7804 hospitalisations due to LRTI observed in 3477 patients with bronchiectasis, 230 hospitalisations involved an AKI diagnosis, an average of 2.9%. However, the percentage increased from less than 2% in 2004 to nearly 5% in 2013. After taking this temporal change into account, AKI was independently associated with older age, male sex, decreased baseline kidney function, previous history of AKI, and a diagnosis of sepsis. In-hospital mortality was 33.0% (76/230) and 6.8% (516/7574), in hospitalisations with and without AKI, respectively (P < 0.001). After adjustment for confounding factors, diagnosis of AKI remained associated with in-hospital mortality (Odds ratio 5.52, 95% confidence interval: 3.62-8.42). CONCLUSIONS: Among people with bronchiectasis hospitalised for infective exacerbations, there is an important subgroup of patients who develop AKI. These patients have substantially increased in-hospital mortality and therefore greater awareness is needed

Self-reported symptoms of chronic cough and breathlessness in working-age men in the city of Izhevsk, Russia: associations with cardiovascular disease risk factors and comorbidities.

INTRODUCTION: Very little is known about the prevalence of respiratory symptoms or their associations with other health conditions in Russia. METHODS: Between 2008 and 2010, a sample of 983 men resident in Izhevsk, Russia, took part in a cross-sectional survey. Presence of respiratory symptoms was determined from self-report of chronic productive cough and breathlessness assessed using the British Medical Research Council (MRC) breathlessness scale. Self-reported physical and mental health were measured using the 12-Item Short-Form Health Survey (SF-12). Hypertension was assessed from mean blood pressure measured at the health check and/or self-reported use of antihypertensive medication. Other comorbidities were assessed from self-report. Logistic regression models were fitted assessing the association between respiratory symptoms and comorbidities. Linear regression models were fitted to investigate the association between respiratory symptoms and self-reported health scores. All models were adjusted for age, education and smoking status. RESULTS: The age-standardised prevalence of cough and breathlessness was 20.9% (prevalence with breathlessness MRC grade 3 or above 3.7%). The majority of men with respiratory symptoms (87.3%) were current smokers. Cough and breathlessness were associated with substantially worse self-reported physical and mental health (test for trend with severity of breathlessness p<0.001). Those with chronic cough and grade 3 or above breathlessness had higher odds of having hypertension (OR 3.03; 95% CI 1.36 to 6.74), diabetes (OR 10.55; 95% CI 2.69 to 41.37), angina pectoris (OR 7.54; 95% CI 3.61 to 15.73), previous myocardial infarction (OR 7.61; 95% CI 2.10 to 27.4) and previous stroke (OR 6.61; 95% CI 1.75 to 23.34) compared with those without respiratory symptoms. CONCLUSIONS: The prevalence of respiratory symptoms was high. Strong associations were found between respiratory symptoms and cardiovascular comorbidities. These are of particular importance given the extremely high level of cardiovascular disease mortality in Russia

Validity and interpretation of spirometric recordings to diagnose COPD in UK primary care.

BACKGROUND: The diagnosis of COPD is dependent upon clinical judgment and confirmation of the presence of airflow obstruction using spirometry. Spirometry is now routinely available; however, spirometry incorrectly performed or interpreted can lead to misdiagnosis. We aimed to determine whether spirometry undertaken in primary care for patients suspected to have COPD was of sufficient quality and whether their spirometry was correctly interpreted. METHODS: Two chest physicians re-read all spirometric readings for both quality of the procedure and interpretation, received as a part of COPD validation studies using data from the Clinical Practice Research Datalink (CPRD). We then used logistic regression to investigate predictors of correct interpretation. RESULTS: Spirometry traces were obtained for 306 patients, of which 221 (72.2%) were conducted in primary care. Of those conducted in primary care, 98.6% (n=218) of spirometry traces were of adequate quality. Of those traces that were of adequate quality and conducted in primary care, and in whom a general practitioner (GP) diagnosis of COPD had been made, 72.5% (n=218) were consistent with obstruction. Historical records for asthma diagnosis significantly decreased odds of correct interpretation. CONCLUSION: The quality of the spirometry procedure undertaken in primary care is high. However, this was not reflected in the quality of interpretation, suggesting an unmet training in primary care. The quality of the spirometry procedure as demonstrated by spirometric tracings provides a re-assurance for the use of spirometric values available in the electronic health care record databases for research purposes

COPD disease severity and the risk of venous thromboembolic events: a matched case-control study.

BACKGROUND: It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE). While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts. METHODS: A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782). COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history. Frequent exacerbators were defined as patients with COPD with ≥ 2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls). Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE. RESULTS: After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR]moderate:mild =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (ORsevere:mild/moderate =1.17; 95% CIs =1.06, 1.26). However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15). CONCLUSION: COPD severity defined by airflow limitation or medication usage, but not exacerbation frequency, appears to be associated with VTE events in people with COPD. This finding highlights the disconnect between disease activity and severity in COPD

Prognostic variables and scores identifying the end of life in COPD: a systematic review.

INTRODUCTION: COPD is a major cause of mortality, and the unpredictable trajectory of the disease can bring challenges to end-of-life care. We aimed to investigate known prognostic variables and scores that predict prognosis in COPD in a systematic literature review, specifically including variables that contribute to risk assessment of patients for death within 12 months. METHODS: We conducted a systematic review on prognostic variables, multivariate score or models for COPD. Ovid MEDLINE, EMBASE, the Cochrane database, Cochrane CENTRAL, DARE and CINAHL were searched up to May 1, 2016. RESULTS: A total of 5,276 abstracts were screened, leading to 516 full-text reviews, and 10 met the inclusion criteria. No multivariable indices were developed with the specific aim of predicting all-cause mortality in stable COPD within 12 months. Only nine indices were identified from four studies, which had been validated for this time period. Tools developed using expert knowledge were also identified, including the Gold Standards Framework Prognostic Indicator Guidance, the RADboud Indicators of Palliative Care Needs, the Supportive and Palliative Care Indicators Tool and the Necesidades Paliativas program tool. CONCLUSION: A number of variables contributing to the prediction of all-cause mortality in COPD were identified. However, there are very few studies that are designed to assess, or report, the prediction of mortality at or less than 12 months. The quality of evidence remains low, such that no single variable or multivariable score can currently be recommended

Cardiovascular outcomes following a respiratory tract infection among adults with non-CF bronchiectasis: a general population based study

Rationale: Studies suggest that people with bronchiectasis are at increased risk of cardiovascular co-morbidities. Objectives: We aimed to quantify the relative risk of incident cardiovascular events following a respiratory tract infection amongst people with bronchiectasis. Methods: Using UK electronic primary care records, we conducted a within-person comparison using the self-controlled case series method. We calculated the relative risk of first time cardiovascular events (either first myocardial infarction [MI] or stroke) following a respiratory tract infection compared with the individual’s baseline risk. Results: Our cohort consisted of 895 individuals with non-CF bronchiectasis with a first MI or stroke and at least one respiratory tract infection. There was an increased rate of first time cardiovascular events in the 91 day period after a respiratory tract infection (Incidence Rate Ratio [IRR] 1.56; 95% CI 1.20 to 2.02). The rate of a first cardiovascular event was highest in the first three days following a respiratory tract infection (IRR 2.73, 95% CI 1.41 to 5.27). Conclusions: These data suggest that respiratory tract infections are strongly associated with a transient increased risk of first time MI or stroke amongst people with bronchiectasis. As respiratory tract infections are six times more common in people with bronchiectasis than the general population, the increased risk has a disproportionately greater impact in these individuals. These findings may have implications for including cardiovascular risk modifications in airway infection treatment pathways in this population