Vidar Søyseth

Statin use is associated with reduced mortality in COPD

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of ischaemic heart disease (IHD). Statins reduce mortality and morbidity in IHD. It has been hypothesised that statin treatment is associated with reduced long-term mortality in patients with COPD. Using a retrospective cohort design, 854 consecutive patients (mean age 70.8 yrs; 51.5% female) with a diagnosis of COPD exacerbation were included in the study at discharge from a Norwegian teaching hospital. Median follow-up was 1.9 yrs, during which 333 patients died. The crude mortality rate per 1,000 person-yrs was 110 in patients treated with statins, and 191 in patients not treated with statins. After adjustment for sex, age, smoking, pulmonary function and comorbidities, the hazard ratio (HR) for statin users versus statin nonusers was 0.57 (95% confidence interval 0.38–0.87). When subdividing statin users and statin nonusers into groups according to concomitant treatment with inhaled corticosteroids (ICS) the following HRs were found: 0.75 (0.58–0.98) for ICS only; 0.69 (0.36–1.3) for statins only; and 0.39 (0.22–0.67) for the combined treatment with statin and ICS compared with no such treatment. Treatment with statins was associated with improved survival after chronic obstructive pulmonary disease exacerbation, while inhaled corticosteroids appeared to increase the survival benefit associated with statin use.

Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease

Background Cardiovascular co-morbidities are common in chronic obstructive pulmonary disease (COPD). Retrospective studies on selected patients have indicated that cardiac troponin elevation is frequent during acute exacerbations of COPD (AECOPD), and that this is associated with poor survival. In the present prospective study the prevalence and prognostic value of elevated cardiac troponin T (cTnT) in unselected patients with AECOPD have been investigated, using a novel high-sensitivity assay (hs-cTnT assay). Methods and results 99 patients hospitalised for AECOPD were included. They were followed until death or study termination. During a median follow-up time of 1.9 years, 57 patients (58%) died. 97 patients (98%) had measurable levels of hs-cTnT and 73 (74%) had hs-cTnT above the normal range (≥14.0 ng/l). The crude mortality rates in patients having hs-cTnT <14.0, 14.0–39.9 and ≥40 ng/l were 4.6, 30.2 and 58.3 per 100 patient-years, respectively. Adjusting for relevant covariables using an extended Cox regression analysis, the HRs (95% CI) for death were 4.5 (1.2 to 16) and 8.9 (2.4 to 32) among patients having hs-cTnT 14.0–39.9 and ≥40 ng/l, respectively, compared with patients with hs-cTnT <14.0 ng/l. The association between mortality and hs-cTnT was strongly modified by heart rate at admission (p<0.001)—that is, the association between mortality and hs-cTnT was stronger among patients with tachycardia. Conclusion Elevated hs-cTnT during AECOPD is frequent, and it is associated with increased mortality. The effect is stronger among patients having tachycardia than among patients with normal heart rate.

Aluminium potroom asthma: the Norwegian experience

Work-related asthma in aluminium potroom workers, is reviewed and discussed, mainly on the basis of own investigations. The occurrence of work-related asthma has been shown to be associated with the duration of potroom employment, although the prevalence of asthmatic symptoms is not significantly different from that of the general population. Typical manifestations of occupational asthma are described in potroom workers, and a close relationship between the levels of fluoride exposure and work-related asthmatic symptoms has been observed. The existence of occupational asthma in aluminium potroom workers has been confirmed by characteristic patterns of repeated peak flow measurements, supported by changes in methacholine responsiveness in workers with suspected work-related asthma. However, no immunological test is available to establish the diagnosis. Methacholine challenge appears to be inappropriate for screening aluminium potroom workers in order to detect work-related asthma. Current smoking, but not self-reported allergy, is a risk factor for potroom asthma. A family history of asthma and previous occupational exposure may have some effect on the risk of developing symptoms. The prognosis of potroom asthma seems to depend on early replacement to unexposed work. The pathogenetic mechanisms are unknown, although some studies indirectly imply a hypersensitivity reaction. Future studies involving specific bronchial challenge appear to be necessary to find the causal agent(s) of aluminium potroom asthma.

Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease, exacerbations of which increase strain on the heart. The prognostic value of elevated circulating levels of cardiac Troponins seen during COPD exacerbations has been investigated. From the Akershus hospital database, 897 patients discharged after treatment for COPD exacerbation in the period 2000–2003 were identified and followed-up until June 30, 2005. Median observation time was 1.9 yrs. In 396 patients, measurements of cardiac-specific troponin T (cTnT) were available. Levels of cTnT ≥0.04 μg·L−1 were considered elevated. Clinical data were retrieved from patient records and date of death was obtained from the Norwegian National Registry. In order to balance the nonrandomised nature of available cTnT measurements, an exposure propensity score (EPS) for cTnT sampling was calculated and used in regression analyses. After adjusting for EPS in Cox regression analyses, elevated cTnT was significantly associated with increased all-cause mortality in the observation period, with a hazard ratio of 1.64 (95% confidence interval 1.15–2.34). In conclusion, chronic obstructive pulmonary disease patients with elevated cardiac-specific Troponin T during exacerbation are at increased risk of death after discharge.

Respiratory symptoms as predictors of all-cause mortality in an urban community: a 30-year follow-up

Objective.  We investigated the relationship between respiratory symptoms and mortality from all causes in a large Norwegian population. We also examined mortality during separate periods of follow‐up.

Relation between exposure to fluoride and bronchial responsiveness in aluminium potroom workers with work-related asthma-like symptoms.

BACKGROUND--The relation between plasma fluoride levels and bronchial responsiveness was investigated in a longitudinal study in aluminium potroom workers who reported work-related asthmatic symptoms. METHODS--From a cross-sectional respiratory survey, 26 men who reported work-related asthmatic symptoms on a validated questionnaire were selected for repeated measurements of bronchial responsiveness to methacholine. Regular analyses of plasma fluoride levels were performed. Exposure to fluoride and total particulates was assessed from routine surveillance of the workplace. Bronchial responsiveness was expressed as the dose-response slope of the line through the origin and last data point. RESULTS--A positive association was found between bronchial responsiveness and plasma fluoride levels, such that an increase in the plasma fluoride level of 10 ng/ml was associated with an increase in the dose-response slope by a factor of 1.11 (95% confidence interval 1.05 to 1.17). Plasma fluoride levels were associated with the total atmospheric fluoride concentration in mg/m3 (beta = 28.1), but not with total particulates in the environment. CONCLUSIONS--Bronchial responsiveness in aluminium potroom workers reporting work-related asthmatic symptoms appears to be related to plasma levels of fluoride. The underlying mechanism is, however, unknown.

NT-proBNP independently predicts long term mortality after acute exacerbation of COPD - a prospective cohort study

BackgroundCardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD). NT-proBNP is an established risk factor in patients with heart failure. NT-proBNP may also be released from the right ventricle. Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD). The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied. Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.MethodsA prospective cohort study of 99 patients with 217 admissions with AECOPD. Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.ResultsMedian follow-up time was 1.9 years, and 57 patients died during follow-up. NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001). After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).ConclusionsNT-proBNP is a strong and independent determinant of mortality after AECOPD.

Respiratory symptoms and 30-year mortality from obstructive lung disease and pneumonia

Background: As little is known about the long term relationship between respiratory symptoms and mortality from non-malignant respiratory diseases, a study was undertaken to investigate the predictive value of respiratory symptoms and symptom load for mortality from obstructive lung disease (OLD) and pneumonia in the long term in a Norwegian population. Methods: In 1972, 19 998 persons aged 15–70 years living in Oslo were randomly selected for a respiratory survey. The response rate was 89%. All were followed for 30 years. The association between cough, asthma-like symptoms, two levels of dyspnoea on exercise, a symptom score, and mortality from OLD and pneumonia were investigated separately for men and women by multivariable analyses, with adjustment for age, occupational exposure to air pollution, and smoking habits. Results: OLD accounted for 43% and pneumonia for 50% of all deaths from respiratory causes. In men the hazard ratio for mortality from OLD varied from 4.0 (95% confidence interval (CI) 2.4 to 6.5) for cough to 9.6 (95% CI 5.1 to 18.3) for severe dyspnoea, and in women from 5.1 (95% CI 2.3 to 11.3) for moderate dyspnoea to 13.0 (95% CI 6.0 to 28.3) for severe dyspnoea. The symptom score was strongly predictive of death from OLD in a dose-response manner. Conclusions: There is a significant, positive, strong association between respiratory symptoms and 30 year mortality from OLD. The association between respiratory symptoms and mortality from pneumonia is weaker and not significant.

Acute exacerbation of COPD is associated with fourfold elevation of cardiac troponin T

Objective To investigate if acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with myocardial injury, expressed as elevated high sensitive cardiac troponin T (hs-cTnT), and to identify determinants of hs-cTnT in chronic obstructive pulmonary disease (COPD) patients. Design In a cross-sectional study, hs-cTnT in patients hospitalised for AECOPD was compared with hs-cTnT in COPD patients in their stable state. Setting The study was conducted at a teaching and a pulmonary rehabilitation clinic. Participants Consecutive admissions to participating units for the years 2010–2011 meeting objective, standardised criteria for AECOPD and stable COPD. Main outcomes Ratio of hs-cTnT in hospitalised AECOPD patients compared with stable COPD patients. Change in the ratio of hs-cTnT per unit increase of relevant covariables. Results The geometric mean of hs-cTnT in the index group was 25.8 ng/l (95% CI 21.1 to 31.7) compared with 4.55 ng/l (95% CI 3.72 to 5.67) in the reference group. After inclusion of relevant covariables, multiple linear regression analyses showed that the ratio between hs-cTnT in AECOPD patients and the references was 4.26 (95% CI 3.02 to 6.00) and that hs-cTnT increased 1.41-fold (95% CI 1.20 to 1.68), for each quartile increase in leucocyte count in stable COPD but not in AECOPD. Higher hs-cTnT levels were also associated with the presence of pathological q-waves (p=0.012) and electrocardiographic left ventricular hypertrophy (p=0.039), long-term oxygen treatment (p=0.002) and decreasing forced expiratory volume in 1 s (p=0.014). A significant univariable association between cTnT and arterial hypoxaemia was also found but this association was attenuated almost to a zero effect after inclusion of relevant covariates. Conclusions AECOPD is associated with higher hs-cTnT as compared with stable COPD. In stable COPD, hs-cTnT appears to be positively associated with indices of COPD severity, whereas we were unable to identify significant determinants of hs-cTnT in AECOPD.

Determinants of cardiac troponin T elevation in COPD exacerbation – a cross-sectional study

BackgroundCardiac Troponin T (cTnT) elevation during exacerbations of chronic obstructive pulmonary disease (COPD) is associated with increased mortality the first year after hospital discharge. The factors associated with cTnT elevation in COPD are not known.MethodsFrom our hospitals database, all patients admitted with COPD exacerbation in 2000–03 were identified. 441 had measurement of cTnT performed. Levels of cTnT ≥ 0.04 μg/l were considered elevated. Clinical and historical data were retrieved from patient records, hospital and laboratory databases. Odds ratios for cTnT elevation were calculated using logistic regression.Results120 patients (27%) had elevated cTnT levels. The covariates independently associated with elevated cTnT were increasing neutrophil count, creatinine concentration, heart rate and Cardiac Infarction Injury Score (CIIS), and decreasing hemoglobin concentration. The adjusted odds ratios (95% confidence intervals in parentheses) for cTnT elevation were 1.52 (1.20–1.94) for a 5 × 106/ml increase in neutrophils, 1.21 (1.12–1.32) for a 10 μmol/l increase in creatinine, 0.80 (0.69–0.92) for a 1 mg/dl increase in hemoglobin, 1.24 (1.09–1.42) for a 10 beats/minute increase in heart rate and 1.44 (1.15–1.82) for a 10 point increase in CIIS.ConclusionMultiple factors are associated with cTnT elevation, probably reflecting the wide panorama of comorbid conditions typically seen in COPD. The positive association between neutrophils and cTnT elevation is compatible with the concept that an exaggerated inflammatory response in COPD exacerbation may predispose for myocardial injury.