Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation ...and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days. Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation. In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg.L(-1) versus 3.4 mg.L(-1). Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators. Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.
Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the ...time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies.
BACKGROUND Although it is presumed that exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased airway inflammation, there is little information available on ...inflammatory markers during an exacerbation and the relationship with severity or time course of recovery. A study was undertaken to investigate the sputum cell and cytokine characteristics of COPD when stable and during an exacerbation. METHODS Induced sputum samples from 57 patients with moderate to severe COPD were analysed (44 samples were taken during a stable period and 37 during an exacerbation). The patients recorded daily symptoms on diary cards. Cell counts and sputum levels of interleukin (IL)-6 and IL-8 were measured. RESULTS Patients with ⩾3 exacerbations/year had higher median stable sputum levels of IL-6 (110 (95% CI 11 to 215) pg/ml) and IL-8 (6694 (95% CI 3120 to 11995) pg/ml) than those with ⩽2 exacerbations/year (22 (95% CI 12 to 93) and 1628 (95% CI 607 to 4812) pg/ml, respectively). Median IL-6 levels were increased during exacerbations compared with stable conditions. The levels of IL-6 during exacerbations were related to the presence of a cold and to the total cell count and eosinophil and lymphocyte numbers, while IL-8 was positively correlated with all sputum cell counts. Sputum cell counts and cytokine levels during an exacerbation did not predict the size and duration of lung function changes in the exacerbation. CONCLUSIONS Patients with more frequent exacerbations have higher baseline sputum cytokine levels, which may predict the frequency of future exacerbations.
Acute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking.
...A prospective cohort study (n=628) of patients with stable chronic heart failure (CHF) secondary to left ventricular systolic dysfunction was used to derive an AHFS prediction model which was then assessed in a prospectively recruited validation cohort (n=462).
Within the derivation cohort, 44 (7%) patients were hospitalised as a result of AHFS during 1 year of follow-up. Predictors of AHFS hospitalisation included furosemide equivalent dose, the presence of type 2 diabetes mellitus, AHFS hospitalisation within the previous year and pulmonary congestion on chest radiograph, all assessed at baseline. A multivariable model containing these four variables exhibited good calibration (Hosmer-Lemeshow p=0.38) and discrimination (C-statistic 0.77; 95% CI 0.71 to 0.84). Using a 2.5% risk cut-off for predicted AHFS, the model defined 38.5% of patients as low risk, with negative predictive value of 99.1%; this low risk cohort exhibited <1% excess all-cause mortality per annum when compared with contemporaneous actuarial data. Within the validation cohort, an identically applied model derived comparable performance parameters (C-statistic 0.81 (95% CI 0.74 to 0.87), Hosmer-Lemeshow p=0.15, negative predictive value 100%).
A prospectively derived and validated model using simply obtained clinical data can identify patients with CHF at low risk of hospitalisation due to AHFS in the year following assessment. This may guide the design of future strategies allocating resources to the management of CHF.
BACKGROUND Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways. It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role ...in exacerbations of chronic obstructive pulmonary disease (COPD). METHODS Seventy one patients with COPD were followed prospectively and sampled for plasma and sputum ET-1 levels when stable and during an exacerbation. Sputum was also examined for cytokines, human rhinovirus, and Chlamydia pneumoniae. RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD (mean (SD) 0.58 (0.31) pg/ml); 28 pairs of stable-exacerbation plasma samples had a mean stable ET-1 level of 0.54 (0.30) pg/ml rising to 0.67 (0.35) pg/ml at exacerbation (mean difference 0.13, 95% confidence interval (CI) 0.04 to 0.21, p = 0.004). Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second (FEV1;r = –0.29, p = 0.022) and forced vital capacity (FVC; r = –0.38, p = 0.002). The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation (Sao 2;r = –0.41, p = 0.036). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 levels were 5.37 (0.97–21.95) pg/ml rising to 34.68 (13.77–51.95) pg/ml during an exacerbation (mean difference 25.14, 95% CI 3.77 to 46.51, p = 0.028). This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels (r = 0.917, p = 0.001) and sputum interleukin (IL)-6 levels (r = 0.718, p = 0.013). CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels. ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD.
To study the prognostic value of rapid-acquisition adenosine stress-rest myocardial perfusion scintigraphy (MPS) on a gamma camera using multipinhole collimation and cadmium-zinc-telluride (CZT) ...detectors. The secondary aim was to assess the diagnostic accuracy of the technique compared with invasive coronary angiography.
Retrospective analysis of 1109 consecutive patients undergoing MPS in a routine clinical setting on a high-efficiency multipinhole gamma camera. MPS acquisition, performed with a standard injection of 550 MBq of (99m)Tc-tetrofosmin, required a mean (±SD) scanning time of 322 ± 51 s. The hard cardiac event rate at a median (inter-quartile range) follow-up of 624 (552-699) days was 0.4% (95% CI 0.1-1.1) in patients with no significant perfusion abnormality versus 6.8% (95% CI 4.3-10.7%, P < 0.001) in those with an abnormal scan. In a sub-group of 165 patients, comparison with obstructive coronary artery disease on X-ray angiography gave a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for rapid-acquisition MPS of 84% (95% CI 74-91), 79% (95% CI 68-87), 82% (95% CI 72-89), 81% (95% CI 70-89), and 82% (95% CI 73-89), respectively.
MPS performed on a CZT solid-state detector camera with multipinhole collimation is an evolutionary development that provides reliable prognostic and diagnostic information, while significantly reducing image acquisition time.
Geometallurgy of uranium deposits Bowell, R.J.; Grogan, J.; Hutton-Ashkenny, M. ...
Minerals engineering,
10/2011, Letnik:
24, Številka:
12
Journal Article
Recenzirano
► Mineralogy of uranium. ► Geometallurgy of uranium. ► Control on processing by uranium speciation. ► Control on uranium extraction by mineralogy.
Mineralogical controls exert significant control ...over the extraction of uranium from its ores. Uranium speciation, associated mineralogy, deportment and uranium mineral availability are all factors for consideration when assessing leachability. This study presents data from laboratory uranium extractions undertaken on several contrasting uranium ores from a wide range of orebodies. The results provide insight into the mineralogical factors of importance when considering uranium extraction. These results are presented within the wider context of geometallurgy and demonstrate how geometallurgical assessment, even at an early stage of mine development, can greatly assist in the design of a suitable extraction scheme.
This study examined inflammatory responses from primary cultured human bronchial epithelial cells in chronic obstructive pulmonary disease (COPD) and the clinical factors modulating them. Epithelial ...cells from bronchoscopic biopsies from 14 patients with COPD ((mean +/- SD) age 74.6 +/- 5.7 yrs, forced expiratory volume in one second (FEV1) 1.21 +/- 0.36 L, FEV1 %, predicted 51.1 +/- 15.8%, 51.5 +/- 24.0 pack-yrs of smoking, inhaled steroid dosage 1237.5 +/- 671.0 microg x day(-1), Medical Research Council (MRC) dyspnoea score 3.18 +/- 1.33) and eight current/exsmokers with normal pulmonary function (age 60.4 +/- 13.5 yrs, FEV1 2.66 +/- 1.27 L, FEV1 % pred 89.6 +/- 17.7%, 49 +/- 44 pack-yrs of smoking, MRC dyspnoea score 1 +/- 0) were grown in primary culture and exposed to 50 ng x mL(-1) tumour necrosis factor-alpha. Stimulated COPD cells produced significantly more interleukin (IL)-6 at 24 and 48 h, and IL-8 at 6 and 24 h than unstimulated COPD cells. This response was not seen in cells from current/exsmokers. IL-6 and IL-8 production was lower in COPD patients taking inhaled steroids. Following an inflammatory stimulus, bronchial epithelial cells in chronic obstructive pulmonary disease show a significant cytokine response not seen in smokers with normal pulmonary function and this may be modified by inhaled steroid therapy.
Background: Although studies have suggested that ozone (O3) and nitrogen dioxide (NO2) may play a role in the pathogenesis of asthma, the underlying mechanisms are not clear. Objective: We aimed to ...investigate the effects of O3 and NO2 on the release of IL-8, GM-CSF, RANTES, and soluble intercellular adhesion molecule 1 (sICAM-1) from human bronchial epithelial cells (HBECs) of nonatopic nonasthmatic subjects (nonasthmatic subjects) and atopic subjects with mild asthma (asthmatic subjects) in vitro. Methods: We cultured HBECs from bronchial biopsy specimens of nonasthmatic and asthmatic subjects; exposed these for 6 hours to air, 10 to 100 ppb O3, or 100 to 400 ppb NO2; and analyzed the release of IL-8, GM-CSF, RANTES, and sICAM-1 after 24 hours’ incubation. Results: There was no significant difference between the constitutive release of IL-8, GM-CSF, and sICAM-1 from HBECs of asthmatic and nonasthmatic subjects. RANTES was detected only in HBECs derived from asthmatic subjects. Exposure of HBECs of asthmatic subjects to both 50 to 100 ppb O3 and 200 to 400 ppb NO2 significantly increased the release of IL-8, GM-CSF, RANTES, and sICAM-1 from these cells after 24 hours of incubation. However, 50 to 100 ppb O3 and 200 to 400 ppb NO2 led to a significant increase in release of only IL-8 and sICAM-1 from HBECs of nonasthmatic subjects after 24 hours’ incubation. A comparison between the pollutant-induced release of mediators demonstrated that 100 ppb O3-induced release of GM-CSF and sICAM-1 was significantly greater in HBECs of asthmatic subjects (medians, 0.59 and 27.4 pg/μg cellular protein, respectively) than in HBECs of nonasthmatic subjects (medians, 0.27 and 14.4 pg/μg cellular protein, respectively; P < .02). Conclusion: These results suggest that O3 and NO2 may modulate airway diseases, such as asthma, by increasing the release of inflammatory mediators from bronchial epithelial cells and that the cells of asthmatic subjects may be more susceptible to the adverse effects of these pollutants. (J Allergy Clin Immunol 2001;107:287-94.)
BACKGROUND Although sputum induction is used as a technique to investigate lower airway inflammation in asthmatic subjects, advantages over spontaneous sputum in patients with chronic obstructive ...pulmonary disease (COPD) have not been investigated. METHODS Samples of spontaneous sputum and sputum induced with 3% hypertonic saline for 14 minutes were collected from 27 patients with chronic obstructive pulmonary disease (COPD) who usually produced spontaneous sputum. Spirometric indices and oxygen saturation (Sao 2) were measured at seven minute intervals. The spontaneous, seven and 14 minute sputum samples were analysed for total and differential cell counts, cell viability, and interleukin 8 levels. RESULTS Analysis of the sputum revealed that median cell viability was higher in the seven minute (62.8%; p = 0.004) and 14 minute (65%; p = 0.001) induced sputum samples than in spontaneous sputum (41.2%). There was no significant difference in total and differential cell counts or in interleukin 8 levels between spontaneous and induced sputum. During the sputum induction procedure the mean (SD) fall in forced expiratory volume in one second (FEV1) was 0.098 (0.111) l (p < 0.001) and in forced vital capacity (FVC) was 0.247 (0.233) l (p < 0.001). There was a small but significant fall in Sao 2 during sputum induction (p = 0.03). CONCLUSIONS Induced sputum contains a higher proportion of viable cells than spontaneous sputum. There are no significant differences between the sputum samples obtained at seven minutes and at 14 minutes of hypertonic saline nebulisation. Sputum induction is safe and well tolerated in patients with COPD.
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