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Biomedical subjects

W MacNee

Publications and source records attributed to W MacNee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Potential mechanisms of adverse pulmonary and cardiovascular effects of particulate air pollution (PM10).

PM10 is the international convention for measuring environmental particulate air pollution. Increases in PM10 have been linked to exacerbations of airways disease and deaths from respiratory and cardiovascular causes. PM10 is a complex and variable mixture but toxicological data suggests that ultrafine particles, transition metals and endotoxins are the most likely components to mediate adverse health effects. Potential mechanisms for the local and systemic adverse effects of PM10 are discussed.

Air Pollutants↗
PubMed2001

Enhanced neutrophil response in chronic obstructive pulmonary disease.

BACKGROUND: Neutrophils are likely to play a major role in the inflammatory response seen in chronic obstructive pulmonary disease (COPD). This study sought to address the hypothesis that an enhanced neutrophil response to proinflammatory agents in COPD may contribute to their recruitment and activation in the lungs. METHODS: Circulating neutrophils were obtained from 10 patients with COPD, eight long term smokers with normal lung function, and eight healthy never smoking controls. The in vitro production of reactive oxygen species (ROS) was measured by the NADPH oxidase method (respiratory burst) and the surface expression of several adhesion molecules (Mac-1, LFA-1 and L-selectin) was measured by flow cytometry. Measurements were obtained under basal conditions and after stimulation with phorbol myristate acetate (PMA) and tumour necrosis factor alpha (TNFalpha). mRNA levels of p22-phox (a subunit of NADPH oxidase) and Mac-1 (CD11b) were also determined by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Patients with COPD showed enhanced respiratory burst compared with smokers with normal lung function, both under basal conditions (mean (SE) fluorescence intensity (MFI) 15.1 (0.5) v 11.6 (0.5); mean difference -3.4 (95% CI of the difference -5.1 to -1.8), p<0.01) and after PMA stimulation (MFI 210 (7) v 133 (10); mean difference -77 (95% CI of the difference -102 to -52), p<0.01). Mac-1 surface expression was also enhanced in patients with COPD, both under basal conditions (MFI 91 (5) v 45 (3); mean difference -46 (95% CI of the difference -61 to -31), p<0.001) and after stimulation with TNFalpha (MFI 340 (15) v 263 (11); mean difference -77 (95% CI of the difference -119 to -34), p=0.001). These differences were also apparent when patients with COPD were compared with non-smokers (p<0.05). The mRNA levels of p22-phox and Mac-1 (CD11b) were similar in patients with COPD and smokers with normal lung function, suggesting that the observed differences were due to post-transcriptional regulation. CONCLUSIONS: These results demonstrate an enhanced neutrophil response to proinflammatory agents in patients with COPD which may contribute to their enhanced recruitment and activation in the lungs of these patients. These findings support those of other studies which have indicated that the neutrophil is likely to play a major role in the pathogenesis of this disease.

Aged↗
PubMed2001

Adenoviral E1A primes alveolar epithelial cells to PM(10)-induced transcription of interleukin-8.

The presence of the adenoviral early region 1A (E1A) protein in human lungs has been associated with an increased risk of chronic obstructive pulmonary disease (COPD), possibly by a mechanism involving amplification of proinflammatory responses. We hypothesize that enhanced inflammation results from increased transcription factor activation in E1A-carrying cells, which may afford susceptibility to environmental particulate matter < 10 microm (PM(10))-mediated oxidative stress. We measured interleukin (IL)-8 mRNA expression and protein release in human alveolar epithelial cells (A549) transfected with the E1A gene (E1A+ve). Both E1A+ve and -ve cells released IL-8 after incubation with TNF-alpha, but only E1A+ve cells were sensitive to LPS stimulation in IL-8 mRNA expression and protein release. E1A+ve cells showed an enhanced IL-8 mRNA and protein response after treatment with H(2)O(2) and PM(10). E1A-enhanced induction of IL-8 was accompanied by increases in activator protein-1 and nuclear factor-kappa B nuclear binding in E1A+ve cells, which also showed higher basal nuclear binding of these transcription factors. These data suggest that the presence of E1A primes the cell transcriptional machinery for oxidative stress signaling and therefore facilitates amplification of proinflammatory responses. By this mechanism, susceptibility to exacerbation of COPD in response to particulate air pollution may occur in individuals harboring E1A.

Adenovirus E1A Proteins↗
PubMed2001

"Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases", summary of the ERS Research Seminar in Budapest, Hungary, September, 1999.

In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases" was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H2O2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.

Antioxidants↗
PubMed2001

Ambient particle inhalation and the cardiovascular system: potential mechanisms.

Well-documented air pollution episodes throughout recent history have led to deaths among individuals with cardiovascular and respiratory disease. Although the components of air pollution that cause the adverse health effects in these individuals are unknown, a small proportion by mass but a large proportion by number of the ambient air particles are ultrafine, i.e., less than 100 nm in diameter. This ultrafine component of particulate matter with a mass median aerodynamic diameter less than 10 microm (PM(10) may mediate some of the adverse health effects reported in epidemiologic studies and for which there is toxicologic evidence to support this contention. The exact mechanism by which ultrafine particles have adverse effects is unknown, but these particles have recently been shown to enhance calcium influx on contact with macrophages. Oxidative stress is also to be anticipated at the huge particle surface; this can be augmented by oxidants generated by recruited inflammatory leukocytes. Atheromatous plaques form in the coronary arteries and are major causes of morbidity and death associated epidemiologically with particulate air pollution. In populations exposed to air pollution episodes, blood viscosity, fibrinogen, and C-reactive protein (CRP) were higher. More recently, increases in heart rate in response to rising air pollution have been described and are most marked in individuals who have high blood viscosity. In our study of elderly individuals, there were significant rises in CRP, an index of inflammation. In this present review, we consider the likely interactions between the ultrafine particles the acute phase response and cardiovascular disease.

Acute Disease↗
PubMed2001

Oxidants/antioxidants and chronic obstructive pulmonary disease: pathogenesis to therapy.

There is now considerable evidence for an increased oxidant burden in smokers, particularly in those smokers who develop chronic obstructive pulmonary disease (COPD), as shown by increased markers of oxidative stress in the airspaces, breath, blood and urine. The presence of increased oxidative stress is a critical feature in the pathogenesis of COPD, since it results in inactivation of antiproteinases, airspace epithelial injury, mucus hypersecretion, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of pro-inflammatory mediators. The sources of the increased oxidative stress in patients with COPD derive from the increased burden of oxidants present in cigarette smoke, or from the increased amounts of reactive oxygen species released from leukocytes, both in the airspaces and in the blood. Antioxidant depletion or deficiency in antioxidants also contributes to oxidative stress. The development of airflow limitation is related to dietary deficiency of antioxidants and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. Oxidative stress also has a role in enhancing the airspace inflammation, which occurs in smokers and patients with COPD through the activation of redox-sensitive transcriptions factors such as NF-kappa B and AP-1, which regulate the genes for pro-inflammatory mediators and protective antioxidant gene expression. Antioxidants that have good bioavailability or molecules that have antioxidant enzyme activity are therefore therapies that not only protect against the direct injurious effects of oxidants, but also may fundamentally alter the inflammatory events which have a central role in the pathogenesis of COPD.

Airway Obstruction↗
PubMed2000

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Blotting, Western↗
PubMed2000

Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation.

Exposure to particulate air pollution (PM(10)) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM(10) induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM(10), endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM(10) could activate nuclear factor-kappa B (NF-kappaB), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM(10) samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-kappaB in A549 cells. Furthermore, increased NF-kappaB activity was observed in the absence of IkappaB degradation. To evaluate the role of iron, A549 cells were exposed to PM(10) previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM(10) were able to activate NF-kappaB, whereas this response was completely abrogated in cells exposed to PM(10) treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM(10) on NF-kappaB activation by exposing alveolar epithelial cells to soluble fractions from PM(10) treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM(10) which activated NF-kappaB, fractions from PM(10) treated with deferoxamine and ferrozine did not stimulate NF-kappaB activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PM(10) did not inhibit NF-kappaB. In summary, PM(10) activates NF-kappaB in A549 cells by an iron-mediated mechanism in the absence of IkappaB degradation.

Adenocarcinoma↗
PubMed2000

Regulation of iNOS expression and glutathione levels in rat liver by oxygen tension.

Molecular oxygen (O(2)) regulates the expression of a variety of genes. We hypothesized that O(2) tension may regulate iNOS expression in rat liver through the production of reactive oxygen species (ROS) and the reduction of intracellular glutathione (GSH) levels. To investigate this hypothesis, we determined the effects of hyperoxia upon iNOS induction (both at the protein and mRNA level) and the intracellular concentration of GSH in an isolated in vitro perfused rat liver preparation. To study the potential involvement of ROS in the intracellular signaling pathway linking changes in oxygen tension to gene expression, we repeated these determinations in the presence of the thiol antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a significant induction of the iNOS protein and mRNA levels paralleled by a significant fall in intracellular GSH concentration. The addition of NAC (1 mM) to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH levels. These results indicate that molecular O(2) regulates the expression of iNOS in rat liver at the transcriptional level, most likely through the production of ROS and the reduction of intracellular GSH levels.

Acetylcysteine↗
PubMed2000

Asthma and PM10.

PM10 (the mass of particles present in the air having a 50% cutoff for particles with an aerodynamic diameter of 10 microm) is the standard measure of particulate air pollution used worldwide. Epidemiological studies suggest that asthma symptoms can be worsened by increases in the levels of PM10. Epidemiological evidence at present indicates that PM10 increases do not raise the chances of initial sensitisation and induction of disease, although further research is warranted. PM10 is a complex mixture of particle types and has many components and there is no general agreement regarding which component(s) could lead to exacerbations of asthma. However pro-inflammatory effects of transition metals, hydrocarbons, ultrafine particles and endotoxin, all present to varying degrees in PM10, could be important. An understanding of the role of the different components of PM10 in exacerbating asthma is essential before proper risk assessment can be undertaken leading to advice on risk management for the many asthmatics who are exposed to air pollution particles.

Air Pollution↗
PubMed2000

Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches.

Glutathione (L-gamma-glutamyl-L-cysteinylglycine, GSH), is a vital intra- and extracellular protective antioxidant. Glutathione is synthesized from its constituent amino acids by the sequential action of gamma-glutamylcysteine synthetase (gamma-GCS) and GSH synthetase. The rate-limiting enzyme in GSH synthesis is gamma-GCS. Gamma-GCS expression is modulated by oxidants, phenolic antioxidants, and inflammatory and anti-inflammatory agents in various mammalian cells. The intracellular GSH redox homeostasis is strictly regulated to govern cell metabolism and protect cells against oxidative stress. Growing evidence has suggested that cellular oxidative processes have a fundamental role in inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox-sensitive transcription factors such as NF-kappaB and AP-1, which differentially regulate the genes for proinflammatory mediators and protective antioxidant genes such as gamma-GCS, Mn-SOD, and heme oxygenase-1. The critical balance between the induction of proinflammatory mediators and antioxidant genes and the regulation of the levels of GSH in response to oxidative stress at the site of inflammation is not known. Knowledge of the mechanisms of redox GSH regulation and gene transcription in inflammation could lead to the development of novel therapies based on the pharmacological manipulation of the production of this important antioxidant in inflammation and injury. This FORUM article features the role of GSH levels in the regulation of transcription factors, whose activation and DNA binding leads to proinflammatory and antioxidant gene transcription. The potential role of thiol antioxidants as a therapeutic approach in inflammatory lung diseases is also discussed.

Animals↗
PubMed2000

Localization of gamma-glutamylcysteine synthetase messenger rna expression in lungs of smokers and patients with chronic obstructive pulmonary disease.

Cigarette smoking results in an oxidant/antioxidant imbalance in the lungs and inflammation, which are considered to be key factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). Glutathione (GSH) is an important protective antioxidant in lung epithelial cells and epithelial lining fluid. De novo GSH synthesis in cells occurs by a two-enzyme process. The rate-limiting enzyme is gamma-glutamylcysteine synthetase (gamma-GCS), in which the heavy subunit (HS) constitutes most of its catalytic activity. The localization and expression of gamma-GCS-HS in specific lung cells as well as possible differences in its expression between smokers with and without COPD have not yet been studied. The purpose of this study was to investigate gamma-GCS-HS expression using messenger RNA in situ hybridization in peripheral lung tissue. We studied 23 current or ex-smokers with similar smoking histories with (n = 11; forced expiratory volume in 1 s [FEV(1)] < 75% predicted) or without COPD (n = 12; FEV(1) < 84% predicted). We assessed the relations between pulmonary gamma-GCS-HS expression, FEV(1) and transforming growth factor-beta1 (TGFbeta(1)), because TGFbeta(1) can modulate gamma-GCS-HS expression in lung epithelial cells. Gamma-GCS-HS is predominantly expressed by airway and alveolar epithelial cells, alveolar CD68+ cells (macrophages), and endothelial cells of both arteries and veins. In subjects with COPD, semiquantitative analysis revealed higher levels of gamma-GCS-HS messenger RNA in alveolar epithelium (1.5 times, p <.04) and a trend for a higher expression in bronchiolar epithelium (1.3 times, p =.075) compared with subjects without COPD. We did not observe a significant correlation between airway and alveolar epithelial gamma-GCS-HS expression and TGFbeta(1) expression (r =.20), FEV(1) percentage predicted (r =.18), or FEV(1)/forced vital capacity ratio (r =.14; p.05). Our results show that gamma-GCS-HS is localized, particularly in lung epithelium, and shows higher expression in smokers with COPD. This suggests a specific role for enhanced GSH synthesis as a mechanism to provide an adaptive response against oxidative stress in patients with COPD.

Aged↗
PubMed2000

Effects of lisinopril and amlodipine on antioxidant status in experimental hypertension.

The objective of this investigation was to compare changes in antioxidant status (together with other metabolites relevant to hypertension) in plasma and cardiac tissue from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY), following 8 weeks of treatment with lisinopril (angiotensin converting enzyme inhibitor) or amlodipine (Ca(2+) channel antagonist) respectively. There was no significant difference in the levels of total antioxidant capacity, retinol, urea, albumin or triglyceride in plasma from SHR or WKY rats, with or without lisinopril or amlodipine treatment. However in SHR rats, levels of alpha-tocopherol were substantially reduced in both plasma (-54% WKY, P<0.01) and cardiac tissue (-43% WKY, P<0.05). Treatment with lisinopril ameliorated reduced levels of plasma alpha-tocopherol in SHR rats, but not in cardiac tissue. Amlodipine treatment had no effect on alpha-tocopherol levels in plasma or cardiac tissue in SHR rats. In SHR rats total cholesterol levels were significantly lower thanWKY controls (-36%, P<0.001). This effect was reversed in lisinopril treated SHR rats (+27%, P<0.01). Plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were reduced in untreated SHR rats (P<0.025) when compared to WKY controls; neither lisinopril nor amlodipine treatment significantly altered these parameters. These findings suggest possible alternative mechanisms of action for lisinopril, and reinforce its use in hypertensive patients or patients with left ventricular hypertrophy.

Amlodipine↗
PubMed2000

Oxidative stress and regulation of glutathione in lung inflammation.

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The human gamma-GCS heavy and light subunits are regulated by AP-1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti-inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro- and anti-inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

Cysteine↗
PubMed2000

Increased calcium influx in a monocytic cell line on exposure to ultrafine carbon black.

Ultrafine particles have been shown to induce pro-inflammatory effects both in vivo and in vitro. Increased expression of pro-inflammatory genes probably requires the activation of specific transcription factors such as nuclear factor kappa B (NF-kappaB) via a number of possible pathways including Ca2+ and reactive oxygen species. The fluorescent dye fura 2, was used to measure cytosolic Ca2+ in the human monocytic cell line, Monomac 6 on exposure to 66 microg x mL(-1) of either ultrafine carbon black (ufCB; diameter 14 nm), carbon black (CB; diameter 260 nm), quartz (diameter 1.45 microm), or medium alone. UfCB but not fine CB induced a 1.6-fold increase (p<0.01) in the resting cytosolic Ca2+ concentration of Monomac 6 cells. In addition ufCB induced a 2.6-fold increase (p<0.001) in the response to the endoplasmic reticulum Ca2+- adenosine triphosphatase (ATPase) inhibitor, thapsigargin, suggesting the Ca2+ release-activated Ca2+ current across the plasma membrane was enhanced. This response was inhibited by the removal of extracellular Ca2+ and by the Ca2+ channel blocker, verapamil. In addition, ufCB stimulated the entry of extracellular Mn2+. Finally, the antioxidants mannitol and nacystelin both inhibited the effects of ufCB on the response to thapsigargin. These data suggest that ultrafine carbon black particles stimulated an increase in cytosolic Ca2+, possibly through the entry of extracellular Ca2+ via Ca2+ channels in the plasma membrane. The particles may in part activate the opening of Ca2+ channels via a mechanism involving reactive oxygen species.

Calcium↗
PubMed2000

Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components.

OBJECTIVES: Particulate air pollution has been shown to cause adverse health effects, and the ultrafine particle component has been implicated. The aim of the present study was to investigate whether an ultrafine particle exerted its effects through transition metals or other soluble factors released from the surface of the particles. METHODS: Both in vitro and in vivo models were used to test the imflammogenicity of carbon black (CB) and ultrafine carbon black (UfCB) and the role of transition metals was investigated by treating the particles with desferrioxamine mesylate (desferal), a transition metal chelator. Rats were instilled with particles and the cell population assessed by bronchoalveolar lavage (BAL). Calcium homeostasis in macrophages was assessed with a fluorimetric technique. RESULTS: UfCB was inflammogenic compared with CB when instilled into Wistar rat lungs, an effect which could not be ameliorated by desferal treatment of the particles. Particle leachates produced no significant inflammation in vivo. In vitro experiments showed that the cytosolic calcium ion concentration in Mono Mac 6 cells was increased significantly after UfCB treatment and treatment of particles with desferal did not alter these effects. Particle leachates had no effect on cytosolic calcium ion concentration. Iron was not detected in leachates of the particles with the desferal assay, however, ng/mg of particles were detectable in citrate leachates with inductively coupled plasma-mass spectrometry (ICP-MS). CONCLUSIONS: The increased inflammogenicity of UfCB compared with CB cannot be explained by soluble transition metals released from or by accumulation of iron at the particle surface. Differences may be accounted for by increased surface area or particle number.

Air Pollutants↗
PubMed2000

Randomized controlled trial of supported discharge in patients with exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: A randomised trial was performed on patients presenting to hospital with an exacerbation of chronic obstructive pulmonary disease (COPD) to compare outcomes in those managed at home with support with those admitted to hospital in the standard manner. METHODS: Over an 18 month period all patients presenting to the Royal Infirmary of Edinburgh on weekdays (n=718) with a diagnosis of an exacerbation of COPD were assessed for inclusion in the trial. Patients with impaired level of consciousness, acute confusion, acute changes on radiography, or an arterial pH of <7.35 or with other serious medical or social reasons for admission were excluded. Patients randomised to home support were discharged with an appropriate treatment package (antibiotics, corticosteroids, nebulised bronchodilators and, if necessary, home oxygen). They were visited by a nurse the following day and thereafter at intervals of 2-3 days until recovery when they were discharged from follow up. Parallel observations were made on patients allocated to normal hospital admission up to the point of discharge. Patients in both groups were assessed at home eight weeks after the initial assessment. RESULTS: Among weekday patients 353 (50%) were considered obligatory admissions, 140 (19%) were admitted because of co-morbidity, 17 (2%) because of poor social circumstances, and 24 (3%) did not consent to the trial. The remaining 184 (26%) were randomised (2:1) either to home support or to a standard hospital admission. The median time to discharge was 7 days for the home support group and 5 days for the admitted group (p<0.01); 25% of the home support group and 34% of the admitted group were readmitted before the final assessment at eight weeks (p>0.05). There were no significant differences between the groups in attendances by GPs and carers or in health status measured eight weeks after the initial assessment. Satisfaction with the service was good. The mean total health service cost per patient was estimated as 877 pounds sterling for the home support group and 1753 pounds sterling for the admitted group. CONCLUSIONS: This study shows that home supported discharge is a well tolerated, safe, and economic alternative to hospital admission for a proportion of patients referred to hospital for admission for an exacerbation of COPD.

Adult↗