Biomedical subjects

E H Walters

Publications and source records attributed to E H Walters.

At least 19 recordsLinked to original sources

PubMed2006

Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma.

BACKGROUND: Subepithelial hypervascularity and angiogenesis in the airways are part of structural remodelling of the airway wall in asthma, but the effects of inhaled corticosteroids (ICS) on these have not been explored. Increased vascularity in asthma may contribute to a number of functional abnormalities. A study was undertaken to explore angiogenic modulation by ICS and its likely regulation via vascular endothelial growth factor (VEGF), its receptors and the angiopoietins. METHODS: A placebo-controlled intervention study with ICS in asthma was performed, examining vascularity, VEGF, its receptors (VEGFR1 and VEGFR2), and angiopoietin-1 (Ang1) to assess which of these factors were changed in the asthmatic airways after ICS treatment. Airway wall biopsy specimens, lavage fluid and cells were obtained from 35 patients with mild asthma randomised to receive ICS or placebo for 3 months, after which bronchoscopic examination and sample collection were repeated. Immunohistochemistry and image analysis were used to obtain quantitative measures of vessels, angiogenic sprouts, VEGF, VEGFR1, VEGFR2 and Ang1 staining in airway biopsy specimens. ELISA was used to assess VEGF concentrations in the lavage fluid. RESULTS: Vessel, VEGF and sprout staining were decreased after 3 months of ICS treatment. VEGF levels remained unchanged. VEGF receptors and Ang1 staining were not reduced after treatment. CONCLUSIONS: The findings of this study support an effect of ICS in downregulating angiogenic remodelling in the airways in asthma, associated with decreasing VEGF activity within the airway wall. The environment of the airways after treatment with ICS, with changes in the balance between VEGF, its receptors, Ang1 and sprouts, appears to be less angiogenic than in untreated asthma.

Administration, Inhalation↗

PubMed2006

Immunosuppressive and cytotoxic therapy for pulmonary sarcoidosis.

BACKGROUND: Immunosuppressive and cytotoxic agents have been used as both an alternative to oral corticosteroids, and as a means of maintaining a low dose of steroids in the treatment of pulmonary sarcoidosis. OBJECTIVES: To determine the efficacy of immunosuppressive and cytotoxic agents in the treatment of pulmonary sarcoidosis. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE and CINAHL were searched for possible randomised trials and bibliographies were checked for other potentially relevant trials. Searches were current as of April 2006. SELECTION CRITERIA: Randomised controlled trials comparing an immunosuppressive or cytotoxic therapy with a control in patients with pulmonary sarcoidosis were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data for entry in to the RevMan 4.2. Pharmaceutical companies and study investigators were contacted for unpublished trials. MAIN RESULTS: Five studies were included in the review. Trials comparing methotrexate, chloroquine, cyclosporin A and pentoxifylline were identified. No data could be combined for a meta-analysis. Data on lung function, chest x-ray scores and dyspnoea were largely inconclusive. Adverse effects were associated with methotrexate, cyclosporin A, chloroquine and pentoxifylline. In two small studies methotrexate and pentoxifylline were associated with a steroid sparing effect. In the methotrexate study this was apparent after 12 months of therapy, but no difference was observed at 6 months. AUTHORS' CONCLUSIONS: The current body of evidence supporting the use of immunosuppressive agents and cytotoxic therapies is limited. Side-effects associated with some of the therapies were severe.

Antineoplastic Agents↗

PubMed2006

Anti-IgE for chronic asthma in adults and children.

BACKGROUND: Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (anti-IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. OBJECTIVES: To determine the efficacy of anti-IgE compared with placebo in patients with allergic asthma SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register for potentially relevant studies (February 2006). SELECTION CRITERIA: Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included as long as they were the same in each arm. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. MAIN RESULTS: Fourteen trials (15 group comparisons) were included in the review, contributing a total of 3143 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led to a significant reduction in inhaled steroid (ICS) consumption compared with placebo (-119 mcg/day (95% CI -154 to -83, three trials)). There were significant increases in the number of participants who were able to reduce ICS by over 50% (odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials)); or completely withdraw their daily ICS intake (OR 2.50 (95%CI 2.00 to 3.13; four trials)). Participants treated with Omalizumab were less likely to suffer an asthma exacerbation with treatment as an adjunct to ICS (OR 0.52, 95%CI 0.41 to 0.65, five trials), or as an ICS tapering agent (OR 0.47, 95% CI 0.37 to 0.60, four trials). AUTHORS' CONCLUSIONS: Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids, but the clinical value of the reduction in steroid consumption has be considered in the light of the high cost of Omalizumab. The impressive placebo effects observed in control groups bring into question the true effect of Omalizumab. Omalizumab was effective in reducing asthma exacerbations as an adjunctive therapy to inhaled steroids, and during steroid tapering phases of clinical trials. Omalizumab was generally well tolerated, although there were more injection site reactions with Omalizumab. Patient and physician assessments of the drug were positive. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS.

Adrenal Cortex Hormones↗

PubMed2006

How have we been managing chronic obstructive pulmonary disease in Australia?

AIM: Although chronic obstructive pulmonary disease (COPD) is a main cause of disability, hospital admissions and premature deaths in Australia, little is known about the community management of COPD in relation to recently published guidelines. The aim of the article was to report on COPD management in a community based cohort. METHODS: A random sample of adults aged between 45 and 70 years drawn from the electoral roll participated in the study. They completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of transfer factor. COPD was defined according to the Global initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Current asthma was defined as wheeze during the last 12 months together with bronchial hyperreactivity. Subjects were classified as either COPD-only, asthma-only or both asthma and COPD. RESULTS: Of 1224 subjects completing spirometry, 39 (3.5%) met the GOLD criteria for stage 2 or 3 COPD, asthma-only was found in 99 (8.9%) subjects and 40 (3.6%) subjects had both asthma and COPD. The COPD-only group was significantly older than the other two groups. More than 40% of subjects with COPD did not have a diagnosis of COPD from their doctors. Only 48.7% of subjects with COPD had ever been prescribed medication for their breathing. More than two-thirds of all subjects had seen a doctor for breathing problems, but very few had seen a general practitioner in the last 12 months and even fewer had respiratory function tests. CONCLUSIONS: Most subjects with COPD are being undertreated. Diagnosis, monitoring and referral systems should be improved. Preventive activities such as influenza vaccination and smoking cessation should be intensified.

Administration, Inhalation↗

PubMed2006

The dynamics and associations of airway neutrophilia post lung transplantation.

UNLABELLED: Bronchoalveolar lavage (BAL) neutrophilia has been repeatedly observed in lung transplant recipients with established bronchiolitis obliterans syndrome (BOS). Little is known of the fluctuations in BAL and airway neutrophilic inflammation post-transplant. This prospective longitudinal study aimed to evaluate the dynamic changes of lung allograft neutrophils with time, immunosuppression, infection and BOS. A total of 28, initially healthy, BOS 0, lung transplant recipients underwent 134 bronchoscopic assessments, including BAL and endobronchial biopsies (EBB) (with immunohistochemistry) over 3-year follow up. Subsequently, 21 developed BOS 0p and 16 ultimately BOS. Compared to controls, there was early and persistent BAL neutrophilia (p < 0.05), contrasting with an initially normal EBB that shows a progressive increased airway wall neutrophil infiltrate. BAL neutrophilia (but not airway wall neutrophilia) was most striking when there was concomitant bronchopulmonary infection, particularly in the patients with BOS. Univariate and multivariate analyses suggested that BAL neutrophilia was linked to markers of infection while EBB neutrophilia was linked with coexistent inflammation with macrophages and lymphocytes. IN CONCLUSION: (i) BAL neutrophilia is predominantly associated with infection; (ii) Airway wall neutrophilia (as monitored by EBB) increases with time post-transplant and is not associated with infection; (iii) By itself, BOS is not the major contributor to BAL and EBB neutrophilia.

Adult↗

PubMed2005

Encasement of bedding does not improve asthma in atopic adult asthmatics.

AIM: We evaluated the impact of impermeable bed covers on asthma in asthmatics with clinically relevant house dust mite (HDM) sensitization. METHODS: The study included 32 HDM-sensitized asthmatics in whom HDM allergy was considered as a significant factor in their asthma. They were randomized into either an intervention group whose bedding was encased with impermeable covers, or a control group who received cotton covers. Before and 3 and 6 months after encasement, dust samples were collected from the bedding and assayed for Der p 1. Clinical outcomes included quality of life, lung function, bronchial reactivity to methacholine, symptoms, medications and peak flow rates. RESULTS: Baseline Der p 1 levels in both the active and the placebo groups were comparable and high (19.2 vs 18.9 microg/g of dust). There was a significant reduction in Der p 1 levels in the active group after 6 months, but not in the placebo group (7.3 vs 21.9 microg/g of dust). Quality of life improved significantly in both the intervention and control groups, but there was no significant difference in the improvements between the groups. There was no significant change in lung function, symptoms, and requirements for medications. CONCLUSIONS: Encasement of bedding significantly reduced the Der p 1 levels. However, this was not sufficient to produce worthwhile clinical improvement in those in whom dust mite avoidance might well have been recommended as part of their clinical management.

Adult↗

PubMed2005

Action plans for chronic obstructive pulmonary disease.

BACKGROUND: The effectiveness of action plans as treatment for chronic obstructive pulmonary disease (COPD) is not known. OBJECTIVES: To assess the efficacy of action plans in the management of COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, CINAHL and the National Research Register of Ongoing Trials. We also searched reference lists of identified studies. The search was completed in August 2004. SELECTION CRITERIA: Randomised controlled trials of action plans in COPD. Studies with a primary diagnosis of asthma excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Investigators were contacted for additional information when necessary. Study results were combined in meta-analyses using the Cochrane Collaboration software RevMan. MAIN RESULTS: There was evidence of a positive effect of action plans on self-management knowledge. The mean difference (MD) for recognition of a severe exacerbation was 2.50; 95% confidence interval 1.04 to 3.96, for self-action in severe exacerbations MD 1.50; 95% confidence interval 0.62 to 2.38 and the use of antibiotics MD 6.00; 95% confidence interval 2.68 to 9.32. There was also evidence of a positive effect on the initiation of antibiotics (odds ratio (OR) 10.16; 95% confidence interval 2.02 to 51.09) and/or oral steroids (OR 6.58; 95% confidence interval 1.29 to 33.62). However, there was no evidence of significant effects on healthcare utilisation, health-related quality of life, lung function, functional capacity, symptom scores, mortality, anxiety, or depression. No trials used as outcomes: number of exacerbations, length of exacerbations, or days lost from work. AUTHORS' CONCLUSIONS: This review shows there is evidence that action plans aid people with COPD in recognising and reacting appropriately to an exacerbation of their symptoms via the self-initiation of antibiotics or steroids. Further research needs to be completed with more comprehensive outcomes measures in order to ascertain whether this results in significantly decreased morbidity and/or mortality.

Behavior Therapy↗

PubMed2005

Oral corticosteroids for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic lung disorder, usually related to cigarette smoking, representing a major and increasing cause of morbidity and mortality. It is defined "as a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases". The use of corticosteroids for their anti-inflammatory effects has been suggested. OBJECTIVES: To assess the effects of oral corticosteroids on the health status of patients with stable COPD. SEARCH STRATEGY: Searches of the Cochrane Airways Group Specialised Register and MEDLINE were carried out in December 2003 and 2004. Review articles and bibliographies were searched. SELECTION CRITERIA: Randomised controlled prospective studies in adults with stable COPD ( post-bronchodilator FEV1 <80% of predicted, FEV1/FVC <70%) and a history of smoking, excluding known asthmatics, in which oral steroid use was compared with placebo and use of co-interventions was matched in both groups. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers. All trials were combined using Review Manager (version 4.2.7). MAIN RESULTS: From 459 titles 24 studies met the inclusion criteria. Treatment lasted three weeks or less in 19 studies, high dose oral steroid was used in 21 studies and subjects had moderate or severe COPD in 15 studies. There was a significant difference in FEV1 after two weeks treatment, WMD 53.30 ml; 95% confidence interval 22.21 to 84.39 favouring oral steroid use compared to placebo when 14 studies with available data (n=396) were combined, with no significant heterogeneity. There was a significant increase in odds for individual patient FEV1 response greater than 20% from baseline with high dose oral steroid treatment compared to placebo, OR 2.71; 95% CI 1.84 to 4.01 (9 studies) . It would be necessary to treat 7 patients (95% CI 5 to 12) with oral corticosteroids to achieve one extra case of increasing FEV1 by more than 20%, with a placebo group risk of 0.13. All differences in health-related quality of life were less than the minimum clinically important difference. There were small statistically significant advantages for functional capacity and respiratory symptom of wheeze with oral steroid treatment but no significant difference in risk of withdrawal from study due to an exacerbation or rate of serious exacerbations over 2 years with low dose oral steroid treatment. There was an increased risk of adverse effects, including increased blood glucose, adrenal suppression and reduced serum osteocalcin. AUTHORS' CONCLUSIONS: There is no evidence to support the long-term use of oral steroids at doses less than 10-15 mg prednisolone though some evidence that higher doses (>/= 30 mg prednisolone) improve lung function over a short period. Potentially harmful adverse effects e.g.. diabetes, hypertension, osteoporosis would prevent recommending long-term use at these high doses in most patients.

Administration, Oral↗

PubMed2005

Prostacyclin for pulmonary hypertension in adults.

BACKGROUND: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Pulmonary hypertension can be idiopathic or associated with other conditions. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation, and can be given orally, subcutaneously, intravenously or inhaled via a nebuliser. OBJECTIVES: To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension. SEARCH STRATEGY: Electronic searches were carried out with pre-specified terms. Searches were current as of July 2004. SELECTION CRITERIA: Two reviewers selected randomised controlled trials (RCTs) involving adults with pulmonary hypertension for inclusion. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes. We sub-grouped data where possible by aetiology of PH (PPH, PH secondary to connective tissue disorder or mixed populations). MAIN RESULTS: Nine RCTs of mixed duration (3 days-52 weeks), recruiting 1175 participants were included (NYHA functional classes II-IV). Intravenous prostacyclin versus usual care (four studies): There were significant improvements in exercise capacity of around 90 metres, cardiopulmonary haemodynamics and NYHA functional class over 3 days-12 weeks. Effects were consistent in primary and secondary pulmonary hypertension. Oral prostacyclin versus placebo (two studies): Short-term data (3-6 months) indicated that there was a significant improvement in exercise capacity, but data from one study of 52 weeks reported no significant difference at 12 months. No significant differences were observed for any other outcome. Subcutaneous treprostinil versus placebo (two studies, 8-12 weeks):One large study reported a significant median improvement in exercise capacity of around 16 metres. Cardiopulmonary haemodynamics and symptom scores favoured treprostinil. Infusion site pain and withdrawals due to adverse events were more frequent with treprostinil. Inhaled prostacyclin versus placebo (one study, 12 weeks):There was a significant increase in exercise capacity of approximately 36 metres. Treatment led to better symptom scores and functional class status than with placebo. Subgroup analyses reported by individual studies showed a better exercise capacity in participants with PPH, than those participants with PH secondary to other diseases. Side effects and adverse events were common in the studies. AUTHORS' CONCLUSIONS: There is evidence that intravenous prostacyclin in addition to conventional therapy at tolerable doses optimised by titration, can confer some short-term benefits (up to 12 weeks of treatment) in exercise capacity, NYHA functional class and cardiopulmonary haemodynamics. There is also some evidence that patients with more severe disease based upon NYHA functional class showed a greater response to treatment.

Adult↗

PubMed2005

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: COPD is a common condition, mainly related to smoking. The burden of the disease is increasing and it is projected to rank fifth in 2020 for the world-wide burden of disease. Acute exacerbations of COPD, usually related to superimposed infection occur commonly and systemic corticosteroids are widely used in their management in combination with other treatments including antibiotics, oxygen supplementation and bronchodilators. OBJECTIVES: To determine the efficacy of corticosteroids, administered either parenterally or orally, on the outcome in patients with acute exacerbations of COPD. SEARCH STRATEGY: Searches were carried out using the Cochrane Airways Group COPD RCT register with additional studies sought in the bibliographies of randomised controlled trials and review articles. Authors of identified randomised controlled trials were contacted for other published and unpublished studies. The last search was carried out in August 2004. SELECTION CRITERIA: Randomised controlled trials comparing corticosteroids, administered either parenterally or orally, with appropriate placebo. Other interventions e.g. bronchodilators and antibiotics were standardised. Clinical studies of acute asthma were excluded. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers. Outcome data was sent to authors for verification. All trials were combined using Review Manager (version 4.2.4) for analyses. MAIN RESULTS: Ten studies were identified that fulfilled the inclusion criteria. There were significantly fewer treatment failures within thirty days in patients given corticosteroid treatment, odds ratio 0.48; 95% confidence interval 0.34 to 0.68 and Hazard Ratio 0.78; 95% confidence interval 0.63 to 0.97. It would have been necessary to treat 9 patients (95%CI 6 to 14) with systemic corticosteroids to avoid one treatment failure in this time period. There was no significant difference in mortality. The early FEV1, up to 72 hours, showed a significant treatment benefit, weighted mean difference 140 mls (95% confidence interval 80-200 mls), although this benefit was not found for later time points. There was a significant improvement in breathlessness and blood gases between 6 - 72 hours after treatment. There was an increased likelihood of an adverse drug reaction with corticosteroid treatment, odds ratio 2.29; 95% confidence interval 1.55 to 3.38. Overall one extra adverse effect occurred for every 6 people treated (95% CI 4 to 10). The risk of hyperglycaemia was significantly increased, odds ratio 5.48; 95% confidence interval 1.58 to 18.96. AUTHORS' CONCLUSIONS: Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment . It increases the rate of improvement in lung function and dyspnoea over the first 72 hours, but at a significantly increased risk of an adverse drug reaction.

Acute Disease↗

PubMed2005

Long-acting beta2-agonists in asthma: an overview of Cochrane systematic reviews.

According to major asthma management guidelines, long-acting beta2-agonists (LABAs) should be used only when asthma remains symptomatic in patients already receiving regular inhaled corticosteroids (ICSs). A large Cochrane systematic review provides evidence that LABAs are safe and beneficial in control of asthma; sub-group analyses indicating that this is true when ICSs are used and in their absence. Two other Cochrane systematic reviews have found that LABAs are more effective than regular short-acting beta2-agonists, and are as effective as theophylline with fewer side-effects. These reviews support guidelines in the use of LABA as additional therapy when asthma is inadequately controlled by ICS at moderate dose. However, guidelines may be too conservative, and more studies in stable mild asthma comparing their use and safety with placebo and ICS are required.

Administration, Inhalation↗

PubMed2005

Changes in indoor allergen and fungal levels predict changes in asthma activity among young adults.

BACKGROUND: Exposures to allergens are thought to be important risk factors for asthma. We conducted a longitudinal study of indoor allergen and fungal levels in Melbourne homes between 1996 and 1998 to examine the effect of changes in allergen exposure upon asthma and associated outcomes. METHODS: Participants were visited at home in 1996 (n=485) and 1998 (n=360), when dust and air samples were collected from their bedrooms and assayed for Der p 1, Fel d 1, ergosterol and fungal propagules. Subjects then attended the lung function laboratory to complete a questionnaire, spirometry, methacholine challenge and skin prick testing. The associations between the change in allergen levels and change in clinical outcomes were examined using multiple logistic and linear regression. RESULTS: Participants whose Cladosporium fungal exposure doubled had 52% greater odds of having had an attack of asthma in the last 12 months. A doubling of fungal exposure was also associated with 53% greater odds of developing atopy. A doubling of Fel d 1 floor levels was associated with 73% increased odds of doctor-diagnosed asthma. A doubling of Der p 1 levels in bed dust was associated with a 64% greater odds of persistent bronchial hyper-reactivity. CONCLUSIONS: These findings provide evidence that changes in indoor levels of fungi and house dust mites can affect the risk of development and persistence of asthma and atopy in adults. Further studies are required to establish any benefit of sustained reductions in indoor allergen exposures, and to determine whether these effects are truly 'allergic' or because of immune stimulation in the airway through other less specific mechanisms.

Adult↗

PubMed2005

Inter-relationships between airway inflammation, reticular basement membrane thickening and bronchial hyper-reactivity to methacholine in asthma; a systematic bronchoalveolar lavage and airway biopsy analysis.

BACKGROUND: Asthma is accepted as a disease characterized by airway inflammation, with evidence that airway structural changes, or 'remodelling' occurs. There are few studies relating airway physiology, inflammation and remodelling, however. We have carried out a study of inter-relationships between airway inflammation, airway remodelling, reticular basement membrane (RBM) thickening, and bronchial hyper-reactivity (BHR), before and after high-dose inhaled corticosteroid (fluticasone propionate 750 microg b.d.), in a group of relatively mild but symptomatic, steroid naïve asthma patients. METHODS: Double-blind, randomized, placebo-controlled, parallel group study of inhaled corticosteroid (ICS) in 35 asthmatics, with bronchoalveolar lavage (BAL) and airway endobronchial biopsy (EBB) for inflammatory cell profiles and EBB for airway remodelling carried out at baseline, 3 and 12 months. RESULTS: At baseline RBM thickening was related to BAL mast cells and EBB eosinophil counts. In turn baseline log EBB EG2 eosinophil count, log%BAL epithelial cells and log RBM thickness explained 55% of the variability in BHR. CONCLUSION: We provide new information that airway inflammation, remodelling, and BHR in asthma are inter-related and improved by ICS therapy. Our data potentially support the need for early and long-term intervention with ICS even in relatively mild asthmatics, and the need to further assess the potential merit of longitudinal BHR testing in management of some patients, as this may reflect both airway inflammation and remodelling.

Asthma↗

PubMed2005

Biological dust exposure in the workplace is a risk factor for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Although the main risk factor is smoking, 15-19% of COPD even in smokers has been attributed to occupational exposures. The aim of this study was to investigate the association between occupational exposure and risk of COPD. METHODS: Participants were part of a cross sectional study of risk factors for COPD. A total of 1232 completed a detailed respiratory questionnaire, spirometric testing and measurement of gas transfer. Job histories were coded according to the International Standard Classification of Occupations. These codes were then used to establish occupational exposures using the ALOHA job exposure matrix. RESULTS: The prevalence of emphysema was 2.4%, chronic obstructive bronchitis 1.8%, and COPD 3.4%. Subjects ever exposed to biological dusts had an increased risk of chronic obstructive bronchitis (OR 3.19; 95% CI 1.27 to 7.97), emphysema (OR 3.18; 95% CI 1.41 to 7.13), and COPD (OR 2.70, 95% CI 1.39 to 5.23). These risks were higher in women than in men. For biological dust, the risk of emphysema and COPD was also significantly increased in both the duration of exposure categories, again in women but not in men. No significant increased risks for COPD were found for mineral dust (OR 1.13; 95% CI 0.57 to 2.27) or gases/fumes (OR 1.63; 95% CI 0.83 to 3.22). CONCLUSION: In this general population sample of adults, occupational exposures to biological dusts were associated with an increased risk of COPD which was higher in women. Preventive strategies should be aimed at reducing exposure to these agents in the workplace.

Aged↗

PubMed2005

Time to death, airway wall inflammation and remodelling in fatal asthma.

Fatal asthma is characterised pathologically by airway wall remodelling, eosinophil and neutrophil infiltration, accumulation of mucus in the airway lumen and smooth muscle shortening. The durations of fatal attacks of asthma show a clear bimodal distribution. Airway smooth muscle contraction and the accumulation of luminal mucus may contribute to death from asthma and relate to time to death. The current authors have examined these two components in uninflated lung tissue in cases of fatal asthma from the second Victorian asthma mortality study. Based on time from onset of symptoms to death, cases fell into two distinct groups: short course <3 (1.5+/-0.6 mean+/-sd) h; and long course >8 (12.3+/-5.9) h. Short course cases had more muscle shortening, higher levels of salbutamol and higher ratios of neutrophils to eosinophils than long course cases, who tended to have more mucus in the lumen. In conclusion, this study confirms the dichotomy of both time to death and the eosinophil/neutrophil ratio in cases of fatal asthma. It suggests that in short course cases acute airway narrowing is due, predominantly, to bronchoconstriction despite higher blood levels of salbutamol. Mucus accumulation may be more important in long course cases.

Adolescent↗

PubMed2004

Decreased lung capillary blood volume post-exercise is compensated by increased membrane diffusing capacity.

The diffusing capacity of the lung for carbon monoxide (DLCO) decreases to below the pre-exercise value in the hours following a bout of intense exercise. Two mechanisms have been proposed: (1) development of pulmonary oedema and (2) redistribution of central blood volume to peripheral muscles causing a reduction in pulmonary capillary blood volume ( V(c)). In the present study DLCO, V(c) and the membrane diffusing capacity ( D(m)) were measured in nine healthy females using a rebreathing method, in contrast to the single breath technique employed in previous studies. DLCO, V(c) and D(m) were measured before and at 1, 2, 3, 16 and 24 h following maximal treadmill exercise. Compared with pre-exercise values, DLCO was depressed by up to 8.9 (3.0)% ( P<0.05) for the first 3 h following exercise, but had returned to pre-exercise values by 16 h post-exercise. V(c) fell by 21.2 (4.1)% ( P<0.05) at 3 h post-exercise, but at the same time D(m) increased by 14.7 (9.1)%. It was concluded that: (1) the increase in D(m) made it unlikely that the fall in DLCO was due to interstitial oedema and injury to the blood gas barrier; (2) on the other hand, the reduction in DLCO following exercise was consistent with a redistribution of blood away from the lungs; and (3) the trend for D(m) and V(c) to reciprocate one another indicates a situation in which a fall in V(c) nevertheless promotes gas transfer at the respiratory membrane. It is suggested that this effect is brought about by the reorientation of red blood cells within the pulmonary capillaries following exercise.

Adaptation, Physiological↗

PubMed2004

Azathioprine as an oral corticosteroid sparing agent for asthma.

BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled by using inhaled steroids. However, for a small group of asthmatics, symptoms can only be controlled by high doses of oral steroids. Continuous use of oral steroid is associated with severe side-effects, but it has been suggested that azathioprine, an immunosuppressive anti-metabolite, often used to reduce the immune response in chronic active hepatitis and severe rheumatoid arthritis, could be useful as an oral steroid sparing agent. There is a need to systematically evaluate the evidence regarding its use to reduce or eliminate oral corticosteroid usage. OBJECTIVES: The objective of this review is to assess the efficacy of adding azathioprine in patients with stable asthma who are dependent on oral corticosteroids with the intention of eventually minimizing or eliminating the use of these steroids. SEARCH STRATEGY: Searches of the Cochrane Airways Group asthma and wheeze trials register were undertaken with predefined search terms. Searches were current as of February 2003 SELECTION CRITERIA: Only studies with a randomised placebo-controlled design met the inclusion criteria for the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for suitability for inclusion in the review. Data were extracted and entered into RevMan 4.2.2. MAIN RESULTS: Two small trials recruiting 23 participants met the inclusion criteria for the review. Participants may have been suffering from comorbid lung disease. No data on oral steroid consumption were reported. No significant differences were observed in the studies for FEV(1), FVC, PaO(2) and symptoms. One study reported a statistically significant difference in SGaw, but the clinical importance of this is uncertain. Due to concerns over the small sample sizes and methodological shortcomings in terms of inadequate washout in one study, and methods used in outcome assessment for both studies, the findings of the studies are not generalisable to the issue of steroid tapering. REVIEWER'S CONCLUSIONS: Currently there is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.

Administration, Inhalation↗

PubMed2004

Anti-IgE for chronic asthma in adults and children.

BACKGROUND: Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. OBJECTIVES: To determine the efficacy of anti-IgE in patients with allergic asthma SEARCH STRATEGY: We searched the Cochrane Airways Group Asthma trials register (February 2003) for potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials examining anti-IgE administered in any manner for any duration. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. MAIN RESULTS: Eight trials were included in the review, contributing a total of 2037 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led to a significant reduction in inhaled steroid consumption compared with placebo: -114 mcg/day (95% CI -150 to -78.13, two trials). There were significant increases in the number of participants who were able to reduce steroids by over 50%: odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials); or completely withdraw their daily steroid intake: OR 2.50, 95%CI 2.00 to 3.13 (four trials). Participants treated with Omalizumab were less likely to suffer an asthma exacerbation with treatment as an adjunct to steroids (OR 0.49, 95%CI 0.38 to 0.64, four trials), or as a steroid tapering agent (OR 0.47, 95% CI 0.37 to 0.60, four trials). REVIEWERS' CONCLUSIONS: Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids, but the mean difference in steroid consumption achieved with Omalizumab was of debatable clinical value. The impressive effects observed in control groups bring into question the true effect of Omalizumab. Omalizumab was effective in reducing asthma exacerbations as an adjunctive therapy to inhaled steroids. Omalizumab was well tolerated, although the safety profile requires longer term assessment. Patient and physician assessment of the drug was positive. Further assessment in paediatric and severe adult populations is necessary, as is double-dummy comparison with inhaled corticosteroids.

Adult↗