Search PubMed⌕ Search

Biomedical subjects

E H Walters

Publications and source records attributed to E H Walters.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effect of inhaled fluticasone propionate on BAL TGF-beta(1) and bFGF concentrations in clinically stable lung transplant recipients.

BACKGROUND: Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs. METHODS: We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations. RESULTS: In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations. CONCLUSIONS: Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.

Administration, Inhalation↗
PubMed2004

Asthma and vaccination history in a young adult cohort.

BACKGROUND: It has been suggested that childhood vaccinations may be associated with the onset of asthma. We investigated the association between asthma, atopy and vaccination history in a cohort of young adults living in Melbourne, Australia. METHODS: Subjects were aged between 22 and 44 years and were surveyed by an interviewer-administered questionnaire. Questions were asked about vaccinations to measles, mumps and rubella (MMR), triple antigen (DTP), hepatitis B and Sabin polio vaccine (OPV). Atopy was assessed by skin prick testing to common aeroallergens. RESULTS: There was no significant association observed for subjects diagnosed with asthma who had received measles or MMR vaccinations compared with those who did not receive measles or MMR vaccinations (RR 1.33, 95% CI 0.98-1.80). Non-significant associations were also observed for OPV and hepatitis B vaccinations (RR 3.27, 95% CI 0.50-21.3 and RR 1.08, 95% CI 0.83-1.41, respectively). However, subjects reporting full immunisation were found to be at higher risk to asthma (RR 1.52, 95% CI 1.09-2.11) but not atopy. CONCLUSIONS: Our results show relatively weak support for the hypothesis that childhood vaccinations may lead to increased risk of asthma, but caution is advised due to possible recall bias.

Adolescent↗
PubMed2004

Fatty acid levels and risk of asthma in young adults.

BACKGROUND: There is current interest in the possible protective effect of long chain (n-3) fatty acids from fish in chronic lung diseases such as asthma. The aim of this community based cross sectional study was to determine whether plasma long chain (n-3) fatty acids, as a measure of dietary intake, differed between 1601 young adults with and without asthma. METHODS: Subjects of mean (SD) age 34.6 (7.1) years completed a detailed respiratory questionnaire, food frequency questionnaire, skin prick testing, and lung function tests including methacholine challenge test for bronchial hyperreactivity (BHR) and had venous blood taken for analysis of plasma fatty acids. Plasma fatty acid levels (%) were analysed using multiple logistic regression with alternative definitions of asthma and atopy as the outcomes. RESULTS: Atopy was not associated with any plasma fatty acid. The n-3 polyunsaturated fatty acids and n-6:n-3 ratio were not consistently associated with asthma or atopy. The n-6 polyunsaturated fatty acid dihomo gamma-linolenic acid (DHGLA) was positively associated with current asthma (OR=1.30, 95% CI 1.06 to 1.60), asthma (OR=1.34, 95% CI 1.13 to 1.60), and doctor diagnosed asthma (OR=1.25, 95% CI 1.06 to 1.48). CONCLUSION: Plasma n-3 fatty acids are not associated with a reduced risk of asthma or atopy among young adults. The association of DHGLA with asthma warrants further research to determine a cause-effect relationship.

Adult↗
PubMed2004

Airway iron and iron-regulatory cytokines in cystic fibrosis.

Iron availability is critical to Pseudomonas aeruginosa. The current authors determined sputum iron, ferritin, microalbumin levels and total cell counts (TCC) in 19 adult patients with cystic fibrosis (CF) during an acute exacerbation and repeated analyses following a median of 12 days antibiotic treatment. The current authors also determined sputum interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha levels because of their putative role in intracellular iron homeostasis. Additional data were obtained from 17 stable CF patients, eight patients with stable chronic obstructive pulmonary disease (COPD) and six normal subjects. Overall, sputum iron, ferritin, microalbumin, IL-1beta and TNF-alpha concentrations and TCCs were significantly elevated in the CF patients compared to those with COPD and normal controls. Sputum ferritin levels were significantly elevated in acute versus stable CF patients and there was a trend for sputum TCC to be higher, but all other inflammatory indices were similar. In the CF patients, sputum iron was positively and strongly related to IL-1beta, TNF-alpha, ferritin and microalbumin levels, but negatively related to forced expiratory volume in one second % predicted. In those acute patients who clinically improved with antibiotics (n=14), there were significant decreases in sputum TCC, iron, ferritin and IL-1beta content, but not TNF-alpha or albumin levels. However, changes in sputum TNF-alpha in acute patients were still closely related to changes in iron, ferritin and albumin content, and changes in IL-1beta were related to changes in sputum ferritin content. Iron and iron-regulatory cytokines may play a role in cystic fibrosis lung disease and the increased iron content may even facilitate Pseudomonas aeruginosa infection.

Adolescent↗
PubMed2003

Inhaled long acting beta agonists for stable chronic asthma.

BACKGROUND: Asthma is a common respiratory disease among both adults and children and short acting inhaled beta-2 agonists are used widely for 'reliever' bronchodilator therapy. Long acting beta-2 agonists were introduced as prospective 'symptom controllers' in addition to inhaled corticosteroid 'preventer' therapy (ICS). OBJECTIVES: This review aimed to determine the benefit or detriment on the primary outcome of asthma control with the regular use of long acting inhaled beta-2 agonists compared with placebo. SEARCH STRATEGY: We carried out searches using the Cochrane Airways Group trial register, most recently in October 2002. We searched bibliographies of identified RCTs for additional relevant RCTs and contacted authors of identified RCTs for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with a placebo, in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. We contacted authors of studies for missing data. MAIN RESULTS: Eighty five studies met the inclusion criteria, 56 parallel group and 29 cross over design. Salmeterol xinafoate was used as long acting agent in 60 studies and formoterol fumarate in 25. The treatment period was two to four weeks in 32 studies, and 12 to 52 weeks in 53 studies. 34 study groups used concurrent inhaled corticosteroid treatment, 21 studies did not permit their use and 35 permitted either inhaled corticosteroid or cromones. There were significant advantages to long acting beta-2 agonist treatment compared to placebo for a variety of measurements of airway calibre including morning peak expiratory flow (PEF) (weighted mean difference (WMD) 26.78 L/min 95%CI 20.36 to 33.20), evening PEF (WMD 19.17 L/min 95%CI 11.63 to 26.73). They were associated with significantly fewer symptoms, less use of rescue medication and higher quality of life scores. The risk of exacerbation was lower in adults using regular inhaled corticosteroids. REVIEWER'S CONCLUSIONS: Long acting beta-2 agonists are effective in the control of chronic asthma, and the evidence supports their use in addition to inhaled corticosteroids, as emphasised in current guidelines. Further research is needed on their use in children under 12 and in mild asthmatics not taking ICS.

Adrenergic beta-Agonists↗
PubMed2003

Self-management education for chronic obstructive pulmonary disease.

BACKGROUND: In asthma, self-management programmes have been proven to be effective. In COPD, their value is not clear. OBJECTIVES: To assess the efficacy of COPD self-management/ education programmes on health outcomes and use of health services SEARCH STRATEGY: We searched the Cochrane Airways Group trial registers, MEDLINE (January 1985 to October 2001), reference lists, and abstracts of medical conferences. We also contacted research groups in the field for ongoing trials and unpublished material. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on physical pulmonary rehabilitation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 12 articles describing 8 randomised-controlled trials and 1 controlled clinical trial. Self-management education was compared with usual care in 8 studies. The studies in this review assessed a broad-spectrum of outcome measures with different follow-up times. Synthesis of the results using meta-analysis was always not possible. The studies showed no effect of self-management education on hospital admissions, emergency room visits, days lost from work and lung function. Inconclusive results were observed on health-related quality of life (HRQoL): studies using the disease specific SGRQ showed a better quality of life in the patients in the intervention group, but only in the activity component where there was heterogeneity between the results of the two included studies. A potential reason for the absence of convincing effects on HRQoL is the limited use of COPD-specific instruments. Inconclusive results were observed on COPD-symptoms and use of other health care resources such as doctor and nurse visits. Self-management education reduced the need for rescue medication, and led to an increased use of courses of oral steroids and antibiotics for respiratory symptoms. REVIEWER'S CONCLUSIONS: The data available for this review are insufficient for forming recommendations. Further research on the effectiveness of self-management programmes should be focussed on behavioural change evaluated in well designed randomised controlled trials with standardised outcomes designed for use in COPD patients, and with long follow-up time so that definite conclusions can be made.

Humans↗
PubMed2003

Immunomodulatory agents for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) or Usual Interstitial Pneumonia (UIP) is a form of chronic fibrosing interstitial pneumonia of unknown aetiology, with progressively deteriorating respiratory function and ultimately death from respiratory failure. Most treatments are intended to suppress inflammation but none has been proven to alter this process. The most widespread approach uses oral corticosteroids; others use immunosuppressive, immunomodulatory or anti-fibrotic agents, alone or with corticosteroids. A Cochrane review of corticosteroids in IPF has found no evidence that they are of benefit. OBJECTIVES: To determine the effect of non-corticosteroid immunosuppressive, anti-fibrotic and immunomodulatory agents in the treatment of IPF(UIP). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library, Issue 2 2003), MEDLINE (January 1966 to April 2003), EMBASE (January 1985 to April 2003) and with additional handsearching. SELECTION CRITERIA: RCTs/CCTs utilising non-corticosteroid immunosuppressive, anti-fibrotic or immunomodulatory agents versus either placebo or corticosteroids alone in adult patients with histological evidence of IPF(UIP) or with a diagnosis consistent with published American Thoracic Society guidelines were included. DATA COLLECTION AND ANALYSIS: We retrieved abstracts of identified articles and reviewed those possibly fulfilling inclusion criteria and included or excluded. Two reviewers assessed the studies for inclusion in the review. Where doubt existed a third reviewer re-assessed the article and consensus was obtained. Methodological quality was assessed using the Jadad scale and the Cochrane assessment of allocation of concealment. MAIN RESULTS: 59 studies were identified. Quality was generally poor. Only three RCT/CCTs were suitable for meta-analysis, two lesser quality RCTs were included in discussion only, 52 studies were excluded and two ongoing trials were identified. Each high quality trial used a different agent (azathioprine, colchicine, interferon-gamma 1b) and meaningful comparisons are not possible. Azathioprine and Interferon were studied as additional therapy, whilst colchicine was compared with oral corticosteroids. Only interferon was shown to produce any significant improvement in pulmonary function and arterial oxygenation. There may be a small (but undefined) long term survival advantage for azathioprine. One of the lower quality studies showed a marginal benefit for cyclophosphamide and prednisone over prednisone alone; the other showed no benefit for azathioprine and prednisone over prednisone alone. There are no high quality studies utilising cyclophosphamide. REVIEWER'S CONCLUSIONS: There is little good quality information regarding the efficacy of non-corticosteroid agents in IPF(UIP). The older agents have generally not been well evaluated. A number of new agents require further evaluation. Currently there is little to justify the routine use of any non-corticosteroid agent in the management of IPF(UIP).

Azathioprine↗
PubMed2003

Colchicine as an oral corticosteroid sparing agent for asthma.

BACKGROUND: Oral corticosteroids are used as a treatment for asthma, but they are often associated with serious side effects. Colchicine is an anti-inflammatory, immuno modulating agent, which could potentially have a beneficial effect in the treatment of asthma as well as act as a steroid-sparing agent. OBJECTIVES: To determine the effectiveness of colchicine as an oral corticosteroid sparing agent for in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register (November 2002), SIGLE (1980 to 2001) and reference lists of potential articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials investigating the addition of colchicine compared to placebo in stable steroid dependent asthmatics. DATA COLLECTION AND ANALYSIS: No trials were found that met the inclusion criteria. MAIN RESULTS: We were unable to perform any meta-analyses. Two small studies have assessed the efficacy of colchicine subsequent to inhaled steroid withdrawal and as a tapering agent in inhaled steroids. Both studies failed to detect a significant difference between colchicine and placebo. REVIEWER'S CONCLUSIONS: No relevant trials have been published, so there is no evidence to indicate that colchicine is beneficial or otherwise in the management of steroid-dependent asthmatic patients. There is a need for well designed randomised controlled trials to be performed.

Adrenal Cortex Hormones↗
PubMed2003

Chloroquine as a steroid sparing agent for asthma.

BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled using inhaled steroids, but for a small group of asthma sufferers, symptoms cannot be controlled using inhaled steroids and instead continuous use of high dosage oral steroids (corticosteroids) are required. However, using high dosage oral steroids for long periods is associated with severe side effects. Steroid-sparing treatments have been sought and one of these is chloroquine. Chloroquine is an anti-inflammatory agent, also used in the treatment of malarial infection and as a second-line therapy in the treatment of rheumatoid arthritis, sarcoidosis and systemic lupus erythematosus. All these diseases are associated with immunologic abnormalities hence the speculation that chloroquine might be used to control severe, poorly controlled bronchial asthma. There is a need to systematically evaluate the evidence regarding its use to reduce or eliminate oral corticosteroid use in asthma. OBJECTIVES: The object of this review was to assess the efficacy of adding chloroquine to oral corticosteroids in patients with chronic asthma who are dependent on oral corticosteroids with the intention of minimising or eventually eliminating the use of these oral steroids. SEARCH STRATEGY: Searches of the Cochrane Airways Group asthma and wheeze trials register were undertaken with predefined search terms in 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 suitable in the review. Data were extracted and entered into RevMan 4.2.2 MAIN RESULTS: One small study was included in the review. No significant findings were reported. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of chloroquine as an oral steroid-sparing agent in chronic asthma. Further trials should optimise oral steroid dosage before addition of the steroid-sparing agent.

Adrenal Cortex Hormones↗
PubMed2003

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: The Cochrane Airways Group trials register was searched for possible randomised trials. Bibliographies were searched for other potentially relevant trials. Searches were current as of February 2001. 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 Review Manager statistical package (MetaView 4.1). Pharmaceutical companies and study investigators were contacted for unpublished trials. MAIN RESULTS: Four studies were included in the review. Trials comparing methotrexate, chloroquine and cyclosporin A 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 and chloroquine. In one small study, methotrexate was associated with a steroid sparing effect after 12 months of therapy, but no difference was observed at 6 months. REVIEWER'S 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↗
PubMed2003

Anti-IgE for chronic asthma.

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. The complexes of Omalizumab and IgE formed as a result of treatment are small and not thought to be able to trigger complement activation or give rise to immune complex mediated pathology. 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 control 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 resulted in a 98 to 99% reduction in free IgE, reductions which were not observed following placebo treatment. Significant increases in the number of participants who were able to reduce (> 50% reduction in daily corticosteroid usage (four trials): odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10; or completely withdraw their daily steroid intake (four trials): OR 2.50, 95%CI 2.00 to 3.13, were observed. Participants treated with Omalizumab were less likely to suffer an asthma exacerbation (stable steroid phase (three trials): OR 0.46, 95%CI 0.35 to 0.61; steroid reduction phase (three trials) OR 0.46, 95% CI 0.36 to 0.59). REVIEWER'S CONCLUSIONS: Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids and was effective in reducing asthma exacerbations. 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 comparison with inhaled corticosteroids.

Anti-Asthmatic Agents↗
PubMed2003

How well do doctors know their patients with severe asthma?

BACKGROUND: Rates of asthma mortality have fallen in Australia since the commencement of the National Asthma Campaign and promotion of the Australian asthma management plan. New strategies are now needed to further reduce mortality. AIM: To examine agreement about key features between asthma patients and their general practitioners (GPs). METHODS: We interviewed: (i) the next of kin of 56 asthma deaths, (ii) 91 asthma patients presenting to emergency departments with acute severe asthma and (iii) 147 of their GPs. RESULTS: Agreement was substantial for usage of oral symptomatic medication, but poor for inhaled symptomatic and preventive medications. There was moderate agreement regarding hospital admissions within the last 12 months among the cases, but little about other markers of severity. There was moderate agreement where the presenting or fatal attack was triggered by an upper respiratory-tract infection or aspirin. The next of kin and GPs agreed about family problems, but not about other psychosocial issues. They also agreed about which cases had been given action plans or verbal instructions, but few other aspects of asthma management. There was also moderate agreement regarding the use of peak flow meters by the controls. CONCLUSIONS: Doctors often have relatively poor insights into self-management practices, social background or trigger factors, even in high-risk patients. This should be considered when planning future campaigns to improve asthma management and further reduce mortality.

Adult↗
PubMed2003

Bronchodilator reversibility in Australian adults with chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Bronchodilator reversibility (BDR) and inhaled corticosteroid (ICS) use were assessed for volunteers who responded to an advertisement requesting current or ex-smokers who were experiencing breathlessness to attend for lung function testing. METHODS: One hundred and fifty-four volunteers responded. Forced expiratory volume (FEV1) was measured before and after 400 microg of salbutamol. Significant BDR was assessed according to guidelines of: (i) the American Thoracic Society (> or =12% plus 200 mL of baseline FEV1 or forced vital capacity), (ii) the British-Thoracic Society (BTS) (> or =15% plus 200 mL of baseline FEV1), (iii) the European Thoracic Society (> or =10% predicted FEV1), and (iv) the most commonly used criteria in Australia and New Zealand (> or =15% of baseline FEV1). RESULTS: One hundred and twenty-three subjects (33 female; 40 current smokers; median pack years 48 (range 5-144)) were suitable for analysis (i.e. had no history of asthma, demonstrable airflow limitation and a forced expiratory ratio (FER) of <70%). Twenty (16%) patients had an FEV1 within the normal range but FER of <70%, 24 (20%) patients had mild disease (FEV1 60-80% predicted), 31 (24%) patients had moderate disease (FEV1 40-59% predicted), and 48 (39%) patients had severe disease (FEV1 <40% predicted), according to BTS criteria. Significant BDR was evident in: (i) 58 (47%) subjects by American criteria, (ii) 26 (21%) subjects by British criteria, (iii) 19 (15%) subjects by European criteria and (iv) 36 (29%) subjects by Australasian criteria. ICS use was reported by 71 (58%) subjects overall and was weakly, but significantly, related to poorer FEV1 (r = -0.2; P < 0.01), and greater BDR (r = 0.3; P < 0.005). CONCLUSION: Chronic obstructive pulmonary disease in Australian volunteers with no history of asthma encompasses many individuals with significant BDR. Interestingly, most volunteers reported ICS use and this was related to poorer spirometry and greater BDR. However, until the underlying immuno-pathology has been determined they cannot be assumed to have "asthma" or even an "asthmatic element".

Adrenal Cortex Hormones↗
PubMed2003

Possible anti-inflammatory effect of salmeterol against interleukin-8 and neutrophil activation in asthma in vivo.

In-vitro data suggest that long-acting beta2-agonists may have a neutrophil-stabilising effect. A reduction in airway wall eosinophil number following introduction of salmeterol in persistent asthma has previously been described. There is currently interest in the "neutrophil system" in asthma, and thus the aim of the present study was to investigate the effect of salmeterol on interleukin (IL)-8, neutrophils and myeloperoxidase (MPO) in persistent asthma. In the same 12-week double-blind parallel-group placebo-controlled study as described previously, the effects on bronchoalveolar lavage fluid (BALF) IL-8, neutrophils and MPO of introducing salmeterol (50 microg b.i.d.) or giving additional inhaled corticosteroid (fluticasone 100 microg b.i.d.) in 45 subjects with persistent asthma already on low/moderate doses of inhaled corticosteroids were further investigated. At baseline, BALF IL-8 but not neutrophil or MPO levels were significantly raised in the asthmatic subjects compared to normal controls. MPO levels correlated strongly with IL-8 levels, and weakly with BALF neutrophil numbers in the asthmatics. Fluticasone treatment resulted in significantly elevated neutrophil numbers, but not MPO or IL-8 levels. In contrast, introducing salmeterol significantly reduced IL-8 and MPO levels, but did not affect BALF neutrophil numbers. Interestingly, salmeterol and fluticasone showed significantly contrasting effects on MPO and neutrophils, and there was a divergent effect on IL-8 levels that almost reached significance. Excessive interleukin-8 levels may be relevant to asthma pathogenesis, even in the setting of moderate-dose inhaled corticosteroid therapy. Reduction in interleukin-8 production and possibly stabilisation of airway neutrophil numbers may explain the greater clinical benefit of adding a long-acting beta2-agonist rather than merely increasing inhaled corticosteroid doses. Indeed, high-dose inhaled corticosteroid therapy alone may promote airway neutrophilia.

Adrenergic beta-Agonists↗
PubMed2002

Nebulised morphine for severe interstitial lung disease.

BACKGROUND: The evidence to support the use of nebulized morphine to improve dyspnoea and exercise limitation in terminally ill patients with chronic lung disease is conflicting. OBJECTIVES: To assess the effectiveness of nebulized morphine in reducing dyspnoea in patients with end-stage interstitial lung disease SEARCH STRATEGY: RCTs and good quality CCTs were identified by searching Medline, Embase, Cinahl as well as the Cochrane controlled clinical trial register. The following search terms were used: (inhaled OR nebulised)/AND/morphine AND/Idiopathic pulmonary fibrosis/or/pulmonary fibrosis/or/idiopathic interstitial pneumonia/or/nonspecific interstitial pneumonia/or/non-specific interstitial pneumonia/or/usual interstitial pneumonia/or/desquamative interstitial pneumonia/or/cryptogenic fibrosing alveolitis/or/interstitial pneumonia/or/idiopathic interstitial lung disease/or/chronic interstitial pneumonia SELECTION CRITERIA: Any RCT and adequate quality CCT in adult patients with ILD that compared nebulized morphine with a control group. DATA COLLECTION AND ANALYSIS: Only one small RCT was identified. MAIN RESULTS: Compared to placebo (normal saline), administration of low-dose nebulized morphine (2.5 and 5.0 mg) to six patients with ILD did not improve maximal exercise performance, and did not reduce dyspnoea during exercise. REVIEWER'S CONCLUSIONS: The hypothesis that nebulized morphine may reduce dyspnoea in patients with interstitial lung disease has not been confirmed in the single small RCT identified.

Analgesics, Opioid↗
PubMed2002

Prostacyclin for pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension (PPH) is progressive, resulting in right ventricular failure. Survival seldom exceeds five years. Pulmonary hypertension can be idiopathic or associated with other conditions. It is common in patients with diffuse scleroderma and the CREST syndrome where it is clinically, haemodynamically and prognostically indistinguishable from idiopathic primary pulmonary hypertension. Prostacyclin is a potent vasodilator and inhibitor of platelet aggregation. Iloprost is a chemically stable derivative of prostacyclin with similar biologic properties and can be given orally, by infusion or nebulised. OBJECTIVES: To determine the efficacy of prostacyclin or one of its analogues in idiopathic primary pulmonary hypertension. SEARCH STRATEGY: A search was carried out using the Cochrane controlled clinical trial register. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving patients with primary pulmonary hypertension were selected by two reviewers. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data extracted independently by two reviewers. Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques. MAIN RESULTS: Four RCTs were included, all of short duration (8-12 weeks). Three compared intravenous epoprostenol with conventional therapy, two were in PPH (n = 81 and n = 21) and one with pulmonary hypertension in scleroderma (n = 111). One compared intravenous Iloprost with placebo in 14 patients with scleroderma. Exercise capacity improved in patients treated with intravenous epoprostenol (Standardised Mean Difference) 0.69, 95% Confidence Intervals (CI) 0.40, 0.97. Several haemodynamic variables improved in the group treated with epoprostenol; e.g. mean pulmonary artery pressure fell: Weighted Mean Difference -6.3 mmHg (95% CI -3.9, -8.7). Mortality was improved Peto Odds Ratio 0.32 (95% CI 0.13, 0.77), although this effect was not significant when analysed using a more conservative random effects model: Odds Ratio 0.32 (95% CI 0.06, 1.58). Side effects and adverse events related to the indwelling catheter (sepsis and thrombosis) were common. REVIEWER'S CONCLUSIONS: Intravenous prostacyclin over 12 weeks improves exercise capacity, NYHA functional class and several cardiopulmonary haemodynamic variables. It may improve mortality.

Antihypertensive Agents↗
PubMed2002

Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma.

BACKGROUND: Selective beta-adrenergic agonists for use in asthma are: short acting (2-6 hours) and long acting (>12 hours). There has been little controversy about using short acting beta-agonists intermittently, but long acting beta-agonists are used regularly, and their regular use has been controversial. OBJECTIVES: To determine the benefit or detriment of treatment with regular short- or long acting inhaled beta-agonists in chronic asthma. SEARCH STRATEGY: A search was carried out using the Cochrane Airways Group register. Bibliographies of identified RCTs were searched for additional relevant RCTs. Authors of identified RCTs were contacted for other published and unpublished studies. SELECTION CRITERIA: All randomised studies of at least two weeks duration, comparing a long acting inhaled beta-agonist given twice daily with any short acting inhaled beta-agonist of equivalent bronchodilator effectiveness given regularly in chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers performed data extraction and study quality assessment independently. Authors of studies were contacted for missing data. MAIN RESULTS: 31 studies met the inclusion criteria, 24 of parallel group and 7 cross over design. Salmeterol xinafoate was used as long acting agent in 22 studies and formoterol fumarate in 9. Salbutamol was the short acting agent used in 27 studies and terbutaline in 5. The treatment period was over 2 weeks in 29 studies, and at least 12 weeks in 20. 25 studies permitted a variety of co-intervention treatments, usually inhaled corticosteroid or cromones. One study did not permit inhaled corticosteroid. Long acting beta-agonists were significantly better than short acting for a variety of lung function measurements including morning PEF (Weighted Mean Difference (WMD) 33 l/min 95% CI 25, 42) or evening PEF (WMD 26 l/min 95% CI 18, 33); and had significantly lower scores for day and night time asthma symptom scores and percentage of days and nights without symptoms. They were also associated with a significantly lower use of rescue medication both during the day and night. Risk of exacerbations was not different between the two types of agent, but most studies were of short duration which limits the power to test for such differences. REVIEWER'S CONCLUSIONS: Long acting inhaled beta-agonists have advantages across a wide range of physiological and clinical outcomes for regular treatment.

Adrenergic beta-Agonists↗