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Biomedical subjects

M Greenstone

Publications and source records attributed to M Greenstone.

At least 19 recordsLinked to original sources
PubMed2003

Short acting beta-2 agonists for bronchiectasis.

BACKGROUND: Bronchiectasis is a condition characterized by an abnormal and irreversible dilatation of the sub segmental airways and it may be caused by a variety of disease processes. Currently medical treatment includes physiotherapy, antibiotics and occasionally mucolytics. Many people with bronchiectasis receive bronchodilator therapy, since many people with the condition show signs of airflow obstruction and bronchial hyper-responsiveness. Evidence on effectiveness of bronchodilator therapy in bronchiectasis has only recently started to be systematically studied. OBJECTIVES: The present review examined the effectiveness of short acting beta-2 agonist therapy in bronchiectasis, as this is the most frequently used treatment for airflow obstruction in people with this condition. SEARCH STRATEGY: We systematically searched four databases: CENTRAL (Issue 2, 2002); MEDLINE (1966 to September 2002); EMBASE (1980 to September 2002); and CINAHL (1982 to September 2002). We also checked bibliographies of all identified RCTs to identify potentially relevant citations. SELECTION CRITERIA: All randomised controlled trials were considered for inclusion, whether single or double blind. The control group was placebo/no treatment or other drug/physical therapy. Participants could be children or adults diagnosed with bronchiectasis by plain-film chest radiograph, bronchography or high resolution computerized tomography. Patients were excluded if they had cystic fibrosis. Any type of short acting beta-2 agonist administered by inhalation or systemic route, used in conjunction with conventional treatment was included. DATA COLLECTION AND ANALYSIS: In the absence of any relevant RCTs, we were unable to extract or analyse data. MAIN RESULTS: We identified 48 articles by the search, the majority of which could be excluded on the basis of the abstract as they were not RCTs. Six articles were retrieved and were all excluded after careful consideration because they were either not RCTs or they did not deal with the question of interest. REVIEWER'S CONCLUSIONS: We failed to identify any RCTs investigating the role of short acting beta agonists in bronchiectasis. Since short acting beta-2 agonist therapy is the most frequently used treatment for airflow obstruction in bronchiectasis, there appears to be the need to investigate the effectiveness of this therapy using an RCT.

Adrenergic beta-Agonists↗
PubMed2003

Long-term antibiotics in the management of non-CF bronchiectasis--do they improve outcome?

In addition to bacteria and inflammatory cells, the sputum of patients with bronchiectasis contains mediators that damage the airway epithelium and promote inflammatory change. The deleterious effects of these mediators, such as neutrophil elastase, reduce host defences and consequently perpetuate the propensity to recurrent infection. This 'vicious cycle' of infection and inflammation in bronchiectasis suggests that long-term antibiotic therapy might be beneficial in these patients by reducing microbial load and, in doing so, inhibit inflammation in the lung allowing tissue repair to occur. Short courses of antibiotics achieve clinical improvements and also have been shown to reduce the levels of harmful mediators in the sputum. This article will cite the studies reported for long-term antibiotic treatment in bronchiectasis and overall there seems to be benefits for patients with chronic sputum purulence. The evidence that supports the postulated pathological mechanisms will also be discussed. Important issues in clinical practice such as the usefulness of antibiotic sensitivities, the evolution of resistance patterns, and drug delivery will also be discussed.

Anti-Bacterial Agents↗
PubMed2002

Physical training for bronchiectasis.

BACKGROUND: The pathophysiology of bronchiectasis may result in the development of dyspnoea and decreased exercise tolerance, both of which can impact on a patient's quality of life and ability to perform activities of daily living. There is little information regarding the benefits of physical training in bronchiectasis: however it is probable that the benefits of physical training in bronchiectasis are at least comparable to benefits demonstrated in other respiratory conditions. There is also no information regarding the effects of non-adherence to prescribed physical training in bronchiectasis. However as in patients with COPD non-adherence may contribute to a deterioration in the patient's condition and conceivably the long term prognosis. OBJECTIVES: The objective of this review is to determine whether a prescribed regime of physical training produces improvements or prevents deterioration in physiological and clinical outcomes in bronchiectasis compared to no physical training. SEARCH STRATEGY: We searched the Cochrane Airways Group specialised register and the Cochrane Controlled Clinical Trials Register. SELECTION CRITERIA: Randomised or quasi randomised controlled trials in which a prescribed regime of physical training are compared to no physical training in patients with bronchiectasis. DATA COLLECTION AND ANALYSIS: Three studies were identified. One was did not meet the inclusion criteria and two appeared in abstract form only. More comprehensive data will be incorporated into this review once data from those two trials are published, and when further data is made available to the authors of this review. MAIN RESULTS: Results from the two studies published in abstract showed that inspiratory muscle training compared to sham or no inspiratory muscle training improved endurance exercise capacity: Weighted Mean Difference (WMD) 264 metres (95% CI 16.4 to 512 metres). PiMax improved: WMD 25 cms H20 (95% CI 11.6 to 38.4 cms H2O )as did quality of life measured with the CRQ: WMD 12.4 units (95% CI 2.4 to 22.5 units). REVIEWER'S CONCLUSIONS: This review only provides evidence of the benefits of inspiratory muscle training and provides no evidence of the effect of other types of physical training (including pulmonary rehabilitation) in bronchiectasis.

Bronchiectasis↗
PubMed2001

Long-acting beta-2-agonists for bronchiectasis.

BACKGROUND: Symptoms of bronchiectasis include chronic productive cough, wheeze, breathlessness and recurrent infections of the lower respiratory tract. Long-acting bronchodilators are being used more frequently in the management of people with this condition. OBJECTIVES: To determine the effectiveness of long-acting bronchodilators in the management of bronchiectasis that is not due to cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Airways Group Bronchiectasis Database made up of trials identified from searching the Cochrane Controlled Trials Register, MEDLINE, EMBASE and hand-searches of leading respiratory journals. The latest searches were performed in May 2001. SELECTION CRITERIA: Randomised controlled trials, with or without masking. DATA COLLECTION AND ANALYSIS: The results of searches were reviewed against pre-specified criteria. MAIN RESULTS: We were unable to identify any randomised controlled trials investigating the effectiveness of long-acting bronchodilator therapy in the management of bronchiectasis. REVIEWER'S CONCLUSIONS: Further research is needed to establish if long-acting bronchodilators have a role in the management of people with bronchiectasis.

Adrenergic beta-Agonists↗
PubMed2001

Oral steroids for bronchiectasis (stable and acute exacerbations).

BACKGROUND: Inflammation plays a significant role in the pathophysiology of bronchiectasis. Two small studies have shown small benefits from inhaled corticosteroids and oral corticosteroids may be of benefit in bronchiectasis OBJECTIVES: To determine the efficacy of oral corticosteroids in acute and stable bronchiectasis SEARCH STRATEGY: The Cochrane Airways Group clinical trials register, derived from MEDLINE, EMBASE and hand searching of major journals, was searched using the terms bronchiectasis AND corticosteroid* OR (beclomethasone, cortisone, deflazacort, hydrocortisone, methylprednisolone, prednisolone, dexamethasone and triamcinolone SELECTION CRITERIA: Only randomised controlled trials were considered DATA COLLECTION AND ANALYSIS: No trials met the inclusion criteria for the review MAIN RESULTS: No randomised controlled trials were identified REVIEWER'S CONCLUSIONS: There are no randomised trials upon which to make recommendations about the use of oral corticosteroids in acute or stable bronchiectasis.

Acute Disease↗
PubMed2001

Anticholinergic therapy for bronchiectasis.

BACKGROUND: Anticholinergic agents block bronchoconstriction mediated by the vagus nerve and may also dry up bronchial secretions. They are effective in obstructive airways disease and may be beneficial in bronchiectasis OBJECTIVES: To determine the effect of anticholinergic therapy in acute exacerbations and stable bronchiectasis. SEARCH STRATEGY: The Cochrane Airways Group clinical trials register was searched using the terms bronchiectasis AND anticholinergic OR ipratropium bromide OR tiotropium OR atropine. SELECTION CRITERIA: Only randomised controlled trials were considered. DATA COLLECTION AND ANALYSIS: Two reviewers assessed the retrieved studies working independently. MAIN RESULTS: Twelve studies were identified, of which six were obtained for further scrutiny. One was translated from Italian. None met the inclusion criteria. REVIEWER'S CONCLUSIONS: No formal recommendations can be made about the use of anticholinergic therapy in acute or stable bronchiectasis based on the literature currently available.

Acute Disease↗
PubMed2001

Oral methyl-xanthines for bronchiectasis.

BACKGROUND: Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis. OBJECTIVES: To determine the efficacy of methylxanthines in the treatment of bronchiectasis. SEARCH STRATEGY: The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine SELECTION CRITERIA: Only randomised controlled trials were to be considered. DATA COLLECTION AND ANALYSIS: The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria. MAIN RESULTS: No randomised controlled trials were identified. REVIEWER'S CONCLUSIONS: Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.

Administration, Oral↗
PubMed2001

Carbonic anhydrase inhibitors for hypercapnic ventilatory failure in chronic obstructive pulmonary disease.

BACKGROUND: Carbonic anhydrase inhibitors such as acetazolamide cause a mild metabolic acidosis and may stimulate breathing. Some patients with severe chronic obstructive pulmonary disease (COPD) develop chronic hypercapnic ventilatory failure. In theory, they may benefit from use of these drugs with a fall in arterial carbon dioxide level (PCO2) and a rise in arterial oxygen (PO2). OBJECTIVES: To determine the effectiveness and safety of acetazolamide in the treatment of hypercapnic ventilatory failure due to COPD SEARCH STRATEGY: The Cochrane Register of Controlled Clinical Trials was searched along with Medline, Embase, Central and CINAHL for relevant randomised control trials. SELECTION CRITERIA: Trials were included in the review provided they were placebo controlled, carried out in patients with stable chronic ventilatory failure due to COPD. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed by two reviewers (PJ and MG) and agreement was reached by consensus. Where data could be aggregated they were analysed using a fixed efefcts model and reported as a weighted mean difference (WMD) and its associated 95% confidence interval (95% CI). MAIN RESULTS: Four trials were included in the review. Of these, two were randomised parallel studies, one was a crossover study and the other had a sequential design. A total of 84 patients were involved. Study quality was mixed and the studies were short (typically two weeks). All studies showed a similar direction and size of effect. In the randomised parallel studies, acetazolamide caused a metabolic acidosis and produced a non-significant fall in PCO2 (WMD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (WMD 1.54 kPa; 95% CI 0.97, 2.11; N=2). One study reported an improvement in sleep but there were no data concerning outcomes such as health status, symptoms, exacerbation rate, hospital admissions or deaths. Side effects were reported infrequently. REVIEWER'S CONCLUSIONS: Acetazolamide can produce a small increase in arterial PO2 and fall in PCO2. These conclusions are drawn from a few small short studies that were not all of high quality. It is not known whether this physiological improvement is associated with clinical benefit.

Acetazolamide↗
PubMed2001

Inhaled hyperosmolar agents for bronchiectasis.

BACKGROUND: Mucus retention in the lungs is a prominent feature of bronchiectasis. The stagnant mucus becomes chronically colonised with bacteria, which elicit a host neutrophilic response. This fails to eliminate the bacteria, and the large concentration of host-derived protease may contribute to the airway damage. The sensation of retained mucus is itself a cause of suffering, and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients. Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions, probably by inducing a liquid flux into the airway surface, which alters mucus rheology in a way favourable to mucociliary clearance. Inhaled dry powder mannitol has a similar effect. Such agents are an attractive approach to the problem of mucostasis, and deserve further clinical evaluation. OBJECTIVES: To determine whether inhaled hyperosmolar substances are efficacious in the treatment of bronchiectasis SEARCH STRATEGY: MEDLINE and Cochrane databases were searched, and leaders in the field contacted. SELECTION CRITERIA: Any trial using hyperosmolar inhalation in patients with bronchiectasis not caused by cystic fibrosis. DATA COLLECTION AND ANALYSIS: One reference were identified by the searches conducted. MAIN RESULTS: Only one trial was identified, a crossover study of 11 patients with bronchiectasis. The outcome measure was tracheobronchial clearance of a particulate radioaerosol after inhalation of dry mannitol on a single occasion, with appropriate controls. Airway clearance doubled in the central and intermediate regions of the lung, but not in the peripheral region, after mannitol administration. No side effects were observed, but two patients were premedicated with nedocromil to prevent bronchospasm. REVIEWER'S CONCLUSIONS: Dry powder mannitol has been shown to improve tracheobronchial clearance in bronchiectasis, as well as cystic fibrosis, asthmatics, and normal subjects. It is not yet available for clinical use. Hypertonic saline has not been specifically tested in bronchiectasis, but improve clearance in these other conditions and in chronic bronchitis. Longer term randomised controlled studies of mannitol and hypertonic saline with clinical endpoints are now needed.

Bronchiectasis↗
PubMed2000

Doxapram for ventilatory failure due to exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: COPD is a progressive illness and in the later stages, exacerbations may lead to ventilatory failure. The combination of hypoxia and hypercapnia can lead to coma and death. Correction of these blood gas abnormalities is a medical emergency. Doxapram is a respiratory stimulant used to stimulate breathing in this setting. OBJECTIVES: The objective of this review was to assess the effects of doxapram on gas exchange and clinical outcomes in people with ventilatory failure due to acute exacerbations of chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted experts in the field, study authors and drug companies. SELECTION CRITERIA: Randomised trials comparing doxapram with other treatments or placebo in people with ventilatory failure due to exacerbations of chronic obstructive pulmonary disease. DATA COLLECTION AND ANALYSIS: One reviewer assessed trial quality and extracted data. MAIN RESULTS: Three trials involving 127 people were included. The trials were of variable quality. Doxapram was marginally superior to placebo in preventing blood gas deterioration (odds ratio 0.38, 95% confidence interval 0.14 to 1.02). In one small study, of 17 patients, doxapram and non-invasive ventilation appeared equally effective in terms of blood gases changes, although there were slightly more deaths with doxapram (odds ratio 11.34, 95% confidence interval 1.00 to 128.03). REVIEWER'S CONCLUSIONS: Doxapram may improve blood gas exchange in the short term, but newer techniques such as non-invasive ventilation may be more effective.

Acute Disease↗
PubMed1998

How long should Atrovent be given in acute asthma?

BACKGROUND: In acute asthma the optimal duration of treatment with combination beta agonist and anticholinergic nebuliser solutions is unknown; most studies have investigated single doses or treatment for up to 12 hours. To determine whether longer treatment with ipratropium bromide might aid recovery a study was undertaken in 106 patients with acute asthma. METHODS: A double blind, randomised, placebo controlled, three group study was performed with all patients receiving ipratropium for 12 hours and salbutamol for 60 hours after admission (both nebulised four hourly), systemic steroids and, if necessary, theophylline. At 12 hours ipratropium was stopped in group I (n = 35) but was continued in the other two groups, and at 36 hours ipratropium was also stopped in group II (n = 35) while patients in group III (n = 36) continued with ipratropium for 60 hours. Spirometric tests were performed before and after salbutamol, and again 30 and 60 minutes after ipratropium or placebo at 12, 36 and 60 hours. Peak flow rates (PEFR) were measured before and after each nebulisation. RESULTS: There were no differences between the groups in PEFR on admission (group I: 214 l/min, group II: 198 l/min, group III: 221 l/min), or mean forced expiratory volume in one second (FEV1) at 12 hours (group I: 1.81, group II: 2.01, group III: 2.21), 36 hours (group I: 2.11, group II: 2.31, group III: 2.41), or at 60 hours (group I: 2.21, group II: 2.31, group III 2.51). Despite this, median time to discharge was significantly higher for patients in group I (5.4 days) than for those in groups II (4.1 days) and III (4.0 days). CONCLUSIONS: Combination nebulised therapy can be continued beyond 12 hours and up to 36 hours after admission with improved recovery time. Lung function testing may not reflect the full benefit of treatment.

Acute Disease↗
PubMed1988

Efficacy of "mucoregulatory" agents in Young's syndrome.

Eight patients with Young's syndrome were treated with four "mucoregulatory" agents for eight weeks in a randomised, open crossover study. There was no improvement in tracheobronchial clearance, pulmonary function, or sperm count.

Adult↗
PubMed1988

Primary ciliary dyskinesia: cytological and clinical features.

Thirty patients with functional and/or morphological abnormalities of respiratory tract cilia were identified. The diagnosis of primary ciliary dyskinesia was based on observed abnormalities of ciliary ultrastructure or beating in vitro (beat pattern, beat frequency or percentage of motile cilia). Beat frequency and motility indices approached the normal range in some cases and suggests that the term 'immotile cilia syndrome' is not appropriate. Morphological abnormalities were most commonly due to deficiency of dynein arms, affecting the outer arms (n = 7), inner arms (n = 3) or both (n = 10). Examples of radial spoke and microtubular defects were also identified but in seven subjects ciliary ultrastructure was normal. In six patients paired samples of nasal and bronchial cilia were obtained and showed consistent abnormalities of motility and ultrastructure. Adenosine triphosphate and adenosine triphosphatase did not restore in vitro motility when added to dynein deficient cilia. The clinical picture was of life-long sinusitis and recurrent bronchial infection but the spectrum was broader than that encompassed by Kartagener's triad (dextrocardia, sinusitis and bronchiectasis). Fourteen patients had normal cardiac situs and definite or highly suggestive evidence of bronchiectasis was present in only 17 patients. Radiological evidence of sinusitis was common but absence of frontal sinuses was not universal. Chronic serous otitis media was a frequent finding but deafness was rarely profound. Fertility problems were common but were not universal in female subjects. Lung function testing revealed evidence of airflow obstruction but this was mild in most cases.

Adenosine Triphosphatases↗