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T J Lasserson

Publications and source records attributed to T J Lasserson.

At least 37 records · Page 2Linked to original sources

Surgery for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea/hypopnoea syndrome(OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated with loud snoring, disrupted sleep and observed apnoeas. Surgery for obstructive sleep apnoea/hypopnoea syndrome aims to alleviate symptoms of daytime sleepiness, improve quality of life, and reduce the signs of sleep apnoea recorded by polysomnography. OBJECTIVES: The objective of this review was to assess the effects of any type of surgery for the treatment of the symptoms of obstructive sleep apnoea/hypopnoea syndrome in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register and reference lists of articles. We contacted experts in the field, research dissemination bodies and other Cochrane Review Groups. Searches were current as of July 2005. SELECTION CRITERIA: Randomised trials comparing any surgical intervention for obstructive sleep apnoea/hypopnoea syndrome with other surgical or non-surgical interventions or no intervention. DATA COLLECTION AND ANALYSIS: Two reviewers assessed electronic literature search results for possibly relevant studies. Characteristics and data from studies meeting the inclusion criteria were extracted and entered into RevMan 4.2. MAIN RESULTS: In the 2005 update for this review eight studies (412 participants) of mixed quality met the inclusion criteria. Data from seven studies were eligible for assessment in the review. No data could be pooled. Uvulopalatopharyngoplasty (UPPP) versus conservative management (one trial): An un validated symptom score showed intermittent significant differences over a 12-month follow-up period. No differences in Polysomnography (PSG) outcomes were reported. Laser-assisted uvulopalatoplasty (LAUP) versus conservative management/placebo (two trials): One study recruited mixed a population, and separate data could not be obtained for this trial. In the other study no significant differences in Epworth scores or quality of life reported. A significant difference in favour of LAUP was reported in terms of apnoea hypopnoea index (AHI) and frequency and intensity of snoring. UPPP versus oral appliance (OA) (one trial): AHI was significantly lower with OA therapy than with UPPP. No significant differences were observed in quality of life. UPPP versus lateral pharyngoplasty (lateral PP) (one trial): No significant difference in Epworth scores, but a greater reduction in AHI with lateral PP was reported. Tongue advancement (mandibular osteotomy) + PPP versus tongue suspension + PPP (one trial): There was a significant reduction in symptoms in both groups, but no significant difference between the two surgery types. Complications reported with all surgical techniques included nasal regurgitation, pain and bleeding. These did not persist in the long term. An additional study assessed the effects of four different techniques. No data were available on between group comparisons. Multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) versus sham placebo and CPAP (one trial): There was an improvement in primary and secondary outcomes of TCRFTA over sham placebo and but no difference in symptomatic improvement when compared with CPAP. AUTHORS' CONCLUSIONS: There are now a small number of trials assessing different surgical techniques with inactive and active control treatments. The studies assembled in the review do not provide evidence to support the use of surgery in sleep apnoea/hypopnoea syndrome, as overall significant benefit has not been demonstrated. The participants recruited to the studies had mixed levels of AHI, but tended to suffer from moderate daytime sleepiness where this was measured. Short-term outcomes are unlikely to consistently identify suitable candidates for surgery. Long-term follow-up of patients who undergo surgical correction of upper airway obstruction is required. This would help to determine whether surgery is a curative intervention, or whether there is a tendency for the signs and symptoms of sleep apnoea to re-assert themselves, prompting patients to seek further treatment for sleep apnoea.

Adult↗

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobic and antiinflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials up to May 2005. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. The full text of any potentially relevant article was reviewed independently by two reviewers. MAIN RESULTS: Seven studies recruiting a total of 416 participants met the inclusion criteria. The quality of reporting of study methodology was generally low. We assembled findings from studies comparing macrolide treatment for at least 4 weeks in adult and pediatric patients treated for chronic asthma. Four studies showed a positive effect on symptoms of macrolides in different types of asthmatic patients. There were limited data available for meta-analysis. There was no significant difference in FEV1 for either parallel or crossover trials. However, there were significant differences in eosinophilic inflammation and symptoms. One large parallel group trial reported significant differences in peak flow but these differences abated within six months of treatment. AUTHORS' CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗

Fluticasone versus placebo for chronic asthma in adults and children.

BACKGROUND: Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. OBJECTIVES: 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register (January 2005), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004). SELECTION CRITERIA: Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Quantitative analyses were undertaken using RevMan 4.2 MAIN RESULTS: Seventy-five studies met the inclusion criteria (14,208 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 23 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/day). High dose FP increased the number of patients who could withdraw from prednisolone: FP 1000-1500 mcg/day Peto Odds Ratio 14.07 (95% CI 7.17 to 27.57). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis. Twenty-one patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP. AUTHORS' CONCLUSIONS: Doses of FP in the range 100-1000 mcg/day are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Administration, Inhalation↗

Fluticasone versus HFA-beclomethasone dipropionate for chronic asthma in adults and children.

BACKGROUND: The relative efficacy of fluticasone (FP) and beclomethasone (BDP) propelled with CFCs has been well established. The potency of HFA-BDP is thought to have been improved with new propellant and some studies suggest that it may equipotent at half the dose of CFC propelled-BDP. There is a need to revisit this question in the light of a potentially more potent new non-CFC propellant. OBJECTIVES: To determine the relative efficacy of FP and HFA-propelled BDP in chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group Specialised Register was searched using pre-specified terms. Searches were current as of March 2005. SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion in the review. We compared either CFC or HFA-propelled FP with HFA-propelled BDP. We made a distinction between HFA-BDP and HFA-BDP extra fine, which dispenses smaller particles of drug, leading to different, usually more peripheral distribution in the airways. Any inhaler device was considered, and there was no restriction on studies with or without spacers. We included studies which assessed HFA-BDP given via either pMDI, breath-actuated MDI, or DPI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion in the review. Data were extracted and entered in to RevMan 4.2 using standard meta-analytical techniques with predefined criteria for exploring statistical heterogeneity. MAIN RESULTS: Seven studies (1230 participants) met the inclusion criteria of the review. One study was conducted in children. Study reporting quality was fair, but all studies were of short duration (three to twelve weeks). Only studies assessing HFA-BDP extra fine in comparison with FP were identified. Lung function was not significantly different between extra fine BDP and FP when compared at the same dose in parallel studies, change in FEV1: 0.04 litres (95% CI -0.03 to 0.11 litres; three studies, 659 adults); change in am PEF: -0.69 litres (95% CI -11.21 to 9.83 litres; two studies, 364 adults). Individual studies reported non-significant findings in symptom scores and quality of life questionnaires. There was no significant difference between FP and HFA-BDP in the risk of study withdrawal, dysphonia or when data were reported as any adverse event. AUTHORS' CONCLUSIONS: There was no significant difference between FP and extra fine HFA-BDP on FEV(1) or peak flow at a dose ratio of 1:1. However, the number of studies and width of the confidence intervals in the analyses do not exclude a clinically meaningful difference between these two drugs. Difficulty in the successful manipulation of the devices studied may be a barrier to the widespread use of MDIs. One paediatric study was included in the review, so extrapolation of the findings of this review to children is limited. Further longer term studies in adults and children with moderate and severe asthma are required.

Administration, Inhalation↗

Macrolides for chronic asthma.

BACKGROUND: Asthma is a chronic disease of the airways in which inflammation of the respiratory mucosa plays a crucial role. The mechanisms responsible for the maintaining of this inflammatory response are only partially known and there is evidence that a role could be paid by chronic infection by intracellular pathogens (such as Chlamydia pneumoniae). Macrolides are antibiotics with both antimicrobic and antiinflammatory activities and thus their use in asthmatic patients could lead to reduction of the airways inflammation and therefore improvement of symptoms and pulmonary function. OBJECTIVES: To determine whether macrolides are effective in the management of patients with chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials up to May 2004. This was also supplemented by manually searching bibliographies of previously published reviews, conference proceedings, and contacting study authors. All languages were included in the initial search. SELECTION CRITERIA: Randomised, controlled clinical trials involving both children and adult patients with chronic asthma treated with macrolides for more than 4 weeks, versus placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently examined all identified articles. The full text of any potentially relevant article was reviewed independently by two reviewers. MAIN RESULTS: Seven studies recruiting a total of 416 participants met the inclusion criteria. The quality of reporting of study methodology was generally low. We assembled findings from studies comparing macrolide treatment for at least 4 weeks in adult and pediatric patients treated for chronic asthma. Four studies showed a positive effect on symptoms of macrolides in different types of asthmatic patients. There were limited data available for meta-analysis. There was no significant difference in FEV1 for either parallel or crossover trials. However, there were significant differences in eosinophilic inflammation and symptoms. One large parallel group trial reported significant differences in peak flow but these differences abated within six months of treatment. AUTHORS' CONCLUSIONS: Considering the small number of patients studied, there is insufficient evidence to support or to refute the use of macrolides in patients with chronic asthma. Further studies are needed in particular to clarify the potential role of macrolides in some subgroups of asthmatics such as those with evidence of chronic bacterial infection.

Anti-Bacterial Agents↗

Inhaled fluticasone at different doses for chronic asthma in adults and children.

BACKGROUND: Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma. OBJECTIVES: 1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma. 2. To test for the presence of a dose-response effect. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register (January 2005) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2004). SELECTION CRITERIA: Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using RevMan (Analyses 1.0.2). MAIN RESULTS: Forty-three studies (45 data sets with 8913 participants) met the inclusion criteria. Methodological quality was high. In asthmatics with mild to moderate disease who were not on oral steroids a dose-response effect was present with FP for change in morning peak expiratory flow (PEF). For low doses (100 versus 200 microg/day) the weighted mean difference (WMD) was 6.29 litres/min, 95% confidence interval (CI) 2.28 to 10.29. Comparing medium (400 to 500 microg/day) to low dose (200 microg/day) FP the WMD was 6.46 litres/min (95% CI 3.02 to 9.89); this effect was more pronounced in one trial with more severely asthmatic children. For FP 100 versus 400 to 500 microg/day the WMD was 8 litres/min (95% CI 1 to 15) and at high versus low doses (800 to 1000 versus 50 to 100 microg/d) the WMD was 22 litres/min (95% CI 15 to 29). When high and medium doses were compared there was no significant difference in the change in morning PEF: at 400 to 500 versus 800 to 1000 microg/day the WMD was 0.16 litres/min (95% CI 6.95 to 6.63). There was no dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 microg/day). People with oral steroid-dependent asthma treated with FP (2000 microg/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 microg/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 microg/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day). AUTHORS' CONCLUSIONS: Effects of fluticasone are dose dependent but relatively small. At dose ratios of 1:2, there are significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 microg/day) as they do on high doses (800 to 1000 microg/day). More work in severe asthma would help to confirm that doses of FP above 500 microg/day confer greater benefit in this subgroup than doses of around 200 microg/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 microg/day.

Administration, Inhalation↗

Corticosteroids for pulmonary sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is a common condition with an unpredictable course. Oral (OCS) or inhaled steroids (ICS) are widely used in its treatment, but there is no consensus about when and in whom therapy should be initiated, what dose should be given and for how long. Corticosteroids given for several months have deleterious side-effects so it is important to know whether they have any maintained benefit in pulmonary sarcoidosis. OBJECTIVES: To determine the randomised controlled trial (RCT) evidence for the benefit of corticosteroids (oral or inhaled) in the treatment of pulmonary sarcoidosis. SEARCH STRATEGY: MEDLINE, EMBASE and CENTRAL were searched using predefined terms. Bibliographies of retrieved RCTs and reviews were searched for additional RCTs. Pharmaceutical companies and authors of identified RCTs were contacted for other published and unpublished studies. Searches are current as of May 2004. SELECTION CRITERIA: Two reviewers independently assessed full text articles for inclusion based upon the following criteria: the study had to be a RCT or controlled clinical trial in adults with histological evidence of pulmonary sarcoidosis, treated with OCS (oral steroids) or ICS (oral steroids), compared with a control. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data extracted independently by two reviewers. The primary outcome was CXR (chest x-ray). Outcomes were analysed as continuous and dichotomous outcomes, using standard statistical techniques. Heterogeneity was explored where it was identified. MAIN RESULTS: Twelve RCTs of variable quality involving 1051 participants met the inclusion criteria of the review. The oral steroid dose was equivalent to prednisolone 4-40 mg/day. OCS: there was an improvement in CXR over 3-24 months (Relative Risk (RR): 1.46 [1.01 to 2.09], 3 studies), but this finding requires cautious interpretation. No other significant differences were identified on secondary outcomes. ICS: Data were inadequate to perform meaningful analysis of data on CXR. Two studies showed no improvement in lung function, In one study there was an improvement in diffusing capacity in the treated group. There were no data on side-effects. In one study symptoms improved at the end of six months of treatment. AUTHORS' CONCLUSIONS: Oral steroids improved the chest X-ray and a global score of CXR, symptoms and spirometry over 3-24 months. However, there is little evidence of an improvement in lung function. There are limited data beyond two years to indicate whether oral steroids have any modifying effect on long-term disease progression. Oral steroids may be of benefit for patients with Stage 2 and 3 disease with moderate to severe or progressive symptoms or CXR changes.

Administration, Inhalation↗

Intravenous aminophylline for acute severe asthma in children over two years receiving inhaled bronchodilators.

BACKGROUND: Since the advent of inhaled beta2-agonists, anticholinergic agents and glucocorticoids, the role of aminophylline in paediatric acute asthma has become less clear. There remains some consensus that it is beneficial in children with acute severe asthma, receiving maximised therapy (oxygen, inhaled bronchodilators, and glucocorticoids). OBJECTIVES: To determine if the addition of intravenous aminophylline produces a beneficial effect in children with acute severe asthma receiving conventional therapy. SEARCH STRATEGY: The Cochrane Airways Group register of trials was used to identify relevant studies. The latest search was carried out in December 2004 SELECTION CRITERIA: Randomised-controlled trials comparing intravenous aminophylline with placebo in addition to usual care in children met the inclusion criteria. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies and extracted data. Disagreement in the selection of trials was resolved by consensus. Attempts were made to contact authors to verify accuracy of data. MAIN RESULTS: Seven trials met the inclusion criteria (380 participants). Methodological quality was high. All studies recruited children with acute severe asthma and requiring hospital admission. Six studies sought participants who were unresponsive to nebulised short-acting beta-agonist and administered systemic steroids to study participants. In two studies where some children were able to perform spirometry, baseline FEV1 was between 35 and 45% predicted. The addition of aminophylline to steroids and beta2-agonist significantly improved FEV1% predicted over placebo at 6-8 hours, 12-18 hours and 24 hours. Aminophylline led to a greater improvement in PEF% predicted over placebo at 12-18 hours. There was no significant difference in length of hospital stay, symptoms, frequency of nebulsations and mechanical ventilation rates. There were insufficient data to permit aggregation for oxygenation and duration of supplemental oxygen therapy. Aminophylline led to a three-fold increase in the risk of vomiting. There was no significant difference between treatment groups with regard to hypokalaemia, headaches, tremour, seizures, arrhythmias and deaths. AUTHORS' CONCLUSIONS: In children with a severe asthma exacerbation, the addition of intravenous aminophylline to beta2-agonists and glucocorticoids (with or without anticholinergics) improves lung function within 6 hours of treatment. However there is no apparent reduction in symptoms, number of nebulised treatment and length of hospital stay. There is insufficient evidence to assess the impact on oxygenation, PICU admission and mechanical ventilation. Aminophylline is associated with a significant increased risk of vomiting.

Acute Disease↗

Inhaled fluticasone versus inhaled beclomethasone or inhaled budesonide for chronic asthma in adults and children.

BACKGROUND: Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. OBJECTIVES: To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register (January 2004) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003). SELECTION CRITERIA: Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed articles for inclusion and methodological quality. One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. MAIN RESULTS: Fifty six studies (12, 119 participants) met the inclusion criteria. Methodological quality was variable. Dose ratio 1:2: FP produced a significantly greater FEV1 (0.14 litres, 95% Confidence Interval (CI) 0.06 to 0.22), morning PEF (11.10 L/min, 95%CI 3.12 to 19.09 L/min) and evening PEF (9.31 L/min, 95%CI 5.12 to 13.5 L/min). This applied to all drug doses, age groups, and delivery devices. No difference between FP and BDP/BUD were seen for trial withdrawals. Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. When given at half the dose of BDP/BUD, FP led to a greater likelihood of pharyngitis. There was no difference in the likelihood of oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured frequently but data presentation was limited. Dose ratio 1:1: FP produced a statistically significant difference in am PEF (9.58 L/min (95% CI 5.20 to 13.97)), pm PEF (7.41 L/min (95% CI 2.61 to 12.22)), and FEV1 (0.09 L (0.02 to 0.17)). The effects on exacerbations were mixed. There was an increase in the incidence of hoarseness, but no significant difference in pharyngitis, candidiasis, or cough. AUTHORS' CONCLUSIONS: Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing hoarseness when given at the same daily dose. Future studies should attempt to establish the relative efficacy of inhaled steroids delivered with CFC-free propellants.

Adult↗

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↗

Inhaled fluticasone versus placebo for chronic asthma in adults and children.

BACKGROUND: Inhaled fluticasone propionate (FP) is a relatively new inhaled corticosteroid for the treatment of asthma. OBJECTIVES: 1. To assess efficacy and safety outcomes in studies that compared FP to placebo for treatment of chronic asthma.2. To explore the presence of a dose-response effect. SEARCH STRATEGY: We searched the Cochrane Airways Group Trial Register (January 2004), reference lists of articles, contacted trialists and searched abstracts of major respiratory society meetings (1997-2004). SELECTION CRITERIA: Randomised trials in children and adults comparing FP to placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Quantitative analyses where undertaken using RevMan Analyses 4.2.7. MAIN RESULTS: Sixty eight studies met the inclusion criteria (11, 104 participants). Methodological quality was high. In non-oral steroid treated asthmatics with mild and moderate disease FP resulted in improvements from baseline compared with placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45 litres); morning PEF (between 27 and 47 L/min); symptom scores (based on a standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use (between 1.2 and 2.2 puffs/d). High dose FP reduced the number of patients dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05 to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness and oral Candidiasis, but 21 patients would need to be treated for one extra to develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to be treated to avoid one extra patient being withdrawn due to lack of efficacy at all doses of FP. AUTHORS' CONCLUSIONS: Doses of FP in the range 100-1000 mcg/d are effective. In most patients with mild-moderate asthma improvements with low dose FP are only a little less than those associated with high doses when compared with placebo. High dose FP appears to have worthwhile oral-corticosteroid reducing properties. FP use is accompanied by an increased likelihood of oropharyngeal side effects.

Administration, Inhalation↗

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults.

BACKGROUND: Cough is a very common symptom presenting to medical practitioners. Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles were searched. The date of last search was 4th April 2004. SELECTION CRITERIA: All randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined criteria for inclusion. Two independent reviewers selected, extracted and assessed data for inclusion. Authors were contacted for further information. Data was analysed as "intention to treat" as well as "treatment received". Paediatric and adults data were considered separately. Sensitivity analyses were performed. MAIN RESULTS: 11 studies (3 paediatric, 8 adults; 383 participants) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H(2) antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Five adult studies comparing PPI (2-3 months) to placebo were analysed for various outcomes in the meta-analysis. Enrollment of subjects for two studies were primarily from medical clinics and another three studies were otolaryngeal clinic patients. Using "intention to treat", pooled data from three studies resulted in no significant difference between treatment and placebo in total resolution of cough. Pooled data revealed no significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analysis. A significant improvement in change of cough scores was found in end of intervention (2-3 months) in those receiving PPI with a standardised mean difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials. Two studies reported improvement in cough after 5 days to 2 weeks of treatment. Significant heterogeneity was found between studies using omeprazole and other PPIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude that GORD treatment with PPI is beneficial for cough associated with GORD in adults. The beneficial effect was only seen in sub-analysis and its effect was small. The optimal duration of such a trial of therapy to evaluate response could not be ascertained in the meta-analysis although two RCTs reported significant change by two weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Data in children are inconclusive. Future paediatric and adult studies are needed whereby studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non acid reflux whilst on therapy.

Adult↗

Inhaled beclomethasone versus placebo for chronic asthma.

BACKGROUND: Inhaled beclomethasone dipropionate (BDP) has been, together with inhaled budesonide, the mainstay of anti-inflammatory therapy for asthma for many years. A range of new prophylactic therapies for asthma is becoming available and BDP has been reformulated using a hydrofluoroalkane-134a (HFA) propellant which is free from chlorofluorocarbon (CFC). OBJECTIVES: The objectives of this review were to: (1) Compare the efficacy of BDP with placebo with both CFC and HFA propellants in the treatment of chronic asthma. (2) Explore the possibility that a dose response relationship exists for BDP in the treatment of chronic asthma. (3) To provide the best estimate of the efficacy of BDP as a benchmark for evaluation of newer asthma therapies. SEARCH STRATEGY: Electronic searches were current as of January 2003. SELECTION CRITERIA: Randomised parallel group design trials for a minimum period of four weeks, in children and adults comparing CFC-BDP or HFA-BDP with placebo in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data; authors were contacted to clarify missing information. We analysed data with RevMan Analyses 1.0.2. MAIN RESULTS: 60 studies recruiting 6542 participants met the inclusion criteria. CFC-BDP (57 studies): In non-oral steroid treated patients, at doses of 400 mcg/day or less CFC-BDP produced significant improvements from baseline in a number of efficacy measures compared with placebo, including forced expiratory volume in one second (FEV1) 360 ml (95% CI 260 to 460); FEV1 (% predicted) WMD 12.41% (95% CI 8.18 to 16.64) and morning peak expiratory flow rate (am PEF) WMD 35.95 L/min (95% CI 27.85 to 44.04). BDP also led to reductions in rescue beta-2 agonist use compared with placebo of -2.32 puffs/d (95% CI -2.55 to -2.09) and reduced the relative risk (RR) of trial withdrawal due to an asthma exacerbation 0.25 (95% CI 0.12 to 0.51). Subgroup analyses based on treatment duration provide support to the proposal that a treatment period of greater than four weeks is required to realise a fuller treatment effect. In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD -4.91 mg/d (95% CI -5.88 to -3.94 mg/d) and greater likelihood of withdrawing oral steroid treatment RR 8.02 (95% CI 3.23 to 19.92). HFA-BDP (3 studies): In non-oral steroid-treated patients, HFA-BDP was significantly more effective than placebo in improving FEV1, morning and evening PEF, FEF25 to 75%, reduced asthma symptoms and beta2-agonists daily consumption. Significant effects for such outcomes were apparent after six weeks of treatment. In oral steroid treated patients, HFA-BDP improved significantly FEV1 and am PEF. The summary estimates for these outcomes suggested a high level of heterogeneity, and divergent aims of the studies may contribute to the variation we observed. Limited data on adverse events were reported. AUTHORS' CONCLUSIONS: This review has quantified the efficacy of CFC-BDP and HFA-BDP in the treatment of chronic asthma and strongly supports its use. Current asthma guidelines recommend titration of dose to individual patient response, but the published data provide little support for dose titration above 400 mcg/d in patients with mild to moderate asthma. There are insufficient data to draw any conclusions concerning dose-response in people with severe asthma.

Administration, Inhalation↗

Interventions to improve compliance with continuous positive airway pressure for obstructive sleep apnoea.

BACKGROUND: Continuous Positive Airways Pressure (CPAP) is currently considered to be the cornerstone of therapy for sleep apnoea (OSA). However compliance with this treatment is frequently poor, which may lead to ongoing symptoms of sleep disruption, daytime sleepiness and poor waking cognitive function. Mechanical and psychological/educational interventions have been proposed to try to increase the hours of use of CPAP therapy. OBJECTIVES: To determine the efficacy of interventions designed to increase compliance with CPAP. SEARCH STRATEGY: We searched the Cochrane Airways Group Sleep Apnoea Specialised Register (January 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing interventions to improve compliance with CPAP usage were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed articles for inclusion in the review and extracted data. Attempts were made to obtain additional unpublished data from the trialists. MAIN RESULTS: 24 studies met the inclusion criteria with 1007 participants. Each of the mechanical interventions was compared with fixed CPAP alone. Auto-CPAP (13 studies): A small, significant difference was observed in compliance but this effect disappeared when we took account of the variation between the studies. There may be a subgroup of patients who respond better than others. Most participants preferred auto-CPAP to fixed CPAP where this was measured. Bi-level PAP (3 studies): No significant differences were observed in compliance. One small study found no difference in preference. Patient titrated CPAP (1 study): No significant difference was observed in compliance. Humidification(1 study): This small study found no significant difference in compliance. Educational/psychological interventions (6 studies): One small study demonstrated superior compliance in patients treated with cognitive behavioural therapy + CPAP versus CPAP alone but only after 12 weeks. In one, larger study intensive support including home visits increased hours of use. No other study demonstrated significant effects in favour of active treatment. REVIEWERS' CONCLUSIONS: The effect of Auto-CPAP in increasing hours of use in unselected patients starting this treatment remains unclear. Different pooled analyses gave conflicting results and it may be that carefully selected participants may respond more favourably than others. The evidence in support of Bi-PAP, self-titration and humidification is lacking and studies are required in these areas. There is some evidence that psychological/educational interventions improve CPAP usage. This requires confirmation in larger studies of longer duration, with rigorous follow-up. The cost-benefit ratio of such interventions requires assessment. Future studies need to consider the effects of treatment in participants who are poorly compliant. The studies assembled were characterised by high machine usage in the control groups, and low withdrawal rates making it less likely that any benefit could be demonstrated.

Adult↗

Oral appliances for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea-hypopnoea is a syndrome characterised by recurrent episodes of partial or complete upper airway obstruction during sleep that are usually terminated by an arousal. Nasal continuous positive airway pressure is the primary treatment for obstructive sleep apnoea-hypopnoea, but many patients are unable or unwilling to comply with this treatment. Oral appliances are an alternative treatment for sleep apnoea. OBJECTIVES: The objective was to review the effects of oral appliance in the treatment of sleep apnoea in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Sleep Apnoea RCT Register. Searches were current as of June 2004. Reference lists of articles were also searched. SELECTION CRITERIA: Randomised trials comparing oral appliance with control or other treatments in adults with sleep apnoea. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and two reviewers extracted data independently. Study authors were contacted for missing information. MAIN RESULTS: Thirteen trials involving 553 participants were included. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. Oral appliances versus control appliances (five studies): Oral appliances reduced daytime sleepiness in two crossover trials (WMD -1.81 [95%CI: -2.72, -0.90]), and improved apnoea-hypopnoea index (AHI) (-13.17 [-18.53 to -7.80] parallel group data - four studies). Oral appliances versus CPAP (seven studies): Oral appliances were less effective than continuous positive pressure in reducing apnoea-hypopnoea index (WMD 13 [95% CI: 7.63, 18.36], parallel studies - two trials; WMD 6.96 [4.82, 9.10] cross-over studies - six trials). However, no significant difference was observed on symptom scores. Nasal continuous positive pressure was more effective at improving minimum arterial oxygen saturation during sleep compared with oral appliance. In two small crossover studies, participants preferred oral appliance therapy to continuous positive airways pressure. Oral appliances versus surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. REVIEWERS' CONCLUSIONS: There is some evidence suggesting that oral appliance improves subjective sleepiness and sleep disordered breathing compared with a control. Nasal continuous positive airways pressure appears to be more effective in improving sleep disordered breathing than oral appliance. Until there is more definitive evidence on the effectiveness of oral appliances, it would appear to be appropriate to restrict oral appliance therapy to patients with sleep apnoea who are unwilling or unable to comply with continuous positive airways pressure therapy.

Adult↗

Acupuncture for chronic asthma.

BACKGROUND: Acupuncture has traditionally been used to treat asthma in China and is used increasingly for this purpose internationally. OBJECTIVES: The objective of this review was to assess the effects of acupuncture for the treatment of asthma or asthma-like symptoms. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register (searched August 2003), the Cochrane Complementary Medicine Field trials register, the Alternative Medicine Database (August 2003) and reference lists of articles. We also contacted trialists and researchers in the field of complementary and alternative medical research. SELECTION CRITERIA: Randomised and possibly randomised trials using needle acupuncture or other forms of stimulation of acupuncture. Any form of control treatment was considered (no treatment in addition to conventional asthma treatment, sham or placebo interventions, active comparator interventions). Studies were included provided outcome was assessed at one week or more. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed trial quality. A reviewer experienced in acupuncture assessed the adequacy of the active and sham acupunctures used in the studies. Study authors were contacted for missing information. MAIN RESULTS: Eleven studies met the inclusion criteria with 324 participants. Trial reporting was poor and trial quality was deemed inadequate to generalise findings. There was variation in the type of active and sham acupunctures, the outcomes measured and time-points presented. The points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Two studies used individualised treatment strategies and one study used a combination strategy of formula acupuncture with the addition of individualised points. No statistically significant or clinically relevant effects were found for acupuncture compared to sham acupuncture. Data from two small studies were pooled for lung function (post-treatment FEV1): Standardised Mean Difference 0.12, 95% confidence interval -0.31 to 0.55). REVIEWER'S CONCLUSIONS: There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment. Further research needs to consider the complexities and different types of acupuncture.

Acupuncture Therapy↗

Homeopathy for chronic asthma.

BACKGROUND: Homeopathy involves the use, in dilution, of substances which cause symptoms in their undiluted form. It is one of the most widespread forms of complementary medicines and is also used to treat asthma. OBJECTIVES: The objective of this review was to assess the effects of homeopathy in people with chronic stable asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register, the Cochrane Complementary Medicine Field trials register, the Glasgow Homeopathic Hospital database, the Münchener Modell database and reference lists of articles. Searches were current as of August 2003. SELECTION CRITERIA: Randomised trials of homeopathy for the treatment of stable chronic asthma, with observation periods of at least one week were included. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken by two reviewers. Trial quality was assessed by the reviewers. MAIN RESULTS: Six trials with a total of 556 people were included. These trials were all placebo-controlled and double-blind, but of variable quality. They used different homeopathic treatments which precluded quantitative pooling of results for the primary outcome. Standardised treatments in these trials are unlikely to represent common homeopathic practice, where treatment tends to be individualised. No trial reported a significant difference on validated symptom scales. There were conflicting results in terms of lung function between the studies. There has been only a limited attempt to measure a 'package of care' effect (i.e., the effect of the medication as well as the consultation, which is considered a vital part of individualised homeopathic practice). REVIEWER'S CONCLUSIONS: There is not enough evidence to reliably assess the possible role of homeopathy in asthma. As well as randomised trials, there is a need for observational data to document the different methods of homeopathic prescribing and how patients respond. This will help to establish to what extent people respond to a 'package of care' rather than the homeopathic intervention alone.

Asthma↗

Inhaled fluticasone versus inhaled beclomethasone or inhaled budesonide for chronic asthma.

BACKGROUND: Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly prescribed inhaled corticosteroids for the treatment of asthma, Fluticasone propionate (FP) is newer agent with greater potency in in-vitro assays. OBJECTIVES: To compare the efficacy and safety of Fluticasone to Beclomethasone or Budesonide in the treatment of chronic asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register (January 2003) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2003). SELECTION CRITERIA: Randomised trials in children and adults comparing Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Quantitative analyses were undertaken using RevMan analyses 1.0.1. MAIN RESULTS: 48 studies (11,479 participants) met the inclusion criteria. Methodological quality was variable. When compared at a FP:BUD/BDP dose ratio of 1:2, fluticasone produced a significantly greater FEV1 (Weighted Mean Difference (WMD) 0.11 litres, 95% Confidence Interval (CI) 0.01 to 0.20 litres), morning PEF (WMD 13 L/min, 95%CI 5 to 22 L/min) and evening PEF (WMD 11 L/min, 95%CI 1 to 20 L/min). This applied to all drug doses, age groups, and delivery devices, although subgroup analyses suggested that the relative benefit of FP may be greater in more severe patients treated with higher doses of inhaled corticosteroid. No difference between fluticasone and beclomethasone or budesonide were seen for trial withdrawals (Peto OR 0.76, 95%CI 0.53 to 1.09). Symptoms and rescue medication use were widely reported but few trials provided sufficient data for analysis. A higher likelihood of pharyngitis (Peto Odds Ratio 2.16; 95% CI 1.43 to 3.24) was apparent when patients were treated with fluticasone at twice the dose of BDP/BUD, although there was unexplained heterogeneity in this effect between trials. There was no difference in the likelihood of oral Candidiasis. Plasma cortisol and 24 hour urinary cortisol were measured frequently but data presentation was limited. REVIEWERS' CONCLUSIONS: Fluticasone given at half the daily dose of beclomethasone or budesonide leads to small improvements in measures of airway calibre, but it appears to have a higher risk of causing side-effects when given at the same daily dose.

Adult↗