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BACKGROUND Limited studies are available on the clinical significance of left ventricular (LV) lead polarity in patients undergoing cardiac resynchronization therapy (CRT), with a recent study suggesting better outcomes with LV true bipolar pacing. OBJECTIVE We aimed to determine whether true bipolar LV pacing is associated with reduced mortality in a large, real-life CRT cohort, followed by remote monitoring. METHODS We analyzed de-identified device data from CRT patients followed by the Boston Scientific LATITUDE remote monitoring database system. Patients with LV bipolar leads paced between the LV ring and LV tip were identified as true bipolar and those with LV bipolar leads paced between LV tip or LV ring and right ventricular (RV) coil were identified as extended bipolar. Patients with unipolar leads were identified as unipolar. RESULTS Of the 59 046 patients included in the study, 2927 had unipolar pacing, 34 390 had extended bipolar pacing, and 21 729 had true bipolar pacing. LV true bipolar pacing was associated with a significant 30% lower risk of all-cause mortality as compared to unipolar pacing (hazards ratio [HR] = 0.70, 95% CI: 0.62-0.79, P

Background Remote monitoring of implantable cardioverter‐defibrillators has been associated with reduced rates of all‐cause rehospitalizations and mortality among device recipients, but long‐term economic benefits have not been studied. Methods and Results An economic model was developed using the PREDICT RM database comparing outcomes with and without remote monitoring. The database included patients ages 65 to 89 who received a Boston Scientific device from 2006 to 2010. Parametric survival equations were derived for rehospitalization and mortality to predict outcomes over a maximum time horizon of 25 years. The analysis assessed rehospitalization, mortality, and the cost‐effectiveness (expressed as the incremental cost per quality‐adjusted life year) of remote monitoring versus no remote monitoring. Remote monitoring was associated with reduced mortality; average life expectancy and average quality‐adjusted life years increased by 0.77 years and 0.64, respectively (6.85 life years and 5.65 quality‐adjusted life years). When expressed per patient‐year, remote monitoring patients had fewer subsequent rehospitalizations (by 0.08 per patient‐year) and lower hospitalization costs (by $554 per patient year). With longer life expectancies, remote monitoring patients experienced an average of 0.64 additional subsequent rehospitalizations with increased average lifetime hospitalization costs of $2784. Total costs of outpatient and physician claims were higher with remote monitoring ($47 515 vs $42 792), but average per patient‐year costs were lower ($6232 vs $6244). The base‐case incremental cost‐effectiveness ratio was $10 752 per quality‐adjusted life year, making remote monitoring high‐value care. Conclusion Remote monitoring is a cost‐effective approach for the lifetime management of patients with implantable cardioverter‐defibrillators.

Background:We hypothesized that survival in implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) patients is predicted by baseline Heart Rate Score.Methods:Heart Rate Score is determined from the atrial paced and sensed histogram of a DDD ICD or CR

Objectives Vitamin D deficiency and Chronic Obstructive Pulmonary Disease (COPD) are both under-recognized health problems, world-wide. Although Vitamin D has long been known for calcemic effects it also has less known noncalcemic effects. Recent data have shown that Vitamin D deficiency is highly prevalent in patients with COPD and correlates with forced expiratory volume in one second (FEV1) and FEV1 decline. The objective of this work was to review the current literature on vitamin D deficiency in relation with COPD. Data source A literature search, using the words “vitamin D” and “COPD”, was undertaken in Pubmed database. Results The noncalcemic effects of vitamin D relating with COPD may be summarised as increasing antimicrobial peptide production, regulation of inflammatory response and airway remodelling. Vitamin D inhibits the production of several proinflammatory cytokines and leads to suppression Th1 and Th17 responses which may be involved in the pathogenesis of COPD. Vitamin D insufficiency may also contribute to chronic respiratory infections and airway colonization so returning vitamin D concentrations to an optimal range in patients with COPD might reduce bacterial load and concomitant exacerbations.Vitamin D is also important for COPD-related comorbodities such as osteoporosis, muscle weakness and cardiovascular diseases. Data about the effect of Vitamin D supplementation on those comorbidities in relation with COPD are been scarce. Conclusion Improving the blood level of Vitamin D into the desired range may have a beneficial effect bones and muscles, but more studies are needed to test to test that hypothesis.

Background and objective Both patients with cardiac diseases as well as those with COPD report an impaired health status. The frequencies of objectively assessed co-morbid cardiac diseases and their impact on health status in patients with COPD are unknown. We aimed to investigate echocardiographic abnormalities and their impact on health status in a large cohort of patients with COPD referred for pulmonary rehabilitation (PR). Methods In this cross-sectional, observational analyses, demographic and clinical characteristics were assessed during an inpatient pre-PR assessment. All patients underwent Doppler echocardiographic evaluation. Health status was assessed using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ). Results A total of 514 patients (55.3% males, age: 64.1 (9.1) years, forced expiratory volume in 1 s (FEV1 ): 48.6 (20.0) % predicted) were included for analyses. Two hundred and seventy-six patients (53.7%) were diagnosed with one or more echocardiographic abnormalities. Most prevalent were left ventricular (LV) hypertrophy (LVH, 31.0%), increased right ventricular systolic pressure (RVSP, 20.4%) and impaired LV ejection fraction (LVEF, 16.5%). Of the 276 patients, 176 (63.8%) with echocardiographic abnormalities did not have these recorded in their medical history. Patients with echocardiographic abnormalities reported a worse health status as assessed with the SGRQ total score (62.5 (17.1) vs 59.3 (17.6) points, P = 0.044). CCQ and CAT did not differ between groups. Conclusion More than half of the patients referred to PR had echocardiographic abnormalities of which two-third did not have them recorded in their medical history. We detected a limited impact of echocardiographic abnormalities on health status.

ICD Characteristics and Survival in Young PatientsIntroduction Indications for implantable cardioverter defibrillators (ICDs) in young patients have expanded and differ from those in older adults. We sought to provide descriptive characteristics and data regarding ICD therapy and outcomes among younger and older ICD recipients. Methods and Results Demographics, device type and programming, remotely transmitted data, shock events, and survival were compared among younger (≤30 years) and older (>30 years) cohorts with ICDs from a single manufacturer followed on a remote network. The younger cohort included 904 patients (1.6% of all implants). This group had more females (46% vs. 25%; P 30 years, P < 0.01). Shock for polymorphic ventricular tachycardia/fibrillation (VT/VF) was more frequent in younger patients (12% vs. 5%; P < 0.01); 39% of all shocks were inappropriate. A 10-fold increased risk of mortality was seen among young patients with shocks for atrial fibrillation/flutter (AF/AFL). Conclusions Differences in survival, shock incidence, and prognostic significance of VT/VF and AF/AFL exist between younger and older ICD recipients. These suggest distinct differences in myocardial substrates and diseases that ultimately impact ICD management.

Introduction Adjudication of thousands of implantable cardioverter defibrillator (ICD)-treated arrhythmia episodes is labor intensive and, as a result, is most often left undone. The objective of this study was to evaluate an automatic classification algorithm for adjudication of ICD-treated arrhythmia episodes. Methods The algorithm uses a machine learning algorithm and was developed using 776 arrhythmia episodes. The algorithm was validated on 131 dual-chamber ICD shock episodes from 127 patients adjudicated by seven electrophysiologists (EPs). Episodes were classified by panel consensus as ventricular tachycardia/ventricular fibrillation (VT/VF) or non-VT/VF, with the resulting classifications used as the reference. Subsequently, each episode electrogram (EGM) data was randomly assigned to three EPs without the atrial lead information, and to three EPs with the atrial lead information. Those episodes were also classified by the automatic algorithm with and without atrial information. Agreement with the reference was compared between the three EPs consensus group and the algorithm. Results The overall agreement with the reference was similar between three-EP consensus and the algorithm for both with atrial EGM (94% vs 95%, P = 0.87) and without atrial EGM (90% vs 91%, P = 0.91). The odds of accurate adjudication, after adjusting for covariates, did not significantly differ between the algorithm and EP consensus (odds ratio 1.02, 95% confidence interval: 0.97–1.06). Conclusions This algorithm performs at a level comparable to an EP panel in the adjudication of arrhythmia episodes treated by both dual- and single-chamber ICDs. This type of algorithm has the potential for automated analysis of clinical ICD episodes, and adjudication of EGMs for research studies and quality analyses.

Background: Approximately 12–21% of implantable cardioverter defibrillator (ICD) patients receive inappropriate shocks. We sought to determine the incidence and causes of noise/artifact and oversensing (NAO) resulting in ICD shocks. Methods: A random sample of 2,000 patients who received ICD and cardiac resynchronization therapy defibrillator shocks and were followed by a remote monitoring system was included. Seven electrophysiologists analyzed stored electrograms from the 5,279 shock episodes. Episodes were adjudicated as appropriate or inappropriate shocks. Results: Of the 5,248 shock episodes with complete adjudication, 1,570 (30%) were judged to be inappropriate shocks. Of these 1,570, 134 (8.5%) were a result of NAO. The 134 NAO episodes were determined to be due to external noise in 76 (57%), lead connector-related in 37 (28%), muscle noise in 11 (8%), oversensing of atrium in seven (5%), T-wave oversensing in two (2%), and other noise in one (1%). The ICD shock itself resulted in a marked decrease in the level of noise in 60 of 134 (45%) NAO episodes, and the magnitude of this effect varied with the type of NAO (58% for external noise, 35% for muscle, 27% for lead/connector, and 0% for oversensing; P = 0.03). There was no significant difference in NAO likelihood based on type of lead (integrated bipolar 89/1,802 vs dedicated bipolar 9/140, P = 0.67). Conclusions: External noise and lead/connector noise were the primary causes, while T-wave oversensing was the least common cause of NAO resulting in ICD shock. Noise/artifact decreased immediately after a shock in nearly half of episodes. The specific ICD lead type did not impact the likelihood of NAO. (PACE 2012;XX:1–7)

Objective The multiple breath wash-out technique (MBW) that measures lung clearance index (LCI) and functional residual capacity (FRC) may be more sensitive than spirometry for identification of early obstructive airways disease. The open MBW setup using mass spectrometry referenced in previous publications is not readily available in the U.S. Our objective was to assess validity and sensitivity of a commercially available device that uses a closed (rebreathing) setup with photoacoustic spectroscopy for MBW testing. Study Design and Methods Subjects aged 5–21 who were either healthy or had a history of cystic fibrosis were enrolled. Subjects completed MBW (Innocor device; Innovision, Denmark) and spirometry; measures obtained included LCI, FRC, and forced expiratory volume in 1 sec, as well as changes in end-tidal carbon dioxide levels (CO2) and tidal volume during MBW testing. Results Seventeen subjects attempted a total of 76 MBW maneuvers; 80% were completed and 60% met criteria for acceptability; most were unacceptable due to errors in the tracer gas curve. Substantial intra-subject variability for LCI and FRC were noted (mean 26% ± 55 and 36% ± 63, respectively). Subjects were also noted to have significant increases in exhaled CO2 and tidal volume during MBW testing. Conclusions In our initial experience using a commercially available closed setup for MBW testing, we found a significant degree of intra-subject variability leading us to suspend testing. Variability could be due to hypercapnea and instability of tidal breathing secondary to the rebreathing setup. Further studies are needed to better understand the closed system MBW setup. Pediatr Pulmonol. 2012; 47:1242–1250. © 2012 Wiley Periodicals, Inc.

Aim. This paper is a report of a study of the application and critique of Rasch analysis to the development of the Dyspnoea‐12 questionnaire; an instrument that measures breathlessness severity. Background. The development of questionnaires has traditionally involved application of classical test theory. Rasch analysis has gained international momentum as a robust application of ‘modern’ psychometric testing for the development of new instruments and the refinement of existing ones. Method. A total of 358 patients [mean age 62 (sd = 8); chronic obstructive pulmonary disease = 123, interstitial lung disease = 129, heart failure = 106], responded to an initial list of 81 items (between May 2006 and February 2008). Hierarchical modelling reduced the list to 34 items. Rasch analysis was used to inform decisions about further item removal and fit to the unidimensional model. Rasch analysis included tests of item response appropriateness, item residual, differential item functioning (including gender and diagnosis) and unidimensionality. Results. Twenty‐two items failed to reach the requirements of the Rasch model and were removed. Reasons included high residuals and item bias associated with gender and diagnosis. The 12‐items conformed to the Rasch unidimensional parameters (number of statistically significant t‐tests 6·7%; confidence interval: 4·4–9·0%). Conclusion. We have presented the steps involved in reducing and refining a large item‐set by identifying those items which possessed the most reliable measurement properties. The Dyspnoea‐12 is reliable and simple to use and should find utility in both practice and research settings. We recommend that nurses consider Rasch analysis in the development of health‐related questionnaires.

Background: The increasing use of remote monitoring with the associated large retrievable databases provides a unique opportunity to analyze observations on implantable cardioverter-defibrillator (ICD) therapies. Adjudication of a large number of stored ICD electrograms (EGMs) presents a unique challenge. The ALTITUDE study group was designed to use the LATITUDE remote monitoring system to evaluate ICD patient outcomes across the United States. Methods and Results: Of 81,081 patients on remote monitoring, a random sample of 2,000 patients having 5,279 shock episodes was selected. The ALTITUDE EGM review committee was comprised of seven electrophysiologists from four institutions. An online EGM adjudication system was designed. Episodes were classified as appropriate (70% of shock episodes) or inappropriate ICD therapies (30%). Light's Kappa was used to assess agreement. Interobserver and intraobserver Kappa scores for dual-chamber ICDs were 0.84 (0.71–0.91) and 0.89 (0.82–0.95), consistent with substantial agreement. Interobserver and intraobserver Kappa scores for single-chamber ICDs were 0.61 (0.54–0.67) and 0.69 (0.59–0.79). The rhythm categories of “nonsustained arrhythmia” and “polymorphic and monomorphic ventricular tachycardia” resulted in the greatest degree of discordant adjudication between reviewers. Conclusions: This method of adjudication of a large volume of stored EGM data prior to device therapies will allow new observations in regards to device performance and has the potential to improve device programming and design. There was substantial interreviewer agreement for rhythm classification. Agreement was greater for dual-chamber compared to single-chamber devices, indicating the atrial lead adds diagnostic value in rhythm interpretation. (PACE 2011; 34:1003–1012)

INTRODUCTION: Randomised controlled trials (RCTs) are considered the least biased method for evaluating drug efficacy and several large long-term RCTs in chronic obstructive pulmonary disease have been published. These usually include drugs with symptomatic benefits and have significant withdrawal rates. OBJECTIVES: We aimed at examining bias due to differential withdrawal in the Towards a Revolution in COPD Health (TORCH) trial. METHODS: We did an observational study nested in the TORCH trial, a placebo-controlled trial of salmeterol/fluticasone propionate combination (SFC) therapy in chronic obstructive pulmonary disease. We included 3057 patients randomly allocated to placebo or SFC in the analyses. We examined rates of withdrawal from the study and analysed change in effect parameters over time and in relation to withdrawal, as well as medication uptake after withdrawal. RESULTS: There was differential withdrawal with a significantly higher withdrawal rate from the group allocated to placebo than to SFC, 44% compared with 34%. Regardless of treatment group, withdrawal was associated with worse baseline lung function and more frequent exacerbations, leading to selection of a study population in better health than those originally recruited. As a result, annualized exacerbation rates in the first 6 months of the study compared with the last 6 months of the study decreased from 6.8 to 0.9 in the placebo group and from 3.0 to 0.8 in the SFC group. Also, use of medications under test in the study was frequent in patients after withdrawal. CONCLUSION: Significant bias may occur in long-term RCTs of registered medications with symptomatic benefits as a result of differential withdrawal.

Background Oral theophylline has, for many years, been used as a bronchodilator in patients with COPD. Despite the introduction of new drugs, and its narrow therapeutic index, theophylline is still recommended for COPD treatment. Objectives To determine the effectiveness of oral theophylline when compared to placebo in patients with stable COPD. Search methods We searched the Cochrane Airways Group trial register and Cochrane Central Register of Controlled Trials Cochrane Controlled Clinical Registers were searched. Selection criteria All studies were randomised controlled trials (RCTs). Data collection and analysis Two reviewers independently abstracted data and asessed the methodological quality. Main results Twenty RCTs met the inclusion criteria. Concomitant therapy varied from none to any other bronchodilator plus corticosteroid (oral and inhaled). The following outcomes were significantly different when compared to placebo. Forced expiratory volume in one second (FEV1) improved with treatment: Weighted Mean Difference (WMD) 100 ml; 95% Confidence Interval (CI) 40 to 160 ml. Similarly for forced vital capacity (FVC): WMD 210 ml 95%CI 100 to 320. Two studies reported an improvement in maximum oxygen consumption (VO2 max); WMD 195 ml/min, 95%CI 113 to 278. At rest, arterial oxygen tension at rest (PaO2) and arterial carbon dioxide tension at rest (PaCO2) both improved with treatment (WMD 3.2 mm Hg; 95%CI 1.2 to 5.1, and WMD -2.4 mm Hg; 95%CI -3.5 to -1.2, respectively). Walking distance tests did not improve (four studies, Standardised Mean Difference 0.30, 95%CI -0.01 to 0.62), neither did Visual Analogue Score for breathlessness in two small studies (WMD 3.6, 95%CI -4.6 to 11.8). The Relative Risk (RR) of nausea was greater with theophylline (RR 7.7; 95%CI 1.5 to 39.9). However, patients' preference for theophylline was greater than that for placebo (RR 2.27; 95%CI 1.26 to 4.11). Very few participants withdrew from these studies for any reason. Authors' conclusions Theophylline has a modest effect on FEV1 and FVC and slightly improves arterial blood gas tensions in moderate to severe COPD. These benefits were seen in participants receiving a variety of different concomitant therapies. Improvement in exercise performance depended on the method of testing. There was a very low dropout rate in the studies that could be included in this review, which suggests that recruited participants may have been known by the investigators to be theophylline tolerant . This may limit the generalisability of these studies.

Background Beclomethasone dipropionate (BDP) and budesonide (BUD) are used widely in the treatment of chronic asthma. The two drugs have different in vitro pharmacokinetic characteristics. It is unclear whether this translates into clinically significant differences in efficacy or safety when treating children and adults with chronic asthma. Objectives To assess clinical outcomes in studies which have compared inhaled BDP and BUD in the treatment of chronic asthma. Search methods We searched the Cochrane Airways Group Trial Register (1999) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997-1999). Selection criteria Prospective, randomised trials comparing BDP to BUD 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. Quantitative analyses where undertaken using Review Manager 4.0.3 with MetaView 3.1. Main results 24 studies met the criteria for inclusion (1174 participants). Methodological quality was variable. A meta-analysis of crossover studies did not demonstrate a significant difference between BDP and BUD for FEV1, morning PEF, evening PEF, asthma symptoms or rescue beta2 agonist use, over a dose range of 400 to 1000 mcg/d. The majority of crossover trials had significant design flaws related to a lack of washout and/or failure to exclude carryover effects so the results must be viewed with caution. A single crossover study with adequate washout showed that BUD 400 mcg/d delivered via Turbohaler dry powder inhaler (DPI) may be more effective than BDP 400 mcg/d delivered via Rotahaler DPI in reducing histamine bronchial hyper-responsiveness: Weighted Mean Difference (WMD) 0.43 log10 PC20 FEV1 (95% Confidence Intervals (CI) 0.05, 0.81 log10 PC20 FEV1). A meta-analysis of two parallel group, dose down-titration studies (231 patients) showed that less BUD delivered via a Turbohaler DPI was required to maintain control in adults asthmatics compared to BDP delivered via metered dose inhaler with or without a spacer: WMD 444 mcg/d (95% CI 332, 556 mcg/d). Authors' conclusions There is limited high quality randomised controlled trial data comparing the relative efficacy of BDP and BUD. Current guidelines (BTS 1997; GINA 1995; NHLBI 1997) assume BDP and BUD to have equal efficacy, such that for each defined level of asthma severity, the recommended doses BDP and BUD are the same. Although there is some data to suggest that BUD via Turbohaler is more effective than BDP via either Rotahaler or MDI (with and without spacer), these comparisons are confounded by use of different delivery devices, and are not sufficient to warrant a change in guideline recommendations.

BACKGROUND: Steroids are a common treatment of chronic asthma as a maintenance therapy in both developed and developing countries across the world. The cost of inhaled steroids means that in developing countries their availability is limited, leading to poorly controlled asthma in patients who are prescribed low dosage inhaled steroids, or the additional use of oral steroids to control patients' asthma. This review seeks to determine what dosage of oral steroids equates to the therapeutic effects of a moderate to high doses of inhaled steroids. OBJECTIVES: To determine therapeutically equivalent doses of inhaled versus oral steroids for adults with chronic asthma. SEARCH METHODS: The Cochrane Airways Group trials register was searched and experts in the field were contacted. Searches were current as of August 2008. SELECTION CRITERIA: Randomised controlled trials were selected of at least 4 weeks duration and included patients over the age of 15 years with chronic asthma. Trials compared inhaled steroids and oral prednisolone or prednisone; where the maximum dose for inhaled steroids was 2000 mcg/day and prednisolone 60 mg (on alternate days). DATA COLLECTION AND ANALYSIS: Two independent reviewers screened 1285 titles and abstracts from the electronic search, bibliography searches and other contacts. Of these, 10 trials met previously defined inclusion criteria. Two reviewers independently extracted study characteristics, and outcome measures. MAIN RESULTS: All trials were small and no data could be pooled. Carry‐over effects were present in at least one cross‐over trial. Data from six trials produced the same pattern, in which prednisolone 7.5‐12 mg/day appeared to be as effective as inhaled steroid 300‐2000 mcg/day. In two trials, inhaled steroid 300‐400 mcg/day was more effective than prednisolone 5 mg/day. All doses of inhaled steroid appeared to be more effective than alternate day doses of prednisolone up to 60 mg on alternate days. Side‐effect data were reported too variably to permit comparisons. A 30% incidence was reported in one study in patients receiving prednisolone 5 mg/day, none were reported in patients on inhaled steroids. AUTHORS' CONCLUSIONS: A daily dose of prednisolone 7.5‐10 mg/day appears to be equivalent to moderate‐high dose inhaled corticosteroids. Side‐effects may be present on low doses, so if there is no alternative to oral steroids, the lowest effective dose should be prescribed.

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 methods The Cochrane Airways Group Specialised Register was searched with predefined search terms. Searches were current as of October 2010. 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 effects model and reported as a weighted mean difference (MD) 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 (MD -0.41 kPa; 95% CI -0.91, 0.09; N=2) and a significant rise in PO2 (MD 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. An update search conducted in October 2005 did not identify any further studies. Authors' 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.

Background Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Cyclosporin is an immunosuppressive agent and has benefits in the treatment of a number of inflammatory disorders. It has therefore been identified as an potentially useful agent in the treatment of chronic severe asthma both in terms of possible efficacy and as a steroid sparing agent. Objectives The objective of this review was to assess the effects of adding cyclosporin to oral steroids in the treatment of chronic steroid dependent asthmatics. Search methods The Cochrane Airways Group Specialised Register and reference lists of identified articles were searched. The most recent search was conducted in September 2010. Selection criteria Randomised trials looking at the addition of cyclosporin compared to placebo in adult steroid dependent asthmatics. Data collection and analysis Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. Main results Three trials fulfilled the criteria for inclusion in the review and a total of 106 patients were recruited into these studies. Data from 98 patients could be analysed. There was a small but significant treatment effect for cyclosporin in terms of steroid dose reduction (SMD -0.5, 95% CI -1.0, -0.04). No meta-analyses could be performed for measures of lung function although one study showed small, but significant improvements in lung spirometry. Authors' conclusions The changes with cyclosporin are small and of questionable clinical significance. Given the side effects of cyclosporin, the evidence available does not recommend routine use of this drug in the treatment of oral corticosteroid dependent asthma. Plain language summary Cyclosporin (the drug for preventing organ rejection after transplant) as an oral corticosteroid sparing agent in stable asthma Some people with asthma need to rely on corticosteroid drugs to control their asthma. Corticosteroids help reduce the inflammation (swelling) of the airways (passages to the lungs) associated with asthma. Long-term use of these drugs may have serious adverse effects, so other ways to try and cut down on the need for corticosteroids are sometimes tried. Cyclosporin is the drug used to prevent organ rejections after transplants, and it can be used for other conditions involving inflammation (such as arthritis). The review of trials found that cyclosporin has a small impact on asthma symptoms, but it has major serious adverse effects.

Background Patients with chronic severe asthma are often dependent on the long term prescription of oral corticosteroids. The use of steroids is associated with serious side effects. Physicians treating such patients continue to search for alternative therapies that reduce the need for chronic dosing with oral steroids. Troleandomycin is a compound that is established as an effective antibiotic but may also have non-antibacterial actions that may be useful in the treatment of asthma. Objectives The objective of this review was to assess the effects of adding troleandomycin to oral steroids in the treatment of chronic steroid dependent asthmatics. Search methods The Cochrane Airways Group Specialised Register and reference lists of identified articles were searched. Searches are current as of September 2010. Selection criteria Randomised trials looking at the addition of troleandomycin compared to placebo in adult steroid dependent asthmatics. Data collection and analysis Trial quality was assessed and data extraction was carried out by two reviewers independently. Study authors were contacted for missing information. Main results Three trials fulfilled the criteria for inclusion in the review and a total of 112 patients were recruited into these studies. Data from 90 patients were analysed. There was no treatment effect for troleandomycin in terms of steroid dose reduction (SMD -0.29, 95% CI -0.75, 0.17). For measures of lung function a meta-analysis of data derived from two of the included studies showed no benefits for added troleandomycin (SMD 0.06 95% CI -0.8, 0.9). Authors' conclusions There is insufficient evidence to support the use of troleandomycin in the treatment of steroid dependent asthma. Plain language summary Troleandomycin as an oral corticosteroid sparing agent in stable asthma Troleandomycin is a macrolide antibiotic with established effects in the treatment of infections. It alters the breakdown of corticosteroid drugs, so may be of benefit in asthma. This review found three small studies, that provide no evidence to justify the use of this drug in asthma.

BACKGROUND Beclomethasone dipropionate (BDP) is available in a wide range of daily doses for the treatment of long-term asthma. OBJECTIVES To assess the evidence for a dose response relationship for BDP in the treatment of long-term asthma. SEARCH STRATEGY We searched the Cochrane Airways Group trial register, Cochrane Controlled Trials Register (The Cochrane Library issue 1 1999) and references lists of articles. Authors and Glaxo Wellcome UK were contacted to identify eligible studies. We also hand searched the proceeding from relevant respiratory society meetings, the British Journal of Clinical Research and the European Journal of Clinical Research for studies. SELECTION CRITERIA Prospective, randomised trials comparing two or more daily doses of BDP in patients over the age of two years with long-term asthma. DATA COLLECTION AND ANALYSIS Trials were selected for inclusion and scored for quality by two reviewers. Data were extracted by one reviewer. Authors were contacted to clarify details of study design and retrieve missing data. MAIN RESULTS 11 trials involving 1614 subjects were included. Methodological quality was variable. Studies rarely gave a clear indication of the degree of asthma control at baseline. Less than two-fold to five-fold dose differences were assessed by different studies. The results are reported as weighted mean differences (WMD) with 95% confidence limits (95% CI). The number of trials (N) contributing to each outcome is stated. In non-oral steroid treated asthmatics a small advantage of BDP 800 mcg/d over 400 mcg/d was apparent for improvement in morning peak expiratory flow rate (PEFR) compared to baseline, WMD 11 L/min (95% CI 4 to 19 L/min) N=2; improvement in forced expired volume in one second (FEV1) compared to baseline, WMD 9 ml (95% CI 3 to 140) N=1; and reduction in night-time symptom score compared to baseline, WMD 0.13 (95% CI 0.04 to 0.22) N=1. Studies that assessed BDP 1000 v 500 mcg/d and BDP 1600 v 400 mcg/d demonstrated significant advantage of higher dose over lower dose for histamine bronchial hyper-responsiveness (BHR) and percentage improvement in FEV1 compared to baseline. No differences between higher and lower daily doses of BDP were apparent for daytime symptoms, withdrawals due to asthma exacerbation, oropharyngeal side effects or measures of hypothalamo-pituitary-adrenal (HPA) function. No difference in prednisolone sparing effect was apparent when comparing high dose and low dose BDP in oral corticosteroid (OCS) dependent patients. REVIEWER'S CONCLUSIONS BDP appears to demonstrate a shallow dose response effect in long-term asthma for a small number of efficacy outcomes over range of daily doses from 400 mcg/d to 1600 mcg/d, although the clinical significance of the improvements afforded by higher doses is questionable.

The reaction of 3,6-diaza-2S,7S-di(2-pyridyl)- octane, S,S-peaen, with Co(II) and O2 in aqueous solution yields a mixture, from which may be isolated three chelate diastereomers after the addition of HCl and HClO4. These are δ-α-[Co(S,S-peaen)Cl2]- ClO4 and its Λ-α and Δ-β analogues. Previous workers had reported that a second β-diastereoisomer could be obtained but it has been shown that this is in fact an isomeric mixture of both Δ-α- and Λ-α- [Co(S,S-peaen)Cl2]ClO4. All three isomers react with oxalate anions to form an apparently unique product Λ-α-[Co(S,S-peaen)ox]+ in aqueous solution and which can be crystallized as its perchlorate salt. Two of the reactions reported represent unusual examples of octahedral inversions.