Background
Non‐invasive ventilation (NIV) with bi‐level positive airway pressure (BiPAP) is commonly used to treat patients admitted to hospital with acute hypercapnic respiratory failure (AHRF) ...secondary to an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
Objectives
To compare the efficacy of NIV applied in conjunction with usual care versus usual care involving no mechanical ventilation alone in adults with AHRF due to AECOPD. The aim of this review is to update the evidence base with the goals of supporting clinical practice and providing recommendations for future evaluation and research.
Search methods
We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and PsycINFO, and through handsearching of respiratory journals and meeting s. This update to the original review incorporates the results of database searches up to January 2017.
Selection criteria
All randomised controlled trials that compared usual care plus NIV (BiPAP) versus usual care alone in an acute hospital setting for patients with AECOPD due to AHRF were eligible for inclusion. AHRF was defined by a mean admission pH < 7.35 and mean partial pressure of carbon dioxide (PaCO2) > 45 mmHg (6 kPa). Primary review outcomes were mortality during hospital admission and need for endotracheal intubation. Secondary outcomes included hospital length of stay, treatment intolerance, complications, changes in symptoms, and changes in arterial blood gases.
Data collection and analysis
Two review authors independently applied the selection criteria to determine study eligibility, performed data extraction, and determined risk of bias in accordance with Cochrane guidelines. Review authors undertook meta‐analysis for data that were both clinically and statistically homogenous, and analysed data as both one overall pooled sample and according to two predefined subgroups related to exacerbation severity (admission pH between 7.35 and 7.30 vs below 7.30) and NIV treatment setting (intensive care unit‐based vs ward‐based). We reported results for mortality, need for endotracheal intubation, and hospital length of stay in a 'Summary of findings' table and rated their quality in accordance with GRADE criteria.
Main results
We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient‐reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.
Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) ‐3.39 days, 95% CI ‐5.93 to ‐0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO2 was observed, but this finding was not statistically significant (MD ‐4.62 mmHg, 95% CI ‐11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO2. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non‐significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) ‐0.16, 95% CI ‐0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between‐group differences.
Authors' conclusions
Data from good quality randomised controlled trials show that NIV is beneficial as a first‐line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH < 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.
Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth ...restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.
To assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs etanercept (Enbrel(®), Pfizer), abatacept (Orencia(®), Bristol-Myers Squibb), adalimumab (Humira(®), AbbVie) and tocilizumab (RoActemra(®), Roche) - with or without methotrexate where indicated for the treatment of JIA (systemic or oligoarticular JIA are excluded).
Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.
Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%.
Four placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY.
The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited.
Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required.
This study is registered as PROSPERO CRD42015016459.
The National Institute for Health Research Health Technology Assessment programme.
This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) ...for heart failure (HF).
To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions.
Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers' submissions to the National Institute for Health and Care Excellence.
Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon.
A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY.
Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups.
In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony.
This study is registered as PROSPERO number CRD42012002062.
The National Institute for Health Research Health Technology Assessment programme.
Current clinical practice is to remove a colorectal polyp detected during colonoscopy and determine whether it is an adenoma or hyperplastic by histopathology. Identifying adenomas is important ...because they may eventually become cancerous if untreated, whereas hyperplastic polyps do not usually develop into cancer, and a surveillance interval is set based on the number and size of adenomas found. Virtual chromoendoscopy (VCE) (an electronic endoscopic imaging technique) could be used by the endoscopist under strictly controlled conditions for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis.
To assess the clinical effectiveness and cost-effectiveness of the VCE technologies narrow-band imaging (NBI), flexible spectral imaging colour enhancement (FICE) and i-scan for the characterisation and management of diminutive (≤ 5 mm) colorectal polyps using high-definition (HD) systems without magnification.
Systematic review and economic analysis.
People undergoing colonoscopy for screening or surveillance or to investigate symptoms suggestive of colorectal cancer.
NBI, FICE and i-scan.
Diagnostic accuracy, recommended surveillance intervals, health-related quality of life (HRQoL), adverse effects, incidence of colorectal cancer, mortality and cost-effectiveness of VCE compared with histopathology.
Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and Database of Abstracts of Reviews of Effects were searched for published English-language studies from inception to June 2016. Bibliographies of related papers, systematic reviews and company information were screened and experts were contacted to identify additional evidence.
Systematic reviews of test accuracy and economic evaluations were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-analyses were conducted, where possible, to inform the independent economic model. A cost-utility decision-analytic model was developed to estimate the cost-effectiveness of VCE compared with histopathology. The model used a decision tree for patients undergoing endoscopy, combined with estimates of long-term outcomes (e.g. incidence of colorectal cancer and subsequent morbidity and mortality) derived from University of Sheffield School of Health and Related Research's bowel cancer screening model. The model took a NHS perspective, with costs and benefits discounted at 3.5% over a lifetime horizon. There were limitations in the data on the distribution of adenomas across risk categories and recurrence rates post polypectomy.
Thirty test accuracy studies were included: 24 for NBI, five for i-scan and three for FICE (two studies assessed two interventions). Polyp assessments made with high confidence were associated with higher sensitivity and endoscopists experienced in VCE achieved better results than those without experience. Two economic evaluations were included. NBI, i-scan and FICE are cost-saving strategies compared with histopathology and the number of quality-adjusted life-years gained was similar for histopathology and VCE. The correct surveillance interval would be given to 95% of patients with NBI, 94% of patients with FICE and 97% of patients with i-scan.
Limited evidence was available for i-scan and FICE and there was heterogeneity among the NBI studies. There is a lack of data on longer-term health outcomes of patients undergoing VCE for assessment of diminutive colorectal polyps.
VCE technologies, using HD systems without magnification, could potentially be used for the real-time assessment of diminutive colorectal polyps, if endoscopists have adequate experience and training.
Future research priorities include head-to-head randomised controlled trials of all three VCE technologies; more research on the diagnostic accuracy of FICE and i-scan (when used without magnification); further studies evaluating the impact of endoscopist experience and training on outcomes; studies measuring adverse effects, HRQoL and anxiety; and longitudinal data on colorectal cancer incidence, HRQoL and mortality.
This study is registered as PROSPERO CRD42016037767.
The National Institute for Health Research Health Technology Assessment programme.
Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment ...for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments.
To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases.
Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked.
Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted.
The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained.
There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection.
Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.
Surgery for obesity Colquitt, Jill L; Picot, Joanna; Loveman, Emma ...
Cochrane database of systematic reviews,
01/2009
2
Journal Article
Recenzirano
Bariatric (weight loss) surgery for obesity is considered when other treatments have failed. The effects of the available bariatric procedures compared with medical management and with each other are ...uncertain. This is an update of a Cochrane review first published in 2003 and previously updated in 2005.
To assess the effects of bariatric surgery for obesity.
Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented with searches of reference lists and consultation with experts in obesity research.
Randomised controlled trials (RCTs) comparing different surgical procedures, and RCTs, controlled clinical trials and prospective cohort studies comparing surgery with non-surgical management for obesity.
Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed trial quality.
Twenty six studies were included. Three RCTs and three prospective cohort studies compared surgery with non-surgical management, and 20 RCTs compared different bariatric procedures. The risk of bias of many trials was uncertain; just five had adequate allocation concealment. A meta-analysis was not appropriate.Surgery results in greater weight loss than conventional treatment in moderate (body mass index greater than 30) as well as severe obesity. Reductions in comorbidities, such as diabetes and hypertension, also occur. Improvements in health-related quality of life occurred after two years, but effects at ten years are less clear.Surgery is associated with complications, such as pulmonary embolism, and some postoperative deaths occurred.Five different bariatric procedures were assessed, but some comparisons were assessed by just one trial. The limited evidence suggests that weight loss following gastric bypass is greater than vertical banded gastroplasty or adjustable gastric banding, but similar to isolated sleeve gastrectomy and banded gastric bypass. Isolated sleeve gastrectomy appears to result in greater weight loss than adjustable gastric banding. Evidence comparing vertical banded gastroplasty with adjustable gastric banding is inconclusive. Data on the comparative safety of the bariatric procedures was limited.Weight loss and quality of life were similar between open and laparoscopic surgery. Conversion from laparoscopic to open surgery may occur.
Surgery is more effective than conventional management. Certain procedures produce greater weight loss, but data are limited. The evidence on safety is even less clear. Due to limited evidence and poor quality of the trials, caution is required when interpreting comparative safety and effectiveness.
Physical training for asthma Pereira, Mônica Corso
São Paulo medical journal,
01/2014, Letnik:
132, Številka:
3
Journal Article
Recenzirano
Odprti dostop
People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning as a consequence of inactivity. Some may restrict ...activities as per medical advice or family influence and this might result in reduced physical fitness. Physical training programs aim to improve physical fitness, neuromuscular coordination and self confidence. Subjectively, many people with asthma report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. Also, as exercise can induce asthma, the safety of exercise programmes needs to be considered.
To gain a better understanding of the effect of physical training on the respiratory and general health of people with asthma, from randomised trials.
We searched the Cochrane Airways Group Specialised Register of trials up to January 2013.
We included randomised trials of people over eight years of age with asthma who were randomised to undertake physical training or not. Physical training had to be undertaken for at least 20 minutes, two times a week, over a minimum period of four weeks.
Two review authors independently assessed eligibility for inclusion and undertook risk of bias assessment for the included studies.
Twenty-one studies (772 participants) were included in this review with two additional 2012 studies identified as 'awaiting classification'. Physical training was well tolerated with no adverse effects reported. None of the studies mentioned worsening of asthma symptoms following physical training. Physical training showed marked improvement in cardiopulmonary fitness as measured by a statistically and clinically significant increase in maximum oxygen uptake (mean difference (MD) 4.92 mL/kg/min; 95% confidence interval (CI) 3.98 to 5.87; P < 0.00001; 8 studies on 267 participants); however, no statistically significant effects were observed for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), minute ventilation at maximal exercise (VEmax) or peak expiratory flow rate (PEFR). Meta-analysis of four studies detected a statistically significant increase in maximum heart rate, and following a sensitivity analysis and removal of two studies significance was maintained (MD 3.67 bpm; 95% CI 0.90 to 3.44; P = 0.01). Although there were insufficient data to pool results due to diverse reporting tools, there was some evidence to suggest that physical training may have positive effects on health-related quality of life, with four of five studies producing a statistically and clinically significant benefit.
This review demonstrated that physical training showed significant improvement in maximum oxygen uptake, though no effects were observed in other measures of pulmonary function. Physical training was well tolerated among people with asthma in the included studies and, as such, people with stable asthma should be encouraged to participate in regular exercise training, without fear of symptom exacerbation. More research is needed to understand the mechanisms by which physical activity impacts asthma management.
Physical training for asthma Carson, Kristin V; Chandratilleke, Madhu G; Picot, Joanna ...
Cochrane database of systematic reviews,
09/2013, Letnik:
2013, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Background
People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning as a consequence of inactivity. Some may ...restrict activities as per medical advice or family influence and this might result in reduced physical fitness. Physical training programs aim to improve physical fitness, neuromuscular coordination and self confidence. Subjectively, many people with asthma report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. Also, as exercise can induce asthma, the safety of exercise programmes needs to be considered.
Objectives
To gain a better understanding of the effect of physical training on the respiratory and general health of people with asthma, from randomised trials.
Search methods
We searched the Cochrane Airways Group Specialised Register of trials up to January 2013.
Selection criteria
We included randomised trials of people over eight years of age with asthma who were randomised to undertake physical training or not. Physical training had to be undertaken for at least 20 minutes, two times a week, over a minimum period of four weeks.
Data collection and analysis
Two review authors independently assessed eligibility for inclusion and undertook risk of bias assessment for the included studies.
Main results
Twenty‐one studies (772 participants) were included in this review with two additional 2012 studies identified as 'awaiting classification'. Physical training was well tolerated with no adverse effects reported. None of the studies mentioned worsening of asthma symptoms following physical training. Physical training showed marked improvement in cardiopulmonary fitness as measured by a statistically and clinically significant increase in maximum oxygen uptake (mean difference (MD) 4.92 mL/kg/min; 95% confidence interval (CI) 3.98 to 5.87; P < 0.00001; 8 studies on 267 participants); however, no statistically significant effects were observed for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), minute ventilation at maximal exercise (VEmax) or peak expiratory flow rate (PEFR). Meta‐analysis of four studies detected a statistically significant increase in maximum heart rate, and following a sensitivity analysis and removal of two studies significance was maintained (MD 3.67 bpm; 95% CI 0.90 to 3.44; P = 0.01). Although there were insufficient data to pool results due to diverse reporting tools, there was some evidence to suggest that physical training may have positive effects on health‐related quality of life, with four of five studies producing a statistically and clinically significant benefit.
Authors' conclusions
This review demonstrated that physical training showed significant improvement in maximum oxygen uptake, though no effects were observed in other measures of pulmonary function. Physical training was well tolerated among people with asthma in the included studies and, as such, people with stable asthma should be encouraged to participate in regular exercise training, without fear of symptom exacerbation. More research is needed to understand the mechanisms by which physical activity impacts asthma management.
Nitric oxide (NO), produced via inducible NO synthase (iNOS), can modulate polarized epithelial processes such as solute transport. Given the high reactivity of NO, we hypothesized that optimal NO ...regulation of polarized epithelial functions is achieved through compartmentalization of iNOS, allowing local NO delivery to its molecular targets. Here, we show that iNOS localizes to the apical domain of epithelial cells within a submembranous protein complex tightly bound to cortical actin. We further show that iNOS can bind to the apical PDZ protein, EBP50 (ezrin-radixin-moesin-binding phosphoprotein 50), an interaction that is dependent on the last three COOH-terminal amino acids of iNOS, SAL, but requires the presence of additional unknown cellular proteins. Mutation of these three COOH-terminal residues abolishes the iNOS-EBP50 interaction and disrupts the apical association of iNOS in transfected cells, showing that this COOH-terminal motif is essential for the correct localization of iNOS in epithelial cells. Apically localized iNOS directs vectorial NO production at the apical proximal tubule epithelial cell surface. These studies define human epithelial iNOS as an apical EBP50-binding protein and suggest that the physical association of iNOS with EBP50 might allow precise NO modulation of EBP50-associated protein functions.
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