Switching from long‐acting beta‐agonist and inhaled corticosteroid to long‐acting beta‐agonist and long‐acting muscarinic antagonist for chronic obstructive pulmonary disease: a case report of inhaled corticosteroid withdrawal

Chronic obstructive pulmonary disease (COPD) is a medical condition characterised by persistent respiratory symptoms and airflow limitation. For the long‐term management of COPD, inhaled therapies are the main approach to maintenance treatment. In order to improve treatment efficacy and tolerability for patients with COPD, recent clinical trials have focused on the withdrawal of inhaled corticosteroids (ICSs), the use of which has been associated with adverse outcomes, including pneumonia. In this case report, a patient with Global Initiative for Chronic Obstructive Lung Disease grade 3 COPD was switched from a combined inhaled therapy of a long‐acting beta‐agonist (LABA) and ICS to a combination of a LABA and a long‐acting muscarinic antagonist (tiotropium/olodaterol) during hospitalisation for an acute exacerbation of COPD in April 2016. He was subsequently maintained in a stable condition, and was able to live and travel independently. This case report of successful ICS withdrawal suggests that, for moderate‐to‐severe COPD, if it is assessed individually, dual therapy of LABA and long‐acting muscarinic antagonist can be highly effective and well‐tolerated. Treatment compliance and lifestyle modifications have been shown to be critical in optimising treatment outcomes.     

Patterns of use of long‐acting bronchodilators in patients with COPD: A nationwide follow‐up study of new users in New Zealand

Background and objective

While several studies have found that prescribing practices do not conform to chronic obstructive pulmonary disease (COPD) treatment guidelines, none have examined longitudinal patterns of use of long‐acting beta₂‐agonist (LABA) and long‐acting muscarinic antagonist (LAMA) therapy across an entire country. We undertook a nationwide follow‐up study to describe treatment patterns in new users of long‐acting bronchodilators.

Methods

National health and pharmaceutical dispensing data were used to identify patients aged ≥45 years who initiated LABA and/or LAMA therapy for COPD between 1 February 2006 and 31 December 2013. Dispensings of LABAs, LAMAs and inhaled corticosteroids (ICSs) were aggregated into episodes of use of therapeutic regimens. Kaplan–Meier curves, sunburst plots and sequence index plots were generated to summarize, respectively, the duration of the first regimen, the sequences in which unique regimens were used and the patterns of use and non‐use during follow‐up.

Results

The study cohort included 83 435 patients with 290 400 person‐years of follow‐up. The most commonly initiated regimen was a LABA with an ICS. ICS use was inconsistent with international guidelines: over‐ and under‐treatment occurred in patients with infrequent and frequent exacerbations, respectively, and ICS monotherapy was common. The median duration of the first regimen was 46 days. Many patients used multiple regimens over time and periods of non‐use were common.

Conclusion

In this nationwide study, patterns of use of LABAs, LAMAs and ICSs were complex and often did not comply with treatment guidelines. Further work is required to address the discrepancy between guidelines and prescribing practices.

     

Comparison of outpatient and home‐based exercise training programmes for COPD: A systematic review and meta‐analysis

Chronic obstructive pulmonary disease is a common, preventable and treatable disease. Exercise training programmes (ETPs) improve symptoms, health‐related quality of life (HRQoL) and exercise capacity, but the optimal setting is unknown. In this review, we compared the effects of ETPs in different settings on HRQoL and exercise capacity. We searched (5 July 2016) the Cochrane Airways Group Specialised Register, ClinicalTrials.gov and World Health Organization trials portal. We selected studies, extracted data and assessed risk of bias with two independent reviewers. We calculated mean differences (MD) with 95% CI. We assessed the quality of evidence using Grades of Recommendation, Assessment, Development and Evaluation. Ten trials (934 participants) were included. Hospital (outpatient) and home‐based ETPs (seven trials) were equally effective at improving HRQoL on the Chronic Respiratory Questionnaire (CRQ) (dyspnoea: MD −0.09, 95% CI: −0.28 to 0.10; fatigue: MD −0.00, 95% CI: −0.18 to 0.17; emotional: MD 0.10, 95% CI: −0.24 to 0.45; and mastery: MD −0.02, 95% CI: −0.28 to 0.25; moderate quality) and on the St George’s Respiratory Questionnaire (SGRQ) (MD −0.82, 95% CI: −7.47 to 5.83, low quality). Hospital (outpatient) and community‐based ETPs (three trials) were equally effective at improving HRQoL (CRQ dyspnoea: MD 0.29, 95% CI: −0.05 to 0.62, moderate quality; fatigue: MD −0.02, 95% CI: −1.09 to 1.05, low quality; emotional: MD 0.10, 95% CI: −0.40 to 0.59, moderate quality; and mastery: MD −0.08, 95% CI: −0.45 to 0.28, moderate quality). There was no difference in exercise capacity. There was low to moderate evidence that outpatient and home‐based ETPs are equally effective. See related Editorial     

Creatine supplementation for patients with COPD receiving pulmonary rehabilitation: A systematic review and meta‐analysis

Background and objective: Creatine improves muscle strength in exercising healthy individuals, and in patients with neuromuscular disease and heart failure. The aim of this study was to assess whether creatine supplementation improves pulmonary rehabilitation (PR) outcomes in patients with COPD. Methods: A systematic review and meta‐analysis was performed of randomized controlled trials published between January 1966 and February 2009 that evaluated the effect of creatine compared with placebo on exercise capacity, muscle strength and health‐related quality of life (HR‐QoL) in patients undergoing PR for COPD. The pooled estimates were expressed as mean differences (MD) or standardized mean differences (SMD). Results: Four randomized controlled trials that included 151 patients were identified. There was no effect of creatine supplementation on exercise capacity (SMD ?0.01, 95% CI: ?0.42 to 0.22, n = 151). Creatine supplementation did not improve lower extremity muscle strength (SMD 0.03, 95% CI: ?0.55 to 0.61, n = 140) or upper limb muscular strength (SMD 0.02, 95% CI: ?0.33 to 0.38, n = 128) compared with placebo. Two studies (n = 48) assessed quality of life using the St. George's Respiratory Disease Questionnaire. There were no differences in HR‐QoL according to domain or total scores. Overall, creatine appeared to be safe and was well tolerated. Quality assessment of the studies showed important limitations. Conclusions: Creatine supplementation does not improve exercise capacity, muscle strength or HR‐QoL in patients with COPD receiving PR. However, important limitations were identified in the quality of the available evidence, suggesting that further research is required in this area.     

Impact of COPD and emphysema on survival of patients with lung cancer: A meta‐analysis of observational studies

Both COPD and emphysema are associated with an increased incidence of lung cancer, but the impacts of these comorbidities on lung cancer prognosis are still unclear. Herein, we conducted a meta‐analysis to clarify whether the presence of these comorbidities indicates poor survival in patients with lung cancer. A comprehensive search was conducted using PubMed, Embase, Web of Science, ASCO Abstracts and Cochrane library for articles published before 1 June 2015. Papers referenced by the obtained articles were also reviewed. Main outcomes were overall survival (OS) and disease‐free survival (DFS) in patients with lung cancer. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using random‐effects models. Subgroup and sensitivity analyses were also conducted. Of 58 full texts reviewed, 26 met our inclusion criteria that were derived from 21 and seven studies examining the impacts of COPD and emphysema on survival of lung cancer, respectively. Meta‐analyses revealed that concomitant COPD was associated with poorer OS (HR, 1.17; 95% CI: 1.10–1.25, n = 20), which was independent of tumour staging, diagnostic criteria of COPD or location, and DFS (HR, 1.52; 95% CI: 1.04–2.23, n = 6) with high heterogeneity (I² = 78%). The presence of emphysema in patients with lung cancer predicted worse OS (HR, 1.66; 95% CI: 1.25–2.22, n = 7), but not poorer DFS. The presence of COPD and emphysema are robust predictors of poor survival in patients with lung cancer. Early detection of these diseases should be taken into account for lung cancer surveillance and management.     

Nutritional support and functional capacity in chronic obstructive pulmonary disease: A systematic review and meta‐analysis

Currently, there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta‐analysis of randomized, controlled trials (RCT) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCT (n = 448) in stable COPD patients investigating the effects of nutritional support (dietary advice (1 RCT), oral nutritional supplements (10 RCT), enteral tube feeding (1 RCT)) versus control on functional outcomes. Meta‐analysis of the changes induced by intervention found that while respiratory function (forced expiratory volume in 1 s, lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (maximal inspiratory mouth pressure +3.86 standard error (SE) 1.89 cm H₂O, P = 0.041; maximal expiratory mouth pressure +11.85 SE 5.54 cm H₂O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved and associated with weight gains of ≥2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta‐analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta‐analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.     

Long‐acting muscarinic antagonist + long‐acting beta agonist versus long‐acting beta agonist + inhaled corticosteroid for COPD: A systematic review and meta‐analysis

Some trials have been conducted to compare long‐acting muscarinic antagonist (LAMA) + long‐acting beta agonist (LABA) versus LABA + inhaled corticosteroids (ICS) for chronic obstructive pulmonary disease (COPD), but no meta‐analysis were reported. Two investigators independently searched for eligible articles using the PubMed, Web of Science and Cochrane databases. Articles in authors' reference files were also regarded as candidates. The eligibility criteria for the current meta‐analysis were original trials written in English comparing the impact of LAMA + LABA and LABA + ICS for COPD patients. A pooled value for the continuous value was calculated using the genetic inverse variance method for mean difference. Incidence of events was evaluated using the odds ratio (OR). Minimal clinically important difference were 50 mL for forced expiratory volume in 1 s (FEV₁), four points for St George Respiratory Questionnaire (SGRQ) and one point for transition dyspnoea index (TDI). We included seven randomized controlled trials and one cross‐over trial with follow‐up period of 6–26 weeks. Compared with LABA + ICS, LAMA + LABA led to significantly greater improvements of trough FEV₁ by 71 (95% CI: 48–95) mL, TDI by 0.38 points (95% CI: 0.17–0.58), less exacerbations with an OR of 0.77 (95% CI: 0.62–0.96) and less pneumonia with an OR of 0.28 (95% CI: 0.12–0.68). Frequencies of any adverse event, serious adverse event, adverse event leading to discontinuation, all‐cause death and change of total score of SGRQ were not different in both arms. LAMA + LABA might be a better option for treating COPD than LABA + ICS.     

A rational approach to single,dual and triple therapy in COPD

The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well‐being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence.     

Long‐term macrolides for non‐cystic fibrosis bronchiectasis: A systematic review and meta‐analysis

Long‐term macrolides are increasingly being prescribed for stable bronchiectasis. This meta‐analysis assessed the clinical effect of this treatment in bronchiectasis. A systematic review and meta‐analysis were carried out. All randomized, controlled trials (RCT) comparing long‐term macrolides with placebo and/or usual medical care, with outcome measures relating to efficacy and safety were selected. Nine RCT recruiting 530 patients were included. Compared with placebo and/or usual medical care, long‐term macrolides significantly reduced the risk of the exacerbations (number of participants with exacerbations (relative risk = 0.70, 95% confidence interval (CI) 0.60–0.82, P < 0.00001); average exacerbations per participant (weighted mean difference = ?1.01, 95% CI ?1.35 to ?0.67, P < 0.00001)), the St George's Respiratory Questionnaire total scores (weighted mean difference = ?5.39 95% CI ?9.89 to ?0.88, P = 0.02), dyspnoea scale (weighted mean difference = ?0.31 95% CI ?0.42 to ?0.20, P < 0.00001), 24‐h sputum volume (P < 0.00001), and attenuated the decline of forced expiratory volume in 1 s (weighted mean difference 0.02 L, 95% CI 0.00–0.04, P = 0.01). Eradication of pathogens (P = 0.06), overall rate of adverse events (P = 0.61), and emergence of new pathogens (P = 0.61) were not elevated, while gastrointestinal events increased significantly with macrolides (P = 0.0001). Macrolide resistance increased, but a meta‐analysis was not possible due to the diversity of parameters. Long‐term use of macrolides appears to be a treatment option for stable bronchiectasis. The results of this review justify further investigation about adding this intervention to the treatment regimens of bronchiectasis.     

Bariatric surgery: a systematic review and network meta‐analysis of randomized trials

The clinical efficacy and safety of bariatric surgery trials were systematically reviewed. MEDLINE, EMBASE, CENTRAL were searched to February 2009. A basic PubCrawler alert was run until March 2010. Trial registries, HTA websites and systematic reviews were searched. Manufacturers were contacted. Randomized trials comparing bariatric surgeries and/or standard care were selected. Evidence‐based items potentially indicating risk of bias were assessed. Network meta‐analysis was performed using Bayesian techniques. Of 1838 citations, 31 RCTs involving 2619 patients (mean age 30–48 y; mean BMI levels 42–58 kg/m²) met eligibility criteria. As compared with standard care, differences in BMI levels from baseline at year 1 (15 trials; 1103 participants) were as follows: jejunoileal bypass [MD: ?11.4 kg/m²], mini‐gastric bypass [?11.3 kg/m²], biliopancreatic diversion [?11.2 kg/m²], sleeve gastrectomy [?10.1 kg/m²], Roux‐en‐Y gastric bypass [?9.0 kg/m²], horizontal gastroplasty [?5.0 kg/m²], vertical banded gastroplasty [?6.4 kg/m²], and adjustable gastric banding [?2.4 kg/m²]. Bariatric surgery appears efficacious compared to standard care in reducing BMI. Weight losses are greatest with diversionary procedures, intermediate with diversionary/restrictive procedures, and lowest with those that are purely restrictive. Compared with Roux‐en‐Y gastric bypass, adjustable gastric banding has lower weight loss efficacy, but also leads to fewer serious adverse effects.