Luke Garske

Systematic review and meta-analysis of randomised controlled trials of gastro-oesophageal reflux interventions for chronic cough associated with gastro-oesophageal reflux

Abstract Objective To evaluate the efficacy of treatment for gastro-oesophageal reflux disease (GORD) on chronic cough in children and adults without an underlying respiratory disease. Design Systematic review and meta-analysis. Data sources Cochrane, Medline, and Embase databases, references from review articles. Included studies Randomised controlled trials on GORD treatment for cough in children and adults without primary lung disease. Two reviewers independently selected studies and extracted paediatric and adult data on primary (clinical failure) and secondary outcomes. Results 11 studies were included. Meta-analysis was limited to five studies in adults that compared proton pump inhibitors with placebo. All outcomes favoured proton pump inhibitors: the odds ratio for clinical failure (primary outcome) was 0.24 (95% confidence interval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to ∞ to benefit 2.5). For secondary outcomes, the standardised mean difference between proton pump inhibitors and placebo was −0.51 (−1.02 to 0.01) for mean cough score at the end of the trial and −0.29 (−0.62 to 0.04) for change in cough score at the end of the trial. Subgroup analysis with generic inverse variance analysis showed a significant mean change in cough (−0.41 SD units, −0.75 to −0.07). Conclusion Use of a proton pump inhibitor to treat cough associated with GORD has some effect in some adults. The effect, however, is less universal than suggested in consensus guidelines on chronic cough and its magnitude of effect is uncertain.

Clinical Outcomes of Indwelling Pleural Catheter-Related Pleural Infections: An International Multicenter Study

BACKGROUND Indwelling pleural catheters (IPCs) offer effective control of malignant pleural effusions (MPEs). IPC-related infection is uncommon but remains a major concern. Individual IPC centers see few infections, and previous reports lack sufficient numbers and detail. This study combined the experience of 11 centers from North America, Europe, and Australia to describe the incidence, microbiology, management, and clinical outcomes of IPC-related pleural infection. METHODS This was a multicenter retrospective review of 1,021 patients with IPCs. All had confirmed MPE. RESULTS Only 50 patients (4.9%) developed an IPC-related pleural infection; most (94%) were successfully controlled with antibiotics (62% IV). One death (2%) directly resulted from the infection, whereas two patients (4%) had ongoing infectious symptoms when they died of cancer progression. Staphylococcus aureus was the causative organism in 48% of cases. Infections from gram-negative organisms were associated with an increased need for continuous antibiotics or death (60% vs 15% in gram-positive and 25% mixed infections, P = .02). The infections in the majority (54%) of cases were managed successfully without removing the IPC. Postinfection pleurodesis developed in 31 patients (62%), especially those infected with staphylococci (79% vs 45% with nonstaphylococcal infections, P = .04). CONCLUSIONS The incidence of IPC-related pleural infection was low. The overall mortality risk from pleural infection in patients treated with IPC was only 0.29%. Antibiotics should cover S aureus and gram-negative organisms until microbiology is confirmed. Postinfection pleurodesis is common and often allows removal of IPC. Heterogeneity in management is common, and future studies to define the optimal treatment strategies are needed.

Sub-inhibitory concentrations of ceftazidime and tobramycin reduce the quorum sensing signals of Pseudomonas aeruginosa

Aim: Concentrations of antimicrobials below minimum inhibitory concentration (subMIC) may reduce the production by Pseudomonas aeruginosa of virulence factors such as elastase. We sought to determine whether the reduction in elastase production may be mediated by a reduction in acyl‐homoserine lactones. Methods: Pseudomonas aeruginosa in broth was exposed to three conditions for ceftazidime and tobramycin: control, 6% MIC and 25% MIC. Elastase was assayed using elastin congo red. N‐(3‐Oxododecanoyl)‐homoserine lactone (C12‐HSL) and N‐butyryl‐homoserine lactone (C4‐HSL) were assayed using biosensor Escherichia coli. Results: Elastase was unchanged with ceftazidime. Elastase was reduced by 16% at 6% MIC tobramycin and reduced by 70% at 25% MIC tobramycin (P<0.0001). As a percentage of control, C12‐HSL was mean 69.4% (SEM 7.3%) at 6% MIC tobramycin, and 31.7% (3.3%) at 25% MIC tobramycin (P=0.0001). C12‐HSL was 78.9% (5.3%) at 6% MIC ceftazidime and was 29.7% (1.8%) at 25% MIC ceftazidime (P=0.0001). Both ceftazidime and tobramycin were associated with reduced C4‐HSL at 6% MIC and 25% MIC (P<0.03). Conclusions: SubMIC tobramycin but not ceftazidime reduced elastase production by P. aeruginosa. In contrast, subMIC concentrations of both antimicrobials reduced C12‐HSL and C4‐HSL. It is unlikely that reduced HSL is the sole explanation for the reduction in elastase.

Successful treatment of shrinking lung syndrome with rituximab in a patient with systemic lupus erythematosus.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE). We report the case of a 27-year-old woman with SLE presenting with a 2-year history of chest pain and progressive dyspnea. Respiratory function tests demonstrated severe restrictive ventilatory impairment. Chest x-ray demonstrated elevated hemi diaphragms and chest computed tomography showed no evidence of interstitial fibrosis, significant pleural disease or pulmonary emboli. Based on a diagnosis of SLS the patient received 4 months of high dose corticosteroids, mycophenolate and pain management with opiates. Her condition deteriorated and she was given a trial of rituximab. This resulted in marked improvement of the clinical condition and respiratory function tests that was maintained for 18 months. Subsequently, the patient represented with a similar clinical picture and another course of rituximab again produced remission. This is the first case report of reproducible remission of SLS in SLE treated with rituximab.

Cardiorespiratory Fitness Is Related to Physical Inactivity, Metabolic Risk Factors, and Atherosclerotic Burden in Glucose-Intolerant Renal Transplant Recipients

The mechanisms of reduced cardiorespiratory fitness (CF) in renal transplant recipients (RTR) have not been studied closely. This study evaluated the relationships between CF and specific cardiovascular risk factors (metabolic syndrome [MS], physical inactivity, myocardial ischemia, and atherosclerotic burden) in glucose-intolerant RTR. Data were recorded on 71 glucose-intolerant RTR (mean age 55 yr; 55% male; median transplant duration 5.7 yr). MS was defined using National Cholesterol Education Programme Adult Treatment Panel III criteria. Resting and exercise stress echocardiography were performed, and myocardial ischemia was identified by new or worsening wall motion abnormalities. Cardiorespiratory fitness was determined using peak oxygen uptake (VO(2)) by expired gas analysis. Atherosclerotic burden was assessed by carotid intima-media thickness (IMT). Mean peak VO(2) was 19 +/- 7 ml/kg per min and was significantly lower than predicted peak VO(2) (29 +/- 6 ml/kg per min; P < 0.001). Patients with MS (63%) had reduced CF (17 +/- 6 versus 22 +/- 8 ml/kg per min; P = 0.001) and were more likely to be physically inactive (76 versus 48%; P = 0.02). CF was reduced in 14 patients with myocardial ischemia (15 +/- 3 versus 20 +/- 7 ml/kg per min; P = 0.05). CF was positively correlated with male gender, height, and physical activity and inversely correlated with number of MS risk factors and IMT (adjusted R(2) = 0.66). Carotid IMT added incremental value to clinical variables in determining VO(2) (adjusted R(2) = 0.65 versus 0.63; P = 0.04). Reduced CF is associated with physical inactivity, MS, and atherosclerotic burden in glucose-intolerant RTR. Further studies should address whether increasing exercise and modifying MS risk factors improve CF in RTR.

Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis

Introduction Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients’ remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. Methods and analysis The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. Ethics and dissemination The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration numbers Australia New Zealand Clinical Trials Registry—ACTRN12611000567921; National Institutes of Health—NCT02045121.

Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial

Importance Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis. Objective To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion. Design, Setting, and Participants This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included. Interventions Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia). Main Outcomes and Measures The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events. Results Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P < .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events). Conclusions and Relevance Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion. Trial Registration anzctr.org.au Identifier: ACTRN12611000567921

Advanced interventional pulmonology procedures: training guidelines from the Thoracic Society of Australia and New Zealand

Training in interventional pulmonology procedures is increasing in popularity. However, the nature of training is difficult to define, particularly with respect to an adequate number of cases. These guidelines approach training not just from a modest number of supervised cases, but also from a range of educational and outcome targets which give a rounded approach to the issue. These include prerequisite skills from basic procedures, the place of simulated training, formal simulation testing, modest procedural outcome and side effect targets, audit presentations, ongoing reading, and hands‐on training expectations. All of this would still be under the supervision of an experienced trainer.

Pseudomonas aeruginosa exposed to sub-inhibitory ceftazidime or tobramycin has reduced homoserine lactones

Background Patients with end stage respiratory disease (ENSD) have an uncertain prognosis, deteriorate rapidly, over a period of days or hours, and commonly die in acute care settings. Introduction The St George end of life pathway was developed in response to evidence that current models of end-of-life care were failing to meet the needs of dying patients. This tool was designed to enable clinicians working in the acute care setting to integrate pivotal palliative care principles in the care of patients. Aim The aim of this observational study was to evaluate the benefits to patients and carers of the endof -life pathway implemented in an acutecare respiratory setting. Method A cohort of dying respiratory patients (n =13), who were placed on the end of life pathway in the period from November 2001 to November 2002, was examined to assess the acceptability and utility of the pathway. This was performed by chart review and staff reflection through a focus group. Results Completed care plans revealed the complexity of symptoms experienced by patients during this vulnerable period of their illness trajectory. Key areas for intervention included management of symptoms such as: pain, respiratory secretions, nausea and vomiting, dyspnoea, personal comfort, psychosocial and spiritual needs. 100% of patients had critical orders and no patients in this cohort received traumatic and unnecessary interventions such as intubation or arterial punctures. Staff described feeling more confident and having more guidance when caring for dying respiratory patients. Conclusion The end of life pathway has proved an important tool for good symptom management and delivery of holistic care. The tool has provided structure and information resources to assist clinicians to care of dying respiratory patients within the acute care setting. This review has confirmed the acceptability and the utility of the end-of-life pathway and underscored the importance of a multidisciplinary approach and a collaborative palliative care model. 01 Respirology (2003) 8, (Suppl.) A1–A65