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Models that predict outcomes, aid prognostication and inform the assessment of urgency for lung transplantation (LT) in CF are in demand. A prognostic score derived from the French adult CF registry to predict death or LT over 3-year follow-up was described in 2017 and validated using Canadian CF registry data. We assessed its performance in the UK CF population. The French prognostic score was applied to untransplanted adults with CF. The index year (2014) and outcomes (Death or LT) were evaluated to 2017. Receiver operator characteristics plots and area under curve (AUC) was computed. 4407 adults with CF met the inclusion criteria. After 3 years, 7.1% (P < 0.001) were dead or had received LT compared to the French (12.8%) and Canadian (9.4%) cohorts. The French score deemed 592 (26.2%) 'High-risk' - death/LT occurred in 189/592 (30.2%), less than previously reported in France and Canada (P < 0.0001). The discriminatory power of the French score was lower (AUC 0.830) than reported. Recalibration yielded only marginal improvement in model performance (AUC 0.833). The French prognostic score does not perform as well in the UK as reported elsewhere. Bespoke UK scores are needed to aid prognostication and inform LT decision-making.

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:11 pages:1171-1190 ispartof: location:United States status: published

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.

BackgroundFosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-β-d-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and β2-microglobulin].MethodsUsing a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin).ResultsUrinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution (FEV1% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens.ConclusionThe addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations.

Introduction: BOS limits survival and quality of life gains post lung transplant (LTx). BOS is defined as a persistent fall in FEV1 to ≤80% of best, after excluding reversible pathologies. However many LTx recipients have evidence of small airway disease with high LCI despite preserved FEV1. Earlier BOS detection may allow intervention before irreversible graft dysfunction; we therefore explored longitudinal outcomes post LTx to see if high LCI predicted progression to BOS. Methods: Prospective evaluation of serial FEV1 in patients previously identified with normal FEV1 but high LCI vs normal FEV1/normal LCI until International Society of Heart and Lung Transplantation (ISHLT) BOS criteria were met. Time to diagnosis of BOS and BOS stage at diagnosis were noted. Results: 24/31 patients with normal FEV1, at a median 4.7 years post op, had high LCI (mean 8.3, SD 0.8). 8 (33%) subsequently developed BOS (median FEV1 72% of baseline, range 31-80, Stage I: 5, II: 2, III: 1) after a median interval of 14 (5-27) months. There was continued decline in FEV1 in 5, of whom 3 have died. A median of 4.6 years post op, 7 patients had normal LCI (mean 6.7, SD 0.2) with normal FEV1. Only 1 met ISHLT BOS criteria, 2 months after the initial LCI reading and remains in Stage I at 22 months. All are alive at a median of 27 months post LCI. Conclusion: These exploratory data suggest that ventilation inhomogeneity due to early small airway disease in LTx recipients, detected as high LCI despite normal FEV1, may independently predict future lung function decline. This hypothesis will be tested more robustly in a 4-year prospective study using an adequately powered sample in our unit.

Background Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade. Methods 51 stable adult double-lung transplant recipients performed sulfur hexafluoride MBW in triplicate on a single occasion, using a closed-circuit Innocor device. BOS grades were derived from serial spirometry according to International Society for Heart and Lung Transplantation criteria and, where available, high-resolution computed tomography (HRCT) evidence of OB was recorded. Results LCI was successfully performed in 98% of patients. The within-visit coefficient of variation for repeat LCI measurements was 3.1%. Mean LCI increased significantly with BOS grades: no BOS (n=15), LCI 7.6; BOS-0p (n=16), LCI 8.3; BOS-1 (n=11), LCI 9.3; BOS-2–3 (n=9), LCI 13.2 (p7) despite a normal forced expiratory volume in 1 s (FEV1) (>80% of baseline). Conclusions LCI measurement in lung transplant recipients is feasible and reproducible. LCI increased with increasing BOS grade. A significant proportion of this cohort had abnormal LCI with preserved FEV1, suggesting early subclinical small airway dysfunction, and supporting a role for MBW in the early identification of BOS., BOS limits post-lung transplant outcomes. LCI and phase III slope indices, derived from MBW measured by a novel closed-circuit technique, increase with BOS severity and may allow detection of mild disease before conventional spirometric methods. http://bit.ly/2L113yC

BackgroundThe demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre.MethodsData were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height.ResultsOf the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (pConclusionsThe way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.

Importance Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, –1.8% [95% CI, –10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration ISRCTN Identifier: ISRCTN47845793

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single-center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a "rescue therapy" in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV-related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.

Introduction UK guidelines for LTx and HTx candidate referral require a minimum of 6 months abstinence from smoking and ALL forms of nicotine replacement before patients can be formally assessed. Our unit adopted this principle and we aimed to investigate smoking habits in a consecutive cohort of such referrals. Methods Prospectively collected urine cotinine levels were used as a patient engagement tool. LTx referrals from August 2010 to April 2018 and HTx referrals from September 2015 to April 2018 who clearly stated they had met the smoking/nicotine abstinence criterion were asked to submit an on-the-spot urine sample at outpatient consultations and inpatient assessments. Cotinine>50 ng/ml indicated active smoking/nicotine use (liquid chromatography mass spectrometry, lower detection limit 5 ng/ml). Results 499 LTx and 149 HTx candidates submitted ≥1 sample during this period; total 977 and 220 samples, mean (range): 2 (1–14) and 1 (1–8)/patient; median self-reported nicotine abstinence 1.9 years (IQR 0.8–4.9) and 1.1 (0.2–2.5) respectively. 25.8% (LTx) and 27.5% (HTx) had elevated first sample cotinine [LTx: mean (range) 171 (6–2100) ng/ml, 102/129>50 ng/ml; HTx 111 (6–1100), 30/41>50 ng/ml]. Smokers were predominantly male (LTx-57.4%; HTx-71%, p Conclusion We found a high prevalence of nicotine ‘mis’-use in patients with advanced pulmonary and cardiac disease selected by referring physicians for consideration of organ transplant having declared long abstinence. Smoking habits changed in both directions with a clear risk of relapse on the waiting list; implications for relapse post-operatively require further study. Urinary cotinine targets can be used to incentivise patients’ behavioural change and set clear expectations within the contract governing relationship with the transplant team.

Introduction Total Lung capacity (TLC) is often measured in patients with advanced lung disease to help inform diagnosis, severity and management. However, some may not manage or tolerate the technical aspects of the gold standard test: whole body plethysmography (Pleth-TLC). N2 washout (N2W-TLC) is often used in lieu but it is unreliable in obstructive conditions and some still find it challenging. As all potential lung transplant candidates undergo thoracic CT during their workup, we hypothesised that CT estimates of total lung volume (CT-TLV) could substitute Pleth-TLC and are superior to N2W-TLC. Methods Prospectively collected data between April 2015–2018. 1–2 mm CT slices were analysed using Vitrea software (version 6.1.1169.10077, Vital Solutions, Toshiba Medical Systems Europe) by a single radiologist. Descriptive statistics were compared with parametric tests. Agreement and bias between methods were examined with Pearson’s correlation and Bland and Altman analysis. Results 202 patients were studied (94 female, mean [SD] age 52 [11] yrs, BMI 25.0 [4.2] kg/m2, COPD/IPF/CF/other n=72/45/21/64). 37 (18.3%) and 50 (24.8%) were unable to perform Pleth and N2W respectively. Paired data were available for comparison of CT vs Pleth (n=160), CT vs N2W (147) and Pleth vs N2W (131), with subgroup analysis into obstructive, restrictive and normal ventilation. Mean [SD] CT-TLV, Pleth-TLC and N2W-TLC were 4.69 [1.95], 5.20 [2.06] and 4.32 [1.71] L respectively, p Conclusion CT estimates of TLC reliably approximate Pleth-TLC and could replace body box measurement in practice, for patient convenience and cost containment. Gastro-oesophageal air, captured by Pleth but not CT, accounts for some of the underestimation. The consistent small bias with a reliable homoscedastic difference between these methods may allow incorporation of a correction factor and wider application of this CT algorithm.

Introduction: Long term outcomes after lung transplant (LTx) are limited by the development of BOS. BOS is defined by the International Society of Heart and Lung Transplantation (ISHLT) as an irretrievable drop in FEV1 below 80% of the best FEV1 post-LTx. HRCT is used to confirm spirometric findings. LCI is a sensitive measure of small airways changes that may identify those with early disease. Aim: To measure LCI in LTx patients and compare with ISHLT and CT grades for BOS. Methods: LCI was measured at routine clinic review in stable double LTx recipients using a closed circuit Innocor device and SF6 washout on room air. BOS grades were derived from serial spirometry and (where available) HRCT according to ISHLT criteria. Results: 30 patients were assessed (15 M), mean (SD) age: 51 (13.8) yrs; time since LTx: 3.5 (2.8) yrs [range 0.3-11.3]. LTx indications were CF (n=7), COPD (13), pulmonary hypertension (6), ILD (4). 22(73%) met ISHLT BOS definitions (≥BOS-0p). LCI in those with BOS grades 2-3 (n=4, mean LCI=15.1) was significantly higher than those with no BOS (n=8, LCI=7.3), BOS-0p (n=12, LCI=8.4) and BOS-1(n=6, LCI=9.3), p 7) but preserved FEV1(>80%). Conclusion: LCI can be successfully measured in LTx patients, and changes with BOS grade. Longitudinal assessments will reveal whether abnormal LCI in those with preserved FEV1 predicts future clinical change.

RATIONALE: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage.OBJECTIVES: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion.METHODS: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo.MEASUREMENTS AND MAIN RESULTS: Co-primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], -12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, -19%; 95% CI, -28 to -11%; P CONCLUSIONS: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26).

A 59-year-old man with bilateral apical emphysema underwent a double lung transplant for end-stagechronic obstructive pulmonary disease leaving remnant right apical native tissue due to pleural adhesions. Initial postoperative course was uneventful until the chest drains were removed. This revealed a small pneumomediastinum, which progressively increased in size causing gross surgical emphysema. Re-insertion of the chest drain stabilised the patient so that the cause could be identified and corrected. Two bronchoscopies excluded anastomotic dehiscence as a cause. Therefore the subcostal wound was refashioned under video-assisted thoracoscopic surgery in case there was a defect. Unfortunately this also failed to halt the air leak; therefore another cause was sought. A multidisciplinary team meeting review of the radiology revealed that the patient9s native bullous tissue was still inflated. Subsequent bronchoscopy revealed a native bronchial communication, due to variant anatomy, proximal to the surgical anastomosis. This was subsequently occluded using a bronchial valve allowing the patient to make a swift recovery.

An elderly patient, with a history of depression with psychosis, presented with breathlessness, a right exudative pleural effusion and a peripheral eosinophilia. The pleural fluid was eosinophil-rich (10% of leucocytes). Olanzapine therapy had been commenced 12 months previously. There was a family history of TB and the patient was of African origin. A full diagnostic work-up ensued including computed tomography of the thorax and local anaesthetic thoracoscopy. The pleura was unremarkable on CT and displayed bland smooth thickening at visual inspection during thoracoscopy. Pleural biopsies demonstrated chronic inflammation with eosinophils but no evidence of granulomatous inflammation or malignancy. Pleural tissue culture did not yield mycobacteria. A diagnosis of olanzapine-induced eosinophilic pleuritis was suspected and the pleural disease resolved with withdrawal of olanzapine.Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.

Aspergillus spp. are the leading cause of invasive fungal infection in lung transplant recipients. We investigated the relationship between the isolation of Aspergillus spp. from the respiratory tract of lung transplant recipients and their risk of mortality.A retrospective, observational cohort study of all patients who received lung allografts between January 1999 and May 2011 at a single UK centre was performed. The time from transplantation to death was analysed using Cox regression models. Isolation of Aspergillus spp. from the respiratory tract was included as a covariate in the Cox regression model.Two hundred-thirteen patients were included. The median follow-up time was 5 years during which 102 patients (47.9%) died. Aspergillus was isolated from 74 (34.7%) patients. Twenty patients (27%) had Aspergillus isolated in the first 60 days post-transplant. Forty-one patients (55.4%) in the Aspergillus group and 61 patients (43.9%) in the non-Aspergillus group died during follow-up. A hazard ratio of 2.2 (95% CI 1.5-3.3; P 0.001) for death following a positive Aspergillus sample was observed.Isolation of Aspergillus spp. from patients following lung transplantation is associated with a significant increase in mortality. Novel preventative strategies are required to minimise the impact of Aspergillus in lung transplant recipients.

Segmental mediolytic arteriopathy (SMA) is an extremely rare condition of uncertain etiology causing degeneration of arterial media, intramural dissection or the rupture of aneurysms. It is recognized as a rare cause of fatal intra-abdominal bleeding. We report the first case of recurrent intra-abdominal bleeding secondary to SMA in a lung transplant patient, with a further complication of lymphoproliferative disease in the transplanted lung. We discuss the pathogenesis, clinical presentation, imaging characteristics and the complexities of management in this case.

Although there are reports of cases of acute renal failure occurring in cystic fibrosis (CF) patients, usually in association with the use of nephrotoxic antibiotic therapy, there have been no studies of renal function in this patient group. We hypothesized that long-term use of intravenous (IV) nephrotoxic antibiotics (aminoglycosides and colistin sulphomethate) may contribute to renal disease in CF patients. In a prospective study, we assessed creatinine clearance as an index of renal function with two techniques (24-hr urine collections and the Cockroft-Gault formula) in a group of 80 stable adult CF outpatients chronically infected with Pseudomonas aeruginosa but with no history of preceding renal disease. Using a multiple linear regression model, we evaluated their renal function in terms of their lifetime IV use of aminoglycosides and colistin. Between 31% (Cockroft-Gault formula method) and 42% (24-hr urine collection method) of patients had a creatinine clearance below normal range. Using either method, there was a strong correlation between aminoglycoside use and diminishing renal function (r=- 0.32, P=0.0055), which was potentiated by the coadministration of colistin (r=- 0.42, P

Extra-corporeal membrane oxygenation (ECMO) is accepted as a salvage therapy to treat life-threatening complications following lung transplantation such as primary graft dysfunction, acute rejection or airway dehiscence. Levitronix Centrimag® (Levitronix LLC, Waltham, MA) is a centrifugal pump that consists of a magnetically levitated bearing-less rotor designed to reduce blood friction. ECMO using the Levitronix Centrimag® pump may be an ideal medium-term support for lung transplant recipients suffering these serious complications. We describe our early experience of using ECMO with Levitronix Centrimag® device and the Hilite hollow fibre membrane oxygenator (Medos Hilite® LT, Medos Medizintechnik AG) in three cases following lung transplantation. The device is technically easy to implant and manage with a low complication rate on minimal anticoagulation.

This article reviews the evidence that pretreatment with nicotine causes a regionally selective sensitization of its stimulatory effects on a pathway, the mesoaccumbens dopamine (DA) system, which has been implicated in the locomotor stimulant response to nicotine and its ability to reinforce self-administration. The sensitization evoked by daily injections of nicotine is associated with a regionally selective downregulation of the control of mesoaccumbens DA neurons by inhibitory autoreceptors and depends upon co-stimulation of NMDA glutamatergic receptors. It is suggested that the sensitization is related to enhanced burst firing of mesoaccumbens neurons, which results in an enhancement of DA release into the extracellular space between the cells where it acts upon putative extrasynaptic dopamine receptors. The studies with NMDA receptor antagonists revealed a dissociation between the expression of sensitized mesoaccumbens DA and locomotor responses to nicotine. It is proposed, therefore, that the sensitized mesoaccumbens DA responses to nicotine may be implicated in psychopharmacological responses to drug concerned more closely with nicotine dependence.

Chronic pulmonary infection with transmissible Pseudomonas aeruginosa strains in individuals with cystic fibrosis (CF) has been reported, raising issues of cross infection and patient segregation. The first such strain to be described (the Liverpool epidemic strain, LES) is now widespread in many UK CF centres. However, whether such infection carries a worse prognosis is unknown. To address this, the clinical course of a group of CF patients chronically infected by LES was compared with that in patients harbouring unique strains.Using P aeruginosa strain genotyping, two cohorts of CF patients attending the Liverpool CF service were identified who were LES positive or negative in 1998 and remained so until 2002. From these, two groups of 12 patients were matched in 1998 for age, spirometric parameters, and nutritional state and their clinical course was followed for 5 years. Patients chronically infected with Burkholderia cepacia were excluded.Patients chronically infected with LES had a greater annual loss of lung function than those not chronically infected by LES (mean difference between groups -4.4% (95% CI -8.1 to -0.9; p0.02)), and by 2002 their percentage predicted forced expiratory volume in 1 second (FEV1) was worse (mean 65.0% v 82.6%, p0.03). Their nutritional state also deteriorated over the study period (mean difference between groups in body mass index -0.7 (95% CI -1.2 to -0.2; p0.01)), such that by 2002 they were malnourished compared with LES negative patients (mean BMI 19.4 v 22.7, p0.02).Chronic infection with the Liverpool epidemic P aeruginosa strain in CF patients confers a worse prognosis than infection with unique strains alone, confirming the need for patient segregation. Since this strain is common in many CF units, strain identification in all CF centres is essential. This can only be carried out using genomic typing methods.

During a diagnostic flexible bronchoscopy an 84 year old patient suffered a sudden reduction in conscious level following a transbronchial lung biopsy. A subsequent computed tomography brain scan confirmed cerebral air emboli. The patient survived following a period of supportive treatment in the critical care unit.Transbronchial lung biopsy may cause disruption of vessels walls within the lung parenchyma. Increased airway pressure, caused by the patient exhaling against a bronchoscope wedged within a segmental bronchi, may subsequently force air bubbles through the vessel wall defects. This may explain the occurrence of air emboli. This is a rare report of air embolism complicating transbronchial lung biopsy and all bronchoscopists should aware of this potentially fatal complication.

Background Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult. Case presentation A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation. Severe post-operative bleeding occurred due to dense intrapleural adhesions of the native lungs. He was re-explored and packed leading to satisfactory haemostasis. He developed a bronchopleural fistula on the 14th post-operative day. The fistula was successfully repaired using pericardial and intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator (VV-ECMO) support. Subsequently his recovery was uneventful. Conclusion The combination of pedicled intercostal and pericardial flaps provide adequate vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a feasible bridge to recovery.

Introduction The insertion of indwelling pleural catheters (IPCs) allows outpatient based management of malignant pleural effusions. This group of patients frequently require chemotherapy and there is concern over infection rates from IPCs which has the potential to delay or prevent such treatment. The infection rate was reported as 10% in a prospective trial of IPCs. In our tertiary pleural service we have elected to routinely prescribe 7 days doxycycline 100 mg once daily following IPC insertion. This study examined our infection rates using this practice. Method Data was collected from a tertiary respiratory and pleural service. Prospective data is collected on all patients undergoing IPC insertion at UHSM. Immediate post-procedure data is collected and a further clinical and case-note review undertaken at 6 months. Pre-defined immediate (post-procedure), early (30 days) complications are recorded. Infection is defined as the prescription of antibiotics (oral or intravenous) for suspected or confirmed pleural infection or drain-site cellulitis. This study is a retrospective review of the prospectively maintained database. To ensure six months of follow-up data for all patients the analysis was restricted to patients undergoing IPC insertion prior to 31/12/2014. Results 62 patients with complete datasets underwent IPC insertion between 01/01/2013 and 31/12/2014. All patients received 7 days of prophylactic doxycycline at a dose of 100 mg OD. One patient (1.6%) suffered drain site cellulitis requiring antibiotics within 30 days of insertion. There were two cases (3.2%) of pleural infection treated with antibiotics (both within 30 days of insertion and required intravenous antibiotics and admission). In these cases the IPCs were not removed but it did fall out in one case where the patient developed delirium with infection. Conclusion The infection rate in this prospectively collected data is lower than rates reported in large prospective randomised controlled clinical trials. This may suggest a benefit from the routine use of prophylactic antibiotics. A randomised controlled trial of prophylactic antibiotics versus no antibiotics following IPC insertion may be warranted.

Introduction The insertion of indwelling pleural catheters (IPCs) allows outpatient based management of pleural effusions and has been shown to be effective as a primary management strategy and following failed attempts at pleurodesis. The presence of septations may be associated with incomplete drainage and may make the procedure more complex. This study aimed to assess if the presence of septations on thoracic ultrasound changed the outcome of IPC insertion and to review complication rates. Method Prospective data is collected for patients undergoing insertion of IPCs at a tertiary pleural referral centre. Pre-procedure thoracic ultrasound is performed in all patients and a grading of septations made; no septations, mild ( 9). Immediate, early (30 days) complications as well as six month follow-up data are recorded. This study is a retrospective analysis of this prospectively maintained database. Results A total of 47 patients with complete datasets were identified between 2013–2014; 34% (16/47) had mild/moderate/severe septations (n = 7, 5, 4 respectively) and 66% (31/47) had no septations. There was no significant difference in the number of patients achieving resolution of pleural effusion and pleurodesis whereby the IPC could be removed according to the presence of septations (pleurodesis in those with no septations 16%, 5/31 vs. 13%, 2/16 in those with septations, p = 1.0). There were no patients in either group in whom the drain was removed due lack of drainage in the context of a persistent pleural collection. There was no significant difference in overall complication rate according to the presence of septations (16%, 5/31, in the no septation group vs 13%, 2/16, in the septation group, p = 1.0). Conclusion These results suggest that the presence of septations on the pre-insertion thoracic ultrasound do not affect the rate of pleurodesis or drain removal due to lack of drainage and persistent pleural effusion. The numbers in the study are small and a limitation is the lack of assessment of post-procedure breathlessness in our patients (e.g. with a visual analogue scale). The presence of septations should not deter consideration of IPC insertion in the management of malignant pleural effusions.

Introduction and objectives Reliable predictors of survival in malignant pleural effusions (MPE) have far reaching applications in clinical practice, not least tailoring individual treatment strategies. The ‘LENT’ score (pleural fluid L actate dehydrogenase; E astern Cooperative Oncology Group performance score; N eutrophil-to-lymphocyte ratio; T umour type) was developed and validated as a clinical prognostic scoring system from three international prospective patient databases. 1 The aim of this study was to evaluate the LENT score in a further UK population of patients with MPE, geographically separate from those in the original study. Methods Our hospital is a large tertiary centre for a physician-led pleural service (including medical thoracoscopy), a regional mesothelioma centre and a regional thoracic surgical centre. A retrospective study of all patients with positive (i.e. diagnostic for malignancy) pleural cytology or histology from 2010 to 2014 was undertaken. This timeframe allowed a minimum of 12 months follow-up for all patients. Survival data was obtained from national death registries. All patients in whom all LENT criteria were available were included in the analysis. A Kaplan-Meier curve and a Cox regression model were used to assess the LENT risk category. Harrell’s C statistic was used to assess the accuracy of the regression model and mortality rates at time points of interest were calculated. Results The LENT score was calculated for 101 patients diagnosed with MPE. The median survival (days, IQR) for the low (n = 18), medium (n = 54) and high risk (n = 29) groups were: 254 (152–602), 102 (40–301) and 16 (7–42). In the high risk group, only 31% of patients survived 1 month and 7% survived 6 months. There is a statistically significant difference in the survival times in the different risk groups according to the log-rank test (p Conclusions The LENT scoring system has again been shown to be a good tool for predicting survival in patients with MPE when applied to a geographically distinct cohort of patients to the original study. The LENT score continues to be a clinically valuable tool in the assessment of patients with MPE. Reference 1 Clive AO, et al . Thorax 2014; 69 (12):1098–104

Renal failure is increasingly being recognised in CF patients, usually as a consequence of long-term nephrotoxic therapy. There is a need for a simple method of assessment of renal function in this patient group. We compared measured creatinine clearance from validated timed urine collections (the generally accepted practical test of glomerular filtration) with 10 formulae used to estimate creatinine clearance in a group of 74 CF adult patients and 29 matched normal controls. Compared to direct measurement, formulae gave a range of values (95% CI for mean bias −13 to +27.9 ml/min). Even those with the best correlation (r=0.7) gave wide error ranges (limits of agreement: −42.3 to 45.9 ml/min). The most commonly used formulae (Cockroft–Gault [CGF] and abbreviated Modification of Diet in Renal Disease [aMDRD]) were not superior to most other formulae tested. Both CGF and aMDRD-derived estimates compared less favourably in CF patients than controls (mean bias: 9.7 vs 3.4 ml/min (p

grading of pulmonary rejection, we could demonstrate that grafts from animals lacking CD26 showed a significant reduction in rejection in comparison to CD26 positive controls. Also, specific differences in leukocyte infiltration were observed. Conclusions: While an increasing rejection over time is observed in all grafts, including the CD26 negative lungs, our results suggest a significant role for CD26 in the rejection process. Thus, inhibition of CD26 may be used as a clinical tool to enhance long term survival after lung transplantation.

Purpose: Apoptosis is initiated in graft cells during acute rejection as a result of immunologic insult. Apoptotic cells have increased expression of mannose which may bind mannose binding lectin leading to complement activation. However, the role of complement is unclear in allograft rejection. This study investigates the role of MBL and complement activation in acute rejection following heart transplantation. Methods and Materials: Blood samples were collected from 42 heart transplant recipients. The serum concentration and functionality of MBL was determined using a quantitative sandwich ELISA. Clinical data was collected from patient notes and statistical analysis was undertaken using SPSS v.11 with p values less than 0.05 being taken as significant. Results: MBL concentration was controlled for demographic variables and immunosuppressive therapy (agent, dose and serum concentration). Individuals with dysfunctional MBL had significantly fewer rejection positive biopsies (6.3 /-3.8%) than those with functional MBL (12.9 /-11.6%), p 0.016. Conclusions: This study indicates that complement activation by MBL contributes to the acute rejection cascade following cardiac transplantation. This is likely to be caused by formation of C4b2a via C2 and C4 cleavage, leading to activation of the membrane attack complex. Increased vascular permeability will occur through C5a release, along with recruitment and activation of neutrophils, monocytes and eosinophils from C3a and C4a.

Although acute renal failure has been described in children with CF in relation to intravenous aminoglycoside use, there are no reports in the adult CF literature. We describe 8 cases of acute renal failure in adult CF patients, all occurring during the use of intravenous aminoglycosides for the treatment of pulmonary exacerbations with an epidemic multi-resistant Pseudomonas aeruginosa strain. Potential contributory factors are discussed. These cases demonstrate another complication of infection by epidemic Pseudomonas strains in CF, and confirm the need for effective segregation policies to prevent this.