Post-lung Transplant Patients Research Articles

High-flow Nasal Oxygen Versus Standard Oxygen During Flexible Bronchoscopy in Lung Transplant Patients: A Randomized Controlled Trial.

Diagnostic and interventional flexible bronchoscopy (FB) is increasingly utilized in complex and high-risk patients. Patients are often sedated for comfort and procedure facilitation and hypoxia is commonly observed in this setting. We hypothesized that high-flow nasal oxygen (HFNO) would reduce the incidence of patients experiencing oxygen desaturation. In this randomized controlled trial, postlung transplant patients booked for FB with transbronchial lung biopsy were assigned to either HFNO or low-flow nasal oxygen (LFNO). The patient and bronchoscopist were blinded to group allocation. The primary endpoint was the proportion of patients experiencing mild desaturation [peripheral oxygen saturation (SpO2)<94%]. Secondary endpoints included desaturation (SpO2<90%), the number of airway interventions required and procedure interruptions, the duration of oxygen desaturation and patient, bronchoscopist and anesthesiologist satisfaction scores. The trial analyzed data from 76 patients (LFNO, n=39; HFNO, n=37). HFNO reduced the proportion of patients experiencing SpO2<94% (43.2% vs. 89.7%, P<0.001) and SpO2<90% (16.2% vs. 69.2%, P<0.001). The FB was interrupted 11 times in 9 patients in the LFNO group, whereas there were no interruptions in the HFNO group. There were no differences in patient and bronchoscopist satisfaction scores between groups, anesthesiologists had higher satisfaction scores when using HFNO (P<0.001). Hypoxia occurred less commonly in postlung transplant patients receiving HFNO during FB. Further studies are warranted in other high-risk populations undergoing longer duration FB.

Inhaled Bile Acids are Implicated in Airway Functional Changes and Cytokine Release

Bile acids are potent TGR5 ligands previously identified in bronchial washings of post-lung transplant patients and have been implicated in airway contractility ex-vivo and derangement of innate immunity. Particularly, metabolomics revealed primary bile acids GCA, GCDCA, CA, CDCA, DCA and TCA as presenting in the largest quantities. We hypothesized that bile acids may also have chronic and acute effects on airway function in vivo by affecting central resistance as well as cytokine release. A/J Mice were administered IP diluted Pentobarbital: tracheostomy/cannulation performed prior to a 20s BA nebulization (1mM BA, 25% EtOH) and incremental methacholine (MCh) challenge. Lung resistance (Rn) measured on Flexivent apparatus. C57BL6 mice were administered a bile acids cocktail of 4mM including GCA, GCDCA, CA, CDCA, DCA and TCA was chronically administered via intranasal instillation for a period of one month. BAL and tissue were collected, cytokine levels were analyzed. Statistical analyses were performed using ANOVA-Bonferroni and Student T Test. In-vivo acute inhalation of BAs prior to MCh challenge showed a general decrease in Rn compared to control. GCA (p=0.005) and GCDCA (p=0.035) showed the greatest decrease in airway resistance upon acute nebulization followed by GLCA (p=0.007) and a trending CDCA (p=0.07), as shown in the figure. Cytokine output from BALs post 1-month instillation revealed a significantly lower level of IL-6 (p=0.0068), IL-1B (p=0.0063), IL-17 (p=0.0273), MIP-1a (p=0.0076), and MIP-1B (p=0.012). The acute and chronic inhalation of bile acids commonly detected as major species in brochoalveolar lavages show an impact on airway resistance by reducing the methacholine induced constriction and affecting cytokine release. Interestingly, cytokines were decreased upon chronic exposure which may indicate a macrophagic inhibition affecting the airway immune responses.

Remote Therapy to Improve Outcomes in Lung Transplant Recipients: Design of the INSPIRE-III Randomized Clinical Trial.

Background.Impaired functional capacity and emotional distress are associated with lower quality of life (QoL) and worse clinical outcomes in post lung transplant patients. Strategies to increase physical activity and reduce distress are needed.Methods.The Investigational Study of Psychological Interventions in Recipients of Lung Transplant-III study is a single site, parallel group randomized clinical trial in which 150 lung transplant recipients will be randomly assigned to 3 months of telephone-delivered coping skills training combined with aerobic exercise (CSTEX) or to a Standard of Care plus Education control group. The primary endpoints are a global measure of distress and distance walked on the 6-Minute Walk Test. Secondary outcomes include measures of transplant-specific QoL, frailty, health behaviors, and chronic lung allograft dysfunction–free survival.Results.Participants will be evaluated at baseline, at the conclusion of 3 months of weekly treatment, at 1-year follow-up, and followed annually thereafter for clinical events for up to 4 years (median = 2 y). We also will determine whether functional capacity, distress, and health behaviors (eg, physical activity, medication adherence, and volume of air forcefully exhaled in 1 second (FEV1), mediate the effects of the CSTEX intervention on clinical outcomes.Conclusions.Should the CSTEX intervention result in better outcomes compared with the standard of care plus post-transplant education, the remotely delivered CSTEX intervention can be made available to all lung transplant recipients as a way of enhancing their QoL and improving clinical outcomes.

A128 JACKHAMMER ESOPHAGUS – A META-ANALYSIS OF PATIENT DEMOGRAPHICS, DISEASE PRESENTATION, MANOMETRY DATA AND TREATMENT OUTCOMES

Abstract Background Jackhammer esophagus (JE) is a newly described esophageal motility disorder characterized by the presence of distal esophageal hypercontractility. However, there is limited data on JE and this entity remains misunderstood. Aims To systematically review the published clinical data on JE and present pooled data on patient demographics, disease presentation, manometry parameters and treatment outcomes from the available literature. Methods We performed a systematic review of clinical series on JE (based on the latest Chicago Classification criteria (v3.0)) through MEDLINE, EMBASE and Web of Science. Patient data from included studies were then extracted and random-effects meta-analyses were performed to calculate and compare pooled data. Results Thirty-seven studies met inclusion criteria reporting on at least one pooled variable. The pooled prevalence of JE was 1.97% [95% CI: 1.39%-2.78%] amongst patients referred for high resolution manometry (HRM) based on eleven studies reporting this data (Figure 1). The mean age at diagnosis was 60.8 years [95% CI: 57.1–64.4] and 65% [95% CI: 58%-72%] of patients were female. JE was significantly more prevalent in post-lung transplant patients and morbidly obese patients undergoing HRM (23.99% [95% CI: 9.00%-38.97%] and 5.18% [95% CI: 1.76%-14.3%] respectively). Dysphagia was the most common presentation of JE (64% [95% CI: 52%-77%]) followed by gastroesophageal reflux disease (GERD) (46% [95% CI: 26%-67%]), regurgitation (39% [95% CI: 10%-67%] and heartburn (34% [95% CI: 22%-45%]). The pooled mean distal contractile integer (DCI) of all ten standard HRM swallows was 9,535 mmHg●s●cm [95% CI: 6,978–12,093] and the pooled mean integrated relaxation pressure (IRP) was 13.9 mmHg [95% CI: 8.2–19.7]. Endoscopic treatment as a whole was more successful than medical treatment in achieving clinical symptom improvement (79% [95% CI: 74%-85%] vs. 63% [95% CI: 47%-79%]; p=0.012). The pooled clinical success rate of peroral endoscopic myotomy (POEM) specifically was 82% [95% CI: 75%-90%]. Conclusions JE is a new motility disorder most commonly presenting with dysphagia. High clinical suspicion is important because the diagnosis can only be made through HRM and treatment outcomes are generally satisfactory. Funding Agencies None

Detection of β-alanyl aminopeptidase as a biomarker for Pseudomonas aeruginosa in the sputum of patients with cystic fibrosis using exogenous volatile organic compound evolution.

A novel, rapid and sensitive analytical method has been developed and applied to 105 sputum samples from patients with cystic fibrosis, including 5 samples from post-lung transplant patients. This new method is specifically targeted to measure β-alanyl aminopeptidase activity which is characteristic of some important Gram-negative pathogens. Of relevance to this study are Pseudomonas aeruginosa and pathogens of the Burkholderia cepacia complex both of which are commonly associated with respiratory infections as well as increased morbidity and mortality in adult cystic fibrosis patients. The analytical method involves the addition of a novel enzyme substrate (i.e. 3-amino-N-(3-fluorophenyl)propanamide) that interacts with β-alanyl aminopeptidase to generate an exogenous volatile organic compound 3-fluoroaniline (LOD 0.02 μg mL−1; LOQ 0.06 μg mL−1). 3-Fluoroaniline was determined at 20 times above its calculated limit of quantification in the sputum samples by HS-SPME-GC-MS and then the results compared with standard culture methods and bacterial identification using MALDI-TOF-MS. Detection of 3-fluoroaniline was possible after only 8 h incubation of the sputum samples with a 95% success rate; this increased to 100% at 24 h which was well within the typical routine timeframe of 48 h. To our knowledge, this is the first demonstration of detection of P. aeruginosa by use of a custom-designed substrate to liberate a detectable and unique VOC. The very high negative predictive value (100% in this study) means such an assay could be appropriate as a screening technique for patients who are not yet colonized by this pathogen.

Susceptibility Testing of Exophiala dermatitidis to Inform Peri-Operative Prophylaxis at Time of Lung Transplantation

Purpose Exophiala dermatitidis is a black fungus that frequently colonises the lungs of people with cystic fibrosis (CF). Mucoid and non-mucoid variants can be detected from the same sputum for some patients, but their role in chronic CF lung disease is not fully understood and attempts at early eradication are not routinely performed. Invasive infections with this species are rare; however in 2014 we reported our first case of fatal, invasive infection with a highly mucoid strain of E. dermatitidis in a 34 year old post lung transplant patient with CF. This prompted us to include peri-operative antifungal prophylaxis for all patients colonised with this species. To inform the choice of optimal antifungal, we performed susceptibility testing of 38 isolates from 34 patients including lung transplant patients. The ability of these isolates to produce biofilm was also investigated. Methods The minimum inhibitory concentration (MIC) of 8 antifungal agents was measured using a commercial broth microdilution assay. Biofilm formation was assessed using a standard in vitro assay using staining with crystal violet. Results Using breakpoints for Candida albicans, all isolates were susceptible to voriconazole and amphotericin B with most isolates also susceptible to itraconazole (89% of isolates) and posaconazole (71% of isolates). In contrast, all isolates were non-susceptible to caspofungin and most isolates (92%) non-susceptible to fluconazole. All strains were inhibited by ketoconazole at ≤0.25 mg/ L whereas MICs of 5-fluorocytosine ranged from 1->64 mg/ L. 31 of 38 isolates were biofilm producers including 4 isolates that were classified as strong biofilm producers. We did not find a correlation between mucoid phenotype and biofilm production. Conclusion E. dermatitidis is commonly found to colonise the lungs of patients with CF, typically produces biofilm, and may rarely produce serious infection post transplantation. We demonstrate in vitro susceptibility to voriconazole and amphotericin B. For patients colonised with this species, we now elect to include voriconazole as part of the peri-operative prophylactic regimen.

Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction after Lung Transplantation

Purpose Primary graft dysfunction (PGD) is the leading course of early death after lung transplantation. Extracorporeal membrane oxygenation (ECMO) was used as the last resort for PGD. The aim of this study is to explore the outcome and predictor for in-house mortality in post-lung transplant patients who required ECMO for PGD. Methods Between January 2006 and December 2015, 1049 cases of lung transplantation were performed at our center. Ninety-six patients (9.15 %) required ECMO support after lung transplantation. And 52 patients (4.96 %) required ECMO support for PGD. We retrospectively collected patient demographics and survival outcome of these patients. Results The mean age was 61.9 years ± 14.9 years. The mean lung allocation score was 49.5 ± 18.3. Seven patients (13.5 %) required veno-arterial ECMO due to concomitant hemodynamical instability. The patients were on ECMO for 5.00 ± 10.6 days. Forty-four patients (84.6 %) were successfully decannulated. There were 23 in-house mortalities. The 90-day, 1-year and 5-year survival of patients who required ECMO after lung transplantation were 67.3 %, 50.0 %, and 31.5 %, respectively. There is no significant difference on survival outcome when compared to the patient group required ECMO post-transplant due to the other causes. Univariate and multivariate analysis indicated that when the patient was placed on ECMO within 48 hours after transplantation, the patient was more likely to prevent in-house mortality regardless of patients’ preoperative conditions or duration of ECMO support. Conclusion Earlier recognition of PGD and initiation of ECMO may be beneficial in this population.

Veno-Venous Extracorporeal Membrane Oxygenation for Respiratory Failure: How Long Is Too Long?

The use of veno-venous extracorporeal membrane oxygenation (VV ECMO) in adults with respiratory failure has steadily increased during the past decade. Recent literature has demonstrated variable outcomes with the use of extended ECMO. The purpose of this study is to evaluate survival to hospital discharge in patients with extended ECMO runs compared with patients with short ECMO runs at a tertiary care ECMO referral center. We retrospectively reviewed all patients on VV ECMO for respiratory failure between August 2014 and February 2017. Bridge to lung transplant, post-lung transplant, and post-cardiac surgery patients were excluded. Patients were stratified by duration of ECMO: extended ECMO, defined as >504 hours; short ECMO as ≤504 hours. Demographics, pre-ECMO data, ECMO-specific data, and outcomes were analyzed. One hundred and thirty-nine patients with respiratory failure were treated with VV ECMO. Overall survival to discharge was 76%. Thirty-one (22%) patients had extended ECMO runs with an 87% survival to discharge. When compared with patients with short ECMO runs, there was no difference in median age, body mass index (BMI), body surface area (BSA), partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) (P/F), and survival to discharge. However, time from intubation to cannulation for ECMO was significantly longer in patients with extended ECMO runs. (p = 0.008). Our data demonstrate that patients with extended ECMO runs have equivalent outcomes to those with short ECMO runs. Although the decision to continue ECMO support in this patient population is multifactorial, we suggest that time on ECMO should not be the sole factor in this challenging decision.

Use of genitofemoral and ilioinguinal and iliohypogastric nerve block during orchiectomy in a post-lung transplant patient. A case report

Abstract The case is presented of a post-lung transplant patient, ASA III, proposed for orchiectomy due to testicular cancer. A combination of iliohypogastric (ILH), ilioinguinal (ILI) and genitofemoral (GF) nerve block together with sedation was used as anaesthetic technique. The inguinal area received sensory innervation mainly from ILI, ILH and GF nerves. The genital branch of the GF nerve supplies innervation to skin of the anterosuperior portion of the scrotum. When performing the echo-guided block of GF nerve, it is necessary to identify the spermatic cord, and administer the local anaesthetic on the inside and periphery of the cord. Peripheral nerve blocks are a valid option for complex patients. Its main advantage is the anaesthesia and analgesia level that it provides without the haemodynamic instability associated with general or neuraxial anaesthesia. GF nerve block provides hemi-scrotal anaesthesia, allowing manipulation and intervention in the inguinal-scrotal area, complementing the anaesthesia provided by ILI and ILH nerve blocks.

Quantifying Frailty in Post-Lung Transplant Patients-Can We Predict Who Will Need Readmission?

Quantifying Frailty in Post-Lung Transplant Patients-Can We Predict Who Will Need Readmission?

Incidence, Predictors, and Outcomes ofEarly Atrial Arrhythmias AfterLungTransplant: ASystematic Review and Meta-Analysis.

This study sought to determine the incidence, predictors, and prognostic implications of early post-lung transplant atrial arrhythmias (AAs). Although frequently encountered, the prognostic implications of early AAs after lung transplant remain uncertain. A systematic review of MEDLINE and the Cochrane Library was conducted for all studies that reported early post-lung transplant AAs. Random-effects DerSimonian-Laird risk ratios (RRs) were calculated for categorical variables and standardized mean difference (SMD) for continuous variables. A total of 12 studies with 3,203 patients (mean age 57 ± 3 years; 52% males) were included. The incidence of early post-lung transplant AAs during hospitalization was 26.6% at mean follow-up duration of 6.7 days. Predictors of post-lung transplant AAs included advanced age (SMD: 0.50; 95% confidence interval [CI]: 0.35 to 0.64), male gender (RR: 1.37; 95% CI: 1.28 to 1.47), history of smoking (RR: 1.23; 95% CI: 1.05 to 1.46), hypertension (RR: 1.35; 95% CI: 1.13 to 1.59), hyperlipidemia (RR: 1.39; 95% CI: 1.18 to 1.63), coronary artery disease (RR: 1.40; 95% CI: 1.12 to 1.7), left atrial diameter (SMD: 0.25; 95% CI: 0.07 to 0.44), and restrictive lung disease (RR: 1.34; 95% CI: 1.13 to 1.59). Post-lung transplant AAs were associated with increased all-cause mortality (adjusted RR: 1.63; 95% CI: 1.22 to 2.19) at mean follow-up of 27.8 months and length of hospital stay (36.5 ± 16.5 days vs. 26.1 ± 14.3 days; p< 0.001). Early AAs post-lung transplant are associated with increased mortality and length of hospital stay.Advanced age, male sex, smoking, hypertension, hyperlipidemia, coronary artery disease, increased left atrial diameter, and restrictive lung disease are independent predictors of early AAs in post-lung transplant patients.

50 Role of reaginic IgE phenomena in Pseudomonas aeruginosa infection in patients with cystic fibrosis

PET using F-FDG is widely used in the diagnosis, monitoring and staging of malignancy. Tissue FDG uptake is determined by metabolic activity and can identify neutrophilic inflammation and in stable patients, enhanced uptake is often absent. We report our experience of PET in three patients with CF and how results helped support clinical decision making. A 38 year old post lung transplant patient presented with recurrent right sided chest pain, fever and elevated CRP. Despite extensive investigation by the transplant unit, no focal abnormality was identified and symptoms failed to resolve with iv antibiotics. PET revealed FDG avidity in the right middle lobe and she required a right middle and upper lobectomy. A 30 year old patient chronically colonised with P. aeruginosa and M. abscessus, developed aggressive lung disease and despite regular intravenous, nebulised and oral antibiotics, continued to decline with a fall in lung function, pyrexia and malaise. PET revealed marked FDP avidity within multiple lung nodules. Treatment was continued with the addition of interferon gamma. Despite a worsening CXR, PET showed significant improvement. These results have helped guide therapy. A 36 year old presented with persistent respiratory symptoms. Sputum was repeatedly culture positive for M. abscessus. There were no clinical or radiological evidence of deterioration. PET was undertaken to exclude active focal inflammation. The scan was unremarkable and a less intense regimen was instituted. Sputum has since been persistently negative for M. abscessus. PET is a useful adjunct to conventional investigations and in selected individuals can be helpful in guiding clinical management.

49 The use of positron emission tomography (PET) in adult patients with cystic fibrosis (CF)

PET using 18F-FDG is widely used in the diagnosis, monitoring and staging of malignancy. Tissue FDG uptake is determined by metabolic activity and can identify neutrophilic inflammation and in stable patients, enhanced uptake is often absent. We report our experience of PET in three patients with CF and how results helped support clinical decision making. A 38 year old post lung transplant patient presented with recurrent right sided chest pain, fever and elevated CRP. Despite extensive investigation by the transplant unit, no focal abnormality was identified and symptoms failed to resolve with iv antibiotics. PET revealed FDG avidity in the right middle lobe and she required a right middle and upper lobectomy. A 30 year old patient chronically colonised with P. aeruginosa and M. abscessus, developed aggressive lung disease and despite regular intravenous, nebulised and oral antibiotics, continued to decline with a fall in lung function, pyrexia and malaise. PET revealed marked FDP avidity within multiple lung nodules. Treatment was continued with the addition of interferon gamma. Despite a worsening CXR, PET showed significant improvement. These results have helped guide therapy. A 36 year old presented with persistent respiratory symptoms. Sputum was repeatedly culture positive for M. abscessus. There were no clinical or radiological evidence of deterioration. PET was undertaken to exclude active focal inflammation. The scan was unremarkable and a less intense regimen was instituted. Sputum has since been persistently negative for M. abscessus. PET is a useful adjunct to conventional investigations and in selected individuals can be helpful in guiding clinical management.

High Prevalence of Spastic Esophageal Motility Disorders in Post-Lung Transplant Patients

Introduction: Gastroesophageal reflux disease (GERD) has been associated with allograft failure and bronchiolitis obliterans syndrome (BOS) in lung transplant recipients, likely due to aspirationmediated lung injury. Through aggressive symptom-driven evaluation for esophageal motility disorders in post-lung transplant patients at our institution, we are able to report the high-resolution esophageal manometry (HRM) findings for a large cohort of these patients. A select number of these patients underwent therapeutic botox injection to the lower esophageal sphincter. We sought to characterize the manometric findings in this population and report on the safety and outcomes of this intervention. Methods: Using a secure integrated database, 99 post-lung transplant patients who underwent HRM between 9/2006-8/2014 were identified. Medical records were reviewed and study data was collected and managed using REDCap (Research Electronic Data Capture) tools. Results: We identified 99 lung transplant patients who underwent HRM testing post-transplant for various esophageal symptomatic indications. The average time post-transplant that HRM was performed was 600 days ± 1049. The demographic characteristics are shown in Table 1. Of the 99 patients in our cohort, 77 had abnormal post-transplant HRM findings. Of these, 51 (51.5%) were found to have a spastic esophageal motility disorder, and 11 of these subsequently underwent lower esophageal sphincter botox injection. Symptomatic improvement was seen in 7 (63.6%) of these patients post-injection, and the 2 patients who had repeat HRM post-botox subsequently had normal findings. Four patients with symptom recurrence received an additional lower esophageal sphincter botox injection and had 100% symptomatic response rate. There were no complications from botox injection.Table 1: Baseline Characteristics of the Cohort Stratified by HRM Findings.Conclusion: We identified a high prevalence of spastic esophageal motility disorders in post-lung transplant patients. Botox injection to the lower esophageal sphincter was given 15 times, with an overall symptomatic response rate of 81.8%. The two patients who had repeat HRM post-botox injection had disappearance of their spastic motility disorder. The development of achalasia has been linked to neuropathic dysfunction of the vagal nerve from operative trauma. Akin to the development of post-lung transplant gastroparesis, we hypothesize that vagal nerve injury is associated with the development of spastic esophageal motility disorders in these patients.Figure 1Figure 2

High Prevalence of Gastroparesis in Post Lung Transplant Patients ACG Fellows-In-Training Award Presidential Poster

Introduction: Gastroparesis after lung transplantation has been described, and is thought to be due to operative vagal nerve injury. By promoting aspiration, gastroparesis may predispose to bronchiolitis obliterans syndrome (BOS), a form of chronic rejection and the primary cause of allograft failure in lung transplant recipients. We aimed to determine the prevalence of post-transplant gastroparesis at our institution and to evaluate the effect of intra-pyloric botox injection on symptoms, gastric emptying, and pulmonary outcomes.Table 1: Baseline Characteristics of the Cohort Stratified by Normal (NGE) or Delayed (DGE) Gastric Emptying, with and without BotoxFigure 1Figure 2Methods: 195 post-lung transplant patients who underwent GES between 7/2003-8/2015 were placed into subgroups: normal gastric emptying (NGE), delayed gastric emptying (DGE), DGE with botox, and DGE without botox. We identified BOS occurrences and timing among each subgroup, and performed Kaplan-Meier estimation of freedom from BOS after transplant and GES. Results: DGE was found in 122 (62.6%) patients. Of these, 47 (38.5%) patients underwent a total of 70 intra-pyloric botox injections. Symptomatic improvement was seen 72.8% of the time. After botox, the absolute 2- and 4-hour % retention found on GES improved by 12.7% and 12.3%, respectively. There were no procedural complications. For patients with available pulmonary clinical data (n=147), the rates of freedom from BOS after transplant and new onset or worsening grade BOS after GES were not significantly different between NGE and DGE subgroups. However, among DGE patients (n=63) BOS occurred sooner and was more often pre-existing at time of GES (Table 2). While pyloric botox injection did not appear to prevent chronic allograft rejection after GES or transplant overall among those with DGE, freedom from BOS appeared to be significantly increased when botox was performed sooner after transplant. Of note, more BOS risk events (acute rejection and bacterial/viral pneumonia) occurred in the DGE v. NGE and botox v. no botox subgroups.Table 2: Baseline Characteristics and Pulmonary Outcomes of the Pulmonary Cohort Stratified by Normal (NGE) or Delayed (DGE) Gastric Emptying, with and without BotoxConclusion: A high prevalence of post-lung transplant gastroparesis was observed, and the majority of patients who underwent pyloric botox injections had successful symptomatic and physiologic motility response. The efficacy of pyloric botox injections in preventing BOS among post-lung transplant patients with gastroparesis remains unclear, though freedom from BOS appeared to be improved when botox was performed soon after transplant. In our cohort, risk factors other than gastric emptying may have played a larger role in the development of chronic allograft rejection.

148 Prevalence of chronic rhinosinusitis and upper airways colonisation in the Welsh adult cystic fibrosis population

Background Symptoms of chronic rhinosinusitis (CRS) have been reported in 11–94% of CF patients. Upper airways (UAW) infection with Psa (evaluated by nasal lavage) has been suggested as a potential reservoir for infection of the lower airways (LAW) (Mainz 2009). CF lung transplant recipients become re-colonised with the same bacteria as those cultured before transplant (Walter 1997). It is likely that this occurs from a bacterial reservoir in the paranasal sinuses (Johansen 2012). Aim To assess the prevalence of CRS symptoms in adults attending the AWACFC as measured by the Sino-Nasal Outcome Test: SNOT-22. To assess the prevalence bacterial isolates from the UAW in our population on nasal lavage. Method All patients completed a SNOT22 at annual review. UAW samples using nasal lavage were taken from patients scoring >30 on SNOT22 or post lung transplant patients. Results 219 patients (128 males, mean FEV 1 67.9%) completed the SNOT-22 of which 43 (20%) scored >30 (suggestive of CRS). 15 patients were post lung transplant of whom 10 (67%) scored >30. Of the patients who were sampled; 19 had Psa (3 post transplant), 18 patients had no growth, 9 Staphylococcus aureus (4 post transplant), 1 Burkholderia multivorans, 1 Pseudomonas fluorescens (post Tx), 1 Klebsiella pneumoniae , 1 Enterobacter . All patients who isolated Psa in the UAW isolated Psa in their LAW. Conclusion The prevalence of Psa in the UAW of our population is less than previously reported (Johansen 2012 (78%), this may be due to the sampling technique, however the UAW and LAW presence of Psa is in keeping with previous studies (Mainz et al. 2009) which suggest the sinuses may be a reservoir for the LAW.

Capnography monitoring in procedural sedation for bronchoscopy.

Capnography monitoring in procedural sedation for bronchoscopy.

BASELINE AUDIT OF SUPPORTIVE CARE PROVISION FOR PATIENTS WHO DIED IN 2010 AND HAD LUNG TRANSPLANTS OR WERE ON THE WAITING LIST AT HAREFIELD HOSPITAL

BackgroundThere is a lack of significant literature on provision of Supportive and Palliative care (SPC) for Lung transplant patients pre and post surgery.AimsA baseline audit of patients was undertaken to...

IP-10 Is a Potential Biomarker of Cystic Fibrosis Acute Pulmonary Exacerbations

BackgroundCystic fibrosis (CF) is characterized by acute pulmonary exacerbations (APE). The CF nasal airway exhibits a similar ion transport defect as the lung, and colonization, infection, and inflammation within the nasal passages are common among CF patients. Nasal lavage fluid (NLF) is a minimally invasive means to collect upper airway samples.MethodsWe collected NLF at the onset and resolution of CF APE and compared a 27-plex cytokine profile to stable CF outpatients and normal controls. We also tested IP-10 levels in the bronchoalveolar lavage fluid (BALF) of CF patients. Well-differentiated murine sinonasal monolayers were exposed to bacterial stimulus, and IP-10 levels were measured to test epithelial secretion.ResultsSubjects hospitalized for APE had elevated IP-10 (2582 pg/mL [95% CL of mean: 818,8165], N=13) which significantly decreased (647 pg/mL [357,1174], P<0.05, N =13) following antimicrobial therapy. Stable CF outpatients exhibited intermediately elevated levels (680 pg/mL [281,1644], N=13) that were less than CF inpatients upon admission (P=0.056) but not significantly different than normal controls (342 pg/mL [110,1061]; P=0.3, N=10). IP-10 was significantly increased in CF BALF (2673 pg/mL [1306,5458], N=10) compared to healthy post-lung transplant patients (8.4 pg/mL [0.03,2172], N=5, P<0.001). IP-10 levels from well-differentiated CF murine nasal epithelial monolayers exposed to Pseudomonas PAO-1 bacteria-free prep or LPS (100 nM) apically for 24 hours were significantly elevated (1159 ± 147, P<0.001 for PAO-1; 1373 ± 191, P<0.001 for LPS vs. 305 ± 68 for vehicle controls). Human sino-nasal epithelial cells derived from CF patients had a similar response to LPS (34% increase, P<0.05, N=6).ConclusionsIP-10 is elevated in the nasal lavage of CF patients with APE and responds to antimicrobial therapy. IP-10 is induced by airway epithelia following stimulation with bacterial pathogens in a murine model. Additional research regarding IP-10 as a potential biomarker is warranted.

The Lung Microbiome and Development of Bronchiolitis Obliterans Syndrome after Pediatric Lung Transplantation

Purpose Bronchiolitis obliterans syndrome (BOS) is a major complication following lung transplant. Infection is a known risk factor for the development of BOS. Microbiome analysis has an advantage over traditional culture as it detects uncultivable organisms. In addition, reduced bacterial diversity has been associated with increases in morbidity and mortality. We hypothesize that significant differences exist in the microbiome of post lung transplant patients with BOS vs. non-BOS. Methods and Materials Ninety-four bronchoalveolar lavage specimens from 21 patients were collected during surveillance bronchoscopies throughout the first year post-transplant. Bacterial DNA was extracted, and the V3V5 variable regions of the 16SrRNA gene were amplified using universal barcoded primers. Subsequent 454 sequencing produced an average of 6,000 reads per sample with an average length of 500 bases. Resulting sequences were analyzed by the Genboree Microbiome Workbench. Results In lung transplant recipients (LTRs) who developed BOS, Firmicutes decreased and Proteobacteria increased over time. Conversely, the non-BOS group revealed a longitudinal increase in Firmicutes and a decreased in Proteobacteria. 33 genera were noted in the BOS compared to 49 genera in the non-BOS group, indicating an overall decreased bacterial diversity in the BOS group. Bacterial diversity was similar in both the groups at 2 weeks post transplant but steadily declined in the BOS group while it increased in the non-BOS group during the first year post transplant. Conclusions Longitudinal genus-level variation clearly differed in the BOS vs. non-BOS groups. Moreover, BOS was associated with reduced bacterial diversity, which has been associated with an increase in morbidity and mortality in previous studies of the lung microbiome. Further studies are required to investigate if a change in the lung microbiome of post-transplant individuals is an indication of the future development of BOS.