Sebastian Lugg

Iron treatment and inflammatory bowel disease: What happens in real practice?

BACKGROUND AND AIMS Iron deficiency anaemia (IDA), the most common extra-intestinal complication of inflammatory bowel disease (IBD), negatively impacts quality of life. We audited the recent practice of anaemia treatment in an unselected IBD population. METHODS A questionnaire was distributed to adult IBD outpatients in a university hospital to assess the form and frequency of iron prescribed, duration of use, side effects, and completion of therapy. The efficacy of treatment was determined by the resolution of anaemia and change in haemoglobin from baseline. RESULTS Of 87 IBD patients (60 patients with Crohns disease, 25 with ulcerative colitis, 2 with microscopic colitis), 85 received various dosing regimens of iron tablets; 15 patients also received IV iron. Side effects were reported in 43 (51%) patients, with no clear relationship to dose prescribed and 26 (32%) patients were unable to complete the intended course. Only 36 (42%) patients completed the course of oral iron without side effects and in these patients, haemoglobin normalised in about 30%. Their median haemoglobin change was 12.5 (5.3-23.5)g/l. The median duration of treatment in those without side effects was 4.5months, and in those with adverse effects was 2months. Only one adverse effect was reported for IV iron. CONCLUSIONS Treatment with oral iron results in failure to control anaemia in 2 out of 3 IBD patients, which is likely in part to be due to the side effects reported by over half of patients. Patients failing to tolerate or adequately respond to therapy should be offered alternative treatment.

Postoperative pulmonary complications and rehabilitation requirements following lobectomy: a propensity score matched study of patients undergoing video-assisted thoracoscopic surgery versus thoracotomy

OBJECTIVES : Video-assisted thoracoscopic surgical (VATS) lobectomy is increasingly used for curative intent lung cancer surgery compared to open thoracotomy due to its minimally invasive approach and associated benefits. However, the effects of the VATS approach on postoperative pulmonary complications (PPC), rehabilitation and physiotherapy requirements are unclear; our study aimed to use propensity score matching to investigate this. METHODS Between January 2012 and January 2016 all consecutive patients undergoing lobectomy via thoracotomy or VATS were prospectively observed. Exclusion criteria included VATS converted to thoracotomy, re-do thoracotomy, sleeve/bilobectomy and tumour size >7 cm diameter (T3/T4). All patients received physiotherapy assessment on postoperative day 1 (POD1), and subsequent treatment as deemed appropriate. PPC frequency was measured daily using the Melbourne Group Scale. Postoperative length of stay (LOS), high dependency unit (HDU) LOS, intensive therapy unit (ITU) admission and in-hospital mortality were observed. Propensity score matching (PSM) was performed using previous PPC risk factors (age, ASA score, body mass index, chronic obstructive pulmonary disease, current smoking) and lung cancer staging. RESULTS Over 4 years 736 patients underwent lobectomy with 524 remaining after exclusions; 252 (48%) thoracotomy and 272 (52%) VATS cases. PSM produced 215 matched pairs. VATS approach was associated with less PPC (7.4% vs 18.6%; P  < 0.001), shorter median LOS (4 days vs 6; P  < 0.001), and a shorter median HDU LOS (1 day vs 2; P  = 0.002). Patients undergoing VATS required less physiotherapy contacts (3 vs 6; P  < 0.001) and reduced therapy time (80 min vs 140; P  < 0.001). More patients mobilized on POD1 (84% vs 81%; P  = 0.018), and significantly less physiotherapy to treat sputum retention and lung expansion was required ( P  < 0.05). CONCLUSIONS This study demonstrates that patients undergoing VATS lobectomy developed less PPC and had improved associated outcomes compared to thoracotomy. Patients were more mobile earlier, and required half the physiotherapy resources having fewer pulmonary and mobility issues.

Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages

Objective Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. Methods AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. Results Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. Conclusions ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.

S16 Simvastatin improves neutrophil migration in elderly patients with septic pneumonia and reduces 6-month mortality and re-admissions: results of the snoopi trial

Introduction and objectives Community acquired pneumonia is a leading infectious cause of death in the elderly and the commonest source of sepsis. Neutrophil functions decline with age, and deteriorate further in sepsis.1 Restoring neutrophil function may improve sepsis outcomes. Recent in-vitro and in-vivo studies suggest simvastatin improves aspects of neutrophil function.2 Adjuvant statin therapy in severely critically ill patients has failed to improve outcomes and may be associated with increased morbidity,4,5 however our ASEPSIS study suggested that early intervention with statins may reduce the progression of sepsis in a ward-based cohort of milder sepsis patients.6 In light of this, we investigated whether oral treatment with simvastatin improved neutrophil function and clinical outcomes in elderly patients with septic pneumonia. Methods ‘SNOOPI’ was a phase-4, randomised controlled trial comparing 7-days of 80mg simvastatin with placebo in patients aged 55 years or over admitted to hospital with septic pneumonia.3 The primary outcome was changes in neutrophil extracellular trap (NETs) formation by day3/4 compared with baseline. Secondary outcomes included neutrophil migration, safety and tolerability, length of stay, readmissions and mortality. Results 61 patients were recruited acute admissions unit at the Queen Elizabeth Hospital Birmingham between 2013 and 2015, with 31 patients randomised to simvastatin and 30 to placebo. Groups were well matched for baseline characteristics, pneumonia and sepsis severity, co-morbidities and biochemical and haematological parameters. There was no significant difference in the primary end-point of change in NETS at day3/4. Directional neutrophil migration (chemotaxis) was significantly improved in patients who received simvastatin at day 3/4 (0.35 ± 0.16 μm/min vs. −0.15 ± 0.17 μm/min; p = 0.033). Simvastatin was well tolerated with no SUSARS, even with the co-prescription of macrolides. At 6-months, patients in the simvastatin group were less likely to have been admitted to hospital or died compared to those in the placebo group (OR: 0.44; 95% CI: 0.21–0.91; p = 0.02) (Figure 1). Conclusions The current study suggests that early intervention with statins in septic pneumonia patients may improve patient outcomes. We propose that one of the mechanistic drivers may be the restoration of sepsis-associated dysregulated neutrophil function. Further larger studies are warranted to confirm whether early intervention with statins in patients with sepsis confer an overall survival benefit. References Alves-Filho JC, Spiller F, Cunha FQ. Neutrophil paralysis in sepsis. Shock 2010;34(Suppl 1):15–21. Sapey E, Greenwood H, Walton G, et al. Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence. Blood 2014;123(2):239–248. Greenwood H, Patel J, Mahida R, et al. Simvastatin to modify neutrophil function in older patients with septic pneumonia (SNOOPI): study protocol for a randomised placebo-controlled trial. Trials 2014;15:332. McAuley DF, Laffey JG, O’Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med 2014;371:1695–1703. The National Heart L, Blood Institute ACTN. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014;370:2191–2200. Patel JM, Snaith C, Thickett DR, et al. Randomised double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Critical Care 2012;16(6):R231. Abstract S16 Figure 1 Kaplan-Meier Curve showing the time (in-days)to either death or re-admission to hospital in patients’ allocated to simvastatin or placebo

S122 Effects of vaped e-cigarette liquid condensate upon human alveolar macrophage function. to vape or not to vape that is the question?

Introduction and objectives Electronic cigarette usage or “vaping” has risen exponentially in recent years in smokers and ex-smokers. Published data suggests that vaping e-cigarette liquid (ECL) may not be as benign as propounded by e-cigarette companies which are increasingly owned by “big tobacco”. Much of the current literature has focused on the effect of non-vaporised ECL – such studies do not fully reflect the exposure of the user, as the process of vaping causes chemical changes in ECL. To investigate the effect of unvaped ECL and vaped e-cig condensate (ECVC) using our novel system, with and without nicotine, on alveolar macrophage (AM) viability and immune responses. Methods We developed a novel method to produce ECVC to allow direct comparison with unvaped ECL. Nicotine concentration as assessed by GFID was 31 mg/ml in ECL and 26 mg/ml in ECVC. AMs were obtained from lung resection tissue and treated with ECVC/ECL ± nicotine. Cell viability was assessed by cell titre aqueous assay, apoptosis, necrosis and markers of macrophage phenotype (CD68, CD80, CD163, CD206) were assessed by flow cytometry. IL-8 release by AMs was assessed by ELISA. Results AM culture with ECL or ECVC resulted in dose dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL (0.8% ECVC vs 5 %ECL, n = 6). 24 hour culture with 1% ECVC resulted in a 5fold increase in AM apoptosis and 2 fold increase in necrosis compared with 1%ECL (p = 0.079, n = 5). Nicotine containing ECVC caused more apoptosis vs nicotine free ECVC (27.2% vs 13.4%, (p = 0.0079,n = 4). Culture with 0.6%ECVC significantly increased supernatant levels of IL-8 compared with 1% ECL (p = 0.015, n = 4). ECVC was also found to affect macrophage phenotype, showing both nicotine dependent/independent regulations of markers of macrophage m1/m2 polarisation (CD80 p = 0.0357, CD163 p = 0.0179, CD206 p = 0.0357, n = 6). Conclusions Our novel system creates ECVC which is sterile, minimises loss of nicotine and prevents dilution of the vapour. Vaped E-cigarette condensate is significantly more toxic to AMs than non-vaped e cigarette liquid. Furthermore, ECVC with nicotine is significantly more toxic than ECVC without Nicotine. Effects shown on inflammatory cytokine production and markers of macrophage polarisation indicate both nicotine dependent and independent effects of ECVC on alveolar macrophages.

S63 Postoperative pulmonary complications and physiotherapy requirements after open thoracotomy versus vats lobectomy: a propensity score-matched analysis

Introduction Video-assisted thoracoscopic surgical (VATS) lobectomy is increasingly used for curative intent lung cancer surgery compared to open thoracotomy due to its minimally invasive approach and associated benefits. However, the effect of the VATS approach on postoperative pulmonary complications (PPC), rehabilitation and physiotherapy requirements is unclear; our study aimed to use propensity score matching to investigate this. Methods Between January 2012 and January 2016 all consecutive patients undergoing lobectomy via thoracotomy or VATS were prospectively observed. Exclusion criteria included VATS converted to thoracotomy, re-do thoracotomy, sleeve/bi-lobectomy and tumour size >7 cm diameter (T3/T4). All patients received physiotherapy assessment on postoperative day 1 (POD1), and subsequent treatment as deemed appropriate. PPC frequency was measured daily using the Melbourne Group Scale.1 Postoperative length of stay (LOS), high dependency unit (HDU) LOS, intensive therapy unit (ITU) admission and in-hospital mortality were observed. Propensity score matching (PSM) was performed using previous identified PPC risk factors (age, ASA score, BMI, COPD, current smoking) and lung cancer staging. Results Over 4 years 736 patients underwent lobectomy with 524 remaining after exclusions; 252 (48%) thoracotomy and 272 (52%) VATS cases. PSM produced 215 matched pairs. VATS approach was associated with less PPC (7.4% Vs 18.6%; p < 0.001), shorter median LOS (4 days vs 6; p < 0.001), and a shorter median HDU LOS (1 day vs 2; p = 0.002) (Table 1). Patients undergoing VATS required less physiotherapy contacts (3 Vs 6; p < 0.001) and reduced therapy time (80 min vs 140; p < 0.001). More patients mobilised on POD1 (84% vs 81%; p = 0.018), and significantly less therapies to treat sputum retention and lung expansion were required (p < 0.05). Abstract S63 Table 1 Postoperative outcomes following open thoracotomy versus VATS. Thoracotomy(n = 215) VATS (n = 215) p value PPC (%) 40 (18.6) 16 (7.4) <0.001 Median Hospital LOS (IQR) 6 (4) 4 (3) <0.001 Median HDU LOS (IQR) 2 (2) 1 (1) 0.002 ITU admission (%) 9 (4.2) 6 (2.8) 0.599 Hospital mortality (%) 5 (2.3) 3 (1.4) 0.724 VATS, video-assisted thorascopic surgery; PPC, postoperative pulmonary complication; LOS, length of stay; HDU, high dependency unit; ITU, intensive therapy unit. Conclusions This study demonstrates that patients undergoing VATS lobectomy developed less PPC and had improved associated outcomes compared to thoracotomy. Patients were more mobile earlier, required half the physiotherapy resources, having fewer pulmonary and mobility issues. Reference Agostini P, et al. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? Thorax 2010;65(9):815–8.

S61 Risk factors and short-term outcomes of developing postoperative pulmonary complications after vats lobectomy

Introduction Postoperative pulmonary complications (PPC), such as pneumonia and atelectasis are associated with poor outcomes following thoracotomy and lung resection, with risk factors identified.1,2 Video-assisted thoracoscopic surgery (VATS) is increasingly performed, however, there are varying reports regarding the incidence of PPC with little is known about their effect on short-term outcomes or potential risk factors. Methods A prospective observational study of consecutive patients undergoing VATS lobectomy was performed in a regional centre (2012–2016). Exclusion criteria included re-do VATS/completion lobectomy. All patients received physiotherapy assessment/intervention as necessary from postoperative day 1 (POD1). The presence of PPC was determined daily using the Melbourne Group Scale. Outcomes included hospital length of stay (LOS), intensive therapy unit (ITU) admission and hospital mortality. Results 287 patients underwent VATS lobectomy, 2 patients undergoing completion lobectomy were excluded. Of 285 patients; 137 were male (48%), median (IQR) age of 69 years (13) and mean (±SD) FEV1 of 87% (±19). PPC developed in 21 patients (7.4%); the median day that PPC developed was postoperative day 3 (Figure 1). Patients who developed a PPC had a significantly longer hospital LOS (4 vs 3 days), higher rate of ITU admission (25% vs 0%) and higher hospital mortality (14% vs 0%) (p < 0.001). Current smoking and COPD diagnosis were significantly different on univariate analysis (p < 0.05), but on forward stepwise logistic regression, only current smoking was a significant independent risk factor for PPC (p = 0.015). Those with PPC required significantly more physiotherapy contacts/time, with more specific pulmonary therapy and emergency out-of-hours therapy. Abstract S61 Figure 1 Day PPC detected following surgery Conclusions Patients undergoing VATS remain at risk of developing a PPC associated with significantly worse short-term morbidity and mortality. Patients that develop a PPC following VATS required increased postoperative physiotherapy compared to non-PPC patients. Current smoking is an independent risk factor for PPC development following VATS, thus vigorous addressing of preoperative smoking cessation is urgently needed. References Agostini P, et al. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? Thorax 2010;65(9):815–8. Lugg ST, et al. Long-term impact of developing a postoperative pulmonary complication after lung surgery. Thorax 2016;71(2):171–6.

P164 Smoking at the time of curative-intent lung cancer surgery increases perioperative complications: is there a role for electronic cigarettes?

Introduction Smoking is a risk factor for postoperative pulmonary complications (PPCs) following curative-intent surgery for lung cancer. Risk modification is via smoking cessation; the role that electronic cigarettes (e-cigarettes) have in preoperative tobacco replacement is a debated topic. Aims Investigate the impact of smoking on postoperative outcome including long-term survival. Assess current smoking habits and attitudes towards preoperative smoking cessation, with emphasis on e-cigarette use. Methods A prospective observational study was carried out on all patients following curative-intent lung cancer resection in a regional thoracic centre over 4 years. Preoperative smoking status was self-reported by all patients. PPCs were assessed daily in hospital using the Melbourne group scale.1 Other data included patient demographics, hospital length of stay (LOS), intensive treatment unit (ITU) admission and mortality data. To assess smoking habits, a questionnaire was given to 105 patients attending the preoperative assessment unit. Results Of 460 patients, 24% were current smokers, 12% ex-smokers 6 weeks duration, and 11% never smoked Compared to never smokers, current smokers had significantly longer hospital LOS in days (9, CI 7–11 vs. 6, CI 4–8; p < 0.001), higher frequency of PPCs (22% vs 2%, p = 0.001) and ITU admissions (14% vs. 0%; p < 0.005). Compared to never smokers, the trend was for reduced survival in current smokers from 1–3 years, but the survival lines converged after this (median follow-up 30 vs. 31 months; p = 0.31). The questionnaire found 24/105 patients were smokers, of these 80% patients had previously tried to quit but only 38% had been specifically approached by health-care professionals about smoking cessation. When asked if they would consider stopping smoking immediately if supplied an e-cigarette, 54% said yes. Conclusions Preoperatively, 1 in 4 patients continue to smoke; the majority have attempted to quit and failed. Current smokers have higher postoperative morbidity with no significant survival difference within our follow-up period. Current methods of preoperative smoking cessation in this population are ineffective; patients appear willing to use e-cigarettes. Further research in this field is urgently needed. Reference 1 Agostini P, et al. Thorax 2010;65:815–18