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.

Early identification of severe community-acquired pneumonia: a retrospective observational study.

Background: Community-acquired pneumonia (CAP) is a leading cause of sepsis worldwide. Prompt identification of those at high risk of adverse outcomes improves survival by enabling early escalation of care. There are multiple severity assessment tools recommended for risk stratification; however, there is no consensus as to which tool should be used for those with CAP. We sought to assess whether pneumonia-specific, generic sepsis or early warning scores were most accurate at predicting adverse outcomes. Methods: We performed a retrospective analysis of all cases of CAP admitted to a large, adult tertiary hospital in the UK between October 2014 and January 2016. All cases of CAP were eligible for inclusion and were reviewed by a senior respiratory physician to confirm the diagnosis. The association between the CURB65, Lac-CURB-65, quick Sequential (Sepsis-related) Organ Failure Assessment tool (qSOFA) score and National Early Warning Score (NEWS) at the time of admission and outcome measures including intensive care admission, length of hospital stay, in-hospital, 30-day, 90-day and 365-day all-cause mortality was assessed. Results: 1545 cases were included with 30-day mortality of 19%. Increasing score was significantly associated with increased risk of poor outcomes for all four tools. Overall accuracy assessed by receiver operating characteristic curve analysis was significantly greater for the CURB65 and Lac-CURB-65 scores than qSOFA. At admission, a CURB65 ≥2, Lac-CURB-65 ≥moderate, qSOFA ≥2 and NEWS ≥medium identified 85.0%, 96.4%, 40.3% and 79.0% of those who died within 30 days, respectively. A Lac-CURB-65 ≥moderate had the highest negative predictive value: 95.6%. Conclusion: All four scoring systems can stratify according to increasing risk in CAP; however, when a confident diagnosis of pneumonia can be made, these data support the use of pneumonia-specific tools rather than generic sepsis or early warning scores.

ARDS following oesophagectomy: a comparison of two trials.

INTRODUCTION: The Beta Agonist Lung Injury Trial-Prevention (BALTI-P) translational substudy and Vitamin D to Prevent Acute Lung Injury Following Oesophagectomy (VINDALOO) trials recruited patients undergoing oesophagectomy, 4 years apart. The acute respiratory distress syndrome (ARDS) rates were lower in the VINDALOO trial. We sought to identify changes between these two trials and identify risk factors for ARDS in oesophagectomy. METHODS: There were data available from 61 patients in the BALTI-P substudy and 68 from VINDALOO. Databases were available for both trials; additional data were collected. Multivariate logistic regression was used to analyse risk factors for ARDS and postoperative complications in the cohorts combined. RESULTS: Logistic regression analysis showed active smoking was associated with an increase in ARDS (OR 3.91; 95% CI 1.33 to 11.5) and dihydropyridine use (OR 5.34;95% CI 1.56 to 18.3). Hospital length of stay was longer for those who took dihydropyridines (median 29 days (IQR 17-42) vs 13 days (IQR 10-18), P=0.0007) or were diabetic (median 25 days (IQR 14-39) vs 13 (IQR 10-19), P=0.023) but not for current smokers (median in never/ex-smokers 13 (IQR 10-23) vs current smokers 15 (IQR 11-20), P=0.73). CONCLUSIONS: Smoking cessation trials should be promoted. Dihydropyridine effects perioperatively require further clinical and mechanistic evaluation. Patients undergoing oesophagectomy are a useful model for studying perioperative ARDS.