Pulmonary injury associated with spray of a water-based nano-sized waterproofing product: a case study

Abstract Background In most reported cases of lung trauma with water proofing products, volatile organic compounds (VOC) have a prominent role. Here we report on a case involving ten workers exposed to a sprayed product containing nanoparticles in a water solution with only a few percent VOC. Case presentation Ten workers suffered from respiratory symptoms following spray impregnation of hardwood furniture using a waterproofing product that contained positively charged fluorinated acrylate copolymer solid cores with a median diameter of 70 nm (1.3 w%) in aqueous suspension with 3.3 w% VOC and 0.3 w% quaternary ammonium. The worker who applied one liter of the product in a wood workshop, using an air mix spray gun, did not report any health complaints. Another worker, who entered the workshop 3 h later and had rolled and smoked two cigarettes, was hospitalized with severe chemical pneumonitis. A chest X-ray (CXR) showed bilateral infiltrative impairment in the lower lobe regions. On the next day a second CXR showed increased patchiness marking in all fields. A high-resolution Computer Tomography (CT)-scan demonstrated extensive bilateral areas of ground-glass opacities predominantly in the lower regions of the upper lobes, the right middle lobe and the apical regions of the lower lobes, compatible with severe chemical pneumonitis. On the following morning, nine workers in an adjacent workplace in the same building, experienced dry cough, chest tightness and substernal pain upon physical exercise. Reconstruction of the spray application in a climate chamber confirmed trimethyl silanol, glycol ethers and fluoroalkenes in the gas phase. Immediately after the spray application, aerosols were observed at a maximum concentration of 6.3 × 104 cm−3. Mass concentrations were 0.095 and 10 mg/m3 in the size ranges 5.6-560 nm and 0.22-30 μm, respectively, decreasing to less than 10 μg/m3 in both size ranges after 15 h. Conclusion The hospitalized worker had smoked cigarettes contaminated with fluoropolymers which is a plausible explanation for the lung trauma. Respiratory symptoms in the nine workers may be caused by inhalation of particles that became airborne by resuspension from surfaces when workers entered the adjacent workplace the next day. A contribution from VOC appears less likely because measurements and modelling showed that concentrations in the mg/m3 range could have occurred only if the building was assumed to be completely airtight

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer

Objectives: As suggested by in-vitro data, we hypothesize that subtypes of ICRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Methods: Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinumbased chemotherapy, were retrieved from hospital databases. Primary objective: to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. Results: 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of ICRAS mutation were G12C (46%), G12V (20%) and G1 2D (10%). Platinum was combined with pemetrexed (n =334), taxanes (n = 68) or gemcitabine (n = 62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; p <0.01). Patients treated with bevacizumab in addition to taxanes (n =38) had the highest ORR (62%). The PFS was significantly improved in patients treated with taxanes compared to pemetrexed (HR = 0.72, p = 0.02), but not OS (HR= 0.87, p = 0.41). In patients with G12V, significantly improved ORR (p <0.01) was observed for taxanes, but not PFS or OS. Patients with G1 2C or G12D mutation had comparable ORR, PFS and OS in all treatment groups. Conclusion: KRAS mutated NSCLC patients treated with taxane-based chemotherapy had best ORR Response to chemotherapy regimens was different in types of ICRAS mutation. Especially patients with G12V had better response to taxane treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved