BackgroundExposure to diesel exhaust causes inflammatory responses. Previous controlled exposure studies at a concentration of 300 μg/m3 of diesel exhaust particles mainly lasted for 1 h. We prolonged the exposure period and investigated how quickly diesel exhaust can induce respiratory and systemic effects.MethodsEighteen healthy volunteers were exposed twice to diluted diesel exhaust (PM1 ~300 μg/m3) and twice to filtered air (PM1 ~2 μg/m3) for 3 h, seated, in a chamber with a double-blind set-up. Immediately before and after exposure, we performed a medical examination, spirometry, rhinometry, nasal lavage and blood sampling. Nasal lavage and blood samples were collected again 20 h post-exposure. Symptom scores and peak expiratory flow (PEF) were assessed before exposure, and at 15, 75, and 135 min of exposure.ResultsSelf-rated throat irritation was higher during diesel exhaust than filtered air exposure. Clinical signs of irritation in the upper airways were also significantly more common after diesel exhaust exposure (odds ratio=3.2, p<0.01). PEF increased during filtered air, but decreased during diesel exhaust exposure, with a statistically significant difference at 75 min (+4 L/min vs. -10 L/min, p=0.005). Monocyte and total leukocyte counts in peripheral blood were higher after exposure to diesel exhaust than filtered air 20 h post-exposure, and a trend (p=0.07) towards increased serum IL-6 concentrations was also observed 20 h post-exposure.ConclusionsDiesel exhaust induced acute adverse effects such as symptoms and signs of irritation, decreased PEF, inflammatory markers in healthy volunteers. The effects were first seen at 75 min of exposure.

BackgroundSerum protein profiles have been investigated frequently to discover early biomarkers for breast cancer. So far, these studies used biological samples collected at or after diagnosis. This may limit these studies' value in the search for cancer biomarkers because of the often advanced tumor stage, and consequently risk of reverse causality. We present for the first time pre-diagnostic serum protein profiles in relation to breast cancer, using the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition) cohort.MethodsIn a nested case-control design we compared 68 women diagnosed with breast cancer within three years after enrollment, with 68 matched controls for differences in serum protein profiles. All samples were analyzed with SELDI-TOF MS (surface enhanced laser desorption/ionization time-of-flight mass spectrometry). In a subset of 20 case-control pairs, the serum proteome was identified and relatively quantified using isobaric Tags for Relative and Absolute Quantification (iTRAQ) and online two-dimensional nano-liquid chromatography coupled with tandem MS (2D-nanoLC-MS/MS).ResultsTwo SELDI-TOF MS peaks with m/z 3323 and 8939, which probably represent doubly charged apolipoprotein C-I and C3a des-arginine anaphylatoxin (C3adesArg), were higher in pre-diagnostic breast cancer serum (p = 0.02 and p = 0.06, respectively). With 2D-nanoLC-MS/MS, afamin, apolipoprotein E and isoform 1 of inter-alpha trypsin inhibitor heavy chain H4 (ITIH4) were found to be higher in pre-diagnostic breast cancer (p < 0.05), while alpha-2-macroglobulin and ceruloplasmin were lower (p < 0.05). C3adesArg and ITIH4 have previously been related to the presence of symptomatic and/or mammographically detectable breast cancer.ConclusionsWe show that serum protein profiles are already altered up to three years before breast cancer detection.

ObjectivesOccupational exposure to particulate air pollution has been associated with an increased risk of cardiovascular disease. However, the risk to welders working today remains unclear. We aimed to elucidate the cardiovascular effects of exposure to welding fumes.MethodsIn a cross-sectional study, structured interviews and biological sampling were conducted for 101 welders and 127 controls (all non-smoking males) from southern Sweden. Personal breathing zone sampling of respirable dust was performed. Blood pressure (BP) and endothelial function (using peripheral arterial tonometry) were measured. Plasma and serum samples were collected from peripheral blood for measurement of C-reactive protein, low-density lipoprotein, homocysteine, serum amyloid A, and cytokines.ResultsWelders were exposed to 10-fold higher levels of particles than controls. Welders had significantly higher BP compared to controls, an average of 5 mm Hg higher systolic and diastolic BP (P≤0.001). IL-8 was 3.4 ng/L higher in welders (P=0.010). Years working as a welder were significantly associated with increased BP (β=0.35, 95%CI 0.13 – 0.58, P=0.0024 for systolic BP; β=0.32, 95%CI 0.16 – 0.48, P<0.001 for diastolic BP, adjusted for BMI) but exposure to respirable dust was not associated with BP. No clear associations occurred between welding and endothelial function, or other effect markers.ConclusionsA modest increase in BP was found among welders compared to controls suggesting that low-to-moderate exposure to welding fumes remains a risk factor for cardiovascular disease.

BackgroundAlthough it has recently been recognised that inflammation is important in the development of work-related musculoskeletal disorders (MSDs), the exact pathophysiological pathways are unknown.MethodsWe investigated serum concentrations of inflammatory cytokines in 35 female supermarket cashiers with repetitive work tasks and work related neck/shoulder complaints, compared with those from 25 women without MSDs (6 supermarket cashiers and 19 middle-school teachers or faculty staff). None of the subjects were pregnant or lactating, and showed no signs of rheumatoid arthritis, systemic lupus erythematosus, cancer, diabetes, coronary artery disease or inadequately controlled hypertension. Serum levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, MCP-1, MIP-1α, MIP-1β, TNF-α, GM-CSF, CTGF and CRP were analysed.ResultsThe women with pain related to MSD had higher serum concentrations of MIP-1β (median, 25th-75th percentile: 90.0 pg/mL, 62.5-110 vs. 73.1 pg/mL, 54.6-88.3; p = 0.018), IL-12 (0.26 pg/mL, 0.26-0.26 vs. 0.26 pg/mL, 0.26-0.26; p = 0.047) and CRP (0.5 mg/L, 0.5-1.6 vs. 0.5 mg/L, 0.5-0.5; p = 0.003), than control subjects. Levels of MIP-1α, MIP-1β and CRP were correlated with the reported intensity of neck/shoulder pain (r = 0.29, p = 0.03 for MIP-1α; r = 0.29, p = 0.02 for MIP-1β and r = 0.43, p = 0.001 for CRP). No statistically significant differences in serum levels were found for the remaining cytokines.ConclusionsOtherwise healthy females with ongoing work-related neck/shoulder pain showed higher serum concentrations of MIP-1β, IL-12 and CRP than controls, and the levels of MIP-1α, MIP-1β and CRP were correlated to pain intensity. These results support previous findings that inflammatory processes play a part in work related MSDs.

Proteomic-based studies of nasal lavage fluid (NLF) may identify molecular pathways associated with disease pathology and new biomarker candidates of upper airway diseases. However, most studies have used rather tedious untargeted MS techniques. Selected reaction monitoring (SRM) is a sensitive and specific technique that can be used with high throughput. In this study, we developed a semiquantitative SRM-based method targeting 244 NLF proteins. The protein set was identified through a literature study in combination with untargeted LC-MS/MS analyses of trypsin-digested NLF samples. The SRM assays were designed using MS/MS data either downloaded from a proteomic data repository or experimentally obtained. Each protein is represented by one to five peptides, resulting in 708 SRM assays. Three to four transitions per assay were used to ensure analyte specificity. The majority (69%) of the assays showed good within-day precision (coefficient of variation ≤ 20%). The accuracy of the method was evaluated by analyzing four samples prepared with varying amounts of four proteins. Peptide and protein ratios were in good agreement with expected ratios. In conclusion, a high throughput screening method for relative quantification of 244 NLF proteins was developed. The method should be of general use in any proteomic study of the upper airways.