Abstract:Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals.Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic indi… Show more
“…LOX products dominated the oxylipin profile, together with CYP metabolites (around 50% of the content for each pathway) in BAL, while LOX metabolites alone were present at the highest relative concentrations in BW (around 75%). Furthermore, BW contained higher levels of oxylipins than BAL, in agreement with Larsson et al [42]. COX products constituted only 5 of 41 oxylipins in the analytical panel and thereby comprised the smallest fraction of the compounds detected.Fig.…”
Section: Resultssupporting
confidence: 90%
“…Analytes that were responsible for the separation in Fig. 8a were mainly 9(10)-EpOME and 12(13)-EpOME (BAL), as well as 13-HODE and 15-HETE (BW); this finding matches the results from previous studies of healthy individuals [42]. The major N -acylethanolamines responsible for the separation were OEA and SEA which were present at higher concentrations in BW than in BAL (Fig.…”
Section: Resultssupporting
confidence: 88%
“…Similar to what was described by Larsson et al [42], it was possible to group samples by lung compartment in separate clusters of BW and BAL samples obtained by a significant OPLS-DA model based on analytes found in 75% of BW or BAL samples (CV-ANOVA = 0.0002, Fig. 7).…”
Section: Resultsmentioning
confidence: 64%
“…Significant differences (Wilcoxon test with α = 0.05) are marked in bold and significant ones after Bonferroni correction ( P value <0.002) are italicized. A comparison was made with literature data on lipid concentrations when present [42, 44]BALBWBAL vs BW
P value
Filtered airBioDE
P value
Filtered airBioDE
P value
Filtered airBioDERef [42]Ref [44]MedianIQRRangeMedianIQRRangeMedianIQRRangeMedianIQRRangeBALBWBALOxylipins Arachidonic acid (20:4n6) derivatives ( n = 11) TXB 2
5.67.52.2–196.8102.1–490.612113.5–36179.50–550.1
0.04
0.264 6-ketoPGF 1α
a
–
–
–
–
–
–
n.a. 4.14.40–153.81.21.8–140.2
n.a.…”
The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m3) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-017-0243-8) contains supplementary material, which is available to authorized users.
“…LOX products dominated the oxylipin profile, together with CYP metabolites (around 50% of the content for each pathway) in BAL, while LOX metabolites alone were present at the highest relative concentrations in BW (around 75%). Furthermore, BW contained higher levels of oxylipins than BAL, in agreement with Larsson et al [42]. COX products constituted only 5 of 41 oxylipins in the analytical panel and thereby comprised the smallest fraction of the compounds detected.Fig.…”
Section: Resultssupporting
confidence: 90%
“…Analytes that were responsible for the separation in Fig. 8a were mainly 9(10)-EpOME and 12(13)-EpOME (BAL), as well as 13-HODE and 15-HETE (BW); this finding matches the results from previous studies of healthy individuals [42]. The major N -acylethanolamines responsible for the separation were OEA and SEA which were present at higher concentrations in BW than in BAL (Fig.…”
Section: Resultssupporting
confidence: 88%
“…Similar to what was described by Larsson et al [42], it was possible to group samples by lung compartment in separate clusters of BW and BAL samples obtained by a significant OPLS-DA model based on analytes found in 75% of BW or BAL samples (CV-ANOVA = 0.0002, Fig. 7).…”
Section: Resultsmentioning
confidence: 64%
“…Significant differences (Wilcoxon test with α = 0.05) are marked in bold and significant ones after Bonferroni correction ( P value <0.002) are italicized. A comparison was made with literature data on lipid concentrations when present [42, 44]BALBWBAL vs BW
P value
Filtered airBioDE
P value
Filtered airBioDE
P value
Filtered airBioDERef [42]Ref [44]MedianIQRRangeMedianIQRRangeMedianIQRRangeMedianIQRRangeBALBWBALOxylipins Arachidonic acid (20:4n6) derivatives ( n = 11) TXB 2
5.67.52.2–196.8102.1–490.612113.5–36179.50–550.1
0.04
0.264 6-ketoPGF 1α
a
–
–
–
–
–
–
n.a. 4.14.40–153.81.21.8–140.2
n.a.…”
The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m3) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE2, 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-017-0243-8) contains supplementary material, which is available to authorized users.
“…Asthma is a complex disease characterized by inflammation throughout the respiratory tract from the large airways to the alveoli. Quantification of lipid metabolites in different regions of the lung, of asthmatics and healthy controls, demonstrated that most differences in the formation of 15-LO-1 derived mediators were detected in the proximal airways and not in BALF [35].…”
Metabolomics protocols are used to comprehensively characterize the metabolite content of biological samples by exploiting cutting-edge analytical platforms, such as gas chromatography (GC) or liquid chromatography (LC) coupled to mass spectrometry (MS) assays, as well as nuclear magnetic resonance (NMR) assays. We have developed novel sample preparation procedures combined with GC-MS, LC-MS, and NMR metabolomics profiling for analyzing bronchial wash (BW) and bronchoalveolar lavage (BAL) fluid from 15 healthy volunteers following exposure to biodiesel exhaust and filtered air. Our aim was to investigate the responsiveness of metabolite profiles in the human lung to air pollution exposure derived from combustion of biofuels, such as rapeseed methyl ester biodiesel, which are increasingly being promoted as alternatives to conventional fossil fuels. Our multi-platform approach enabled us to detect the greatest number of unique metabolites yet reported in BW and BAL fluid (82 in total). All of the metabolomics assays indicated that the metabolite profiles of the BW and BAL fluids differed appreciably, with 46 metabolites showing significantly different levels in the corresponding lung compartments. Furthermore, the GC-MS assay revealed an effect of biodiesel exhaust exposure on the levels of 1-monostearylglycerol, sucrose, inosine, nonanoic acid, and ethanolamine (in BAL) and pentadecanoic acid (in BW), whereas the LC-MS assay indicated a shift in the levels of niacinamide (in BAL). The NMR assay only identified lactic acid (in BW) as being responsive to biodiesel exhaust exposure. Our findings demonstrate that the proposed multi-platform approach is useful for wide metabolomics screening of BW and BAL fluids and can facilitate elucidation of metabolites responsive to biodiesel exhaust exposure. Graphical Abstract Graphical abstract illustrating the study workflow. NMR Nuclear Magnetic Resonance, LC-TOFMS Liquid chromatography-Time Of Flight Mass Spectrometry, GC Gas Chromatography-Mass spectrometry.
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