Background: Exposure to wood smoke has been shown to contribute to adverse respiratory health eff... more Background: Exposure to wood smoke has been shown to contribute to adverse respiratory health effects including airway infections, but the underlying mechanisms are yet unclear. A preceding study failed to confirm any acute inflammation or cell influx in bronchial wash (BW) or bronchoalveolar lavage (BAL) 24 h after wood smoke exposure but showed unexpected reductions in leukocyte numbers. The present study was performed to investigate responses at an earlier phase, regarding potential development of acute inflammation, as well as indications of cytotoxicity. Methods: In a double-blind, randomised crossover study, 14 healthy participants were exposed for 2h to filtered air and diluted wood smoke from incomplete wood log combustion in a common wood stove with a mean particulate matter concentration of 409 µg/m3. Bronchoscopy with BW and BAL was performed 6 hours after exposure. Differential cell counts, assessment of DNA-damage and ex vivo analysis of phagocytic function of phagocyto...
Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed h... more Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. Methods Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3), as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (Cyp1A1) and subfamily B, Polypeptide 1 (Cyp1B1) were examined to confirm ...
Background Snus usage is commonly touted as a safer alternative to cigarette smoking. However, re... more Background Snus usage is commonly touted as a safer alternative to cigarette smoking. However, recent studies have demonstrated possible adverse cardiovascular effects in chronic snus users. The present study evaluates the effects of chronic snus use on vascular function by assessing central arterial stiffness and endothelial vasodilatory function in healthy chronic snus users as compared to matched non-users. Methods and results Fifty healthy males (24 snus users, 26 age-matched controls) with a mean age of 44 years were included in the study. Arterial stiffness was assessed employing both pulse wave velocity and pulse wave analysis. Endothelial vasodilatory function was measured by venous occlusion plethysmography, utilizing intra-arterial administration of acetylcholine, glyceryl trinitrate and bradykinin to further gauge endothelium-dependent and -independent vasodilatory function. Arterial stiffness was significantly higher in chronic snus users as compared to controls: pulse w...
Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a ... more Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is not yet well understood. We hypothesized that oxylipin release from lung injury could be detected in bronchoalveolar lavage fluid and in plasma. In a porcine model of surfactant depletion, ventilation with hyperinflation was assessed. Bronchoalveolar lavage and plasma samples were analyzed for 37 different fatty acid metabolites (oxylipins). Over time, hyperinflation altered concentrations of 4 oxylipins in plasma (TXB2, PGE2, 15-HETE and 11-HETE), and 9 oxylipins in bronchoalveolar lavage fluid (PGF2α, PGE2, PGD2, 12,13-DiHOME, 11,12-DiHETrE, 13-HODE, 9-HODE, 15-HETE, 11-HETE). Acute lung injury caused by high tidal volume ventilation in this porcine model was associated with rapid changes in some elements of the oxylipin profile, detectable in lavage fluid, and plasma. These oxylipins may be relevant in the pathogenesis of acute lung injury by hyperinflation.
Lung function data from 14 subjects before (pre), immediately after (post) and 24 h after experim... more Lung function data from 14 subjects before (pre), immediately after (post) and 24 h after experimental exposure to filtered air and wood smoke. Data are given as mean with ± SD. (DOCX 46 kb)
FENO data from 14 healthy subjects sampled before (pre), immediately after (post) and 24 h after ... more FENO data from 14 healthy subjects sampled before (pre), immediately after (post) and 24 h after experimental exposure to filtered air and wood smoke. Data are given as mean with ± SD. (DOCX 45 kb)
Scatterplot of inflammatory cells in the bronchial epithelium after air and wood smoke exposure. ... more Scatterplot of inflammatory cells in the bronchial epithelium after air and wood smoke exposure. (PDF 49 kb)
Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to f... more Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb)
Table S1a. Differential cell counts of leukocytes of in BAL fluid, given in number of cells/ml*10... more Table S1a. Differential cell counts of leukocytes of in BAL fluid, given in number of cells/ml*104. Table S1b. Differential cell counts of leukocytes of in BAL fluid, given in percent. Table S2. Flow cytometry analysis of lymphocytes in BAL fluid, given in percent. Table S3. Flow cytometry analysis of NKT-like cell subpopulations in BAL fluid, given in percent. (DOCX 28â kb)
Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease... more Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease worldwide. The mechanisms by which wood smoke exhibits its effects on human health are not well und ...
American Journal of Respiratory and Critical Care Medicine, 2016
Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Rep... more Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies
Vitamin C (ascorbate, AscH2 + dehydroascorbate, DHA) is an important low-molecular weight antioxi... more Vitamin C (ascorbate, AscH2 + dehydroascorbate, DHA) is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role, little is known about its transport and the regulation of intra-cellular concentrations in the lung. Whilst several vitamin C transporters are identified, such as sodium-ascorbate co-transporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting the AscH2 oxidation product DHA, knowledge of their presence and distribution in the human lung is limited (GLUTs) or unknown (SVCTs). We hypothesised that these transporters are present within the bronchial airways and play a vital role in the regulation of epithelial and respiratory tract lining fluid vitamin C concentrations. We investigated the distribution of these transporters in endobronchial biopsies obtained by bronchoscopy from 16 mild asthmatics and 16 age-matched healthy controls. Positive staining was found in blood vessels for SVCT1 and 2; with SVCT 2 and G...
Background: Exposure to wood smoke has been shown to contribute to adverse respiratory health eff... more Background: Exposure to wood smoke has been shown to contribute to adverse respiratory health effects including airway infections, but the underlying mechanisms are yet unclear. A preceding study failed to confirm any acute inflammation or cell influx in bronchial wash (BW) or bronchoalveolar lavage (BAL) 24 h after wood smoke exposure but showed unexpected reductions in leukocyte numbers. The present study was performed to investigate responses at an earlier phase, regarding potential development of acute inflammation, as well as indications of cytotoxicity. Methods: In a double-blind, randomised crossover study, 14 healthy participants were exposed for 2h to filtered air and diluted wood smoke from incomplete wood log combustion in a common wood stove with a mean particulate matter concentration of 409 µg/m3. Bronchoscopy with BW and BAL was performed 6 hours after exposure. Differential cell counts, assessment of DNA-damage and ex vivo analysis of phagocytic function of phagocyto...
Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed h... more Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. Methods Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3), as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (Cyp1A1) and subfamily B, Polypeptide 1 (Cyp1B1) were examined to confirm ...
Background Snus usage is commonly touted as a safer alternative to cigarette smoking. However, re... more Background Snus usage is commonly touted as a safer alternative to cigarette smoking. However, recent studies have demonstrated possible adverse cardiovascular effects in chronic snus users. The present study evaluates the effects of chronic snus use on vascular function by assessing central arterial stiffness and endothelial vasodilatory function in healthy chronic snus users as compared to matched non-users. Methods and results Fifty healthy males (24 snus users, 26 age-matched controls) with a mean age of 44 years were included in the study. Arterial stiffness was assessed employing both pulse wave velocity and pulse wave analysis. Endothelial vasodilatory function was measured by venous occlusion plethysmography, utilizing intra-arterial administration of acetylcholine, glyceryl trinitrate and bradykinin to further gauge endothelium-dependent and -independent vasodilatory function. Arterial stiffness was significantly higher in chronic snus users as compared to controls: pulse w...
Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a ... more Inflammatory signaling pathways involving eicosanoids and other regulatory lipid mediators are a subject of intensive study, and a role for these in acute lung injury is not yet well understood. We hypothesized that oxylipin release from lung injury could be detected in bronchoalveolar lavage fluid and in plasma. In a porcine model of surfactant depletion, ventilation with hyperinflation was assessed. Bronchoalveolar lavage and plasma samples were analyzed for 37 different fatty acid metabolites (oxylipins). Over time, hyperinflation altered concentrations of 4 oxylipins in plasma (TXB2, PGE2, 15-HETE and 11-HETE), and 9 oxylipins in bronchoalveolar lavage fluid (PGF2α, PGE2, PGD2, 12,13-DiHOME, 11,12-DiHETrE, 13-HODE, 9-HODE, 15-HETE, 11-HETE). Acute lung injury caused by high tidal volume ventilation in this porcine model was associated with rapid changes in some elements of the oxylipin profile, detectable in lavage fluid, and plasma. These oxylipins may be relevant in the pathogenesis of acute lung injury by hyperinflation.
Lung function data from 14 subjects before (pre), immediately after (post) and 24 h after experim... more Lung function data from 14 subjects before (pre), immediately after (post) and 24 h after experimental exposure to filtered air and wood smoke. Data are given as mean with ± SD. (DOCX 46 kb)
FENO data from 14 healthy subjects sampled before (pre), immediately after (post) and 24 h after ... more FENO data from 14 healthy subjects sampled before (pre), immediately after (post) and 24 h after experimental exposure to filtered air and wood smoke. Data are given as mean with ± SD. (DOCX 45 kb)
Scatterplot of inflammatory cells in the bronchial epithelium after air and wood smoke exposure. ... more Scatterplot of inflammatory cells in the bronchial epithelium after air and wood smoke exposure. (PDF 49 kb)
Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to f... more Soluble components in the peripheral blood from experimental exposure of 14 healthy subjects to filtered air and wood smoke. Samples were collected before (pre), at 24 h and 44 h after exposure, to air and wood smoke. Data are given as medians with interquartile range. (DOCX 62 kb)
Table S1a. Differential cell counts of leukocytes of in BAL fluid, given in number of cells/ml*10... more Table S1a. Differential cell counts of leukocytes of in BAL fluid, given in number of cells/ml*104. Table S1b. Differential cell counts of leukocytes of in BAL fluid, given in percent. Table S2. Flow cytometry analysis of lymphocytes in BAL fluid, given in percent. Table S3. Flow cytometry analysis of NKT-like cell subpopulations in BAL fluid, given in percent. (DOCX 28â kb)
Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease... more Indoor smoke from combustion of solid biomass fuel is a major risk factor for respiratory disease worldwide. The mechanisms by which wood smoke exhibits its effects on human health are not well und ...
American Journal of Respiratory and Critical Care Medicine, 2016
Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Rep... more Increased Mmp-12 And Decreased Surfactant Protein A In The Airways Of Individuals With COPD - Report From A Bronchoscopy Investigation Based On The Obstructive Lung Disease In Northern Sweden (olin) Studies
Vitamin C (ascorbate, AscH2 + dehydroascorbate, DHA) is an important low-molecular weight antioxi... more Vitamin C (ascorbate, AscH2 + dehydroascorbate, DHA) is an important low-molecular weight antioxidant at the air-lung interface. Despite its critical role, little is known about its transport and the regulation of intra-cellular concentrations in the lung. Whilst several vitamin C transporters are identified, such as sodium-ascorbate co-transporters (SVCT1/2) and glucose transporters (GLUTs), the latter transporting the AscH2 oxidation product DHA, knowledge of their presence and distribution in the human lung is limited (GLUTs) or unknown (SVCTs). We hypothesised that these transporters are present within the bronchial airways and play a vital role in the regulation of epithelial and respiratory tract lining fluid vitamin C concentrations. We investigated the distribution of these transporters in endobronchial biopsies obtained by bronchoscopy from 16 mild asthmatics and 16 age-matched healthy controls. Positive staining was found in blood vessels for SVCT1 and 2; with SVCT 2 and G...
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Papers by Jamshid Pourazar