| 1. |
- Brown, J L, et al.
(författare)
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Lower airways inflammation in allergic rhinitics : a comparison with asthmatics and normal controls
- 2007
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 37:5, s. 688-695
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic rhinitis (AR) and asthma represent a continuum of atopic disease. AR is believed to pre‐dispose an individual to asthma. Compared with asthmatics and normal controls, the inflammatory response in the lower airways of rhinitics is not fully elucidated. To test the hypothesis that the inflammatory response in the airways of subjects with AR is at a level intermediate between that in normal controls and asthmatics, we have characterized bronchial inflammation and cytokine mRNA levels in non‐asthmatic allergic rhinitics and compared it with subjects with allergic asthma and with normal controls.Methods: Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into glycol methacrylate resin for immunohistochemical analysis of cellular inflammation and snap frozen for semi‐quantitative PCR analysis of cytokine mRNA levels.Results: Airway inflammation in rhinitic subjects was characterized by an increase in submucosal eosinophils, mast cells and the mRNA expression of TNF‐α, at an intermediate level between healthy and asthmatics. In addition, CD3+ and CD8+ lymphocytes in the epithelium, the endothelial expression of vascular adhesion molecule‐1 and IL‐1β mRNA were higher in the allergic rhinitics compared with both normal controls and asthmatics, whereas growth‐related oncogene α‐mRNA was decreased in AR compared with both healthy and asthmatics. Airway inflammation in the asthmatic group was characterized by higher numbers of eosinophils and mast cells, together with an increase in TNF‐α‐mRNA compared with both healthy and rhinitics. IFN‐γ mRNA was the highest in normal controls and lowest in the asthmatics.Conclusions: In individuals with AR the present data suggest an intermediate state of airway inflammation between that observed in normal individuals and subjects with clinical asthma. It is also indicated that IFN‐γ production by CD8+ T lymphocytes could be protective against the development of airway hyperresponsiveness. Further work is needed to evaluate this hypothesis.
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| 2. |
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| 3. |
- Friberg, Maria, 1979-, et al.
(författare)
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Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response
- 2023
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Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- 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 2-related factor 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) versus post-filtered air in a randomized double blind study, 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 AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed.Results: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression.Conclusion: These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.
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| 4. |
- Stenfors, Nikolai, et al.
(författare)
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Ozone exposure enhances mast-cell inflammation in asthmatic airways despite inhaled corticosteroid therapy.
- 2010
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Ingår i: Inhalation Toxicology. - : Informa Healthcare. - 0895-8378 .- 1091-7691. ; 22:2, s. 133-139
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Tidskriftsartikel (refereegranskat)abstract
- Asthmatics are recognised to be more susceptible than healthy individuals to adverse health effects caused by exposure to the common air pollutant ozone. Ozone has been reported to induce airway neutrophilia in mild asthmatics, but little is known about how it affects the airways of asthmatic subjects on inhaled corticosteroids. We hypothesised that ozone exposure would exacerbate the pre-existent asthmatic airway inflammation despite regular inhaled corticosteroid treatment. Therefore, we exposed subjects with persistent asthma on inhaled corticosteroid therapy to 0.2 ppm ozone or filtered air for 2 h, on 2 separate occasions. Lung function was evaluated before and immediately after exposure, while bronchoscopy was performed 18 h post exposure. Compared to filtered air, ozone exposure increased airway resistance. Ozone significantly enhanced neutrophil numbers and myeloperoxidase levels in airway lavages, and induced a fourfold increase in bronchial mucosal mast cell numbers. The present findings indicate that ozone worsened asthmatic airway inflammation and offer a possible biological explanation for the epidemiological findings of increased need for rescue medication and hospitalisation in asthmatic people following exposure to ambient ozone.
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| 5. |
- Torén, Kjell, 1952, et al.
(författare)
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Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study
- 2020
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Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(<5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(<5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(>= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.
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| 6. |
- Bosson, Jenny A, et al.
(författare)
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Peripheral blood neutrophilia as a biomarker of ozone-induced pulmonary inflammation
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ozone concentrations are predicted to increase over the next 50 years due to global warming and the increased release of precursor chemicals. It is therefore urgent that good, reliable biomarkers are available to quantify the toxicity of this pollutant gas at the population level. Such a biomarker would need to be easily performed, reproducible, economically viable, and reflective of ongoing pathological processes occurring within the lung.METHODOLOGY: We examined whether blood neutrophilia occurred following a controlled ozone challenge and addressed whether this could serve as a biomarker for ozone-induced airway inflammation. Three separate groups of healthy subjects were exposed to ozone (0.2 ppm, 2h) and filtered air (FA) on two separate occasions. Peripheral blood samples were collected and bronchoscopy with biopsy sampling and lavages was performed at 1.5h post exposures in group 1 (n=13), at 6h in group 2 (n=15) and at 18h in group 3 (n=15). Total and differential cell counts were assessed in blood, bronchial tissue and airway lavages.RESULTS: In peripheral blood, we observed fewer neutrophils 1.5h after ozone compared with the parallel air exposure (-1.1±1.0x10(9) cells/L, p<0.01), at 6h neutrophil numbers were increased compared to FA (+1.2±1.3x10(9) cells/L, p<0.01), and at 18h this response had fully attenuated. Ozone induced a peak in neutrophil numbers at 6h post exposure in all compartments examined, with a positive correlation between the response in blood and bronchial biopsies.CONCLUSIONS: These data demonstrate a systemic neutrophilia in healthy subjects following an acute ozone exposure, which mirrors the inflammatory response in the lung mucosa and lumen. This relationship suggests that blood neutrophilia could be used as a relatively simple functional biomarker for the effect of ozone on the lung.
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| 7. |
- Gouveia-Figueira, Sandra C., et al.
(författare)
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Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust
- 2018
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Ingår i: Analytica Chimica Acta. - : Elsevier. - 0003-2670 .- 1873-4324. ; 1018, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF(2 alpha), 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p < 0.003). Hence, the majority of the responsive lipid metabolites were monohydroxy fatty acids. We conclude that it is possible to detect alterations in circulating bioactive lipid metabolites in response to biodiesel exhaust exposure using LC-MS/MS, with emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes.
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| 8. |
- Gouveia-Figueira, Sandra, et al.
(författare)
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Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure
- 2017
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Ingår i: Analytical and Bioanalytical Chemistry. - : SPRINGER HEIDELBERG. - 1618-2642 .- 1618-2650. ; 409:11, s. 2967-2980
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu g/m(3)) 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, Nacylethanolamines, and related lipid metabolites in the collected BWand 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.
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| 9. |
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| 10. |
- Kumar, Abhinav, et al.
(författare)
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Differences in the coronal proteome acquired by particles depositing in the lungs of asthmatic versus healthy humans
- 2017
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Ingår i: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 13:8, s. 2517-2521
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Tidskriftsartikel (refereegranskat)abstract
- Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLFs). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative profile of the RTLF proteome and provided insight into the evolved corona; information that may be used in future to improve drug targeting to the lungs by inhaled medicines. The asthmatic coronal proteome displayed a reduced contribution of surfactant proteins (SP-A and B) and a higher contribution of α1-antitrypsin. Pathway analysis suggested that asthmatic RTLFs may also be deficient in proteins related to metal handling (e.g. lactoferrin). This study demonstrates how the composition of the corona acquired by inhaled nanoparticles is modified in asthma and suggests depressed mucosal immunity even in mild airway disease.
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