| 1. |
- Söderling, Ann-Sofi, et al.
(författare)
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A derivatization assay using gaschromatography/negative chemical ionization tandem mass spectrometry to quantify 3-nitrotyrosine in human plasma
- 2003
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Ingår i: J Mass Spectrom. ; 38:11
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Tidskriftsartikel (refereegranskat)abstract
- Endogenous free or protein-associated 3-nitrotyrosine (3-NT) has been proposed as a biomarker of in vivo oxidative damage caused by nitrating agents. Isotopic dilution assay gaschromatographic/mass spectrometric (GC/MS) techniques have been employed to measure endogenous 3-NT levels. However, the quantitative normal plasma values reported so far are inconsistent. The results vary between the assays; they may have been influenced by in vitro artifactual nitration of tyrosine to 3-NT. In this study, a simple and artifact-free derivatization method for quantifying the endogenous 3-NT content of biological samples by GC/negative chemical ionization MS/MS is presented. The method is based on reduction of the nitro group of the molecule by dithionite, heptafluorobutyric acylation and subsequent methyl derivatization, di-O-methyldi-N-heptafluorobutyryl being the major derivative. The results showed excellent GC and MS properties, such as low background and a favorable fragmentation pattern. Endogenous 3-NT was unequivocally quantified using collision-induced dissociation in the selected reaction monitoring mode, whereas co-elution of unknown compounds interfered in the selected-ion monitoring mode. We found that tyrosine was nitrated in the presence of nitrate anions and heptafluorobutyric anhydride, but the product appeared as a di-O-methylmono-N-heptafluorobutyryl derivative. Therefore, artifactually formed 3-NT did not contribute to the measured endogenous 3-NT level owing to its different derivative structure. The method was applied to determine endogenous 3-NT in human plasma and plasma proteins. A detection limit of 0.03 nM for (13)C(6)-labeled 3-NT in plasma samples was established and the response was linear over a concentration range of 0-50 nM (R(2) > 0.999). The endogenous free 3-NT level (mean +/- SD) in ultrafiltered plasma samples from 12 healthy adults was 0.74 +/- 0.30 nM. The mean concentration of 3-NT in their plasma total proteins was 0.60 +/- 0.40 pmol mg(-1). Hence, the described method is selective, eliminates the problem of artifactual nitration and is feasible for the quantification of free and protein-associated 3-NT in biological samples such as plasma.
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| 2. |
- Barnes, H., et al.
(författare)
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Occupation versus environmental factors in hypersensitivity pneumonitis: population attributable fraction
- 2020
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Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite well-documented case series of hypersensitivity pneumonitis (HP), epidemiological data delineating relative contributions of risk factors are sparse. To address this, we estimated HP risk in a case-referent study of occupational and nonoccupational exposures. Methods: We recruited cases of HP by ICD-9 codes from an integrated healthcare delivery system (IHCDS) and a tertiary medical care centre. We drew referents, matched for age and sex, from the IHCDS. Participants underwent comprehensive, structured telephone interviews eliciting details of occupational and home environmental exposures. We employed a hierarchical analytic approach for data reduction based on the false discovery rate method within clusters of exposures. We measured lung function and selected biomarkers in a subset of participants. We used multivariate logistic regression to estimate exposure-associated odds ratios (ORs) and population attributable fractions (PAFs) for HP. Results: We analysed data for 192 HP cases (148 IHCDS; 44 tertiary care) and 229 referents. Occupational exposures combined more than doubled the odds of developing HP (OR 2.67; 95% CI 1.73-4.14) with a PAF of 34% (95% CI 21-46%); nonoccupational bird exposure also doubled the HP odds (OR 2.02; 95% CI 1.13-3.60), with a PAF of 12% (3-21%). Lung function and selected biomarkers did not substantively modify the risk estimates on the basis of questionnaire data alone. Discussion: In a case-referent approach evaluating HP risk, identifiable exposures accounted, on an epidemiological basis, for approximately two in three cases of disease; conversely, for one in three, the risk factors for disease remained elusive.
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| 3. |
- Larsson, Per, et al.
(författare)
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Exhaled particles as markers of small airway inflammation in subjects with asthma
- 2017
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961. ; 37:5, s. 489-497
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Tidskriftsartikel (refereegranskat)abstract
- Exhaled breath contains suspended particles of respiratory tract lining fluid from the small airways. The particles are formed when closed airways open during inhalation. We have developed a method called Particles in Exhaled air (PExA((R))) to measure and sample these particles in the exhaled aerosol. Here, we use the PExA((R)) method to study the effects of birch pollen exposure on the small airways of individuals with asthma and birch pollen allergy. We hypothesized that birch pollen-induced inflammation could change the concentrations of surfactant protein A and albumin in the respiratory tract lining fluid of the small airways and influence the amount of exhaled particles. The amount of exhaled particles was reduced after birch pollen exposure in subjects with asthma and birch pollen allergy, but no significant effect on the concentrations of surfactant protein A and albumin in exhaled particles was found. The reduction in the number of exhaled particles may be due to inflammation in the small airways, which would reduce their diameter and potentially reduce the number of small airways that open and close during inhalation and exhalation.
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| 4. |
- Larsson, Per, et al.
(författare)
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The effect of exhalation flow on endogenous particle emission and phospholipid composition
- 2017
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048. ; 243, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- Exhaled particles constitute a micro-sample of respiratory tract lining fluid. Inhalations from low lung volumes generate particles in small airways by the airway re-opening mechanism. Forced exhalations are assumed to generate particles in central airways by mechanisms associated with high air velocities. To increase knowledge on how and where particles are formed, different breathing manoeuvres were compared in 11 healthy volunteers. Particles in the 0.41-4.55 mu m diameter range were characterised and sampled. The surfactant lipid dipalmitoylphosphatidylcholine (DPPC) was quantified by mass spectrometry. The mass of exhaled particles increased by 150% (95% CI 10-470) for the forced exhalation and by 470% (95% CI 150-1190) for the airway re-opening manoeuvre, compared to slow exhalations. DPPC weight percent concentration (wt%) in particles was 2.8 wt% (95%CI 1.4-4.2) and 9.4 wt% (95%CI 8.0-10.8) for the forced and the airway re-opening manoeuvres, respectively. In conclusion, forced exhalation and airway re-opening manoeuvres generate particles from different airway regions having different DPPC concentration.
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| 5. |
- Lärstad, Mona, 1971, et al.
(författare)
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Determination of ethane, pentane and isoprene in exhaled air--effects of breath-holding, flow rate and purified air
- 2007
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Ingår i: Acta Physiol (Oxf). - : Wiley. - 1748-1708. ; 189:1, s. 87-98
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Exhaled ethane, pentane and isoprene have been proposed as biomarkers of oxidative stress. The objectives were to explore whether ethane, pentane and isoprene are produced within the airways and to explore the effect of different sampling parameters on analyte concentrations. METHODS: The flow dependency of the analyte concentrations, the concentrations in dead-space and alveolar air after breath-holding and the influence of inhaling purified air on analyte concentrations were investigated. The analytical method involved thermal desorption from sorbent tubes and gas chromatography. The studied group comprised 13 subjects with clinically stable asthma and 14 healthy controls. RESULTS: Ethane concentrations decreased slightly, but significantly, at higher flow rates in subjects with asthma (P = 0.0063) but not in healthy controls. Pentane levels were increased at higher flow rates both in healthy and asthmatic subjects (P = 0.022 and 0.0063 respectively). Isoprene levels were increased at higher flow rates, but only significantly in healthy subjects (P = 0.0034). After breath-holding, no significant changes in ethane levels were observed. Pentane and isoprene levels increased significantly after 20 s of breath-holding. Inhalation of purified air before exhalation resulted in a substantial decrease in ethane levels, a moderate decrease in pentane levels and an increase in isoprene levels. CONCLUSION: The major fractions of exhaled ethane, pentane and isoprene seem to be of systemic origin. There was, however, a tendency for ethane to be flow rate dependent in asthmatic subjects, although to a very limited extent, suggesting that small amounts of ethane may be formed in the airways.
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| 6. |
- Lärstad, Mona, 1971
(författare)
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Exhaled markers of oxidative stress in the airways
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breath contains a number of different molecules, some of which may have potential use as markers for oxidative stress in the airways during chronic airway inflammation. The major objectives were to develop and validate methods for quantifying five potential exhaled markers of oxidative stress: malondialdehyde (MDA) and free 3-nitrotyrosine (3-NT) in exhaled breath condensate (EBC) and ethane, pentane and isoprene in exhaled air, and to test the applicability of the methods. A further goal was to evaluate the effect of different collection variables on ethane, pentane and isoprene levels and to explore whether these compounds are formed in the airways. The developed MDA method was based on derivatization with thiobarbituric acid, high-performance liquid chromatography (HPLC) and fluorescence detection. The limit of detection (LOD) was low (4.1 nM) and the response was linear in the concentration range examined (0.020-1.0 µM). Within-assay precision was 4% and between-assay precision 9%. Samples could be stored for one month at 20C and three months at 80C without losses. The method for determining exhaled ethane, pentane and isoprene involved pre-concentration on a multibed sorbent tube, thermal desorption and endcut gas chromatography (GC) with flame ionization detection (FID). The LODs were 5, 2 and 6 pmol/sample for ethane, pentane and isoprene, respectively. The analyte responses were linear and the repeatability was 7%, 10% and 12%, for the respective analytes. Certified levels of ethane and pentane agreed well with the measured levels. Ethane and pentane were stable for up to six days of storage in sample tubes. Isoprene levels were not stable during storage in the sample tubes used here, but using a modified tube sorbent, levels were stable for up to two days. Moreover, a method employing GC/negative chemical ionization (NCI)/tandem mass spectrometry (MS) was established for quantifying 3-NT in EBC. The detection limit was 0.56 pM (corresponding to 3 amol/µL injected) and a good linear relationship between added (0.025-5.0 nM) and measured 3-NT levels was observed. Within-day and between-day precision was 11% and 12%, respectively. No artifactual nitration was observed during sample processing. 3-NT levels were much lower compared to reported levels, based on immunochemical measurements.The possible production of ethane, pentane and isoprene in the airways was evaluated by studying the flow-dependency of analyte concentrations, as well as concentrations in dead space and alveolar air after subjects held their breath. The concentration of these substances in breath obtained after inhaling purified air was also examined. To this end, novel collection equipment was constructed. The major fractions of exhaled ethane, pentane and isoprene seem to be of systemic origin, but there was a tendency for ethane to be slightly flow-dependent in subjects with asthma, i.e. the concentration decreased at a higher flow-rate in subjects with asthma. When measuring ethane and pentane, it is important to take ambient air concentrations into account. In conclusion, valid methods to quantify MDA and 3-NT in EBC, as well as for ethane, pentane and isoprene in exhaled air, were developed. These methods may be feasible tools for monitoring airway oxidative stress.
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| 7. |
- Lärstad, Mona, 1971, et al.
(författare)
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Selective quantification of free 3-nitrotyrosine in exhaled breath condensate in asthma using gas chromatography/tandem mass spectrometry.
- 2005
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Ingår i: Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society. - : Elsevier BV. - 1089-8603. ; 13:2, s. 134-44
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Tidskriftsartikel (refereegranskat)abstract
- Reactive nitrogen species can cause oxidative modifications of certain amino acid residues in proteins, notably the modification of tyrosine to 3-nitrotyrosine (3-NT), which is a potentially useful marker of oxidative stress. Since lung diseases are associated with airway inflammation and oxidative stress, quantification of 3-NT in exhaled breath condensate (EBC) may provide a non-invasive means for monitoring ongoing inflammatory processes. 3-NT-like immunoreactivity has previously been detected in EBC, but no definitive evidence for the presence of 3-NT in EBC is available. Here, a method based on gas chromatography/negative ion chemical ionization/tandem mass spectrometry was established for the quantification of free 3-NT in EBC. The detection limit was 0.56 pM (corresponding to 3.0 amol microl(-1) sample injected) and the method was found to give linear results (r2 > 0.999) in the concentration range of 0-5.0 nM. The coefficient of variation (CV) for within-day and between-day precision were 11 and 12%, respectively. No artifactual nitration was observed during sample processing. The method was applied to study subjects with asthma (n = 8), and healthy subjects (n = 10), but only a slight non-significant increase in 3-NT levels was found in the former group (median [interquartile ranges]; 99 [50-547] amol s(-1) vs. 75 [35-147] amol s(-1)). No correlation with exhaled nitric oxide (NO), pulmonary function or EBC levels of total protein was observed. The 3-NT levels were much lower compared to previously reported levels, based on immunochemical measurements. The method does not allow the simultaneous quantification of tyrosine in samples.
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| 8. |
- Lärstad, Mona, 1971, et al.
(författare)
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Surfactant Protein A in Exhaled Endogenous Particles Is Decreased in Chronic Obstructive Pulmonary Disease (COPD) Patients: A Pilot Study
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Background Exhaled, endogenous particles are formed from the epithelial lining fluid in small airways, where surfactant protein A (SP-A) plays an important role in pulmonary host defense. Based on the knowledge that chronic obstructive pulmonary disease (COPD) starts in the small airway epithelium, we hypothesized that chronic inflammation modulates peripheral exhaled particle SP-A and albumin levels. The main objective of this explorative study was to compare the SP-A and albumin contents in exhaled particles from patients with COPD and healthy subjects and to determine exhaled particle number concentrations. Patients with stable COPD ranging from moderate to very severe (n = 13), and healthy nonsmoking subjects (n = 12) were studied. Subjects performed repeated breath maneuvers allowing for airway closure and re-opening, and exhaled particles were optically counted and collected on a membrane using the novel PExA1 instrument setup. Immunoassays were used to quantify SP-A and albumin. COPD patients exhibited significantly lower SP-A mass content of the exhaled particles (2.7 vs. 3.9 weight percent, p = 0.036) and lower particle number concentration (p<0.0001) than healthy subjects. Albumin mass contents were similar for both groups. Decreased levels of SP-A may lead to impaired host defense functions of surfactant in the airways, contributing to increased susceptibility to COPD exacerbations. SP-A in exhaled particles from small airways may represent a promising non-invasive biomarker of disease in COPD patients.
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| 9. |
- Moradi, Faraidoun, et al.
(författare)
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Gendered lived experiences of marriage and family following exposure to chemical warfare agents: content analysis of qualitative interviews with survivors in Halabja, Kurdistan-Iraq.
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- To study gendered experiences of the long-term effects of a chemical warfare agent (CWA; sulfur mustard).Qualitative face-to-face semi-structured in-depth interview study using content analysis approach with thematic analysis and anthropological inquiries.The city of Halabja in the Kurdistan Region of Iraq.Survivors of CWA (n=16, female:male 10:6, mean age 45.5 years (range 34 to 67)) with lung damage diagnosis and with a range of sociodemographic variables.Latent content was expressed as: To get or not to get married? Two categories-social abandonment and uncertain marriage-emerged as expressions of the manifest content. The majority of the participants showed uncertainty as a central concern that affects all decision-making in their private and social life. Uncertainty over marriage and family were huge, corresponding to their fear of giving birth to children with congenital birth defects. Exposure to CWAs was conceptualised in terms of stigmatised illnesses, and consequently resulted in loneliness and social isolation, leading to negative impacts on other aspects of professional and social life. The results demonstrated a gendered pattern: CWA-exposed women were more affected psychosocially than CWA-exposed men. More CWA-exposed women were unemployed, divorced or single, or lived under vulnerable circumstances compared with men.Survivors of CWA exposure have developed a sense of gendered uncertainty around getting married and building a family. Sulfur mustard-exposed women, in particular, long to be desired in the community as they face social exclusion. Survivors should be provided evidence-based consultancy to optimise their decision-making around marriage and other social and family challenges.
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| 10. |
- Moradi, Faraidoun, et al.
(författare)
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Health perspectives among Halabja’s civilian survivors of sulfur mustard exposure with respiratory symptoms—A qualitative study
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Background In 1988, Halabja came under heavy chemical warfare attack using chemicals such as sulfur mustard (SM). Thousands of survivors of SM exposure in the city today live with multiple health complaints, such as severe, long-lasting respiratory symptoms; but their perceptions of health have never been adequately researched. We aimed to explore current major health concern topics in civilian survivors with long-term respiratory symptoms. Method Sixteen subjects (f:m10:6, mean age 45.5 years (range 34–67)) were interviewed. Study participants were recruited in 2016 via a purposive sampling strategy among civilian survivors of chemical warfare in the city of Halabja in Kurdistan-Iraq. A qualitative research design was applied including semi-structured, face-to-face interviews. Data was analyzed using systematic text condensation. Results The analysis yielded fourteen themes related to: (1) General health: all participants described a deterioration in physical and psychological health, following the SM exposure, foremost involving respiratory symptoms, fatigue, sleeping disorders, ocular problems, depressive symptoms, and anxiety; (2) Quality of life: most notably, they reported a limited family life, limited social relations, lack of work ability, and concern about their financial situation. Moreover, many lived in constant fear of a renewed attack; (3) access to health care services: all participants reported that they had no, or only poor, access to health care services and limited access to specialist care, and all reported lack of financial resources to obtain treatment. Conclusions The post-exposure somatic and psychosocial effects such as respiratory symptoms of CWA are plausible contributor to poor general health and quality of life among survivors. We conclude that multidisciplinary interventions are needed to tackle the biopsychosocial complications in survivors of SM exposure to minimize further health damage in the future, as well as to promote their health-related quality of life.
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