| 1. |
- Bredberg, Anna, et al.
(författare)
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Comparison of Exhaled Endogenous Particles from Smokers and Non-Smokers Using Multivariate Analysis
- 2013
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Ingår i: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 86:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking, along with many respiratory diseases, has been shown to induce airway inflammation and alter the composition of the respiratory tract lining fluid (RTLF). We have previously shown that the phospholipid and protein composition of particles in exhaled air (PEx) reflects that of RTLF. In this study, we hypothesized that the composition of PEx differs between smokers and non-smokers, reflecting inflammation in the airways. Objective: It was the aim of this study to identify differences in the phospholipid composition of PEx from smokers and non-smokers. Methods: PEx from 12 smokers and 13 non-smokers was collected using a system developed in-house. PEx was analysed using time-of-flight secondary ion mass spectrometry, and the mass spectral data were evaluated using multivariate analysis. Orthogonal partial least squares (OPLS) was used to relate smoking status, lung function and pack years to the chemical composition of RTLF. The discriminating ions identified by OPLS were then used as explanatory variables in traditional regression analysis. Results: There was a clear discrimination between smokers and non-smokers according to the chemical composition, where phospholipids from smokers were protonated and sodiated to a larger extent. Poor lung function showed a strong association with higher response from all molecular phosphatidylcholine species in the samples. Furthermore, the accumulated amount of tobacco consumed was associated with variations in mass spectra, indicating a dose-response relationship. Conclusion: The chemical composition of PEx differs between smokers and nonsmokers, reflecting differences in the RTLF. The results from this study may suggest that the composition of RTLF is affected by smoking and may be of importance for lung function.
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| 2. |
- Almstrand, Ann-Charlotte, et al.
(författare)
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Effect of Airway Opening on Production of Exhaled Particles.
- 2010
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 108:3, s. 584-588
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Tidskriftsartikel (refereegranskat)abstract
- The technique of sampling exhaled air is attractive because it is non-invasive, and so allows repeated sampling with ease and no risk for the patient. Knowledge of the biomarkers' origin is important in order to correctly understand and interpret the data. Endogenous particles, formed in the airways, are exhaled and reflect chemical composition of the respiratory tract lining fluid. However, the formation mechanisms and formation sites of these particles are unknown. We hypothesize that airway opening following airway closure cause production of airborne particles that are exhaled. The objective of this study was to examine production of exhaled particles following varying degrees of airway closure. 10 healthy volunteers performed 3 different breathing manoeuvres in which the initial lung volume preceding an inspiration to total lung capacity was varied between functional residual capacity (FRC) and residual volume (RV). Exhaled particle number concentrations in the size interval 0.30-2.0 mum were recorded. Number concentrations of exhaled particles showed a 2-18 fold increase after exhalations to RV compared to exhalations where no airway closure was shown (8500 (810-28000) vs. 1300 (330-13000) particles/expired litre, p=0.012). The difference was most noticeable for the smaller size range of particles (<1 mum). There were significant correlations between particle concentrations for the different manoeuvres. Our results show that airway reopening following airway closure is an important mechanism for formation of endogenous exhaled particles and that these particles originate from the terminal bronchioles. Key words: exhaled particles, airway closure, breath.
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| 3. |
- Almstrand, Ann-Charlotte, et al.
(författare)
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TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.
- 2012
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Ingår i: The European respiratory journal: official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 39:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.
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| 4. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 5. |
- Bredberg, Anna, et al.
(författare)
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Analysis of manganese and iron in exhaled endogenous particles
- 2014
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Ingår i: Journal of Analytical Atomic Spectrometry. - 0267-9477 .- 1364-5544. ; 29, s. 730-735
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many full-time welders experience some sort of respiratory disorder e.g., asthma, bronchitis and metal fume fever. Thus, welding aerosols are thought to cause airway inflammation. There is a need for markers of welding aerosols in exposure assessments, and as most welding aerosols contain manganese and iron, these metals may possibly be used as an indicator. We have previously developed a novel non-invasive technique to collect endogenous particles in exhaled air (PEx). This study is designed to i) develop a method for analysis of manganese and iron in PEx and ii) investigate whether the manganese and/or iron content of PEx changes after exposure to welding aerosols. Methods: Nine individuals were experimentally exposed to welding fumes. PEx was collected at three time points for each individual; before, after and 24 hour after exposure. Analyses of PEx samples were performed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: Four out of nine individuals showed an increase in manganese and iron levels after exposure to welding aerosols. The mean manganese and iron concentration increased from,
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| 6. |
- Bredberg, Anna, et al.
(författare)
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Exhaled Endogenous Particles Contain Lung Proteins.
- 2012
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:2, s. 431-440
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:We recently developed a novel, noninvasive method for sampling nonvolatile material from the distal airways. The method is based on the collection of endogenous particles in exhaled air (PEx). The aim of this study was to characterize the protein composition of PEx and to verify that the origin of PEx is respiratory tract lining fluid (RTLF).METHOD:Healthy individuals exhaled into the sampling device, which collected PEx onto a silicon plate inside a 3-stage impactor. After their extraction from the plates, PEx proteins were separated by SDS-PAGE and then analyzed by LC-MS. Proteins were identified by searching the International Protein Index human database with the Mascot search engine.RESULTS:Analysis of the pooled samples identified 124 proteins. A comparison of the identified PEx proteins with published bronchoalveolar lavage (BAL) proteomic data showed a high degree of overlap, with 103 (83%) of the PEx proteins having previously been detected in BAL. The relative abundances of the proteins were estimated according to the Mascot exponentially modified protein abundance index protocol and were in agreement with the expected protein composition of RTLF. No amylase was detected, indicating the absence of saliva protein contamination with our sampling technique.CONCLUSIONS:Our data strongly support that PEx originate from RTLF and reflect the composition of undiluted RTLF.
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| 7. |
- Carlsen, Hanne Krage, et al.
(författare)
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Exposure to traffic and lung function in adults: A general population cohort study
- 2015
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the association between living near dense traffic and lung function in a cohort of adults from a single urban region. Design: Cross-sectional results from a cohort study. Setting: The adult-onset asthma and exhaled nitric oxide (ADONIX) cohort, sampled during 2001-2008 in Gothenburg, Sweden. Exposure was expressed as the distance from participants' residential address to the nearest road with dense traffic (>10 000 vehicles per day) or very dense traffic (>30 000 vehicles per day). The exposure categories were: low (>500 m; reference), medium (75-500 m) or high (<75 m). Participants: The source population was a population-based cohort of adults (n=6153). The study population included 5441 participants of European descent with good quality spirometry and information about all outcomes and covariates. Outcome measures: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured at a clinical examination. The association with exposure was examined using linear regression adjusting for age, gender, body mass index, smoking status and education in all participants and stratified by sex, smoking status and respiratory health status. Results: We identified a significant dose-response trend between exposure category and FEV1 (p=0.03) and borderline significant trend for FVC (p=0.06) after adjusting for covariates. High exposure was associated with lower FEV1 (-1.0%, 95% CI -2.5% to 0.5%) and lower FVC (-0.9%, 95% CI -2.2% to 0.4%). The effect appeared to be stronger in women. In highly exposed individuals with current asthma or chronic obstructive pulmonary disease, FVC was lower (-4.5%, 95% CI -8.8% to -0.1%). Conclusions: High traffic exposure at the residential address was associated with lower than predicted FEV1 and FVC lung function compared with living further away in a large general population cohort. There were particular effects on women and individuals with obstructive disease.
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| 8. |
- Keen, Christina, et al.
(författare)
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Supplementation With Fatty Acids Influences the Airway Nitric Oxide and Inflammatory Markers in Patients With Cystic Fibrosis
- 2010
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 50:5, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. Patients and Methods: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. Results: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. Conclusions: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.
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| 9. |
- Kim, Jeong-Lim, et al.
(författare)
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Impact of occupational exposures on exacerbation of asthma: a population-based asthma cohort study.
- 2016
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Ingår i: BMC pulmonary medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a prevalent chronic disease and occupation contributes to approximately 15 % of cases among adults. However, there are still few studies on risk factors for work-exacerbated asthma. The current study investigated the association between asthma exacerbations and occupational exposures.The study comprised all currently working adults (n = 1356) who reported ever asthma in prior population-based cohorts. All subjects completed a questionnaire about exposures, occupations and exacerbations of asthma. Exposure to high and low molecular weight agents, irritating agents and asthmagens were classified using the asthma-specific job exposure matrix for northern Europe (N-JEM). Severe exacerbation of asthma was defined as sought emergency care at a hospital, admitted to a hospital overnight, or made an urgent visit to a primary care physician or district medical office due to breathing problems during the last 12 months. Moderate exacerbation was defined as both being not severe exacerbation and an additional visit to a primary care physician or district medical office, or had extra treatments with corticosteroid tablets. Mild exacerbation was defined as being neither severe nor moderate exacerbation, and increasing usage of inhaled corticosteroids. Multiple logistic regression was applied to investigate the association between exacerbation of asthma and occupational exposures while adjusting for potential confounders.Approximately 26 % of the working asthmatics reported exacerbation, and more than two-thirds of them had moderate or severe exacerbation. From 23 to 49 % of the asthmatics reported occupational exposure to a variety of different types of agents. Exposure to any gas, smoke or dust (OR 1.7[95 % CI 1.2-2.6]) was associated with severe exacerbation of asthma, as were organic dust (OR 1.7[1.2-2.5]), dampness and mold (OR 1.8[1.2-2.7]), cold conditions (OR 1.7[1.1-2.7]), and a physically strenuous job (OR 1.6[1.03-2.3]). Asthmagens and low molecular weight agents classified by the N-JEM were associated with mild exacerbation, with OR 1.6[1.1-2.5] and OR 2.2[1.1-4.4], respectively.Self-reported exposure to any gas, smoke or dust, organic dust, dampness and mold, cold conditions and physically strenuous work, and jobs handling low molecular weight agents were associated with exacerbation of asthma. Reduction of these occupational exposures may help to reduce exacerbation of asthma.
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| 10. |
- 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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