| 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. |
- Selldén, Tilia, 1996, et al.
(författare)
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Radiographic airway abnormalities in untreated early rheumatoid arthritis are associated with peripheral neutrophil activation
- 2023
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of the lung for the initiation and progression of rheumatoid arthritis (RA) is still unclear. Up to 10% of RA patients develop interstitial lung disease which remains a clinical challenge. Understanding early disease mechanisms is of great importance. The objective of this study was to determine whether there is an association between peripheral neutrophil phenotypes and presence of pulmonary abnormalities (PA) on chest high-resolution computed tomography (HRCT) in untreated early RA (ueRA).MethodsClinical data and blood were collected, and HRCT performed at diagnosis on 30 consecutive anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) positive ueRA patients. HRCTs were evaluated for the presence of RA-associated parenchymal, airway and/or pleural abnormalities. Expression of phenotype markers on neutrophils were determined by flow cytometry. Levels of calprotectin, ACPA and RF were measured using immunoassays.ResultsThe frequency of having any PA was 60%. Airway abnormalities were present in 50%, parenchymal nodules in 43% and interstitial lung abnormalities (ILA) in 10%. Unsupervised multivariate data analysis showed clustering of any PA with neutrophil activation, parameters of inflammation and RF titres. In univariate analysis, the patients with PA displayed significantly increased CD11b and decreased CD62L expression on neutrophils (1.2-fold, p = 0.014; 0.8-fold, p = 0.012) indicating activation and significantly increased RF IgM titre and CRP (5.7-fold, p = 0.0025; 2.3-fold, p = 0.0035) as compared to no PA. Titres of RF, but not ACPA, correlated with expression of the neutrophil activation marker CD11b. A stratified analysis demonstrated that airway involvement was the PA subtype with the strongest association with neutrophil activation.ConclusionWe report a strong association between radiographic airway findings and activation of circulating neutrophils in early RA supporting a role of innate immunity and the lung at disease onset. Our results also indicate different contributions of RF and ACPA in the RA pathogenesis.
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| 3. |
- 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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| 4. |
- 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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| 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. |
- Garcia-Ryde, Martin, et al.
(författare)
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Lung Fibroblasts from Chronic Obstructive Pulmonary Disease Subjects Have a Deficient Gene Expression Response to Cigarette Smoke Extract Compared to Healthy
- 2023
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Ingår i: International journal of chronic obstructive pulmonary disease. - 1178-2005. ; 18, s. 2999-3014
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIM: Cigarette smoking is the most common cause of chronic obstructive pulmonary disease (COPD) but more mechanistic studies are needed. Cigarette smoke extract (CSE) can elicit a strong response in many COPD-related cell types, but no studies have been performed in lung fibroblasts. Therefore, we aimed to investigate the effect of CSE on gene expression in lung fibroblasts from healthy and COPD subjects.PATIENTS AND METHODS: Primary lung fibroblasts, derived from six healthy and six COPD subjects (all current or ex-smokers), were either unstimulated (baseline) or stimulated with 30% CSE for 4 h prior to RNA isolation. The mRNA expression levels were measured using the NanoString nCounter Human Fibrosis V2 panel (760 genes). Pathway enrichment was assessed for unique gene ontology terms of healthy and COPD.RESULTS: At baseline, a difference in the expression of 17 genes was found in healthy and COPD subjects. Differential expression of genes after CSE stimulation resulted in significantly less changes in COPD lung fibroblasts (70 genes) than in healthy (207 genes), with 51 genes changed in both. COPD maintained low NOTCH signaling throughout and upregulated JUN >80%, indicating an increase in apoptosis. Healthy downregulated the Mitogen-activated protein kinase (MAPK) signaling cascade, including a ≥50% reduction in FGF2, CRK, TGFBR1 and MEF2A. Healthy also downregulated KAT6A and genes related to cell proliferation, all together indicating possible cell senescence signaling.CONCLUSION: Overall, COPD lung fibroblasts responded to CSE stimulation with a very different and deficient expression profile compared to healthy. Highlighting that stimulated healthy cells are not an appropriate substitute for COPD cells which is important when investigating the mechanisms of COPD.
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| 8. |
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| 9. |
- 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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| 10. |
- Larsson, Per, et al.
(författare)
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Surfactant protein A and albumin in particles in exhaled air.
- 2012
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Ingår i: Respiratory medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 106:2, s. 197-204
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Tidskriftsartikel (refereegranskat)abstract
- In this study we test the hypothesis that endogenous particles in exhaled air (PEx), non-invasively sampled from lower airways, are well suited for the analysis of respiratory tract lining fluid (RTLF) proteins, i.e., surfactant protein A (SP-A) and albumin. Ten healthy volunteers were included in the study and participated in two sampling sessions. Blood, exhaled breath condensate (EBC) and PEx were collected at each session. 100L of breath were collected for each exhaled sample. Serum and exhaled samples were analyzed for SP-A using an in-house ELISA. Albumin was analyzed in exhaled samples using a commercial ELISA kit. SP-A detection rates were 100%, 21%, and 89% for PEx, EBC and serum, respectively. Albumin was detected in PEx, but not in EBC. SP-A measurements in PEx showed good repeatability with an intra-individual coefficient of variation of 13%. Both SP-A and albumin showed significant correlation to mass of PEx (r(s)=0.93, p<0.001 and r(s)=0.86, p=0.003, respectively). Sampling and analysis of PEx is a valid non-invasive method to monitor RTLF proteins sampled from the lower respiratory tract, as demonstrated here by example of SP-A and albumin analysis.
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