scholarly journals A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways

2021 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Annotation Database ◽  
Epithelial Lining Fluid ◽  
Go Annotation ◽  
Non Invasive ◽  
Invasive Method ◽  
Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥2.9 z-score), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc).ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

scholarly journals A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

2020 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Annotation Database ◽  
Epithelial Lining Fluid ◽  
Go Annotation ◽  
Non Invasive ◽  
Invasive Method ◽  
Never Smokers

Abstract BackgroundBreath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and constitute a potential source of biomarkers reflecting pathological processes in the small airways.ObjectiveOur aim was to investigate if PExA method may be useful for discovery of biomarkers that reflect pathology of small airways.Methods10 healthy controls and 20 subjects with asthma, of whom 10 with small airway dysfunction (SAD), were examined using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with SAD as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with small airway dysfunction. The results suggest that PEx based proteomics is an novel and promising approach to study respiratory diseases with small airway involvement.

scholarly journals A Novel Non-invasive Method Allowing for Discovery of Pathologically Relevant Proteins From Small Airways

2021 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlen ◽  
Emilia Viklund ◽  
...  
Keyword(s):  
Research Question ◽  
Extracellular Proteins ◽  
Small Airway ◽  
Small Airways ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Annotation Database ◽  
Go Annotation ◽  
Cross Sectional Design ◽  
Never Smokers

Abstract BackgroundThere is a lack of early and precise biomarkers for personalized respiratory medicine. Breath contains an aerosol of droplet particles, which are formed from the epithelial lining fluid when the small airways close and re-open during inhalation succeeding a full expiration. These particles can be collected by impaction using the PExA® method (Particles in Exhaled Air), and are derived from an area of high clinical interest previously difficult to access, making them a potential source of biomarkers reflecting pathological processes in the small airways.Research questionOur aim was to investigate if PExA method is useful for discovery of biomarkers that reflect pathology of small airways.Methods and analysis10 healthy controls and 20 subjects with asthma, of whom 10 with small airway involvement as indicated by a high lung clearance index (LCI ≥2.9 z-score), were examined in a cross-sectional design, using the PExA instrument. The samples were analysed with the SOMAscan proteomics platform (SomaLogic Inc). ResultsTwo hundred-seven proteins were detected in up to 80% of the samples. Nine proteins showed differential abundance in subjects with asthma and high LCI as compared to healthy controls. Two of these were less abundant (ALDOA4, C4), and seven more abundant (FIGF, SERPINA1, CD93, CCL18, F10, IgM, IL1RAP). sRAGE levels were lower in ex-smokers (n=14) than in never smokers (n=16). Gene Ontology (GO) annotation database analyses revealed that the PEx proteome is enriched in extracellular proteins associated with extracellular exosome-vesicles and innate immunity.ConclusionThe applied analytical method was reproducible and allowed identification of pathologically interesting proteins in PEx samples from asthmatic subjects with high LCI. The results suggest that PEx based proteomics is a novel and promising approach to study respiratory diseases with small airway involvement.

Values of T/QRS ratio in pregnancies complicated by intrauterine growth restriction

2016 ◽  
Vol 44 (7) ◽  
Author(s):  
Tomasz Fuchs
Keyword(s):  
Intrauterine Growth Restriction ◽  
Well Being ◽  
Study Groups ◽  
Growth Restriction ◽  
Healthy Controls ◽  
Value Differences ◽  
Intrauterine Growth ◽  
Non Invasive ◽  
Invasive Method ◽  
Ratio Variables

AbstractAims:To evaluate values of T/QRS ratio in normal pregnancies and those complicated by intrauterine growth restriction (IUGR) using non-invasive method with transabdominal electrodes. Assessment of fetal well-being in IUGR pregnancies.Methods:Fetal electrocardiograms were recorded and analyzed by KOMPOREL software from ITAM (Zabrze, Poland) and T/QRS ratios were automatically calculated. Doppler velocimetry of the middle cerebral artery and umbilical artery was carried out. The study group consisted of IUGR pregnancies with normal cerebroplacental ratios (CPRs) (n=110), IUGR pregnancies with decreased CPRs (n=29), and healthy controls (n=549). Analyses were performed between the study groups and by gestational age. T/QRS ratio variables and CPRs were calculated. Analysis of variance and linear regression were performed.Results:Maximum values, maximum minimal value differences, and standard deviations of T/QRS ratio were significantly different between the IUGR group with reduced CPRs and normal CPRs (P=0.0009, P=0.0000, P=0.0034, respectively) as well as between the IUGR group with reduced CPRs and healthy controls (P=0.0000, P=0.0001, P=0.0009, respectively). Mean maximum values in the IUGR group with reduced CPRs exceeded normal values.Conclusions:T/QRS ratio may be useful in assessing fetal well-being in IUGR pregnancies; however, future studies are needed to determine typical ranges of T/QRS ratio in pregnancies complicated by IUGR.

scholarly journals A non-invasive olfactory bulb measure dissociates Parkinson’s patients from healthy controls and discloses disease duration

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Behzad Iravani ◽  
Artin Arshamian ◽  
Martin Schaefer ◽  
Per Svenningsson ◽  
Johan N. Lundström
Keyword(s):  
Olfactory Bulb ◽  
Disease Duration ◽  
Motor Symptom ◽  
Healthy Controls ◽  
Non Invasive ◽  
Odor Processing ◽  
Potential Development ◽  
Theta Frequency ◽  
Invasive Method ◽  
Early Biomarker

AbstractOlfactory dysfunction is a prevalent non-motor symptom of Parkinson’s disease (PD). This dysfunction is a result of neurodegeneration within the olfactory bulb (OB), the first processing area of the central olfactory system, and commonly precedes the characteristic motor symptoms in PD by several years. Functional measurements of the OB could therefore potentially be used as an early biomarker for PD. Here, we used a non-invasive method, so-called electrobulbogram (EBG), to measure OB function in PD and age-matched healthy controls to assess whether EBG measures can dissociate PDs from controls. We estimated the spectrogram of the EBG signal during exposure to odor in PD (n = 20) and age-matched controls (n = 18) as well as identified differentiating patterns of odor-related synchronization in the gamma, beta, and theta frequency bands. Moreover, we assessed if these PD-EBG components could dissociate PD from control as well as their relationship with PD characteristics. We identified six EBG components during the initial and later stages of odor processing which dissociated PD from controls with 90% sensitivity and 100% specificity with links to PD characteristics. These PD-EBG components were related to medication, disease duration, and severity, as well as clinical odor identification performance. These findings support using EBG as a tool to experimentally assess PD interventions, potentially aid diagnosis, and the potential development of EBG into an early biomarker for PD.

scholarly journals Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253825
Author(s):  
Emilia Viklund ◽  
Björn Bake ◽  
Laith Hussain-Alkhateeb ◽  
Hatice Koca Akdeva ◽  
Per Larsson ◽  
...  
Keyword(s):  
Lung Function ◽  
Inflammatory Responses ◽  
Protein A ◽  
Surfactant Protein ◽  
Small Airway ◽  
Surfactant Protein A ◽  
Normal Lung ◽  
Small Airways ◽  
Current Smoking ◽  
Never Smokers

Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.

Software-based Detection of Acute Rejection Changes in Face Transplant

2021 ◽  
Author(s):  
Miguel I. Dorante ◽  
Branislav Kollar ◽  
Marian Bittner ◽  
Alice Wang ◽  
Yannick Diehm ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Mixed Models ◽  
Allograft Rejection ◽  
Healthy Controls ◽  
Non Invasive ◽  
Face Transplant ◽  
Marginal Means ◽  
Invasive Method ◽  
The Mean ◽  
R Value

Abstract Background An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking. Methods A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons. Results Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79–18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43–21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96–27.28). Conclusion This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

scholarly journals Smoking induces sex-specific changes in the small airway proteome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Spela Kokelj ◽  
Jörgen Östling ◽  
Benjamin Georgi ◽  
Karin Fromell ◽  
Kristina Nilsson Ekdahl ◽  
...  
Keyword(s):  
Drug Targets ◽  
Protein Profile ◽  
Protein Composition ◽  
High Sensitivity ◽  
Small Airway ◽  
Strong Impact ◽  
Small Airways ◽  
Active Smoking ◽  
Former Smokers ◽  
Never Smokers

Abstract Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. Conclusions The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.

scholarly journals Proteomic Patterns of Nipple Aspirate Fluids Obtained by SELDI-TOF: Potential for New Biomarkers to Aid in the Diagnosis of Breast Cancer

2001 ◽  
Vol 17 (4) ◽  
pp. 301-307 ◽  
Author(s):  
Cloud P. Paweletz ◽  
Bruce Trock ◽  
Marie Pennanen ◽  
Theodore Tsangaris ◽  
Collette Magnant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Ionization Time ◽  
Non Invasive ◽  
Abnormal Mammogram ◽  
Surface Enhanced ◽  
Invasive Method ◽  
Nipple Aspirate Fluids ◽  
New Biomarkers

Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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