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 ◽  
...  

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.

2021 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  

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.


2020 ◽  
Author(s):  
Jörgen Östling ◽  
Marleen Van Geest ◽  
Henric K Olsson ◽  
Sven-Erik Dahlén ◽  
Emilia Viklund ◽  
...  

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.


2011 ◽  
Vol 41 (10) ◽  
pp. 2141-2147 ◽  
Author(s):  
J. P. Koning ◽  
D. E. Tenback ◽  
R. S. Kahn ◽  
M. G. Vollema ◽  
W. Cahn ◽  
...  

BackgroundMovement disorders and schizotypy are both prevalent in unaffected siblings of patients with schizophrenia and both are associated with the risk of developing psychosis or schizophrenia. However, to date there has been no research into the association between these two vulnerability factors in persons with an increased genetic risk profile. We hypothesized that unaffected siblings of patients with non-affective psychosis have more movement disorders and schizotypy than healthy controls and that these co-occur.MethodIn a cross-sectional design we assessed the prevalence and inter-relationship of movement disorders and schizotypy in 115 unaffected siblings (mean age 27 years, 44% males) and 100 healthy controls (mean age 26 years, 51% males). Movement disorders were measured with the Abnormal Involuntary Movement Scale (AIMS), the Unified Parkinson Disease Rating Scale (UPDRS), the Barnes Akathisia Rating Scale (BARS), and one separate item for dystonia. Schizotypy was assessed with the Structured Interview for Schizotypy – Revised (SIS-R).ResultsThere were significant differences in the prevalence of movement disorders in unaffected siblings versus healthy controls (10% v. 1%, p<0.01) but not in the prevalence of schizotypy. Unaffected siblings with a movement disorder displayed significantly more positive and total schizotypy (p=0.02 and 0.03 respectively) than those without. In addition, dyskinesia correlated with positive schizotypy (r=0.51, p=0.02).ConclusionsThe association between movement disorders (dyskinesia in particular) with positive and total schizotypy in unaffected siblings suggests that certain vulnerability factors for psychosis or schizophrenia cluster in a subgroup of subjects with an increased genetic risk of developing the disease.


2019 ◽  
Vol 28 (spe) ◽  
Author(s):  
Fay Williams ◽  
Bruna Brands

ABSTRACT Objective: determine the prevalence of drug use and to investigate the relationship between knowledge of consequences and drug consumption as well as the relationship between academic performance and drug consumption among university undergraduate students in Jamaica. Method: the study uses a cross sectional design. A total of 250 undergraduate students were selected through a randomized cluster sampling process. A modified survey instrument consisting of over 70 items relating to socio-demographics, knowledge of consequences, drug consumption and academic performance measures was used to test the research question and hypothesis. Results: the findings revealed low levels of drug usage as well as problematic usage, however, there was a weak negative yet statistically significant correlation between the academic performance and alcohol use (r=-.139, p=.028) which suggested that an increase in alcohol usage is associated with reduction in academic performance. The independent T test also revealed a statistically significant difference between those who used alcohol and those who did not use alcohol in the past 12 months based on academic performance. Conclusion: the findings will inform policy decisions regarding drug use and the provision of intervention services. It is recommended that this research should be extended to other universities in Jamaica.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253825
Author(s):  
Emilia Viklund ◽  
Björn Bake ◽  
Laith Hussain-Alkhateeb ◽  
Hatice Koca Akdeva ◽  
Per Larsson ◽  
...  

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.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1357
Author(s):  
Stefania Principe ◽  
Job J.M.H. van Bragt ◽  
Cristina Longo ◽  
Rianne de Vries ◽  
Peter J. Sterk ◽  
...  

Breath analysis using eNose technology can be used to discriminate between asthma and COPD patients, but it remains unclear whether results are influenced by smoking status. We aim to study whether eNose can discriminate between ever- vs. never-smokers and smoking <24 vs. >24 h before the exhaled breath, and if smoking can be considered a confounder that influences eNose results. We performed a cross-sectional analysis in adults with asthma or chronic obstructive pulmonary disease (COPD), and healthy controls. Ever-smokers were defined as patients with current or past smoking habits. eNose measurements were performed by using the SpiroNose. The principal component (PC) described the eNose signals, and linear discriminant analysis determined if PCs classified ever-smokers vs. never-smokers and smoking <24 vs. >24 h. The area under the receiver–operator characteristic curve (AUC) assessed the accuracy of the models. We selected 593 ever-smokers (167 smoked <24 h before measurement) and 303 never-smokers and measured the exhaled breath profiles of discriminated ever- and never-smokers (AUC: 0.74; 95% CI: 0.66–0.81), and no cigarette consumption <24h (AUC 0.54, 95% CI: 0.43–0.65). In healthy controls, the eNose did not discriminate between ever or never-smokers (AUC 0.54; 95% CI: 0.49–0.60) and recent cigarette consumption (AUC 0.60; 95% CI: 0.50–0.69). The eNose could distinguish between ever and never-smokers in asthma and COPD patients, but not recent smokers. Recent smoking is not a confounding factor of eNose breath profiles.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Spela Kokelj ◽  
Jörgen Östling ◽  
Benjamin Georgi ◽  
Karin Fromell ◽  
Kristina Nilsson Ekdahl ◽  
...  

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.


Crisis ◽  
2020 ◽  
pp. 1-7
Author(s):  
Laura R. Umphrey ◽  
John C. Sherblom ◽  
Paulina Swiatkowski

Abstract. Background: Cultivating positive feelings of self in relationships with others can affect perceptions of belongingness and burdensomeness. Aims: The present study examines the relationships of self-compassion, hope, and emotional control to thwarted belongingness, perceived burdensomeness, and suicidal ideation. Method: Participants were 481 college students who completed scales measuring self-compassion, hope, emotional control, thwarted belongingness, perceived burdensomeness, and suicidal ideation. Results: Correlation and parallel mediation analysis results show relationships between self-compassion, hope, and emotional control with perceived burdensomeness, thwarted belongingness, and suicidal ideation. Limitations: The study is limited by its cross-sectional design, sample demographics, and inability to distinguish between individuals with suicidal ideation and those who attempt suicide. Conclusion: The results show that the relationships of self-compassion, hope, and emotional control to perceived burdensomeness, thwarted belongingness, and suicidal ideation are worth further investigation.


Author(s):  
Caspar C. Berghout ◽  
Jolien Zevalkink ◽  
Abraham N. J. Pieters ◽  
Gregory J. Meyer

In this study we used a quasiexperimental, cross-sectional design with six cohorts differing in phase of treatment (pretreatment, posttreatment, 2-year posttreatment) and treatment type (psychoanalysis and psychoanalytic psychotherapy) and investigated scores on 39 Rorschach-CS variables. The total sample consisted of 176 participants from four mental health care organizations in The Netherlands. We first examined pretreatment differences between patients entering psychoanalysis and patients entering psychoanalytic psychotherapy. The two treatment groups did not seem to differ substantially before treatment, with the exception of the level of ideational problems. Next, we studied the outcome of psychoanalysis and psychoanalytic psychotherapy by comparing the Rorschach-CS scores of the six groups of patients. In general, we found significant differences between pretreatment and posttreatment on a relatively small number of Rorschach-CS variables. More pre/post differences were found between the psychoanalytic psychotherapy groups than between the psychoanalysis groups. More research is needed to examine whether analyzing clusters of variables might reveal other results.


2018 ◽  
Vol 1 (2) ◽  
pp. 58
Author(s):  
Setia Budi ◽  
Ria Dila Syahfitri

The rate of stroke incidence is about 200 per 100,000 people throughout the world. This study aims to determine the Relation Suffer Stroke With Independence Level In Neurology Polyclinic TK II DR Ak Gani Palembang Year Hospital 2017. The research method used is descriptive quantitative with cross sectional design that is done by interviewing techniques with questionnaires on 42 respondents with Accidental sampling technique. This research was conducted in August 2017. Data analysis used is univariate data analysis and bivariate data analysis with one way anova test result. The results of univariate analysis showed that the duration of the respondents suffering from stroke was between 2.10 years to 3.38 years. Also found that most respondents were at the level of independence f; independent, except bathing, dressing, moving, and one other function with a total of 12 respondents. The results showed that there was a significant relationship between the long suffering stroke with the level of independence with the value of p value 0.025. For that the need for rehabilitation to patients and families of patients in order to help improve the independence of stroke patients in doing their daily activities. Keywords : Long Suffer Stroke, Level of Independence


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