| 1. |
- Blomberg, Anders, et al.
(author)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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In: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Journal article (peer-reviewed)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 2. |
- Frick, Inga-Maria, et al.
(author)
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Constitutive and Inflammation-Dependent Antimicrobial Peptides Produced by Epithelium Are Differentially Processed and Inactivated by the Commensal Finegoldia magna and the Pathogen Streptococcus pyogenes.
- 2011
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In: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 187, s. 4300-4309
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Journal article (peer-reviewed)abstract
- Epithelial linings serve as physical barriers and produce antimicrobial peptides (AMPs) to maintain host integrity. Examples are the bactericidal proteins midkine (MK) and BRAK/CXCL14 that are constitutively produced in the skin epidermal layer, where the anaerobic Gram-positive coccoid commensal Finegoldia magna resides. Consequently, this bacterium is likely to encounter both MK and BRAK/CXCL14, making these molecules possible threats to its habitat. In this study, we show that MK expression is upregulated during inflammation, concomitant with a strong downregulation of BRAK/CXCL14, resulting in changed antibacterial conditions. MK, BRAK/CXCL14, and the inflammation-dependent antimicrobial β-defensins human β-defensin (hBD)-2 and hBD-3 all showed bactericidal activity against both F. magna and the virulent pathogen Streptococcus pyogenes at similar concentrations. SufA, a released protease of F. magna, degraded MK and BRAK/CXCL14 but not hBD-2 nor hBD-3. Cleavage was seen at lysine and arginine residues, amino acids characteristic of AMPs. Intermediate SufA-degraded fragments of MK and BRAK/CXCL14 showed stronger bactericidal activity against S. pyogenes than F. magna, thus promoting survival of the latter. In contrast, the cysteine-protease SpeB of S. pyogenes rapidly degraded all AMPs investigated. The proteins FAF and SIC, released by F. magna and S. pyogenes, respectively, neutralized the antibacterial activity of MK and BRAK/CXCL14, protein FAF being the most efficient. Quantitation and colocalization by immunoelectron microscopy demonstrated significant levels and interactions of the molecules in in vivo and ex vivo samples. The findings reflect strategies used by a permanently residing commensal and a virulent pathogen, the latter operating during the limited time course of invasive disease.
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| 3. |
- Levitsky, Adrian, et al.
(author)
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Early symptoms and sensations as predictors of lung cancer : a machine learning multivariate model
- 2019
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- The aim of this study was to identify a combination of early predictive symptoms/sensations attributable to primary lung cancer (LC). An interactive e-questionnaire comprised of pre-diagnostic descriptors of first symptoms/sensations was administered to patients referred for suspected LC. Respondents were included in the present analysis only if they later received a primary LC diagnosis or had no cancer; and inclusion of each descriptor required >= 4 observations. Fully-completed data from 506/670 individuals later diagnosed with primary LC (n = 311) or no cancer (n = 195) were modelled with orthogonal projections to latent structures (OPLS). After analysing 145/285 descriptors, meeting inclusion criteria, through randomised seven-fold cross-validation (six-fold training set: n = 433; test set: n = 73), 63 provided best LC prediction. The most-significant LC-positive descriptors included a cough that varied over the day, back pain/aches/discomfort, early satiety, appetite loss, and having less strength. Upon combining the descriptors with the background variables current smoking, a cold/flu or pneumonia within the past two years, female sex, older age, a history of COPD (positive LC-association); antibiotics within the past two years, and a history of pneumonia (negative LC-association); the resulting 70-variable model had accurate cross-validated test set performance: area under the ROC curve = 0.767 (descriptors only: 0.736/background predictors only: 0.652), sensitivity = 84.8% (73.9/76.1%, respectively), specificity = 55.6% (66.7/51.9%, respectively). In conclusion, accurate prediction of LC was found through 63 early symptoms/sensations and seven background factors. Further research and precision in this model may lead to a tool for referral and LC diagnostic decision-making.
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| 4. |
- olin, maria, et al.
(author)
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Patients’ experience of their health changes when under investigation for pulmonary disease – the ongoing PEK-Lung project
- 2015
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In: European Clinical Respiratory Journal. ; 2:28179
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Conference paper (other academic/artistic)abstract
- Introduction: The majority of patients with lung cancer (LC) are diagnosed in advanced stages. Increased specificity about symptoms associated with LC might enable earlier diagnosis. This may allow timely alleviation of symptom distress and increase curative surgical treatment as an option. In this project, we study patients’ subjective experiences of early health changes prior to LC diagnosis and link these changes to biomarker analyses. Method: Patients at initial evaluation at one ambulatory unit at Department of Respiratory Medicine, Karolinska University Hospital, Solna, Sweden, are asked to participate in the project. Patients complete an interactive individualized web-based questionnaire on a touchpad, consisting of 10 subject areas based on 163 descriptors generated through qualitative interviews. An assistant is available for further instructions or assistance. Blood samples are taken for the biobank. Results: From November 3, 2014, to March 1, 2015, 231 new patients were registered at the clinic, of which 195 were invited to participate (12 were excluded due to language difficulties and 24 cancelled their Clinical appointment). In total, 122 (63%) of the patients fulfilling the inclusion criteria were included. Lack of time and fatiguewere commonreasons for non-participation. Our ambition is to include 500 patients. Discussion: This project is a unique collaboration, beginning with patient experiences, including research input spanning from bench to bedside, and driven by a nursing perspective. Challenges for feasibility, especially anchoring, ownership, and communication demands, will be discussed. Keyword: COPD
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| 5. |
- Allhorn, Maria, et al.
(author)
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Human IgG/FcgammaR Interactions Are Modulated by Streptococcal IgG Glycan Hydrolysis.
- 2008
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: The human pathogen Streptococcus pyogenes produces an endoglycosidase, EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG. IgG-binding to Fc gamma receptors (FcgammaR) on leukocytes triggers effector functions including phagocytosis, oxidative burst and the release of inflammatory mediators. The interactions between FcgammaR and the Fc domain of IgG depend on the IgG glycosylation state. METHODOLOGY/PRINCIPAL FINDINGS: Here we show for the first time that EndoS hydrolyzes the heavy chain glycan of all four human IgG subclasses (IgG1-4), in purified form and in a plasma environment. An inactive form of EndoS, obtained by site-directed mutagenesis, binds IgG with high affinity, in contrast to wild type EndoS that only transiently interacts with IgG, as shown by Slot-blotting and surface plasmon resonance technology. Furthermore, EndoS hydrolysis of the IgG glycan influences the binding of IgG to immobilized soluble FcgammaR and to an erythroleukemic cell line, K562, expressing FcgammaRIIa. Incubation of whole blood with EndoS results in a dramatic decrease of IgG binding to activated monocytes as analyzed by flow cytometry. Moreover, the IgG bound to K562 cells dissociates when cells are treated with EndoS. Likewise, IgG bound to immobilized FcgammaRIIa and subsequently treated with EndoS, dissociates from the receptor as analyzed by surface plasmon resonance and Western blot. CONCLUSIONS/SIGNIFICANCE: We provide novel information about bacterial enzymatic modulation of the IgG/FcgammaR interaction that emphasizes the importance of glycosylation for antibody effector functions. Moreover, EndoS could be used as a biochemical tool for specific IgG N-glycan hydrolysis and IgG purification/detection, or as a potential immunosuppressing agent for treatment of antibody-mediated pathological processes.
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| 6. |
- Almstrand, Ann-Charlotte, et al.
(author)
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An explorative study on respiratory health among operators working in polymer additive manufacturing
- 2023
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In: Frontiers in Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- Additive manufacturing (AM), or 3D printing, is a growing industry involving a wide range of different techniques and materials. The potential toxicological effects of emissions produced in the process, involving both ultrafine particles and volatile organic compounds (VOCs), are unclear, and there are concerns regarding possible health implications among AM operators.The objective of this study was to screen the presence of respiratory health effects among people working with liquid, powdered, or filament plastic materials in AM. MethodsIn total, 18 subjects working with different additive manufacturing techniques and production of filament with polymer feedstock and 20 controls participated in the study. Study subjects filled out a questionnaire and underwent blood and urine sampling, spirometry, impulse oscillometry (IOS), exhaled NO test (FeNO), and collection of particles in exhaled air (PEx), and the exposure was assessed. Analysis of exhaled particles included lung surfactant components such as surfactant protein A (SP-A) and phosphatidylcholines. SP-A and albumin were determined using ELISA. Using reversed-phase liquid chromatography and targeted mass spectrometry, the relative abundance of 15 species of phosphatidylcholine (PC) was determined in exhaled particles. The results were evaluated by univariate and multivariate statistical analyses (principal component analysis). ResultsExposure and emission measurements in AM settings revealed a large variation in particle and VOC concentrations as well as the composition of VOCs, depending on the AM technique and feedstock. Levels of FeNO, IOS, and spirometry parameters were within clinical reference values for all AM operators. There was a difference in the relative abundance of saturated, notably dipalmitoylphosphatidylcholine (PC16:0_16:0), and unsaturated lung surfactant lipids in exhaled particles between controls and AM operators. ConclusionThere were no statistically significant differences between AM operators and controls for the different health examinations, which may be due to the low number of participants. However, the observed difference in the PC lipid profile in exhaled particles indicates a possible impact of the exposure and could be used as possible early biomarkers of adverse effects in the airways.
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| 7. |
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| 8. |
- Andree, Maria, et al.
(author)
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Knowledge Products from Close-To-Practice Research
- 2024
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In: Round table presentation at the NERA-conference, 6-8 March, Malmö University.
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Conference paper (other academic/artistic)abstract
- ‘Close-to-practice research’ has received increased attention across the Nordic countries. Following the British Education Research Association (BERA), the notion of ‘close-to-practice research’ is used to refer to educational research that is based on problems in practice, often involves researchers working in partnership with practitioners in schools and addresses issues of relevance to practitioners. This roundtable focuses on how close-to-practice research can contribute to the knowledge base of the teaching profession by bringing together perspectives from didactics, school improvement and educational policy. More specifically, the interest is directed toward what characterizes the knowledge produced through practice-based research that may have significance for teachers' professional knowledge base and practice. The roundtable conversation builds on a previous analysis of what kinds of knowledge products are generated in didactic close-to-practice research where teachers and researchers work together within the research environment Stockholm Teaching & Learning Studies. As a result of this analysis a typology of knowledge products was proposed including: (i) descriptions of knowing, (ii) teaching design, (iii) didactic examples and (iv) methodological tools. It has been proposed that additional knowledge products may be developed, such as artifacts to be used in teaching (e.g. lesson plans, visual representations). The roundtable will include the following points of discussion: 1) a brief presentation of the typology, 2) challenging and developing the typology of knowledge products proposed by previous research by investigating different cases of close-to-practice research from traditions of action research and practice-developing research within subject-didactics, and 3) discussing how the notion of knowledge products may contribute to advancing the conversation on cumulativity in the field of educational research in general, and in relation to syntheses of close-to-practice research in particular. The participants will be engaged in conversations on the desirability and feasibility of striving towards cumulativity.
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| 9. |
- Artigas Soler, María, et al.
(author)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Journal article (peer-reviewed)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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| 10. |
- Assenhöj, Maria, et al.
(author)
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Occupational exposure and health surveys at metal additive manufacturing facilities
- 2023
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In: Frontiers In Public Health. - : FRONTIERS MEDIA SA. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- Introduction: Additive manufacturing is a novel state-of-the art technology with significant economic and practical advantages, including the ability to produce complex structures on demand while reducing the need of stocking materials and products. Additive manufacturing is a technology that is here to stay; however, new technologies bring new challenges, not only technical but also from an occupational health and safety perspective. Herein, leading Swedish companies using metal additive manufacturing were studied with the aim of investigating occupational exposure and the utility of chosen exposure- and clinical markers as predictors of potential exposure-related health risks.Methods: Exposure levels were investigated by analysis of airborne dust and metals, alongside particle counting instruments measuring airborne particles in the range of 10 nm-10 mu m to identify dusty work tasks. Health examinations were performed on a total of 48 additive manufacturing workers and 39 controls. All participants completed a questionnaire, underwent spirometry, and blood and urine sampling. A subset underwent further lung function tests.Results: Exposure to inhalable dust and metals were low, but particle counting instruments identified specific work tasks with high particle emissions. Examined health parameters were well within reference values on a group level. However, statistical analysis implied an impact on workers kidney function and possible airway inflammation.Conclusion: The methodology was successful for investigating exposure-related health risks in additive manufacturing. However, most participants have been working <5 years. Therefore, long-term studies are needed before we can conclusively accept or reject the observed effects on health.
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