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- Horvath, I., et al.
(författare)
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A European Respiratory Society technical standard: exhaled biomarkers in lung disease
- 2017
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:4
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Tidskriftsartikel (refereegranskat)abstract
- Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.
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- Almeida, R. P., et al.
(författare)
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Effect of Cognitive Reserve on Age-Related Changes in Cerebrospinal Fluid Biomarkers of Alzheimer Disease
- 2015
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 72:6, s. 699-706
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. OBJECTIVE To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which A beta 42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/A beta 42 and p-tau/A beta 42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013. MAIN OUTCOMES AND MEASURES Cerebrospinal fluid levels of A beta 42, t-tau, p-tau, t-tau/A beta 42, and p-tau/A beta 42. RESULTS There were significant age x CR interactions for CSF t-tau (beta [SE] = -6.72 [2.84], P = .02), p-tau (beta [SE] = -0.71 [0.27], P = .01), t-tau/A beta 42 (beta [SE] = -0.02 [0.01], P = .02), and p-tau/A beta 42 (beta [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. CONCLUSIONS AND RELEVANCE In a sample composed of a cognitively normal group and a cognitively impaired group, higher CR was associated with a diminution of age-related alterations in CSF biomarkers of AD. This suggests one pathway through which CR might favorably alter lifetime risk for symptomatic AD.
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- Schultz, Stephanie A, et al.
(författare)
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Cardiorespiratory Fitness Attenuates the Influence of Amyloid on Cognition.
- 2015
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Ingår i: Journal of the International Neuropsychological Society : JINS. - 1469-7661. ; 21:10, s. 841-50
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer's disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer's Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841-850).
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- Cuevas Ocaña, Sara, et al.
(författare)
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ERS International Congress 2022 : highlights from the Basic and Translational Science Assembly
- 2023
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Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
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Forskningsöversikt (refereegranskat)abstract
- In this review, the Basic and Translational Science Assembly of the European Respiratory Society provides an overview of the 2022 International Congress highlights. We discuss the consequences of respiratory events from birth until old age regarding climate change related alterations in air quality due to pollution caused by increased ozone, pollen, wildfires and fuel combustion as well as the increasing presence of microplastic and microfibres. Early life events such as the effect of hyperoxia in the context of bronchopulmonary dysplasia and crucial effects of the intrauterine environment in the context of pre-eclampsia were discussed. The Human Lung Cell Atlas (HLCA) was put forward as a new point of reference for healthy human lungs. The combination of single-cell RNA sequencing and spatial data in the HLCA has enabled the discovery of new cell types/states and niches, and served as a platform that facilitates further investigation of mechanistic perturbations. The role of cell death modalities in regulating the onset and progression of chronic lung diseases and its potential as a therapeutic target was also discussed. Translational studies identified novel therapeutic targets and immunoregulatory mechanisms in asthma. Lastly, it was highlighted that the choice of regenerative therapy depends on disease severity, ranging from transplantation to cell therapies and regenerative pharmacology.
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- Reitsema, R., 1994-, et al.
(författare)
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ABERRANT PHENOTYPE OF CIRCULATING ANTIGEN PRESENTING CELLS IN GIANT CELL ARTERITIS AND POLYMYLAGIA RHEUMATICA
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1071-1071
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping diseases occurring exclusively in people older than 50 years. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. In GCA tissues, DCs may be prone to activation, leading to chemokine production and recruitment of CD4+ T-cells and monocytes to the arterial wall. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.Objectives: We aimed to investigate the phenotype of the circulating monocytes and DCs in GCA and PMR patients.Methods: APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). Using a 13-colour panel, we identified three monocyte subsets: classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. DC subsets were subdivided in CD303+CD11c- plasmacytoid DCs (pDCs), CD11c+CD141+ conventional DCs (cDC1) and CD11c+CD1c+ conventional DCs (cDC2). Each of these subsets was analysed for expression of pattern recognition receptors (Toll-like receptor 4 (TLR4), TLR2) and activation markers (CD86, Programmed Death- Ligand 1 (PD-L1), CD40, HLA-DR, CD11c) by assessing the mean-fluorescence intensity of these markers. Data were analysed by conventional gating strategies and by unsupervised tSNE.Results: GCA and PMR patients displayed a monocytosis, which was due to increases in classical and intermediate monocyte counts, whereas the proportion of non-classical monocytes was reduced. Intermediate monocytes of GCA patients had significantly higher TLR2 expression, a similar trend was observed in non-classical monocytes of GCA and PMR patients. A divergent pattern was observed in the expression of activation markers on classical versus non-classical monocytes: classical monocytes of GCA/PMR patients appeared to be less activated, whereas non-classical monocytes showed an increased marker expression compared to HCs (Figure 1). Even though no differences were observed in DC counts in the peripheral blood, cDC2 counts correlated negatively with CRP levels (r=-0.60 for GCA, r=-0.55 for PMR).Conclusion: Circulating non-classical monocytes, but not DCs, display an activated phenotype in GCA and PMR patients at diagnosis. These cells are thought to be pro-inflammatory, representing the end stage of monocyte maturation in the blood. In contrast, classical monocytes show reduced expression of activation markers in GCA and PMR patients, potentially signalling either an immature or exhausted phenotype. Shown is the mean fluorescence intensity (MFI) of CD11c on the surface of monocyte subsets and CD1c+ conventional dendritic cells (cDC2). Data are shown for patients with giant cell arteritis (GCA) or polymyalgia rheumatica (PMR) and age-matched healthy controls (HCs), n=15 for each group. Statistics by Mann Whitney U. CD11c expression data for pDCs (no CD11c expression) and cDC1 (too small population) are not shown.
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