ABSTRACT
BACKGROUND: A predisposition to exacerbations is being recognized as a distinct phenotype with "previous exacerbations" representing the strongest clinical factor associated with future exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, "past exacerbation status" must be included as a confounding factor. OBJECTIVE: This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma. METHODS: We evaluated clinical parameters from 105 severe asthmatics yearly for 3 years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non-exacerbators (CNE, subjects who did not experience any exacerbation over the 3-year period); (ii) consistent frequent exacerbators (CFE, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1 year, throughout the 3-year period); and (iii) intermittent exacerbators (IE). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2-related biomarkers, in addition to the "past exacerbation status." RESULTS: Thirty-nine subjects were classified as CNE, 15 as CFE, and 51 as IE. Frequent exacerbations in the previous year predicted exacerbations for the following year (P < .001). Among the several Th2-related biomarkers, only FeNO was associated with exacerbation status. When we analysed the data after the second visit, the impact of FeNO on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (P < .05). CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the "past exacerbation history."
Subject(s)
Asthma/epidemiology , Adolescent , Adult , Asthma/diagnosis , Biomarkers , Child , Child, Preschool , Comorbidity , Disease Progression , Female , Follow-Up Studies , Humans , Infant , Male , Middle Aged , Nitric Oxide , Phenotype , Prognosis , Respiratory Function Tests , Severity of Illness Index , Surveys and Questionnaires , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. In this study, diffusional kurtosis imaging and diffusion tensor imaging were used to investigate whether the former provides additional information regarding microstructural changes in the gray and white matter of adult patients with Moyamoya disease. MATERIALS AND METHODS: MR imaging (diffusional kurtosis imaging and DTI) was performed in 23 adult patients with Moyamoya disease and 23 age-matched controls. Three parameters were extracted from diffusional kurtosis imaging (mean kurtosis, axial kurtosis, and radial kurtosis), and 4, from DTI (fractional anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity). Voxelwise analysis for these parameters was performed in the normal-appearing brain parenchyma. The association of these parameters with neuropsychological performance was also evaluated. RESULTS: Voxelwise analysis revealed the greatest differences in fractional anisotropy, followed, in order, by radial diffusivity, mean diffusivity, and mean kurtosis. In patients, diffusional kurtosis imaging parameters were decreased in the dorsal deep white matter such as the corona radiata and superior longitudinal fasciculus (P < .01), including areas without DTI abnormality. Superior longitudinal fasciculus fiber-crossing areas showed weak correlations between diffusional kurtosis imaging and DTI parameters compared with tissues with a single-fiber direction (eg, the corpus callosum). Diffusional kurtosis imaging parameters were associated with general intelligence and frontal lobe performance. CONCLUSIONS: Although DTI revealed extensive white matter changes, diffusional kurtosis imaging additionally demonstrated microstructural changes in ischemia-prone deep white matter with abundant fiber crossings. Thus, diffusional kurtosis imaging may be a useful adjunct for detecting subtle chronic ischemic injuries.
Subject(s)
Brain Ischemia/diagnostic imaging , Brain/diagnostic imaging , Brain/pathology , Diffusion Tensor Imaging/methods , Moyamoya Disease/diagnostic imaging , Adult , Brain Ischemia/etiology , Chronic Disease , Female , Humans , Male , Middle Aged , Moyamoya Disease/complicationsABSTRACT
One of the unanswered questions in the study of fatigue is how cracks nucleate at stresses far below the static fracture strength. Previous theories show possible qualitative mechanisms that may operate in a crystal at room and low temperatures but none provides a quantitiative theory of this phenomenon. We show here a quantitative mechanism of fatigue crack initiation.With a small initial stress field, two closely located thin slices slide in opposite directions under cyclic loading. The increase of the local plastic strain with cycles of loading is calculated. The local plastic shear strain, positive in one slice and negative in the other, reaches 100 per cent at the free surface in a few hundred cycles. These large strains clearly cause the start of an extrusion or intrusion and fatigue crack nucleation.
