Characteristics of eosinophilic and non-eosinophilic asthma during treatment with inhaled corticosteroids.

OBJECTIVE: Eosinophilic inflammation in the respiratory tract is a hallmark of bronchial asthma. In naïve cases, the inflammatory profile is associated with disease severity and reactivity to inhaled corticosteroids (ICS). Sustained airway eosinophilia has been reported during ICS treatment. However, the immunological characteristics of these cases are not known and it is unclear if this situation contributes to asthma control. This study was performed to determine the answer of these questions. METHODS: To compare phenotypes of eosinophilic and non-eosinophilic asthma (EA and NEA, respectively) under ICS treatment, clinical data were obtained from asthmatic subjects (n = 22) and healthy controls (n = 10), and the leukocyte compositions of induced sputum and peripheral blood were determined. T lymphocyte profiles in systemic blood were assessed by flow cytometry. RESULTS: A higher frequency of emergency room visits was observed in the NEA group, which had a higher neutrophil count relative to the total inflammatory cell population in induced sputum than the EA group (59.5 versus 36.6%; p < 0.01). The fraction of helper T (Th)17 lymphocytes as well as the ratio of Th17 to regulatory T cells (Treg) in the peripheral blood was higher in the NEA than in the EA group (0.24 versus 0.13; p < 0.05). CONCLUSIONS: Th17 were more prevalent than Treg cells in the peripheral blood of NEA patients under ICS treatment, corresponding to neutrophil-dominant airway inflammation and a severe asthmatic phenotype. Thus, an imbalance in Th17/Treg may be associated with the pathogenesis of NEA in patients undergoing ICS treatment.

Cluster analysis identifies characteristic phenotypes of asthma with accelerated lung function decline.

OBJECTIVE: While the majority of individuals with asthma retain normal lung function over time, some exhibit accelerated lung function decline. Preservation of lung function is an important aspect of asthma management. Whether the asthma guidelines can prevent lung function decline remains controversial. This study was performed to determine the distribution of asthmatic subjects with greater lung function decline and to identify characteristic clinical features of such subjects treated in accordance with clinical guidelines by using hierarchical cluster analysis. METHODS: Eighty-six asthmatic subjects without a history of smoking were assessed with respect to eight variables selected from clinical phenotypes by using step-wise multiple regression analysis. Hierarchical cluster analysis using Ward's method generated a dendrogram for estimation of the number of clusters within the population and the differences between them. RESULTS: Three distinct clusters were identified. Cluster 1 (n = 40) comprised women with late-onset asthma. Cluster 2 (n = 17) comprised subjects with early-onset asthma, atopy and long disease duration. Cluster 3 (n = 29) predominantly comprised older men who had late-onset asthma, a lower prevalence of exacerbation and a lower predicted % forced expiratory volume in 1 s (FEV1) at baseline. Subjects in cluster 3 showed a mean decline in FEV1 of 69 mL/year, which was the greatest lung function decline among the three clusters. CONCLUSION: We identified a subgroup of patients with accelerated lung function decline despite appropriate asthma treatment based on guidelines constructed by using subjective symptoms.

Novel assay to detect increased level of neutralizing anti-interferon gamma autoantibodies in non-tuberculous mycobacterial patients.

Subjects exposed to non-tuberculous mycobacterium (NTM) species do not always develop an active disease, which likely reflects underlying host susceptibility factors. Recent reports have shown that anti interferon gamma (IFN-γ) neutralizing autoantibodies (IFN-γ Ab) are associated with the development of disseminated NTM in patients without known evidence of immunodeficiency. The purpose of this study is to establish the screening method if subjects have IFN-γ Ab. Whole blood was obtained from patients with disseminated NTM, those with pulmonary NTM, and healthy controls. The neutralizing capacity to IFN-γ activity was assessed as an inhibition of Signal Transducer and Activation of Transcription 1 (STAT-1) phosphorylation in leukocyte after stimulation with exogenous IFN-γ by flow cytometer. The strength of phosphorylation was described as STAT1 phosphorylation index. Antigen capture assay was performed to measure the relative titer of Immunoglobulin-G fraction of IFN-γ Ab. STAT1 phosphorylation by IFN-γ was significantly inhibited in the leukocytes from patients with disseminated NTM compared to that in healthy subjects, while this inhibition was not observed in patients with pulmonary NTM. All subjects with inhibited STAT1 phosphorylation had high titer of Immunoglobulin-G that reacted with IFN-γ in the antigen capture assay. The measurement of STAT1 phosphorylation index in whole blood leukocytes and antigen capture assay are simple and useful method for detection of anti-IFN-γ neutralizing autoantibodies, and is valuable in the pathophysiological diagnosis of disseminated NTM patients without obvious immunodeficiency.

Radio frequency alternating electromagnetic field enhanced tetraruthenium polyoxometalate electrocatalytic water oxidation.

Application of radio frequency (RF) electromagnetic waves enhances the electrocatalytic water oxidation by protonated tetraruthenium polyoxometalate ([Ru4(µ-O)4(µ-OH)2(H2O)4(γ-SiW10O36)2]10-). In particular, an enhancement factor of 3.6 is achieved when the level of proton substitution of protonated tetraruthenium polyoxometalate is changed from zero to 9 under application of RF at 200 MHz.

Enhancement of Fixed-bed Flow Reactions under Microwave Irradiation by Local Heating at the Vicinal Contact Points of Catalyst Particles.

The formation of local high temperature regions, or so-called "hot spots", in heterogeneous reaction systems has been suggested as a critical factor in the enhancement of chemical reactions using microwave heating. In this paper, we report the generation of local high temperature regions between catalyst particles under microwave heating. First, we demonstrated that reaction rate of the dehydrogenation of 2-propanol over a magnetite catalyst was enhanced 17- (250 °C) to 38- (200 °C) fold when heated with microwave irradiation rather than an electrical furnace. Subsequently, the existence of microwave-generated specific local heating was demonstrated using a coupled simulation of the electromagnetic fields and heat transfer as well as in situ emission spectroscopy. Specific high-temperature regions were generated at the vicinal contact points of the catalyst particles due to the concentrated microwave electric field. We also directly observed local high temperature regions at the contact points of the particles during microwave heating of a model silicon carbide spherical material using in situ emission spectroscopy. We conclude that the generation of local heating at the contact points between the catalyst particles is a key factor for enhancing fixed-bed flow reactions under microwave irradiation.

Proton-Enhanced Dielectric Properties of Polyoxometalates in Water under Radio-Frequency Electromagnetic Waves.

Electromagnetic waves, such as microwaves, have been used to enhance various chemical reactions over polyoxometalates. The dielectric properties of catalysts are among the relevant parameters facilitating catalytic reactions under electromagnetic radiation. This study describes the dielectric properties of polyoxometalate catalysts in aqueous and organic solutions to understand the mechanism of interactions between polyoxometalates and electromagnetic waves. Specific loss factors of polyoxometalates were observed at lower frequencies (<1 GHz) by the ionic conduction of the polyoxometalate solution. The evolution of ionic conduction depended strongly on cations rather than anions. Proton-type polyoxometalates exhibited significantly higher loss factors than other cations did. The activation energy for ionic conduction in protonated silicotungstic acid (H4SiW12O40) was significantly low in water (7.6⁻14.1 kJ/mol); therefore, the high loss factor of protonated polyoxometalates in water was attributed to the proton relay mechanism (i.e., Grotthuss mechanism). The results suggested that the proton relay mechanism at the radio-frequency band is critical for generating selective interactions of polyoxometalates with applied electromagnetic fields.