Summary
Secretory IgA (SIgA) is a well‐known mucosal‐surface molecule in first‐line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been ...emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non‐IPF subjects. An in‐vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐β and interleukin (IL)‐8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA‐induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF‐β and IL‐8.
Secretory IgA is a well‐known mucosal‐surface molecule in first‐line defense against extrinsic pathogens and antigens. It is unclear whether it plays a pathological role in lung diseases. In the present study, we showed that accumulated mucus in the airspaces of idiopathic pulmonary fibrosis lungs contained abundant SIgA in direct contact with the epithelia of remodeled tissue, and that SIgA bound to the surface of A549 cells, leading to production of profibrotic and inflammatory cytokines, VEGF, TGF‐β and IL‐8.
▶ Polycrystalline CHA zeolite layers could be formed using gels containing strontium. ▶ The membranes show excellent dehydration performances for ethanol solutions. ▶ The influence of synthesis gel ...on the membrane performance was discussed.
CHA-type zeolite membranes with excellent dehydration performance can be prepared on a porous α-Al
2O
3 support tube by the secondary growth of seeds in a synthesis gel containing strontium. The permeation flux and separation factor of the membrane were 2.89
kg
m
−2
h
−1 and >100,000, respectively, for a 50
mol% ethanol solution at 313
K. In this work, the CHA-type zeolite membranes were prepared using the gel with different compositions to discuss the influences of the synthesis gel composition on the morphology, composition, and dehydration performance of the CHA-type zeolite membrane. As a result, the CHA-type zeolite membrane could be prepared in the gel with the following compositions: SiO
2/Al
2O
3
=
2–16; H
2O/SiO
2
=
65–250; H
2O/(K
2O
+
SrO)
=
100–400; SrO/(K
2O
+
SrO)
=
0.10–0.85. Furthermore, the CHA-type zeolite membrane was ion-exchanged with lithium, sodium, rubidium, and cesium ions, and the dehydration performances of the ion-exchanged membranes were also determined. Based on these results, the effect of strontium for the membrane preparation was discussed in this paper.
There is increasing recognition of asthma-COPD overlap syndrome (ACOS), which shares some features of both asthma and COPD; however, the prevalence and characteristics of ACOS are not well ...understood. The aim of this study was to investigate the prevalence of ACOS among patients with COPD and its characteristics using a stepwise approach as stated in the recent report of the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).
This multicenter, cross-sectional, observational study enrolled outpatients who were receiving medical treatment for COPD. Clinical data, including spirometry results, were retrieved from medical records. For symptom assessment, patients were asked to complete the Clinical COPD questionnaire and the modified British Medical Research Council questionnaire.
Of the 1,008 patients analyzed, 167 (16.6%) had syndromic features of ACOS. Of the total number of patients, 93 and 42 (9.2% and 4.2%) also had a predefined clinical variability of ≥12%/≥200 mL and ≥12%/≥400 mL in forced expiratory volume in 1 second (FEV
), respectively, and therefore were identified as having ACOS. Conversely, the number of patients who had either syndromic or spirometric feature of ACOS was 595 (59.0%, ≥12%/≥200 mL FEV
clinical variability), and 328 patients (32.5%, ≥12%/≥400 mL FEV
clinical variability) had both the features. Patients identified as having ACOS were of significantly younger age, had a shorter duration of COPD, lower number of pack-years, better lung function, milder dyspnea symptoms, and higher peripheral blood eosinophil values compared with patients with COPD alone. The rate of exacerbations in the previous year was not significantly different between the ACOS and COPD groups.
Using a stepwise approach, as stated in the GINA/GOLD report, the proportions of patients identified as having ACOS were found to be 9.2% and 4.2% (depending on the FEV
variability cutoff used) among the 1,008 outpatients medically treated for COPD in a real-life clinical setting.
The prevalence and mortality of chronic obstructive pulmonary disease (COPD) in elderly patients are increasing worldwide. Low body mass index (BMI) is a well-known prognostic factor for COPD. ...However, the obesity paradox in elderly patients with COPD has not been well elucidated. We investigated the association between BMI and in-hospital mortality in elderly COPD patients.
Using the Diagnosis Procedure Combination database in Japan, we retrospectively collected data for elderly patients (>65 years) with COPD who were hospitalized between July 2010 and March 2013. We performed multivariable logistic regression analysis to compare all-cause in-hospital mortality between patients with BMI of <18.5 kg/m2 (underweight), 18.5-22.9 kg/m2 (low-normal weight), 23.0-24.9 kg/m2 (high-normal weight), 25.0-29.9 kg/m2 (overweight), and ≥30.0 kg/m2 (obesity) with adjustment for patient backgrounds.
In all, 263,940 eligible patients were identified. In-hospital mortality was 14.3%, 7.3%, 4.9%, 4.3%, and 4.4%, respectively, in underweight, low-normal weight, high-normal weight, overweight, and obese patients. Underweight patients had a significantly higher mortality than low-normal weight patients (odds ratio OR: 1.55, 95% confidence interval CI: 1.48-1.63), whereas lower mortality was associated with high-normal weight (OR: 0.76, CI: 0.70-0.82), overweight (OR: 0.73, CI: 0.66-0.80), and obesity (OR: 0.67, CI: 0.52-0.86). Higher mortality was significantly associated with older age, male sex, more severe dyspnea, lower level of consciousness, and lower activities of daily living.
Overweight and obese patients had a lower mortality than low-normal weight patients, which supports the obesity paradox.
Nanocrystallization of amorphous alloys induced by electronic energy deposition has been frequently reported in recent years. In this paper, the crystallization of amorphous Fe85B15 alloy was ...performed by electron irradiation with 2 MeV electrons up to a flux of 4.0 X 1024 m-2 s-1. It was found that at 298 K, nanocrystalline Fe-B intermetallic phases formed prior to alpha-Fe phase, while at 463 K, only the alpha-Fe phase was observed. This phenomenon cannot be interpreted in terms of the electron-beam heating, but may be attributed to the irradiation-induced increases in the short-range order and atomic diffusivity. Theoretical analysis also showed that the maximum-temperature rise driven by beam heating is much lower than that required for thermal crystallization. Our work offers strong evidence that the irradiation-induced crystallization in amorphous alloys is not a thermal activation process.
The effect of pre-straining at and below 823K prior to hot forging at 973K on the magnetic properties of hot-deformed Nd–Fe–B magnets was examined. Nd–Fe–B alloys prepared in this study could be ...hot-forged, even at 723K. Both the squareness and the coercivity of the magnetization curves at room temperature were improved by pre-straining at 773K or below, owing to the suppression of the formation of non-aligned coarse Nd2Fe14B grains.
Mandarin translation of
Background and purpose: The voltage‐gated Na+ channels (Nav) and their corresponding current (INa) are involved in several cellular processes, crucial to metastasis of cancer ...cells. We investigated the effects of eicosapentaenoic (EPA), an omega‐3 polyunsaturated fatty acid, on INa and metastatic functions (cell proliferation, endocytosis and invasion) in human and rat prostate cancer cell lines (PC‐3 and Mat‐LyLu cells).
Experimental approach: The whole‐cell voltage clamp technique and conventional/quantitative real‐time reverse transcriptase polymerase chain reaction analysis were used. The presence of Nav proteins was shown by immunohistochemical methods. Alterations in the fatty acid composition of phospholipids after treatment with EPA and metastatic functions were also examined.
Key results: A transient inward Na+ current (INa), highly sensitive to tetrodotoxin, and NaV proteins were found in these cells. Expression of NaV1.6 and NaV1.7 transcripts (SCN8A and SCN9A) was predominant in PC‐3 cells, while NaV1.7 transcript (SCN9A) was the major component in Mat‐LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed to inhibit proliferation in PC‐3 cells. Exposure to EPA produced a rapid and concentration‐dependent suppression of INa. In cells chronically treated (up to 72h) with EPA, the EPA content of cell lipids increased time‐dependently, while arachidonic acid content decreased. Treatment of PC‐3 cells with EPA decreased levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis.
Conclusion and implications: Treatment with EPA inhibited INa directly and also indirectly, by down‐regulation of Nav mRNA expression in prostate cancer cells, thus inhibiting their metastatic potential.
Mandarin translation of
Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal ...adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD.
We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy.
Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67-0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference.
Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD.
Background
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small‐vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially ...life‐threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in‐hospital mortality, using a national inpatient database in Japan.
Methods
We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in‐hospital mortality.
Results
A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In‐hospital deaths occurred in 97/2195 patients (4.4%). Higher in‐hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio‐cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies.
Conclusions
Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.
PDF
