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Background Distinguishing between patients with allergic bronchopulmonary aspergillosis (ABPA) and Aspergillus fumigatus (Af)-sensitized asthmatic patients without ABPA is sometimes difficult owing to the IgE-cross-reactivity between Af and other fungal allergens. Objective To establish the usefulness of molecular-based allergy diagnostics using allergen components from Af in distinguishing ABPA from Af-sensitized asthma without ABPA. Methods Sera from Japanese patients with ABPA (n = 53) and Af-sensitized asthma without ABPA (n = 253) were studied. The levels of IgE and IgG antibodies to allergen components from Af and IgE antibodies to different fugal allergen extracts were measured by ImmunoCAP. Comorbid atopic dermatitis (AD) was taken into consideration in the sensitization profile analysis. Results Patients with ABPA possessed significantly higher levels of IgE antibodies to Asp f 1, and Asp f 2 than asthmatic patients without ABPA. The areas under the receiver operating characteristic curves for the levels of IgE to Asp f 1 and Asp f 2 as diagnostic markers of ABPA were 0.75 and 0.78, respectively. The presence of IgE positivity to Asp f 1 and/or Asp f 2 resulted in increased sensitivity while losing little specificity. Comorbid AD was associated with higher levels of IgE to Asp f 6 (manganese superoxide dismutase from Af, a ubiquitous pan-allergen in fungi) and low but positive levels of IgE to other Af-components, which hampered the serological discrimination of ABPA. Conclusions and clinical relevance The levels of IgE to Asp f 1 and/or Asp f 2 can effectively differentiate ABPA from Af-sensitized asthma, suggesting that the amounts of IgE specific for these molecules are markers for genuine Af-sensitization in ABPA. However, comorbid AD must be taken into consideration in the interpretation of high IgE to Asp f 6. Establishing of IgE-sensitization profiles using panel of Af-allergen components provides valuable information for distinguishing genuine vs. cross-reactive sensitization in Af-sensitized patients.

Background and objective Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. Methods Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). Results The percentage of subjects with osteoporosis (T-score ≤ −2.5), osteopenia (T-score between −1 and −2.5) and a normal BMD (T-score ≥ −1) was 15.2%, 35.9% and 48.9%, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (−1.83 vs. −0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P

Cigarette smoke (CS) induces oxidative stress, which disables macrophage function. In this study, we examined whether Resolvin E1 (RvE1), a pro-resolving mediator known to enhance macrophage functions, attenuates the damage of macrophages by CS extract (CSE) induced oxidative stress. RvE1 blocked p47phox translocation to plasma membrane induced by CSE in a macrophage cell line, RAW264.7 cells, resulting in suppression of superoxide production. Furthermore, pretreatment of RAW264.7 cells with RvE1 restored the phagocytic activity and reduced cell death induced by treatment of CSE. These results suggest that RvE1 plays important roles in preserving macrophage function under CS-induced oxidative stress., Highlights ▸ Resolvin E1 plays a part in protecting macrophage function from damage by cigarette smoke. ▸ RvE1 blocks CSE-induced ROS production in a macrophage cell line, RAW264.7. ▸ RvE1 suppresses the translocation of p47phox to membranes induced by CSE. ▸ RvE1 attenuates the damage of phagocytosis function and cell death induced by CSE.

BACKGROUND AND OBJECTIVE Whether beta(2)-adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to beta(2)-agonist medications remains controversial, partly due to factors that may confound pharmacogenetic associations, including age, cigarette smoking and airway remodelling. To overcome these problems, we performed an analysis using parameters that reflected the specific bronchodilator response to beta(2)-agonists. METHODS The increases in FEV(1) after inhalation of procaterol hydrochloride (Delta FEV(1) procaterol) or oxitropium bromide (Delta FEV(1) oxitropium), and after sequential inhalation of procaterol and oxitropium (total airway reversibility), were measured in 81 Japanese patients with moderate to severe asthma. Approximately 3 kb of the DNA sequence of the coding and 5'-flanking regions of ADRB2 were genotyped by direct sequencing and PCR-restriction fragment length polymorphism assay. RESULTS The mean age of the participants was 54 years, and 38 (47%) were smokers. Although Delta FEV(1) procaterol and Delta FEV(1) oxitropium adjusted for predicted FEV(1) were not associated with ADRB2 polymorphisms, the ratio of Delta FEV(1) procaterol to total airway reversibility was significantly associated with the ADRB2 A46G genotype (P < 0.05). Patients who were homozygous for the A46 allele (arginine at amino acid 16) were more responsive than carriers of the G46 (glycine 16) allele (P = 0.008). Multivariate linear regression analysis showed that Delta FEV(1) procaterol was correlated with the number of A46 alleles (P = 0.014), and also with total airway reversibility (P < 0.001) and smoking index in current smokers (P = 0.009). CONCLUSIONS The ADRB2 A46G polymorphism was associated with a relatively greater bronchodilator responsiveness to beta(2)-agonists even in elderly asthmatic patients and smokers.

Background and objective: Vascular endothelial growth factor (VEGF) is known to contribute to the development of pulmonary oedema, and has been suggested to have a protective role against lung injury. To determine the role of VEGF in acute lung injury (ALI) and ARDS, VEGF levels were measured in lung epithelial lining fluid (ELF) collected from patients with ALI/ARDS. Methods: Forty patients with ALI/ARDS underwent bronchoscopic microsampling to collect ELF on days 0 (onset of ALI/ARDS), 1, 3, 5, 7 and 10, unless the patient was extubated or had died. Twelve patients, who underwent bronchoscopy for examination of small, peripheral pulmonary nodules, served as controls. Results: The initial (day 0) levels of VEGF in ELF of the ALI/ARDS patients who survived and those who did not were 5.5 ng/mL (IQR: 2.3–19.7) and 1.7 ng/mL (IQR: 0.0–6.4), respectively. On days 0, 5, 7 and 10, the VEGF levels in ELF were significantly greater in survivors than in non-survivors (P

We report the first case of thoracic empyema associated with Campylobacter curvus infection. A 65-year-old woman with a history of bronchiectasis presented with acute cough and phlegm. The patient reported dyspnoea and left chest pain accompanied by left pleural effusion, despite treatment with sitafloxacin. Curved Gram-negative rods, eventually identified as C. curvus using 16S ribosomal RNA- and atpA-specific polymerase chain reaction (PCR) and sequencing, were cultured in anaerobic condition of pleural effusion together with Peptostreptococci. The patient recovered after thoracic drainage and treatment with ampicillin/sulbactam and clindamycin. C. curvus, an anaerobe present in human oral cavity, can be associated with extra-oral infections such as empyema.

This article presents an analytical approach to estimating the seismic random response of MDOF elastoplastic structural systems with bilinear hysteretic characteristics under saturation control force. Active saturation control is used for both seismic safety and vibration mitigation under severe earthquake excitation. Numerical calculations are carried out for five-degree-of-freedom systems, and the efficiency of the theoretical saturation control approach is examined from two viewpoints of random seismic response and energy response. Considering the inability to install a saturation control system in actual structural systems, much more realistic nonlinear control systems are developed and examined from the control efficiency viewpoint through simulation analysis based on the earthquake accelerogram recorded during the Hyogo-ken Nanbu earthquake.

Background and objective Mutation of bone morphogenetic protein receptor type 2 (BMPR2) is a cause of pulmonary arterial hypertension (PAH). We measured the prevalence of this mutation and its impact on the phenotypes and long-term clinical outcomes in Japanese patients. Methods Between 1999 and 2007, we consecutively enrolled and, until March 2012, followed 49 Japanese patients with PAH, including nine familial cases from seven families. We genotyped BMPR2, using direct sequencing and multiplex ligation-dependent probe amplification, to examine (i) the prevalence of BMPR2 mutations and gene rearrangement, (ii) the relationship between BMPR2 genotype and clinical phenotypes, and (iii) the long-term clinical outcomes of mutation carriers versus non-carriers under state-of-the-art medical therapy. Results BMPR2 mutations were present in four of the seven families (57%) and in 14 of the 40 patients (35%) with sporadic PAH. The mean age at onset of PAH was 37.4 years in BMPR2 carriers, versus 25.9 years in non-carriers (P = 0.0025). The gender distribution and hemodynamic status at time of diagnosis were similar regardless of the mutation status. The 5-year survival rate after diagnosis of PAH was 88.5% in BMPR2 mutation carriers versus 80.9% in non-carriers (ns). Conclusions The prevalence of BMPR2 mutations in Japanese with PAH was similar to that reported in other populations. At onset of PAH, BMPR2 mutation non-carriers were, on average, younger than carriers, possibly due to the heterogeneity of this subpopulation. With state-of-the-art therapy, the long-term survival of patients with PAH was high, regardless of the mutation status.

An optimal control force of elastoplastic hysteretic structural seismic response is derived and the possible simplification of this force is examined. Based on this simplification, a velocity-feedback type of control force with saturation is considered in order to examine the influence of an insufficient control force on elastoplastic structural seismic response. The seismic response is estimated based on the probabilistic approach, where the equivalent linearization is valid for both nonlinear hysteretic characteristics of the restoring force and nonlinear saturation characteristics of the control force. Numerical examples are given for bilinear hysteretic systems with single degrees of freedom.

An analytical approach to the optimum structural design parameters is developed on the basis of seismic reliability and inter-story response distribution. An earthquake-like stationary random excitation being assumed, probabilistic earthquake response is estimated as the solution of a simple simultaneous algebraic equation. Based on this probabilistic earthquake response, the optimum parameters are determined by selecting seismic structural reliability and an inter-story response distribution index as objective functions. The validity of this approach is demonstrated by examining the perspective and contour lines of the objective functions regarded as a function of design parameters for elastic structural systems with six degrees of freedom. The possible application of this approach is also presented to the determination of elasto-plastic structural parameters with bi-linear hysteretic characteristics. Other aspects of the approach's validity are also examined from the response distribution viewpoint for the elastic structural system with recorded strong earthquake motions. The influence of the higher modal response and the earthquake's predominant angular frequency on the optimum parameters are also discussed.

An analytical representation of the bilinear hysteretic characteristic is presented. Using this representation, the response of a single-degree-of-freedom bilinear hysteretic system subjected to non-stationary random excitation is examined by equivalent linearization. An ordinary differential equation is derived for the covariance matrix of the response. Numerical examples are presented and the accuracy of the approach is demonstrated. Extension of the approach to a wider class of hysteretic systems is discussed.