Relationship between sputum clusterin levels and childhood asthma.

BACKGROUND: Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation-associated diseases. Clusterin levels in childhood asthma have not been evaluated. OBJECTIVES: (1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness. METHODS: This study included 170 children aged 5-18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme-linked immunosorbent assay. RESULTS: Children with stable asthma had a higher clusterin level than healthy controls [4540 (3872-5651) pg/mL vs. 3857 (1054-4369) pg/mL, P < 0.001]. The clusterin level was also more elevated in eosinophil-dominant sputum than in non-eosinophilic sputum in stable asthma [5094 (4243-6257) pg/mL vs. 4110 (1871-4839) pg/mL, P = 0.0017]. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma [1838 (350-4790] pg/mL vs. 4540 (3872-5651) pg/mL, P < 0.001]. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = -0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters. CONCLUSIONS AND CLINICAL RELEVANCE: Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti-inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.

Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is the second leading cause of reported transfusion-related fatalities in the United States. While its occurrence has been previously investigated after red cell and plasma transfusion, no data are available regarding its association with platelet transfusion. Our goal was to determine the rate of platelet-associated TACO at our university medical centre. STUDY DESIGN AND METHODS: This study had retrospective and prospective analyses. The 13-year retrospective analysis served to determine the historical rate of platelet-associated TACO by passive reporting. The 30-day prospective analysis included active surveillance of all non-emergently issued and non-operative platelet recipients ≥16 years old with no transfusions in the previous 6 h determined by analysis of blood bank product issue records. Data collected included demographics, vital signs pre- and posttransfusion, fluid balances, supplemental oxygen use, reports of dyspnoea, and infusion rates. For the prospective analysis, all variables were collected within 24 h of transfusion from the medical record and, when necessary, interviews with care providers and/or patients. RESULTS: In the retrospective analysis, 366 reactions were reported, of which 6 (1·6%) were TACO. The historical rate of TACO was 1:5997 transfused platelet units. During the prospective analysis, 225 eligible patients received a total of 334 units of platelets. The average platelet transfusion volume was 261 ± 26 ml, and the average infusion rate was 391 ± 198 ml/h. Two unreported TACO reactions were discovered and characterized by new-onset hypertension, crackles on lung auscultation, dyspnoea, hypoxia and supplemental oxygen requirements which resolved completely with diuresis. The rate of TACO during this prospective analysis was 1:167 transfused platelet units. CONCLUSION: Platelet-associated TACO is greatly underestimated by passive reporting in the adult patient population.

Pandemic influenza virus, pH1N1, induces asthmatic symptoms via activation of innate lymphoid cells.

BACKGROUND: The pandemic strain of the influenza A virus (pH1N1) in 2009 caused many complications in patients. In this study, we introduce asthmatic symptoms as a complication of pH1N1 infection in children, not having a relationship with asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1-infected children and elucidate the underlying mechanisms of airway hyper-responsiveness (AHR) induced in a murine model of pH1N1 infection. METHODS: As a retrospective study, pH1N1-infected children who were hospitalized with moderate to severe acute asthmatic symptoms were enrolled and administered a methacholine challenge test (MCT) at 3 months post-discharge. Additionally, the induction of AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The effect of the innate immune response on the development of AHR following pH1N1 infection was investigated. RESULTS: More than 70% of the pH1N1-infected children without a pre-infection diagnosis of asthma had a negative response on the MCT. None of these children had recurrent wheezing or asthma during the 3 years following pH1N1 infection. The development of AHR in pH1N1-infected mice was associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2). CONCLUSIONS: This study demonstrates that pH1N1 infection directly induces transient asthmatic symptoms in patients regardless of their medical history. pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type cytokine secretion in mice via the activation of ILC2; it may be activated independently of adaptive immunity.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Inhibition of immediate-type allergic reaction by Rosa davurica Pall. in a murine model.

We studied the effect of Rosa davurica Pall. (Rosaceae) fruits (RdF) on immediate-type allergic reactions. RdF completely inhibited compound 48/80-induced systemic anaphylactic shock at the dose of 1 g/kg. When RdF was given as pretreatment, at concentrations ranging from 0.0001 to 1 g/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. RdF inhibited the passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody dose dependently. RdF also inhibited the histamine release induced by compound 48/80 or anti-DNP IgE from the rat peritoneal mast cells (RPMC). Moreover, RdF had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that RdF may contain compounds with actions that inhibit mast cell degranulation in the rat.

7-feruloylloganin: an iridoid glucoside from stems of Lonicera insularis.

A new iridoid glucoside, 7-feruloylloganin (1), was isolated from stems of Lonicera insularis, along with six known lignans including (-)-pinoresinol, 9alpha-hydroxypinoresinol, balanophonin, erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-[2-formyl-(E)-vinyl]-2-methoxyphenoxy]-propane-1,3-diol, threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-[2-formyl-(E)-vinyl]-2-methoxyphenoxy]-propane-1,3-diol and buddlenol A. The structure of 1 was determined by analyses of 2D NMR (1H-1H COSY, HMQC and HMBC) and HRFABMS.