Add-on therapy with montelukast in the treatment of Henoch-Schönlein purpura.

BACKGROUND: Previous studies suggested that leukotrienes (LT) were involved in the pathogenesis of Henoch-Schönlein purpura (HSP). This study investigated the efficacy of an add-on therapy with montelukast in the treatment of HSP. METHODS: In this four-center, double-blind, placebo-controlled, parallel paired comparative study, 130 children with HSP were divided into two large groups: 84 patients without nephritis and 46 patients with nephritis. For each pair of patients with the same severity of disease, one subject was randomly allocated to one subgroup and the other allocated to the other subbroup; one subgroup received routine treatment plus placebo treatment, while the other subgroup received routine treatment plus montelukast treatment for 3 months. The efficacy was determined using Severity Scale Score (SSS). Blood eosinophil count, eosinophil cationic protein (ECP), IgE, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-17, LTB4 , and urinary LTE4 were measured. RESULTS: Add-on therapy with montelukast alleviated the symptoms of HSP including purpura, abdominal pain, stool occult blood, arthritis, proteinuria and hematuria, and, accordingly, shortened the length of hospital stay, and lowered blood eosinophil count, ECP, IgE, IL-4, IL-5, IL-6, IL-8, IL-17, LTB4 , and urinary LTE4 production, and also lowered the HSP relapse rate during the 3 months of treatment, but did not alter the outcome of nephritis at the end of follow up. CONCLUSIONS: Add-on therapy with montelukast alleviated the symptoms of HSP. HSP may be improved by add-on therapy with a leukotriene receptor antagonist.

Elevated expressions of 15-lipoxygenase and lipoxin A4 in children with acute poststreptococcal glomerulonephritis.

Anti-inflammatory effects of the 15-lipoxygenase (15-LO) derivatives lipoxin A(4) (LXA(4)) and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) have been documented in many experimental models of acute inflammation. However, the expression levels of 15-LO and its products in human renal diseases remain unknown. This study investigated the expression levels of LXA(4), leukotriene B(4) (LTB(4)), and 15-LO in leukocytes and glomeruli obtained from 22 children with acute poststreptococcal glomerulonephritis (APSGN), and determined the modulatory effects of both 15-S-HETE and LXA(4) on LTB(4) synthesis in leukocytes and LTB(4)-evoked chemotaxis of polymorphonuclear leukocytes (PMNs) obtained from children during the first 3 days after onset of APSGN. Expression levels of both LXA(4) and 15-LO in leukocytes and glomeruli were up-regulated during the acute phase of disease, further peaking between days 10 and 14, and remained increased after 6 to 8 weeks of APSGN onset. In contrast, blood and urinary levels of LTB(4) as well as the number of glomerular PMNs peaked during the acute phase of disease and then decreased during the resolution phase. Administration of both 15-S-HETE and LXA(4) in vitro inhibited LTB(4)-induced chemotaxis of PMNs and production of LTB(4) from leukocytes obtained from patients with APSGN. The current study provides further support for an anti-inflammatory role for 15-LO products in human nephritis through both antagonism and inhibition of leukotriene synthesis and its biological activity.

[Reversed changes of the 15-lipoxygenase product lipoxin A4 and the 5-lipoxygenase product leukotriene C4 in children with asthma].

OBJECTIVE: To investigate the expressions of 15- and 5-lipoxygenases in leukocytes and the changes of the levels of blood lipoxin A4 (LXA4) and leukotriene C4 (LTC4) in children with asthma. METHODS: The mRNA levels of 15- and 5-lipoxygenases in leukocytes were assessed by RT-PCR, and the levels of blood LXA4 and LTC4 were determined by ELISA, in 106 children with mild, moderate and severe asthma. Forty healthy children served as the controls. RESULTS: In children with mild, moderate and severe asthma, the relative mRNA levels of 15-lipoxygenase in leukocytes were 1.78 ± 0.56, 1.28 ± 0.45 and 0.58 ± 0.22 (F = 16.72, P < 0.01), respectively, and all were higher than that of the controls (0.26 ± 0.12, P < 0.05). The levels of blood LXA4 were (5.52 ± 1.97), (1.86 ± 0.72) and (0.81 ± 0.36) µg/L (F = 22.59, P < 0.01), respectively, decreasing with the severity of asthma, and all were higher than that of the controls [(0.04 ± 0.01) µg/L, P < 0.05]. There was a positive correlation between PEF, FEV(1) and blood LXA4. The relative levels of 5-lipoxygenase mRNA in leukocytes were 0.26 ± 0.12, 0.79 ± 0.34 and 1.21 ± 0.52, respectively in children with asthma of mild, moderate and severe degree (F = 18.64, P < 0.01), which showed an increase with the severity of the disease, and all of which were higher than that of the controls (0.12 ± 0.05, P < 0.05). The levels of blood LTC4 were (22.4 ± 8.2), (54.6 ± 28.4) and (118.7 ± 41.1) ng/L (F = 25.91, P < 0.01), respectively, also showing an increase with the severity of asthma, and were higher than that of the controls [(6.8 ± 2.5) ng/L, P < 0.05]. There was a negative correlation between PEF, FEV1 and blood LTC4. CONCLUSION: The reversed changes of 15-lipoxygenase product LXA4 and 5-lipoxygenase product LTC4 in children with asthma of mild, moderate and severe degree suggests that insufficiency of LXA4, an physiological antagonist to leukotrienes, and an overproduction of LTC4, may be involved in the pathogenesis of worsening of asthma in children.

Characteristics of respiratory syncytial virus-induced bronchiolitis co-infection with Mycoplasma pneumoniae and add-on therapy with montelukast.

BACKGROUND: The influence of Mycoplasma pneumoniae (MP) infection on bronchiolitis remains unclear. Additionally, reports on the efficacies of leukotriene receptor antagonists in the treatment of bronchiolitis have been inconclusive. METHODS: Children with respiratory syncytial virus (RSV)-induced bronchiolitis were divided into two groups: RSV+MP group and RSV group. Each group was randomly divided into two subgroups: one received routine and placebo treatment, while the other received routine and montelukast treatment for 9 months. The cumulative numbers of wheezing episodes and recurrent respiratory tract infections were recorded. Blood parameters were determined. RESULTS: Patients in the RSV+MP group exhibited an older average age, fever, more frequent flaky and patchy shadows in chest X-rays, more frequent extrapulmonary manifestations, and longer hospital stays compared with patients in the RSV group. Additionally, higher baseline blood eosinophil counts, eosinophil cationic protein (ECP), total immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL-4/interferon-γ ratios, leukotriene (LT) B4, and LTC4, and lower baseline lipoxin A4 (LXA4)/LTB4 ratios were observed in the RSV+MP group compared with the RSV group. Montelukast treatment decreased the cumulative numbers of recurrent wheezing episodes and recurrent respiratory tract infections at 9 and 12 months. This efficacy may be related to the montelukast-induced reductions in peripheral eosinophil counts, ECP and total IgE, as well as the montelukast-dependent recovery in T helper (Th) 1/Th2 balance and LXA4/LTB4 ratios in children with bronchiolitis. CONCLUSIONS: RSV bronchiolitis with MP infection was associated with clinical and laboratory features that differed from those of RSV bronchiolitis without MP infection. Add-on therapy with montelukast for 9 months was beneficial for children with bronchiolitis at 9 and 12 months after the initiation of treatment.

[Marine Emission Inventory and Its Temporal and Spatial Characteristics in the City of Shenzhen].

To analyze the characteristic of marine emission in Shenzhen City, activity-based and fuel-based approaches were utilized to develop the marine emission inventory for the year of 2010, using the vessel files from the Lloyd's register of shipping (LR) and vessel track data from the automatic identification system (AIS). The marine emission inventory was temporally (resolution: 1 hour) and spatially (resolution: 1 km x 1 km) allocated based on the vessel track data. Results showed that total emissions of SO2, NO(x), CO, PM10, PM2.5 and VOCs from marine vessels in Shenzhen City were about 13.6 x 10(3), 23.3 x 10(3), 2.2 x 10(3), 1.9 x 10(3), 1.7 x 10(3) and 1. x 10(3) t, respectively. Among various types of marine vessels, emission from container vessels was the highest; for different driving modes, hotelling mode was found with the largest mission. Marine emissions were generally higher in the daytime, with vessel-specific peaks. For spatial distributions, in general, marine emissions were zonally distributed with hot spots in the western port group, Dapeng Bay and the key waterway.

Reversed changes of lipoxin A4 and leukotrienes in children with asthma in different severity degree.

OBJECTIVES: To investigate the expressions of 15-lipoxygenase (15-LO) and 5-lipoxygenase (5-LO) in leukocytes and the changes of blood lipoxin A(4)(LXA(4)), leukotriene (LT)B(4) and LTC(4) in children with asthma, and to explore the relationship between the blood eicosanoids and one of serum high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-5, IL-8 and IL-13 and IgE in children with asthma. STUDY DESIGN: One hundred six asthmatic children were divided into three groups, that is, mild persistent asthmatic group, moderate persistent asthmatic group and severe persistent asthmatic group. Forty healthy children were served as controls. METHODOLOGY: The expressions of 15-LO and 5-LO mRNA in leukocytes were assessed by reverse transcription-polymerase chain reaction, and the blood LXA(4), LTB(4), LTC(4), IL-5, IL-8, and IL-13 were determined with enzyme-linked immunosorbent assay. Serum hsCRP was determined with latex-enhanced immuno-turbidimetry kits. RESULTS: The leukocytic 15-LO expression and blood LXA(4) were gradually decreased, and the leukocytic 5-LO expression, blood LTB(4), LTC(4), IL-5, IL-8, IL-13, and hsCRP were gradually increased in children with asthma from mild degree to moderate and severe degree. There were positive correlations between blood LXA(4) and one of the peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV(1)) percent-predicted values, and negative correlations between blood LTC(4) and one of the PEF and FEV(1) percent-predicted values in children with asthma. There were negative correlations between blood LXA(4) and one of the IL-5, IL-8, IL-13, and hsCRP levels, and positive correlations between one of blood LTB(4), LTC(4) and one of the IL-5, IL-8, IL-13 and hsCRP levels in children with asthma. CONCLUSIONS: The reversed changes between 15-LO, its product LXA(4) and 5-LO, its products LTB(4) and LTC(4) in children with asthma from mild, moderate to severe degree were found, suggesting that insufficient generation of LXA(4) and overproduction of LTs may be the reason for the asthmatic children whose illness become more serious.

Inverse temporal changes of lipoxin A4 and leukotrienes in children with Henoch-Schönlein purpura.

The pathogenesis of Henoch-Schönlein purpura (HSP) is not clearly understood. It remains unclear how changes of lipoxin A(4) (LXA(4)) that acts as a "braking signal" in inflammatory process occur in patients with HSP. In this study, we determined the temporal changes of blood and urinary LXA(4), Leukotriene (LT)B(4) and urinary LTE(4) in 49 children with HSP. Inverse temporal changes between gradually increased blood and urinary LXA(4) and gradually decreased blood and urinary LTB(4) and urinary LTE(4) were found in patients with HSP. Furthermore, both 15-S-hydroxyeicosatetraenoic acid and LXA(4) inhibited the LTB(4)-induced chemotaxis of leukocytes and release of LTB(4) from leukocytes obtained from the patients in the active phase of HSP. In 22 children with HSP nephritis, concordant with the gradually increased severity of mesangial proliferation and proteinuria, the glomerular expressions of 15-lipoxygenase and the levels of urinary LXA(4) gradually decreased and the glomerular expressions of LTC(4) synthase and the urinary LTE(4) and LTB(4) gradually increased. The levels of blood and urinary LXA(4) in patients with HSP nephritis were lower than those in patients with purpura alone in early resolution of HSP. The levels of blood and urinary LTB(4) and urinary LTE(4) in the patients with HSP nephritis were higher than those in patients with purpura alone in early resolution of HSP. There was positive correlation between blood LTB(4) and serum C-reactive protein in 49 children with HSP. These data suggest that LTs may play a proinflammatory and profibrotic role in the pathogenesis of HSP, and insufficiency of LXA(4) may be responsible for the patients with HSP whose illness become more serious.