The 2002 Japanese Pediatric Guideline for the Treatment and Management of Asthma

ABSTRACTThe Japanese Pediatric Asthma Guideline was revised in November of 2002. The guideline, the JPGL2002, has several characteristics different from other asthma guidelines. One of the important differences is the classification of asthma severity ; the frequencies of asthma symptoms in Steps 2, 3 and 4 of the JPGL2002 are similar to those of Steps 1, 2 and 3, respectively, of the Global Initiative for Asthma (GINA). In the JPGL2002, infantile asthma is classified separately, considering the necessity of special concern due to the characteristic features, and three different protocols for long-term management are provided according to the patients' ages : younger than 2 years, 2 to 5 years, and older than 5 years. For patients older than 5 years, inhaled glucocorti- costeroid (ICS) is recommended for asthma with symptoms more than once a month but less than once a week (Step 2). The GlNA classifies this as Step 1 and does not recommend the use of ICS. The recommended dosages of ICS for Steps 3 and 4 of the JPGL2002 are, however, smaller than those for Steps 2 and 3, respectively, of the GINA. It should be clarified in future studies whether or not such a use of ICS can lead to earlier and more frequent remission of asthma, hopefully resulting in the asthma being outgrown

Effects of antioxidants and NO on TNF-α-induced adhesion molecule expression in human pulmonary microvascular endothelial cells

SummaryPro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium. Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-α signaling and upregulate gene expression. We therefore evaluated the effects of pyrrolidine dithiocarbamate (PDTC; 0.1 mM) and spermine NONOate (Sper-NO; 1mM) on adhesion molecule expression and nuclear factor kappa B (NF-κB) activation induced by TNF-α(10ng/ml) in cultured human pulmonary microvascular endothelial cells (PMVEC). Treatment of cells with TNF-α for 4h significantly induced the surface expression of E-selectin and ICAM-1. Treatment with TNF-α for 8h significantly induced the surface expression of E-selectin, ICAM-1 and VCAM-1. The upregulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1h. 8-Bromo-cyclic GMP (1mM) had no such effect, suggesting that the NO donor's effect was non-cGMP-dependent. The mRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2h were decreased significantly by the above two pretreatments. N-acetylcysteine (10mM) and S-nitroso-N-acetylpenicillamine (1mM) had little inhibitory effects on the cell surface and mRNA expression of these adhesion molecules stimulated by TNF-α. Treatment with TNF-α for 4h enhanced HL-60 leukocyte adhesion to human PMVEC, the effect of which was inhibited significantly by pretreatment with PDTC or Sper-NO. These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part through blocking the activation of NF-κB. Although our in vitro results cannot be directly extrapolated to the in vivo situation, they suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung

Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome

Older boys benefit from higher initial prednisolone therapy for nephrotic syndrome.BackgroundA long course of the initial prednisolone therapy has been shown to be more effective than standard-course therapy in reducing relapse rates in children with idiopathic nephrotic syndrome, but it is commonly accompanied by corticosteroid toxicities. There has been no study on prednisolone dosage for the effective treatment of nephrotic syndrome.MethodsSixty-eight children (42 boys and 26 girls) with an initial attack of nephrotic syndrome were randomly allocated into two different long-course treatment groups. Patients in Group 1 received a daily prednisolone dose of 60 mg/m2 for six weeks, followed by an alternate-day dose of 40 mg/m2 for six weeks. Patients in Group 2 had a daily dose of 40 mg/m2 instead of 60 mg/m2.ResultsFour children in each group did not respond within six weeks. Group 1 was associated with a significantly earlier response but more frequent corticosteroid toxicities than Group 2. Boys in Group 1 had a higher rate of sustained remission than boys in Group 2 (P = 0.0073), especially boys four years old or more (P = 0.0027), but girls did not show a significant difference (P = 0.863). Boys four years old or more in Group 1 had a course of frequent relapsing less often than those in Group 2 (2 of 13 vs. 6 of 8, P = 0.0075).ConclusionThese findings indicate that efficient prednisolone doses may vary between sexes and ages, and that a higher initial prednisolone therapy may be of greater benefit to older boys

Role of dendritic cells in Th1/Th2 balance: A novel therapeutic target of allergic diseases

Considerable evidence supports the role of dendritic cells (DC) in the pathogenesis of allergic diseases. Dendritic cells, as the most potent antigen-presenting cells (APC) for the induction of primary immune response to antigen, are deeply involved in the differentiation of na'i've T cells into Th2 cells, thereby developing the development of allergic sensitization. After sensitization, DC may also function as a major APC to control the activation and clonal expansion of memory Th2 cells. In addition, DC are able to produce chemokines to recruit Th2 cells into inflammatory sites, indicating DC are important agents in various phases of allergic inflammation. Recently, we have demonstrated that monocyte chemotactic protein-1 not only regulates the homing of DC, but also modulates DC function. The present paper reviews the role of DC in the regulation of the Th2 response in allergic diseases and discusses the possibility of a new therapeutic strategy targeting chemokine-mediated regulation of DC function

Development of antigen-specific IgE antibodies in atopic and non-atopic infants: Diagnostic value of low levels of IgE against egg white in infants with atopic dermatitis

To analyze the development of antigen-specific IgE in infants and its clinical usefulness, the levels of IgE antibodies against egg white (f1) and cows’ milk (f2) in 33 sera from cord blood, 118 sera from atopic dermatitis (AD) infants and 197 sera from non-atopic control infants were measured by using the CAP radioallergo-sorbent test (RAST) fluoro enzyme immunoassay (FEIA) system, which has a detection limit of 0.15 Ua/mL for f1 and 0.20 Ua/mL for f2. No antigen-specific IgE was detected in cord blood, whereas in infants younger than 6 months of age, 38.5% of AD infants and 6.6% of the non-atopic controls showed IgE against f1 (≥ 0.70 Ua/mL) and 14.3 and 4.0%, respectively, showed low levels (0.15–0.70 Ua/mL) of the IgE. When the cut-off point for positive versus negative f1 RAST was set at 0.15 or 0.35 Ua/mL instead of 0.70 Ua/mL, the significance of the difference in f1 RAST-positive and -negative proportions between atopic and non-atopic infants did not change. Repeated examination of f1 RAST revealed later positive conversion in the majority of AD patients, with no detectable or very low levels (0.15-0.35 Ua/mL) of f1 -specific IgE. In infants at 6 months of age or older, 44.4 and 12.0% of AD patients and non-atopic controls, respectively, showed IgE against f1 (≥ 0.70 Ua/mL) and 37.1 and 22.6%, respectively, showed low levels (0.15-0.70 Ua/mL) of the IgE. These results suggest that f1 RAST at a concentration of 0.15 Ua/mL or higher has diagnostic value for egg allergy in AD infants, especially in infants younger than 6 months of age. The f1 RAST should be examined repeatedly in AD infants with low levels of IgE against f1. Similar results were obtained for f2-specific IgE, but there was a significant decrease in the specificity when the cut-off point was set at 0.20 Ua/mL