Toshiyuki Nishimuta

Effects of airborne particulate matter on respiratory morbidity in asthmatic children.

Background The effects of airborne particulate matter (PM) are a major human health concern. In this panel study, we evaluated the acute effects of exposure to PM on peak expiratory flow (PEF) and wheezing in children. Methods Daily PEF and wheezing were examined in 19 asthmatic children who were hospitalized in a suburban city in Japan for approximately 5 months. The concentrations of PM less than 2.5 µm in diameter (PM2.5) were monitored at a monitoring station proximal to the hospital. Moreover, PM2.5 concentrations inside and outside the hospital were measured using the dust monitor with a laser diode (PM2.5(LD)). The changes in PEF and wheezing associated with PM concentration were analyzed. Results The changes in PEF in the morning and evening were significantly associated with increases in the average concentration of indoor PM2.5(LD) 24 h prior to measurement (-2.86 L/min [95%CI: -4.12, -1.61] and -3.59 L/min [95%CI: -4.99, -2.20] respectively, for 10-µg/m3 increases). The change in PEF was also significantly associated with outdoor PM2.5(LD) concentrations, but the changes were smaller than those observed for indoor PM2.5(LD). Changes in PEF and concentration of stationary-site PM2.5 were not associated. The prevalence of wheezing in the morning and evening were also significantly associated with indoor PM2.5(LD) concentrations (odds ratios = 1.014 [95%CI: 1.006, 1.023] and 1.025 [95%CI: 1.013, 1.038] respectively, for 10-µg/m3 increases). Wheezing in the evening was significantly associated with outdoor PM2.5(LD) concentration. The effects of indoor and outdoor PM2.5(LD) remained significant even after adjusting for ambient nitrogen dioxide concentrations. Conclusion Indoor and outdoor PM2.5(LD) concentrations were associated with PEF and wheezing among asthmatic children. Indoor PM2.5(LD) had a more marked effect than outdoor PM2.5(LD) or stationary-site PM2.5.

Circadian Variation in Nasal Reactivity in Children with Allergic Rhinitis: Correlation with the Activity of Eosinophils and Basophilic Cells

Background: In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells. Methods: Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured. Results: Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity. Conclusion: These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.

Effect of hourly concentration of particulate matter on peak expiratory flow in hospitalized children: A panel study

BackgroundLittle information is available on the possible association between hourly short-term air pollution and peak expiratory flow (PEF) in asthmatic children.MethodsPEF was measured twice daily, from October through December, 2000, in 17 children aged 8 to 15 years hospitalized with severe asthma. A total of 1198 PEF measurements were made at 7 a.m. and 1175 at 7 p.m. Measurements were conducted immediately prior to medication under the guidance of trained nurses. PEF changes were estimated in 10-μg/m3 increments of particulate matter with a 50% cut-off aerodynamic diameter of ≤2.5 μm (PM2.5), with adjustment for sex, age, height, and temperature. Lagged-hour exposures of up to 24 hours were examined.ResultsIncreased 24-hour mean concentration of PM2.5 was associated with a decrease in both morning and evening PEF (-3.0 l/minute; 95%CI: -4.6, -1.4 and -4.4 l/minute; 95%CI: -7.1, -1.7, respectively). In addition, hourly concentrations of PM2.5 and PEF showed a significant association between some lags of PM2.5 and PEF. Effect size was almost -3 l/minute in both morning and evening PEF for an hourly PM2.5 concentration of 10 μg/m3 in several lags. Even after adjustment for other air pollutants, some of the significant associations with PEF remained.ConclusionAmong hospitalized children with severe asthma, increased hourly concentration of PM2.5 was associated with a decrease in PEF.

Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood‐onset asthma

The thromboxane A2 receptor (TBXA2R) gene is associated with asthma, but no functional genetic variations are known to associate with the disease or its related phenotypes.

Association Study of Matrix Metalloproteinase-12 Gene Polymorphisms and Asthma in a Japanese Population

Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population. Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro. Results: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00–2.56, p = 0.047; OR 1.40, 95% CI 1.04–1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-β. Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue.

The expression level of cutaneous lymphocyte antigen on T-cells as a predictor for the tolerance to hen's egg-induced eczema.

Low levels of the expression of cutaneous lymphocyte antigen (CLA) on peripheral blood T-cells stimulated with chicken ovalbumin can be a predictive marker for the acquisition of tolerance to hen’s egg in patients with egg-induced atopic dermatitis (AD). Skin manifestations associated with food allergy are clinically classified into two types, immediate and nonimmediate, i.e. delayed. These are urticaria and AD, respectively. The radio-allergosorbent test (RAST) is a sensitive in vitro procedure for diagnosis and sometimes can be used as a marker for disease activity in immediate-type food allergy [4]. In contrast, there have been few sensitive allergen-specific blood tests reported as disease activity markers for delayed-type food allergy [4]. Some years ago, Abernathy-Carver et al. [1] reported that T-cells, especially those expressing CLA, play an important role in food-induced AD. After in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with casein, milk-allergic patients with AD showed a significantly greater percentage of CLA+ Tcells than patients with milk-induced gastroenteritis or non-atopic, healthy control subjects. Later, Reekers, et al. [3] reported the induction of CLA on allergenstimulated T-cells in pollen-related food-induced AD. However, as far as we know, CLA expression on egg allergen-stimulated T-cells, especially in relation to disease activity, has not been reported, although hen’s egg is the most common cause of food-related AD in early childhood [6]. In this study we examined the expression of CLA on T-cells stimulated with ovalbumin (OVA) in egg-allergic AD patients in whom hen’s egg was eliminated from the diet, and compared the level with the results of the hen’s egg challenge test to test the efficiency of CLA expression on T-cells as a disease marker for hen’s egg induced AD. A group of 17 patients (age 10–94 months, mean age, 40 months) with a history of eczema when exposed to hen’s egg in whom hen’s egg was eliminated from the diet were included in the study. RAST score to egg white was 0–4 (mean 2.7). All patients underwent a doubleblind, placebo-controlled food challenge test to hen’s egg as previously described [5]. PBMCs (2.0·10 5 ) were