Chiharu Okada

Inflammatory Markers in Exhaled Breath Condensate from patients with Asthma.

Background and objective:  Evaluation of airway inflammation is important for the diagnosis and treatment of asthma. Exhaled breath condensate (EBC) is a minimally invasive method for assessing inflammation and may be useful for monitoring airway inflammation in asthma. The aims of this study were to establish an EBC collection method, to assess biomarkers reflecting asthmatic airway inflammation, and to determine the relationship of these biomarkers with asthma severity and lung function.

Nationwide Cross-Sectional Population-Based Study on the Prevalences of Asthma and Asthma Symptoms among Japanese Adults

Background: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. Methods: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20–79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. Results: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20–79 years were 10.1% (95% CI: 9.7–10.5%) and 4.2% (95% CI: 4.0–4.5%), respectively. The prevalences among young adults aged 20–44 years were 9.3% (95% CI: 8.7–9.9%) and 5.3% (95% CI: 4.8–5.8%), respectively. The prevalence of current asthma was highest in females aged 30–39 years in comparison with the other gender and age groups. Conclusions: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.

The prevalence of rhinitis and its association with smoking and obesity in a nationwide survey of Japanese adults

Rhinitis is a common disease, and its prevalence is increasing worldwide. Several studies have provided evidence of a strong association between asthma and rhinitis. Although smoking and obesity have been extensively analyzed as risk factors of asthma, associations with rhinitis are less clear.

Effect of cetirizine on human eosinophil superoxide generation, eosinophil chemotaxis and eosinophil peroxidase in vitro

Cetirizine, a potent H1-antagonist, has been reported to inhibit eosinophil migration into human skin. We, therefore, further evaluated the effect of cetirizine on eosinophil function, including superoxide anion generation, chemotaxis, and eosinophil peroxidase (EP) release. In allergic subjects, superoxide anion generation 60 min after platelet-activating factor (PAF) activation was inhibited by concentrations of cetirizine ranging from 0.01 to 1 microgram/ml (2.612 x 10(-8) to 2.612 x 10(-6) M). No significant inhibition was observed in normal subjects. PAF (10(-6) M)-induced eosinophil chemotaxis was also inhibited by cetirizine. In allergic subjects, percent inhibitions were 47.5 +/- 6.1% at 0.01 microgram/ml, 50.8 +/- 5.1% at 0.1 microgram/ml and 58.9 +/- 6.4% at 1 microgram/ml of cetirizine. In allergic subjects, N-formyl-methionyl-lencyl-phenylalanine induced eosinophil chemotaxis was inhibited by cetirizine, although EP release was not. These results suggest cetirizine has effects on eosinophils which can not be explained by H1-blockade alone.

Inhibitory effects of formoterol on platelet-activating factor induced eosinophil chemotaxis and degranulation.

A new long-acting beta 2-agonist, formoterol, has been reported to have a greater efficacy and duration of action in asthmatic patients as compared to conventional beta 2-agonists. We recently demonstrated that formoterol inhibited antigen-induced late asthmatic response (LAR) and accompanying airway eosinophilia in guinea pigs. In this study, we investigated the direct effect of formoterol in vitro on human eosinophil function, focusing on platelet-activating factor (PAF)-induced eosinophil chemotaxis and eosinophil cationic protein (ECP) release. Purified normodense eosinophils were separated by discontinuous gradient from 12 mild asthmatic patients. Formoterol in concentrations of 1-100 microM significantly inhibited PAF-induced eosinophil chemotaxis in a dose-dependent manner with a concentration of drug required to produce 50% inhibition (IC50) of 10.16 microM; % inhibition: 22.9 +/- 13.0% (1 microM), 51.6 +/- 12.7% (10 microM), 75.0 +/- 11.3% (100 microM). When formyl-methionyl-leucyl-phenylamine (FMLP) was used as a chemoattractant, a similar inhibition of eosinophil chemotaxis by formoterol was observed; % inhibition: 13.1 +/- 5.0% (1 microM). 47.7 +/- 7.6% (10 microM), 65.5 +/- 16.5% (100 microM). A conventional beta 2-agonist, salbutamol, at doses to 100 microM did not show any inhibitory effects on PAF-induced eosinophil chemotaxis. Formoterol in concentrations of 1-100 microM also significantly inhibited PAF-induced ECP release from eosinophils; % inhibition: 21.7 +/- 9.0% (1 microM), 39.3 +/- 7.4% (10 microM), 39.6 +/- 8.4% (100 microM). In the presence of phosphodiesterase inhibitors, theophylline or isobutylmethyl xanthine (IBMX), the inhibition by formoterol on PAF-induced ECP release was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of formoterol on the late asthmatic phenomena in guinea pigs

We investigated the effects of formoterol, a new, long-acting, selective beta 2-adrenoceptor agonist, on the antigen-induced late asthmatic response (LAR) and airway inflammation in guinea pigs. Animals were sensitized by exposure to aerosolized ovalbumin (2% in saline). After antigen challenge, preceded by administration of an H1-receptor antagonist, specific airway conductance was measured with a two-chambered whole-body plethysmograph. An aerosolized solution of formoterol, isoproterenol, or saline was inhaled 15 minutes before challenge. Bronchoalveolar lavage (BAL) was performed 24 hours after challenge. The provocative concentrations of histamine required to decrease specific airway conductance by 50% were obtained before challenge, at 24 hours, and at 72 hours after challenge. The LAR (52.7% +/- 7.7% of the baseline; p less than 0.02) was observed 6 to 8 hours after antigen challenge. An increased cellular influx in BAL (mainly eosinophils and macrophages) and an increased bronchial responsiveness to histamine occurred 24 hours after antigen challenge. Formoterol completely inhibited the LAR and the cellular increase in BAL; however, isoproterenol failed to prevent either the cellular infiltration or the LAR. Formoterol also decreased the antigen-induced increase in bronchial reactivity. These findings suggest that formoterol has inhibitory effects on the underlying inflammatory processes in antigen-induced asthma in addition to prolonged bronchodilation.

Association between Body Mass Index and Asthma among Japanese Adults: Risk within the Normal Weight Range

Background: Increasing amounts of data have shown that some Asian populations are more susceptible to increased weight and development of noncommunicable disease than Western populations. However, little is known about the association between increased weight, particularly within the normal range, and the development of asthma among Asian populations. Methods: To examine the association between increased body mass index (BMI) and asthma among Japanese adults, data from a nationwide population-based cross-sectional survey of asthma prevalence in Japan were analyzed (n = 22,962; age range 20–79 years). BMIs were classified into 7 categories considering WHO recommendations (cutoff points: 17.00, 18.50, 23.00, 25.00, 27.50 and 30.00), and the association between BMI and the prevalences of asthma as well as asthma symptoms were assessed by multivariate logistic regression. Results: The prevalences of obesity (BMI ≧30.00) in this population were relatively low (males 3.0%, females 2.3%). BMI categories of 25.00 or higher in both genders were significantly associated with an increased risk of asthma compared with the reference category (BMI 18.50–22.99). Even in females with a BMI of 23.00–24.99, the prevalence of asthma significantly increased (adjusted odds ratio 1.49, 95% confidence interval 1.16–1.92) compared with that in the reference category. Conclusions: An increase in the prevalence of asthma among Japanese females starts at a BMI of 23.00, which was relatively lower than those reported from Western countries. This finding suggests that the Japanese population is likely to have asthma with a lesser degree of obesity than Western populations.

A Study of Clinical Features of Cough Variant Asthma

Patients with cough variant asthma (CVA) and classic asthma are frequently among subjects who present at clinics complaining of a chronic persistent cough. To reveal the features of CVA, we examined the differences in the clinical appearance between CVA and classic asthma. Ten CVA subjects and 11 classic asthmatics were enrolled in the study; they were recruited among patients who presented at the National Minamiokayama Hospital complaining of a chronic cough. The number of eosinophils in peripheral blood was 256 ± 45.8/µl in CVA and 400 ± 123/µl in classic asthma. Eosinophils represented 67% of the cells of sputum in CVA and 82% in classic asthma. Bronchial responsiveness to methacholine was Dmin 1.37 ± 0.56 U in CVA and 0.71 ± 0.46 U in classic asthma. There was no significant difference in these three parameters. There was only a significant difference in v̇25 between CVA and classic asthma, 80.0 ± 6.9 and 52.2 ± 10.0%, respectively. Eosinophil inflammation was almost the same in both CVA and classic asthma.

Eosinophil Accumulation and Activation in Antigen-Induced Late Asthmatic Response in Guinea Pigs

The purpose of this study was to investigate the participation of airway eosinophils in the antigen-induced late asthmatic response (LAR) and increased airway responsiveness in the guinea pig model of asthma. After antigen challenge, guinea pigs sensitized with aerosolized ovalbumin showed a late-phase decrease in specific airway conductance, which was accompanied by airway hyperresponsiveness to histamine, eosinophilia in the bronchoalveolar lavage fluid (BALF), decreased BALF eosinophil density, and increased generation of superoxide anions from purified BALF eosinophils. We demonstrated an association of the LAR with eosinophil accumulation and activation in the airway.

Density distribution and density conversion of neutrophils in allergic subjects

We investigated the density distribution of neutrophils in peripheral blood of allergic subjects. We divided neutrophils into four groups: fraction 1 (density greater than 1.085), fraction 2 (1.081 less than density less than or equal to 1.085), fraction 3 (1.077 less than density less than or equal to 1.081) and fraction 4 (density less than or equal to 1.077). The percentage of neutrophils in fraction 2 in allergic rhinitis (AR) subjects or asthmatics was lower than that in normals (p less than 0.01). The percentage of neutrophils in fraction 3 and fraction 4 from AR or asthmatics was greater than that in normals (fraction 3, p less than 0.01; fraction 4, p less than 0.05). In neutrophils from AR subjects (fraction 3), chemotaxis to N-formyl-methionyl-leucyl-phenylalanine or platelet-activating factor (PAF) was enhanced compared to fraction 2. PAF (10(-7) M) changed the density of neutrophils (p less than 0.01), which were inhibited by WEB 2086 (p less than 0.05). Furthermore, granulocyte-macrophage colony-stimulating factor changed the density of neutrophils (p less than 0.01). These findings suggest that biological agents may activate neutrophils and convert their density resulting in neutrophils with lower density in allergic subjects.