Effects of the Addition of Beta2-agonist Tulobuterol Patches to Inhaled Corticosteroid in Patients with Asthma

ABSTRACTBackgroundWhether the additive effects of the tulobuterol patch (TP), the world’s first transdermal beta2-agonist preparation, are useful in asthma patients receiving inhaled corticosteroid (ICS) is unclear. To examine the add-on effects of TP on bronchial hyperresponsiveness and reduction of the percentage of sputum eosinophils, and to compare add-on effects of TP, slow-release theophylline (SRT), and a leukotriene receptor antagonist (LTRA) in patients with asthma receiving ICS.MethodsStudy 1: We randomly allocated 24 patients with asthma receiving ICS alone in equal numbers to either control treatment (ICS alone at conventional doses) or TP treatment (ICS at conventional doses plus TP at 2 mg/day). Following a 2-week observation period, patients received the allocated drug regimens for 4 weeks. Methacholine challenge test and measurement of percentage of eosinophils in hypertonic saline- induced sputum were performed before and after the treatment period. Study 2: We compared add-on effects of TP, SRT, and LTRA in 65 patients with asthma receiving ICS alone, using spirometry and peak expiratory flow (PEF). Participants in these studies had experienced decrease in morning PEF to <80% of the predicted value at least twice a week.ResultsStudy 1: In the TP group, improvement of bronchial hyperresponsiveness and decrease in percentage of sputum eosinophils both indicated a statistically significant difference (p < 0.01, and p < 0.05, respectively). These findings were not observed in the control group. Study 2: forced expiratory volume in 1 second (FEV1) and PEF markedly increased after treatment with TP compared with treatment with SRT or LTRA.ConclusionsThese findings suggest that TP can be used as a long-term add-on controller for patients with asthma receiving ICS

Function of Monocytes in the Retired Workers of the Okunojima Poison Gas Factory

Monocyte function of poison gas workers was determined and the following results were obtained. 1) No difference in cytostatic activity could be observed between poison gas workers and their controls. 2) Phagocytic activity of poison gas workers was slightly depressed when compared with that of the controls, but the difference was not significant. By duration of work, it was observed that the group with duration of work exceeding five years had a significantly lower value when compared with the group with duration of work being less than two years. 3) Chemotactic activity of poison gas workers tended to be depressed when compared with that of the controls. The activity tended to be more depressed the longer the duration of work. 4) A significant positive correlation was observed between cytostatic activity and phagocytic activity

Detection of Lymphocyte Subsets by Monoclonal Antibodies in Aged and Young Humans

With the use of Leu-series monoclonal antibodies, peripheral blood lymphocyte subsets in aged and young humans were determined. 1) In comparison with young individuals, Leu-1+ cells and Leu-2a+ cells were decreased, whereas Leu-7+ cells and Leu-3a/Leu-2a were increased in aged individuals. 2) No sex difference could be observed in lymphocyte subsets. 3) PHA response of lymphocytes showed a negative correlation with Leu-2a+ cells and a positive correlation with Leu-3a/Leu-2a in aged individuals

Production of Interleukin 2 in Human Peripheral Blood Lymphocytes: Optimal Condition for its Culture

For the assay of the production of Interleukin 2 (IL-2) in human peripheral blood lymphocytes (human PBL), a study was made on the optimal condition for its culture. 1) The optimal condition for the production of IL-2 was considered to be incubation time of 24 hr, number of PBL of 1 x 106 cells/ml, and phytohemagglutinin-M (PHA-M) concentration of 1 — 5% 2) By one way mixed lymphocyte reaction (one way MLR), IL-2 activity similar in level to that by PHA-M stimulation could also be obtained. It was maximal at the 4th day of culture. 3) By PHA-P (0.06%) stimulation, IL-2 could also be produced similar to that by PHAM stimulation but it decreased in the order of Con A, PWM and PPD and hardly any production of IL-2 could be observed by LPS

Interleukin-2 Production and Lymphocyte Proliferation in Aged and Young Humans

A study was made on the effect of aging on the production of Interleukin-2 (IL-2) and lymphocyte proliferation of human peripheral blood lymphocytes. 1) In comparison with young individuals, IL-2 production tended to decrease in aged individuals, while lymphocyte proliferation showed a significant decrease. 2) A significant correlation was observed between IL-2 production and lymphocyte proliferation in both the aged and young human populations. 3) IL-2 production showed a negative correlation with Leu-2a positive rate and a positive correlation with Leu-3a/Leu-2a ratio in aged individuals

Immune Functions of Former Poison Gas Workers I. Mitogenic response of lymphocytes and serum factors

The relation of depressed immune function to carcinogenesis has been estimated in the living body. The authors have measured the immunological parameters in former poison gas workers, a group having a high risk of carcinogenesis, for comparison with age matched normal controls and the following results were obtained. 1) With regard to serum factors, no significant difference could be demonstrated between normal controls and poison gas workers in such immunoglobulins as IgG, IgA, and IgM, in acute phase reactants such as α1-AT, α1-AG, α2-HS and C3 and in such tumor markers as CEA, ferritin, and β2-microglobulin. Furthermore, no difference could be observed in the positive rate of immune complex and in complement activity. 2) No difference could be observed between the two groups with regard to tuberculin skin reaction and number of lymphocytes, but the longer the duration of work at the poison gas factory, the more significant was the increase in those who showed negative tuberculin skin reaction. 3) In comparison with normal controls, mitogenic response to PHA showed a significant decrease in poison gas workers, but no significant difference could be seen in mitogenic response to Con A and PPD and in mixed lymphocyte reaction. 4) No significant difference could be demonstrated between the two groups in the inhibitory effects of serum on mitogenic response to PHA and Con A and on mixed lymphocyte reaction

Demographic and Clinical Characteristics of Patients with Severe Asthma in the Asian Pacific Region : data from the International Severe Asthma Registry (ISAR)

Peer reviewe

Development of a questionnaire to evaluate asthma control in Japanese asthma patients

Background: The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. Methods: A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. Results: The intra-class correlation coefficients (ICCs) were within the range of 0.55–0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were −0.78, −0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001). Conclusions: The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients. Clinical Trial registration: UMIN00001658

Examination of the cut-off values for a questionnaire used to evaluate asthma control in Japanese asthma patients

Background: The Japan Asthma Control Survey (JACS) questionnaire, developed as a tool for measuring asthma control levels in Japanese asthma patients, was previously tested for its reliability and validity. However, many of the patients enrolled in the original validation study had mild asthma; thus a re-evaluation including severe cases was required to calculate more reliable cut-off values. Methods: Pooled analysis of data from the original validation study and the subsequent medication guidance study including adult patients with severe asthma was conducted to calculate the JACS questionnaire cut-off values and to assess their sensitivity and specificity for identifying “well-controlled”, “not well-controlled”, and “poorly controlled” asthma as described in the Asthma Prevention and Management Guideline 2015 (JGL2015). The data were from 353 patients with mild to severe persistent asthma classified according to JGL2015. Results: The JACS questionnaire cut-off values were 8.0 (sensitivity, 67.9%; specificity, 81.9%) for “well-controlled” and “not well-controlled” and 4.8 (sensitivity, 85.3%; specificity, 53.3%) for “not well-controlled” and “poorly controlled”. Conclusions: JACS cut-off values can be expected to be more useful for evaluating asthma control status in clinical practice and clinical research, thus improving asthma treatment, in Japan. This analysis was the original validation study (UMIN000016589) and the subsequent medication guidance study (UMIN000024353). Keywords: Asthma control, Cut-off values, JACS, Japanese, Questionnair