Kyotaro Ide

Involvement of the p38 MAPK pathway in IL‐13‐induced mucous cell metaplasia in mouse tracheal epithelial cells

Background and objective:  IL‐13 has been shown to play a pivotal role in mucous cell metaplasia, which is an important feature of the pathogenesis of asthma. However, the signalling pathways evoked by IL‐13 in airway epithelial cells remain unclear. This study investigated the signalling mechanism of IL‐13‐induced mucous cell metaplasia in primary cultures of mouse tracheal epithelial cells (mTEC).

Superoxide generation by alveolar macrophages from aged rats: improvement by in vitro treatment with IFN-γ

Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but it is unclear whether or not this is due to the inability of these cells to be activated. To elucidate this, we investigated the capacity of AM from young (16-week-old) and aged (100-week-old) rats to become primed with recombinant rat interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)-elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma production by the spleen cells of young and aged animals. The data indicated that AM freshly harvested from non-sensitized aged rats produced less O2- than those from young animals. A similar result was obtained in BCG-sensitized rats. However, AM from aged rats were primed with in vitro treatment with IFN-gamma for increased rate of O2- production to an equivalent level of that by AM from young animals. In addition, the ability of spleen cells to produce IFN-gamma was well maintained in aged rats. These results suggest that AM function is suppressed in the lungs of aged animals. Our observation that the decreased AM function in aged rats can be reversed is important because it suggests that appropriate treatment may reduce the incidence and mortality of respiratory infections in the elderly.

Epithelial‐mesenchymal transition induced by transforming growth factor‐β1 in mouse tracheal epithelial cells

Background and objective:  Epithelial‐mesenchymal transition (EMT) is the process by which differentiated epithelial cells undergo a phenotypic transition to mesenchymal cells. This process may occur in certain fibrotic diseases that involve airway remodelling. However, few studies have directly proved the occurrence of EMT in primary cultures of airway epithelial cells. The aim of this study was to clarify whether airway epithelial cells can differentiate into mesenchymal cells through EMT.

Effects of suplatast tosilate on cytokine profile of bronchoalveolar cells in allergic inflammation of the lung

Objective: Suplatast tosilate is an anti‐allergic agent that inhibits IgE antibody production. It appears to have an inhibitory effect on the production of Th2 cytokines (interleukin (IL)‐4, IL‐5) in vitro. In the present study, we investigated the effects of suplatast on eosinophil infiltration and cytokine mRNA expression in bronchoalveolar lavage (BAL) fluid in a Brown Norway (BN) rat model of bronchial asthma.

Effect of Switching from Salmeterol Fluticasone to Formoterol Budesonide Combinations in Patients with Uncontrolled Asthma

BACKGROUND Combination therapy with an inhaled corticosteroid (ICS) and a long-acting β(2)-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen. METHODS This was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV(1), and fractional exhaled nitric oxide (FeNO) at the end of treatment period. RESULTS Eighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV(1) values improved significantly, but not FeNO values, after switching from SFC to FBC. CONCLUSIONS Switching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.