Effects of Cough Training and Inspiratory Muscle Training on Cough Strength in Older Adults: A Randomized Controlled Trial.

PURPOSE: While the need for preventive strategies to reduce the incidence of aspiration pneumonia has been indicated, it is also important to investigate effective training methods to improve cough function, which is associated with the development of aspiration pneumonia. This study aimed to investigate whether a 4-week home-based unsupervised cough training (CT) or inspiratory muscle training (IMT) program was effective in improving cough strength in older adults. METHODS: Fifty-three ambulatory older adults without airflow limitations were randomly assigned to one of three groups: a CT group (n = 18), an IMT group (n = 18), or a control group (n = 17). The CT and IMT groups performed home-based unsupervised training with a device for 4 weeks. Cough strength (cough peak flow), forced vital capacity, and respiratory muscle strength were assessed at the 4-week and 16-week follow-up. Intention-to-treat analyses were performed to investigate differences between the three groups using linear mixed models. RESULTS: At the 4-week follow-up, the CT group showed significant increases in cough peak flow and forced vital capacity compared with the control group, while the IMT group showed significant increases in inspiratory muscle strength compared with the cough training and control groups. At the 16-week follow-up, the CT group showed a significant increase in cough peak flow compared with the IMT group. CONCLUSION: These preliminary results suggest that a 4-week home-based CT program may have short-term effectiveness in improving cough peak flow in ambulatory older adults. TRIAL REGISTRATION: This trial was registered on UMIN-CTR on 01/05/2018 (UMIN000031656).

A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosis.

OBJECTIVE: Tissue fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc), and an increasing number of promising molecular targets for antifibrotic therapies have been described recently. Transforming growth factor beta (TGFbeta) is well known to be the principal factor that leads to tissue fibrosis. The present study was undertaken to investigate the ability of HSc025, a novel small compound that antagonizes TGFbeta/Smad signaling through the activation of nuclear translocation of Y-box binding protein 1, to prevent tissue fibrosis in vitro or in mouse models of SSc. METHODS: Human dermal fibroblasts were exposed to HSc025 at various concentrations in the presence of TGFbeta, and levels of collagen or fibronectin expression were determined. HSc025 (15 mg/kg/day for 14 days) was administered orally to tight skin mice and to mice with bleomycin-induced pulmonary fibrosis. Improvement of tissue fibrosis was evaluated by histologic or biochemical examination in each model. RESULTS: Pretreatment with HSc025 prevented Smad-dependent promoter activation, in a dose-dependent manner; however, HSc025 had no effect on TGFbeta-induced phosphorylation of Smad3. The inhibitory effects of HSc025 on TGFbeta-induced collagen or fibronectin expression were also confirmed in vitro. Orally administered HSc025 significantly reduced hypodermal thickness and hydroxyproline content in tight skin mice, and markedly decreased the histologic score and hydroxyproline content in the lungs of bleomycin-treated mice. CONCLUSION: These results demonstrate that HSc025 is a novel inhibitor of TGFbeta/Smad signaling, resulting in the improvement of skin and pulmonary fibrosis. Orally available HSc025 might therefore be useful in the treatment of SSc.

Clinical and bacteriological evaluation of the efficacy of piperacillin in children with pneumonia.

We aimed to prospectively evaluate the clinical and bacteriological effects of piperacillin in children with pneumonia. Twenty-eight patients (6 months to 5 years of age) with pneumonia were treated with piperacillin. In the same period, 95 strains of Haemophilus influenzae and 41 strains of Streptococcus pneumoniae were isolated in our department and the minimum inhibitory concentration (MIC) of piperacillin was determined. The clinical efficacy of piperacillin was excellent in 4 cases, good in 23, and fair in 1; the response rate was 96.4% (27/28). Among the isolates from our department, there were 4 strains (9.8%) of penicillin-susceptible S. pneumoniae (PSSP), 32 strains (78.0%) of penicillin-intermediate-resistant S. pneumoniae (PISP), and 5 strains (12.2%) of penicillin-resistant S. pneumoniae (PRSP). Against S. pneumoniae, the MIC50 and MIC90 for piperacillin were 0.5 microg/ml and 2 microg/ml, respectively. Panipenem showed the best results, followed by piperacillin, ampicillin, and flomoxef. Among the isolates from our department, there were 51 strains (53.7%) of beta-lactamase-negative ampicillin-susceptible H. influenzae, 42 strains (44.2%) of beta-lactamase-negative ampicillin-resistant H. influenzae, 1 strain (1.1%) of beta-lactamase-positive ampicillin-resistant H. influenzae, and 1 strain (1.1%) of beta-lactamase-positive amoxicillin-clavulanic acid-resistant H. influenzae. The MIC50 and MIC90 for piperacillin against H. influenzae were 0.0625 microg/ml and 0.125 microg/ml, respectively. Tazobactam/piperacillin and piperacillin showed the best results, followed by panipenem, ampicillin, and flomoxef. Piperacillin proved to be very useful for the treatment of pneumonia in children.