Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro

Kazuhito Asano1, Yusuke Shikama2, Yasuhiro Shibuya2, Hiroaki Nakajima2, Ken-ichi Kanai3, Naohiro Yamada3, Harumi Suzaki31Division of Physiology, School of Nursing and Rehabilitation Sciences; 2Respiratory Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan; 3Department of Otolaryngology, School of Medicine, Showa University, Tokyo, JapanBackground: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with an accumulation of inflammatory cells. There is also increasing evidence that metalloproteinases (MMPs) may contribute to the pathogenesis of COPD, but the influence of agents that used for the treatment of COPD is not well understood.Objective: We evaluated whether tiotropium bromide hydrate (TBH), a M3 muscarinic receptor antagonist, could inhibit MMP production from lung fibroblasts (LFs) in response to tumor necrosis factor (TNF)-α stimulation.Methods: LFs were established from normal lung tissues taken from patients with lung tumors. LFs (5 × 105 cells/ml) were stimulated with TNF-α in the presence of various concentrations of TBH. After 24 h, culture supernatants were obtained and assayed for the levels of MMPs and tissue inhibitor of metalloproteinases (TIMPs) by ELISA. The influence of TBH on mRNA expression of MMPs and TIMPs in 4 h-cultured cells was also examined by real-time RT-PCR. Furthermore, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) in LFs treated with TBH for 4 h was examined by ELISA.Results: TBH at more than 15 pg/ml inhibited the production of MMP-2 from LFs after TNF-α stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected by TBH through the suppression of both mRNA expression and transcription factor, NF-κB, activation in LFs induced by TNF-α stimulation.Conclusion: These results suggest that the attenuating effect of TBH on MMP-2 production from LFs induced by inflammatory stimulation may be additional beneficial therapeutic effects not directly relating to its bronchodilatory effects.Keywords: tiotropium, lung fibroblasts, matrix metalloproteinases, suppression, in vitr

Hemoptysis following Talc Pleurodesis in a Pneumothorax Patient

The purpose of this article is to report a case of hemoptysis occurring in combination with secondary spontaneous pneumothorax following chemical pleurodesis by talc. A Japanese male with cancer of renal pelvis was found with the left pneumothorax and multiple lung metastases. A computed-tomography scan revealed severe emphysema throughout the lungs. Talc pleurodesis was employed to arrest air leakage. The patient developed hemoptysis 45 minutes after talc injection into the thorax. This is the first report of hemoptysis following talc pleurodesis. The agent could induce severe inflammation in capillary vessels of the lung following visceral pleura infiltration

Respiratory rhythm affects recalibration of body ownership

Abstract Change in body perception requires recalibration of various sensory inputs. However, it is less known how information other than sensations relates to the recalibration of body perception. Here, we focused on the relationship between respiration and cognition and investigated whether respiratory rhythms are related to the recalibration of hand perception. We built a visual feedback environment, in which a mannequin hand moved in conjunction with its own respiratory rhythm, and participants performed an experiment under conditions in congruency/incongruency for spatial and temporal factors. The temporal and spatial congruency between own respiratory rhythm and the mannequin hand markedly facilitated the phenomenon of hand ownership sense transfer to the mannequin hand, while incongruency had little effect on the change in hand ownership. The finding suggests that an internal model in the brain allows respiratory rhythms to be involved in the adaptation of the body’s neural representations

Clarithromycin-resistant Mycobacterium Shinjukuense Lung Disease: Case Report and Literature Review

Mycobacterium shinjukuense is a species of non-tuberculous mycobacteria newly reported in 2010. Herein, we report on an 85-year-old woman with M. shinjukuense lung disease. Radiographic examinations showed consolidation with bronchiectasis, which responded transiently to clarithromycin monotherapy. After 1 year of monotherapy, the diagnosis was established and drug susceptibility testing revealed elevated minimum inhibitory concentration for clarithromycin. The patient was then treated successfully with a combination of antituberculosis drugs. The transient response to clarithromycin suggested that the M. shinjukuense had acquired resistance to clarithromycin. Appropriate treatment for M. shinjukuense lung disease has not yet been established; therefore, it is important to accumulate information from case reports

In-hospital blood collection increases the rate of indeterminate results in interferon-gamma release assays

Background: The interferon (IFN)-γ release assay (IGRA) has recently been established as a method to evaluate the infection status of tuberculosis instead of the tuberculin skin test. However, indeterminate results can create challenges to interpretation. The IGRA has been available in Japan since 2005, including the recently launched QuantiFERON-TB Gold Plus (QFT-plus) assay. Objectives: The aim of this study was to investigate the clinical features and predictors of indeterminate results by the QFT-plus test in routine practice. Methods: This was a cross-sectional study of 1258 patients. Multivariate logistic regression models were employed to investigate the clinical factors related to indeterminate results by the QFT-plus. Results: Overall, 91.8% of results were found to be conclusive and 8.2% were indeterminate. The QFT-plus indeterminate results were predominantly due to a low level of IFN-γ production by mitogens. Multivariate analysis indicated that an indeterminate result was significantly associated with age, sex, corticosteroid use, autoimmune disease, and inpatient setting. Conclusion: Certain types of individuals are at higher risk of an indeterminate IGRA result. The QFT-plus test for hospitalized patients should be avoided as much as possible, and it is better to perform the test for those patients in outpatient settings

Combination of anti-glycopeptidolipid-core IgA antibody and clinical features for diagnosing potential nontuberculous mycobacterium pulmonary disease in routine practice

Background: The anti- Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. Objectives: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. Methods: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. Results: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. Conclusions: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs