Additive efficacy of short-acting bronchodilators on dynamic hyperinflation and exercise tolerance in stable COPD patients treated with long-acting bronchodilators.

The purpose of this study was to clarify the additive efficacy of short-acting ß(2)-agonists (SABA) or muscarinic antagonists (SAMA) on dynamic hyperinflation and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) who had been treated with long-acting bronchodilators. Thirty-two patients with stable COPD who had been treated with long-acting bronchodilators, including long-acting muscarinic antagonists (LAMA), were examined by pulmonary function tests, dynamic hyperinflation evaluated by the method of step-wise metronome-paced incremental hyperventilation, and the incremental shuttle walking test before and after inhalation of SABA or SAMA. The additive efficacy of the two drugs was analyzed. Inhalation of SABA and SAMA improved airflow limitation and dynamic hyperinflation in stable COPD patients who had been treated with LAMA. Inhalation of SABA decreased respiratory resistance and the difference in respiratory resistance at 5 Hz and 20 Hz. On the whole, the additive efficacy of SABA on airflow limitation and dynamic hyperinflation was superior to that of SAMA. Furthermore, inhalation of SABA resulted in relief of breathlessness during exercise and significant improvement in exercise capacity. Inhalation of SABA resulted in significant improvement in exercise tolerance, which may have been due to improvement in dynamic hyperinflation. Single use of SABA before exercise, in addition to regular treatment with LAMA, may therefore be useful in stable COPD patients.

Effects of a synthetic protease inhibitor (gabexate mesilate) and a neutrophil elastase inhibitor (sivelestat sodium) on acid-induced lung injury in rats.

The present study was designed to examine the combined effects of a synthetic protease inhibitor, gabexate mesilate, with a specific neutrophil elastase inhibitor, sivelestat sodium, on acid-induced lung injury. Adult male Sprague-Dawley rats weighing 300-350 g were anaesthetised intraperitoneally with pentobarbitone sodium and the right jugular vein was cannulated. Following tracheostomy, rats were ventilated mechanically and underwent intratracheal instillation of hydrochloric acid (HCl, 0.1N 1.5 ml/kg) or normal saline. Gabexate mesilate (10mg/kg, i.p.) and/or sivelestat sodium (10mg/kg/h, i.v.) were administered 30 min before HCl instillation. Bronchoalveolar lavage fluid samples were obtained 5h after HCl instillation. In bronchoalveolar lavage fluid, the HCl-induced increases in total nucleated cell counts, neutrophil counts, optical density at 412 nm as an index of pulmonary haemorrhage, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) were significantly attenuated by either gabexate mesilate or sivelestat sodium treatment. Gabexate mesilate or sivelestat sodium treatment also significantly attenuated the wet to dry weight ratio induced by HCl. However, combined treatment with both gabexate mesilate and sivelestat sodium did not show additive effects on HCl-induced lung injury, compared with single treatments. These findings suggested that gabexate mesilate and sivelestat sodium each exhibited protective effects on acid-induced lung injury, but that synergistic effects of both agents are limited in this acid-induced lung injury model.

Polymyxin B-immobilized fiber column hemoperfusion treatment for drug-induced severe respiratory failure: report of three cases.

The effects of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) treatment for acute exacerbation of interstitial pneumonia have been reported. Here, we report 3 severe cases of drug-induced interstitial lung disease (DI-ILD) that were treated with PMX-DHP. Two DI-ILD cases were caused by methotrexate, and the third case was caused by the herbal medicine sanmotsu-ogon-to. The arterial oxygen tension/inspiratory oxygen fraction ratio improved during PMX-DHP treatment in all 3 patients. Finally, 2 patients survived and 1 died. The study findings indicate that PMX-DHP treatment is a viable option for the management of acute respiratory failure in patients with DI-ILD.

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji).

BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. METHODS: Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. RESULTS: Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. CONCLUSIONS: Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.

Effects of granulocyte colony-stimulating factor (G-CSF) and neutrophil elastase inhibitor (ONO-5046) on acid-induced lung injury in rats.

It has been suggested that neutrophils play an important role in acid-aspirated lung injury. We examined the effects of the high dose of granulocyte-colony stimulating factor (G-CSF), which is capable of increasing peripheral neutrophils, and a specific neutrophil elastase inhibitor (ONO-5046) on acid lung injury in rats. Animals were anesthetized and normal saline (NS, 2 mL kg(-1)) or hydrochloric acid (HCl, 0.1 N 2 mL kg(-1)) was then instilled into trachea. Thirty minutes before HCl instillation, G-CSF (150 microg kg(-1)) was injected subcutaneously or ONO-5046 (10 mg kg(-1) h(-1)) was infused continuously into the right jugular vein. Animals were ventilated during the experiments. Five hours after HCl or NS instillation, bronchoalveolar lavage fluid (BALF) and lung tissue samples were obtained. Total nuclear cell count, absorbance, albumin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC), neutrophil elastase in BALF, wet-to-dry (W/D) ratio were measured. HCl aspiration markedly increased these values in BALF and W/D ratio. Both ONO-5046 and G-CSF attenuated the parameters increased by acid-induced lung injury in rats. The data suggests that neutrophils play an important role in acid-induced lung injury. However, high-dose G-CSF does not exacerbate acid-aspirated lung injury in rats, although this agent causes an increase in peripheral neutrophils.

T-wave alternans in patients with right ventricular tachycardia.

Microvolt T-wave alternans has been proposed as a new risk marker for ventricular arrhythmias. However, the clinical significance of T-wave alternans in patients with ventricular tachycardia (VT) originating from the right ventricle has been unknown. The study population consisted of 20 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic VT. T-wave alternans was measured during bicycle exercise testing using the CH 2000 system. Of the 7 patients with ARVC, 6 (86%) were positive for T-wave alternans. On the other hand, only 1 (8%) of 13 patients with idiopathic VT originating from the right-ventricular outflow tract was positive for T-wave alternans.