Plasma branched-chain amino acid levels and muscle energy metabolism in patients with chronic obstructive pulmonary disease.

BACKGROUND & AIMS: Although several studies have shown that plasma concentrations of branched-chain amino acids (BCAAs) are reduced in patients with chronic obstructive pulmonary disease (COPD), little is understood about how low concentrations of BCAAs limit exercise in such patients. The present study investigated whether plasma BCAAs are related to energy metabolism in exercising muscle using (31)P-magnetic resonance spectroscopy (MRS). METHODS: We analyzed the plasma amino acid profiles of 23 male patients with COPD (aged 69.2+/-5.1 years) and of 7 healthy males (aged 64.1+/-6.0 years). We normalized the exercise intensity of repetitive lifting by adjusting the weight to 7% of the maximal grip power. The intracellular pH and the phosphocreatine (PCr) index (PCr/(PCr+Pi); Pi, inorganic phosphate) were calculated from MR spectra. We evaluated the relationship between intracellular pH and PCr index at the completion of exercise and the plasma BCAA concentration. RESULTS: Glutamine concentrations were elevated in patients with COPD compared with healthy individuals. Plasma concentrations of BCAAs correlated with intracellular pH and PCr index at the completion of exercise. CONCLUSIONS: The findings are consistent with the notion that BCAAs affect muscle energy metabolism during exercise in patients with COPD.

Deoxygenated hemoglobin/myoglobin kinetics of forearm muscles from rest to exercise in patients with chronic obstructive pulmonary disease.

Exercise capacity is frequently decreased in patients with chronic obstructive pulmonary disease (COPD), and muscle dysfunction is one factor in this reduction. Studies using (31)-phosphorus magnetic resonance spectroscopy ((31)P-MRS) have shown that phosphocreatine (PCr) and muscle pH (pHi) are significantly decreased in patients with COPD during mild exercise, suggesting the early activation of anaerobic glycolysis in their muscles. Thus, muscle oxygenation states during exercise might differ between patients with COPD and healthy individuals. We simultaneously measured oxygenation state and pHi in the muscles of patients with COPD during the transition from rest to exercise (on-transition) using near infrared spectroscopy (NIRS) and (31)P-MRS. Sixteen patients with COPD (aged 68.6 +/- 7.5 years) and 7 healthy males (controls; aged 63.3 +/- 7.5 years) performed dynamic handgrip exercise (lifting a weight by gripping at a rate of 20 grips per min for 3 min). Patients were classified based on pHi data at the completion of exercise as having a normal (>or= 6.9; n = 8) or a low (< 6.9; n = 8) pHi. The deoxygenated hemoglobin/myoglobin (deoxy-Hb/Mb) in NIRS recordings remained constant or slightly decreased initially (time delay), then increased to reach a plateau. We calculated the time delay and the time constant of deoxy-Hb/Mb kinetics during the on-transition. The time delay was shorter in the group with a low pHi than in the controls. These findings might reflect a slower increase in O(2) delivery in patients with a low pHi, which might partly account for altered muscle energy metabolism.

Gefitinib-induced lung injury successfully treated with high-dose corticosteroids.

A 55-year-old man was treated with gefitinib for disseminated pleural lesions, 1 year after resection of the left lower lobe for non-small cell lung cancer. After 6 weeks of continuous daily treatment with oral gefitinib, he developed dyspnoea on exertion and a non-productive cough. CXR and CT revealed focal areas of ground-glass opacity (GGO) in the right upper lobe. Despite gefitinib being discontinued, high-resolution CT revealed extension of GGO and restructuring of lung parenchyma, suggesting acute interstitial pneumonia. Transbronchial biopsy revealed acute-phase diffuse alveolar damage. After administration of methylprednisolone pulse therapy (1 g/day intravenously) for three consecutive days, the areas of GGO shrank on high-resolution CT and symptoms resolved. Diffuse alveolar damage caused by gefitinib can be successfully treated in the early phase with high-dose corticosteroids. Patients receiving gefitinib should be carefully examined for symptoms and undergo CT if their condition deteriorates.

Functional residual capacity and airway resistance in rats of COPD model induced by systemic hyaluronidase.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is characterized by obstructive bronchiolitis and parenchymal destruction. In animal models, air space enlargement induced by intratracheal elastase is augmented by prior depletion of lung hyaluronan by hyaluronisase. Recently our colleagues reported that intravenous hyaluronisaein in the absence of elastase produced emphysema-like alveolar dilation [1]. In this study we measured functional residual capacity (FRC) and airway resistance (Raw) in the rats with hyaluronidaseinduced experimental COPD. MATERIALS AND METHODS: Hyaruonidase (20 mg/kg) was administered from the caudal vein of 19 male Wistar rats (COPD rats). Two weeks after the injection, FRC and Raw were measured with bodyplethysmogarph. RESULTS: Thickness or inflammatory cell infiltrations were not apparent in the bronchus of the COPD rat while alveolar distension was obvious. The mean FRC of the COPD rats (6.22 ± 1.00 ml, mean ± SD) was significantly larger than that of Control rats (5.48 ± 0.85 ml). There was no statistical significance between the mean Raw of the COPD rats (0.28 ± 0.08 cmH2O/ml/s) and that of the control rats (0.28 ± 0.13 cmH2O/ml/s). CONCLUSION: Systemic administration of hyaluronidase produced pulmonary overinflation but did not bronchial constriction. We speculate that hyaluonidase-induced COPD simulates panlobular emphysema.

Anti-inflammatory effect of Pelteobagrus nudiceps extract on rat model of CFA-induced pulmonary tuberculous granuloma.

We investigated the effectiveness of supportive therapy with a fish-oil extract called repair tuberculosis (RTB) in anti-tuberculosis treatment, and the underlying mechanism of action. The active component of RTB is the unsaturated fatty acid docosatetraenoic acid (C(22)H(36)O(2)), which was reported to induce the resorption and healing of pulmonary lesions in patients with severe pulmonary tuberculosis. We administered RTB to a rat model of CFA-induced pulmonary tuberculous granuloma (RTB group), and compared the results with those in a control group, which did not receive RTB. Histological examination of the lungs showed a significantly smaller area of granuloma in the RTB group than in the control group. IFN-gamma levels in bronchoalveolar lavage fluid (BALF) were higher in the RTB group than in the control group, suggesting that Th1-type immune reaction is activated in the RTB group. Moreover, significantly enhanced expression of inducible nitric oxide synthase mRNA in lung tissue was observed in the RTB group. Superoxide production by cells recovered from BALF was attenuated in the RTB group. There were no difference in IL-4 levels in BALF, or in expression of TNF-alpha mRNA in lung tissue between the RTB and control groups. The above results suggest that RTB activates Th1-type cellular immune reaction, promotes absorption of lesions, and inhibits the generation of cytotoxic substances.