Aya Yoshioka

Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema

This study examined the role of cysteine proteinases and their inhibitor in the development of emphysema in comparison with neutrophil elastase (NE) complexed with alpha1-protease inhibitor (NE-alpha1-PI), which was previously demonstrated to be increased in bronchoalveolar lavage (BAL) fluid from subjects with subclinical emphysema. Eight nonsmokers and 31 current smokers with (n=17) and without (n=14) emphysema, as evidenced by lung computed tomographic scans, were studied. The concentrations of immunologically detected cathepsin L and cystatin C, but not cathepsin B, were significantly increased in BAL fluid from the smokers with emphysema compared with those without emphysema, although the activity of cathepsin L, measured using a synthetic substrate and cathepsin L, released from cultured alveolar macrophages at 24 h, did not show any significant difference between the two groups. When comparison was made only for the subjects aged <60 yrs, the difference between the two groups disappeared for cathepsin L, but remained for NE-alpha1-PI. There was no significant correlation between the level of cathepsin L and that of NE-alpha1-PI in BAL fluid from the subjects with emphysema. In conclusion, increased levels of cathepsin L and cystatin C were demonstrated in bronchoalveolar lavage fluid from subjects with subclinical emphysema. However, the roles of cathepsin L and neutrophil elastase in the development of emphysema may vary between subjects and between the young and the old.

Pulmonary function is diminished in older asymptomatic smokers and ex-smokers with low attenuation areas on high-resolution computed tomography

OBJECTIVES The relation between pulmonary function and low attenuation areas (LAAs) on high-resolution computed tomography (HRCT) is not clear in subclinical pulmonary emphysema. Accordingly we examined pulmonary function and HRCT in asymptomatic community-based volunteers. DESIGN The existence of LAAs on CT was evaluated independently by three respiratory physicians who were blind to the pulmonary function test data and smoking histories of the subjects. The LAA grade was assessed by a visual scoring method from 0 to 5, and the individual LAA score and the values of pulmonary function tests were compared. PARTICIPANTS 57 subjects aged from 32 to 82 years [mean 62 +/- (SD) 11] years were enrolled in the study. RESULTS LAAs were found in 20 of the 49 subjects who were current or ex-smokers but in none of the 8 who never smoked. LAAs observed were mostly less than 25% of the total areas of the lungs. Although all mean values were within normal limits, the forced expiratory volume in 1 s (%pred), maximal expiratory flow at 50% of forced vital capacity (%pred), diffusing capacity of the lungs for carbon monoxide (DLCO; %pred) and diffusing capacity for carbon monoxide per unit alveolar volume (DLCO/VA; %pred) were all significantly less in those with LAAs than in those without LAAs. There was also a significant tendency for DLCO %pred and DLCO/VA %pred to decrease as the LAA scores increased. CONCLUSION Those who have LAAs on CT have a small but significant deterioration in pulmonary function tests even if the LAAs observed are minimal or mild in degree. Longitudinal studies will be necessary to determine whether LAAs on CT identify the subjects who will develop airflow obstruction over time.

Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.

High Titer of Acquired Factor V Inhibitor Presenting with a Pseudo-deficiency of Multiple Coagulation Factors

Acquired coagulation factor inhibitor is a rare coagulation disorder. We herein report a patient with acquired factor V inhibitor showing a decrease in multiple coagulation factor activities. A high titer of factor V inhibitor presumably led to a marked inhibition of factor V activity in the specific factor-deficient plasma used in coagulation factor activity assays based on either an activated partial thromboplastin time (APTT) or prothrombin time (PT) clotting assay, resulting in false low values of the coagulation activity. We re-examined the coagulation factor activity using several dilutions of the patients plasma and confirmed that the high factor V inhibitor titer had caused an apparent decrease in multiple coagulation factor activities.