Although previous authors have reported single data point, yearly changes in respiratory function have not been examined in combined pulmonary fibrosis and emphysema (CPFE). To quantify the annual changes in respiratory function of patients with CPFE and to examine the difference in survival between CPFE patients and patients with idiopathic pulmonary fibrosis without emphysema (IPF alone), 26 patients with CPFE and 33 IPF alone patients, whose respiratory function had been monitored for at least a year, were selected. The baseline of vital capacity percent predicted (VC% pred) in CPFE patients was greater than that in IPF-alone patients (86.6+/-24.0% vs. 72.8+/-19.4%, p=0.018). The annual decrease in VC% pred was significantly less in CPFE patients than in IPF-alone patients (-1.2+/-4.8% vs. -8.0+/-7.4%, p<0.001). Baseline ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC%) in CPFE patients was lower than that in IPF-alone patients (76.6+/-8.5% vs. 85.2+/-6.7%, p<0.001). In the CPFE group, FEV(1)/FVC% tended to decrease with time (-0.5+/-2.2% per year), but, in contrast, it increased in IPF-alone patients (+1.1+/-3.4% per year) (p=0.036). Baseline of diffusing capacity percent predicted (DLco% pred) was significantly lower in CPFE patients than in IPF-alone patients (45.3+/-15.0% vs. 60.7+/-19.8%, p=0.003). The annual decrease in DLco% pred was lower in CPFE patients than in IPF-alone patients (-3.7+/-7.9% vs. -10.7+/-8.8%, p=0.042). There was no significant difference in the survival duration between 26 CPFE and 33 IPF-alone patients according to Kaplan-Meier analysis. Ventilatory and gas-exchange deterioration during the course of IPF became mild when emphysema was coexistent.

We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO-6818) on acute lung injury and pulmonary emphysema induced by human neutrophil elastase (HNE). Young male Wistar rats were divided into four treatment groups: (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl-cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO-6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100 mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO-6818 was administered orally 1 hour before HNE application. Six hours after HNE application, neutrophil counts and hemoglobin concentration in bronchoalveolar lavage fluid and lung tissue myeloperoxidase activity were determined. Eight weeks after the application, FRC, TLC, lung compliance, and mean linear intercept were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE-induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO-6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung. ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement.

The underlying mechanisms of lung endothelial injury after intestinal ischemia-reperfusion (I/R) injury are not fully known. Here we investigated the effects of posttreatment with a neutrophil elastase inhibitor (NEI; ONO-5046) on lung injury after intestinal I/R injury in a rat model. Intestinal I/R was produced by 90 min of ischemia followed by either 60 or 240 min of reperfusion. For all experimental groups, the endothelial permeability index increased, neutrophil H(2)O(2) production increased in the pulmonary vasculature blood, neutrophil counts increased in bronchoalveolar lavage fluid (BALF), and the cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-3 levels were increased in BALF after 240 min (P < 0.01). In rats treated with NEI from 60 min after reperfusion, the lung endothelial permeability index was significantly reduced (P < 0.05), whereas neutrophil H(2)O(2) production in pulmonary vasculature blood and neutrophil count in BALF were significantly suppressed by NEI (P < 0.05 and P < 0.01, respectively). In addition, NEI significantly suppressed the increase of CINC-1 and CINC-3 levels in BALF (P < 0.05). Our study clearly indicates that posttreatment with NEI reduces neutrophil activation in the pulmonary vessels and neutrophil accumulation in the lungs and suggests that ONO-5046, even when administered after the primary intestinal insult, can prevent the progression of lung injury associated with intestinal I/R.

Gefitinib monotherapy is effective and relatively well tolerated in chemotherapy-naïve elderly patients with advanced NSCLC. Gefitinib has potential as a first-line therapeutic option in elderly patients with advanced NSCLC.

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