Serum oxidative stress in patients with pulmonary Mycobacterium avium complex disease.

BACKGROUND: The mechanism of progressive airway destruction in incurable chronic infection of the lung - termed pulmonary Mycobacterium avium complex (pMAC) disease - is currently unknown. The involvement of oxidative stress in a variety of progressive chronic respiratory diseases has been previously reported. It has been hypothesized that oxidative stress may be involved in the progression of airway destruction in pMAC disease. PATIENTS AND METHODS: The study included 28 untreated patients with pMAC disease. The level of serum oxidative stress was quantitatively evaluated through the diacron reactive oxygen metabolites (d-ROMs) test, which indirectly measures the level of hydroperoxide in the serum. In addition, patients were divided into three groups based on the severity shown in the computed tomographic image. RESULTS: The level of serum oxidative stress exceeded the normal range (250-300 U.Carr [Carratelli Units]) in all patients with pMAC disease (mean: 495.5 ± 102.6 U.Carr; minimum-maximum: 340-734 U.Carr). The level of serum oxidative stress in patients with severe disease was significantly higher compared with that observed in patients with mild disease (434.6 ± 30.2 vs. 583.4 ± 95.1, respectively, p = 0.009). CONCLUSIONS: In patients with pMAC disease, an elevation was observed in the level of serum oxidative stress. This increase in oxidative stress was more pronounced in patients with severe disease.

Efficacy of recombinant human soluble thrombomodulin for the treatment of acute exacerbation of idiopathic pulmonary fibrosis: a single arm, non-randomized prospective clinical trial.

BACKGROUND: Coagulation abnormalities are involved in the pathogenesis of acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF). The administration of recombinant human soluble thrombomodulin (rhTM), which has both anti-inflammatory and anticoagulant activities, improves outcomes and respiratory function in patients with acute respiratory distress syndrome. Therefore, we conducted a prospective clinical study to examine the effects of rhTM on respiratory function, coagulation markers, and outcomes for patients with AE-IPF. METHODS: After registration of the protocol, the patients with AE-IPF who satisfied the study inclusion criteria were treated daily with 380 U/kg of rhTM for 7 days and steroid pulse therapy. The concomitant administration of immunosuppressants and polymyxin B-immobilized fiber column treatment was prohibited. The sample size was 10 subjects. The primary study outcome was the improvement of PaO2/FiO2 ratio a week after treatment initiation. Secondary outcomes were change in D-dimer level over time and 28-day survival rate in patients without intubation. Study data were compared with historical untreated comparison group, including 13 patients with AE-IPF who were treated without rhTM before the registration. RESULTS: The mean PaO2/FiO2 ratio for the rhTM treatment group (n = 10) on day 8 significantly improved compared with that on day one (two-way analysis of variance, p = 0.01). The mean D-dimer level tended to decrease in the rhTM group on day 8, but the change was not significant. The 28-day survival rate was 50 % higher in the rhTM group than in the historical untreated comparison group, but the difference was not significant. A post hoc analysis showed that overall survival time was significantly longer in the treated group compared with that of the historical untreated comparison group (p = 0.04, log-rank test). CONCLUSION: rhTM plus steroid pulse therapy improves respiratory functions in patients with AE-IPF and is expected to improve overall patient survival without using other combination therapies. TRIAL REGISTRATION: The study was registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) in October 2012 (UMIN000009082).

Change in serum marker of oxidative stress in the progression of idiopathic pulmonary fibrosis.

BACKGROUND: Increased oxidative stress is supposed to be involved in the etiology of idiopathic pulmonary fibrosis (IPF). It was reported that oxidative stress values measured by a spectrophotometric technique (d-ROMs test) were significantly higher in IPF patients than in controls, and were negatively correlated with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO). However, the relationship between progression of IPF over time and change in serum oxidative stress marker remains unclarified. AIMS: This study aimed to investigate the change in serum oxidative stress marker during progression of IPF. SUBJECTS AND METHODS: The levels of oxidative stress in blood samples of 43 treatment-naïve IPF patients were measured by the d-ROMs test. FVC and DLCO were measured concurrently. The changes in oxidative stress and pulmonary function were evaluated in 27 untreated patients 6 months later. Oxidative stress levels of 13 patients with acute exacerbation of IPF (AE-IPF) and 30 healthy controls were also evaluated. RESULTS: Oxidative stress values [median, interquartile range (IQR); Carratelli units (U.CARR)] were significantly higher in 43 IPF patients than in controls (366, 339-443 vs. 289, 257-329, p < 0.01) and were significantly increased 6 months later in 27 untreated patients (353, 311-398 at baseline to 385, 345-417 at follow-up, p < 0.01). The increase in oxidative stress values (24.0, 6.0-49.0 U.CARR/6 months) was negatively correlated with baseline DLCO (rs = -0.44, p < 0.05) and FVC changes after 6 months (rs = -0.54, p < 0.01). Oxidative stress values were significantly higher in IPF patients with acute exacerbation than in those with stable disease (587, 523-667 vs. 366, 339-443 U.CARR, respectively; p < 0.01). CONCLUSIONS: Serum oxidative stress values increased with disease progression in IPF patients.