Statins and outcome after hospitalization for COPD exacerbation: a prospective study.

BACKGROUND: Retrospective studies have shown that the use of statins is associated with reduced mortality and decreased hospitalizations from COPD, but data from prospective studies are lacking. METHODS: We followed-up prospectively 245 patients admitted to hospital for exacerbations of COPD (ECOPD) with monthly evaluations for one year. The role of statins on outcomes was evaluated by Cox regression analysis after proper adjustments for age, gender, BMI, current smoking status, Charlson comorbidity index and COPD stage. Health-related quality of life (HRQoL) was evaluated by Saint George's Respiratory Questionnaire. RESULTS: There was no effect of statins on either 30-day or 1-year mortality. Patients receiving statins presented a lower total number of ECOPD during the 1-year follow up (2.1 ± 2.7 vs. 2.8 ± 3.2 ECOPD/patient respectively, p = 0.037). After proper adjustments, the use of statins was associated with a lower risk for ECOPD [HR: 0.656 (95% CI: 0.454-0.946)] and severe ECOPD [HR: 0.608 (95%CI: 0.381-0.972)]. The group of statins presented better improvement in HRQoL at 2, 6 and 12 months (p < 0.001). CONCLUSIONS: The use of statins in patients hospitalized for ECOPD was associated with a lower risk for subsequent ECOPD and severe ECOPD and improved HRQoL. These data support a possible beneficial role for these agents in COPD.

Systemic oxidative stress in patients with pulmonary sarcoidosis.

BACKGROUND: A local redox imbalance has been reported in pulmonary sarcoidosis. However, so far no study has described a systemic redox imbalance in this context. The aim of the present study was to evaluate the systemic oxidative stress in patients with sarcoidosis and determine its relationship to treatment and indices of disease severity. METHODS: 35 patients with histologically proven pulmonary sarcoidosis and 13 healthy volunteers were included in the study. All patients were studied during a stable phase of their disease. Systemic oxidative stress was quantified in serum with the use of a commercially available spectrophotometric method (D-ROM test) which determines overall oxidative stress, by measuring total hydroperoxides. Oxidative stress was expressed in conventional units, i.e. Carratelli Units (UCarr), where 1 UCarr corresponds to 0.8 mg/L H(2)O(2). RESULTS: Serum oxidative stress levels were significantly higher in patients with sarcoidosis compared to those of normal subjects (390+/-25 vs 300+/-18 UCarr respectively, p=0.04). Patients not receiving systemic corticosteroids had higher levels of oxidative stress compared to steroid-treated patients (461.5+/-38 vs 315+/-20, p<0.01) and compared to controls (461.5+/-38 vs 300+/-18 UCarr, p<0.01). Oxidative stress did not correlate with diffusion lung capacity (DLCO), partial arterial oxygen tension (PaO(2)), MRC dyspnoea scale or chest X-ray stage. CONCLUSIONS: Systemic oxidative stress is increased in patients with stable pulmonary sarcoidosis who do not receive systemic corticosteroids. This finding suggests a sustained oxidative burden even when clinical, functional and radiological criteria indicate disease stability.

Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. METHODS: Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. RESULTS: Serum VEGF levels were higher in systemic sclerosis patients with sPAP >or= 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D(LCO) were independent predictors of systolic pulmonary artery pressure. CONCLUSION: Serum VEGF levels are increased in systemic sclerosis patients with sPAP >or= 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.

The Medical Research Council dyspnea scale in the estimation of disease severity in idiopathic pulmonary fibrosis.

BACKGROUND: Medical Research Council (MRC) chronic dyspnea scale, used for the estimation of disability due to dyspnea, may serve as a simple index of disease severity and extent in patients with idiopathic pulmonary fibrosis (IPF). However, its relationship with other commonly used measures has not been evaluated. METHODS: The association of MRC chronic dyspnea scale with lung function indices and high-resolution computerized tomography (HRCT) scores such as the total interstitial disease score (TIDs) and the fibrosis score (Fs) was examined in 26 untreated patients with IPF sequentially recruited over a period of 3 years. The aim of this observational study was to explore the relationship between dyspnea, impairment of lung function and CT estimation of disease severity in patients with IPF. RESULTS: The MRC dyspnea score was significantly associated with FVC, FEV1, TLC, DLCO, PaO2, and PaCO2 and with both HRCT scores. In multiple regression analysis only the FVC (OR = 0.85, 95% CI = 0.75-0.95, P = 0.004) and PaCO2 (OR = 0.69, 95% CI = 0.50-0.95, P = 0.02) correlated with dyspnea. Furthermore, both TIDs and Fs were negatively associated with FVC, FEV1, TLC and PaO2. In multiple regression analysis only the FVC correlated with both TIDs (r2 = 0.57, P = 0.0001) and Fs (r2 = 0.46, P = 0.0005). CONCLUSIONS: These observations suggest that the MRC dyspnea scale could offer useful information about the estimation of severity in patients with IPF. Furthermore among functional indices the FVC seems to be the best estimator of disease severity and extent.

Clinical, functional and biochemical changes during recovery from COPD exacerbations.

The pathways underlying chronic obstructive pulmonary disease exacerbations (ECOPD) remain unclear. This study describes the clinical, functional and biochemical changes during recovery from ECOPD. Thirty hospitalized patients with Anthonisen's type-I ECOPD were evaluated on days 0 (admission), 3, 10 and 40. A five-symptom score (TSS), performance status and quality of life were evaluated. Post-bronchodilator spirometry, blood gases, oxidative stress, C-reactive protein (CRP), serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and fibrinogen were also measured. Patients were classified as early- or late-recoverers, based on whether dyspnea had returned to pre-exacerbation level by day 10. Most clinical, functional and biochemical parameters improved during follow-up. CRP and IL-6 levels reduced on Day 3 (p<0.05), whereas SAA on Day 10 (p<0.01). TNF-alpha was reduced on Days 3 and 10, but on Day 40 its levels returned to baseline. Fibrinogen and WBC reduced only by day 40. TSS and dyspnea were correlated inversely with FEV(1) on days 3, 10 and 40. Although late-recoverers had lower FEV(1) on admission, none of the reported measurements on admission and day 3 predicted early recovery. During recovery from ECOPD, symptomatic improvement correlates only with post-bronchodilator FEV(1) whereas systemic inflammatory burden subsidence does not correlate with clinical and functional changes. Although late-recoverers have lower FEV(1) on admission, none of the measured parameters is able to predict early symptomatic recovery.

Serum levels of oxidative stress as a marker of disease severity in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal illness characterized by progressive fibrosis resulting in severe dyspnea and impairment of lung function. Although the mechanisms by which lung fibrosis develops are not fully ascertained, recent findings suggest that oxidative stress may play an important role in the pathogenesis of tissue fibrosis. AIM: To evaluate the oxidative stress in the serum of patients with IPF and to explore the relationship between oxidative stress levels, dyspnea and impairment of lung function. MATERIAL AND METHODS: Blood samples from 21 untreated patients with IPF, sequentially recruited over a period of 2 years, and 12 controls were analyzed. The level of oxidative stress in the blood was determined through a spectrophotometric procedure (D-ROMs test). FVC and DLCO were measured in all patients. The level of dyspnea was assessed by the Medical Research Council (MRC) chronic dyspnea scale. RESULTS: Serum levels of oxidative stress were significantly increased in patients with IPF compared to controls (mean+/-SEM: 356.8+/-14 and 201+/-10 Carratelli units respectively, p<0.001). Oxidative stress was negatively associated with FVC (p<0.01, r=-0.79) and with DLCO (p<0.01, r=-0.75). Furthermore, oxidative stress was significantly correlated with MRC dyspnea score (p<0.01, r=0.87). Oxidative stress measurements were highly reproducible on two consecutive measurements in the same patients. CONCLUSION: The levels of systemic oxidative stress are enhanced in patients with IPF and could provide useful information about the classification of IPF severity. Strategies to reduce the oxidant burden in IPF may be beneficial in reducing the progressive deterioration of these patients.