Airway inflammatory markers in chronic obstructive pulmonary disease patients and healthy smokers.

BACKGROUND: Cigarette smoke with its toxic ingredients leads to chronic inflammations in the airways. OBJECTIVES: In this study, the effect of cigarette smoke on the levels of inflammatory markers, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) in induced sputum was investigated. MATERIALS AND METHODS: Twenty patients with chronic obstructive pulmonary disease (COPD) (group I), 20 healthy smokers (group II), and 20 healthy nonsmokers (group III) were included in the study. The levels of IL-6, IL-8, and TNF-α in induced sputum were measured in these groups, and comparison analysis between the groups and correlation analysis for smoking load (pack-years) and spirometric parameters were performed. RESULTS: Mean age of the patients in groups I, II, and III were 61.2 ± 1.7, 58.2 ± 1.6, and 59.1 ± 5.4 years, respectively (P > 0.05). Smoking loads of group I and group II were 38.6 ± 2.1 and 29.5 ± 2.3 pack-years, respectively (P < 0.05). All cytokine levels were significantly higher in group I than groups II and III (P < 0.05). In addition to this, mean cytokines levels were significantly higher in group II than group III (P < 0.05). Smoking load of group II subjects was positively correlated with IL-6, IL-8, and TNF-α in induced sputum (P < 0.05). CONCLUSIONS: We found that inflammatory marker levels in induced sputum were significantly higher in COPD patients and smokers than nonsmokers. Moreover, there was a moderate positive correlation between IL-6, IL-8, and TNF-α levels and smoking load in the healthy smokers. We think that further studies are needed to determine whether higher levels of cytokine levels in sputum might be helpful in predicting the healthy smokers who will develop COPD in future.

Effects of iloprost on bleomycin-induced pulmonary fibrosis in rats compared with methyl-prednisolone.

OBJECTIVE: Prostacyclin (PGI2) has been shown to inhibit the expression of pro-inflammatory and pro-fibrotic mediators in pulmonary fibrosis. In this study, we aimed to test the preventive effects of intraperitoneally administered iloprost, a stable PGI2 analog, on bleomycin-induced pulmonary fibrosis in rats and to compare the effects of iloprost with the effects of methyl-prednisolone, a traditional therapy. METHODS: Rats were randomly allocated into four groups: 1. Saline alone (n=6); 2. Bleomycin+placebo (n=7); 3. Bleomycin+methyl-prednisolone (n=7); 4. Bleomycin+iloprost (n=7). Fibrotic changes in the lungs were demonstrated by analyzing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content. RESULTS: Fibrosis was made in the lungs of rats by bleomycin experimentally. Fibrosis scores in the methyl-prednisolone and the iloprost groups were significantly lower than in the placebo group (p<0.05). Furthermore, the score of the iloprost group was significantly lower than the score of the methyl-prednisolone group. The hydroxyproline content was significantly less in the methyl-prednisolone and the iloprost groups (p<0.05). In the placebo group, the neutrophil percentage in bronchoalveolar lavage was significantly higher than in the other groups, whereas the macrophage percentage in placebo group was significantly lower (p<0.05). CONCLUSION: Iloprost has protective effect on the pulmonary fibrosis induced by bleomycin and it may be more effective in decreasing fibrotic changes than methyl-prednisolone.

Venous thromboemboli and exacerbations of COPD.

The aim of the present study was to determine the prevalence of and risk factors for venous thromboembolism (VTE) in exacerbations of chronic obstructive pulmonary disease (COPD). COPD patients hospitalised with an exacerbation were included consecutively. Symptoms, signs and clinical, haematological and epidemiological parameters on admission were noted. All patients underwent computed tomographic angiography and ultrasonographic examination for deep vein thrombosis and pulmonary embolism (PE). Wells and Geneva scores were calculated. Patients were followed-up for 1 yr in order to determine mortality. Deep vein thrombosis and PE were detected in 14 and 18 patients, respectively. The prevalence of VTE was three times higher in patients with an exacerbation of unknown origin than in patients with an exacerbation of known origin (p = 0.016). Of patients with VTE, 20 (95%) had high D-dimer levels. The negative predictive value of D-dimer testing was 0.98. Although the moderate- and high-risk categories of both the Wells and Geneva methods covered all PE patients, the Wells method identified 49% less potential patients for PE investigation. Mortality at 1 yr was higher (61.9% versus 31.8%) in VTE patients (p = 0.013). VTE is a common problem in COPD patients hospitalised with an exacerbation, leading to high long-term mortality. D-dimer levels and the Wells criteria can be used to determine whether or not these patients are assessed for a thromboembolic event.

Assessment of B-type natriuretic peptide in patients with pneumonia.

The mammalian heart synthesises and secretes B-type natriuretic peptide (BNP), which has potent diuretic, natriuretic and vascular smooth muscle-relaxing effects as well as complex interactions with the hormonal and nervous systems. Recent studies described that BNP was acute phase reactant. In this study, we aimed to evaluate BNP levels in patients with pneumonia. Twenty-one patients with pneumonia and 21 healthy control subjects were enrolled in this study. Their serum levels of BNP were measured in addition to the standard evaluations. Leucocyte count [19.3 (13.2-25.7) 10(6)/ml vs. 9.55 (3.7-13.9) 10(6)/ml, p < 0.001], erythrocyte sedimentation rate [73 (57-81) mm/h vs. 35 (4-55) mm/h, p < 0.001], C-reactive protein (CRP) [127.72 (27-290) mg/l vs. 13.19 (3-41) mg/l, p < 0.001] and BNP [53.1 (17-91) pg/ml vs. 16.24 (1-38) pg/ml, p < 0.001] levels significantly decreased after treatment period. Initial BNP levels were significantly higher than control groups (53.10 +/- 15.07 pg/ml vs. 18.62 +/- 14.05 pg/ml, p < 0.001) and decreased after treatment to the levels comparable with control subjects. BNP levels correlated with CRP levels at admission (r = 0.716, p < 0.001). We have shown that BNP levels show a transient increase in patients with pneumonia and correlate well with CRP.

The role of nebulised budesonide in the treatment of exacerbations of COPD.

The present study was designed to evaluate the hypothesis that nebulised budesonide (NB) might be an alternative to systemic corticosteroids (SC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (ECOPD). Patients hospitalised with ECOPD (n = 159) were randomised into three groups. Group 1 received only standard bronchodilator treatment (SBDT), group 2 received SC (40 mg prednisolone) plus SBDT, and group 3 received NB (1,500 microg q.i.d.) plus SBDT. Improvement during 10-day hospitalisation was compared with exacerbation and rehospitalisation rates after discharge. While mean+/-sd age was 64.1+/-8.9 yrs (female/male = 0.1), mean forced expiratory volume in one second (FEV(1)) at admission was found to be 37.2+/-12.2% predicted. Arterial blood gases and spirograms recovered faster in groups 2 and 3. While improvements in arterial oxygen tension (P(a,O(2))) and forced vital capacity (FVC) in group 2, and improvements in P(a,O(2)), FVC and FEV(1) in group 3, became significant at 24-h control, the first significant improvement in group 1 appeared in arterial oxygen saturation at 72-h control. The mean improvement of P(a,O(2)) after 10 days was 1.20 and 1.06 kPa (9 and 8 mmHg) higher in group 2 and 3, respectively, than in group 1. Blood glucose exhibited an upward trend only in group 2. The study demonstrates that nebulised budesonide may be an effective and safe alternative to systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease.

Factors affecting survival of hospitalised patients with COPD.

Factors determining in-hospital mortality and long-term survival of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood. The aim of the present study was to assess the parameters related to in-hospital mortality and long-term survival after hospitalisation of patients with AECOPD. Clinical and epidemiological parameters on admission in 205 consecutive patients hospitalised with AECOPD were prospectively assessed. Patients were followed-up for 3 yrs. Factors determining short- and long-term mortality were analysed. In total, 17 patients (8.3%) died in hospital. In-hospital mortality was significantly associated with lower arterial oxygen tension (P(a,O2)), higher carbon dioxide arterial tension, lower arterial oxygen saturation and longer hospital stay. The overall 6-month mortality rate was 24%, with 1-, 2- and 3-yr mortality rates of 33%, 39% and 49%, respectively. Cox regression analysis revealed that long-term mortality was associated with longer disease duration (relative risk (RR) = 1.158), lower albumin (RR = 0.411), lower P(a,O2) (RR = 0.871) and lower body mass index (RR = 0.830). When the model was run for the time elapsed since first hospitalisation, it also appeared as statistically significant (RR = 1.195). These findings show that patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease have poor short- and long-term survival. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, disease duration and time elapsed since the first hospitalisation.