The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation. Pre-treatment measurements were used in this study. Demographics, sputum microbiology, heart rate, oxygen saturation, lung function were recorded. Blood samples were obtained for white blood count (WBC), C-Reactive Protein (CRP), and plasma neutrophil elastase/AAT complexes (pNEC). Neutrophil elastase (NE), neutrophil elastase/AAT complexes (sNEC), interleukin-8 (IL-8), TNF-receptor 1 (sTNFr), and myeloperoxidase (MPO) were measured in sputum and urinary desmosine concentration determined. Patients with Bc had significantly higher levels of pNEC, 332?±?91.4 ng/ml (mean?±?SEM) versus 106?±?18.2 ng/ml (P?=?0.0005) and sNEC, 369?±?76.6 ng/ml versus 197?±?36.0 ng/ml compared to those who were not. Five deaths were reported at the end of 1 year, (four with Bc) (P?=?0.011). Patients who subsequently died had significantly lower lung function FEV1, 1.2?±?0.2 L versus 2.0?±?0.1 L (P?=?0.03) and FVC, 2?±?0.3 L versus 3.1?±?0.2 L (P?=?0.01), compared to those that survived. There was significantly higher NE activity, 3.6?±?1.6 U/ml versus 1.5?±?0.6 U/ml (P?=?0.03), pNEC, 274?±?99 ng/ml versus 142?±?30 ng/ml (P?=?0.05), MPO, 163?±?62 mcg/ml versus 54?±?6.9 mcg/ml (P?=?0.03), and urinary desmosines 108?±?19.9 pM/mg creatinine versus 51.1?±?3.3 pM/mg creatinine (P?=?0.001), in those patients who subsequently died compared to those that survived. These data suggest there is increased neutrophil degranulation in patients infected with Bc and these patients have a poor outcome.

An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours

Background/Aims:Mid-gut carcinoids (MGC) are the most common of the gastrointestinal carcinoid tumours. There is a lack of reliable prognostic indicators for MGC. Cox-2 and Bcl-2 were evaluated as prognostic biomarkers in a cohort of well-characterised non-appendiceal MGC. Methods: Tissue from the primary MGC tumours of 37 patients was subjected to immunohistochemical detection of Cox-2 and Bcl-2. In 9 cases tissue from secondary lesions was also examined. The study assessed whether tumour-associated Cox-2 and Bcl-2 expression were related to patient survival. Results: Cox-2 expression was demonstrated in 30/36 primary tumours. When all tumours were analysed Cox-regression analysis indicated a trend towards worsening survival with increasing Cox-2 histoscore (intensity x proportion; hazard ratio 1.53, 95%CI 0.93, 2.52; p=0.09). Analysis of Cox-2 positive tumours revealed a highly significant association between increasing histoscore and decreased survival (hazard ratio 3.03, 95%CI 1.33, 6.91, p=0.008). Tumour-associated Bcl-2 expression had no effect on patient survival (hazard ratio 1.12, 95% CI 0.42, 2.99 p=0.82). There was no significant association between Cox-2 and Bcl-2 expression (ï?£2 p=0.16), or Cox-2 histoscore and Bcl-2 expression (MWU p=0.59). Analysis of the Cox-2 histoscores of primary tumours and their corresponding secondary lesions, revealed a statistically significant trend towards increasing histoscore in the latter (Wilcoxon p=0.04). Conclusions: This study has provided evidence that Cox-2 expression in primary MGC may be associated with a more negative prognostic outlook.