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Background-Non-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation. The second aim was to determine the long term survival of patients treated with and without NIV. Methods-In this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998. Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic factors were identified using logistic regression analysis. All patients were followed until death or 1 January 1999. The trend in improved survival was attributable to prevention of death during the index admission. Conclusion-Initial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation. NIV reduces this risk and progress should be monitored using change in respiratory rate and pH. The long term survival after NIV is suYciently good to render treatment appropriate. (Thorax 2001;56:708-712) Results-At

Objective To evaluate the cost effectiveness of standard treatment with and without the addition of ward based non-invasive ventilation in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUNDNon-invasive ventilation (NIV) reduces the need for intubation and the mortality associated with an exacerbation of chronic obstructive pulmonary disease (COPD). This study aimed to identify factors that could be used to stratify patients according to their risk of requiring invasive mechanical ventilation. The second aim was to determine the long term survival of patients treated with and without NIV.METHODSIn this prospective multicentre randomised controlled trial 118 patients were allocated to standard treatment and 118 to NIV between November 1996 and September 1998. Arterial blood gas tensions and respiratory rate were recorded at enrolment and after 1 and 4 hours. Prognostic factors were identified using logistic regression analysis. All patients were followed until death or 1 January 1999.RESULTSAt enrolment the H+ concentration (OR 1.22 per nmol/l, 95% CI 1.09 to 1.37, p<0.01) and Paco2 (OR 1.14 per kPa, 95% CI 1.14 to 1.81, p<0.01) were associated with treatment failure. Allocation to NIV was protective (OR 0.39, 95% CI 0.19 to 0.80). After 4 hours of treatment improvement in acidosis (OR 0.89 per nmol/l, 95% CI 0.82 to 0.97, p<0.01) and fall in respiratory rate (OR 0.92 per breaths/min, 95% CI 0.84 to 0.99, p=0.04) were associated with success. Median length of survival was 16.8 months in those treated with NIV and 13.4 months in those receiving standard treatment (p=0.12). The trend in improved survival was attributable to prevention of death during the index admission.CONCLUSIONInitial pH and hypercapnia can be used to stratify groups of patients according to their risk of needing intubation. NIV reduces this risk and progress should be monitored using change in respiratory rate and pH. The long term survival after NIV is sufficiently good to render treatment appropriate.

Background: Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumor. In this study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. Materials and method: A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case was analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TUNEL (TdT-mediated dUTP-nick end-labelling) and Ki-67 positive cells, respectively. The proliferative/apoptotic index (P/A) was calculated for each case. Results: Statistical analysis demonstrated significant differences among the tissue groups for both indices (P < 0.0001). The Als and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P = 0.0001 and P < 0.0001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04), whereas it was decreased (NS) from hyperplasia to preinvasive lesions. A strong positive correlation between the Als and the Pls was found (r = 0.83; P < 0.0001). Conclusion: These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma, the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia to preinvasive lesions there is an imbalance in favour of apoptosis.