Abstract. Budweiser S, Riedl SG, Jörres RA, Heinemann F, Pfeifer M (Centre for Pneumology, Hospital Donaustauf, Donaustauf, Germany; Institute and Outpatient Clinic for Occupational and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany; Department of Internal Medicine II, University of Regensburg, Regensburg, Germany). Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation. J Intern Med 2007; 261: 375-383.Objectives. The incidence of obesity-hypoventilation syndrome (OHS) has greatly increased over time, but data on long-term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV).Design. Retrospective descriptive analysis of patients with OHS and NPPV up to 10 years.Methods. Long-term mortality and predictors of survival were assessed. Additionally, we evaluated changes in lung function, blood gas and laboratory parameters 5.7 ± 2.5 months after initiation of NPPV.Results. 126 patients (BMI 44.6 ± 7.8 kg m )2 ; PaCO 2 55.5 ± 7.7 mmHg) were followed for 41.3 ± 27.6 months. Upon follow-up, blood gases (daytime and nighttime), as well as pulmonary function improved, whilst haemoglobin and BMI decreased (P < 0.001 each). Adherence to NPPV was high (94.5% continuing NPPV 6.5 ± 2.3 h day )1 ).All-cause mortality was 12.7%, with 1-, 2-and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO 2 <50 mmHg, C-reactive protein ‡ 5.1 mg L )1 , leucocytes ‡ 7.8 · 10 3 ll )1 , or pH ‡ 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO 2 , pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO 2 by ‡23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival. Conclusion.Gas exchange and lung function in OHS were improved after initiation of NPPV. Hypoxemia, high pH and elevated inflammation markers predicted poor survival. Overall, NPPV was well tolerated and survival was excellent when compared with data from historical matched controls.

Stearoyl-coenzyme A desaturase (SCD) is a key regulator of membrane fluidity, turns over rapidly, and represents a prototype for selective degradation of resident proteins of the endoplasmic reticulum. Using detergent-solubilized, desaturase-induced rat liver microsomes we have characterized a protease that degrades SCD. Degradation of SCD in vitro is highly selective, has a half-life of 3-4 h, and generates a 20-kDa C-terminal fragment of SCD. The N terminus of the 20-kDa fragment was identified as Phe 177 . The cleavage site occurs in a conserved 12-residue hydrophobic segment of SCD flanked by clusters of basic residues. The SCD protease remains associated with microsomal membranes after peripheral and lumenal proteins have been selectively removed. SCD protease is present in normal rat liver microsomes and cleaves purified SCD. We conclude that rapid turnover of SCD involves a constitutive microsomal protease with properties of an integral membrane protein.

Long-term domiciliary NPPV normalizes hypercapnia and markedly improves hypoxemia as well as polycythemia in OHS patients. In addition, NPPV leads to a significant reduction in restrictive ventilatory disturbance, predominantly by increasing ERV. Application of high inspiratory pressures and good adherence to therapy are presumed to be the basis for the beneficial effects of NPPV in OHS.

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In patients with severe chronic hypercapnic COPD receiving NIV at high inspiratory pressure levels and showing high adherence to this therapy, long-term survival was significantly higher than in non-ventilated patients. Patients displaying more severe disease according to known risk factors seemed to benefit most from long-term NIV.