Preserving oxygenation during walking in severe chronic obstructive pulmonary disease: noninvasive ventilation versus oxygen therapy.

BACKGROUND: Physical activity is known to cause significant deoxygenation in patients with severe chronic obstructive pulmonary disease (COPD). Although noninvasive positive pressure ventilation (NPPV) has been shown to improve oxygenation and physical activity in these patients, no practical approach for the application of NPPV during walking has yet been established. OBJECTIVE: To elucidate the most effective approach to preserving oxygenation during walking in patients with severe COPD receiving long-term NPPV. METHODS: Three 12-min walking tests were performed in a randomized cross-over design on 3 consecutive days, comparing the usual and double dosages of oxygen versus NPPV plus the usual dosage of oxygen. The ventilator and oxygen tank were placed in a backpack. RESULTS: Eleven patients (FEV(1) 26 +/- 9% predicted) completed the study, while 8 patients refused to walk with NPPV, due to the weight of the ventilatory device (7.3 kg with NPPV vs. 3.1 kg without). PaO(2) changes during walking differed [p = 0.01, repeated-measures (RM)-ANOVA], whereas dyspnea was unchanged. The difference in PaO(2) change was 14.0 +/- 16.6 mm Hg (unadjusted p = 0.0036, critical level = 0.017, RM-ANOVA) in favor of NPPV compared to the usual dosage of oxygen. Changes in FEV(1), tidal volume and inspiratory impedance were in favor of NPPV-aided exercise (all p < 0.05, RM-ANOVA). Walking distance was reduced under NPPV (555 +/- 227 m) compared to the usual (619 +/- 210 m) and double (622 +/- 215 m) dosages of oxygen (p = 0.024, RM-ANOVA). CONCLUSIONS: NPPV plus supplemental oxygen, but not oxygen alone, preserves oxygenation during walking in patients with severe COPD. However, dyspnea and walking distance were not improved due to the burden of carrying the heavy ventilatory equipment in a backpack.

Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements.

BACKGROUND AND OBJECTIVE: Acenocoumarol (AC) is a coumarin derivative, vitamin K antagonist anticoagulant drug. It has a narrow therapeutic index and shows large pharmacokinetic and pharmacodynamic interindividual variability. Our objective was to investigate the association between AC dose requirements to achieve a target level of anticoagulation and genetic polymorphisms of genes possibly associated with its metabolism (CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP3A5) and transport (ABCB1). METHODS: Ninety-six Bulgarian patients treated orally with AC for at least 3 months were included. They were separated into three groups according to their AC dose requirement, i.e. low, medium and high. RESULTS AND DISCUSSION: CYP2C9*1/*3 (associated with an intermediate CYP2C9 activity), CYP2C9*2/*2, and CYP2C9*2/*3 genotypes (associated with a low CYP2C9 activity) were more prevalent in the group with low dose requirement of AC compared with the other two groups (P = 0.003). The frequency of CYP2C9*1/*1 genotype, which is associated with an extensive CYP2C9 activity, was higher in the group of patients with high dose requirements (79%), compared with the groups of the medium and low dose requirements (67% and 21% respectively). In addition, the ABCB1 2677GG/3435CC haplotype was associated with use of lower AC dose, whereas the 2677TT/3435TT and 2677GT/3435TT haplotypes were associated with use of higher AC dose (P = 0.03). The distribution of polymorphisms of other genes did not show significant differences between the three groups. CONCLUSION: In vivo, cytochromes P450 isoforms other than CYP2C9 [DOSAGE ERROR CORRECTED] were not significantly associated with dose requirement of AC. In our Bulgarian patients, the presence of CYP2C9*2 or/and CYP2C9*3 alleles, as well as the ABCB1 2677GG/3435CC haplotype were associated with low dose requirement of AC.