Chronic obstructive pulmonary disease (COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers (citrate synthase, β-hydroxyacyl-CoA dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC-1α, PPAR-α, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF-α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochondrial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF-α stimulation. TNF-α also reduced mitochondrial respiration in a nuclear factor kappaB (NF-κB) -dependent manner. Importantly, TNF-α-induced NF-κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochondrial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF-α impairs muscle oxphen in a NF-κB-dependent manner.
OSA severity was independently associated with cholesterol and TG concentrations.
Background. Alveolar hypoxia is the most important mechanism leading to pulmonary arterial vasoconstriction, remodelling and pulmonary hypertension. Patients with Obstructive Sleep Apnoea Syndrome (OSAS) experience multiple short periods of alveolar hypoxia during apnoeic episodes. However, the question as to whether these hypoxic episodes are responsible for the development of permanent pulmonary hypertension is still debatable. We aimed to investigate the relationship between the episodes of nocturnal desaturation and pulmonary haemodynamics in two distinct group patients: with pure OSAS or an overlap syndrome. Methods: We studied 67 patients with severe OSAS (means: age 45±8 years, AHI 62±22, FEV1 3.6±0.8 L = 97±16% of predicted PaO2 72±10 mmHg, PaCO2 40±4 mmHg) and 17 patients with an overlap syndrome (OS), means: age 51±5 years, AHI 64±19, FEV1 1.5±0.7 = 43±16% of predicted PaO2 57±9 mmHg). All subjects underwent pulmonary artery catheterisation with pressure and flow recordings and an overnight full sleep study. Results. On average patients with OSAS had nocturnal desaturation (mean overnight SaO2 = 87±5%) and normal PPA (15.8±4.6 mmHg). Only 11 out of 67 subjects (16%) presented with pulmonary hypertension. Patients with OS had nocturnal desaturation (mean overnight SaO2 = 80.2±8.5%) and mild pulmonary hypertension (PPA 24.2±7.4 mmHg). Only three out of 17 patients had normal pulmonary arterial pressure. Conclusions. In patients with severe OSAS, pulmonary hypertension is rare (16%) and is related best to the severity of the disease and to obesity. In OS patients diurnal pulmonary hypertension is frequent but does not correlate with the severity of nocturnal desaturation.
Chronic obstructive pulmonary disease (COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers (citrate synthase, fi‐hydroxya‐cyl‐CoA dehydrogenase, and cytochrome c oxidase IV) and regulators (PGC‐1α, PPAR‐α, and Tfam) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF‐α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochon‐drial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF‐α stimulation. TNF‐α also reduced mito‐chondrial respiration in a nuclear factor kappaB (NF‐κB) ‐dependent manner. Importantly, TNF‐α‐induced NF‐κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochon‐drial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF‐α impairs muscle oxphen in a NF‐κB‐dependent manner.—Remels, A. H. V., Gosker, H. R., Schrauwen, P., Hommelberg, P. P. H., Sliwinski, P., Polkey, M., Galdiz, J., Wouters, E. F. M., Langen, R. C. J., Schols, A. M. W. J. TNF‐α impairs regulation of muscle oxidative phenotype: implications for cachexia? FASEBJ. 24, 5052–5062 (2010). http://www.fasebj.org
The MESAM 4 system, developed to monitor breathing sounds, heart rate, arterial oxygen saturation (SaO 2 ) and body position, was proposed as a screening method for obstructive sleep apnoea (OSA). The aim of the study was to assess the accuracy of hand-scoring versus automatic-scoring in screening for obstructive sleep apnoea.The study population consisted of 56 patients, 51 males, and 5 females, mean age 47±10 yrs, suspected of having obstructive sleep apnoea. Full polysomnography and MESAM 4 recordings were performed simultaneously. The apnoea+hypop-noea index was hand-scored in polysomnography and in MESAM 4. The handscoring in MESAM 4 was based on analysis of breathing sounds, heart rate and SaO 2 changes taken together. The automatic-scoring system of MESAM 4 calculated oxygen desaturation index, heart rate variation index and intermittent snoring index.The diagnosis of obstructive sleep apnoea (apnoea+hypopnoea index ≥10) was established by polysomnography in 37 patients. Sensitivity and specificity of handscored MESAM 4 diagnosis were 100 and 63%, respectively. Sensitivity and specificity of MESAM 4 diagnosis with automatic-scoring were: from oxygen desaturation index 100 and 27%; from heart rate variation index 81 and 74%; and from intermittent snoring index 92 and 16%, respectively.We suggest that hand-scoring of MESAM 4 is more accurate than automaticscoring in screening for obstructive sleep apnoea. Eur Respir J., 1994Respir J., , 7, 1771 Monitoring of physiological phenomena during sleep is more helpful in the recognition of OSA, than looking for signs which can be observed during wakefulness and are only indirectly connected with sleep-disordered breathing, i.e. nonspecific changes of the flow-volume loop or articulation of certain vowels.Simultaneous recording of several variables should, in principle, give better results than single parameter analysis. Such a device should be characterized by its noninvasiveness (interpreted as resulting in no interruption of sleep), accuracy and high stability of recording lasting for several hours, and also its simplicity in application and scoring [10].It seems that the MESAM 4 (Madaus Inc., Germany) fulfils these criteria. Its use was previously reported by STOOHS and GUILLEMINAULT [11]. However, in their study only automatic analysis of recorded variables was considered. The aim of this validation study was to assess the accuracy of hand-scoring versus automatic-scoring of MESAM 4 in screening for OSA. Material and methods PatientsWe studied patients who were referred to the sleep laboratory suspected of having sleep/wake disorders. They underwent general clinical examination and filled a typical sleep questionnaire, based on the Marburg questionnaire [12], in the presence of their bed-partners. The next step in the study consisted of eligible subjects complaining either of loud and irregular snoring or excessive daytime somnolence, or whose bed-partner observed apnoeic pauses during sleep.Fifty six patients were admitted to the study, 51 males and...
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