Sex differences in COPD-related quadriceps muscle dysfunction and fibre abnormalities.

In chronic obstructive pulmonary disease (COPD), lower limb dysfunction is associated with reduced exercise capacity, increased hospitalizations and mortality. We investigated sex differences in the prevalence of quadriceps dysfunction and fibre abnormalities in a large COPD cohort, controlling for the normal sex differences in health. We compared existing data from 76 male and 38 female COPD patients where each variable was expressed as a function of gender-specific normal values (obtained from 16 male and 14 female controls). Female COPD patients had lower quadriceps muscle strength and peak workload on a maximal incremental cycle ergometry protocol compared to male patients. Female patients had a smaller type II fibre cross-sectional area (CSA) compared to male patients, suggesting a greater female preponderance to fibre atrophy, although this result was largely driven by a few male patients with a large type II fibre CSA. Female patients had significantly higher concentrations of a number of plasma pro-inflammatory cytokines including tumour necrosis factor alpha and interleukin 8 (IL8), but not lower levels of physical activity or arterial oxygenation, compared to males. Our data confirm results from a previous small study and suggest that female COPD patients have a greater prevalence of muscle wasting and weakness. Larger studies investigating sex differences in COPD-related muscle atrophy and weakness are needed, as the results will have implications for monitoring in clinical practice and for design of clinical trials evaluating novel muscle anabolic agents.

Noninvasive ventilation and lung volume reduction.

As parenchymal lung disease in chronic obstructive pulmonary disease becomes increasingly severe there is a diminishing prospect of drug therapies conferring clinically useful benefit. Lung volume reduction surgery is effective in patients with heterogenous upper zone emphysema and reduced exercise tolerance, and is probably underused. Rapid progress is being made in nonsurgical approaches to lung volume reduction, but use outside specialized centers cannot be recommended presently. Noninvasive ventilation given to patients with acute hypercapnic exacerbation of chronic obstructive pulmonary disease reduces mortality and morbidity, but the place of chronic non-invasive ventilatory support remains more controversial.

Yin Yang 1 expression and localisation in quadriceps muscle in COPD.

INTRODUCTION: Yin Yang 1 (YY1) is a transcriptional repressor that inhibits muscle gene expression and myogenesis. YY1 has not previously been investigated in the skeletal muscle of patients with COPD. The aims of this study were to investigate YY1 expression and localisation in the quadriceps muscle of COPD patients compared to healthy age-matched controls, and examine the relationship between YY1 expression and localisation and quadriceps muscle fibre cross-sectional area (CSA) in COPD patients. PATIENTS AND METHODS: 15 COPD patients and 8 age-matched controls underwent lung and quadriceps function assessments and a percutaneous quadriceps biopsy. Quadriceps muscle fibre CSA and fibre proportions and YY1 localisation were determined by immunofluorescence. YY1 was immunoprecipitated from muscle and YY1 levels assessed by western blotting. RESULTS: YY1 levels were inversely correlated with type IIx and type I fibre CSA in patients and controls, though YY1 levels were not significantly different between the groups. Nuclear localisation of YY1 was demonstrated in the patients but not in controls. CONCLUSION: YY1 expression is associated with smaller quadriceps fibre CSA in COPD and nuclear localisation of YY1 was found in muscle of patients but not controls. Regulation of YY1 appears altered in COPD and may be implicated in COPD-related muscle atrophy.

Distinguishing obstructive from central sleep apnea events: diaphragm electromyogram and esophageal pressure compared.

BACKGROUND: Distinguishing central sleep apnea (CSA) from obstructive sleep apnea (OSA) can be clinically important because different types of apnea may require different treatment approaches. Academically, this distinction is important for investigating the pathological mechanism of different types of sleep apnea. Conventional polysomnography (PSG) with recording of chest and abdominal movement may overestimate the frequency of CSA, leading to inappropriate treatment of sleep-disordered breathing. We hypothesized that diaphragm electromyogram (EMGdi) could be a useful technique to assess neural respiratory drive and respiratory effort and, therefore, to distinguish accurately CSA from OSA. METHODS: A multipair esophageal electrode catheter mounted with a balloon was used to record the EMGdi and esophageal pressure (Pes) during overnight PSG. Nineteen patients were included in the study, 12 of whom had previously been identified as having central apnea-hypopnea on a diagnostic PSG undertaken for symptoms that suggest OSA and 7 of whom were known to have heart failure. RESULTS: A good relationship was found between the swing of Pes and the root mean (+/- SD) square of the EMGdi during OSA events (0.89 +/- 0.10). About one third of CSA events diagnosed by uncalibrated respiratory inductance plethysmography could not be confirmed by Pes or EMGdi. No difference was found in the number of CSAs diagnosed by Pes (1,319) vs EMGdi (1,293; p > 0.01). CONCLUSIONS: We conclude that both Pes and EMGdi measurements are useful in accurately differentiating central from obstructive respiratory events. Conventional PSG with recording of chest and abdominal movement overestimates the frequency of CSA events.