Quadriceps muscle weakness is an important component of chronic obstructive pulmonary disease (COPD). We hypothesised that quadriceps weakness would also be a feature of restrictive lung disease due to scoliosis. We studied 10 patients with severe scoliosis (median (interquartile range (IQR)) forced expiratory volume in 1 s (FEV1) 35.3 (11)% predicted), 10 patients with severe COPD (FEV1 26.5 (9.0)% pred) and 10 healthy age-matched adults. We measured quadriceps strength, exercise capacity and analysed quadriceps muscle biopsies for myosin heavy-chain (MyHC) isoform expression and the presence of oxidative stress. Both groups exhibited quadriceps weakness with median (IQR) maximal voluntary contraction force being 46.0 (17.0) kg, 21.5 (21.0) kg and 31.5 (11.0) kg, respectively (p = 0.02 and 0.04, respectively, for each patient group against controls). Oxidative stress was significantly greater in the quadriceps of both restrictive and COPD patients. The scoliosis patients exhibited a decrease in the proportion of MyHC type I compared with controls; median (IQR) 35.3 (18.5)% compared with 47.7 (9.3)%, p = 0.028. The scoliosis patients also showed an increase in MyHC IIx (26.3 (15.5)% compared with 11.3 (13.0)%, p = 0.01. Quadriceps weakness is a feature of severe scoliosis; the similarities between patients with scoliosis and patients with COPD suggest a common aetiology to quadriceps weakness in both conditions.

Background: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. The objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function and exercise capacity.Methods: We conducted a cross sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and seven healthy controls. Subsequently, selected cytokines (tumour necrosis factor (TNF)alpha, TNF alpha receptors I and II, interleukin (IL) 6, interferon c, transforming growth factor (TGF) beta and vascular endothelial growth factor (VEGF)), as well as protein carbonylation (oxidative stress index) were determined using an enzyme linked immunosorbent assay (ELISA) in all muscles.Results: Compared with controls, the vastus lateralis of patients with COPD showed significantly lower protein ELISA levels of TNF alpha, which positively correlated with their quadriceps function, TNF alpha receptor II and VEGF. Protein ELISA levels of IL6, interferon gamma and TGF alpha did not differ between patients and controls. Quadriceps protein carbonylation was greater in patients and inversely correlated with quadriceps strength among them.Conclusions: These findings do not support the presence of a proinflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.

Assessment of quadriceps endurance is of interest to investigators studying human disease. We hypothesized that repetitive magnetic stimulation (rMS) of the intramuscular branches of the femoral nerve could be used to induce and quantify quadriceps endurance. To test this hypothesis, we used a novel stimulating coil to compare the quadriceps endurance properties in eight normal humans and, to confirm that the technique could be used in clinical practice, in eight patients with advanced chronic obstructive pulmonary disease (COPD). To validate the method, we compared in vivo contractile properties of the quadriceps muscle with the fiber-type composition and oxidative enzyme capacity. We used a Magstim Rapid(2) magnetic nerve stimulator with the coil wrapped around the quadriceps. Stimuli were given at 30 Hz, a duty cycle of 0.4 (2 s on, 3 s off), and for 50 trains. Force generation and the surface electromyogram were measured throughout. Quadriceps twitch force, elicited by supramaximal magnetic stimulation of the femoral nerve, was measured before and after the protocol. Quadriceps muscle biopsies were analyzed for oxidative (citrate synthase, CS) and glycolytic (phosphofructokinase, PFK) enzyme activity and myosin heavy chain isoform protein expression. The time for force to fall to 70% of baseline (T(70)) was shorter in the COPD group than the control group: 55.6 +/- 26.0 vs. 121 +/- 38.7 s (P = 0.0014). Considering patients and controls together, positive correlations were observed between T(70) and the proportion of type I fibers (r = 0.68, P = 0.004) and CS-to-PFK ratio (CS/PFK) (r = 0.67, P = 0.005). We conclude that quadriceps endurance assessed using rMS is feasible in clinical studies.

Diaphragm paralysis may occur after traumatic phrenic nerve injury. Here we report three patients in whom right hemi-diaphragmatic paralysis developed after cardiac radiofrequency ablation. We hypothesise that local focused thermal energy at the time of the ablation may have caused direct neuronal damage by axonal coagulation necrosis. The prognosis for this type of injury may be reasonably good; two of the three patients fully recovered diaphragm function by 1 year.

Background: Prognosis in chronic obstructive pulmonary disease ( COPD) is poorly predicted by indices of air flow obstruction, because other factors that reflect the systemic nature of the disease also influence prognosis.Objective: To test the hypothesis that a reduction in quadriceps maximal voluntary contraction force ( QMVC) is a useful predictor of mortality in patients with COPD.Methods: A mortality questionnaire was sent to the primary care physician of 184 patients with COPD who had undergone quadriceps strength measurement over the past 5 years. QMVC was expressed as a percentage of the patient's body mass index. The end point measured was death or lung transplantation, and median ( range) follow- up was 38 ( 1 - 54) months.Results: Data were obtained for 162 patients ( 108 men and 54 women) with a mean ( SD) percentage of forced expiratory volume in 1 s ( FEV1) predicted of 35.6 ( 16.2), giving a response rate of 88%. Transplantfree survival of the cohort was 93.5% at 1 year and 87.1% at 2 years. Cox regression models showed that the mortality risk increased with increasing age and with reducing QMVC. Only age ( HR 1.72 ( 95% CI 1.14 to 2.6); p = 0.01) and QMVC ( HR 0.91 ( 95% CI 0.83 to 0.99); p = 0.036) continued to be significant predictors of mortality when controlled for other variables in the multivariate analysis.Conclusion: QMVC is simple and provides more powerful prognostic information on COPD than that provided by age, body mass index and forced expiratory volume in 1 s.

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 ± 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor‐evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus–response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1–5 ms) and was more facilitated at long interstimulus intervals (9–20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.