Six patients were established on home NIV. When studied, the ventilator users had been on home NIV for a median 33 (range 3–93) months. At the time of their initiation onto NIV the mean PaCO2 had been 7.5 (1.2) kPa and PaO2 6.5 (1.3). FEV1, TLCO and FRC were 24.8 (4.8), 54

(21) and 149.7 (31)% predicted respectively. The indication for NIV was symptomatic hypercapnia and/or recurrent episodes of Type II respiratory failure. Their lung function and other characteristics at the time of the study are described in Table 1 and it should be noted that the ventilator users’ blood gas parameters had improved significantly with treatment. At the time of the study the two patient groups did not differ significantly in their degree PR-171 manufacturer of airflow obstruction or lung volumes, but ventilator users had less severe impairment of gas transfer. One ventilated and two unventilated patients declined esophageal catheters so only non-invasive measures were available. We measured lung volumes, gas transfer (Compact Lab System, Jaeger, Germany) and arterialized capillary blood gas tensions. Esophageal and gastric pressures were measured using catheters passed conventionally connected to differential pressure transducers (Validyne, CA, USA), amplified

and displayed online together with transdiaphragmatic Panobinostat molecular weight pressure (Pdi), using LabView software (National Instruments) ( Baydur et al., 1982). Maximum sniff nasal pressure (SNiP) was used as a measure of inspiratory muscle strength ( Laroche et al., 1988). End-tidal CO2 was determined via a nasal catheter connected to a capnograph Tenoxicam (PK Morgan Ltd, Gillingham, Kent, UK). Twitch transdiaphragmatic pressure was assessed using bilateral anterolateral magnetic phrenic nerve stimulation

as described elsewhere ( Mills et al., 1996). The response to TMS was recorded with surface Ag/AgCl electrodes. Electrode position was optimized using supramaximal phrenic nerve stimulation which also provided compound motor action potential (CMAP) amplitude and latency. Signals were acquired into an EMG machine (Synergy, Oxford Instruments, Oxford, UK) with band-pass filtering of signals less than 10 Hz or greater than 10 kHz. To give an assessment of expiratory muscle responses rectus abdominis response was recorded using surface electrodes. TMS was delivered using Magstim 200 Monopulse units linked via a Bistim timing device (The Magstim Company, Wales) and a 110 mm double cone coil positioned over the vertex (Demoule et al., 2003a and Sharshar et al., 2003). Stimuli were delivered at resting end expiration, assessed from the esophageal and transdiaphragmatic pressure traces, throughout the study and stimuli were repeated if there was evidence of inspiratory activity. An interval of at least 30 s between stimulations was respected. Motor threshold was defined as the lowest stimulator output producing a MEP of ≥50 μV in ≥5 of 10 trials (Rossini et al., 1994).