Severe PVA was identified in the majority of patients, irrespective of pathophysiological disease state. This was not associated with ineffective ventilation as evidenced by gas exchange.

RationaleHospitalised patients with acute exacerbation of COPD may deteriorate despite treatment, with early readmission being common.ObjectivesTo investigate whether neural respiratory drive, measured using second intercostal space parasternal muscle electromyography (EMGpara), would identify worsening dyspnoea and physician-defined inpatient clinical deterioration, and predict early readmission.MethodsPatients admitted to a single-site university hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory capacity (IC), EMGpara, routine physiological parameters, modified early warning score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of deterioration were recorded daily until discharge. Readmissions at 14 and 28 days post discharge were recorded.Measurements and main results120 patients were recruited (age 70±9 years, forced expiratory volume in 1 s (FEV1) of 30.5±11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale, was associated with increases in EMGpara%max and MEWS, whereas an increase in EMGpara%max alone was associated with physician-defined inpatient clinical deterioration. Admission-to-discharge change (Δ) in the normalised value of EMGpara (ΔEMGpara%max) was inversely correlated with ΔFEV1 (r=−0.38, p<0.001) and ΔIC (r=−0.44, p<0.001). ΔEMGpara%max predicted 14-day readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR 1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to 1.66), also predicted 28-day readmission in the whole cohort.ConclusionsMeasurement of neural respiratory drive by EMGpara represents a novel physiological biomarker that may be helpful in detecting inpatient clinical deterioration and identifying the risk of early readmission among patients with exacerbations of COPD.Trial registrationNCT01361451.

A nuclear magnetic resonance (NMR) technique has been devised to probe the structures of disordered, partially folded states of proteins at the level of individual amino acid residues. Chemically induced dynamic nuclear polarization (CIDNP) is first generated in exposed aromatic side-chains of the denatured state and then transferred to the high-resolution NMR spectrum of the native state by stimulating rapid refolding of the protein. Crucial improvements in sensitivity were achieved by carrying out the polarization-producing photochemistry in a deoxygenated sample of the disordered state of the protein in a magnetic field of 4.0 T and recording the (1)H NMR spectrum of the refolded native state at 9.4 T (400 MHz). Application of this method to the low pH molten-globule state of alpha-lactalbumin reveals remarkably nativelike environments for the aromatic residues in the primary hydrophobic core of the protein. This result provides compelling evidence that the detailed fold of a protein can be established prior to the formation of the cooperative close-packed native structure.