Comparison of different levels of positive expiratory pressure on chest wall volumes in healthy children and patients with fibrosis

ABSTRACT Positive Expiratory Pressure (PEP) improves lung function, however, PEP-induced changes are not fully established. The aim of this study was to assess the acute effects of different PEP levels on chest wall volumes and the breathing pattern in children with Cystic Fibrosis (CF). Anthropometric data, lung function values, and respiratory muscle strength were collected. Chest wall volumes were assessed by Optoelectronic plethysmography at rest and during the use of different PEP levels (10 and 20 cm H2O), randomly chosen. Eight subjects with CF (5M, 11.5±3.2 years, 32±9.5 kilograms) and seven control subjects (4M, 10.7±1.5 years, 38.2±7.8 kilograms) were recruited. The CF group showed significantly lower FEF values 25-75% (CF: 1.8±0.8 vs. CG: 2.3±0.6) and FEV1/FVC ratio (CF: 0.8±0.1 vs. CG: 1±0.1) compared with the control group (p<0.05). Different PEP levels increased the usual volume in chest wall and its compartments in both groups; however, this volume was significantly higher in the control group compared with the CF group during PEP20 (CW: 0.77±0.25 L vs. 0.44±0.16 L; RCp: 0.3±0.13 L vs. 0.18±0.1 L; RCa: 0.21±0.1 L vs. 0.12±0.1 L; AB: 0.25±0.1 L vs. 0.15±0.1 L; p<0.05 for all variables). Minute ventilation was significantly higher during PEP compared with breathing at rest in both groups (p<0.005). End-expiratory volume was also higher during PEP compared with breathing at rest for chest wall and pulmonary rib cage in both groups (p<0.05). Different PEP levels may increase chest wall volumes in CF patients

Protein–ligand structure guided by backbone and side-chain proton chemical shift perturbations

International audienceThe fragment-based drug design approach consists of screening libraries of fragment-like ligands, to identify hits that typically bind the protein target with weak affinity ( 100μM –5 mM). The determination of the protein–fragment complex 3D structure constitutes a crucial step for uncovering the key interactions responsible for the protein–ligand recognition, and for growing the initial fragment into potent active compounds. The vast majority of fragments are aromatic compounds that induce chemical shift perturbations (CSP) on protein NMR spectra. These experimental CSPs can be quantitatively used to guide the ligand docking, through the comparison between experimental CSPs and CSP back-calculation based on the ring current effect. Here we implemented the CSP back-calculation into the scoring function of the program PLANTS. We compare the results obtained with CSPs measured either on amide or aliphatic protons of the human peroxiredoxin 5. We show that the different kinds of protons lead to different results for resolving the 3D structures of protein–fragment complexes, with the best results obtained with the Hα protons