Agreement of MBW outcomes between setups is poor and explained by nitrogen measurement techniques and breathing pattern.

Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs and reduce its administration frequency. Here, we evaluated the enzymatic activity of rhDNase conjugated to a two-arm 40 kDa polyethylene glycol (PEG40) in CF sputa. Rheology data indicated that both rhDNase and PEG40-rhDNase presented similar mucolytic activity in CF sputa, independently of the purulence of the sputum samples as well as of their DNA, actin and ions contents. The macroscopic appearance of the samples correlated with the DNA content of the sputa: the more purulent the sample, the higher the DNA concentration. Finally, quantification of the enzymes in CF sputa following rheology measurement suggests that PEGylation largely increases the stability of rhDNase in CF respiratory secretions, since 24-fold more PEG40-rhDNase than rhDNase was recovered from the samples. The present results are considered positive and provide support to the continuation of the research on a long acting version of rhDNase to treat CF lung disease.

In adults with non-cystic fibrosis bronchiectasis and mucus hypersecretion, autogenic drainage improved ventilation inhomogeneity. LCI change may be the result of the maximum recruited lung volume and the amount of cleared mucus secretion. (ClinicalTrials.gov registration NCT02411981.).

BACKGROUND: Recent technological advances in nebulization permit researchers to target specific parts of the lungs by modifying delivery method. The aim of this study was to compare the central and peripheral targeted modalities of administration. METHODS: Lung and regional deposition of inhaled technetium-99m diethylene triamine penta-acetic was measured by scintigraphy after peripheral and central targeted modalities of administration with an Akita device in 6 healthy subjects. RESULTS: Drug targeting nebulization delivered a large amount of drug into the peripheral part of the lung independent of the modality (outer-to-inner deposition ratio of 1.24 ؎ 0.21 vs 1.22 ؎ 0.14 for central and peripheral modalities, respectively), but there was no difference in lung deposition (whole-body deposition, 83.3 ؎ 6.5% vs 82.8 ؎ 7.3%, P ‫؍‬ .86) or regional deposition (P ‫؍‬ .77) between both modalities. The extrathoracic deposition was < 20% of the wholebody deposition, without a difference between modalities (P ‫؍‬ .86). CONCLUSIONS: This study shows for the first time that choosing 2 different specific drug targeting nebulization modes does not influence the amount of drug delivered into the lung in healthy male subjects. Moreover, the modes do not modify the site of deposition under the conditions of our study.