| Autor: |
Fleming JS; 1National Institute of Health Research Biomedical Research Unit in Respiratory Disease, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.; 2Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Conway J; 1National Institute of Health Research Biomedical Research Unit in Respiratory Disease, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.; 3Faculty of Health Sciences, University of Southampton, Southampton, United Kingdom., Bennett MJ; 1National Institute of Health Research Biomedical Research Unit in Respiratory Disease, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Tossici-Bolt L; 2Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Guy M; 2Department of Medical Physics, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Blé FX; 4Precision Medicine and Genomics, Innovative Medicines and Early Development, AstraZeneca, Royston, United Kingdom., McCrae C; 5Respiratory Inflammation and Autoimmunity (RIA) Innovative Medicines and Early Development Unit, AstraZeneca Gothenburg, Mölndal, Sweden., Carlsson M; 6Global Medicines Development, AstraZeneca Gothenburg, Mölndal, Sweden., Bondesson E; 7Clinical Studies Sweden, Forum South, Skane University Hospital, Lund, Sweden. |
| Abstrakt: |
Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls ( n = 9), (2) smoking controls who were current smokers with normal lung function ( n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis ( n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV 1 ) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements ( p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls ( p = 0.007) and COPD ( p < 0.0001). It also correlated with FEV 1 ( p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD. |
