title: Peripheral resistance: a link between global airflow obstruction and regional ventilation distribution.
abstract: Airflow obstruction and heterogeneities in airway constriction and ventilation distribution are well-described prominent features of asthma. However, the mechanistic link between these global and regional features has not been well defined. We speculate that peripheral airway resistance (R(p)) may provide such a link. Structural and functional parameters are estimated from PET and HRCT images of asthmatic (AS) and nonasthmatic (NA) subjects measured at baseline (BASE) and post-methacholine challenge (POST). Conductances of 35 anatomically defined proximal airways are estimated from airway geometry obtained from high-resolution computed tomography (HRCT) images. Compliances of sublobar regions subtended by 19 most distal airways are estimated from changes in regional gas volume between two lung volumes. Specific ventilations (sV) of these sublobar regions are evaluated from 13NN-washout PET scans. For each pathway connecting the trachea to sublobar region, values of R(p) required to explain the sV distribution and global airflow obstruction are computed. Results show that R(p) is highly heterogeneous within each subject, but has average values consistent with global values in the literature. The contribution of R(p) to total pathway resistance (R(T)) increased substantially for POST (P < 0.0001). The fraction R(p)/R(T) was higher in AS than NA at POST (P < 0.0001) but similar at BASE (range: 0.960-0.997, median: 0.990). For POST, R(p)/R(T) range was 0.979-0.999 (NA) and 0.981-0.995 (AS). This approach allows for estimations of peripheral airway resistance within anatomically defined sublobar regions in vivo human lungs and may be used to evaluate peripheral effects of therapy in a subject specific manner.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. mint.wongviriyawong@gmail.com
authors.forename: C
authors.initials: C
authors.lastname: Wongviriyawong
authors.forename: R S
authors.initials: RS
authors.lastname: Harris
authors.forename: E
authors.initials: E
authors.lastname: Greenblatt
authors.forename: T
authors.initials: T
authors.lastname: Winkler
authors.forename: J G
authors.initials: JG
authors.lastname: Venegas
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000175:diagnosis / Q000503:physiopathology*; D000403:Airway Resistance; D000704:Analysis of Variance; D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction; D016085:Bronchoconstrictor Agents; D016022:Case-Control Studies; D003198:Computer Simulation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride; D008953:Models, Anatomic; D008954:Models, Biological; D061330:Multidetector Computed Tomography; D049268:Positron-Emission Tomography; D011312:Pressure; D012123:Pulmonary Ventilation; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride