Greater parallel heterogeneity of airway narrowing and airway closure in asthma measured by high-resolution CT.
BACKGROUND
Heterogeneous airway narrowing and closure are characteristics of asthma. However, they have never been quantified by direct measurements of parallel sister airways obtained from image data, and the anatomical basis of these processes remains unknown.


METHODS
Seven normal and nine asthmatic subjects underwent high-resolution CT, before and after methacholine challenge. Mean lumen areas of the entire airways were measured in 28 and 24 parallel sister airway pairs (a pair of airways arising from the same bifurcation) respectively (range 1.0-8.7 mm diameter). Heterogeneous narrowing was defined as the median difference in percentage narrowing between parallel sister airways. Forced oscillatory respiratory resistance (Rrs) and spirometry were measured before and after methacholine challenge conducted while supine.


RESULTS
The airways of asthmatics were smaller at baseline, and following bronchoconstriction there were similar decreases in FEV1, increases in Rrs and mean narrowing of airways for asthmatic and non-asthmatic groups. Non-asthmatics required higher doses of methacholine than asthmatics to achieve the same changes. However, parallel heterogeneity (median (IQR) 33% (27-53%) vs 11% (9-18%), p<0.001) and airway closure (24.1% and 7.7%, p=0.001, χ(2)) were greater in asthmatics versus non-asthmatics.


CONCLUSIONS
We found clear evidence of differences in airway behaviour in the asthmatic group. Asthmatic airways were narrower at baseline and responded to inhaled methacholine by more heterogeneous narrowing of parallel sister airways and greater airway closure.
The Woolcock Institute of Medical Research, Glebe, New South Wales, Australia The Northern and Central Clinical Schools, The University of Sydney, Sydney, New South Wales, Australia Cooperative Research Centre for Asthma and Airways, Glebe, New South Wales, Australia.
J R
JR
Dame Carroll
Macquarie University Hospital, Macquarie University, North Ryde, New South Wales, Australia.
J S
JS
Magnussen
The Woolcock Institute of Medical Research, Glebe, New South Wales, Australia The Northern and Central Clinical Schools, The University of Sydney, Sydney, New South Wales, Australia Cooperative Research Centre for Asthma and Airways, Glebe, New South Wales, Australia The George Institute for Global Health, Sydney, New South Wales, Australia.
N
N
Berend
The Woolcock Institute of Medical Research, Glebe, New South Wales, Australia The Northern and Central Clinical Schools, The University of Sydney, Sydney, New South Wales, Australia Cooperative Research Centre for Asthma and Airways, Glebe, New South Wales, Australia.
C M
CM
Salome
The Woolcock Institute of Medical Research, Glebe, New South Wales, Australia The Northern and Central Clinical Schools, The University of Sydney, Sydney, New South Wales, Australia Cooperative Research Centre for Asthma and Airways, Glebe, New South Wales, Australia Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
G G
GG
King
D000328:Adult; D001249:Asthma / Q000000981:diagnostic imaging*; D016535:Bronchial Hyperreactivity / Q000175:diagnosis; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D016210:Methacholine Chloride; D012119:Respiration; D016683:Supine Position / Q000502:physiology; D014057:Tomography, X-Ray Computed / Q000379:methods; D055815:Young Adult
D016210:Methacholine Chloride
Asthma; Asthma Mechanisms; Imaging/CT MRI etc; Lung Physiology