Small-airway obstruction and emphysema in chronic obstructive pulmonary disease.
BACKGROUND
The major sites of obstruction in chronic obstructive pulmonary disease (COPD) are small airways (<2 mm in diameter). We wanted to determine whether there was a relationship between small-airway obstruction and emphysematous destruction in COPD.


METHODS
We used multidetector computed tomography (CT) to compare the number of airways measuring 2.0 to 2.5 mm in 78 patients who had various stages of COPD, as judged by scoring on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) scale, in isolated lungs removed from patients with COPD who underwent lung transplantation, and in donor (control) lungs. MicroCT was used to measure the extent of emphysema (mean linear intercept), the number of terminal bronchioles per milliliter of lung volume, and the minimum diameters and cross-sectional areas of terminal bronchioles.


RESULTS
On multidetector CT, in samples from patients with COPD, as compared with control samples, the number of airways measuring 2.0 to 2.5 mm in diameter was reduced in patients with GOLD stage 1 disease (P=0.001), GOLD stage 2 disease (P=0.02), and GOLD stage 3 or 4 disease (P<0.001). MicroCT of isolated samples of lungs removed from patients with GOLD stage 4 disease showed a reduction of 81 to 99.7% in the total cross-sectional area of terminal bronchioles and a reduction of 72 to 89% in the number of terminal bronchioles (P<0.001). A comparison of the number of terminal bronchioles and dimensions at different levels of emphysematous destruction (i.e., an increasing value for the mean linear intercept) showed that the narrowing and loss of terminal bronchioles preceded emphysematous destruction in COPD (P<0.001).


CONCLUSIONS
These results show that narrowing and disappearance of small conducting airways before the onset of emphysematous destruction can explain the increased peripheral airway resistance reported in COPD. (Funded by the National Heart, Lung, and Blood Institute and others.).
University of British Columbia James Hogg Research Centre, St. Paul's Hospital, Vancouver, BC, Canada.
John E
JE
McDonough
Ren
R
Yuan
Masaru
M
Suzuki
Nazgol
N
Seyednejad
W Mark
WM
Elliott
Pablo G
PG
Sanchez
Alexander C
AC
Wright
Warren B
WB
Gefter
Leslie
L
Litzky
Harvey O
HO
Coxson
Peter D
PD
Paré
Don D
DD
Sin
Richard A
RA
Pierce
Jason C
JC
Woods
Annette M
AM
McWilliams
John R
JR
Mayo
Stephen C
SC
Lam
Joel D
JD
Cooper
James C
JC
Hogg
D000368:Aged; D000402:Airway Obstruction / Q000000981:diagnostic imaging* / Q000209:etiology; D000403:Airway Resistance; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000209:etiology; D014057:Tomography, X-Ray Computed / Q000379:methods