Small-airway obstruction and emphysema in chronic obstructive pulmonary disease.

TitleSmall-airway obstruction and emphysema in chronic obstructive pulmonary disease.
Publication TypeJournal Article
Year of Publication2011
AuthorsMcDonough, JE, Yuan, R, Suzuki, M, Seyednejad, N, W Elliott, M, Sanchez, PG, Wright, AC, Gefter, WB, Litzky, L, Coxson, HO, Paré, PD, Sin, DD, Pierce, RA, Woods, JC, McWilliams, AM, Mayo, JR, Lam, SC, Cooper, JD, Hogg, JC
JournalN Engl J Med
Volume365
Issue17
Pagination1567-75
Date Published2011 Oct 27
ISSN1533-4406
KeywordsAged, Airway Obstruction, Airway Resistance, Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Tomography, X-Ray Computed
Abstract

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.).

DOI10.1056/NEJMoa1106955
Alternate JournalN. Engl. J. Med.
PubMed ID22029978
PubMed Central IDPMC3238466
Grant ListHL062194 / HL / NHLBI NIH HHS / United States
HL084922 / HL / NHLBI NIH HHS / United States
HL084948 / HL / NHLBI NIH HHS / United States
HL090806 / HL / NHLBI NIH HHS / United States
P50 HL084922 / HL / NHLBI NIH HHS / United States
P50 HL084922-05 / HL / NHLBI NIH HHS / United States
P50 HL084948-05 / HL / NHLBI NIH HHS / United States
R01 HL062194-07 / HL / NHLBI NIH HHS / United States
R01 HL090806 / HL / NHLBI NIH HHS / United States
R01 HL090806-04 / HL / NHLBI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada