Small-Airway Obstruction and Emphysema in Chronic Obstructive Pulmonary Disease

Small-Airway Obstruction and Emphysema in Chronic Obstructive Pulmonary Disease

J.E. Mc Donough and Others

October 27, 2011

N Engl J Med 2011; 365: 1567-75

Emphysema - A Disease of Small Airways or Lung Parenchyma?

W. Mitzner

October 27, 2011

N Engl J Med 2011; 365; 17

Editorial

National Heart, Lung and Blood institute (1984) defined basis of Emphysema

"A condition of the lung characterized by abnormal, permanent enlargement of airspaces DISTAL to the terminal bronchiole accompanied by the destruction of their walls, without obvious fibrosis"

methods:

• multidetector CT (sR 0.6-1.0mm) comparing no. of airways measuring 2.0-2.5mm in 78 patients with various stages of COPD (GOLD scale) in isolated lungs from transplanted COPD patients with CLE & PLE and in donor (control) lungs.
• micro CT (sR 16.24um) was used to: measure the extent of emphysema (linear); no. of terminal bronchioles/mm of lung vol.; min. diameter and cross-sectional area of terminal bronchioles.
• histological analysis counting small airways/cm2 and measuring airway wall thickness

• small airways (<2mm) are the major site of obstruction in COPD

• Poiseuille's Law: resistance to flow is inversely related to the reduction in the radius

• since loss of half of these small airways will double the TPR (parallel arrangement) -> an increase of X40 has been shown in COPD patients

• more easily explained by generalized narrowing than by loss of airways.

• determine whether there is a relationship between small-airway obstruction and emphysematous destruction in COPD

no. of airways measuring 2.0-2.5mm in diameter is reduced in higher GOLD stages

discussion:

• total no. of terminal bronchioles and total cross-sectional areas are severly reduced in CLE & PLE phenotypes of GOLD stage IV lungs.
• comparison of no. of terminal bronchioles with alveolar dimensions (linear intercept) show that narrowing and loss of terminal bronchioles preceeds microscopical emphysematous destruction in CLE.
• microCT precisely identifies individual terminal bronchioles
• microCT terminal bronchioles/mm lung vol. + total lung volume via multidetector CT give estimate to no. of termianl bronchioles

limitations:

• airways 2.0-2.5mm in microCT dissapear or narrowed?

widespread narrowing and loss of smaller conducting airways before emphysematous destruction in CLE and PLE -> explanation for the X40 increase in small airway resistance in COPD patients

• multidetector CT scans shows reduced no. of small airways per lung pair (according to GOLD score)

• multidetector CT broncial tree reconstruction: height of column=no. of airways in each generation. CLE airway no. is lower and <2.5mm airways are missing/narrowed for resolution

mean linear intercept (um) & no. of terminal bronchioles compared to control group

• apex-> base CLE & PLE
• reduced number of terminal bronchioles/mm of lung vol.

timeline of pathology:

• peripheral airway and parenchyma: elastic fiber bundles from trachea to smallest airway give airway lumen appearance

• if lost: recoil with obstruction of small airway
• if however, small airway inflammation leads to self damage (as previously thought) then distal acini and alveoli support will be lost

questions:

• how do larger airways connect to remaining distal acini if terminal bronchi are necrotized?

Finally:

• reconsider emphysema definition to include small airways beyond absence of obvious fibrosis
• permanent enlargment of distal airspaces can serve as structural biomarkers being secondary result of small airway inflammation and destruction

toda!