Chest
Volume 131, Issue 5, May 2007, Pages 1372-1378
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Original Research: COPD
The Association Between Small Airway Obstruction and Emphysema Phenotypes in COPD

https://doi.org/10.1378/chest.06-2194Get rights and content

Background

Airflow limitation in COPD is due to a variable combination of small airway obstruction and centrilobular emphysema (CLE) and/or panlobular emphysema (PLE), but the relationship between these three different phenotypes is poorly understood. This study compares the severity of small airway obstruction in both forms of emphysema and determines its relationship with FEV1.

Methods

We compared the lung histology of nonsmoking control subjects without emphysema (n = 10) to that of patients with CLE (n = 30) and PLE with (n = 8) and without α1-antitrypsin (AAT) deficiency (n = 11). The degree of airspace enlargement was measured using the mean interalveolar wall distance (IAWD) [mean linear intercept, Lm], and the evenness of airspace destruction was assessed by the coefficient of variation (CV) of the IAWD. The severity of small airway obstruction was determined by dividing total wall area by the length of the basement membrane to obtain wall thickness.

Results

Lm was greater in all three subgroups of emphysema than in control subjects, and in AAT deficiency than in PLE or CLE. The CV of IAWD was greater in AAT deficiency and CLE than in control subjects and in CLE than in AAT deficiency or PLE. Although small airway wall thickness was greater in CLE and PLE with AAT deficiency than in control subjects, the association between wall thickness and both Lm and FEV1 was observed only in CLE.

Conclusions

Small airway wall thickening occurs in CLE and PLE with AAT deficiency but is more closely associated with degree of emphysema and airflow limitation in CLE.

Section snippets

Subject Population

The study group consisted of 10 nonsmoking control subjects with normal spirometry and no microscopic emphysema and 49 subjects with a microscopic diagnosis of emphysema. All subjects required lung resection for either small peripheral lung tumors (n = 38), LVRS (n = 3), or lung transplantation for advanced COPD (n = 18) in Vancouver, Canada. All of the subjects gave informed consent for their participation in the study,21 and the protocol was approved by the Hospital and University of British

Results

Table 2 summarizes the measurements of alveolar dimensions and small airway wall thickness in four groups. Lm was higher in AAT deficiency, PLE, and CLE than in nonsmoking control subjects (p < 0.002, respectively) and also in AAT deficiency than in PLE or CLE (p < 0.01, respectively). CV of IAWD was greater in AAT deficiency and CLE (p < 0.002, respectively) than in control subjects and in CLE than in AAT deficiency or PLE (p < 0.002, respectively). Small airway wall thickness was greater in

Discussion

Emphysema contributes to the decrease in expiratory flow by reducing the elastic recoil pressure available to drive air out of the lungs,3 whereas obstruction in the small airways is most closely associated with a remodeling process that thickens the airway walls.11 However, as both small airway obstruction and emphysema are commonly present within the lungs of individuals with COPD, it is difficult to determine which component of the disease provides the most appropriate therapeutic target.

The

REFERENCES (34)

  • Mc LeanKH

    The pathogenesis of pulmonary emphysema

    Am J Med

    (1958)
  • HoggJC et al.

    Site and nature of airway obstruction in chronic obstructive lung disease

    N Engl J Med

    (1968)
  • MeadJ et al.

    Significance of the relationship between lung recoil and maximum expiratory flow

    J Appl Physiol

    (1967)
  • LaennecRTH
    (1834)
  • ShapiroSD et al.

    The pathogenesis of chronic obstructive pulmonary disease: advances in the past 100 years

    Am J Respir Cell Mol Biol

    (2005)
  • MatsubaK et al.

    The number and dimensions of small airways in emphysematous lungs

    Am J Pathol

    (1972)
  • LeopoldJG et al.

    The centrilobular form of hypertrophic emphysema and its relation to chronic bronchitis

    Thorax

    (1957)
  • BignonJ et al.

    Parenchymal, bronchiolar, and bronchial measurements in centrilobular emphysema

    Thorax

    (1970)
  • LinhartovaA et al.

    Small airways in severe panlobular emphysema: mural thickening and premature closure

    Am Rev Respir Dis

    (1983)
  • HoggJC et al.

    The nature of small-airway obstruction in chronic obstructive pulmonary disease

    N Engl J Med

    (2004)
  • KimWD et al.

    Centrilobular and panlobular emphysema in smokers: two distinct morphologic and functional entities

    Am Rev Respir Dis

    (1991)
  • SaettaM et al.

    Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications

    Eur Respir J

    (1994)
  • WilliamsLNA et al.

    Relation between small airways disease and parenchymal destruction in surgical lung specimens

    Thorax

    (1990)
  • FinkelsteinR et al.

    Morphometry of small airways in smokers and its relationship to emphysema type and hyperresponsiveness

    Am J Respir Crit Care Med

    (1995)
  • Hernandex-ZentenoRJ et al.

    Morphometry and mast cells inflammation in COPD small airways according to emphysema type [abstract]

    Proc Am Thorac Soc

    (2005)
  • TalamoRC et al.

    Familial emphysema and α1-antitrypsin deficiency

    N Engl J Med

    (1966)
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    University of British Columbia, Vancouver, Canada. This work was performed at The James Hogg iCAPTURE Center of Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.

    Drs. Kim, English, Yee, and Levy and Mr. Ling have no conflicts of interest to disclose. Dr. Coxson received $11,000 in 2003 for serving on an advisory board for GlaxoSmithKline. In addition, he is the coinvestigator on two multicenter studies sponsored by GlaxoSmithKline and has received travel expenses to attend meetings related to the project. He has three contract service agreements with GlaxoSmithKline to quantify the CT scans in subjects with COPD. A percentage of his salary between 2003 and 2006 (US $15,000/yr) derives from contract funds provided to a colleague Peter D. Paré by GlaxoSmithKline for the development of validated methods to measure emphysema and airway disease using CT. There is no financial relationship between any industry and the current study.

    Dr. Pare is the principal investigator of a project funded by GlaxoSmithKline to develop CT-based algorithms to quantitate emphysema and airway disease in COPD. With collaborators he has received approximately $300,000 to develop and validate these techniques. The funds he has applied solely to the research to support programs and technicians. He is also principal investigator of a Merck Frosst-supported research program to investigate gene expression in the lungs of patients who have COPD. He and collaborators have received approximately $200,000 for this project. These funds have supported the technical personnel and expendables involved in the project.

    Dr. Hogg has served as a consultant to Altana Pharmaceuticals in 2003, 2004, and 2005, and also served on the Canadian advisory board for GlaxoSmithKline for 1 year in 2003. He has participated as a speaker in scientific meetings and courses organized and financed by various pharmaceutical companies, including AstraZeneca, Altana Pharmaceuticals, and GlaxoSmithKline. He serves as the principal investigator on a joint Canadian Institute of Health Research and industry-sponsored grant, supported one third by the Canadian Institute of Health Research and two thirds by industry. This grant application was funded after peer review by the regular Canadian Institute of Health Research mechanism, and the funds received from industry are directly related to the operating costs of the study.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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