Chest
Original Research: COPDThe Association Between Small Airway Obstruction and Emphysema Phenotypes in COPD
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)
The pathogenesis of pulmonary emphysema
Am J Med
(1958)- et al.
Site and nature of airway obstruction in chronic obstructive lung disease
N Engl J Med
(1968) - et al.
Significance of the relationship between lung recoil and maximum expiratory flow
J Appl Physiol
(1967) - (1834)
- et al.
The pathogenesis of chronic obstructive pulmonary disease: advances in the past 100 years
Am J Respir Cell Mol Biol
(2005) - et al.
The number and dimensions of small airways in emphysematous lungs
Am J Pathol
(1972) - et al.
The centrilobular form of hypertrophic emphysema and its relation to chronic bronchitis
Thorax
(1957) - et al.
Parenchymal, bronchiolar, and bronchial measurements in centrilobular emphysema
Thorax
(1970) - et al.
Small airways in severe panlobular emphysema: mural thickening and premature closure
Am Rev Respir Dis
(1983)
The nature of small-airway obstruction in chronic obstructive pulmonary disease
N Engl J Med
Centrilobular and panlobular emphysema in smokers: two distinct morphologic and functional entities
Am Rev Respir Dis
Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications
Eur Respir J
Relation between small airways disease and parenchymal destruction in surgical lung specimens
Thorax
Morphometry of small airways in smokers and its relationship to emphysema type and hyperresponsiveness
Am J Respir Crit Care Med
Morphometry and mast cells inflammation in COPD small airways according to emphysema type [abstract]
Proc Am Thorac Soc
Familial emphysema and α1-antitrypsin deficiency
N Engl J Med
Cited by (57)
Small airways disease in patients with alpha-1 antitrypsin deficiency
2023, Respiratory MedicineGeneration-based study of airway remodeling in smokers with normal-looking CT with normalization to control inter-subject variability
2021, European Journal of RadiologyCitation Excerpt :Some studies have investigated airway alterations in COPD patients, and several studies have reported airway thickening in COPD patients [6,19,20]. Donohue et al. [21] reported that pack-years of smoking were associated with thicker airway walls, and Kim et al. [22] found that thickening of small airway walls was associated with the degree of emphysema and airflow limitations. These previous studies all reported airway wall thickness as Pi10 or WT%, which are measurements of airway wall thickness relative to the luminal diameter or perimeter.
Understanding COPD: A vision on phenotypes, comorbidities and treatment approach
2016, Revista Portuguesa de Pneumologia (English Edition)Citation Excerpt :There is a real need to identify specific attributes in order to group the heterogeneous COPD population into different phenotypes, and guide a patient oriented therapeutic approach. Several phenotypes have already been proposed,2–21 but the understanding of which attributes define which groups of patients remains a challenge. It is recognized that future studies should focus on establishing simple algorithms based on the most discriminant features for assigning patients to specific phenotypes.
Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial
2016, Respiratory MedicineCitation Excerpt :This is exemplified by degradation of extracellular matrix (ECM) [6,7]. This degradation results in the destruction of alveoli and airway remodelling which is a hallmark of moderate to severe COPD [8]. These observations characterize the neutrophilic inflammatory cascade as a candidate target for COPD.
Pulmonary function parameters in high-resolution computed tomography phenotypes of chronic obstructive pulmonary disease
2015, American Journal of the Medical SciencesMultidetector Computed Tomographic Imaging in Chronic Obstructive Pulmonary Disease. Emphysema and Airways Assessment.
2014, Radiologic Clinics of North AmericaCitation Excerpt :This study along with many additional investigations has shown that COPD should be classified based on the extent of emphysema in combination with others parameters, including airway dimensions.2,62,89,133 Also, the extent of small airway remodeling was greater in patients with CLE than in those with PLE, and no association was found between small airway wall thickening and the severity of emphysema in patients with PLE.130 The cumulative knowledge of COPD phenotyping shows that identifying the main cause(s) of airflow limitation in patients with COPD is crucial for determining the appropriate therapeutic strategy.119,134
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).