Patterns of Retention of Particulate Matter in Lung Tissues of Patients With COPD: Potential Role in Disease Progression

doi:10.1378/chest.10-2281

Chest

Volume 140, Issue 6, December 2011, Pages 1540-1549

https://doi.org/10.1378/chest.10-2281 Get rights and content

Background

Particulate matter (PM) is present in lung tissues of smokers and urban dwellers. This study was designed to quantify the burden of PM in different lung tissues of subjects with COPD and determine its relationship to disease severity.

Methods

Surgical lung tissue samples from nonsmokers (control subjects) were compared with those from smokers with normal spirometry and subjects in the four other categories of the GOLD (Global Initiative for Obstructive Lung Disease) classification of COPD severity using quantitative histologic techniques.

Results

PM was present in the lung parenchyma, blood vessel walls, airways, lymphoid follicles, and alveolar macrophages. The total burden of PM (volume fraction [Vv]) in all tissues of the lung was higher in smokers than nonsmokers (P < .001) and also in smokers with airflow obstruction compared with the smokers with normal spirometry (P < .01). There was an incremental increase in total PM burden with increased COPD severity that peaked in GOLD II and then trended downward in GOLD III and IV COPD. This same pattern of PM retention was also observed in alveolar walls. The total burden of PM in lung tissues correlated with a decline in FEV₁/FVC as well as pack-years smoking. mRNA expression of fibrinogen (γ chain) correlated with total lung burden of PM and burden of PM in lung parenchyma (r² = 0.22, P < .001).

Conclusions

We conclude that retained PM is widely distributed in lung tissues of subjects with COPD and that cigarette smoke exposure and airflow obstruction are associated with retention of PM in lung tissues. We attribute the downward trend in PM burden in severe COPD to either less deposition and retention or selective removal of PM containing tissues by emphysematous destruction.

Section snippets

Tissue Collection

The source of the lung tissue examined in this study has been described in detail elsewhere.²⁸ Briefly, lung tissue from 65 patients who required lung resection either as treatment of lung cancer or in preparation for lung transplantation for advanced COPD were used. These 65 subjects include nonsmoking control subjects (n = 11) whose lungs were resected for small lung tumors, including five with carcinoids and six with carcinomas; smokers without airflow obstruction (GOLD [Global Initiative

Results

Table 1 shows the demographic data of the study population. There were no significant differences in age or smoking pack-years between the different groups. There were no statistical differences in gender distribution between groups. In the control nonsmoking group, 18% of subjects were men. Eight of the subjects had a significant occupational exposure (construction industry and mining), and these subjects were evenly distributed between groups. In three subjects no occupational exposure

Discussion

The results presented here show that inhaled PM is retained in different lung tissue compartments (even in never-smoking subjects) with the largest amount (in volume) of PM retained in alveolar walls. In all subjects, the amount of PM retention in the whole lung was significantly higher in subjects with COPD compared with subjects without COPD (Fig 2A). In addition, comparing just smokers with a similar amount of cigarette smoke exposure, PM retention was greater in those subjects with abnormal

Conclusion

The present results show that PM is retained in lung tissues in both nonsmokers and smokers, which is consistent with the contributions of both environmental and tobacco smoking sources to the PM burden in the lung. In addition, they also show alveolar walls accumulate more PM than conducting airways, blood vessels, or lymphatic tissues and that the majority of PM retained in the lung is deposited deep into the lung. There is an association between the accumulation of PM and COPD severity that

Acknowledgments

Author contributions: Mr Ling: contributed to performing the majority of the morphometric analysis and writing the first draft of the manuscript.

Dr McDonough: contributed to the tissue processing, mean linear intercept measurements, and revision of the manuscript.

Mr Gosselink: contributed to the gene expression studies and revision of the manuscript.

Dr Elliott: contributed to collecting the lung tissues, processing the tissues for storage, coordinating the patient/tissue selection process, and

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Funding/Support: This work was supported by the British Columbia Lung Association, the Heart and Stroke Foundation of Canada, and the Canadian Institutes of Health Research. Dr van Eeden was supported by a scholarship from the Michael Smith Foundation for Health Research and the Canadian Institute for Health Research. He is a senior scholar with the Michael Smith Foundation for Health Research and CIHR/GSK professor in Chronic Obstructive Pulmonary Disease.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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Chest

Original ResearchCOPDPatterns of Retention of Particulate Matter in Lung Tissues of Patients With COPD: Potential Role in Disease Progression

Background

Methods

Results

Conclusions

Section snippets

Tissue Collection

Results

Discussion

Conclusion

Acknowledgments

Mutat Res

Am J Pathol

J Allergy Clin Immunol

Fundam Appl Toxicol

Fundam Appl Toxicol

J Biol Chem

Global initiative for chronic obstructive lung diseases (GOLD): time to act

Eur Respir J

Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease-2008 update-highlights for primary care

Can Respir J

Why does airway inflammation persist after the smoking stops?

Thorax

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

N Engl J Med

Ongoing airway inflammation in patients with COPD who do not currently smoke

Thorax

Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

Inhal Toxicol

Short term fluctuations in air pollution and hospital admissions of the elderly for respiratory disease

Thorax

An association between air pollution and mortality in six U.S. cities

N Engl J Med

Long-term air pollution exposure and living close to busy roads are associated with COPD in women

Respir Res

Chronic pulmonary disease in rural women exposed to biomass fumes

Clin Invest Med

Biomass fuels are the probable risk factor for chronic obstructive pulmonary disease in rural South China

Thorax

The pathology of chronic obstructive pulmonary disease

Annu Rev Pathol

Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro

Thorax

Systemic response to ambient particulate matter: relevance to chronic obstructive pulmonary disease

Proc Am Thorac Soc

Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma

Am J Respir Crit Care Med

Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse

Am J Respir Crit Care Med

Dose-dependent cigarette smoking-related inflammatory responses in healthy adults

Eur Respir J

Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers

Eur Respir J

Original Research
COPD
Patterns of Retention of Particulate Matter in Lung Tissues of Patients With COPD: Potential Role in Disease Progression