Chest
Volume 128, Issue 4, October 2005, Pages 3055-3064
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Opinions and Hypotheses
COPD: A Dust-Induced Disease?

https://doi.org/10.1378/chest.128.4.3055Get rights and content

Various reports have demonstrated the importance of small airway inflammation in the development of airflow limitation and progression of COPD. This hypothesis proposes that the pathogenesis of COPD mirrors a chronic inhalational dust-induced disease. The putative inorganic dust in cigarette smoke is aluminum silicate or kaolinite, a common component of clay soils. Kaolinite has been recovered in the alveolar macrophages of smokers and has been reported as a constituent of tobacco products. The origin of kaolinite in tobacco products remains unknown, and possible potential sources are proposed. On inhalation, kaolinite deposition in the distal lung may promote macrophage accumulation within the terminal airways leading to a respiratory bronchiolitis. In the susceptible smoker, important genetic, environmental, immunologic, and mechanical factors interact and modulate this small airway inflammation, ultimately leading to the pathologic lesion of emphysema. Further studies into the effects of kaolinite on macrophage function and the subsequent development of respiratory bronchiolitis could lead to prevention of COPD at its precursor lesion.

Section snippets

Respiratory Bronchiolitis and the Pathogenesis of COPD: Anatomic and Physiologic Correlations

The respiratory bronchioles are the “bridge” between bronchioles and alveolar spaces and serve both air-conducting and gas exchange functions. In 1957, Leopold and Gough22 described the anatomic link between respiratory bronchiolitis and emphysema in postmortem studies. In 1974, Niewoehner et al23 reported the consistent finding of respiratory bronchiolitis in young asymptomatic smokers. In the largest published clinicopathologic study of current and ex-smokers, Fraig and colleagues24 confirmed

Respiratory Bronchiolitis and the Pathogenesis of COPD: Radiologic and Histologic Correlations

Early, subclinical COPD and its accompanying small airway disease and emphysema are grossly underestimated by currently available insensitive techniques: chest radiographs and pulmonary function tests (PFTs).23464748 The high-resolution CT scan (HRCT) identifies abnormalities within the secondary pulmonary lobule with detection of structures as small as 0.5 mm in size. The normal respiratory bronchioles, at 0.3 to 0.5 mm, are below the HRCT sensitivity. Nevertheless, inflammation of the

Is Respiratory Bronchiolitis Merely a Surrogate Marker of Cigarette Smoking or Is It Pathogenic for COPD?

Respiratory bronchiolitis is found in the majority of smokers.2324255253 Nevertheless, most smokers (> 70%) do not have clinically significant COPD or airway obstruction.54 This suggests that respiratory bronchiolitis with its accumulation of atypical macrophages in the distal lung may be a marker of cigarette smoking and not a pathogenic step in the development of COPD.24 Nevertheless, a simple explanation for this apparent paradox is proposed. COPD is a complex disease influenced by multiple

Cigarette Smoke Induces Inflammatory Cell Influx Into the Peripheral Lung

The mechanisms for cigarette smoke-induced inflammatory cell and macrophage influx into the lung are various and have been reviewed.411121659 Snider59 has elucidated the cytokines and macrophage products essential to inflammatory cell chemotaxis into the lung.59 Cigarette smoke triggers the activation of nuclear factor-κB in pulmonary epithelial and resident macrophages, promoting transcription of inflammatory genes such as chemoattractant proteins, adhesion molecules, and proinflammatory

Kaolinite Is the Main Component of Intracellular Inclusions in Pulmonary Macrophages

An important clue to the molecule or particulate matter responsible for the inflammatory effect of cigarette smoke comes from the macrophages themselves. The macrophages of smokers contain characteristic brown-pigmented cytoplasmic inclusions believed to be byproducts of cigarette smoke. Brody and Craighead26 performed electron microscopy of the atypical pulmonary macrophages isolated from human smokers. The needle-shaped inclusions, as previously detected by light microscopy, were shown to be

Kaolinosis, a Predominantly Nodular and Fibrotic Pneumoconiosis

Kaolin is mined for commercial use in the preparation of glossy paper, ceramics, adhesives, rubber products, and plastics.73 Mining in the United States is located along a “fall line” that separates the Piedmont plateau and the coastal planes from Georgia to South Carolina.87 Kaolinosis is an occupational lung disease associated with mining and processing of kaolin and kaolinite. Clay obtained during mining is dehydrated by vacuum filtration, air-dried, and purified into kaolin. The respirable

Conclusion

Respiratory bronchiolitis is associated with early emphysema and is perhaps the most common pathologic lesion of human lung. It is a lesion that appears to be reversible on smoking cessation.23245299 We suggest that kaolinite is the inorganic dust component of cigarette smoke that is responsible for the cellular and cytokine responses necessary for the development of a chronic respiratory bronchiolitis. In the proper detrimental genetic and environmental context, a natural progression from

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