Pneumoconiosis pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Karol Gema Hernández, M.D. [2]
Overview
Pneumoconiosis is an interstitial lung disease caused by the accumulation of different dust particles in the alveolar space. As the particles accumulate, the body's elimination mechanisms begin to fail, resulting in activation of chemotactic factors that exacerbate the inflammatory response, and subsequently leading to fibrosis.
Pathophysiology
The pathogenesis of pneumoconiosis starts with the inhalation of mineral, metallic or dust particles. The most common particles that cause pneumoconiosis are:
- Silica (quartz, cristobalite, or tridymite silica polymorphs)
Other dust particles may also lead to pneumoconiosis, such as hydrated magnesium silicate, hydrous aluminium silicate, bauxite, cobalt, beryllium and iron.
Shown below is a table summarizing the dust exposure associated with pneumocociosis.
| Disease | Dust |
|---|---|
| Asbestosis | Asbestos |
| Silicosis | Silica |
| Coal workers’ pneumoconiosis | Coal dust |
| Talcosis | Hydrated aluminium silicate |
| Mixed dust pneumoconiosis | Coal dust, smoke from fires, and silicates |
| Kaolin- induced pneumoconiosis | Hydrous aluminum silicate |
| Aluminum- induced pneumoconiosis | Bauxite (Al2O3) |
| Hard- metal disease (giant cell pneumonitis) | Cobalt |
| Berylliosis | Beryllium |
| Silicosiderosis | Silica and iron |
In a normal scenario, when the alveolar and interstitial macrophages in the bronquioles engulf the particles, they are eliminated aided by the mucocilliary system, expelled by mucus or through the lymphatic system. When particles increase in number and exposure continues, the elimination mechanism fails and macrophages begin to accumulate and therefore trigger an immune response. The macrophages, especially in perivascular and peribronquiolar regions, are then entrapped by reticulin, which is secreted by fibroblasts. If the macrophages lyse, more reticulin is released, and the response is augmented. As the accumulation increases the alveolar walls either protrude into alveolar spaces or obliterate them. The fibrogenic potential of dust also causes collagen fibers to develop.
The determinants for the rate of disease progression are the accumulative dose; that is based in duration and intensity of exposure, the fiber type and individual susceptibility. Particles reach the terminal bronquioles and start a cellular reaction, which leads to a chronic inflammatory response based on oxidative injury and profibrotic growth factors and cytokines.
Asbestos fibers need to be greater to 3 μm in diameter in order to penetrate the distal lung. Fibers greater than 5 μm are phagocytosed incompletely and retained in tissues who, initiate cellular reaction resulting in fibrogenesis.
The physiology of macrophage activation is subject to several theories. The macrophages are mainly derived by peripheral blood monocytes and, from local replication. The recruitment of monocytes from peripheral blood occurs in response to several chemotactic factors. Boitelle et al [1] suggested that one of the most potent chemotactic factor for peripheral blood monocytes is monocyte chemoattractant protein- 1 (MCP- 1), suggesting its role in chronic macrophagic infammation. MCP- 1 is a 76 amino acid peptide that results from activation by mediators such as TNF- α. MCP- 1 activates monocytes, and also increases their cytostatic activity, their release of lysosomal enzymes and cytokines (IL1, IL6), and monocyte expression of adhesion molecules (CD11c/CD18, CD11b/CD18).
Some studies in bronchoalveolar lavage made by Vanhée et al [2] showed a large influx of mononuclear phagocytes, with the subsecuent production of neutrophil chemotactic factors, fibronectin, and IL6 and TNF α. The alveolar macrophages in coal miners with massive fibrosis, secreted two main profibrotic factors; platelet-derived growth factor (PDGF) and insulin-like growth factor- 1 (IGF-1), whereas, the patients with simple pneumoconiosis secreted transforming- growth factor- β (TGF- β). This suggested a potential protective effect of TGF- β on the development of pulmonary fibrosis.
The risk for pneumoconiosis among constructions workers is evident, but Tjoe et al concluded there is not a clear-cut relationship between exposure and body’s response. This is hard due to the heterogeneity in exposure levels, as well as dust composition and the possible modification of toxicity by other factors present in dust.
References
- ↑ Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B; et al. (1997). "MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis". Eur Respir J. 10 (3): 557–62. PMID 9072984.
- ↑ Vanhée D, Gosset P, Boitelle A, Wallaert B, Tonnel AB (1995). "Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis". Eur Respir J. 8 (5): 834–42. PMID 7656959.