Occupational lung disease pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hadeel Maksoud M.D.[2]
Overview
Occupational lung diseases include the pneumoconioses (interstitial lung diseases), hypersensitivity pneumonitis, bronchiolitis, byssinosis, and occupational asthma. 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 lead to fibrosis. Hypersensitivity pneumonitis or extrinsic allergic alveolitis and its subcategories of, bronchiolitis, byssinosis, and occupational asthma are all part of the respiratory systems’ over reactivity towards inhalants.
Pathophysiology
Pathogenesis of pneumoconioses
- The pathogenesis of pneumoconiosis starts with the inhalation of mineral, metallic, or dust particles.[1][2][3][4]
- The most common particles that cause pneumoconiosis are:
- Asbestos
- Silica (quartz, cristobalite, coesite, or tridymite silica polymorphs)
- Structural differences between the polymorphs of silica, are important because of the different degrees of biological reactivity they present, making some of them more toxic than others. The biological reactivity makes quartz more toxic, followed by tridymite, cristobalite, coesite, and finally stishovite.
- Coal
- Other dust particles may also lead to pneumoconiosis, such as hydrated magnesium silicate, hydrous aluminum silicate, bauxite, cobalt, beryllium, and iron.
- When particles reach the distal lung, the mucocilliary and lymphatic system take care of their elimination.
- Dust fibers must be less than 3 μm in diameter in order to penetrate the distal lung.
- Fibers greater than 5 μm are phagocytosed incompletely and retained in tissues.
- When particles increase in number, macrophages are activated to engulf those particles.
- Reticulin is then secreted by fibroblasts to entrap macrophages, as an attempt to control the excess of dust particles.
- The physiology of macrophage activation is subject to several theories:
- The macrophages are mainly derived from peripheral blood monocytes and, from local replication.
- The recruitment of monocytes from peripheral blood occurs in response to several chemotactic factors suggest that one of the most potent chemotactic factors for peripheral blood monocytes is monocyte chemoattractant protein - 1 (MCP - 1), suggesting its role in chronic macrophage inflammation.
- TNFα activates MCP - 1 expression. MCP - 1 is a 76 amino acid peptide that activates monocytes, also increases its cytostatic activity, and the expression of monocyte adhesion molecules such as CD11c/CD18 and CD11b/CD18.
- As exposure continues, the elimination system begins to fail, leading to release of reactive oxygen species. These in turn exacerbate the inflammatory response, with the release of more cytokines, such as TNF and interleukins, which subsequently lead to fibrogenesis.
- In asbestosis, the macrophages cannot eliminate the fibers, and cause needle-like formations containing iron to coalesce, these bodies are known as asteroid bodies.
- In coal worker’s pneumoconiosis, coal dust trapped within the coalesced macrophages give a coal macule seen on x-ray.
- The determinants for the rate of disease progression are the accumulative dose; that is based on duration and intensity of exposure, the fiber type and individual susceptibility.
- The underlying pathogenic mechanisms that lead to pulmonary fibrosis in pneumoconiosis suggest a potential protective effect of TGF- β on the development of pulmonary fibrosis.
- The alveolar macrophages in coal miners with massive fibrosis, secretes two main profibrotic factors; platelet-derived growth factor (PDGF) and insulin-like growth factor 1 (IGF - 1), whereas, the patients with simple pneumoconiosis secretes transforming growth factor - β (TGF - β). This reinforces that TGF- β has a possible protective effect against the development of pulmonary fibrosis.
Pathogenesis of hypersensitivity pneumonitis
- Hypersensitivity is thought to develop via a two-hit hypothesis.[1][5]
- Those with a genetic predisposition (no specific genes have been consistently associated) or a heavier than normal exposure will become sensitized.
- The second hit occurs with exposure to an antigen resulting in the manifestation of disease or its progression.
- Acute hypersensitivity is thought to be a type III hypersensitivity reaction.
- Subacute and chronic hypersensitivity reactions are type IV hypersensitivity reactions.
- CD4+ Th1 and Th17 cells are presented with antigens by dendritic cells and alveolar macrophages.
- In response, an inflammatory cascade is triggered with the release of IFN ‒ γ, TNF, IL ‒ 17, and IL - 22.
- The continuous presence of a numerous cytokines and chemokines causes mononuclear cells, macrophages, and fibroblasts to continually infiltrate the lung tissue.
- Vast numbers of lymphocytes infiltrate the lung tissue intent on causing apoptosis, IL - 17 inhibits the lymphocytes from doing so.
- As a result, this leads to the development of non-caseating granulomas and inflammation of the small airways, which is known as bronchiolitis.
- In the chronic pattern of disease, a cytokine pattern lead primarily by CD4+ Th2 takes place, which is associated with the development of fibrosis in the lung.
- Hallmarks for hypersensitivity pneumonitis include, cholesterol clefts, centrilobular fibrosis, peribronchiolar and bridging fibrosis.
Biological Reactivity of Different Dust Particles
- Each dust particle has a different degree of biological reactivity.[3][4]
- This variability is due to properties in the surface of the particles.
- In the case of silica, there are two theories explaining their biological reactivity:
- One theory states that silica is a hydrogen donor, whereas biological macromolecules are hydrogen acceptors, creating strong hydrogen bonds that contribute to the damage.
- The second theory states that at a pH of 7.0, silica is negatively charged, and therefore attracts alveolar macrophages, and activates the generation of reactive oxygen species and cytokines.
Shown below is a table summarizing the dust exposure associated with pneumoconiosis:
| Disease | Dust |
|---|---|
| Coal workers’ pneumoconiosis | Coal dust |
| Silicosis | Silica |
| Asbestosis | Asbestos |
| Talcosis | Hydrated magnesium silicate |
| Kaolin - induced pneumoconiosis | Hydrous aluminum silicate |
| Mixed dust pneumoconiosis | Coal dust, smoke from fires, and silicates |
| Aluminum - induced pneumoconiosis | Bauxite (Al2O3) |
| Berylliosis | Beryllium |
| Silicosiderosis | Silica and iron |
| Hard - metal disease (giant cell pneumonitis) | Cobalt |
Associated Conditions
Conditions associated with occupational lung disease include:[1]
- Asthma
- Chronic bronchitis
- Emphysema
- Allergic rhinitis
- Idiopathic pulmonary fibrosis
- Hives
- Eczema
- Mesothelioma
- Non-small cell lung cancer
- Tuberculosis
- Pleural effusion
- Pleural plaques and fibrosis
- Pulmonary edema
Caplan syndrome
- Caplan syndrome is a rare complication of coal worker's pneumoconiosis that occurs simultaneously with rheumatoid arthritis.[6]
- In this syndrome, the joint manifestations of rheumatoid arthritis present with bilateral, peripheral lung nodules.
- These nodules are unique from other pneumoconiotic nodules in that they develop rapidly over a period of weeks and may form cavities or become calcified.
Gross Pathology
- On gross pathology, dilated airways, destruction and distortion of lung tissue, and discoloration of lung tissue are characteristic findings of occupational lung disease.[7]
Microscopic Pathology
- On microscopic histopathological analysis, calcification, central necrosis, dense collagen, and sometimes malignant cells are characteristic findings of occupational lung disease.[8]
References
- ↑ 1.0 1.1 1.2 Castranova V, Vallyathan V (2000). "Silicosis and coal workers' pneumoconiosis". Environ Health Perspect. 108 Suppl 4: 675–84. PMC 1637684. PMID 10931786.
- ↑ name="pmid9072984">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.
- ↑ 3.0 3.1 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.
- ↑ 4.0 4.1 McLoud TC (1991). "Occupational lung disease". Radiol. Clin. North Am. 29 (5): 931–41. PMID 1871262.
- ↑ name="pmid9072984">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.
- ↑ name="pmid9072984">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.
- ↑ name="pmid9072984">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.
- ↑ name="pmid9072984">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.