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==Overview==
==Overview==
== Pathogenesis ==
[[Occupational lung disease|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 [[Hypersensitivity pneumonitis|extrinsic allergic alveolitis]] and its subcategories of,  [[bronchiolitis]], [[byssinosis]], and [[occupational asthma]] are all part of the respiratory systems’ over reactivity towards inhalants.  
Coal dust that enters the lungs can neither be destroyed nor removed by the body. The particles are engulfed by resident alveolar or interstitial [[macrophage]]s and remain in the lungs, residing in the connective tissue or pulmonary [[lymph node]]s. Aggregations of carbon-laden macrophages can be visualized under a microscope as granular, black areas. In serious cases, the lung may grossly appear black. These aggregations can cause inflammation and fibrosis, as well as the formation of nodular legions within the lungs. The centres of dense legions may become necrotic due to [[ischaemia]], leading to large cavities within the lung.


== Appearance ==
==Pathophysiology==
Simple CWP is marked by the presence of 1-2mm nodular aggregations of anthracotic macrophages, supported by a fine collagen network,  within the lungs. Those 1-2mm in diameter are known as ''coal macules'', with larger aggregations known as ''coal nodules''. These structures occur most frequently around the initial site of coal dust accumulation - the upper regions of the lungs around [[respiratory bronchiole]]s<ref name="robspath">{{cite book | title=Robbins Pathologic Basis of Disease| last=Cotran| coauthors=Kumar, Collins| publisher=W.B Saunders Company| location=Philadelphia| id=0-7216-7335-X}}</ref>.


Continued exposure to coal dust following the development of simple CWP may result in its progression to complicated CWP, which generally requires a number of years to develop. Large, black, fibrotic scars 2-10cm in diameter are present, with accompanying decreased lung function. The lung itself appears blackened. A minority of these cases progresses to [[progressive massive fibrosis]] (PMF), the most serious form of CWP.
===Pathogenesis of pneumoconioses===
* The pathogenesis of [[pneumoconiosis]] starts with the inhalation of [[mineral]], [[Metal|metallic]], or [[dust]] particles.<ref name="pmid10931786">{{cite journal| author=Castranova V, Vallyathan V| title=Silicosis and coal workers' pneumoconiosis. | journal=Environ Health Perspect | year= 2000 | volume= 108 Suppl 4 | issue=  | pages= 675-84 | pmid=10931786 | doi= | pmc=PMC1637684 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10931786  }} </ref><ref>name="pmid9072984">{{cite journal| author=Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B et al.| title=MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis. | journal=Eur Respir J | year= 1997 | volume= 10 | issue= 3 | pages= 557-62 | pmid=9072984 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9072984  }} </ref><ref name="pmid7656959">{{cite journal| author=Vanhée D, Gosset P, Boitelle A, Wallaert B, Tonnel AB| title=Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. | journal=Eur Respir J | year= 1995 | volume= 8 | issue= 5 | pages= 834-42 | pmid=7656959 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7656959  }} </ref><ref name="pmid1871262">{{cite journal |vauthors=McLoud TC |title=Occupational lung disease |journal=Radiol. Clin. North Am. |volume=29 |issue=5 |pages=931–41 |year=1991 |pmid=1871262 |doi= |url=}}</ref>


* 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, [[Macrophage|macrophages]] are activated to engulf those particles.
* [[Reticulin]] is then secreted by [[Fibroblast|fibroblasts]] to entrap [[Macrophage|macrophages]], as an attempt to control the excess of dust particles.
* The physiology of [[macrophage]] activation is subject to several theories:
** The [[Macrophage|macrophages]] are mainly derived from peripheral blood [[Monocyte|monocytes]] and, from local replication.
** The recruitment of [[Monocyte|monocytes]] from peripheral blood occurs in response to several chemotactic factors suggest that one of the most potent chemotactic factors for peripheral blood [[Monocyte|monocytes]] is monocyte chemoattractant protein - 1 (MCP - 1), suggesting its role in chronic macrophage inflammation.
** [[Tumor necrosis factor-alpha|TNFα]] activates MCP - 1 expression. MCP - 1 is a 76 amino acid peptide that activates [[Monocyte|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 [[Cytokine|cytokines]], such as [[Tumor necrosis factors|TNF]] and [[Interleukin|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 [[Macrophage|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 beta|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|IGF - 1]]), whereas, the patients with simple [[pneumoconiosis]] secretes [[TGF beta|transforming growth factor - β]] (TGF - β). This reinforces that [[TGF beta|TGF- β]] has a possible protective effect against the development of [[pulmonary fibrosis]].


Anthracosis is the asymptomatic accumulation of carbon without a consequent cellular reaction. Such accumulation can be found in varying degrees among most urban dwellers and in tobacco smokers. Inhaled coal dust becomes a problem when the body's natural mechanisms for defending against and processing the dust becomes overwhelmed and, subsequently, overreactive.
=== Pathogenesis of hypersensitivity pneumonitis ===
* [[Hypersensitivity]] is thought to develop via a two-hit hypothesis.<ref name="pmid10931786">{{cite journal| author=Castranova V, Vallyathan V| title=Silicosis and coal workers' pneumoconiosis. | journal=Environ Health Perspect | year= 2000 | volume= 108 Suppl 4 | issue=  | pages= 675-84 | pmid=10931786 | doi= | pmc=PMC1637684 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10931786  }} </ref><ref>name="pmid9072984">{{cite journal| author=Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B et al.| title=MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis. | journal=Eur Respir J | year= 1997 | volume= 10 | issue= 3 | pages= 557-62 | pmid=9072984 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9072984  }} </ref>
* 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.
** Individuals without an ability to suppress the expression of [[Th1]] and [[Th2]] cells via T regulatory cells are susceptible to a second hit.
* [[Acute hypersensitivity]] is thought to be a [[type III hypersensitivity]] reaction.
* Subacute and chronic hypersensitivity reactions are [[type IV hypersensitivity]] reactions.
** CD4<sup>+</sup> Th1 and Th17 cells are presented with antigens by [[Dendritic cell|dendritic cells]] and alveolar [[Macrophage|macrophages]].
** In response, an inflammatory cascade is triggered with the release of [[Interferon|IFN ‒ γ]], [[Tumor necrosis factors|TNF]], [[IL17A|IL ‒ 17]], and IL - 22.
** The continuous presence of a numerous [[cytokines]] and [[chemokines]] causes [[Monocyte|mononuclear cells]], [[Macrophage|macrophages]], and [[Fibroblast|fibroblasts]] to continually infiltrate the [[lung]] tissue.
** Vast numbers of [[Lymphocyte|lymphocytes]] infiltrate the lung tissue intent on causing [[apoptosis]], IL - 17 inhibits the [[Lymphocyte|lymphocytes]] from doing so.
** As a result, this leads to the development of non-caseating [[Granuloma|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]].


Inhaled coal dust reaches the terminal bronchioles, and the carbon is engulfed by alveolar and interstitial macrophages. Phagocytosed coal particles are transported by macrophages up the mucociliary elevator and are expelled in the mucus or through the lymphatic system.
===Biological Reactivity of Different Dust Particles===
* Each dust particle has a different degree of biological reactivity.<ref name="pmid7656959">{{cite journal| author=Vanhée D, Gosset P, Boitelle A, Wallaert B, Tonnel AB| title=Cytokines and cytokine network in silicosis and coal workers' pneumoconiosis. | journal=Eur Respir J | year= 1995 | volume= 8 | issue= 5 | pages= 834-42 | pmid=7656959 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7656959  }} </ref><ref name="pmid1871262">{{cite journal |vauthors=McLoud TC |title=Occupational lung disease |journal=Radiol. Clin. North Am. |volume=29 |issue=5 |pages=931–41 |year=1991 |pmid=1871262 |doi= |url=}}</ref>
* 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 bond|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 [[Macrophage|macrophages]], and activates the generation of [[reactive oxygen species]] and [[Cytokine|cytokines]].
''Shown below is a table summarizing the dust exposure associated with pneumoconiosis:''
{| class="wikitable"
! style="background:#4479BA; color: #FFFFFF;" align="center" |Disease
! style="background:#4479BA; color: #FFFFFF;" align="center" |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]]
|}


When this system becomes overwhelmed, the dust-laden macrophages accumulate in the alveoli and may trigger an immune response. (The lungs must be exposed for a significant amount of time to dust particles 2-5 µm in diameter in order for the dust to be retained in the alveoli.) Fibroblasts involved in this response secrete reticulin, which entraps the macrophages. If the macrophages lyse, the fibroblastic response is augmented and more reticulin is laid down in the area.
==Associated Conditions==
Conditions associated with occupational lung disease include:<ref name="pmid10931786">{{cite journal| author=Castranova V, Vallyathan V| title=Silicosis and coal workers' pneumoconiosis. | journal=Environ Health Perspect | year= 2000 | volume= 108 Suppl 4 | issue=  | pages= 675-84 | pmid=10931786 | doi= | pmc=PMC1637684 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10931786  }} </ref>
* [[Asthma]]
* [[Chronic bronchitis]]
* [[Emphysema]]
* [[Allergic rhinitis]]
* [[Idiopathic pulmonary fibrosis]]
* [[Hives]]
* [[Eczema]]
* [[Mesothelioma]]
* [[Non small cell lung cancer|Non-small cell lung cancer]]
* [[Tuberculosis]]
* [[Pleural effusion]]
* Pleural plaques and [[fibrosis]]
* [[Pulmonary edema]]


Coal that contains silica lyses macrophages faster and stimulates the fibroblasts to add more collagen to the network. The lymphatic tree is contained in the pulmonary interstitium, along with arterial and venous vessels. If these macrophages have partially migrated up the lymphatic vessels, arterioles can become strangulated from the resultant interstitial fibrosis. As more and more dying macrophages, fibroblasts, reticulin, and collagen are deposited along the vascular tree, the vessels become compromised, and ischemic necrosis ensues.
===Caplan syndrome===
*[[Caplan syndrome]] is a rare complication of coal worker's pneumoconiosis that occurs simultaneously with [[rheumatoid arthritis]].<ref>name="pmid9072984">{{cite journal| author=Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B et al.| title=MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis. | journal=Eur Respir J | year= 1997 | volume= 10 | issue= 3 | pages= 557-62 | pmid=9072984 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9072984  }} </ref>


Areas of focal deposition of coal dust and pigment-laden macrophages are known as coal macules and are the histologic hallmark of coal worker’s pneumoconiosis. As these macules extend, they join other macules in the vicinity, forming discrete areas of interstitial fibrosis. This growing collagen network causes distention of the respiratory bronchioles, forming focal areas of emphysema. Widespread areas of focal emphysema can accrue without significant respiratory impairment.
*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.


A study of autopsied coal miners and non-miners conducted by Kuempel et al showed that inhalation of respirable coal dust is a highly significant predictor of emphysema severity beyond other contributory factors, including cigarette smoking, race, and age at death. [3, 4]
==Gross Pathology==
*On gross pathology, dilated airways, destruction and distortion of [[lung]] tissue, and discoloration of [[Lung (Zang)|lung]] tissue are characteristic findings of occupational lung disease.<ref>name="pmid9072984">{{cite journal| author=Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B et al.| title=MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis. | journal=Eur Respir J | year= 1997 | volume= 10 | issue= 3 | pages= 557-62 | pmid=9072984 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9072984  }} </ref>


Depending on factors that are still not fully understood, the macules may arrest or may continue to enlarge and form nodules that produce progressive massive fibrosis when they coalesce. This process can be exacerbated by tuberculosis or rheumatoid factor, which accelerates the rate of progression of focal ischemic necrosis and fibrosis.
[[Image:cwp.jpg|thumb|center|500px|Source:wikimediacommons, shows coal worker's pneumoconiosis complicated by progressive massive fibrosis by Yale Rosen from USA - Coal worker's pneumoconiosis - AnthracosilicosisUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31127927]]


Progressive massive fibrosis in association with rheumatoid arthritis is known as Caplan syndrome. Caplan first described this condition in 1953. He noticed that miners with rheumatoid arthritis had changes on chest radiographs similar to those of progressive massive fibrosis, although the distribution in the lungs was different. Unlike lesions caused by progressive massive fibrosis, which congregate in the upper lobes, these new lesions (subsequently known as Caplan lesions) tend to coalesce in the peripheral lung fields.
==Microscopic Pathology==
 
*On microscopic histopathological analysis, [[calcification]], central necrosis, dense [[collagen]], and sometimes malignant cells are characteristic findings of occupational lung disease.<ref>name="pmid9072984">{{cite journal| author=Boitelle A, Gosset P, Copin MC, Vanhee D, Marquette CH, Wallaert B et al.| title=MCP-1 secretion in lung from nonsmoking patients with coal worker's pneumoconiosis. | journal=Eur Respir J | year= 1997 | volume= 10 | issue= 3 | pages= 557-62 | pmid=9072984 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9072984  }} </ref>
Pathologically, the nodule exhibits a central area of coal dust and necrotic collagenous tissue lying in concentric rings. Surrounding these rings is an area of neutrophils with palisading fibroblasts. Caplan nodules tend to progress faster than lesions associated with progressive massive fibrosis and may precede the onset of rheumatoid lesions. Sixty-two percent of miners with peripheral nodules have positive serology findings for rheumatoid factor. [5]
 
Research is currently underway to further understand the inciting factors in the inflammatory process. Boitelle et al [6] have suggested that chemokines released to attract alveolar macrophages may be a plausible target for further pharmaceutical intervention to arrest the inflammatory process, which leads to destruction and fibrosis. Levels of monocyte chemoattractant protein-1 have been found to be increased in bronchoalveolar lavage specimens taken from patients with simple coal worker’s pneumoconiosis or progressive massive fibrosis compared with controls. This chemokine, which attracts and activates monocytes, is responsible for the domino effect of respiratory burst, further cell recruitment, and release of lysosomal enzymes. This chemokine may be a key factor in the chronic inflammation of the macrophage, which is central to the pathophysiology of coal worker’s pneumoconiosis. [6]
 
Other interesting areas that may become promising are the antioxidants selenium and glutathione peroxidase. Both substances have been found to be at lower concentrations in patients who have been exposed to coal-mine dust and tobacco smoke compared with control subjects. This suggests a consumptive process and a weakened defense against reactive oxygen species, which cause cellular damage and potentiate coal worker’s pneumoconiosis and progressive massive fibrosis. [7]
 
In a 2005 study by Huang et al, [8] a correlation has been found between bioavailable iron (BAI), pyrite concentration, and the regional progression of lung disease. BAI is iron that dissolves in 10 mmol/L phosphate solution at pH 4.5, which mimics the interior of lysosomes. Huang et al [8] found an increased prevalence of coal worker’s pneumoconiosis and progressive massive fibrosis at Pennsylvania mines, where BAI values are higher, compared with Utah mines, where BAI levels are lower. They also demonstrated that pyrite-containing coal contributed to the higher prevalence of progression to coal worker’s pneumoconiosis and progressive massive fibrosis in Pennsylvania. McCunney et al have suggested that iron, not quartz, is the active agent in coal responsible for coal worker’s pneumoconiosis. [9]
 
When mixed with water, pyrite produces hydrogen peroxide [10, 11] and hydroxyl radicals. [12, 13] These reactive agents have been shown to degrade yeast RNA, ribosomal RNA, and DNA. [11] Cohn et al [14] demonstrated that these pyrite-induced reactive oxygen species can be implicated as the cause of the cellular damage and chronic inflammation that lead to chronic disease in the lungs of coal miners. In order to proceed to RNA degradation, the concentration of sulfur (pyrite) in the coal necessary to produce hydrogen peroxide and hydroxyl radicals must exceed 1%. [14] These findings suggest that personnel at individual mines can measure the amount of sulfur in its coal and implement proper measures to ensure that miners in these high-risk areas either have improved protective gear or decreased long-term exposure to coals with increased BAI.
 
A case control study by Wang et al in China found that polymorphism in the E-selectin (an adhesion molecule participating in multiple inflammatory processes) gene (SELE) and smoking increased vulnerability to coal worker's pneumoconiosis. [15]


==References==
==References==
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{{Reflist|2}}
{{Reflist|2}}


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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 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

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:

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]

Caplan syndrome

  • 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]
Source:wikimediacommons, shows coal worker's pneumoconiosis complicated by progressive massive fibrosis by Yale Rosen from USA - Coal worker's pneumoconiosis - AnthracosilicosisUploaded by CFCF, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=31127927

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. ↑ 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.
  2. ↑ 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. ↑ 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. ↑ 4.0 4.1 McLoud TC (1991). "Occupational lung disease". Radiol. Clin. North Am. 29 (5): 931–41. PMID 1871262.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
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