Silicosis is a fibrotic lung disease (pneumoconiosis) caused by the inhalation of respirable crystalline silica dust, most commonly quartz. It is one of the oldest recognized occupational diseases, historically affecting miners, quarry and foundry workers, sandblasters, and stonemasons; a contemporary epidemic is driven by the fabrication of engineered ("artificial") stone benchtops, which have a very high crystalline-silica content. Inhaled silica particles that reach the alveoli are phagocytosed by alveolar macrophages, destabilize the phagolysosome, and activate the NLRP3 inflammasome, driving a self-perpetuating cycle of macrophage death, re-uptake of silica, chronic inflammation, and fibroblast activation. The characteristic lesion is the silicotic nodule — a whorled, hyalinized collagen nodule containing birefringent silica particles, with upper-lobe predominance. Disease presents along a spectrum: chronic simple silicosis (after 10-30 years of exposure), accelerated silicosis (5-10 years), and acute silicosis / silicoproteinosis (after intense exposure over months to a few years). Nodules can coalesce into progressive massive fibrosis. Silica exposure also raises the risk of tuberculosis (silicotuberculosis), lung cancer, chronic obstructive pulmonary disease, chronic kidney disease, and autoimmune disease. There is no curative therapy; management is supportive and prevention through dust control is paramount.
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name: Silicosis
creation_date: "2026-07-16T00:00:00Z"
category: Environmental Lung Disease
parents:
- Pneumoconiosis
- Occupational Lung Disease
disease_term:
preferred_term: silicosis
term:
id: MONDO:0005960
label: silicosis
description: >-
Silicosis is a fibrotic lung disease (pneumoconiosis) caused by the inhalation
of respirable crystalline silica dust, most commonly quartz. It is one of the
oldest recognized occupational diseases, historically affecting miners,
quarry and foundry workers, sandblasters, and stonemasons; a contemporary
epidemic is driven by the fabrication of engineered ("artificial") stone
benchtops, which have a very high crystalline-silica content. Inhaled silica
particles that reach the alveoli are phagocytosed by alveolar macrophages,
destabilize the phagolysosome, and activate the NLRP3 inflammasome, driving a
self-perpetuating cycle of macrophage death, re-uptake of silica, chronic
inflammation, and fibroblast activation. The characteristic lesion is the
silicotic nodule — a whorled, hyalinized collagen nodule containing birefringent
silica particles, with upper-lobe predominance. Disease presents along a
spectrum: chronic simple silicosis (after 10-30 years of exposure), accelerated
silicosis (5-10 years), and acute silicosis / silicoproteinosis (after intense
exposure over months to a few years). Nodules can coalesce into progressive
massive fibrosis. Silica exposure also raises the risk of tuberculosis
(silicotuberculosis), lung cancer, chronic obstructive pulmonary disease,
chronic kidney disease, and autoimmune disease. There is no curative therapy;
management is supportive and prevention through dust control is paramount.
classifications:
harrisons_chapter:
- classification_value: RESPIRATORY
ilo_disease_category:
- classification_value: pneumoconiosis_from_fibrogenic_mineral_dust
notes: >-
ILO List of Occupational Diseases (revised 2010), item 2.1.1
"Pneumoconioses caused by fibrogenic mineral dust (silicosis,
anthraco-silicosis, asbestosis)" — silicosis is named in the item text.
Silicosis is occupational by definition, so unlike asthma or COPD there is
no non-occupational form this assignment could over-claim.
- classification_value: silicotuberculosis
notes: >-
ILO item 2.1.2 "Silicotuberculosis", listed separately from 2.1.1. Applies
to the entry's silicotuberculosis presentation; silicosis markedly
increases tuberculosis risk, and the ILO list treats the combination as a
distinct recognised item.
eu_occupational_category:
- classification_value: silicosis
notes: >-
European schedule of occupational diseases (Commission Recommendation
2003/670/EC as amended), Annex I item 301.11 "Silicosis", under chapter 3
(diseases caused by inhalation). The European schedule is finer-grained
here than the ILO list, which folds silicosis and asbestosis into the
single item 2.1.1.
- classification_value: silicosis_combined_pulmonary_tuberculosis
notes: >-
Annex I item 301.12 "Silicosis combined with pulmonary tuberculosis",
the European counterpart of ILO item 2.1.2.
references:
- reference: PMID:22534002
title: "Silicosis."
has_subtypes:
- name: Chronic Silicosis
display_name: Chronic (Simple) Silicosis
description: >-
The classic and most common form, following prolonged relatively low-level
exposure and usually appearing 10–30 years after first exposure.
Characterized by small rounded upper-zone nodules (simple nodular
silicosis) that may coalesce into progressive massive fibrosis (complicated
silicosis / conglomerate masses). The three silicosis forms are separated by
exposure intensity and time from exposure to symptom onset.
evidence:
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "According to the intensity of exposures and onset of initiation of clinical symptoms silicosis is classified into three groups of acute, chronic and accelerated forms."
explanation: "Sources the three-way subtype division used here, and the two axes (exposure intensity and time to symptom onset) that separate the forms."
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Silicosis, caused by inhaling dust containing free crystalline silica, typically has a chronic course, with the numbers of silicosis patients declining globally."
explanation: "Confirms the chronic course as the typical form against which the accelerated and acute forms are the rarer exceptions."
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: OTHER
snippet: "Chronic simple silicosis (resulting from long-term exposure to relatively low concentrations of silica dust and also usually appearing 10-30 years after first exposure)"
explanation: Defines the standard chronic-silicosis exposure pattern and 10–30-year latency window.
- name: Accelerated Silicosis
description: >-
Follows higher-concentration exposure and conventionally develops 5–10 years
after first exposure. A histologically confirmed case after roughly two years
of very intense unprotected sandblasting illustrates an unusually fast extreme,
rather than defining the subtype. Accelerated disease has correspondingly rapid
radiographic and functional progression and a poor prognosis. Increasingly
reported in engineered-stone fabrication workers.
evidence:
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "According to the intensity of exposures and onset of initiation of clinical symptoms silicosis is classified into three groups of acute, chronic and accelerated forms."
explanation: "Sources the three-way subtype division used here, and the two axes (exposure intensity and time to symptom onset) that separate the forms."
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The condition resulted from ~2 years of very intense exposure without appropriate personal protective equipment while sandblasting."
explanation: "Histologically confirmed accelerated silicosis after only two years of very intense exposure, illustrating a fast extreme beyond the conventional 5–10-year window."
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: OTHER
snippet: "accelerated silicosis that develops 5–10 years after first exposure to higher concentrations of silica dust"
explanation: Defines accelerated silicosis by higher exposure intensity and the standard 5–10-year latency window.
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The case demonstrates a rare but largely preventable disease with serious health effects and a poor prognosis."
explanation: "Supports the rarity and poor prognosis of the accelerated form."
- name: Acute Silicosis
display_name: Acute Silicosis (Silicoproteinosis)
description: >-
The rarest form, developing a few weeks to five years after intense exposure
to fine silica. Characterized histologically by alveolar filling with
lipoproteinaceous material resembling pulmonary alveolar proteinosis
(silicoproteinosis), rapidly progressive dyspnea, and high mortality. Note
that the silicoproteinosis histology and mortality claims rest on the wider
clinical literature rather than on a source curated in this entry.
evidence:
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "According to the intensity of exposures and onset of initiation of clinical symptoms silicosis is classified into three groups of acute, chronic and accelerated forms."
explanation: "Sources the three-way subtype division used here, and the two axes (exposure intensity and time to symptom onset) that separate the forms."
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Much rarer are the acute and subacute forms."
explanation: "Supports the rarity of the acute form relative to chronic silicosis; does not itself document the silicoproteinosis histology."
- reference: PMID:25191413
reference_title: "Silicosis among Stone- Cutter Workers: A Cross-Sectional Study."
supports: SUPPORT
evidence_source: OTHER
snippet: "acute silicosis that develops a few weeks to five years after exposure to high concentrations of repairable silica dust"
explanation: Defines acute silicosis by high-intensity exposure and a latency of weeks to five years.
pathophysiology:
- name: Alveolar Macrophage Phagocytosis of Respirable Silica
description: >-
Respirable crystalline silica particles (aerodynamic diameter <10 microns)
deposit in the terminal bronchioles and alveoli, where they are recognized
and internalized by alveolar macrophages via scavenger receptors. This
uptake is the initiating event of silicosis.
role: trigger
locations:
- preferred_term: pulmonary alveolus
term:
id: UBERON:0002299
label: alveolus of lung
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: phagocytosis
term:
id: GO:0006909
label: phagocytosis
modifier: INCREASED
downstream:
- target: Phagolysosomal Membrane Rupture and Cathepsin B Release
- target: Reactive Oxygen Species Generation
evidence:
- reference: PMID:18604214
reference_title: "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
NALP3 activation required phagocytosis of crystals, and this uptake
subsequently led to lysosomal damage and rupture.
explanation: >-
Establishes phagocytic uptake of silica crystals as the required first
step that leads on to lysosomal damage.
- name: Phagolysosomal Membrane Rupture and Cathepsin B Release
description: >-
The reactive silanol-rich surface of internalized silica damages the
phagolysosomal membrane, causing lysosomal destabilization and rupture with
leakage of the protease cathepsin B into the cytosol.
role: driver
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
downstream:
- target: NLRP3 Inflammasome Assembly and Caspase-1 Activation
evidence:
- reference: PMID:18604214
reference_title: "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
inhibition of either phagosomal acidification or cathepsin B activity
impaired NALP3 activation.
explanation: >-
Implicates phagolysosomal acidification and released cathepsin B as the
link between lysosomal rupture and downstream inflammasome activation.
- name: Reactive Oxygen Species Generation
description: >-
Silica surface radicals and mitochondrial dysfunction in silica-laden
macrophages generate reactive oxygen species, which (together with potassium
efflux) provide a second signal for inflammasome activation.
role: driver
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: response to reactive oxygen species
term:
id: GO:0000302
label: response to reactive oxygen species
modifier: INCREASED
downstream:
- target: NLRP3 Inflammasome Assembly and Caspase-1 Activation
evidence:
- reference: PMID:18577586
reference_title: "The Nalp3 inflammasome is essential for the development of silicosis."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Activation of the Nalp3 inflammasome by silica required both an efflux of
intracellular potassium and the generation of reactive oxygen species.
explanation: >-
Demonstrates reactive oxygen species (with potassium efflux) as a required
signal for silica-induced NLRP3 inflammasome activation.
- name: NLRP3 Inflammasome Assembly and Caspase-1 Activation
description: >-
Lysosomal rupture/cathepsin B and reactive oxygen species converge to drive
assembly of the NLRP3-ASC-caspase-1 inflammasome in silica-laden macrophages,
activating caspase-1.
role: driver
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: NLRP3 inflammasome complex assembly
term:
id: GO:0044546
label: NLRP3 inflammasome complex assembly
modifier: INCREASED
downstream:
- target: IL-1beta and IL-18 Maturation and Secretion
- target: Macrophage Pyroptosis and Silica Re-uptake
evidence:
- reference: PMID:18604214
reference_title: "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
silica and aluminum salt crystals activated inflammasomes formed by the
cytoplasmic receptor NALP3.
explanation: >-
Confirms crystalline silica as a direct activator of the NALP3(NLRP3)
inflammasome.
- reference: PMID:18577586
reference_title: "The Nalp3 inflammasome is essential for the development of silicosis."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Stimulation of macrophages with silica results in the activation of
caspase-1 in a Nalp3-dependent manner.
explanation: >-
Demonstrates NLRP3(Nalp3)-dependent caspase-1 activation on silica
stimulation of macrophages.
- name: IL-1beta and IL-18 Maturation and Secretion
description: >-
Active caspase-1 cleaves pro-IL-1beta and pro-IL-18 into their mature forms,
which are secreted to drive the downstream inflammatory response.
role: driver
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: interleukin-1 beta production
term:
id: GO:0032611
label: interleukin-1 beta production
modifier: INCREASED
downstream:
- target: Neutrophilic Alveolitis and Inflammatory Amplification
evidence:
- reference: PMID:18577586
reference_title: "The Nalp3 inflammasome is essential for the development of silicosis."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Macrophages deficient in components of the Nalp3 inflammasome were
incapable of secreting the proinflammatory cytokines interleukin (IL)-1beta
and IL-18 in response to silica.
explanation: >-
Shows NLRP3(Nalp3)-inflammasome-dependent secretion of mature IL-1beta and
IL-18 in silica-exposed macrophages.
- name: Macrophage Pyroptosis and Silica Re-uptake
description: >-
Silica is cytotoxic to macrophages, triggering inflammatory cell death
(pyroptosis/apoptosis). Dying macrophages release their silica load, which is
re-engulfed by newly recruited macrophages — a self-perpetuating "frustrated
phagocytosis" cycle that sustains inflammation even after exposure ends.
role: driver
cell_types:
- preferred_term: alveolar macrophage
term:
id: CL:0000583
label: alveolar macrophage
biological_processes:
- preferred_term: pyroptotic inflammatory response
term:
id: GO:0070269
label: pyroptotic inflammatory response
modifier: INCREASED
- preferred_term: macrophage apoptotic process
term:
id: GO:0071888
label: macrophage apoptotic process
modifier: INCREASED
downstream:
- target: Alveolar Macrophage Phagocytosis of Respirable Silica
- target: Neutrophilic Alveolitis and Inflammatory Amplification
evidence:
- reference: PMID:18604214
reference_title: "Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
silica crystal uptake can initiate apoptotic cell death with concomitant
release of ingested silica particles, which are re-engulfed by other
alveolar macrophages inducing a cycle of sustained inflammation
explanation: >-
Directly supports the frustrated-phagocytosis cycle — silica-induced
macrophage death releases silica that is re-engulfed, perpetuating
inflammation.
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Impairment of lung function increases with disease progression, even after
the patient is no longer exposed.
explanation: >-
Indirect clinical correlate — disease progresses after exposure ends — but
does not itself demonstrate macrophage death or re-uptake. Evidence source
OTHER (review); marked PARTIAL.
- name: Neutrophilic Alveolitis and Inflammatory Amplification
description: >-
Secreted IL-1beta, IL-18, TNF-alpha, and chemokines recruit neutrophils and
monocytes into the alveolar space, amplifying a chronic inflammatory response
(alveolitis) that drives the transition to fibrosis.
role: driver
cell_types:
- preferred_term: neutrophil
term:
id: CL:0000775
label: neutrophil
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
- preferred_term: neutrophil chemotaxis
term:
id: GO:0030593
label: neutrophil chemotaxis
modifier: INCREASED
downstream:
- target: Fibroblast-to-Myofibroblast Activation
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Phagocytosis of crystalline silica in the lung causes lysosomal damage,
activating the NALP3 inflammasome and triggering the inflammatory cascade
with subsequent fibrosis.
explanation: >-
Places the inflammatory cascade between inflammasome activation and
fibrosis in the silicosis pathway. Evidence source OTHER (review).
- name: Fibroblast-to-Myofibroblast Activation
description: >-
Pro-fibrotic mediators (TGF-beta, PDGF, TNF-alpha) released by activated
macrophages recruit and activate lung fibroblasts, driving their
differentiation into collagen-secreting myofibroblasts — the central
effector step of silicotic fibrosis.
role: central_effector
conforms_to: "fibrotic_response#Mesenchymal Cell Activation"
locations:
- preferred_term: lung
term:
id: UBERON:0002048
label: lung
cell_types:
- preferred_term: fibroblast
term:
id: CL:0000057
label: fibroblast
- preferred_term: myofibroblast
term:
id: CL:0000186
label: myofibroblast cell
biological_processes:
- preferred_term: TGF-beta receptor signaling
term:
id: GO:0007179
label: transforming growth factor beta receptor signaling pathway
modifier: INCREASED
downstream:
- target: Excess Collagen Deposition and Silicotic Nodule Formation
evidence:
- reference: PMID:18577586
reference_title: "The Nalp3 inflammasome is essential for the development of silicosis."
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
the inflammatory response and subsequent development of pulmonary fibrosis
after inhalation of silica is dependent on the Nalp3 inflammasome.
explanation: >-
In vivo mouse evidence that the inflammasome-driven inflammatory response
is required for the pulmonary fibrosis produced by fibroblast activation.
Evidence source MODEL_ORGANISM (murine inhalation model).
- name: Excess Collagen Deposition and Silicotic Nodule Formation
description: >-
Activated myofibroblasts deposit excess type I and III collagen and other
extracellular matrix, producing the pathognomonic silicotic nodule — a
concentric, whorled, hyalinized collagen nodule containing birefringent
silica particles — that coalesces into progressive massive fibrosis.
role: effector
conforms_to: "fibrotic_response#Excessive ECM Deposition"
locations:
- preferred_term: lung
term:
id: UBERON:0002048
label: lung
cell_types:
- preferred_term: myofibroblast
term:
id: CL:0000186
label: myofibroblast cell
biological_processes:
- preferred_term: collagen biosynthetic process
term:
id: GO:0032964
label: collagen biosynthetic process
modifier: INCREASED
- preferred_term: extracellular matrix organization
term:
id: GO:0030198
label: extracellular matrix organization
modifier: INCREASED
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Phagocytosis of crystalline silica in the lung causes lysosomal damage,
activating the NALP3 inflammasome and triggering the inflammatory cascade
with subsequent fibrosis.
explanation: >-
Supports fibrosis (excess ECM/collagen deposition) as the terminal outcome
of the silicosis cascade. Evidence source OTHER (review).
environmental:
- name: Occupational Respirable Crystalline Silica Exposure
exposure_term:
preferred_term: exposure to respirable crystalline silica
term:
id: ECTO:7000030
label: exposure to silica dust
exposure_classifications:
hazard_agent_type:
- classification_value: CHEMICAL
notes: >-
Respirable crystalline silica is a mineral dust, classified as a
chemical agent in the occupational-hygiene scheme (ILO section 1.1 /
European schedule chapter 1), not as a physical agent.
exposure_route:
- classification_value: INHALATION
notes: >-
Only the respirable fraction reaching the alveoli is pathogenic; the
route is what defines the exposure, hence "respirable" in the name.
exposure_duration:
- classification_value: CHRONIC
notes: >-
ATSDR chronic duration (365 days and longer), matching classic chronic
silicosis after 10-30 years of exposure. Accelerated and acute silicosis
follow INTERMEDIATE-duration heavy exposure, as in engineered-stone
benchtop work.
- classification_value: INTERMEDIATE
notes: >-
ATSDR intermediate duration (15-364 days), the exposure pattern behind
acute silicosis/silicoproteinosis and the accelerated form driving the
contemporary engineered-stone epidemic.
iarc_carcinogen_group:
classification_value: GROUP_1
notes: >-
IARC classifies crystalline silica dust in the form of quartz or
cristobalite as Group 1, carcinogenic to humans (lung cancer). This is a
hazard identification about the agent; the lung-cancer risk it refers to
is a separate outcome from silicosis itself, though the two share the
exposure. Silicosis is not a cancer.
ghs_health_hazard_class:
- classification_value: STOT_REPEATED_EXPOSURE
notes: >-
Silicosis is the archetypal specific target organ toxicity from repeated
exposure — a non-lethal, organ-specific effect (lung) accumulating over
prolonged exposure rather than an acute toxic response.
exposome_domain:
- classification_value: SPECIFIC_EXTERNAL
notes: >-
An identifiable individual-level occupational agent, in Wild's specific
external domain rather than the general external environment.
notes: >-
Silicosis is caused by inhalation of respirable crystalline silica (quartz,
cristobalite, tridymite). Classic high-risk work includes hard-rock mining,
quarrying, tunneling, sandblasting, foundry work, ceramics, and stone
masonry. A contemporary epidemic of accelerated and acute silicosis is
driven by cutting and polishing engineered (artificial) stone benchtops,
which contain a much higher proportion of crystalline silica than natural
stone.
evidence:
- reference: PMID:39134395
reference_title: "Autoimmune diseases, autoantibody status and silicosis in a cohort of 1238 workers from the artificial stone benchtop industry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A modern epidemic of silicosis is emerging internationally, associated
with dry processing of engineered stone with high (>90%) RCS content.
explanation: >-
Documents the contemporary engineered/artificial-stone exposure driving a
resurgent silicosis epidemic, and the very high respirable crystalline
silica (RCS) content of the material.
influences_mechanisms:
- target: Alveolar Macrophage Phagocytosis of Respirable Silica
environmental_effect: TRIGGERS
causal_link_type: DIRECT
description: >-
Dust-generating work liberates crystalline silica in the respirable size
range, which is what reaches the terminal bronchioles and alveoli to be
internalized by alveolar macrophages.
evidence:
- reference: PMID:39134395
reference_title: "Autoimmune diseases, autoantibody status and silicosis in a cohort of 1238 workers from the artificial stone benchtop industry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A modern epidemic of silicosis is emerging internationally, associated
with dry processing of engineered stone with high (>90%) RCS content.
explanation: >-
Ties the occupational process to the respirable crystalline silica
content of the dust generated, the particulate species the alveolar
macrophage then phagocytoses.
genetic:
- name: TNF
gene_term:
preferred_term: TNF
term:
id: hgnc:11892
label: TNF
association: >-
Host susceptibility/severity modifier — TNF-alpha promoter polymorphisms
(notably -238A and -308A) are associated with predisposition to, and greater
severity of, silicosis among silica-exposed workers. These are common
regulatory variants that amplify the TNF-alpha-driven inflammatory response
to inhaled silica; they modify risk but are neither necessary nor sufficient
without exposure.
relationship_type: SUSCEPTIBILITY
variant_origin: GERMLINE
evidence:
- reference: PMID:11874815
reference_title: "Polymorphisms in the tumor necrosis factor-alpha gene promoter may predispose to severe silicosis in black South African miners."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Susceptibility to silicosis is in part genetically determined.
explanation: >-
Establishes a heritable host-susceptibility component layered on the
obligate silica exposure.
- reference: PMID:11874815
reference_title: "Polymorphisms in the tumor necrosis factor-alpha gene promoter may predispose to severe silicosis in black South African miners."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
miners with severe silicosis were significantly more likely than controls
to have -238A
explanation: >-
Case-control association of the TNF-alpha -238A promoter allele with severe
silicosis in exposed miners.
notes: >-
Additional candidate susceptibility/modifier loci reported in the literature
include IL1RN (IL-1 receptor antagonist), IL1B, IL6, and the
glutathione-S-transferase detoxification genes (GSTM1/GSTT1/GSTP1); effects
are modest and population-dependent. No genome-wide-significant common causal
locus is established, consistent with silicosis being an environmentally
caused disease with polygenic susceptibility modification.
phenotypes:
- category: Respiratory
name: Dyspnea
description: >-
Progressive exertional breathlessness is the cardinal symptom, reflecting
restrictive and/or obstructive impairment from fibrosis.
phenotype_term:
preferred_term: Dyspnea
term:
id: HP:0002094
label: Dyspnea
clinical_course: PROGRESSIVE
evidence:
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The patient's initial symptoms were progressive cough, dyspnoea and weight loss."
explanation: "Histologically confirmed silicosis presenting with progressive cough and dyspnoea as the initial symptoms."
- category: Respiratory
name: Cough
description: Chronic cough, often with sputum production.
phenotype_term:
preferred_term: Cough
term:
id: HP:0012735
label: Cough
temporality: CHRONIC
evidence:
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The patient's initial symptoms were progressive cough, dyspnoea and weight loss."
explanation: "Histologically confirmed silicosis presenting with progressive cough and dyspnoea as the initial symptoms."
- category: Respiratory
name: Pulmonary Fibrosis
description: >-
Nodular interstitial fibrosis with upper-lobe predominance; coalescence
produces progressive massive fibrosis.
phenotype_term:
preferred_term: Pulmonary fibrosis
term:
id: HP:0002206
label: Pulmonary fibrosis
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Silicosis is a fibrotic lung disease caused by inhalation of free
crystalline silicon dioxide or silica.
explanation: >-
Establishes pulmonary fibrosis as the defining pathological phenotype of
silicosis. Evidence source OTHER as this is a review article.
- category: Respiratory
name: Restrictive Ventilatory Defect
description: Reduced lung volumes on pulmonary function testing as fibrosis advances.
phenotype_term:
preferred_term: Restrictive ventilatory defect
term:
id: HP:0002091
label: Restrictive ventilatory defect
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Impairment of lung function increases with disease progression, even after
the patient is no longer exposed.
explanation: >-
Supports progressive impairment of lung function (restrictive/obstructive
deterioration) as disease advances. Evidence source OTHER (review).
- category: Respiratory
name: Respiratory Insufficiency
description: End-stage disease progresses to respiratory failure and cor pulmonale.
phenotype_term:
preferred_term: Respiratory insufficiency
term:
id: HP:0002093
label: Respiratory insufficiency
clinical_course: PROGRESSIVE
- category: Immunological
name: Increased Susceptibility to Tuberculosis
description: >-
Silica impairs alveolar-macrophage killing of Mycobacterium tuberculosis,
markedly increasing the risk of active and latent tuberculosis
(silicotuberculosis).
phenotype_term:
preferred_term: Pulmonary tuberculosis
term:
id: HP:0032262
label: Pulmonary tuberculosis
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Mycobacterial diseases, airway obstruction, and lung cancer are associated
with silica dust exposure.
explanation: >-
Supports the established association of silica exposure with mycobacterial
(tuberculous) disease. Evidence source OTHER (review).
- reference: PMID:17439668
reference_title: "Silica, silicosis and tuberculosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
silicosis and silica dust-associated tuberculosis (TB), in particular, are
the two diseases that remain high on the list of occupational health
priorities in low-income countries
explanation: >-
A dedicated silica-TB review highlighting the strong link between silica
exposure/silicosis and tuberculosis. Evidence source OTHER (review).
- category: Neoplastic
name: Increased Lung Cancer Risk
description: >-
Crystalline silica is an IARC Group 1 human carcinogen; silica exposure and
silicosis increase the risk of lung cancer, with a synergistic effect from
cigarette smoking.
phenotype_term:
preferred_term: Neoplasm of the lung
term:
id: HP:0100526
label: Neoplasm of the lung
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Mycobacterial diseases, airway obstruction, and lung cancer are associated
with silica dust exposure.
explanation: >-
Supports the established association of silica dust exposure with lung
cancer. Evidence source OTHER (review).
- category: Respiratory
name: Airway Obstruction
description: >-
Silica exposure is associated with chronic airflow obstruction / COPD,
contributing to a mixed obstructive-restrictive pattern especially with
concurrent smoking.
phenotype_term:
preferred_term: Airway obstruction
term:
id: HP:0006536
label: Airway obstruction
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Mycobacterial diseases, airway obstruction, and lung cancer are associated
with silica dust exposure.
explanation: >-
Supports the association of silica dust exposure with airway obstruction.
Evidence source OTHER (review).
- category: Immunological
name: Autoantibody Positivity and Connective-Tissue Disease Association
description: >-
Silica is a potent immune adjuvant; exposed workers show elevated rates of
antinuclear and extractable-nuclear antibodies and increased risk of
connective-tissue/autoimmune disease (rheumatoid arthritis and Caplan
syndrome, systemic sclerosis, SLE, ANCA-associated vasculitis).
phenotype_term:
preferred_term: Antinuclear antibody positivity
term:
id: HP:0003493
label: Antinuclear antibody positivity
evidence:
- reference: PMID:39134395
reference_title: "Autoimmune diseases, autoantibody status and silicosis in a cohort of 1238 workers from the artificial stone benchtop industry."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The proportion of workers with detectable ANAs or ENAs was considerably
higher than the 5%-9% expected in the general population
explanation: >-
Cohort evidence that silica-exposed (artificial-stone) workers have
autoantibody (ANA/ENA) positivity above general-population baseline,
supporting the silica-autoimmunity association.
treatments:
- name: Silica Exposure Cessation and Dust Control
description: >-
Removal from further silica exposure and workplace dust-control measures are
the foundation of management and the only effective form of prevention.
treatment_term:
preferred_term: therapeutic avoidance of environmental exposure
term:
id: NCIT:C15900
label: Lifestyle Therapy
- name: Supportive Care
description: >-
Oxygen therapy, pulmonary rehabilitation, bronchodilators, vaccination, and
management of complications. No therapy reverses established fibrosis.
treatment_term:
preferred_term: supportive care
term:
id: NCIT:C15747
label: Supportive Care
evidence:
- reference: PMID:22534002
reference_title: "Silicosis."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
As yet, no curative treatment exists, but comprehensive management
strategies help to improve quality of life and slow deterioration.
explanation: >-
Establishes that management is supportive — no curative therapy exists.
Evidence source OTHER (review).
- name: Whole-Lung Lavage
description: >-
Considered in acute silicosis/silicoproteinosis to remove alveolar
lipoproteinaceous material and dust.
treatment_term:
preferred_term: therapeutic procedure
term:
id: NCIT:C49236
label: Therapeutic Procedure
- name: Lung Transplantation
description: Definitive option for end-stage silicosis with respiratory failure.
treatment_term:
preferred_term: organ transplantation
term:
id: NCIT:C15289
label: Organ Transplantation
evidence:
- reference: PMID:30053129
reference_title: "A case of accelerated silicosis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The patient was a candidate for lung transplantation."
explanation: "A single case report documents transplant candidacy in advanced silicosis; it does not provide transplantation outcomes."
- name: Pirfenidone (Investigational Antifibrotic)
description: >-
Pirfenidone, an oral antifibrotic approved for idiopathic pulmonary
fibrosis, is being investigated for silicosis on the rationale that
silicosis shares TGF-beta-driven fibrogenic mechanisms with IPF. It is
investigational and not yet standard-of-care for silicosis.
therapeutic_modality: SMALL_MOLECULE
target_mechanisms:
- target: Fibroblast-to-Myofibroblast Activation
treatment_effect: INHIBITS
description: >-
Pirfenidone attenuates TGF-beta-driven fibroblast-to-myofibroblast
activation and collagen deposition, targeting the fibrotic effector node.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: pirfenidone
term:
id: CHEBI:32016
label: pirfenidone
evidence:
- reference: clinicaltrials:NCT05118256
reference_title: "An Open, Randomised, Controlled and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
we decide to study the efficacy of pirfenidone in reducing metabolic,
inflammatory, and fibrogenic lung disease in patients with artificial
stone silicosis and progressive massive fibrosis (PMF).
explanation: >-
A clinical trial evaluating pirfenidone specifically in artificial-stone
silicosis with PMF, supporting its investigational antifibrotic use.
clinical_trials:
- name: NCT05118256
phase: PHASE_II
status: UNKNOWN
description: >-
Open, randomised, controlled single-center trial assessing pirfenidone for
reducing pulmonary metabolic, inflammatory, and fibrogenic activity in
patients with artificial-stone silicosis and progressive massive fibrosis.
target_phenotypes:
- preferred_term: Pulmonary fibrosis
term:
id: HP:0002206
label: Pulmonary fibrosis
evidence:
- reference: clinicaltrials:NCT05118256
reference_title: "An Open, Randomised, Controlled and Unicenter Clinical Trial to Assess the Efficiency of Pirfenidone for the Reduction of Pulmonary Metabolic, Inflammatory and Fibrogenic Activity in Patients With Silicosis Due to Artificial Stone and PMF"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
At the moment, there is no curative treatment for the disease, and the
only therapeutic option is lung transplantation
explanation: >-
The trial rationale confirms the absence of curative therapy and motivates
investigating antifibrotic pirfenidone in silicosis/PMF.
datasets:
- accession: geo:GSE264182
title: Iron-induced oxidative stress alters the transcriptome of bronchoalveolar lavage cells in silicosis
description: Elevated iron levels are observed in silicosis patients, leading alveolar macrophages to increase ferritin production in response to this cellular stress. Our study employed a multi-omic approach to investigate how excess iron/ferritin influences the molecular profile of bronchoalveolar lavage (BAL) cells. Thirty-one participants were included, with RNA sequencing conducted on BAL cells from stone benchtop industry workers diagnosed with simple or complicated silicosis, compared to a cohort with no disease. BAL fluid (BALF) was analysed using gas chromatography-mass spectrometry (GC-MS) to screen for 498 volatile organic compounds (VOCs).
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: BULK_RNA_SEQ
sample_count: 19
publication: PMID:39485079
notes: Identified by GEO DataSets index search for Silicosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE288887
title: Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis
description: The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: SINGLE_CELL_RNA_SEQ
sample_count: 10
publication: PMID:38985878
notes: Identified by GEO DataSets index search for Silicosis (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Overview. Silicosis is a chronic, irreversible, fibrotic interstitial lung disease (a pneumoconiosis) caused by the inhalation of respirable crystalline silica (RCS, silicon dioxide, SiO₂). Inhaled silica particles are phagocytosed by alveolar macrophages, triggering a self-perpetuating cycle of macrophage death, inflammation, and progressive collagen deposition that produces the pathognomonic silicotic nodule and, in advanced disease, progressive massive fibrosis (PMF). It is one of the oldest recognized occupational diseases and is entirely preventable but incurable.
Key identifiers: - MONDO: MONDO:0005960 - ICD-10-CM: J62 (Pneumoconiosis due to dust containing silica); J62.8 (other silica-containing dust); J62.0 (talc) - ICD-11: CA60.0 (Silicosis) - MeSH: D012829 (Silicosis) - OMIM: Not applicable — no single-gene Mendelian entry; silicosis is not a Mendelian disorder - Orphanet: Not a rare disease per Orphanet (common occupational disease) - SNOMED CT: 40122008 (Silicosis)
Synonyms / alternative names: Miner's phthisis, grinder's asthma/disease, potter's rot, stonemason's disease, "the dust disease," pneumosilicosis, silicotic fibrosis. Subtype-linked terms: acute silicosis (acute silicoproteinosis/silicolipoproteinosis), accelerated silicosis, chronic (simple and complicated) silicosis, conglomerate silicosis (= PMF).
Data derivation. Information is drawn overwhelmingly from aggregated disease-level resources (occupational-disease registries, surveillance programs such as Australia's Queensland screening program and US state case series, and clinical/pathology literature) rather than single-patient EHR records. The engineered-stone outbreak literature draws on clinical case series and lung-transplant/autopsy cohorts.
The sole necessary cause is inhalation of respirable crystalline silica — particles generally <5–10 µm aerodynamic diameter that reach the alveoli. Crystalline polymorphs, in order of typical toxicity relevance: - Quartz (most common) — CHEBI/chemical: silicon dioxide, SiO₂ - Cristobalite and tridymite — higher-temperature polymorphs, more fibrogenic; generated by heating/calcining quartz and abundant in engineered-stone processing - Freshly fractured silica (cutting, grinding, drilling) is more toxic than aged dust because fresh surfaces carry reactive silanol/radical groups.
Amorphous silica (e.g., diatomaceous earth in native form) is far less fibrogenic; calcination converts it to cristobalite, raising risk.
Genetic factors modulate who develops disease and how severely among the exposed; they are neither necessary nor sufficient: - TNF-α promoter polymorphisms (−308 G/A, −238 G/A): the −308A allele is associated with increased silicosis risk, especially in Asian populations; −238 promoter variants associated with severe silicosis in Black South African miners (PMID:11874815). Meta-analytic adjusted OR for −238 was reported very high (~20.9) in one cohort. - IL-1 receptor antagonist (IL-1RA / IL1RN) +2018 polymorphism: associated with susceptibility and severity (OR ~4.0). - Candidate-gene meta-analyses also implicate variants in IL-1β, IL-6, GSTM1/GSTT1/GSTP1 (glutathione-S-transferases), and HLA class II genes, with modest and population-dependent effects. No genome-wide-significant common causal locus is established.
Silicosis is a paradigm of gene–environment interaction: an obligate environmental exposure whose fibrotic outcome is modulated by host inflammatory-gene polymorphisms (TNF-α, IL-1RA, GST detoxification genes). The interaction is quantitative (risk/severity modulation) rather than qualitative — no host genotype confers disease without silica exposure.
Silicosis is often asymptomatic for years, especially in the simple chronic form. Phenotypes below are grouped by type with suggested HPO terms.
Respiratory symptoms/signs: - Dyspnea / exertional breathlessness — HP:0002094 (Dyspnea); the dominant symptom, progressive. Frequent, especially in complicated disease. - Chronic cough — HP:0031246 (Chronic cough) / HP:0012735 (Cough). Common, often productive. - Sputum production — HP:0033709 (Abnormal sputum) / HP:0031508. - Chest pain/tightness — HP:0100749 (Chest pain). - Wheezing — HP:0030828 (Wheezing). - Hemoptysis — HP:0002105 (Hemoptysis); should prompt evaluation for superimposed tuberculosis or PMF cavitation. - Cyanosis — HP:0000961 (Cyanosis); late/severe. - Bibasilar/diffuse crackles — HP:0030830 (Crackles); prominent in acute silicoproteinosis. - Digital clubbing — HP:0001217 (Clubbing); variable, less typical than in IPF.
Physical/systemic manifestations: - Fatigue — HP:0012378 (Fatigue). - Weight loss — HP:0001824 (Weight loss); acute/advanced disease. - Respiratory failure — HP:0002878 (Respiratory failure); end-stage. - Pulmonary hypertension / cor pulmonale — HP:0002092 (Pulmonary arterial hypertension); complication of advanced fibrosis. - Pneumothorax — HP:0002107 (Pneumothorax); complication.
Laboratory / imaging abnormalities: - Restrictive (± mixed obstructive) ventilatory defect — HP:0002091 (Restrictive ventilatory defect); reduced FVC, reduced DLCO on pulmonary function testing. - Pulmonary fibrosis — HP:0002206 (Pulmonary fibrosis). - Pulmonary nodules / reticulonodular opacities — HP:0031451 (Pulmonary nodule); upper/mid-lobe predominant small rounded opacities (ILO shapes q/r). - Hilar/mediastinal lymphadenopathy with "eggshell" calcification — HP:0100721 (Hilar lymphadenopathy); eggshell calcification is characteristic. - Elevated inflammatory/autoimmune serology — antinuclear antibodies, rheumatoid factor, ANCA may be positive (see Section 6/complications).
Phenotype characteristics by clinical form: | Form | Onset (latency) | Severity | Progression | Frequency | |---|---|---|---|---| | Chronic simple | 10–30+ y | Mild–moderate, often asymptomatic | Slow, may be stable | Most common historically | | Chronic complicated (PMF) | decades | Severe | Progressive (can progress after exposure ends) | ~subset of chronic | | Accelerated | 3–10 y | Moderate–severe | Rapid | Rising sharply (engineered stone) | | Acute (silicoproteinosis) | weeks–<5 y | Very severe | Rapid, often fatal | Rare, very high exposure |
Age of onset: adult; engineered-stone accelerated silicosis strikingly presents in the 3rd–5th decade. Progression: can continue after cessation of exposure, particularly complicated/PMF forms.
Quality-of-life impact. Advanced silicosis produces severe exertional limitation, oxygen dependence, inability to work (major socioeconomic impact given young affected workers), and psychological burden; PMF and lung-transplant candidacy indicate profound QoL reduction. No silicosis-specific validated instrument dominates; generic tools (SF-36, EQ-5D, St George's Respiratory Questionnaire) are used.
Not applicable as a Mendelian disorder. Silicosis has no causal gene, no pathogenic germline/somatic variant catalog, no ClinVar/HGMD pathogenic-variant set, and no chromosomal abnormality. It is not inherited.
What exists is susceptibility/modifier genetics (see Section 2): - Modifier/susceptibility genes: TNF (HGNC:11892; TNF-α −308/−238 promoter SNPs), IL1RN (IL-1 receptor antagonist, +2018), and candidate variants in IL1B, IL6, GSTM1/GSTT1/GSTP1, and HLA class II. Effects are small-to-moderate, population-specific, and function as risk/severity modifiers. - Variant classification: These are common-population regulatory polymorphisms, not ACMG "pathogenic" variants — the ACMG/AMP framework does not apply to a complex environmental trait. - Functional consequence: promoter variants alter cytokine expression levels (e.g., higher TNF-α transcription with −308A), amplifying the inflammatory/fibrotic response to silica.
Epigenetics: Silica exposure induces epigenetic reprogramming in lung cells and macrophages — DNA-methylation changes and dysregulated microRNAs are implicated in fibrogenesis (e.g., downregulation of miR-205-5p → ↑E2F1/SKP2 → impaired Beclin1-mediated autophagy; downregulation of miR-503 → ↑VEGFA/FGFR1 → ERK/MAPK activation). These are acquired, exposure-driven changes, not heritable disease mutations.
Silicosis pathogenesis is a well-characterized causal cascade centered on the alveolar macrophage and the NLRP3 inflammasome.
Phagocytosis, lysosomal membrane permeabilization, NLRP3 inflammasome activation, pyroptosis and apoptosis, ROS/oxidative stress, autophagy/mitophagy dysregulation, EMT, chronic inflammation, and fibrogenesis. ER stress in alveolar macrophages contributes to fibrogenesis (unfolded protein response).
Silica is a chronic immune adjuvant/immunotoxicant: it drives Th17/IL-17A responses, dysregulates regulatory T cells, and promotes autoantibody production, mechanistically linking silicosis to autoimmune disease (rheumatoid arthritis, systemic sclerosis, SLE, ANCA-associated vasculitis; Caplan syndrome = silicosis + seropositive RA with cavitating nodules). Silica-impaired macrophage function underlies the ~30-fold increased tuberculosis risk.
Transcriptomic and proteomic studies of silica-exposed lungs/macrophages show upregulation of inflammasome, TGF-β/SMAD, ECM, and EMT gene programs; single-cell and organotypic lung stem/progenitor models have demonstrated NLRP3-mediated epithelial injury and aberrant regeneration. RAGE (receptor for advanced glycation end-products) modulates the fibrotic response in murine silica models.
NLRP3/caspase-1/IL-1β axis, P2X7 receptor, TGF-β signaling, ROS (antioxidants: N-acetylcysteine), and autophagy restoration are active preclinical/clinical targets (Section 12).
1,000 engineered-stone silicosis cases identified worldwide since first reports ~2010 (Spain, Israel), then Australia and the US.
Diagnosis rests on the triad: (1) exposure history, (2) characteristic imaging, (3) exclusion of alternatives — biopsy is usually unnecessary.
Imaging (cornerstone): - Chest radiograph classified by the ILO International Classification of Radiographs of Pneumoconioses — small rounded opacities (profusion, shapes typically q/r), upper-zone predominance; large opacities (A/B/C) define complicated disease/PMF; "eggshell" calcification of hilar nodes. - HRCT (higher sensitivity/specificity than CXR): centrilobular and subpleural micronodules, upper/mid-lobe predominance, conglomerate masses (PMF, often with surrounding emphysema and calcification), lymphadenopathy. RadLex/DICOM-coded.
Functional tests: - Spirometry/full PFTs: restrictive, mixed, or (with smoking) obstructive pattern; reduced DLCO; reduced 6-minute walk distance / desaturation in advanced disease.
Laboratory / biomarkers: - No validated diagnostic serum biomarker in routine use; research candidates include serum SP-D, KL-6/MUC1, CC16, and inflammatory cytokines. - Autoimmune serologies (ANA, RF, ANCA) when overlap syndromes suspected. - Tuberculosis screening is mandatory (IGRA/tuberculin, sputum studies) given silicotuberculosis risk.
Histopathology (when biopsy performed): whorled, concentric hyalinized collagen silicotic nodules with birefringent particles under polarized light; acute form shows alveolar filling with PAS-positive lipoproteinaceous material (silicoproteinosis, resembling alveolar proteinosis). Mineralogical analysis (SEM-EDX) can confirm silica.
Genetic testing: Not applicable for diagnosis (no causal gene). WGS/WES/panels/karyotype/FISH/CMA have no diagnostic role. Genotyping for susceptibility SNPs is research-only.
Clinical criteria / differential diagnosis. No DSM/formal consensus "criteria set" beyond exposure + imaging pattern; occupational-medicine society guidance (ATS, ACOEM, ILO) applies. Differential: coal-workers' pneumoconiosis, sarcoidosis (both can give upper-zone nodules and hilar adenopathy), tuberculosis, metastatic pulmonary calcification, hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, berylliosis, pulmonary Langerhans cell histiocytosis. Exposure history and mineralogy distinguish silicosis.
Screening. Occupational surveillance of exposed workers (periodic ILO-classified CXR/HRCT + spirometry + TB screening), as in the Queensland engineered-stone program — a secondary-prevention model. No newborn/carrier/genetic screening (non-genetic disease).
No disease-reversing therapy exists; management is supportive, complication-directed, and increasingly antifibrotic-experimental. Suggested MAXO terms noted.
Foundational / supportive care (MAXO:0000950 supportive care): - Exposure cessation (remove worker from silica) — essential first step. - Smoking cessation (MAXO behavioral/counseling terms). - Oxygen therapy for hypoxemia (MAXO:0035008 oxygen therapy / supplemental oxygen). - Pulmonary rehabilitation (MAXO:0000915 rehabilitation / physiotherapy). - Vaccination — influenza, pneumococcal (± SARS-CoV-2) to reduce respiratory infections (MAXO:0001017 vaccination). - Prompt treatment of respiratory infections.
TB prevention/treatment: - Screening and treatment of latent/active tuberculosis with standard antimycobacterial regimens (isoniazid, rifampicin, etc.) — critical given silicotuberculosis risk (MAXO:0000058 pharmacotherapy / antibiotic therapy).
Pharmacotherapy (limited evidence): - Corticosteroids — may modestly reduce inflammation/alveolitis in some accelerated/acute cases; not disease-modifying for established fibrosis. - Antifibrotics — pirfenidone and nintedanib: approved for IPF, showing benefit in silicosis animal models and small clinical studies (reducing inflammation/fibrosis, pulmonary hypertension in early disease); under active clinical investigation (e.g., NCT05118256, pirfenidone in complicated silicosis). Not yet standard-of-care/approved for silicosis. - N-acetylcysteine (antioxidant) — protective in murine silicosis models; adjunctive human use investigational. - Investigational/preclinical targeted agents: NLRP3 inflammasome inhibitors, IL-1 blockade, P2X7 antagonists, TGF-β pathway inhibitors, metformin, trehalose (autophagy inducers), and nanoparticle-targeted pulmonary delivery.
Procedural: - Whole-lung lavage (WLL) — reduces dust/inflammatory burden; most useful in early and accelerated silicosis and acute silicoproteinosis; use cautiously in advanced disease (MAXO — therapeutic bronchopulmonary lavage / therapeutic procedure). - Lung transplantation — the only definitive option for end-stage PMF/respiratory failure; increasingly performed in young engineered-stone patients (MAXO:0010039 organ transplantation).
Pharmacogenomics: Not applicable (no genotype-guided silicosis drug therapy established).
Treatment strategy: stage-based — remove exposure + supportive care + TB/infection and complication management for all; antifibrotic trials/WLL for progressive early disease; transplantation for end-stage. Personalized/precision approaches are investigational.
Prevention is the only truly effective intervention — silicosis is 100% preventable.
Silicosis is modeled by inducing silica exposure (not genetic engineering), making animal models highly relevant.
Verified identifiers should be confirmed against the local MONDO/HP/CL/GO adapters before entry (per the dismech anti-hallucination SOP). Suggested key references for curation (verify PMIDs and quote exact abstract substrings with just fetch-reference before use):
Curation caveat (dismech SOP): Two references are already cached in this branch (
PMID_18577586,PMID_18604214) — verify their content and snippets before citing. Every PMID, ontology term (MONDO:0005960, HP/CL/GO/CHEBI IDs suggested above), and snippet in this report must be independently verified withjust fetch-referenceandjust validate-terms-filebefore entering the KB, per the anti-hallucination workflow. The GBD-derived numeric burden figures and engineered-stone case counts should be pinned to the specific source table and quoted exactly.
Sources (web): - PMC11847043 — Global scenario of silica-associated diseases - Frontiers Pharmacology 2024 — Role of inflammation in silicosis - PMC11917111 — Engineered stone silicosis review - PMC12005022 — Deadly Countertops - PMC11898348 — GBD 2021 silicosis burden - PMC12055836 — GBD pneumoconiosis 1990–2021 - PMID:11874815 — TNF-α polymorphisms, South African miners - PMC11585218 — Candidate gene polymorphism meta-analysis - PMC10179659 — Treatment drugs for silicosis - NCT05118256 — Pirfenidone in complicated silicosis - Merck Manual — Silicosis - Wikipedia — Silicosis - MalaCards — Silicosis (identifiers) - ICD-10 J62