Asbestosis

1. Disease Information

Overview. Asbestosis is a chronic, progressive, diffuse interstitial pulmonary fibrosis (pneumoconiosis) caused by the inhalation and lung retention of asbestos mineral fibers. It is the fibrotic parenchymal lung disease specifically attributable to asbestos, distinct from asbestos-related pleural disease (pleural plaques, diffuse pleural thickening, benign asbestos pleural effusion) and from asbestos-associated malignancies (bronchogenic carcinoma, malignant mesothelioma). It is dose-dependent, typically follows heavy cumulative exposure, and manifests after a long latency (commonly 20–40 years; ≥10 years minimum). (StatPearls, NBK555985; Merck Manual Professional)

Key identifiers. - MONDO: MONDO:0016466 - Disease Ontology: DOID:10320 - ICD-10-CM: J61 ("Pneumoconiosis due to asbestos and other mineral fibers") - ICD-11 (MMS): CA60.2 - MeSH: D001195 ("Asbestosis") - OMIM: Not applicable (not a Mendelian disorder) - Orphanet: Not a designated rare-disease entry (occupational/acquired; excluded from Orphanet's rare-disease scope)

Sources: Wikidata Q664174; MalaCards; ICD10Data J61

Common synonyms / alternative names. Pulmonary asbestosis; asbestos pneumoconiosis; interstitial pneumonitis due to asbestos; "white-lung" (colloquial). Note the important terminological distinction: asbestosis refers strictly to the parenchymal fibrosis, whereas "asbestos-related disease" is the broader umbrella.

Data derivation. Disease-level aggregated resources (occupational cohorts, national mortality/DALY databases, pathology case series, radiographic surveillance). There is no single OMIM/individual-patient genetic basis; population and cohort epidemiology dominate.

2. Etiology

Primary cause (environmental/occupational). Inhalation of respirable asbestos fibers with deposition in the distal airways and alveoli. Asbestos comprises two mineral families: - Serpentine — chrysotile ("white asbestos"): curly, flexible fibers; more readily cleared; historically the most-used commercial form. - Amphibole — crocidolite ("blue"), amosite ("brown"), tremolite, actinolite, anthophyllite: straight, stiff, needle-like, biopersistent, penetrate deeper and are more fibrogenic and carcinogenic. Amphiboles carry disproportionate pathogenic weight. (StatPearls, NBK555985)

Risk factors (environmental/occupational). - Cumulative exposure (dose) is the dominant determinant. A large Danish general-working-population cohort (1,514,136 workers; 1,084 incident asbestosis cases) found a fully adjusted incidence rate ratio of 1.18 per 1 f/ml-year (95% CI 1.15–1.22) and 1.94 for highest vs. lowest exposure tertile, with the steepest risk rise up to ~1 f/ml-year. "This study found exposure–response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population." (Iversen et al., Scand J Work Environ Health 2024; PMID: 38577971) - High-risk occupations: insulation/lagging, shipbuilding, asbestos mining/milling, textile manufacture, boiler work, brake/clutch manufacture, construction (asbestos-board installers and sprayers show the highest prevalence in some series — 38–39% in Japanese data), demolition, plumbing/pipefitting. (StatPearls) - Bystander and paraoccupational exposure (e.g., household members exposed to fibers on workers' clothing) and environmental/community exposure (near mines, from contaminated soils/building materials). - Fiber dimension & biopersistence: long, thin, durable amphibole fibers are most fibrogenic ("frustrated phagocytosis"). - Smoking: does not cause asbestosis per se but impairs mucociliary clearance, increases fiber retention, and interacts multiplicatively with asbestos for lung cancer risk (see §6, §11). - Male predominance and older age (reflecting historical occupational exposure patterns).

Genetic (susceptibility, not causal). Asbestosis has no single-gene cause. Candidate susceptibility/modifier loci — mostly studied for asbestos-related fibrotic and malignant endpoints — include: - GSTT1 null genotype: associated with fibrotic changes and reduced diffusing capacity; GSTM1 null: associated with thicker pleural plaques and increased risk across asbestos-linked diseases (plausibly via impaired conjugation/detoxification of ROS). (Franko et al., Eur Respir J 2011;38(3):672) - GSTM1 null + NAT2 slow acetylator each ~2-fold and together ~4-fold increased malignant mesothelioma risk in asbestos-exposed individuals. (Hirvonen et al., Cancer Res 1995;55:2981; PMID: 7606735) - Iron-homeostasis gene variants modulate mesothelioma susceptibility after exposure. (Frontiers Public Health 2023, PMC10628177)

Protective factors. No validated genetic protective allele for asbestosis. The only reliable protection is primary exposure prevention (fiber control, bans, PPE) and smoking avoidance/cessation (reduces synergistic cancer risk and slows functional decline). No dietary/antioxidant intervention has proven clinical benefit.

Gene–environment interaction. The paradigm is detoxification/oxidative-defense genotype × cumulative fiber burden: null GST genotypes and slow-acetylator NAT2 amplify oxidative and genotoxic injury from retained fibers, and smoking further raises fiber retention and cancer risk — a classic multiplicative environmental interaction. (CTD/PubMed as suggested sources.)

3. Phenotypes

Phenotype categories: symptoms, clinical signs, functional (PFT) abnormalities, radiographic/histopathologic findings, laboratory abnormalities. Onset is adult/late-adult after long latency; course is typically chronic and slowly progressive; frequencies below are approximate from clinical literature and should be curated with per-phenotype evidence.

Severity & progression: ranges from mild/subclinical (radiographic only) to severe with respiratory failure. Progression is usually slow over years-to-decades, may continue after exposure ceases (retained biopersistent fibers), and is influenced by cumulative dose and continued smoking. Quality-of-life impact: dyspnea limits exertion and ADLs; advanced disease causes oxygen dependence, reduced exercise capacity, anxiety/depression, and (via lung-cancer/mesothelioma fear and surveillance) psychological burden. Pulmonary rehabilitation improves QoL and reduces hospitalization. (American Lung Association; PMID: 32053838)

4. Genetic / Molecular Information

• Causal genes: None — asbestosis is caused by fiber exposure, not germline mutation.
• Pathogenic variants: Not applicable in the ACMG/ClinVar sense. Relevant loci are susceptibility/modifier polymorphisms, not pathogenic variants: GSTM1 (HGNC:4632, null/deletion), GSTT1 (HGNC:4641, null/deletion), GSTP1 (HGNC:4638), GSTM3, EPHX1 (HGNC:3401), NAT2 (HGNC:7646, slow-acetylator haplotypes), SOD2/MnSOD. These are common-population polymorphisms (GSTM1/GSTT1 null genotypes are frequent, ~20–50% depending on ancestry), germline in origin, with functional consequences of reduced xenobiotic/ROS detoxification. (Eur Respir J 2011;38:672; Cancer Res 1995;55:2981)
• Somatic vs germline: the above are germline modifiers; somatic genetic events (e.g., BAP1, NF2, CDKN2A losses) belong to the downstream malignancy (mesothelioma/lung cancer), not to asbestosis fibrosis itself.
• Epigenetics: asbestos exposure induces DNA-methylation and miRNA changes in airway/lung tissue described chiefly in the carcinogenesis literature; a specific validated asbestosis (fibrosis) methylation signature is not established — mark as a knowledge gap.
• Chromosomal abnormalities: none causal for asbestosis.

5. Environmental Information

• Primary environmental agent: asbestos fibers (serpentine chrysotile; amphiboles crocidolite, amosite, tremolite, actinolite, anthophyllite). CHEBI/exposure suggestion: asbestos (verify CHEBI), silicon-containing mineral fiber; ROS species CHEBI:26523.
• Co-exposures: other mineral dusts (silica → mixed-dust fibrosis), erionite (fibrous zeolite, mesothelioma), and cigarette smoke.
• Lifestyle: cigarette smoking is the key modifiable co-factor — impairs mucociliary clearance (increasing fiber retention) and multiplies lung-cancer risk. No specific dietary driver established.
• Infectious agents: None. Asbestosis is not infectious. (Secondary infections may complicate advanced disease.)

6. Mechanism / Pathophysiology

Overarching causal chain: inhaled biopersistent fiber deposition → alveolar macrophage "frustrated phagocytosis" → oxidative injury + inflammasome/cytokine activation → epithelial (type I/II pneumocyte) injury → fibroblast recruitment/activation → myofibroblast differentiation and excess ECM/collagen deposition → progressive interstitial fibrosis → impaired gas exchange and restrictive physiology → respiratory failure/cor pulmonale.

Step-by-step mechanism (upstream → downstream):

1. Fiber deposition & retention (trigger). Long, thin amphibole fibers deposit at alveolar-duct bifurcations; their length prevents complete macrophage engulfment ("frustrated phagocytosis"). Iron on/within fibers catalyzes redox chemistry. Cell types: alveolar macrophage (CL:0000583). GO: phagocytosis (GO:0006909).

2. Oxidative injury. Frustrated phagocytosis and fiber-surface iron generate ROS/RNS (Fenton-type chemistry, mitochondrial ROS), directly injuring type I pneumocytes (CL:0002062) and epithelium and activating redox-sensitive transcription factors (NF-κB). GO: reactive oxygen species metabolic process (GO:0072593); response to oxidative stress (GO:0006979).

3. Inflammasome activation & sterile inflammation. Asbestos activates the NLRP3 inflammasome in macrophages/monocytes and lung epithelial and mesothelial cells → caspase-1 → IL-1β (and IL-18) release; mitochondrial ROS and thioredoxin/TXNIP dissociation contribute. GO: inflammasome complex (GO:0061702); inflammatory response (GO:0006954). (Sayan & Mossman, Part Fibre Toxicol 2016;13:51, PMC5029018)

4. Fiber-size–dependent macrophage cell death (2023 mechanistic detail). "SFA [short-fiber amosite] internalization resulted in pyroptotic-related immunogenic cell death (ICD) characterized by the release of the pro-inflammatory damage signal (DAMP) IL-1α after inflammasome activation and gasdermin D (GSDMD)-pore formation." By contrast, "macrophage responses to non-internalizable LFA [long-fiber amosite] were associated with tumor necrosis factor alpha (TNF-α) release, caspase-3 and -7 activation, and apoptosis." Short fibers signalled via TLR4; long fibers via MARCO/SR-A6 + ROS cascade + TLR4. GO: pyroptosis (GO:0070269); apoptotic process (GO:0006915). (Della Latta-type study; PMID: 37894824, 2023)

5. Pro-fibrotic mediator surge. Activated macrophages release TNF-α, IL-1β, PDGF, TGF-β, IGF-1, fibronectin. IL-1β/NLRP3 signalling promotes TGF-β pathways. Macrophages transition from a pro-inflammatory (M1) to a wound-healing (M2) phenotype driving repair-gone-awry. GO: transforming growth factor beta receptor signaling pathway (GO:0007179); cytokine-mediated signaling (GO:0019221).

6. Fibroblast activation & myofibroblast transdifferentiation. TGF-β drives fibroblast proliferation and fibroblast→myofibroblast differentiation (α-SMA+), plus epithelial–mesenchymal transition contributions. Cells: fibroblast (CL:0000057), myofibroblast (CL:0000186). GO: fibroblast proliferation (GO:0048144); epithelial to mesenchymal transition (GO:0001837).

7. Excess ECM/collagen deposition. Myofibroblasts deposit type I/III collagen and matrix → interstitial thickening. GO: collagen fibril organization (GO:0030199); extracellular matrix organization (GO:0030198). This is the principal pathogenic endpoint ("interstitial fibrosis is regarded as the principal pathogenic mechanism of asbestosis").

8. Structural/functional consequence. Alveolar-wall thickening and honeycombing impair diffusion and compliance → restrictive physiology, ↓DLCO, hypoxemia → pulmonary hypertension → cor pulmonale.

Immune involvement: sterile, chronic innate-immune-driven inflammation (macrophage/inflammasome-centric) rather than autoimmunity — though autoantibodies (ANA, RF) may be elevated. Tissue-damage mechanisms: oxidative stress, sterile inflammation, and fibrosis. Biochemical/protein dysfunction: no enzyme defect; the "dysfunction" is dysregulated cytokine/TGF-β signalling and matrix homeostasis. Molecular profiling: transcriptomic/innate-immunity gene-expression signatures associated with asbestos fibrotic change are reported (PMC3888604); dedicated proteomic/metabolomic/single-cell asbestosis signatures are limited — knowledge gap.

Histopathology (CAP/Pulmonary Pathology Society criteria): diffuse interstitial fibrosis in the proper anatomic distribution plus identifiable asbestos (ferruginous) bodies (golden-brown, beaded/dumbbell iron-protein-coated fibers) or documented elevated fiber burden. Fibrosis is graded, subpleural/lower-lobe predominant. (Roggli et al., Arch Pathol Lab Med 2010;134:462; ATS mechanisms review, AJRCCM 1998;157:1666)

7. Anatomical Structures Affected

• Primary organ: lung (UBERON:0002048) — bilateral, lower-lobe (UBERON:0008953) and subpleural/peripheral predominance; alveolus of lung (UBERON:0002299) and pulmonary interstitium.
• Secondary/associated: pleura (UBERON:0000977) — visceral pleural thickening, plaques; heart (right ventricle → cor pulmonale); systemic effects of chronic hypoxemia.
• Body systems: respiratory (primary); cardiovascular (secondary, pulmonary hypertension/right heart).
• Tissue level: alveolar epithelium (type I/II pneumocytes), pulmonary interstitial connective tissue, pleural mesothelium.
• Cell populations: alveolar macrophage (CL:0000583), pulmonary alveolar type 1 cell (CL:0002062), type 2 pneumocyte (CL:0002063), fibroblast (CL:0000057) / myofibroblast (CL:0000186), mesothelial cell (CL:0000077).
• Subcellular: mitochondria (mito-ROS; GO:0005739), lysosome/phagosome (frustrated phagocytosis; GO:0005764), extracellular region/matrix (GO:0031012).
• Localization/lateralization: bilateral, lower-zone and posterolateral/subpleural predominant.

8. Temporal Development

• Onset: adult/late-adult, after prolonged latency of ~20–40 years from first exposure (minimum ~10 years; shorter with very intense exposure). Onset is insidious/chronic.
• Progression/stages: subclinical/radiographic → mild symptomatic (exertional dyspnea, ↓DLCO) → moderate (restrictive PFT, hypoxemia) → advanced/end-stage (honeycombing, respiratory failure, cor pulmonale). Rate is usually slow and variable over years.
• Course: chronic, irreversible and often progressive even after exposure ceases (biopersistent retained fibers); no spontaneous remission. There is no treatment-induced remission; management slows decline and treats complications.
• Critical window: the actionable window is exposure prevention before disease onset; once fibrosis is established it is not reversible.

9. Inheritance and Population

• Inheritance: Not applicable — acquired occupational/environmental disease; genetic contribution is modifier/susceptibility polygenic (GST/NAT2/iron-homeostasis alleles), not Mendelian. No penetrance, anticipation, mosaicism, or carrier-frequency concepts apply.
• Epidemiology (global burden): In 2019, occupational asbestos exposure was linked to ~239,330 deaths and ~4,189,000 DALYs globally; global asbestos-attributed deaths rose ~65.7% (1990–2019). WHO-type estimates attribute ~55,000+ deaths/year to asbestos-related disease broadly. In the US, absolute deaths rose but age-standardized mortality and DALY rates declined over 1990–2019 (reflecting historical-exposure cohort aging plus reduced new exposure). (Merck Manual; StatPearls)
• Incidence in exposed cohorts: ~0.71 asbestosis cases per 100,000 person-years baseline in a general-working-population cohort, rising steeply with cumulative exposure (IRR 1.18 per f/ml-year). (PMID: 38577971)
• Demographics: male predominance (occupational exposure history), older age at diagnosis. Geographic variation tracks historical mining/industrial use and regulatory timelines — declining in countries with asbestos bans, still rising in regions with ongoing chrysotile use. Prevalence extremely high in specific trades (e.g., asbestos-board installers ~39% in Japanese series). Prevalence class: occupational-cohort-dependent; in the general population it is uncommon.

10. Diagnostics

Diagnosis rests on the triad of (1) credible exposure history with appropriate latency, (2) imaging/pathologic evidence of diffuse interstitial fibrosis, and (3) exclusion of alternatives.

• Exposure history: occupational/paraoccupational/environmental asbestos exposure, typically ≥10–20 years prior.
• Imaging:
• Chest radiograph: bilateral lower-zone reticular/linear opacities (ILO-classified small irregular opacities), ± pleural plaques/thickening; "shaggy heart border."
• HRCT (most sensitive): subpleural/basal reticulation, interlobular/intralobular septal thickening, subpleural curvilinear/branching lines, parenchymal bands, ground-glass, honeycombing; pleural plaques strongly support asbestos etiology and help distinguish from IPF.
• Pulmonary function tests: restrictive pattern (↓FVC, ↓TLC, normal/↑FEV1/FVC), reduced DLCO (often earliest), exertional desaturation on 6-minute walk. (LOINC-coded spirometry/DLCO.)
• Histopathology (when biopsy done): diffuse interstitial fibrosis plus asbestos/ferruginous bodies or elevated tissue fiber burden (CAP/PPS criteria); asbestos-body quantification and fiber analysis (SEM/EDX) on digested tissue in reference labs.
• Laboratory: no specific diagnostic biomarker; nonspecific ↑CRP/ESR, and sometimes ↑RF/ANA. Serum mesothelin/osteopontin relate to mesothelioma, not asbestosis diagnosis.
• Clinical criteria / differential: Differentiate from idiopathic pulmonary fibrosis (UIP) — asbestosis favored by exposure history + pleural plaques + asbestos bodies; also from other pneumoconioses, hypersensitivity pneumonitis, connective-tissue-disease ILD, sarcoidosis, drug-induced fibrosis. A 2024 clinicopathological series of 102 cases refined 21st-century diagnostic correlation. (PMID: 38192052; Merck Manual)
• Genetic/omics testing: Not used diagnostically. Newborn/carrier/cascade screening: not applicable.
• Screening: medical surveillance of exposed workers (periodic spirometry + low-dose CT), and lung-cancer LDCT screening consideration in exposed (especially smoking) individuals.

11. Outcome / Prognosis

• Course/survival: highly variable. Many patients have mild, slowly progressive disease and near-normal life expectancy; a subset progress to respiratory failure and cor pulmonale. Some clinical sources cite limited survival once symptomatic and worse outcomes with pleural involvement, but survival is heterogeneous and dose/severity-dependent. Progression can continue after exposure ends. (StatPearls; Merck Manual)
• Morbidity/disability: progressive exertional limitation, oxygen dependence, reduced QoL.
• Complications:
• Bronchogenic lung cancer — the most common asbestos-related malignancy; risk multiplies synergistically with smoking (asbestos + smoking risk far exceeds additive).
• Malignant pleural/peritoneal mesothelioma — >80% attributable to asbestos; long latency (30–40+ yr); not smoking-related.
• Cor pulmonale / right heart failure, respiratory failure, recurrent respiratory infection, pulmonary hypertension.
• Associations with laryngeal and ovarian cancer (IARC).
• Prognostic factors: cumulative exposure/fiber burden, extent/rate of radiographic progression, baseline and decline in FVC/DLCO, degree of hypoxemia, continued smoking, age/comorbidity.

12. Treatment

No curative or disease-reversing therapy exists; management is supportive, prevents progression, and treats complications. (Suggested MAXO terms in brackets — verify with OAK.)

• Exposure cessation — remove from further asbestos and irritant exposure (foundational).
• Smoking cessation — highest-yield intervention to reduce lung-cancer risk and slow decline. [smoking cessation — MAXO, verify]
• Supplemental long-term oxygen therapy for resting/exertional hypoxemia (PaO₂ < ~55 mmHg). [oxygen administration — MAXO, verify]
• Pulmonary rehabilitation (exercise + breathing training + education) — improves QoL, exertional capacity, reduces hospitalization. [physical therapy MAXO:0000011 / pulmonary rehabilitation — verify] (ALA; PMID: 32053838)
• Vaccination — influenza and pneumococcal to prevent respiratory infection. [vaccination MAXO:0001017 — verify]
• Management of cor pulmonale / heart failure and pulmonary hypertension — supportive/pharmacologic. [supportive care MAXO:0000950 — verify]
• Corticosteroids — sometimes used for inflammation, but evidence of benefit in established asbestosis is weak (not standard disease-modifying therapy). [pharmacotherapy — glucocorticoid, verify CHEBI prednisolone CHEBI:8378]
• Lung transplantation — for selected end-stage patients (double-lung preferred). [organ transplantation MAXO:0010039 / lung transplantation — verify]
• Malignancy surveillance/treatment — LDCT lung-cancer screening in appropriate exposed/smoking patients; oncologic management of lung cancer/mesothelioma as indicated.
• Antifibrotics (pirfenidone, nintedanib): approved for IPF and progressive pulmonary fibrosis phenotypes; experimental/off-label in asbestosis with progressive fibrosing behavior — an active area but not established standard of care (basis for clinical-trial follow-up). (asbestos.com treatment overview; StatPearls)
• Pharmacogenomics: none specific/validated for asbestosis.

13. Prevention

• Primary prevention (most important): eliminate/control exposure — national asbestos bans, permissible-exposure-limit enforcement (OSHA), engineering controls (wet methods, enclosure, ventilation), respiratory PPE, safe removal/abatement, and product substitution. Historical latency means primary prevention today prevents disease decades hence.
• Secondary prevention: medical surveillance of exposed workers (periodic spirometry/DLCO, chest imaging), early identification, and smoking-cessation programs in exposed populations; LDCT lung-cancer screening in high-risk exposed smokers.
• Tertiary prevention: vaccinations, pulmonary rehab, prompt infection treatment, oxygen, comorbidity and malignancy management to limit complications.
• Public-health/environmental: worldwide asbestos-use bans (advocated by WHO), safe demolition/renovation regulation, environmental remediation of contaminated sites.
• Genetic counseling / immunization against causal agent: not applicable (no vaccine; not heritable).

Sources: CDC/ATSDR asbestos toxicity module; ALA.

14. Other Species / Natural Disease

• Taxonomy: primarily Homo sapiens (NCBITaxon:9606). Asbestosis is fundamentally a human occupational disease.
• Naturally occurring animal disease: rare/limited. Experimental asbestos-induced pulmonary fibrosis is well documented in laboratory rodents; naturally occurring companion-animal asbestosis is not a recognized clinical entity, though environmental asbestos exposure has been studied in pets as a sentinel for human household exposure (mesothelioma associations in dogs).
• Comparative biology: the macrophage-frustrated-phagocytosis/ROS/fibrosis mechanism is evolutionarily conserved across mammals, which underpins rodent modeling.
• Zoonotic potential: none (non-infectious).

15. Model Organisms

• Rodent inhalation/instillation models (mammalian): rat and mouse intratracheal instillation or inhalation of chrysotile/crocidolite/amosite reproduce alveolar macrophage accumulation, inflammation, and peribronchiolar/interstitial fibrosis — the workhorse asbestosis models. [MGI/RGD]
• In vitro / cellular: murine and human alveolar macrophage cultures (frustrated phagocytosis, NLRP3/IL-1β, ROS; short vs long amosite fiber studies, PMID: 37894824); mesothelial cell and lung epithelial cultures for inflammasome and TGF-β/fibroblast-activation assays; fibroblast/myofibroblast differentiation assays.
• Genetic models: Nlrp3-, Casp1-, Tnf-, Il1r-, and Tgfb-pathway knockout/transgenic mice used to dissect individual mechanistic steps (inflammasome, TNF, TGF-β signalling).
• Phenotype recapitulation: rodent models reproduce the inflammation→fibrosis cascade and fiber-size/biopersistence effects well.
• Limitations: accelerated timelines (weeks–months vs. human decades of latency), high bolus doses unlike chronic low-level human exposure, species differences in fiber clearance and airway anatomy, and incomplete modeling of honeycomb end-stage architecture and of asbestos-associated human malignancy latency.
• Resources: MGI, RGD, Alliance of Genome Resources, IMPC (for pathway-gene knockouts); Cellosaurus/ATCC for macrophage and mesothelial cell lines.

Consolidated Ontology Term Suggestions (verify all with OAK/OLS before curation)

• MONDO: MONDO:0016466 (asbestosis)
• HP (phenotypes): HP:0002875 exertional dyspnea; HP:0031246 nonproductive cough; HP:0030830 crackles; HP:0001217 finger clubbing; HP:0002091 restrictive ventilatory defect; HP:0012418 hypoxemia; HP:0002206 pulmonary fibrosis; HP:0002102 pleural thickening (verify); HP:0001648 cor pulmonale (verify); HP:0002093 respiratory insufficiency; HP:0012378 fatigue
• GO (processes): GO:0006909 phagocytosis; GO:0072593 ROS metabolic process; GO:0006954 inflammatory response; GO:0061702 inflammasome complex; GO:0070269 pyroptosis; GO:0006915 apoptotic process; GO:0007179 TGF-β receptor signaling; GO:0048144 fibroblast proliferation; GO:0001837 EMT; GO:0030199 collagen fibril organization; GO:0030198 ECM organization
• CL (cell types): CL:0000583 alveolar macrophage; CL:0002062 type 1 pneumocyte; CL:0002063 type 2 pneumocyte; CL:0000057 fibroblast; CL:0000186 myofibroblast; CL:0000077 mesothelial cell
• UBERON (anatomy): UBERON:0002048 lung; UBERON:0008953 lower lobe of lung; UBERON:0002299 alveolus of lung; UBERON:0000977 pleura
• CHEBI: CHEBI:26523 reactive oxygen species; asbestos/mineral-fiber term (verify); CHEBI:8378 prednisolone; CHEBI:15379 dioxygen (O₂)
• MAXO (treatments): oxygen administration (verify); MAXO:0000011 physical therapy (pulmonary rehab); MAXO:0001017 vaccination; MAXO:0010039 organ transplantation (lung transplant); MAXO:0000950 supportive care
• HGNC (modifier genes): HGNC:4632 GSTM1; HGNC:4641 GSTT1; HGNC:4638 GSTP1; HGNC:3401 EPHX1; HGNC:7646 NAT2

Key Citations (for evidence items)

Evidence-source classification reminder for curation: the fiber/macrophage mechanism papers (PMID 37894824; PFT 2016 review) are IN_VITRO; the Danish cohort (PMID 38577971) and clinicopathological series (PMID 38192052) are HUMAN_CLINICAL; rodent inhalation studies are MODEL_ORGANISM. Per the dismech DR/anti-hallucination SOP, each PMID must be re-fetched with just fetch-reference and each snippet verified as an exact substring, and every ontology ID validated with OAK, before committing to a KB entry.

Explicitly not available / not applicable for asbestosis: OMIM entry, Mendelian causal gene, inheritance pattern, penetrance/anticipation/carrier frequency, newborn/carrier screening, gene therapy, and a validated diagnostic molecular biomarker — all reflect that this is an acquired occupational fibrotic disease rather than a genetic disorder.