Michael I. Greenberg, MD, MPH,
Javier Waksman, MD, and John Curtis, MD
Silicosis is a potentially fatal, irreversible, fibrotic pulmonary disease that
may develop subsequent to the inhalation of large amounts of silica dust
over time. In most circumstances, silicosis only develops subsequent to
substantial occupational exposures. The disease has a long latency period
and may clinically present as an acute, accelerated, or chronic disease.
The pathophysiology of chronic silicosis involves chronic inflammation
arising as a result of the accumulation of various inflammatory mediatorsand fibrogenic factors. Under the influence of these factors, pulmonarysilicoproteinosis develops as eosinophilic proteinaceous material accu-mulates in the pulmonary alveolar spaces. The rate of disease progressionappears to depend upon the rate of silica deposition in the lungs, as wellas the total amount of crystalline silica that is actually retained in the lung.
In some cases, silicosis may be associated with the concomitant develop-
ment of other diseases, including tuberculosis, cancer, or autoimmune disease.
Currently, no cure or effective treatment is available for silicosis.
Due to the association between occupational exposure to silica and the
subsequent development of silicosis, a variety of federal and state agencieshave initiated strict regulations aimed at preventing the development ofsilicosis in certain workers. These regulations generally emphasize ade-quate ventilation on job sites and limiting the amount of time workersmay spend in potentially exposing environments.
Respiratory disease associated with occupational exposure to crystalline
silica has been described throughout history. Hippocrates described acondition of “breathlessness” in miners, and in 1690, Lohneiss noted thatwhen “the dust and stones fall upon the lungs, the men have lung disease,breathe with Bernardo Ramazzini studied so-called “miners’phthisis,” and other trades of the day wherein workers inhaled substantial
Dis Mon 2007;53:394-4160011-5029/2007 $32.00 ϩ 0doi:10.1016/j.disamonth.2007.09.020
amounts of dusts. These dust-related afflictions have been known by variousnames, including “miners’ phthisis,” “dust consumption,” “mason’s disease,”“grinders’ asthma,” “potters’ rot,” and “stonecutters’ These prob-lems are now collectively referred to as silicosis. Peacock and Greenhowreported finding silica dust in the lungs of miners in the 1860s, and 10years later, Visconti used the term “silicosis” to describe the diseasecaused by inhalational exposure to
Statistical and epidemiological analyses have contributed important
information towards understanding silicosis. At the turn of the 20thcentury, the Metropolitan Life Insurance Company reported that workersfrom foundries, quarries, and machine shops were absent from worksubstantially more frequently than other workers. This constituted the firstmodern suggestion of the clinical importance of silica exposure. How-ever, it was not until the so-called Hawk’s Nest Tunnel disaster of theearly 1930s that silicosis was clearly defined as an important public healthconcern.
The Hawk’s Nest Tunnel was a hydroelectric power project constructed
by blasting into massive natural rock formations in the area of GauleyBridge, West Virginia. The construction techniques used in this projectdid not employ so-called wet-drilling techniques to reduce drilling andblasting-related dust. Consequently, enormous amounts of construction-related dusts were generated during the course of this During theproject, it was noted that a number of workers became ill and many diedfrom what appeared to be a nondescript, yet severe, form of respiratorydisease. Pneumonia was noted as the cause of death in many of theworkers and company doctors for the project dubbed the respiratoryproblems plaguing these workers
When the drilling and blasting phase of the Hawks Nest project was
complete, an epidemic of silicosis was identified among men who hadworked at the Gauley Bridge site. Four hundred drillers died, andlung-related disabilities were reported in the majority of survivingInvestigations eventually revealed that blasting for the HawksNest project actually involved the disruption of rock formations com-posed largely of pure silica. Eventually it was shown that the exposuresat Gauley Bridge involved prolonged and unprotected exposure times inconjunction with extremely high levels of pure silica liberated into theimmediate breathing space of workers.
Investigators working with the U.S. Public Health Service first classi-
fied silicosis by state, industry, and job description. Since then, a varietyof occupations have been identified as having the potential to be associatedwith silica exposure. These occupations are listed in The Occupa-
Industrial processes and activities associated with silica
granite and other sourcesof crystalline silica
tional Safety and Health Administration (OSHA) has reported that as manyas two million American workers may be chronically exposed to crystallinesilica.Of these workers, roughly 100,000 are employed in what may beconsidered potentially “high-risk” settings, such as sandblasting, rockdrilling, roof bolting, and foundry-related industries.In 2002, theNational Institute for Occupational Safety and Health (NIOSH) publishedan updated report entitled “Work-Related Lung Disease Surveillance Re-This report indicated that approximately one-third of all decedentswho had silicosis from 1990 through 1999 had been employed in theconstruction and mining industries
Chemical Properties of Silica
Silica refers to the chemical compound SiO (silicon dioxide) that
occurs in two specific and distinct forms: amorphous and crystallineand The word “crystalline” implies that the silicon andoxygen atoms are oriented and related to each other in a fixed pattern asopposed to the random fashion that predominates in the amorphous formof silica. Crystalline silica naturally exists in a polymerized tetrahedralframework producing several polymorphs. These polymorphs are afunction of the temperature and pressure: alpha quartz (or quartz), themost common polymorph found on the earth’s surface, is stable over mosttemperatures and pressures found in the earth’s crust. In contrast, betaquartz is stable at high temperatures, whereas tridymite and cristobalite
Most frequently recorded industries on death certificates, US residents aged 15 years
and over: selected states and years
Blast furnaces, steelworkers, rolling/finishing mills
Nonmetallic mining/quarrying (except fuel)
Nonmetallic mineral and stone products, miscellaneous
Machinery (except electrical; not elsewhere classified)
Synonyms for crystalline
CSQZDQ 12Min-U-SilSil-Co-SilSnowitSykron F300Sykron F600
are stable only at high temperatures and low pressures. Other silicapolymorphs include coesite and stishovite. These may be encountered ata wide range of temperatures but only in a high-pressure environment andtherefore they may be created during a variety of industrial processesincluding ceramic manufacturing, foundry processes, and any otherindustrial operation wherein quartz may become heated to hightemperatures at elevated pressures. The most common crystallineforms of silica involved in workplace exposures include quartz,tridymite, and cristobalite. Silica may also occur naturally and atvarying concentrations in rocks such as sandstone (67% silica) andgranite (25 to 40% silica).
Synonyms for amorphous
Silicates are structures composed of silicon dioxide bound to cations
such as magnesium, aluminum, or iron. Examples of silicates includemica, soapstone, talc tremolite, Portland Cement, and others.
Opal, diatomaceous earth (tripolite), silica-rich fiberglass, fume silica,
mineral wool, and silica glass (vitreous silica) are common amorphousforms of silica. Other forms of amorphous silica are listed in Dusts composed of amorphous silica, with the exception of fiberglass, arenot generally considered to be harmful to
Quartz, cristobalite, and some forms of tridymite are inherently
piezoelectric. Piezoelectricity is a property that produces oppositeelectric charges on opposite sides of the physical structure whenpressure is applied directly to the crystal. This phenomenon occurs incrystalline silica because the chemical structure does not have a center,reflecting an inversion symmetry. In addition, the opposite sides of thesecrystals have dissimilar surfaces and carry opposite electrical charges. Itis theorized that these piezoelectric characteristics may play a role in thepathophysiology of silica-related illness by the generation of oxygen freeradicals produced on the cleaved surfaces of silica molecules and as aresult of silica-damaged alveolar Silanol (SiOH)groups present on the surface of silica particles are capable of forminghydrogen bonds with oxygen and nitrogen groups found in biologic cell
Secondary disorders common in
BronchitisEmphysemaChronic obstructive pulmonary diseaseSclerodermaRheumatoid arthritisSystemic lupus erythematosusRenal disease
membranes, which then may lead to a loss of membrane structure,lysosomal leakage, and tissue damage. These processes may all contributeto the development of lung Experimental data suggest thatthere is a distinct fibrogenic order of potency for these materials asfollows: tridymite Ͼ cristobalite Ͼ quartz
Occupational Exposure to Silica
Workers engaged in specific occupations, such as abrasive blasting,
may have the potential for medically important exposures to crystallinesilica. The American College of Occupational and Environmental Med-icine (ACOEM) considers that silica exposure today is still widespreadand the estimated death rate due to silicosis in the United States may bein the range of 200 to 300 individuals per It has been noted thatsome workers may have the potential for silica exposure even despiteefforts to limit and control occupationally based
Abrasive blasting operations use a variety of abrasive compounds to
clean and/or add texture to various industrial materials for a variety ofpurposes. For example, the shipbuilding and automotive industries utilizeabrasive blasting in a variety of Sand has historically beenused as the primary abrasive material in sandblasting, and these tech-niques may, at times, result in elevated concentrations of crystalline silicasuspended in the air surrounding blasting operations. Recently, newtechniques have attempted to utilize substitute abrasives and agents inblasting operations. These alternative abrasive compounds contain reducedconcentrations of silica and may include varying amounts of coal slag,hematite, smelter slag, minerals, metals, or synthetic abrasives. Nonetheless,these methods may still generate silica-containing dust especially in circum-stances where the surfaces to be abraded contain silica.
Silicosis and Construction Work
Approximately one million American workers are employed in heavy
construction jobs, with 39% of these individuals engaged in road and
street construction According to a 2002 NIOSH report derivedfrom death certificate information, 13.4% of decedents who succumbed tosilicosis from 1990 to 1999 were employed in the construction
Rehabilitation of the U.S. national highway infrastructure has gained recent
focus and legislation has accelerated spending for this purpose. Increasedhighway construction may lead to increased potential for exposure tocrystalline silica dust in some Unfortunately, to date, few extensiveor long-term surveillance projects have been completed to monitor highwayrepair processes as possible sources of silica exposure. This is due in part tothe fact that these jobs do not typically generate the large amounts ofrespirable silica associated with other occupational activities such as abrasiveblasting or A so-called “cut-and-repair” technique for roadmaintenance, utilizing quick-setting concrete, has become popular since themid 1980s. This method reportedly may produce varying quantities ofsilica-containing dust during the cutting, break-up, and removal processof concrete road surfaces. Depending upon the nature and extent ofexposure, this process may thus pose a potential risk for silica exposurefor some workers involved in highway repair and construction.
Pathologic Mechanisms in Silicosis
A number of clinical and pathologic varieties of silicosis have been
identified including simple, or nodular, silicoisis, silicoproteinosis (acutesilicosis), complicated silicosis (progressive massive fibrosis), and interstitialfibrosis.
The postmortem examination of silicotic lungs (simple silicosis) reveals
dark pulmonary tissue in conjunction with associated enlarged andfibrotic hilar and peribronchial lymph nodes. Pulmonary nodules in thelung parenchyma are usually present and are typically located in the upperlobes. The characteristic lesions may have variable degrees of calcifica-tion and may range from only a few millimeters to more than a centimeterin diameter. The condition, known as progressive massive fibrosis (PMF)or complicated silicosis, is said to develop when the above describedpulmonary lesions coalesce forming pulmonary masses 2 cm or larger.
PMF may progress to a stage of central necrosis with cavitation.
Secondary infections with a variety of mycobacterial organisms includingMycobacterium tuberculosis, Mycobacterium kansasii,
and Mycobacte-rium intracellulare
may also develop. Microscopic sections may revealsilica-containing macrophages and reticulin fibers. These areas mayorganize, forming the classic silicotic lung nodules that represent theclassic X-ray findings consistent with chronic silicosis. These nodules
have been described as “histologic tornadoes” with a “quiet” center ofhyaline and collagen fibers concentrically arranged around the The periphery of these “tornadoes” contain a variety of inflammatorycells (macrophages, lymphocytes) progressing away from the center. Thisoutward configuration induces a fibrous reaction in normal vessel, airway,and pleural
Polarized light microscopy usually reveals the presence of crystalline
silica particles as areas of weak birefringence in the center of silicoticnodules. The birefringence sometimes observed inside nodules are theresult of inhaled silicate particles, which are mixed with silica dust. Themicroscopic findings reveal periodic acid–Schiff stained positive alveolarexudate and cellular infiltrates in the walls of the alveoli, histologicallyknown as silicoproteinosis.
Acute silicosis may involve a variety of different mechanisms of injury
when compared with chronic silicosis. In lungs affected by acute silicosis,electron microscopy reveals hypertrophic type II pneumocytes lining thealveoli. These hypertrophic pneumocytes may produce excessive amountsof proteinaceous material and surfactant protein and the alveoli may thenbecome filled with protein-containing Excessive free-radicalformation may also contribute to the development of silicotic lung diseasein the acute setting. Freshly fractured silica may contain higher propor-tions of free radicals than intact silica and thus may generate a strongerinflammatory Freshly fractured silica, by definition, con-tains abundant cleaved particle surfaces, where surface reactive oxygenspecies such as peroxides and hydroperoxides tend to Thepresence of excessive free radicals thus produced may result in alteredactivation of transcription factors leading to cell and/or DNA Occupations such as sandblasting and rock drilling have been docu-mented to produce freshly fractured silica particles and acute silicosis hasbeen historically associated with those occupations
Chronic silicosis is associated with chronic inflammatory changes
within the alveoli. This condition of chronic alveolitis may ultimatelyresult in the development of pulmonary fibrosis. The exact mechanism forthis has not yet been fully elucidated, but it is believed that it is initiatedwhen alveolar macrophages phagocytize silica particles in an attempt toclear them from the lung. Freshly fractured silica appears to be morereactive within alveolar macrophages than aged silica (eg, sand). When
silica particles are not efficiently cleared from the lung by alveolarmacrophages, these alveolar macrophages may become damaged. Mac-rophages damaged in this way are thought to become stimulated andrelease reactive oxygen species, reactive nitrogen species (RNS), andexcess free Transcription factors (NFkB and activator pro-tein-1) may then be released triggering the production and release ofinflammatory cytokines (TNF-␣, IL-1␤, and IL-6), proteases, and arachi-donic acid metabolites (leukotriene-B4, prostaglandin E2). When alveolarmacrophages containing silica die, they release silica particles that arethen re-engulfed by other alveolar macrophages, thus inducing a cycle ofThis cycle is accompanied by the movement of neutrophils andlymphocytes to the areas of injury resulting in further inflammatorychanges. Inflammatory cytokines including interleukin 1 (IL-1), tumornecrosis factor-␣, arachidonic acid metabolites (eg, leukotrienes), andchemokines such as IL-8, macrophage inflammatory protein (MIP)-2,MIP-1␣, MIP-1␤, and monocyte chemoattractant proteins all appear to beinvolved in this inflammatory In addition, macrophage-derived fibrogenic factors such as platelet-derived growth factors, trans-forming growth factors (TGF)-␣ and -␤, epidermal growth factor, andinsulin-like growth factor-1 are released as the body initiates reparativemeasures. A constant production of fibrotic factors appears to contributeto the evolution of silicotic lesions by recruiting type II pneumocytes andfibroblasts that produce large amounts of fibronectin and Scar tissue results, and the pulmonary architecture then becomes perma-nently altered. Laboratory treatment of mice with an antibody to TNF-␣has been shown to decrease the production of MIP-2, inflammation, andthe subsequent pulmonary
Former miners with severe silicosis-related lung disease have been found to
have a higher incidence of single nucleotide polymorphisms of TNF-␣, aswell as greater gene– gene and gene— gene environment It hasbeen proposed that alveolar macrophages may be activated, but not killed,when silica particles are engulfed. This phenomenon is implied by the findingthat bronchoalveolar-lavage fluid from silica-exposed humans shows mor-phologic signs of activation within local This macrophageactivation may then lead to collagenase production and resultant lungparenchymal lung
Particle Burden in Silicosis
A number of studies have investigated the relationship that may exist
between pulmonary silica burden and the subsequent development ofsilicosis. Nagelschmidt summarized the historical data regarding silica
toxicity and describes a possible association between increasing cumula-tive weight of retained silica in the lung and increasing severity ofHowever, there may also an association between the pres-ence or absence of other minerals and the development of silicosis.
Exposure to 4 to 10 grams of total dust and/or 1 to 3 grams of pure quartzis associated with silicosis. The percentage of quartz contained in the dustmay be as high as 18% or more. In rapidly developing silicosis the dustquartz content usually exceeds 30% but may be even higher in someinstances. Exposures of this magnitude may be found in some goldmining and some foundry work. If there is concomitant exposure to other,nonfibrogenic dusts, then the same weight of silica may produce onlyminor silicotic lung changes. Varied dust exposure is typical for hematiteor coal miners. This “interactive dust phenomenon” may demonstrate theabsorption of other dust types onto the surface of silica particles,consequently decreasing the toxicity of inhaled silica in humans.
Because there are different mineralogic types of silica particles, research
has been conducted to investigate the different pathogenic potentials of thoseparticles. The exact relationship between fibrotic potential and the specificsilica subtype has not yet been fully elucidated. However data haveconsistently shown that tridymite, cristobalite, and quartz are generallymore fibrogenic than amorphous
Clinical Presentation of Chronic Silicosis
Chronic or classical silicosis is the most common clinical form of
silicosis. This form of silicosis develops only after decades of repeatedexposure to high concentrations of silica dust. Since symptoms maynot develop for as long as 45 years following exposure, the diagnosisin asymptomatic patients requires radiographic Inthese cases, the physical examination may reveal stigmata of associateddisease, including emphysema and/or cor pulmonale. Nodular lesionspredominantly located in the upper lobes may be present on chestradiograph. lists secondary disorders common in silicosis.
Chronic silicosis not usually associated with mycobacterial infections
and tends to be mild and not disabling. However, chronic silicosis maydevelop into PMF, a serious and debilitating subset of the disease.
Chronic silicosis can be radiographically distinguished from acute diseasepresentations by virtue of large upper lobe opacities in conjunction withsmall, diffuse nodular lesions. Basilar emphysematous changes may alsobe apparent on chest X-ray. Patients with PMF are often noted to behypoxic at rest and are prone to mycobacterial infections and spontaneouspneumothoraces and may ultimately develop fatal respiratory failure.
Patients may also present with a condition known as accelerated
silicosis. This condition is associated with profound silica exposuresoccurring over a relatively shorter time course when compared withchronic silicosis. Accelerated silicosis is typically related to an exposurehistory in the range of 5 to 15 In many cases of acceleratedsilicosis, disease progression is evident even though the patient may havebeen promptly removed from continuing silica exposure. Acceleratedsilicosis has been associated with a variety of autoimmune disorders.
Clinical Presentation of Acute Silicosis
Acute silicosis differs both histologically and pathologically from
chronic silicosis. Accurate diagnosis of acute silicosis is essential as thereare significant implications for the patients who present with this form ofdisease. Acute silicosis has a low rate of occurrence and the Hawk’s Nestdisaster described above represents the most extensive recorded epidemicof acute
Patients diagnosed with acute silicosis may report substantial occupa-
tional exposures to silica which occurred, in some cases, over a relativelyshort amount of time. Specific occupations have been associated withthe development of acute silicosis, including silica flour processing,tombstone sandblasting, and surface These jobs resultin exposure to mechanically broken, cleaved, or fractured silica particlesfrom the grinding and cutting Presenting symptoms mayinclude dyspnea, fatigue, weight loss, fever, and pleuritic pain. Pathologicchanges consistent with acute silicosis include the filling of alveolarspaces with eosinophilic-granular material, similar to that observed inaccelerated The clinical course for acute silicosis is oftendramatic as there may be rapid progression to respiratory failure from aloss of pulmonary function and impaired gas
Diagnosis of Silicosis
The diagnosis of silicosis is based on a clearly documented history of
substantial silica exposure, usually in the occupational setting. Casualexposures are generally not considered to be important causes for thedevelopment of silicosis. In conjunction with a history consistent withmedically important exposures to silica, chest radiographs confirmingthe presence of nodular opacities are important. It is important toremember that the differential diagnosis for silicosis is extensive andincludes diseases that have a similar presenting profile, includingfungal infections, miliary tuberculosis, sarcoidosis, and idiopathicpulmonary fibrosis.
For both chronic and accelerated silicosis, chest radiography usually
reveals nodular opacities in the upper lung field. Thoracic lymph nodescalcify in a characteristic pattern, often referred to as “eggshell”calcification. However, this eggshell pattern of lymph node calcifica-tion is not specific and may also be seen with sarcoidosis, radiation-treated Hodgkin’s disease, blastomycosis, scleroderma, amyloidosis,and Progressive massive fibrosis is often characterizedby large fibrotic masses in conjunction with a distortion of the lungarchitecture often involving an upward displacement of the mediastinaland hilar structures attributable to volume loss. In addition, lower areas ofthe lung may appear hyperventilated and emphysematous, often inconjunction with multiple bullae.
Acute silicosis may be differentiated from chronic silicosis on chest
X-ray based on the phenomenon of acute alveolar filling, causing aground-glass appearance of the lung fields. Linear opacities in the lowerlobes may foretell the initiation of fibrosis and enlargement of the hilarnodes may also be prominent.
Pathologic findings and chest radiographs may not always
Chest X-rays may demonstrate only minimal changes even in the face ofextensive fibrosis. High-resolution computed tomography of the chest isthe imaging study of choice to evaluate nodules, as well for the detectionof emphysematous pulmonary changes. High-resolution computed to-mography may also help differentiate confluent lesions from simpleOther pulmonary imaging modalities such as magnetic reso-nance imaging and digitized radiography may be useful adjuncts in thediagnosis and monitoring of silicosis.
Pulmonary function tests may be normal early in the course of simple
silicosis. However, with disease progression, a restrictive and/or obstruc-tive pattern may emerge. A reduction in the volume of exhaled air over1 second, as well as reduced forced vital capacity, decreased diffusingcapacity, total lung capacity, and lung compliance, may be manifest insevere cases and in cases of progressive Flow parametersmay be altered due to airway obstruction resulting from fibrosis andconsequent abnormalities of the underlying lung-architecture. It is impor-tant to remember the importance of noting coexisting factors (eg, tobaccosmoking and pulmonary infections) when evaluating pulmonary functiontests. It is also important to remember that bronchoalveolar lavage is notgenerally helpful in diagnosing silicosis as patients exposed to silica mayhave silica and increased protein levels in lung washings, regardless of thestage of the disease or the specific disease
Classiﬁcation of Silicosis
The International Labor Office (ILO) has standardized the radiographic
classification by providing guidelines for grading A varietyof factors are taken into consideration when grading cases of silicosis,including the degree of pleural involvement as well as the size, shape, andprofusion of The quality of the X-ray image is also a criticalfactor in that poor-quality X-rays may be confounding and interfere withaccurate radiological classification.
Based on ILO standards, round pulmonary nodules measuring 1.5 to 3
mm are designated as “p
,” and those measuring 3 to 10 mm are designated“r
.” Irregularly shaped nodules are termed “s
,” and “u
.” Largenodules are designated “A
” if each is larger than 1 cm and the aggregatediameters are less than 5 cm; “B
” nodules are larger than 5 cm and havean aggregate diameter less than that of the right upper lobes, and “C
”nodules have a combined area larger than the right upper lobe. Concom-itant pleural involvement is characterized with regard to the presence anddegree of calcification, thickening, or effusion.
Treatment of Silicosis
A variety of treatment modalities aimed at decreasing the pulmonary
inflammatory response to silica are available. However, no consistentlyeffective treatment regimen has yet been developed. The use of whole-lung lavage techniques may improve symptoms in some patients. How-ever, these patients usually do not demonstrate sustained improvement inpulmonary function Corticosteroids and aluminum citratehave been used in pharmacologic treatment protocols with varyingsuccess for silicosis. One limited, controlled study did demonstrate animprovement in both inflammatory bronchoalveolar lavage and pulmo-nary function tests when corticosteroids were Anotherreport indicated acute silicosis was reversed by corticosteroid However, most authorities believe that corticosteroids have, at best,limited efficacy in the treatment of silicosis. The administration ofinhaled aluminum citrate powder theoretically coats silica particlesretained within the lung, thus reducing the solubility of these particles.
Some controlled studies have shown a degree of symptomatic improve-ment using inhaled aluminum citrate; however, no change in either theobjective disease parameters or overall mortality was Adverse effects may be associated with the administration of aluminumcitrate and these may outweigh any positive treatment outcome. Based onserial chest radiographs, pulmonary function tests, and pulmonary lavage,
aluminum lactate aerosols did not favorably influence the course of thedisease in silicotic
-oxide (PVPNO) has been shown to concentrate
silica particles inside of cells and consequently has improved thefunctional capabilities of some patients by slowing the course of dis-PVPNO, acting as a hydrogen acceptor, has been shown to coatthe surface of silica particles and thereby decrease the potential for silicatoxicity in both in vitro and in vivo PVPNO decreases thegeneration of reactive oxygen species and possibly reduces silica-inducedDNA damage by selectively blunting the active sites at the particleHowever, animal studies suggest that the efficacy of PVPNOmay be limited by its potential for kidney and liver toxicity. Othertherapies that are currently being evaluated include the use of alveolarmacrophage inhibitors and monoclonal antibodies directed against
Unfortunately, none of the currently proposed therapies have clearly
reduced the mortality associated with silicosis. Consequently it is criti-cally important that comorbid problems, such as mycobacterial infections,tuberculosis, and other pulmonary infections, be identified and treatedpromptly in all silicosis patients. Symptomatic patients with chest X-rayssuggestive of silicosis should have a purified protein derivative placedintradermally as soon as possible and a positive purified protein derivativeshould prompt consideration of antituberculous therapy. Steroid therapyshould not commence until it is clear that any coexisting mycobacterialinfection has resolved. Some authorities have suggested that patientsshould be treated empirically with isoniazid during steroid therapy toprevent activation of undiagnosed mycobacterial Individ-uals diagnosed with silicosis should be promptly removed from anyfurther exposure to silica and treated with bronchodilators and supple-mental oxygen as required.
Illnesses Associated with Silicosis
A variety of illnesses have been identified as being associated with the
different forms of silicosis as follows.
Early observers noted that silicosis and tuberculosis frequently coex-
isted. The clinical introduction of radiography, as well as the introductionof tuberculin tests and sputum staining, allowed physicians to distinguishsilicosis from other respiratory diseases, including tuberculosis. Today,the risk of developing tuberculosis has been substantially reduced by
improved respiratory dust protection as well as the development ofantibiotics active against mycobacteria. Nevertheless, mycobacterial in-fections continue as common complications associated with all forms ofSilicotic patients are often diagnosed with atypical mycobac-teria, including Mycobacterium avium intracellulare
and M. kansasii
. Thestandard of care for all patients suffering from silicosis requires athorough search for the presence of mycobacterial species, especially ifthere are any documented functional or clinical declines in the patients’condition.
Currently, much controversy exists with regard to the potential carci-
nogenicity of inhaled In 1987, the International Agency forResearch on Cancer (IARC) stated that despite “sufficient evidence” thatsilica poses a carcinogenic threat to laboratory animals, there was only“limited evidence” to link silica to human carcinogenicity. At that time,silica was classified by IARC as a Group 2B carcinogen (“probablycarcinogenic” to An IARC subgroup subsequently reclassifiedcrystalline silica as a Group 1 carcinogen (“carcinogenic to humans”)based on an exhaustive reevaluation of the literature published through
A review of the literature was undertaken in 2000 by another group of
researchers using different inclusion and exclusion criteria from the onesemployed for the 1997 IARC investigation. This more recent review didnot find any evidence for a causal association between silicosis and lungThis assessment included studies that were not confounded bysmoking or known exposure to specific occupational carcinogens. Theassessment also looked at studies that were essentially free of bias, thatused appropriate reference groups, and that did not involve compensationagreements. However, studies that could have included confoundingexposures to chemicals such as radon, arsenic, or polycyclic aromatichydrocarbons were not excluded as long as there was no demonstratedassociation with silicosis. According to a recently promulgated evidence-based statement from the ACOEM, the risk for cancer in silicotic persons“appears to be greatest in workers with silicosis who smoke.” TheACOEM document goes on to state “the cancer risk to silica-exposedworkers without silicosis (especially if they are not smokers) is less cleardespite continuing research, some of which has yielded disparate re-
One study was unable to demonstrate an increase in the risk for lung
cancer among silicosis patients who had a history of chronic bronchitis or
The same study reported that the risk for lung cancer wasincreased in those patients who did not have either chronic bronchitis orThese investigators theorized that the presence of obstructivepulmonary disease may cause silica to be deposited in the more proximalregions of the lung preferentially, thereby potentially decreasing the riskof silicosis and lung With regard to the question of a causalassociation between silicosis and lung cancer, the main scientific uncer-tainty involves whether the lung cancer rates reported in descriptivestudies are confounded by smoking history, socioeconomic status differ-ences, and inappropriate comparison populations. It is also possible thatsome exposure-response studies may have failed to identify a realrelationship between silica exposure and lung cancer (if one exists). It isimportant to note that significant cancer risks in subjects listed on silicosisregistries in the past may have been the result of selection and diagnosticbias. Consideration of the possible relationship between silica exposureand lung cancer conferring the same increased risk to subjects withoutsilicosis and whether it is justifiable to assume that quartz and cristobalitehave similar health effects are all important
It has been suggested that silicosis may be associated with rheumatoid
arthritis, scleroderma, lupus, and progressive systemic Some silicosis patients may have serum antinuclear antibodies, rheuma-toid factor, and elevated serum concentrations of various immunoglobu-lins and immune In addition, renal disease without pulmo-nary changes has been associated with silica exposure and may manifestas nephritic syndrome or renal failure. Specifically, some workers whoare involved in the production of industrial sand, as well as ceramic andgranite workers, reportedly have an increased incidence of end-stage renalAn increased incidence of renal disease, including nephriticsyndrome and glomerulonephritis, has been reported in Bedouin tribespeople who are exposed to frequent dust storms, as well as individualswho may have consumed water contaminated with In such cases,immune complexes located in the glomerulus may be responsible for therenal
Preventative Measures Against Silicosis
Ever since the first century A.D. when Pliny the Elder recommended
that miners “envelop their faces with loose bladders, which enable themto see without inhaling the fatal virtually all occupational
regulatory bodies have advocated the use of respiratory protection againstexposure to potentially hazardous industrial dusts.
Today, a variety of engineering controls and personal protective
measures have been developed for sandblasters. Fully enclosed andventilated blasting chambers may be utilized to minimize human expo-sure to the dust generated during these operations. These chamberscontain a series of baffles designed to selectively extract dust from thechamber environment. The venting system maintains a slight negativepressure within the chamber to pull the exhausted air away from theworkers’ zone of inhalation.
Personal protective equipment is recommended for sandblasters and
others working in similar environments. This equipment includes cover-alls, boots, and properly fitted helmets supplied with filtered air. Blastingchambers and ventilation-filtration systems should be inspected and testedfor integrity and functionality on a regular basis and workers should notspend extended periods of time inside a blasting chamber. A designatedobserver should oversee the process from a vantage point outside thechamber.
Open-air sandblasting may not be as well monitored or controlled as
closed sandblasting chambers. This type of sandblasting optimally shouldoccur a safe distance away from other workers, and adequate ventilationshould be provided. Workers employing open air sandblasting techniquesshould wear adequate respiratory protection. If the abrasive being usedcontains silica, the respirator should be a type “CE,” pressure-demand,abrasive-blast-supplied air respirator having an assigned protection factorrating of 2000.
Federal guidelines have been established to minimize worker exposure
to silica particles. The current permissible exposure limit for occupationalexposure to respirable crystalline silica, as promulgated by OSHA, is an8-hour, time-weighted average of 10 mg per cubic millimeter of air. Thisis two hundred times the recommended exposure limit currently promul-gated by In 2001, the American Conference of IndustrialHygienists adopted a threshold limit value of 0.05 mg/m3 for respirablecrystalline This parallels the recommended exposure limitproposed by NIOSH in Internationally, standards may differ. Inthe U.S., sandblasting abrasive should contain less than 1% free silica,whereas in Great Britain, industrial abrasives containing silica werebanned in 1950.
Silicosis-associated mortality has decreased over the last several de-
cades. In the 1920s and 1930s, there were roughly 1000 deaths annuallyattributed to However, during the most recent several decades,
silicosis mortality has declined to less than 200 deaths per year in the lateDespite this improvement in statistics, regulatory complianceis often difficult to monitor, and violations may occur. A 1983 reportrevealed that a substantial number of U.S. foundries reportedly did notpractice control of silica inhalation, and approximately one-third of theworkers at these sites may have been exposed to airborne silica parti-NIOSH’s 2002 Work-Related Lung Disease Surveillance Report
indicates that, from 1993 to 1999, a total of 16 states had geometric meanrespirable quartz exposure levels in non-mining industries exceeding therecommended exposure limit of 0.05 mg/m3, as determined by samplesobtained by NIOSH research further reported that silicosis casestend to be associated with worksites using silica-based abrasives, as wellas worksites with poor ventilation and poorly controlled work In addition, worksites with inadequate respiratory protection and work-sites that have not established medical surveillance programs are reportedto be at higher risk for Samples collected during inspectionsof the construction and fabricated metal product industries revealedthat over one-third of samples exceeded the permissible exposureConsequently, it is clear that continued efforts are needed totrain and supervise workers to promote worker safety with regard tosilica exposure.
The 1987 NIOSH Sentinel Event Notification System for Occupational
Risks program advocated case-based surveillance and follow-upmeasures for occupational injury and disease associated with silicosis,as well as a variety of other occupational health conditions. With aseven-state network, silicosis and silica exposure are monitored viaphysician/hospital reporting, death certificates, and worker’s compen-sation In 1996, OSHA began a so-called “Special EmphasisProgram” to reduce or eliminate the occupational incidence of silicosisarising from exposure to crystalline silica. This program focused onworkplace inspections where silica exposure was expected.Consequentto IARC’s reclassification of crystalline silica as a human carcinogenicagent, there has been considerable controversy regarding the need tolower permissible exposure
Silicosis has been a historically important occupational disease and
continues to be a concern. Workers who may be exposed to highconcentrations of free crystalline silica in unprotected settings may be atrisk for developing pulmonary fibrosis, mycobacterial infection includingtuberculosis, autoimmune disease, and lung cancer.
To reduce the incidence of industrial silica exposure, it is important to
evaluate the degree of exposure, type, and source of exposure. Optimally,silica-containing materials should be replaced; work processes should beisolated and enclosed; adequate ventilation should be provided, and personalprotective equipment used at all times of possible silica exposure. Even withsuch measures, some settings may witness rates of exposure that exceedOSHA Silicosis is expected to be an occupational medicalconcern for the foreseeable future on a worldwide scale since manycountries do not maintain or enforce appropriate regulations controllingsilica exposure for workers.
Muetterties M, O’Halloran Schwarz L, Wang R. Sandblasters. In: Greenberg M,editor. Occupational, Industrial, and Environmental Toxicology, 2nd ed. Philadel-phia, PA: Mosby, 2003.
American Conference of Governmental Industrial Hygienists. Threshold limit valuesand biological exposure indices. American Conference of Governmental IndustrialHygienists (ACGIH): Cincinnati, OH, 2002.
Valiante DJ, Schill DP, Rosenman KD, et al. Highway repair: a new silicosis threat.
Am J Public Health 2004;94(5):876-80.
Hunter D. The Disease of Occupations. Little, Brown, Boston, MA: 1962.
Jordan J. Hawk’s Nest. West Virginia Historical Society Quarterly 1998;12(1):1-3.
Cherniak M. The Hawk’s Nest Incident: America’s Worst Industrial Disaster. NewHaven, CT: Yale University Press, 1986.
Occupational Safety and Health Administration (OSHA). 1218-AB70-2040. Occupa-tional Exposure to Crystalline Silica. OSHA: 2004; 9, 2004).
National Institute for Occupational Safety and Health (NIOSH). Work-RelatedLung Disease Surveillance Report 2002. Publication No. 2003-111; Cincinnati,OH: National Institute for Occupational Safety and Health, 2003.
Mossman BT, Churg A. Mechanisms in the pathogenesis of asbestosis and silicosis.
Am J Respir Crit Care Med 1998;157(5 Pt 1):1666-80.
Williamson BJ, Pastiroff S, Cressey G. Piezoelectric properties of quartz andcristobalite airborne particulates as a cause of adverse health effects. Atmos Environ2001;35:3539-42.
Castranova V. Signalling pathways controlling the production of inflammatorymediators in response to crystalline silica exposure: role of reactive oxygen/nitrogen species. Free Radic Biol Med 2004;37(7):916-25.
Wiessner JH, Henderson Jr, JD Sohnle PG, et al. The effect of crystal structure onmouse lung inflammation and fibrosis. Am Rev Respir Dis 1988;138(2):445-50.
Zaidi SH, King EJ, Harrison CV, et al. Fibrogenic activity of different forms of freesilica; the action of fused silica, quartz, cristobalite, and tridymite on the livers ofmice. AMA Arch Ind Health 1956;13(2):112-21.
King EJ, Mohanty GP, Harrison CV, et al. The action of flint of variable sizeinjected at constant weight and constant surface into the lungs of rats. Br J Ind Med1953;10(2):76-92.
American College of Occupational and Environmental Medicine. Policy andPosition Statement: Medical surveillance of workers exposed to crystalline silica.
U.S. Environmental Protection Agency (EPA). Compilation of Air PollutantEmission Factors, AP-42. In: Stationary Point and Area Sources, 5th ed., Vol. 1.
Washington, DC: EPA, 1995.
Susi P. New abrasive blasting methods needed. OnCenter: the newsletter of thecenter to protect workers’ rights (CPWR). 2004;4(1):3.
Fujimura N. Pathology and pathophysiology of pneumoconiosis. Curr Opin PulmMed 2000;6(2):140-4.
Dubois CM, Bissonette E, Rola-Pleszczynski M. Asbestos fibers and silica particlesstimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatoryrole of leukotriene B4. Am Rev Respir Dis 1989;139(5):1257-64.
Hoffman EO, Lamberty J, Pizzolato P, et al. The ultrastructure of acute silicosis.
Arch Pathol 1973;96(2):104-7.
Dalal NS, Shi XL, Vallyathan V. ESR spin trapping and cytotoxicity investigationsof freshly fractured quartz: mechanism of acute silicosis. Free Radic Res Commun1990;9(3-6):259-66.
Heffner JE, Repine JE. Pulmonary strategies of antioxidant defense. Am RevRespir Dis 1989;140(2):531-54.
Fubini B, Hubbard A. Reactive oxygen species (ROS) and reactive nitrogen species(RNS) generation by silica in inflammation and fibrosis. Free Radic Biol Med2003;34(12):1507-16.
Ding M, Chen F, Shi X, et al. Disease caused by silica: mechanisms of injury anddisease development. Int Immunopharmacol 2002;2(2-3):173-82.
Surrat P, Winn W, Brody A. Acute silicosis in tombstone sandblasters. Am RevRespir Dis 1977;115:521.
Miller BE, Bakewell WE, Katyal SL, et al. Induction of surfactant protein (SP-A)biosynthesis and SP-A mRNA in activated type II cells during acute silicosis in rats.
Am J Respir Cell Mol Biol 1990;3(3):217-26.
Oghiso Y, Kubota Y. Enhanced interleukin 1 production by alveolar macrophagesand increase in Ia-positive lung cells in silica-exposed rats. Microbiol Immunol1986;30(11):1189-98.
Schmidt JA, Oliver CN, Lepe-Zuniga JL, et al. Silica-stimulated monocytes releasefibroblast proliferation factors identical to interleukin 1. A potential role for interleukin1 in the pathogenesis of silicosis. J Clin Invest 1984;73(5):1462-72.
Davis GS, Pfeiffer LM, Hemenway DR. Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in murine silicosis. J Environ Pathol ToxicolOncol 1998;17(2):99-114.
Yucesoy B, Vallyathan V, Landsittel DP, et al. Association of tumor necrosisfactor-alpha and interleukin-1 gene polymorphisms with silicosis. Toxicol ApplPharmacol 2001;172(1):75-82.
Takemura T, Rom WN, Ferrans VJ, et al. Morphologic characterization of alveolarmacrophages from subjects with occupational exposure to inorganic particles. AmRev Respir Dis 1989;140(6):1674-85.
Bagchi N. What makes silica toxic? Br J Ind Med 1992;49(3):163-6.
Heppleston AG, Styles JA. Activity of a macrophage factor in collagen formationby silica. Nature 1967;214(87):521-2.
Nagelschmidt G. The relation between lung dust and lung pathology in pneumo-coniosis. Br J Ind Med 1960;17:247-59.
King EJ, Mohanty GP, Harrison CV, et al. The action of different forms of puresilica on the lungs of rats. Br J Ind Med 1953;10(1):9-17.
Symanski H. Delayed onset sandstone pneumoconiosis: a case report. Am J IndMed 1981;2(2):101-102.
Cohen C, Fireman E, Ganor E, et al. Accelerated silicosis with mixed-dust pneumo-coniosis in a hard-metal grinder. J Occup Environ Med 1999;41(6):480-5.
Duchange L, Brichet A, Lamblin C, et al. Acute silicosis. Clinical, radiologic,functional, and cytologic characteristics of the broncho-alveolar fluids. Observa-tions of 6 cases. Rev Mal Respir 1998;15(4):527-34.
Banks DE, Morring KL, Boehlecke BA, et al. Silicosis in silica flour workers. AmRev Respir Dis 1981;124(4):445-50.
Banks DE, Bauer MA, Castellan RM, et al. Silicosis in surface coalmine drillers.
Castranova V, Kang JH, Ma JK, et al. Effects of Bisbenzylisoquinoline alkaloids onalveolar macrophages: correlation between binding affinity, inhibitory potency, andantifibrotic potential. Toxicol Appl Pharmacol 1991;108(2):242-52.
Gross BH, Schneider HJ, Proto AV. Eggshell calcification of lymph nodes: anupdate. AJR Am J Roentgenol 1980;135(6):1265-8.
Wagner GR, Attfield MD, Parker JE. Chest radiography in dust-exposed miners:promise and problems, potential and imperfections. Occup Med 1993;8(1):127-41.
Begin R, Bergeron D, Samson L. Assessment of silicosis in exposed workers. AJRAm J Roentgenol 1987;148(3):509-14.
Cowie RL. The influence of silicosis on deteriorating lung function in gold miners.
Wang XR, Christiani DC. Respiratory symptoms and functional status in workersexposed to silica, asbestos, and coal mine dusts. J Occup Environ Med 2000;42(11):1076-84.
ILO (International Labor Office). Classification of radiographs of the pneumoco-niosis. ME Rad Photogr 1981;57(1):2-17.
International Labor Office. Guidelines for the use of the ILO International Classifica-tion of radiographs of Pneumoconiosis. Revised Edition 2000. International laborOrganization, Geneva, Switzerland.
Banks DE, Cheng YH, Weber SL, et al. Strategies for the treatment of pneumon-coniosis. Occup Med 1993;8(1):205-32.
Sharma SK, Pane JN, Verma K. Effect of prednisolone treatment in chronicsilicosis. Am Rev Respir Dis 1991;143(4 Pt 1):814-21.
Goodman GB, Kaplan PD, Stachura I, et al. Acute silicosis responding tocorticosteroid therapy. Chest 1992;101(2):366-70.
Kennedy MC. Aluminium powder inhalations in the treatment of silicosis of potteryworkers and pneumonconiosis of coal-miners. Br J Ind Med 1956;13(2):85-101.
Begin R, Masse S, Dufresne A. Further information on aluminium inhalation insilicosis. Occup Environ Med 1995;52(11):778-80.
Chen SY, Lu XR. Clinical studies of the therapeutic effect of kexiping on silicosis.
In: Institute of Occupational Medicine: Proceedings of the Therapeutic Effect ofKexiping on Silicosis; Beijing: CAPM Press, 1970.
Graham WG. Silicosis. Clin Chest Med 1992;13(2):253-67.
Chang KC, Leung CC, Tam CM. Tuberculosis risk factors in a silicotic cohort inHong Kong. Int J Tuberc Lung Dis 2001;5(2):177-84.
Chan CK, Leung CC, Tam CM, et al. Lung cancer mortality among a cohort of menin a silicotic register. J Occup Environ Med 2000;42(1):69-75.
Steenland K, Sanderson W. Lung cancer among industrial sand workers exposed tocrystalline silica. Am J Epidemiol 2001;153(7):695-703.
International Agency for Research on Cancer (IARC). Silica, crystalline mono-graphs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 68.
Lyon, France: International Agency for Research on Cancer; 1997.
International Agency for Research on Cancer (IARC). Silica, some silicates, coaldust and para-aramid fibrils. In: IARC: IARC Monograph on the Evaluation ofCarcinogenic Risks to Humans. Vol. 68. Lyon, France: International Agency forResearch on Cancer; 1997.
Hessel PA, Gamble JF, Gee JB, et al. Silica, silicosis, and lung cancer: a responseto a recent working group report. J Occup Environ Med 2000;42(7):704-20.
Cocco P, Rice CH, Chen JQ, et al. Non-malignant respiratory diseases and lungcancer among Chinese workers exposed to Silica. J Occup Environ Med 2000;42(6):639-44.
Soutar CA, Robertson A, Miller BG, et al. Epidemiological evidence on thecarcinogenicity of silica: factors in scientific judgement. Ann Occup Hyg 2000;44(1):3-14.
Brown LM, Gridley G, Olsen JH, et al. Cancer risk and mortality patterns amongsilicotic men in Sweden and Denmark. J Occup Environ Med 1997;39(7):633-8.
Doll NJ, Stankus RP, Hughes J, et al. Immune complexes and autoantibodies insilicosis. J Allergy Clin Immunol 1981;68(4):281-5.
Koeger AC, Lang T, Alcaix D, et al. Silica-associated connective tissue disease. Astudy of 24 cases. Medicine (Baltimore) 1995;74(5):221-37.
McDonald AD, McDonald JC, Rando RJ, et al. Cohort mortality study of NorthAmerican Industrial Sand Workers. I. Mortality from lung cancer, silicosis andother causes. Ann Occup Hyg 2001;45(3):193-9.
Rapiti E, Sperati A, Miceli M, et al. End stage renal disease among ceramic workersexposed to silica. Occup Environ Med 1999;56(8):559-61.
Goldsmith JR, Goldsmith DF. Fiberglass or silica exposure and increased nephritisor ESRD (end-Stage renal disease). Am J Ind Med 1993;23(6):873-81.
Osorio AM, Thun MJ, Novak RF, et al. Silica and glomerulonephritis: case reportand review of the literature. Am J Kidney Dis 1987;9(3):224-30.
Brown HV. The history of industrial hygiene: a review with special reference tosilicosis. Am Ind Hyg Assoc J 1965;26(3):212-26.
Oudiz J, Brown JW, Ayer HE, et al. A report on silica exposure levels in UnitedStates foundries. Am Ind Hyg Assoc J 1983;44(5):374-6.
National Institute for Occupational Safety and Health (NIOSH). Request forAssistance in Preventing Silicosis and Deaths from Sandblasting: Alert. NIOSHPublication No. 92-102; U.S. Department of Health and Human Services, U.S.
Government Printing Office: Washington, DC, 1992.
National Institute for Occupational Safety and Health (NIOSH). Criteria for aRecommended Standard: Occupational Exposure to Crystalline Silica. DHEWPublication 75-120. Washington, DC: U.S. Department of Health, Education, andWelfare, Public Health Service, Centers for Disease Control, 1974.
National Institute for Occupational Safety and Health (NIOSH). Work-RelatedLung Disease Surveillance Report 1999. Publication No. 2000-105. Cincinnati,OH: National Institute for Occupational Safety and Health, 1999.
Centers for Disease Control: Surveillance fir silicosis, 1993—Illinois, Michigan,New Jersey, North Carolina, Ohio, Texas, and Wisconsin. MMWR 1997;46(No.
Occupational Safety and Health Administration (OSHA). National News ReleaseUSDL: 96-172. Washington, DC, Occupational Safety and Health Administration,May 8, 1996.
Rosenman KD, Reilly MJ, Rice C, et al. Silicosis among foundry workers.
Implication for the need to revise the OSHA standard. Am J Epidemiol 1996;144(9):890-900.
Valiante DJ, Rosenman KD. Does silicosis still occur? JAMA 1989;262(21):3003-7.
Material Safety Data Sheet Albendazole MSDS Section 1: Chemical Product and Company Identification Product Name: Albendazole Contact Information: Catalog Codes: SLA3505 Sciencelab.com, Inc. 14025 Smith Rd. CAS#: 54965-21-8 RTECS: FD1100000 US Sales: 1-800-901-7247 International Sales: 1-281-441-4400 TSCA: TSCA 8(b) inventory: No products were found. CI#: Not
cambells mushroom soup hungry Jack boxed mashed potatoes water, mushrooms, cream (milk), vegetable oil potato flakes ( sodium bisulfite , bha and citric acid ( corn, cottonseed, canola and/or soybean ), added to protect color and flavor), contains 2% or modified food starch , contains less than 2 % of: less of: monoglycerides , partially hydrogenated bleached enriched flo