Mohammad Tohidi M.D. Professor of Internal Medicine Department of Pulmonary Medicine Ghaem Hospital MUMS Mashh

1. Mohammad Tohidi M.D. Professor of Internal Medicine Department of Pulmonary Medicine Ghaem Hospital MUMS Mashhad IRAN

2. Silicosis

3. Case Scenario(1) • 57 year old retired non-smoker man referred with the cc of dry cough for 1year.In addition he has had mild ED but no other complaint. Past Hx & system review were negative.His VS,general PE & chest exam were normal.Chest X ray showed diffuse reticulonodular pattern There were no hilar enlargement & calcification.

4. Case Scenario(2) • HRCT scan of the lung revealed small rounded opacities & thickening of alveolar septa no ground glass pattern,hilar adenopathy & pleural effusion.He had >30 years Hx of stone cutting & grinding.With this Hx & immaging studies, in the absence of another causes,diagnosis of simple silicosis was apparent.

9. DEFINITION • Silicosis is a fibrotic lung disease attributable to the inhalation of crystalline silica, usually in the form of quartz and, less commonly, as cristobalite and tridymite • Amorphous silica is relatively nontoxic

10. Introduction • Silicosis (also known as Grinder's disease and Potter's rot) is a form of occupational lung disease caused by inhalation of crystalline silica dust, and is marked by inflammation and scarring in forms of nodular lesions in the upper lobes of the lungs.

11. Where’s it come from? Crystalline forms of silica (Silicon Dioxide or SiO2) include quartz, cristobalite, and tridymite. Quartz is the most common type, and is a major component of rocks including granite, slate, and sandstone.

13. Silica • Silica is the second most common mineral on earth. It is found in sand, many rocks such as granite, sandstone, flint and slate, and in some coal and metallic ores.

14. Silica • The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine silica dust.

15. Silicosis – history • This respiratory disease was first recognized in 1705 by Ramazzini who noticed sand-like substances in the lungs of stonecutters

16. Silicosis – history Full description by Bernardino Ramazzini (1633-1714) in early 18th century. “...when the bodies of such workers are dissected, they have been found to be stuffed with small stones.”Diseases of Workers (De Morbis Artificum Diatriba, 1713).

17. Silicosis – history • The name silicosis (from the Latin silex or flint) was attributed to Visconti in 1870

18. Silicosis - history • First U.S. description in 19th century. • Term silicosis introduced in 1870, from Latin silex, or flint. • Prevalence increased markedly with introduction of mechanized mining. • Came to national attention 1930-1931 with construction of Hawk’s Nest Tunnel in Gauley Bridge, West Virginia. Called “the worst industrial accident in U.S. history.” At least 764 tunnel workers died from silicosis. Hawk’s Nest disaster led to Congressional hearings in 1936, and new laws protecting workers in many states. • Prevalence of silicosis has greatly declined in recent decades because of effective industrial hygiene measures.

19. Silicosis - history • The full name for this disease when caused by the specific exposure to fine silica dust found in volcanoes is pneumonoultramicroscopicsilicovolcanoconiosis, and at 45 letters it is the longest word in any of the major English dictionaries.

20. Silicosis - history • The prevalence of silicosis led some men to grow what is called a miner's mustache, in an attempt to intercept as much dust as possible.

21. Diseases Associated with Exposure to Silica Dust(1) • Silicosis Chronic silicosis Accelerated silicosis Acute silicosis (silicoproteinosis)(fine dust, intense exposure , high silica) Progressive massive fibrosis • Chronic Obstructive Pulmonary Disease Emphysema Chronic bronchitis Mineral dust-induced small airway disease

22. Diseases Associated with Exposure to Silica Dust(2) Lung CancerMycobacterial InfectionMycobacterium tuberculosis Nontuberculous Mycobacteria Immune-Related DiseasesProgressive systemic sclerosis Rheumatoid arthritis Chronic renal disease Systemic lupus erythematosus

23. Pulmonary Toxicology • Particle size is critical. • Peak dust inhalation occurs with particles having a diameter of 0.5 to 3 microns (μm). • RCS is invisible to the human eye. • Pulmonary clearance mechanisms: macrophages & the mucociliary escalator

24. The induction period between initial silica exposure and development of radiographically detectable nodular silicosis is usually 10 years. Shorter induction periods are associated with heavy exposures, and acute silicosis may develop within 6 months to 2 years following massive silica exposure.

25. Silicosis is an occupational hazard to mining, sandblasting, quarry, ceramics and foundry workers, as well as grinders, stonecutters and those continually exposed to silica dust.

26. Variety of occupations • Construction, and surface and underground rock drilling • Foundries are also a main source of silica dust • workers involved with the repair, rehabilitation, or demolition of concrete structures

27. Variety of occupations • New types of pneumoconiosis often turn out to be silicosis in an industry not previously thought to be at risk or a mixed-dust pneumoconiosis in which silica is implicated with other dusts • Silicosis is often the result of exposure in the remote past and not in the current workplace

28. Pathology(1) • When small silica dust particles are inhaled, they can embed themselves deeply into the tiny alveolar sacs and ducts in the lungs, where oxygen and carbon dioxide gases are exchanged. There, the lungs cannot clear out the dust by mucous or coughing

29. Pathology(2) • Characteristic lung tissue pathology in nodular silicosis consists of fibrotic nodules with concentric "onion-skinned" arrangement of collagenfibers, central hyalinization, and a cellular peripheral zone, with lightly birefringent particles seen under polarized light

31. Pathology(3) • In acute silicosis, microscopic pathology shows a periodic acid-Schiff positive alveolar exudate (alveolar lipoproteinosis) and a cellular infiltrate of the alveolar walls

32. Silicosis

33. PATHOGENESIS(1) • There is agreement that freshly fractured silica, such as that generated during sandblasting, is more toxic to the alveolar macrophages than is "aged" silica • clay components, may adhere to the surfaces of silica particles, producing "coated" silica, which is less toxic than uncoated silica dust • the incidence of silicosis is decreased by concomitant exposure to other dusts

34. PATHOGENESIS(2) 4 The intensity of the exposure determines the nature of the lung injury. Low-intensity exposure generally produces aggregates of fibrosis with relative sparing of the lung architecture, whereas high-intensity exposure causes widespread pulmonary inflammation and collagen deposition 5 Individual susceptibility to the disease may play a role

35. Particles engulfed by macrophages: transported upward and removed from lungs retained in the lung “Frustrated Phagocytosis” cascade of toxic effects inflammatory process pneumoconiosis fibrosis in the lung tissue

36. Pathogenesis(3) • When fine particles of silica dust are deposited in the lungs, macrophages that ingest the dust particles will set off an inflammation response by releasing tumor necrosis factors, interleukin-1, leukotriene B4 and other cytokines. In turn, these stimulate fibroblasts to proliferate and produce collagen around the silica particle, thus resulting in fibrosis and the formation of the nodular lesions

37. Pathogenesis(4) • Furthermore, the surface of silicon dust can generate silicon-based radicals that lead to the production of hydroxyl and oxygen radicals, as well as hydrogen peroxide, which can inflict damage to the surrounding cells

38. Silicosis • MC chronic occupational disease in the world • caused by inhalation of crystalline silicon dioxide (silica). • Acute silicosis -accumulation of a lipoproteinaceous material within alveoli • Chronic silicosis - slowly progressing, nodular, Fibrosing pneumoconiosis • Pathogenesis • crystalline forms -more fibrogenic (quartz –worst) • silica particles lung macrophages ingest them  activation and release of mediators  IL-1, TNF, oxygen-derived free radicals • Anti-TNF monoclonal antibodies can block lung collagen accumulation in mice • Morphology. • Early stages –tiny nodules in the upper zones • disease progresses–nodules coalesce into hard, collagenous scarscentral softening and cavitation (due to superimposed tuberculosis or to ischemia) • X-ray–egg shell calcification in the lymph nodes • Advanced stage - PMF • Histology • Nodular lesions -concentric layers of hyalinized collagen surrounded by a dense capsule • Birefringent silica particles in polarized microscopy

39. EPIDEMIOLOGY • The prevalence of silicosis is difficult to estimate • the reported cases have been estimated to represent only one third of the total cases of silicosis • In calculating an individual's risk for silicosis, duration and intensity of exposure are of primary interest but peak exposure also may be important.

40. EPIDEMIOLOGY(cont’d) • In the United States, NIOSH has estimated that at least 1.7 million workers are exposed to silica, of whom between 1500 and 2360 will develop silicosis each year

41. Prevalence • Silicosis is the most common occupational lung disease worldwide, it occurs everywhere but is especially common in developing countries

42. Silicosis deaths - decliningwww.cdc.gov/mmwr1,157 (1968) 148 (2002)

43. CLINICAL FEATURES(1) • The main symptom is breathlessness, first noted during exertion and later at rest as the large working reserve of the lung is diminished. In chronic silicosis, in the absence of other respiratory disease, even this symptom may be absent • a patient with chronic silicosis may present without symptoms for assessment of an abnormal chest radiograph

44. CLINICAL FEATURES(2) • The appearance of breathlessness may mark the development of a complication such as progressive massive fibrosis or tuberculosis, or may reflect associated airway disease • Cough and sputum production are common symptoms and usually relate to chronic bronchitis, but may reflect the development of tuberculosis or lung cancer

45. CLINICAL FEATURES(3) • Chest pain is not a feature of silicosis, nor are systemic symptoms such as fever and weight loss, which should be attributed to tuberculosis or lung cancer until proven otherwise. • Clubbing is also not a feature of silicosis

46. CLINICAL FEATURES(4) • In accelerated and acute silicosis, the time scale of symptom evolution is in years or months rather than decades. In acute silicosis, breathlessness may become disabling within months, followed by impaired gas exchange Cyanosis Cor pulmonale Respiratory insufficiency

47. Patients with silicosis are particularly susceptible to tuberculosis (TB) infection - known as silicotuberculosis. The reason for the increased risk - 10-30 fold increased incidence - is not well understood. It is thought that silica damages pulmonary macrophages, inhibiting their ability to kill mycobacteria

48. Types of Silicosis (1) Chronic silicosis Occurs after 15-20 years of exposure to moderate to low levels of silica dust. Chronic silicosis itself is further subdivided into: simple complicated silicosis(PMF)

49. Chronic silicosis • This is the most common type of silicosis. Patients with this type of silicosis may not have obvious symptoms, so a chest X-ray is necessary to determine if there is lung damage.

50. (2) Asymptomatic silicosis Early cases of the disease do not present any symptoms