Financial Disclosure Statement Something Old, Something New, - - PDF document

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Occupational and Environmental Lung Disease: Something Old, Something New, Something Unbreakable, and Something Blue

Robert Cohen, MD, FCCP

Division of Pulmonary and Critical Care Medicine Northwestern University Feinberg School of Medicine

Financial Disclosure Statement

n I have no relevant financial relationships

Goals of today’s talk

n Something Old:

n Describe recent outbreak of progressive

massive fibrosis n Something New:

n Discuss occupational and environmental

anthracofibrosis n Something Unbreakable:

n Describe hard metal lung disease

n Something Blue:

n Describe Indium Tin Oxide Lung Disease

Case – Something Old

n 55-year-old underground coal miner

from Kentucky

n Underground miner for 23 years n Worked mainly as a roof bolter and

longwall shear operator

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Longwall Shear Operator

1992 1999

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2003

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Resurgence of a Debilitating and Entirely Preventable Respiratory Disease among Working Coal Miners

Blackley DJ, Laney AS, Halldin CN – AJRCCM 2014;190(6):708-709

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1/1/15–8/17/16, a total of 60 patients with PMF

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49 had their radiograph taken during 2016.

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Surveillance data have indicated a resurgence of PMF in recent years, but the cases described in this report represent a large cluster not discovered through routine surveillance.

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416 Case of PMF from 3 Clincs

Blackley et. al. JAMA 319:5 p. 500-501

PMF cases found in retired miners who never participated in NIOSH CWHSP.

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Why don’t miners participate?

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Holes in the social safety net:

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1985 – 2005, employment in the Appalachia coal mining industry declined by 56% due to

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Cost of coal relative to oil and natural gas

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Increased mechanization

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Shift to contract labor n

Fear of job loss

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Fear of disease and associated disability

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Mistrust of government

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Myth that Black Lung Was Eliminated

n 1998 Review of Coal Workers’ Health

Scheme concluded that pneumoconiosis was not a problem

n Changed surveillance program into fitness for

work program

n Anyone could take CXRs and no standards

for whom or how the images were classified

n Images sent to the Government – but not

reviewed

n No central data capture or processing

Black Lung Rediscovered

n Several miners had been diagnosed with

• ther diseases than black lung – i.e.

Sarcoidosis

n Reviewed images which were consistent with

CWP

n Review of chest imaging of random sample of

300 miners found 18 new cases

n The dust hit the fan

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Discovery of Cases Lead to Parliamentary Investigation

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Miners with Black Lung

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Union

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Industry

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Government Regulators

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Thoracic Society

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Radiology Society

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College of Occupational Medicine

Australian Federal Government Australian Federal Government Investigation – February 2016

n Congressional Hearings – 3 days of testimony

n Witnesses from Labor, Industry, Government, and miners

with black lung

“Black lung in whatever form is totally preventable.”

n Dr Brian Plush, Particulate Matter Scientist, University of Wollongong

n “The number 1 thing is to mitigate and control the

dust before the disease even starts.”

n Professor Robert Cohen, Consultant, Queensland Department of

Natural Resources and Mines

n “I said to my wife that if I had found out then that I

was going to be like this I would have got out of the mine straight away. It has buggered my life.”

n Mr Percy Verrall, former coal miner, diagnosed with Coal Workers‘

eumoconiosis in 2015

Queensland Parliament Investigation Report Issued May 2017

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Something New: Anthracofibrosis – Occ and Environmental Disease

n Described 1998 by Chung et. al. n 1320 cases summarized by 2011. Gupta et.

al.

n Associated with biomass fuel exposure n Women n Elderly n Associated with RML syndrome and

segmental atelectasis.

n Pneumonia and cancer implicated as well.

Anthracofibrosis

n Bronchial anthracofibrosis – Pilaniya et. al.

n Obstructive impairments n Decreased 6-minute walk distance n Desaturation. n Most patients were women n Associated with RML syndrome and

segmental atelectasis. n Associated with TB – Kunal et. al.

Anthracofibrosis – Occupation

n Bakers n Farmers n Miners n Dust exposed workers

n Tile factory n Asbestos, coal, slate

Anthracofibrosis – with ILD

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Case – Something Unbreakable

n 55 y/o male with PMH of increasing SOB for

10 years to the point where he cannot climb more than one flight of stairs

n Chronic cough for 10 years with clear, yellow,

• r green sputum production

n 2011 à progressive hypoxemia and bilateral

infiltrates at OSH.

n Underwent VATS with anthracosis with mild

adhesions

Case

n 38 year old man presented with abdominal

pain

n CT abdomen incidentally revealed lower zone

abnormalities in the lungs.

n He had never smoked and had no history of

previous lung disease or drug abuse .

n Examination revealed early clubbing, and

bilateral late inspiratory crackles in the lower zones.

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Case – Continued

n Only job was working 16 years in a company

manufactured machine components made of stainless steel, nickel, chrome, aluminium, bronze and tungsten carbide.

n CT chest showed cystic air spaces and

fibrosis.

n PFTs: mild restriction and obstruction. (TLC

80%, FVC 88% , FEV1 72 % FEV1/FVC 67%, DLCO 37%.

Surgical Path Path Results

n Multinucleated giant cells were found in

airspaces, with a ‘cannibalistic’ appearance typical for giant cell interstitial pneumonitis (GIP ).

n SEM/EDS findings, showed high numbers of

individual metal particles in situ 57/100 consecutive particles contained tungsten.

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History

n Hard metals first manufactured in Germany in

early 1900s.

n Tugsten reacts with carbon and then is “sintered”

with cobalt to make hard metal cutting tools.

n Sintering compacts powdered Tungsten Carbide

into a Cobalt Matrix using very high pressure or heat but without melting.

n Several decades later, case reports of a

pneumoconiosis began to appear with CXR abnormalities.

n HMDLD as GIP described by Liebow -1975

Hard Metal Lung Disease (HMLD)

• r Cobalt Lung

n Occupational lung disease with 3 possible

physiologic reactions:

n Occupational asthma n Hypersensitivity pneumonitis-like syndrome n Giant cell interstitial pneumonia (GIP)

n Exposed to dust in production of tungsten

carbide

n Thought to be related to cobalt use as a

binder with 5-25% when tungsten and carbide are heated

Pathophysiology

n Cobalt is key to the

disease process as animal studies from 1950s with instillation

• f tungsten and cobalt

produced disease, but tungsten alone did not.

n Workers using

diamond-studded tools can use cobalt as well and get the same disease with no exposure to tungsten

PFTs

n Typically show restrictive lung defect with

reduction in DLCO

n This may be reversible in early stages n In end-stage disease, an obstructive defect

may also develop when cystic changes predominate.

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CT Findings: Diffuse centriolobular micronodular opacities in middle and lower lobes (corresponds to centrilobular fibrosis with giant cell accumulation in the airways), Subpleural curvilinear densities, GGOs. May also get extensive reticular opacities, traction bronchiectasis, irregular linear opacities, and/or consolidation.

BAL

n Increased total cell counts n Increased lymphocytes and eosinophils n Decreased CD4/CD8 ratio n May see bizarre multinucleated giant cells

(diagnostic)

n Elemental analysis can be done of these cells

to look for tungsten

Giant Cell Interstitial Pneumonia

Low Power: Centrilobular inflammation and fibrosing lesions High Power: Irregular multinucleated giant cells in alveolar spaces

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Elemental Analysis

n Key in the disease is detection of the

• ffending element which can be done either

liquid (digesting pathologic specimen) or solid (preferred).

n Solid analysis is done with an electron probe

microanalyzer that use spectrometers to detect the various elements

n Normally looking for tungsten

EPMA Data – Moriayam et. al. Diagnostic Criteria for HMLD

n History of hard metal exposure n HRCT chest with centrilobular micronodular

• pacities

n Giant cells on BAL and/or GIP on biopsy n Elemental analysis

Treatment

n First, remove the exposure

n May improve spontaneously

n May add corticosteroid therapy

n Prednisone 40-60 mg/day n Methylprednisolone 1 g/day x 3 days

n May require second agent such as

cyclophosphamide, azathioprine, or cyclosporine.

n Lung transplantation

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And…. Something Blue

nIndium tin oxide – lung

disease

nInterstitial fibrosis nPulmonary alveolar

proteinosis (PAP)

nEmphysema

Indium-Tin Oxide (ITO)

n Main application: liquid crystal displays

(LCDs); other use: touch screens

Indium-Tin Oxide (ITO)

n Indium oxide is a semiconductor doped with tin oxide

to form ITO. The process is also sintering (9 parts indium; 1 part tin)

n Sintering - the process of compacting and forming

a solid material by heat and/or pressure without melting to the point of liquefaction.

n Applied as thin film by “sputtering”

n Sputtering - particles are ejected from a solid

target material due to bombardment by energetic

• particles. Sputter deposition is a physical vapor

deposition of thin film deposition by sputtering.

Toxicology

n Pulmonary

n PAP – in animal studies and humans n Emphysema n Interstitial fibrosis

n Carcinogenicity – no data to suggest a

human carcinogen.

n No data on reproductive effects

• Bomhard. Environ Tox and Pharm 58 (2018) 250-258

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Case Reports and Series

n 2003: Japanese worker, fatal case of

“interstitial pneumonia”; surface grinder x 3 years

n 2005: Japanese worker, same factory, grinder

x 4 years, pulmonary fibrosis

n 2007 Japanese series, 23 workers with CT

changes of fibrosis.

n 2016 Japanese worker with severe

progressive emphysema

High-resolution computed tomography scans on prone position of a worker with no history of smoking, who had been employed at an indium tin oxide target production facility for 7 years (sintering room for 4 years and indium oxide powder room for 3 years). Subpleural interlobular interstitial thickening in both lower lung fields (arrows).

Subclinical interstitial lung damage in workers exposed to indium compounds (Korea). Choi et al Ann Occ Environ Med 2013

U.S. Studies – Cummings et. al.

n Case reports of PAP

n Case 1 - 49 year old reclamation operator,

symptoms began after 9 months, died 7 years later

n Case 2 - 39 year old ITO operator, symptoms began 6-

9 months after hire n Study of ITO workers: 87 workers evaluated –

compared plasma indium to respiratory outcomes

n Correlated with dyspnea, decreased FEV1, and

FVC.

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Pulmonary Alveolar Proteinosis

X-ray analysis of tissue documenting indium and tin

Conclusions:

n Voluntary medical surveillance doesn’t work

without protections for participating workers

n Mandatory medical surveillance doesn’t work

without high quality testing, interpretation, and centralized data collection.

n Always consider occupation in fibrosing lung

disease and COPD – i.e. Anthracofibrosis, HMLD, ITO

n New exposures may result in unusal/rare lung

disease like GIP and PAP

The agent most likely to be the cause of hard metal lung disease is:

A.Diamonds B.Cobalt C.Carbon D.Nickel

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Indium Tin Oxide (ITO) exposure has has been shown to cause all of the following except:

• A. Pulmonary alveolar proteinosis
• B. Emphysema

C.Lung cancer D.Interstitial fibrosis

Anthracofibrosis has been associated with the following except:

• A. Decreased lung function
• B. Mineral dust exposure

C.Hard metal exposure D.Biomass fuel exposure