Beryllium Disease:Increasing Awareness/Protecting Worker Health

L.B. Sandy Rock, MD, MPHRisk Communicator

Beryllium Disease

Hazardso Berylliumo Asbestoso Hexavalent Chromiumo Silica (dust)?o Allergens o (Tobacco)o Fumes/exhaust

Potential Causes of Occupational Lung Diseaseat the Hanford Site (in order of worker concern 2011)

What is CBD?

BerylliumoWhat and where (and why?)

Exposureo How and how much

Sensitizationo BeLPT

Lung diseaseo “Systemic granulomatous disease”o Chronic lung disease---varying severity

Also…Class IA carcinogen

Beryllium Disease

Outcome objectives:

After actively participating in this discussion, attendees will be able to o 1) describe the characteristics of chronic beryllium disease

(and how it is diagnosed); o 2) explain how and where exposure to beryllium can occur

(and the importance of occupational history); o 3) identify the uncertainties inherent in delineating

environmental testing, exposure, diagnostic testing, treatment, and all levels of prevention (thus, why it is so challenging an occupational disease).

Beryllium Disease

Case Study 1

A 52-year-old male former Health Physics Technician at Hanford worked in several areas now known to have been beryllium contaminated. Ten years ago he developed a mild to moderate pneumonitis after exposure to chemical vapors from a storage tank; chest x-ray revealed hilar adenopathy compatible with sarcoidosis and biopsy confirmed the diagnosis. He was treated with systemic corticosteroids initially, and, later, by inhalation. Because of work history and sarcoidosis diagnosis, beryllium sensitization blood test was performed and was negative for four consecutive years; on the fifth year, he had a positive test followed by a positive confirmatory test “just a few months after stopping inhaled cortisone.”

Beryllium Disease

Case Study 2

A 50-year-old male power operator worked for many years in the 300 Area at Hanford, a known beryllium-contaminated area. He heard about the Voluntary Beryllium Program but was reluctant at first to join it. He had no health problems. At coworkers’ urging, he later entered the program and had a negative initial blood test for beryllium sensitization; one year later, he had positive tests. He is angry that his first test was negative since he “continued to work in possible beryllium contaminated buildings.”

Beryllium Disease

Pre/Post Quiz

Both of the above patients were referred to a major medical center known for expertise in beryllium disease and both were diagnosed with CBD. Neither one has developed symptoms or required any treatment to date.

Questions: 1. Patients with a work history in all but which job category and presenting with a sarcoidosis-like syndrome should be

tested for Beryllium Disease?o Nuclearo Sporting equipmento Ceramico Fast Foodo Electronic

2. What test distinguishes Chronic Beryllium Disease from sarcoidosis?o BeLPTo LeBPTo Lipotropin, bloodo Speckled macrophage testo Transbronchial biopsy

3. Many workers express anxiety about being tested for CBD. Which of the following is the least of their concerns? o Job losso Loss of insurabilityo Lack of compensation programso Lack of specific treatmento Uncertainty in diagnosis

Beryllium Disease

Quiz (cont’d)

4. What nationally-recognized center is considered the most knowledgeable about CBD? o Scripps Memorial Hospitalo National Jewish MC, Denvero University of Virginiao Tulane University Medical Centero Mayo Clinic

5. An evaluation for Chronic Beryllium Disease would include all of the following EXCEPT:o Chest x-ray (PA/Lat)o Bronchoscopy with lavage and biopsyo Node biopsy for beryllium particle spectroscopy

o DLCO diffusiono Spirometry

Beryllium Disease

Beryllium

Beryllium is amazingly versatile as a metal alloy and is used in dental appliances, golf clubs, non-sparking tools, wheelchairs, automobiles, bicycle frames and electronics.

Beryllium Disease

•Atomic number = 4•Atomic weight = 9 •High tensile strength •High heat capacity •Excellent electrical conductivity •High stiffness (modulus

of elasticity)

Main industries

nuclear production/fabrication facilitiesaerospaceaircraft manufacture and maintenancecomputerdental laboratories/ceramics telecommunications foundries and metal reclamation

Beryllium Disease

Industrial UsesGyroscopes, guidance systems, accelerometers Reactor rods (controls fission reactions) X-ray windows Spark-free tools (strengthens copper) Consumer products: Mountain bikes, golf clubs,

baseball bats, electronics, ceramics, fishing rods, space shuttle/aviation, brakes

[Fluorescent lights]

Beryllium Disease

What and…

Beryllium in the environmento Ash

• Volcanic– Mt St Helens

• Fly Ash– Coal-fired power plants– Incinerators

Berylo Gemstone

• Emerald, aquamarine, goshenite, and davidsonite

Beryllium particles (fine) and beryllium oxideo Likely sensitizerso Occur in refining and other processing of beryllium metal

Beryllium Disease

… how much?

Do we know?o Probably THE most contentious issue

Genetics-- HLA-DPB polymorphismso “Glu69”

• HLA-DPB1-Glu69 marker– glutamine residue at position 69 (Glu 69+) of the B1 chain of

the HLA-DPB moleculePermissible Exposure Level

o A workplace determination• OSHA• ACGIH• DOE/CBDPP

Beryllium Disease

Numbers (aka “epidemiology”)

CBD in the general population?o = Sarcoidosis + BeLPT positivity

CBD in workerso Industries

• Nuclear weapons production among many others• Ceramics

o DOE sites• Hanford• Rocky Flats• Others

Historyo First described 1933 Germany/discovered 1943 in U.S./ Fluorescent lamp

manufacturing (more acute lung disease known since 1930’s)

Beryllium Disease

…at Hanford…

from 11/97-1/11---Sensitized: 113CBD: 32Workers tested: 5752 (through 10/1/10)

Workers in Be medical programs: 4476 (1/11/11)

oBe-Worker—3257oBe-Program-Voluntary (formerly “Previous Worker”)—1219

Beryllium Disease

Newly Diagnosed Beryllium Sensitized Workers, FY10

Beryllium Disease

16 newly diagnosed Beryllium Sensitized workers in FY10o 4 on initial screening for beryllium work clearance with no prior Hanford

work history and with significant other DOE/DOD work history• Including previous employment in facilities such as Palo Verde,

Shearon Harris, INL moving beryllium waste containers, non-Hanford radioactive waste disposal,

o 2 with prior Hanford work history and potential significant non-Hanford DOE/DOD experience• Including previous employment in facilities such as INL from 1989-

1993, US Navyo 10 with no reported non-Hanford (or any other) work experience

InsidiousExposure oDust---processing, grinding, etching

SensitizationoNo stigma

CBDoMild symptoms in most, at first

Beryllium Disease

What happens…

Exposure- Sensitizationo Lungo Skin (significance?)o 2-15%?

Sensitization Granuloma formation in lungs (CBD)o 20-100%?

CBD diminished pulmonary functiono Variable course: obstruction; restriction; ↓ gas

transport (O2, CO2) (↓DLCO)

Beryllium Disease

Evaluation

Laboratory Studieso Blood BeLPT • test of choice –beryllium sensitization –peripheral blood mononuclear cells exposed in vitro to

beryllium salts at varying concentrations for variable time intervals –cell proliferation in the presence of beryllium indicates a

positive test result. –performed only in selected specialized laboratories (Oak Ridge; U

Penn; Nat’l Jewish, Denver; Cleveland Clinic)

Beryllium Disease

Evaluation, cont’d

Imaging Studieso Chest x-ray:• normal in about half of the patients with documented

chronic beryllium disease (CBD)• hilar adenopathy and/or increased interstitial markings.

o High-resolution CT (HRCT) scan, chest • more sensitive • ground glass opacification (see the image next slide),

parenchymal nodules, or septal lines• negative in 25% of patients with documented CBD.

Beryllium Disease

A high-resolution CT scan of the chest showing the typical ground glass appearance in a patient with chronic beryllium disease, or berylliosis.

Beryllium Disease

Evaluation, cont’d

Other Testso Pulmonary function tests include the following:

• Spirometry • Lung volumes • Diffusing capacity of lung for carbon monoxide (DLCO)

o Arterial blood gases o Cardiopulmonary exercise

With disease progression, spirometry may show evidence of obstruction, restriction, or both. (In an early study in 40 patients with advanced CBD, an obstructive pattern was observed in 39% of patients, a restrictive pattern in 20%, and a low DLCO in 36%.)

The DLCO declines over the course of the disease. The most sensitive test is abnormalities in gas exchange during exercise.

Laser microprobe mass spectrographic (LAMMS) analysis can be used to detect beryllium in histologic sections from lung biopsy specimens. This test is not necessary for the diagnosis and is not widely available.

Beryllium Disease

Evaluation

Procedureso Flexible fiberoptic bronchoscopy with BAL and transbronchial biopsies (TBBX)

• to confirm a suspected diagnosis of CBD. – Patients with CBD usually have BAL lymphocytosis (>20% lymphocytes).– The BeLPT test also can be performed on BAL cells. – A minimum of 6 high-quality biopsies should be obtained to optimize

the yield. If TBBX results are negative but suspicion high, consider repeat bronchoscopy.

o Open lung biopsy may need to be performed if repeat bronchoscopy findings still are negative.

Histologic Findingso The hallmark of CBD is the presence of nonnecrotizing granulomas on lung

biopsy (see the image below). These granulomas are histopathologically indistinguishable from sarcoid granulomas

Beryllium Disease

Normal lung tissue

~200x

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Granulomatous lung tissue

~200x

Beryllium Disease

How is it treated?

Sensitizationo Prevent further exposureo Evaluate and re-evaluate

• Referrals– National Jewish Medical Center (NJH;Denver)

Chronic Beryllium Diseaseo A type of chronic lung diseaseo Specialist evaluation & directed careo No controlled studies for CBD therapy are available. Based on the pathogenesis

of the disease (immune-mediated) and due to the similarities with sarcoidosis, CBD is treated with corticosteroids. When corticosteroid therapy fails or in patients who develop significant adverse effects, methotrexate (MTX) may be considered

Maintain good general health!

Beryllium Disease

How is it prevented?

The usualo Administrative Controlso Engineering Controlso PPEo Training/Work practiceso Pre-planning/Hazard Awareness

The unusualo Sampling/monitoring (specifically for Be; controversy over

“safe” levels)o CBDPP

• enhances worker protection by detailing guidance and standards for monitoring, prevention of exposure, medical surveillance, and work practices

Beryllium Disease

CBDPP

Chronic Beryllium Disease Prevention Program10 CFR 850 (DOE program rule)AMH, DOE, Site contractors committeeSite-wide

Beryllium Disease

Necessary research

Quantifying levels of sensitization and chronic beryllium disease in various work settings and worker populations

Understanding airborne beryllium exposure and the characteristics associated with risk of disease among

exposed workers (as well as risk of aggravating disease) Understanding how different routes of exposure

contribute to disease risk Understanding the genetic risk factors associated with

disease

Beryllium Disease

BHSC

The Beryllium Health and Safety Committee (BHSC) is committed to preventing beryllium sensitization and chronic Beryllium Disease (CBD) and other adverse health effects that can be cased by workplace exposure to beryllium.

The Mission of the BHSC will be accomplished by: Promoting the safe use of beryllium Obtaining a better understanding of exposure risks Improving exposure monitoring Fostering improved controls Accumulating and disseminating information concerning beryllium process best work

practices, as well as, data from the health studies concerning the hazards associated with beryllium

Training / mentoring of beryllium health professionals Identifying and promoting research that has the potential to enhance or improve our

worker safety programs

Beryllium Disease

B.A.G.

Beryllium Awareness GroupAffected workersOpen and closed meetings, monthly

o Open: 1st Wed/mo @ HAMMER Rm 31, 1:30-4:30 PMo Closed: 3rd Wed

-----------Be Registry--The DOE Beryllium-Associated Worker Registry is a complex-wide

internal program to help DOE conduct and improve its [CBDPP]. 10 CFR 850.39 specifies beryllium recordkeeping and reporting requirements for both DOE federal and contractor employees. [It] contains data on DOE contractor and federal workers, the jobs they performed, their beryllium exposure monitoring results, results from screening tests for chronic beryllium diseases, and the results from subsequent medical diagnostic procedures.

Beryllium Disease

Outcome objectives:

After actively participating in this discussion, attendees will be able to o 1) describe the characteristics of chronic beryllium disease

(and how it is diagnosed); o 2) explain how and where exposure to beryllium can occur

(and the importance of occupational history); o 3) identify the uncertainties inherent in delineating

environmental testing, exposure, diagnostic testing, treatment, and all levels of prevention (thus, why it is so challenging an occupational disease).

Beryllium Disease

Pre/Post Quiz

Both of the above patients were referred to a major medical center known for expertise in beryllium disease and both were diagnosed with CBD. Neither one has developed symptoms or required any treatment to date.

Questions: 1. Patients with a work history in all but which job category and presenting with a sarcoidosis-like syndrome should be

tested for Beryllium Disease?o Nuclearo Sporting equipmento Ceramico Fast Foodo Electronic

2. What test distinguishes Chronic Beryllium Disease from sarcoidosis?o BeLPTo LeBPTo Lipotropin, bloodo Speckled macrophage testo Transbronchial biopsy

3. Many workers express anxiety about being tested for CBD. Which of the following is the least of their concerns? o Job losso Loss of insurabilityo Lack of compensation programso Lack of specific treatmento Uncertainty in diagnosis

Beryllium Disease

Quiz (cont’d)

4. What nationally-recognized center is considered the most knowledgeable about CBD? o Scripps Memorial Hospitalo National Jewish MC, Denvero University of Virginiao Tulane University Medical Centero Mayo Clinic

5. An evaluation for Chronic Beryllium Disease would include all of the following EXCEPT:o Chest x-ray (PA/Lat)o Bronchoscopy with lavage and biopsyo Node biopsy for beryllium particle spectroscopy

o DLCO diffusiono Spirometry

Beryllium Disease

Beryllium Corrective Action Plan (BeCAP)

A result of concerns brought to DOE through the Hanford Advisory Board (HAB)o HAB influenced by various parties

• BAG• Activists• Elected government officials

o Driven by perception that workers were becoming BeS DOE HQ sent team from Health, Safety and Security office

o Numerous interviews and records review (non-medical)o Evaluation took place for two weeks March 2010o Report released to public June 2010

Corrective Action Plan (BeCAP) developed and approved o “Final” agreed-upon Corrective Action Plan August 30, 2010 and accepted by DOE on

9/22/2010 All Hanford contractors responsible for meeting deadlines to complete assigned “opportunities for

improvement” over the coming months.

Beryllium Disease

Summary

Beryllium exposure can cause a granulomatous lung disease in workers who develop a lymphocyte-mediated sensitization to the metal. Workers in diverse industries are at risk because beryllium's properties are critical to nuclear, aerospace, telecommunications, electronic, metal alloy, biomedical, and semiconductor industries. The occupational air concentration standard's failure to protect beryllium workers is driving many scientific and occupational health advances. These developments include study of bioavailability of different physicochemical forms of beryllium, medical surveillance to show effectiveness of skin protection in preventing sensitization in high-risk processes, gene-environment interaction, transgenic mice for use in experimental research, and risk-based management of industrial exposures in the absence of effective exposure-response information. Beryllium sensitization and disease prevention are paradigms for much broader public health action in both occupational and general population settings.

Beryllium Disease

Practice Commitments

I will make the following changes in my practice:

Include comprehensive work history in patient charts

Consider BeLPT in patients with sarcoidosis, particularly those with relevant work history

****** (TBD by attendees)

Beryllium Disease