occurs in both sarcoidosis and CBD, and both diseases occur in all racial groups. Thus, such features
should not be used to differentiate CBD and sarcoidosis in an individual.

Chronic sarcoidosis is an uncommon condition, with a prevalence in the USA estimated at about
50 -150 per 100,000!”. Sarcoidosis is much less common than CBD in Be-exposed workers, which has a
prevalence estimated to range from about 0.1%-7% (0.1 - 7 per 100).2'8

An abnormal BeLPT test, documentation of BeS, is the most definitive way to confirm CBD ina
patient that has been diagnosed with sarcoidosis. However, there are a number of reasons why a worker
with CBD may not have a documented abnormal BeLPT test and be misdiagnosed as having sarcoidosis.

Steroids and other immunosuppressive medications used to treat CBD, sarcoidosis and other
chronic lung conditions can suppress the proliferation response of blood and /or lung lymphocytes to
beryllium, resulting in a false negative BeLPT. This is currently noted in the Procedure Manual Chpt 2-
1000: “If the claimant has a history of steroid use, a false negative BeLPT .... can occur”. Section Sc
(Beryllium Sensitization; False negative results).

False negative BeLPT tests have also been documented in patients even if not on immune-
suppressive medications.'?”>4 The BeLPT test performed on lung lavage cells, while more sensitive
than the peripheral blood BeLPT, can also have false negatives due to smoking, immunosuppressive
treatment and other factors.”>

The BeLPT is not a routine clinical test and is rarely performed, except in the fraction of
beryllium-exposed workers enrolled in a beryllium medical surveillance program. Thus it is common for
covered beryllium employees, despite outreach efforts by DOE, DOL and others, not to have had a
BeLPT test performed. This is currently noted in the Procedure Manual Chpt 2-1000: “Jfexhaustive
efforts produce little or no results (BeLPT testing) ..... the CE can accept the claim. (Section 5c).

Our review of Part B lung CBD decisions found cases of workers who met the definition of a
“covered beryllium employee” and had been diagnosed with pulmonary sarcoidosis, but their CBD
claims had been incorrectly adjudicated and denied. Some cases had BeLPT tests that were likely false
negatives. Others had never had a BeLPT test performed, either because the employee had not been in a
beryllium surveillance program and/or the provider (including at DOE sites) did not consider CBD
and/or never obtained the BeLPT test.

Our review of cases also demonstrated that most clinicians, even board-certified pulmonary and
occupational medicine physicians, know little about CBD, BeS, BeLPT testing, or their patient’s work
history. This unfortunately was true for some current CMCs, despite the current Procedure Manual and
training materials.

In summary, in situations where a “covered beryllium employee” under Part B or E has been
diagnosed with pulmonary sarcoidosis, that employee is more likely to have CBD than sarcoidosis and
should be diagnosed with CBD. Such claims should be adjudicated as CBD, even if the BeLPT is
normal (may be false negative test), the BeLPT was never performed, or the diagnosis of pulmonary
sarcoidosis was made based on a biopsy of extra-pulmonary tissue, such as a lymph node or skin.

The current Procedure Manual (Chpt 2-1000) and EEOICPA Circular 08-07 state the same, that
sarcoidosis is not an appropriate diagnosis in a covered beryllium employee, and explain how to accept a
claim for CBD in this setting, including when the BeLPT is normal or was never performed.

However, the current wording in the Procedure Manual Chpt 2-1000 and related training materials
is confusing, inconsistent and requires substantial revision. For example (Chpt 2-1000; Section 10):

“Presumption of CBD, Diagnosis of Sarcoidosis, and History of Beryllium Exposure......Under Part B,
the DEEOIC recognizes that a diagnosis of pulmonary sarcoidosis, especially in cases with pre--1993
diagnosis dates, could represent a misdiagnosis for CBD. As such, a diagnosis of pulmonary sarcoidosis

14



Recommendations related to Part B Lung Disease
Responses to Comments and Questions from the DOL

This document contains the responses of the DOL Advisory Board on Toxic Substances and
Worker Health to the DOL’s Comments and Questions, and 2 specific recommendations and rationale.
The comments also address many of the concerns regarding Part B claims that workers and others have
expressed to the Advisory Board.

The comments, recommendations and rationale are based on the following: The Subcommittee’s
analysis of data on Part B cases; a review of approximately 80 Part B case adjudications (selected
records on); a review of relevant sections of EEOICPA and the 2004 Part E Addendum; relevant DOL
Procedure Manuals, Circulars, and training materials; Advisory Board meetings to date and comments
submitted to the Advisory Board; visits to Oak Ridge, TN and Hanford, WA sites; the relevant published
medical literature, and our collective expertise.


10. Culver DA. Beryllium disease and sarcoidosis: still besties after all these years? Eur Respir J
2016;47:1625-8.

11. Mayer AS, Hamzeh N, Maier LA. Sarcoidosis and chronic beryllium disease: similarities and
differences. Semin Respir Crit Care Med 2014:35:316-29.

12. Muller-Quernheim J, Gaede KI, Fireman E, Zissel G. Diagnoses of chronic beryllium disease
within cohorts of sarcoidosis patients. Eur Respir J 2006;27:1190-5.

13. Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir
Crit Care Med 2011;183:573-81. PMC3081278:PMC3081278.

14. Judson MA. The diagnosis of sarcoidosis. Clin Chest Med 2008;29:415-27, viii.

15. Judson MA. The Clinical Features of Sarcoidosis: A Comprehensive Review. Clin Rev Allergy
Immunol 2015;49:63-78.

16. Judson MA. Sarcoidosis: clinical presentation, diagnosis, and approach to treatment. Am J Med
Sci 2008;335:26-33.

17. Baughman RP, Field S, Costabel U, et al. Sarcoidosis in America. Analysis Based on Health Care
Use. Ann Am Thorac Soc 2016;13:1244-52.

18. Kreiss K, Day GA, Schuler CR. Beryllium: a modem industrial hazard. Annu Rev Public Health
2007;28:259-77.

19. Newman LS, Mroz MM, Balkissoon R, Maier LA. Beryllium sensitization progresses to chronic
beryllium disease: a longitudinal study of disease risk. Am J Respir Crit Care Med 2005;171:54-60.

20. Bobka CA, Stewart LA, Engelken GJ, Golitz LE, Newman LS. Comparison of in vivo and in vitro
measures of beryllium sensitization. J Occup Environ Med 1997;39:540-7.

21. Stange AW, Furman FJ, Hilmas DE. The beryllium lymphocyte proliferation test: Relevant issues
in beryllium health surveillance. Am J Ind Med 2004;46:453-62.

22. Stokes RF, Rossman MD. Blood cell proliferation response to beryllium: analysis by receiver-
operating characteristics. J Occup Med 1991;33:23-8.

23. Heldt GH, Deubner DC. The beryllium bronchoalveolar lavage lymphocyte proliferation test:
indicator of beryllium sensitization, inflammation or both? Inhal Toxicol 2015;27:262-71.

24. Borak J, Woolf SH, Fields CA. Use of beryllium lymphocyte proliferation testing for screening of
asymptomatic individuals: an evidence-based assessment. J Occup Environ Med 2006;48:937-47.

25. Maier LA. Is smoking beneficial for granulomatous lung diseases? Am J Respir Crit Care Med
2004; 169:893-5.

26. Baughman RP, Nagai S, Balter M, ct al. Defining the clinical outcome status (COS) in sarcoidosis:
results of WASOG Task Force. Sarcoidosis Vasc Diffuse Lung Dis 2011;28:56-64.

27. Middleton DC, Fink J, Kowalski PJ, Lewin MD, Sinks T. Optimizing BeLPT criteria for
beryllium sensitization. Am J Ind Med 2008;51:166-72.

28. Middleton DC, Mayer AS, Lewin MD, Mroz MM, Maier LA. Interpreting borderline BeLPT
results. Am J Ind Med 2011;54:205-9. PMC4347846.

29. Occupational Health Best Practices: State of Washington; 2015.

http://www .Ini.wa.gov/ClaimsIns/Files/OMD/MedTreat/Clinical GuidelinefortheDiagnosisofBerylliumS
ensitizationandChronicBerylliumDisease.pdf

18


The PFT findings in CBD, similar to the findings in sarcoidosis, are variable and non-specific, and
can also fall within normal limits. Thus normal lung function, airflow obstruction, restriction (reduced
lung volumes), low diffusing capacity, and mixed air flow obstruction / restriction can be seen in CBD.
With more advanced CBD, a reduced diffusing capacity (DLCO) and restriction are more common, but
other PFT findings can be present.

Of note, it is important to compare lung function results with prior testing when available, as there
can be significant declines in lung function, but values can still fall within normal ranges.> A recent
American Thoracic Society (ATS) document provides guidance to performing and interpreting
spirometry related to work exposures.>

3) Lung pathology consistent with CBD.

In most instances, a physician’s statement with medical rationale confirming that pathologic
test results are consistent with CBD is sufficient to support claim. Additional guidance on lung
pathology findings consistent with CBD would be useful.

Response:

The typical lung pathology in CBD is a non-caseating granuloma that is indistinguishable from
sarcoidosis. The granulomas can be well formed or a loose collection of epitheliod cells. The
granulomas can be in the lung itself, in chest lymph nodes or in other organs, such as the skin, liver or
nose. However, granulomas are not always seen on lung pathology.”*

Other findings that are consistent with CBD include: interstitial infiltrates (lymphocytes,
monocytes, plasma cells), and multinucleated giant cells. In more advanced disease, progressive fibrotic
changes can be seen, including diffuse fibrosis, fibrotic nodules, foreign body granulomas,
calcifications, cystic-honeycomb changes, and bronchiectasis.** These findings are also seen in other
chronic interstitial lung diseases, such as sarcoidosis, chronic hypersensitivity pneumonitis, and
idiopathic pulmonary fibrosis.

The text in the Procedure Manual Chpt 2-1000 regarding pathology contains some inaccuracies
and requires revision. For example:

“a mediastinal lymph node biopsy interpreted by a physician as evidence of “lung pathology
consistent with CBD” may be used to establish CBD. A mediastinal lymph node biopsy is not the
equivalent of a “lung biopsy” and, as such, does not substitute for such in the assessment of a post-1993
CBD claim. The evidence has to be interpreted as “lung pathology.” A mediastinal lymph node is not
dispositive proof of CBD in the same way as a lung biopsy.” (Section 7 Post-1993 Criteria)

Comment: A mediastinal (or any chest) lymph note biopsy showing findings consistent with CBD
IS the equivalent of a lung biopsy and CAN be substituted for a lung biopsy. Lymph nodes (or
extrapulmonary sites) are sometimes biopsied instead of lung tissue to reduce the risk of complications
such as pneumothorax. The wording above should be deleted.

“Ifa pathology report does not include a physician’s interpretation... the CE obtains clarification
from a treating physician or CMC.” (Section 6f).

Comment: Pathology reports ARE a physician’s description and interpretation of the findings.
With non-malignant lung diseases such as CBD, sarcoidosis, or asbestosis, the pathologic findings
commonly are non-specific, so reports frequently describe the pathologic findings, such as
granulomatous lung inflammation, inflammatory or fibrotic changes, but do not provide a specific
diagnosis such as CBD. Thus any of the pathologic findings noted above in a worker with BeS should be
considered diagnostic for CBD. The pathologist’s report does NOT need to state that the findings are
consistent with CBD.

10


Recommendation #3

Revision of sections of the Procedure Manual and related materials relevant to Part B conditions

The Advisory Board recommends a substantial revision of sections of the Procedure Manual and
related materials relevant to Part B conditions, taking into consideration the comments in this document
and other feedback from the Advisory Board.

Rationale

Sections of the current Procedure Manual and related materials are inconsistent, confusing, and at
times medically inaccurate, which can hinder proper adjudication of Part B claims.

Endorsement

The Advisory Board endorses a presumption of chronic beryllium disease (CBD) in situations
with a diagnosis of sarcoidosis in an individual who meets the definition of a “covered beryllium
employee” under Part E or Part B.

Rationale

This presumption already exists, as stated in EEOICPA Circular No. 08-07 and EEOICPA
Procedure Manual Chapter 2-1000. However, implementation of this presumption has been
problematic. Revising the relevant Sections of the Procedure Manual and training materials, within the
statutory limitations of EEOICPA, should help alleviate this problem.


Recommendation #2

Definition of ‘chronic respiratory disorder”

The Advisory Board recommends that the following criteria be used to define a clinical course
consistent with a “chronic respiratory disorder” for use in evaluating pre-1993 CBD claims:

i) Respiratory symptoms (e.g. shortness of breath, cough) that are chronic*, and
ii) One of the following:

a) Abnormal pulmonary function tests (PFTs), or

b) Abnormal chest imaging (chest x-ray or CT scan), or

c) Hypoxemia, or

d) Use of respiratory medications such as asthma or COPD inhalers.

*“Chronic” indicates symptoms (or medication usage) that are present for more than three months, to
differentiate from symptoms (or medication usage) related to an acute infection or other problem that
resolves. If the Claims Examiner cannot determine, based on the record, whether the condition was
present for more than three months, then the case should be referred to a CMC to determine if the
condition was a chronic respiratory disorder.

Rationale

The current Procedure Manual and training materials contain several different and at times
inconsistent criteria for a “Chronic respiratory disorder” for use in evaluating pre-1993 CBD claims. It is
recognized that there is no one perfect criteria given the variability in clinical presentations,
documentation by clinicians, access to medical care, medical record availability, the co-occurrence of
acute and chronic lung conditions, and other factors. The recommended criteria are intended to provide
greater consistency and ease of use.


Response:

For those who are sensitized to beryllium the American Thoracic Society recommends periodic
medical monitoring every 2 to 3 years, or sooner if there is concern about progression’. This evaluation
should include a review of symptoms, physical examination and pulmonary function testing. If
deterioration is noted, (or prior chest imaging warrants follow-up evaluation), a chest CT scan is
recommended. Further evaluation, such as bronchoscopy or lung biopsy or cardiopulmonary exercise
testing, is considered on a case-by-case basis.”?

2. Chronic Beryllium Disease
DOL Comments / Questions:
A) Pre-1993 CBD

1) Characteristic chest radiographic or computed tomography (CT) abnormalities. More clear
guidance on chest radiographic abnormalities consistent with CBD would be useful.

Response:

The radiographic abnormalities (chest x-ray and CT scan) seen with CBD are variable and non-
specific. In addition to small nodules in the lung parenchyma (considered the most common finding),
ground glass opacities, bronchial wall thickening, thickened interlobular septa, lymphadenopathy (hilar,
mediastinal), and no radiographic abnormalities are also seen. With more advanced disease, interstitial
fibrosis, honeycombing, subpleural cysts, traction bronchiectasis and calcifications can be seen.?*

The chest xray and chest CT scan imaging findings that can be seen with CBD are generally
described appropriately in Chapter 2-1000 (Section 6, pgs 5-6). Parts of the text are confusing and would
benefit from editing. Specific suggested edits include:

Discussion regarding granulomas (Section 6 pg 5): Whether a granuloma is caseating or not is
determined by pathologic examination of lung tissue and not chest imaging. This text should be removed
from the chest x-ray section.

Similar to sarcoid granulomas, CBD granulomas can become calcified. Thus the sentence “A
calcified granuloma is not characteristic of CBD” is incorrect and should be removed.

The EEOICPA statutory criteria refer to “characteristic chest x-ray or CT abnormalities”. Any of
the imaging findings noted in the Training manual or above that are “consistent with” or “seen with”

CBD” are also “characteristic abnormalities”.

2) Restrictive or obstructive lung physiology testing or diffusing lung capacity defect. Pulmonary
function test (PFT) is used as diagnostic tool for specific illnesses (i.e. asthma, COPD). Are PFT
results within certain ranges consistent with CBD?

Response:

Pulmonary function tests (spirometry, lung volumes, diffusing capacity) evaluate how well lungs
work, such as airflow, lung size, ability to provide oxygen, and can help diagnose lung diseases,
including CBD and COPD. Thus PFTs can identify abnormalities in how a person’s lung function, but
do not diagnose specific illnesses such as CBD, silicosis or COPD.


Advisory Board on Toxic Substances and Worker Health
Recommendations and Other Actions— Adopted at June 19, 2017 Meeting

Recommendations

1. Presumption for Solvent-Related Hearing Loss p.2
2. Definition of “Chronic Respiratory Disorder” p.6
3. Revision of sections of the Procedure Manual
and related materials relevant to Part B conditions p.7
Endorsement
Presumption of chronic beryllium disease (CBD) p.7

in claimants with sarcoidosis

Responses to DOL’s Specific Comments and Questions p. 8


The Procedure manual Chapter 2-1000 and training materials at times provide inconsistent and/ or
inaccurate descriptions of a “chronic respiratory disorder” and require revision. For example:

1) “Whether to use the pre- or post- 1993 CBD criteria depends upon the totality of the medical

evidence, including when the employee was tested for, diagnosed with, and/or treated for a chronic
respiratory disorder.” (Section 6)

2) “If the earliest dated document showing that the employee was either treated for or diagnosed with a
chronic respiratory disorder is dated prior to January 1, 1993, the pre-1993 CBD criteria should be
used. Evidence of a chronic respiratory disorder includes records communicating existence of a long-
term, prolonged pulmonary disease process. References to acute pulmonary conditions, such as short-
term pulmonary distress associated with temporary viral or bacterial infection do not qualify as a
chronic respiratory disorder. Pulmonary testing performed in occupational or medical settings, which

identify abnormalities, are not appropriate to document a chronic respiratory disorder, unless
interpreted as such...” (Section 6; CBD Pre 1993)

Comment: When a patient is “tested, treated for or diagnosed” can be very different time periods; the
terms should be used consistently. As noted, chronic respiratory conditions may be present for years
before they come to medical attention and are diagnosed as a chronic respiratory condition. They also
may initially be diagnosed as an infection or acute bronchitis. Pulmonary function tests are generally not
performed when patients are acutely ill (per ATS guidelines).> Thus abnormalities noted on PFTs
(obstructive, restrictive, reduced DLCO) that are performed properly in either an occupational or
medical setting generally DO indicate a chronic respiratory disorder. Of note, per ATS guidelines,
interpretations on PFTs reports describe the physiologic abnormalities present but do not state whether
such findings document a chronic respiratory disorder such as CBD or COPD.’

3) “Clinical course consistent with chronic respiratory disorder may include the following .....:
(1) Hypoxemia requires supplemental oxygen...

(2) Air flow obstruction (e.g., COPD...) and asthma/wheezing--like symptoms require inhalers ....
(3) Right heart failure, Cor pulmonale...

(4) Pulmonary Hypertension ...

(5) Respiratory infections (pneumonia, acute bronchitis) ...

(6) Sarcoidosis: corticosteroid drugs ...”

(Section 6g CBD Pre-1993 Criteria)

Comment: The text above is not consistent with other parts of Chpt 2-1000 and / or medical guidelines.
For example, patients can have sarcoidosis but not be on corticosteroids.

Replacing the current multiple criteria for a “chronic respiratory condition” in the Procedure

manual Chapter 2-1000 and training materials with a consistent standard for pre 1993 CBD such as the
one noted above should facilitate implementation of EEOICPA.

12


B. Post-1993 CBD Criteria

DOL Comments / Questions: CBD criteria are: Beryllium sensitivity AND lung pathology consistent
with CBD, including lung pathology, CT scan, and PFT consistent with CBD.

Issue 1. Clarification of the diagnostic and interpretive meaning of “characteristic of CBD” to
differentiate between CBD and other lung disease.

Response:

Lung pathology, chest imaging, and PFT findings considered “consistent with CBD” are described
above and should be the same for Pre-CBD and Post-CBD diagnostic criteria. As noted, these test results
are not unique to CBD, and it is not possible to differentiate CBD from sarcoidosis, discussed further
below.

Issue 2. Consistent and uniform standard for judging medical evidence for the pre or post 1993 as
evidence of a “chronic respiratory disorder”.

Response:

A consistent standard should be used to define a “chronic respiratory disorder” for Part B lung
conditions. A “chronic respiratory disorder” is one of the diagnostic criteria for pre-1993 CBD, not post
1993 CBD. Thus the proposed standard below is relevant only for pre-1993 CBD diagnoses.

Chronic respiratory disorders such as CBD or COPD commonly are present and progress slowly
for years before they come to the medical attention especially when present in those who are not under
regular respiratory medical surveillance. Chronic respiratory conditions also frequently are initially
recognized after an acute infection or event and may initially be misdiagnosed as an acute illness such as
bronchitis or pneumonia.

A consistent standard for judging whether medical evidence meets the pre-1993 conditions for
“chronic respiratory disorder” is the following:

i) Respiratory symptoms (e.g. shortness of breath, cough) that are chronic* PLUS

ii) ONE of the following:
a) Abnormal pulmonary function tests (PFTs) OR

b) Abnormal chest imaging (chest x-ray or CT scan) OR

c) Hypoxemia, OR

d) Chronic use of respiratory medications such as asthma or COPD inhalers
The criteria for abnormal! PFT or chest imaging are as described above.

*“Chronic” indicates symptoms (or medication usage) that are present for more than three months, to
differentiate from symptoms (or medication usage) related to an acute infection or other problem that
resolves. If the Claims Examiner cannot determine, based on the record, whether the condition was
present for more than three months, then the case should be referred to a CMC to determine if the
condition was a chronic respiratory disorder.

11


RESPONSES TO DOL’S SPECIFIC COMMENTS AND QUESTIONS
1. Beryllium Sensitivity

DOL Comments / Questions:

1) Consistency of testing results among the different diagnostic facilities

Response:

National Jewish Medical Center (Denver, CO), Oak Ridge Associated Universities (ORAU), and
the Cleveland Clinic (Cleveland, OH) are the only laboratories in the U.S. that we are aware of that
currently perform the beryllium lymphocyte proliferation test (BeLPT) on a regular basis. These
laboratories have extensive experience performing the BeLPT test. Consistency between these
laboratories does not appear to be an on-going issue. Additional laboratories would likely increase
problems with the accuracy and reproducibility of performing BeLPT testing.

2) Reinterpretation of “normal” test outcomes as abnormal by a consulting physician.

Response:

A patient’s BeLPT report from the lab performing the test should not be reinterpreted by a
consulting physician.

However, the quality and interpretation of the standard clinical tests used to evaluate patients with
pulmonary disorders (chest x-ray and CT scans, pulmonary function testing, lung pathology), can be
quite variable and significant inter-observer variability can occur!, These tests involve interpretation of
multiple images, visual patterns, and/or data points, and treating or consulting physicians routinely re-
review the studies themselves or with the appropriate specialist (e.g. chest radiologist, pulmonary
pathologist). Proper interpretation also can require comparison to prior testing results if available.

3) New and more relevant science on diagnostic tools for evaluating beryllium sensitivity?
Response:

Although there is ongoing research, including work on biomarkers for BeS and CBD, there are no
additional or better clinical diagnostic tests for BeS or CBD that are available at this time.

Of note, patch testing to beryllium, which involves putting a test amount of beryllium on the
patient’s skin, is no longer recommended to assess sensitization to beryllium, as performing the test can
induce beryllium sensitization in someone not previously sensitized.” Skin patch testing is referred to as
a possible diagnostic test for BeS throughout the EEOICPA Procedure Manual (Chpt 2-1000) and
related training materials, which creates confusion and should be removed. Also tissue beryllium levels
should not be used to diagnose BeS or CBD.

4) Definition of beryllium medical monitoring i.e. expected medical regimen for monitoring sensitivity
to determine if it has progressed to CBD,


References

Campo-P; Morata-TC; Hong-O. Chemical exposure and hearing loss. Dis Mon 2013 Apr; 59(4):119-
138 http://dx.doi.org/10.1016/j.disamonth.2013.01.003.

Dement J, Ringen K, Welch L, Bingham E, Quinn P. Surveillance of hearing loss among older
construction and trade workers at Department of Energy nuclear sites. Am J Ind Med. 2005
Nov;48(5):348-58.

EU-OSHA — European Agency for Safety and Health at Work 2009. Combined exposure to Noise and
Ototoxic Substances. Authors: Pierre Campo, Katy Maguin, Stefan Gabriel, Angela Mller, Eberhard
Nies, Maria Dolores Solé Gémez, Esko Toppila https://osha.europa.ev/en/.../combined-exposure-to-
noise-and-ototoxic-substances.

Nordic Expert Group: Johnson, A and Morata, T. 2010. Occupational exposure to chemicals and
hearing impairment. http://hdl.handle.net/2077/23240


Under Part E, if there is a diagnosis of pulmonary sarcoidosis,but no affirmative evidence in the form
of a positive BeLPT or BeLTT exists, the CE adjudicates the condition as sarcoidosis, not CBD.”

Comment: A diagnosis of pulmonary sarcoidosis most likely (not “could”) represents a misdiagnosis of
CBD. This is the case whether or not the CBD claim is made pre or post 1993, the BeLPT is positive or
negative, or the employee is applying under Part B or Part E.

An example of alternate text for Chapter 2-1000 that meets the statutory criteria of EEOICPA
Parts B and E and can be used to diagnose CBD in a covered beryllium employee with sarcoidosis is as
follows:

“4 diagnosis of pulmonary sarcoidosis is not medically appropriate in a covered beryllium
employee under Part B or Part E as the employee most likely has CBD that has been misdiagnosed as
sarcoidosis. In these situations, the CE is to consider the diagnosis of sarcoidosis to be a diagnosis of
CBD. The following should be documented to determine this diagnosis:

a) When sarcoidosis is diagnosed in a “covered beryllium employee” under Part B or Part E,
pulmonary sarcoidosis should be documented as noted above. The presence of granulomas
(=granulomatous inflammation) on tissue biopsy should be documented. The tissue where granulomas
are identified can be extrapulmonary, such as skin, nose, or lymph nodes. In such cases pulmonary
involvement can be documented based on PFT or chest imaging findings, as noted above,!*?6

b) The results of any available BeLPT testing should be documented. If the BeLPT test is normal,
reasons for a false negative BeLPT (such as immunosuppressive treatment) should be documented.
Repeat BeLPT testing is not indicated when there is a diagnosis of pulmonary sarcoidosis in a covered
beryllium worker, as the appropriate diagnosis is CBD, whether or not BeLPT testing is abnormal. If
BeLPT testing was not performed, the reason should be noted, such as the worker is deceased or was
not in a beryllium medical surveillance program.”

Rationale for using the same CBD / sarcoidosis presumption criteria under Part B and E:

The current wording regarding adjudicating CBD / sarcoidosis claims under Part B and E is
confusing. (Procedure Manual: Chpt 2-1000 Section 10).

The statutory requirements of EEOICPA Part E require that the Secretary of Labor of determine
that ‘it is at least as likely as not that exposure was a significant factor in aggravating, contributing to,
or causing the illness”. The Procedure Manual states for Part E claims: “In cases where there is .... a
diagnosis of pulmonary sarcoidosis and a positive BeLPT, the CE is to obtain a physician's opinion
regarding whether it is ‘at least as likely as not’ that exposure was a significant factor in aggravating,
contributing to, or causing CBD”. In CBD / sarcoidosis cases this Part E statutory requirement has
already been met and exceeded. A physician’s opinion is not needed
This requirement can be eliminated.

Our understanding is that a claim accepted under Part B as CBD will also be accepted under Part
E, and if a claim for CBD is denied under Part B, it will also be denied under Part E. Thus, although the
wording of EEOICPA Part B and E differ, different criteria for CBD / sarcoidosis under Part B and Part
E appears to be confusing.

A claim for CBD that is denied under Part B can be accepted under Part E as another chronic lung
condition, such as pneumoconiosis, according to the statutory requirements of Part E. Relevant to Part E
claims more broadly, “At least as likely or not” and “significant factor in aggravating or contributing to

15


B-reading of chest x-rays remains important for medical surveillance of exposed workers and can
be used to diagnose pneumoconioses, but are not required by EEOICPA. Chest CT scans are now
commonly used to evaluate individual patients with chronic lung diseases such as CBD, silicosis, and
pneumoconiosis.

OTHER COMMENTS:

1) Chapter 2-1000 of the Procedure Manual likely has undergone several revisions. Its current wording
is confusing, contains inaccuracies in certain sections and would benefit from a major revision and
streamlining. Much of the inaccurate and/or confusing information, such as the discussion of calcified
granulomas or the significance of granulomas in chest lymph nodes vs. lung tissue, is NOT part of the
statutory requirements of EEOICPA (or the 2004 Part E Amendment) and should be removed. The Part
B subcommittee would be willing to assist the DOL in revising the Procedure Manual.

2) As noted above, most pulmonary and occupational medicine physicians, including likely many
CMCs, do not have experience diagnosing occupational lung diseases such as CBD. Our review of 80
Part B case adjudications supports these concerns. Revising and updating the Procedure manual is
warranted but does not address issues related to the quality and oversight of the CMCs and claims
examiners, and other components of the EEOICPA claims adjudication process.

References

1. Tomassetti S, Piciucchi S, Tantalocco P, Dubini A, Poletti V. The multidisciplinary approach in
the diagnosis of idiopathic pulmonary fibrosis: a patient case-based review. Eur Respir Rev 2015;24:69-
77.

2. Balmes JR, Abraham JL, Dweik RA, et al. An official American Thoracic Society statement:
diagnosis and management of beryllium sensitivity and chronic beryllium disease. Am J Respir Crit
Care Med 2014;190:e34-59.

3. Council NR. Managing Health Effects of Beryllium Exposure. Washington, DC: The National
Academies Press; 2008. https://www.nap.edw/catalog/12464/managing-health-effects-of-beryllium-

exposure.
4. Cox CW, Rose CS, Lynch DA. State of the art: Imaging of occupational lung disease. Radiology

2014;270:681-96.

5.  Redlich CA, Tarlo SM, Hankinson JL, et al. Official American Thoracic Society technical
standards: spirometry in the occupational setting. Am J Respir Crit Care Med 2014;189:983-93.

6.  Freiman DG, Hardy HL. Beryllium disease. The relation of pulmonary pathology to clinical
course and prognosis based on a study of 130 cases from the U.S. beryllium case registry. Hum Pathol
1970; 1:25-44.

7. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur
Respir J 2005;26:948-68.

8. Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible
bronchoscopy in adults: accredited by NICE. Thorax 2013;68 Suppl 1:i1-i44.

9. | Nguyen W, Meyer KC. Surgical lung biopsy for the diagnosis of interstitial lung disease: a review
of the literature and recommendations for optimizing safety and efficacy. Sarcoidosis Vasc Diffuse Lung
Dis 2013;30:3-16.

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xylene, n-hexane, and carbon disulfide. In human studies, health effects have found from solvent
mixtures containing methyl-ethyl ketone and methyl-isobutyl-ketone as well. The EU Agency report
also concluded that due to limitations in the human studies, there are no clear data on dose-response
relationships nor clear effects on auditory thresholds in humans (EU-OSHA — European Agency for
Safety and Health at Work 2009).

Experiments with rats have shown that combined exposure to noise and solvents such as toluene,
styrene, benzene, and trichloroethylene induced synergistic adverse effects on hearing. Even given the
limitations the review found in the human epidemiologic studies, the report concluded “Overall, in
combined exposure to noise and organic solvents, interactive effects may be observed depending on the
parameters of noise (intensity, impulsiveness) and the solvent exposure concentrations. In case of
concomitant exposures, solvents can exacerbate noise-induced impairments even though the noise
intensity is below the permissible limit value.” Although exposure to noise is not assessed by EEOICPA
(noise is not a hazard covered by the statute), a significant proportion of the workers who qualify under
this presumption will have had substantial noise exposure (Dement et al, 2005)

These two reviews summarize many years of research, and allow us to conclude that hearing loss
in humans can be attributed to a range of organic solvents. We can also conclude that it is likely that
there is a synergistic effect between noise exposure at work and exposure to these solvents.

Animal experiments are generally done with one chemical at a time while human exposure is often
to amix of chemicals. Toluene, xylene, MEK, and MIBK are often present when a worker is exposed
to a mixture of organic solvents. Therefore, it is reasonable to base a presumption on combined
exposure to organic solvents rather than requiring evidence of exposure to one of the specific solvents
studied in animal experiments.

As noted above there is limited information on which to base an assessment of toxic dose in
humans. At least one study of human exposures to toluene showed hearing loss at levels of 50 ppm for 7
years, with one other study showing effects after 5 years of exposure. For styrene one study showed
health effects with a mean exposure at 14 ppm over working lifetime. Since many of the studies looked
at populations with long-term exposure solvents these numbers should not be considered a threshold
below which there is no harm from solvents.

Based on the limited human data a presumption that requires at least 7 years of cumulative
exposure to organic solvents is reasonable. Since health effects have been reported at levels well below
the current OSHA PEL of 200 ppm, exposures occurring now could be still injurious if continued over
many years.

We have recommended that a claim with solvent exposure between 5 and 7 years of exposure be
reviewed by an IH. The intent is to have an assessment of that specific worker’s occupational history to
determine if in those 5+ years of exposure he/she had more intensive or frequent exposure to organic
solvents that would be equivalent to at least 7 years in the average solvent-exposed jobs across the
complex.


Recommendation #1

Presumption for Solvent-Related Hearing Loss

A claim would meet the presumption for solvent-related hearing loss if there is:

(1) A diagnosis of sensorineural hearing loss, and
(2) Significant solvent exposure

Significant solvent exposure is defined as having any one of the following exposures:

(1) Work for at least a total of 7 years (or equivalent) in any of the job titles on the job title
list in current presumption, or in any construction or maintenance job,
OR
(2) Reported exposure to one or more of the following: styrene toluene, MEK, MIBK, N-
hexane, xylene, ethylbenzene TCE, or carbon disulfide on the Occupational Health
Questionnaire (OHQ), or evidence for exposure to organic solvents in the Site Exposure
Matrices (SEM), for at least a total of 7 years (or equivalent),
OR
(3) Reported exposures to organic solvent mixtures on the OHQ, or evidence for exposure to
organic solvent mixtures in the SEM, for at least a total of 7 years (or equivalent),
OR
(4) Solvent exposure for at least a total of 7 years (or equivalent) established through work
history and DDWLP.

Additionally, claims examiners should not routinely deny claims for solvent induced hearing loss
if the worker has had fewer than 7 years of exposure, does not have a Direct Disease Linked Work
Processes (DDLWP) for task, or is not in a labor category on list. Claims that do not meet the
requirements set forth here but do have reported exposure to organic solvents for at least 5 years
cumulative should be sent for IH review.

Rationale

There is sufficient animal data, primarily from studies in rats, to conclude that several specific
organic solvents cause hearing loss. Because of their metabolism, rats are considered comparatively
good animal models for the investigation of the ototoxic properties of aromatic solvents in humans.
Epidemiologic studies in humans exposed both to combined solvents as the individual solvents
identified as ototoxic in rat studies; these confirmed the results of animal experiments, and found effects
on hearing from combined solvents as well. The research supporting these statements is well
summarized in a document produced collaboratively in 2010 by NIOSH and the Nordic Expert Group,
which is a collaboration among the Institutes of Environmental and Occupational Health in Norway,
Finland, Denmark, Iceland and Sweden (Nordic Expert Group 2010).

In 2009, the European Agency for Safety and Health at Work produced a report looking
specifically at the effects of combined exposures to noise and ototoxic substances, including interaction
between organic solvents and noise, on hearing. This working group concluded that “Good evidence”
(at least in animal studies) has been accumulated on the adverse effects on hearing of the following
solvents: toluene, ethylbenzene, n-propyl-benzene, styrene and methyl styrenes, trichloroethylene, p-

2


Issue 3. Necessitating lung lavages or lung biopsy on critically ill or elderly patients
Response:

Bronchoscopy with lung lavage and/or lung biopsy is generally contraindicated in critically ill or
elderly patients due to the risks of the procedures, which include bleeding, intubation and ventilation,
pneumothorax and infection.®°

Issue 4. Obtaining clarity on the specific diagnostic markers required for CBD in the pre or post 1993
diagnostic requirements.

Response:

As noted above, there is no one single diagnostic test for CBD and no specific diagnostic markers
“required for CBD”. There are also no new or additional diagnostic tests available to diagnose CBD.
The text of Chapter 2-1000 regarding pre and post 1993 CBD diagnostic criteria would benefit from
revision and greater consistency as noted above and below.

Issue 5. Clearer guidance on the relationship between sarcoidosis and CBD
Response:

The Advisory Board endorses a presumption of chronic beryllium disease (CBD) in situations
with a diagnosis of sarcoidosis in an individual who meets the definition of a “covered beryllium
employee” under Part E or Part B. This presumption already exists, as stated in EEOICPA Circular No.
08-07 and EEOICPA Procedure Manual Chapter 2-1000. However, implementation of this
presumption has been problematic. Revising the current text of the relevant Sections of the Procedure
Manual (Chpt 2-1000) and training materials should alleviate this problem.

Several key features regarding sarcoidosis and CBD should be clarified:

Sarcoidosis is as a multisystem granulomatous disorder that clinically and pathologically is
difficult to differentiate from CBD.'*? The granulomas seen histologically in both conditions are
indistinguishable and both can have extrapulmonary involvement. Sarcoidosis predominantly affects the
lungs and thoracic (hilar and mediastinal) lymph nodes, but can also involve other organs including the
skin, nose, liver, heart, other lymph nodes and the musculoskeletal system. About 90% of sarcoidosis
patients have pulmonary involvement.

The diagnosis of sarcoidosis is typically based on a tissue biopsy that shows non-caseating
granulomas in one of the affected organs (such as skin, nose, liver, lymph nodes, lung) along with the
patient’s clinical presentation and other diagnostic tests.'>'>-'® The organ biopsied (e.g. skin, nose)
usually indicates the safest way to obtain diagnostic tissue, not what organs are involved. Thus
pulmonary sarcoidosis not uncommonly is diagnosed by biopsy of an organ such as skin or lymph
nodes, rather than lung tissue. In such cases lung involvement is usually confirmed by chest imaging

and/or pulmonary function testing.
Published articles may highlight certain features that are more common in sarcoidosis vs.

CBD, '!! For example, extra pulmonary involvement is more common in sarcoidosis than CBD, and the
prevalence of sarcoidosis is higher in blacks than Caucasians. However, extrapulmonary involvement

13


an illness” should be defined, as many clinicians, including CMCs based on our review of cases, are not
familiar with the terminology.

For clarification, the “presumption of CBD when sarcoidosis” discussion above relates to
beryllium employees diagnosed with sarcoidosis. If a worker has evidence of lung disease and/or BeS
but has NOT been diagnosed with sarcoidosis, then the Part B CBD criteria should be used to document
a diagnosis of CBD and the Part E criteria used for other chronic respiratory conditions.

6. Recommendations or advice relating to conditions that are normal and usual consequential
illnesses to CBD

Response:

The March 2016 update of Chapter 2-1500 Consequential Conditions, Exhibit 1 contains a list of
disorders secondary to CBD and to CBD treatment (steroids). The list includes pulmonary hypertension,
right heart failure, respiratory infections, GERD, decreased bone density, diabetes and osteoporosis. The
Advisory Board agrees with the use of this list of conditions.

7. Input or suggestion regarding assessment of negative BeLPT as either false negative or borderline
due to drug interference or other treatment modalities

Response:

Beryllium sensitization is defined by EEOICPA as a single abnormal BeLPT, which most
commonly is performed on fresh peripheral blood cells.

The BeLPT result is occasionally reported as “borderline”. Two “borderline” BeLPT tests have
been shown to give about the same predictive value for beryllium sensitization as 1 abnormal (positive)
BeLPT test.2’78 Thus a person with two ‘borderline” BeLPT tests should be considered sensitized

to beryllium (BeS), and further BeLPT testing is not indicated.
The BeLPT is not a perfect test for BeS. False negative and positive BeLPT results can occur for

several reasons, as noted above.”

3. Chronic silicosis
Comments / Questions:

1. Clear guidance on the certification requirements for B-readers and how that is documented on B-
reader test results.

Response:
NIOSH provides a list of all certified B readers and also describes the B-reader certification

process on its website. https://wwwn.cdc.gov/niosh-thd/cwhsp/ReaderList.aspx. A claims examiner (and
others) can verify that a B reader is currently certified by checking the NIOSH website.

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