Washington Administrative Code › Title 296 - Labor and Industries, Department of › Chapter 296-850 - BERYLLIUM › Section 296-850-190 - Appendix B-Considerations when using the blood beryllium lymphocyte proliferation test in the screening and evaluation of beryllium sensitization-Nonmandatory

Current through Register Vol. 24-14, July 15, 2024
Purpose:
The purpose of this appendix is to provide medical
				information and recommendations to aid physicians and other licensed
				health care professionals (PLHCPs) regarding compliance with the
				medical surveillance provisions of the beryllium standard. Appendix B
				is for informational and guidance purposes only and none of the
				statements in Appendix B should be construed as imposing a mandatory
				requirement on employers that is not otherwise imposed by the
				beryllium standard (chapter 296-850 WAC, Beryllium). The complete
				medical surveillance requirements for examinations and procedures
				under this chapter are described in WAC 296-850-155.
Chronic Beryllium Disease and Beryllium
				Sensitization:
Chronic beryllium disease (CBD) is a chronic
				granulo-matous (inflammatory) disease primarily of the lung, caused
				by exposure to beryllium that meets the diagnostic criteria published
				in the
Department of Labor and Industries Clinical Guideline
				for the Diagnosis of Beryllium Sensitization and Chronic Beryllium
				Disease
. Some patients diagnosed with CBD remain free of
				symptoms following diagnosis, while others develop progressive
				worsening of clinically significant disease. (Balmes et al. 2014.
				Page e54) "Medical therapy of CBD is directed at suppressing the
				immune response to beryllium and subsequent granuloma formation and
				fibrosis." (Ibid)
Summarizing their review of the development of
				beryllium sensitization, the Federal Occupational Safety and Health
				Administration (OSHA) described how the immune systems of sensitized
				workers have been activated to react to beryllium exposures such that
				subsequent exposure to beryllium can progress to serious lung
				disease. (OSHA 2017, page 2492) According to this rule, sensitized
				workers are considered to be confirmed positive if supported by two
				abnormal BeLPT test results, an abnormal and a borderline test
				result, or three borderline test results, or any cases confirmed by
				the criteria published in the
Department of Labor and
				Industries Clinical Guideline for the Diagnosis of Beryllium
				Sensitiza-tion and Chronic Beryllium Disease
. It also means
				the result of a more reliable and accurate test indicating a person
				has been identified as having beryllium sensitization.
It is prudent to remove sensitized workers from
				further exposure to beryllium. (Balmes et al. 2014; OSHA 2017)
Additional information regarding beryllium
				sensitization and chronic beryllium disease are included in the
Department of Labor and Industries Clinical Guideline for the
				Diagnosis of Beryllium Sensitization and Chronic Beryllium
				Disease
, which may be requested from the department.
The Beryllium Lymphocyte Proliferation
				Test:
The beryllium lymphocyte proliferation test is
				performed by taking lymphocytes from either bronchoalveolar lavage
				fluid (the BAL BeLPT) or peripheral blood (the blood BeLPT), culturing them
in vitro
, and exposing them to
				beryllium sulfate to stimulate lymphocyte proliferation. The
				observation of beryllium-specific proliferation indicates beryllium
				sensitization.
While test results from either the blood BeLPT or the
				BAL BeLPT can be used to confirm sensitization to beryllium, (L&I
				Clinical Beryllium Guideline) it is the blood BeLPT that is typically
				used when screening for beryllium sensitization. Abnormal and
				borderline test results are considered "other than normal" in that
				they form the basis for diagnosing beryllium sensitization according
				to the diagnostic criteria used by this rule. Under these diagnostic
				criteria, no single blood BeLPT result can be used to diagnose
				beryllium sensitization.
The sensitivity of the BeLPT refers to its ability to
				correctly yield an other than normal result (i.e., abnormal or
				borderline) in those who are truly sensitized to beryllium. The
				specificity of the test refers to its ability to correctly yield a
				normal result in those who are not sensitized to beryllium.
Per Stange et al. (2004) and Middleton et al. (2006),
				for a single blood BeLPT the sensitivity is 0.723, and the
				specificity is 0.9737.
Abnormal or borderline results in workers who are in
				fact not sensitized to beryllium are considered false positives.
				Normal results in workers who are truly sensitized to beryllium are
				considered false negatives.
The diagnostic criteria for confirmed positive
				beryllium sensitization used by this rule requires any single
				abnormal or borderline blood BeLPT result be confirmed, which reduces
				the risk of unsensitized workers being falsely labeled as sensitized
				by false positive results of the blood BeLPT.
With a sensitivity of 0.723, a single blood BeLPT
				would be expected to falsely yield a negative result in nearly thirty
				percent of truly sensitized workers who undergo the test. Testing
				algorithms have been published that use multiple blood BeLPTs to
				reduce false negative results while continuing to control the risk of
				false positives. (Middleton et al. 2006, L&I Clinical Beryllium
				Guideline)
Thus, by controlling the sequence and number of
				blood BeLPTs he or she orders, the ordering provider exerts
				significant control over the risk that workers who are truly
				sensitized to beryllium could be falsely labeled as unsensitized due
				to false negative results of the blood BeLPT.
The following is
				designed to provide information to assist the ordering provider who
				tailors these decisions to the needs of the population and
				individuals being tested.
These published testing algorithms reduce the risk of
				false negatives by using split-sample blood beryllium lymphocyte
				proliferation testing, which is the measurement of blood lymphocyte
				proliferation in two laboratory tests when a single sample of blood
				is split into two samples and sent to two independent laboratories,
				whereupon the lymphocytes are challenged with a soluble beryllium
				salt and two results returned. (Welch et al. 2004; Middleton et al.
				2006; Balmes et al. 2014, OSHA 2017)
The highest sensitivity for performing beryllium
				sensiti-zation testing using the blood BeLPT (86%) described in NIOSH
				beryllium rulemaking testimony (NIOSH page 32) relies upon a testing
				algorithm that requires either one or two rounds of testing, where
				split-sample blood BeLPTs are performed at each round. Thus, a
				minimum of two initial blood BeLPTs are obtained from independent
				laboratories in this testing algorithm, followed if needed by a
				second simultaneously-obtained pair. (Middleton et al. 2006)
An alternative algorithm with a lower sensitivity
				(65.7%) uses a single blood BeLPT for the initial round of testing.
				If the initial result is abnormal or borderline, this triggers a
				second round of testing with a split-sample blood BeLPT.
				(Ibid)
Round two split-sample testing:
Although not required by this rule, providers should
				consider the advantages of using split-sample testing for the second
				round of blood BeLPT testing, compared to single-sample
				testing:
*If only a single blood BeLPT is performed during a
				second round of testing, nearly thirty percent of truly sensitized
				workers would be expected to have a false negative test result and
				additional evaluation recommended.
*Split-sample testing for the second round decreases
				the risk of such false-negative results
*Based on published blood BeLPT performance
				characteristics (Stange et al. 2004; Middleton et al. 2006) false
				negative tests are more common than false positives (unless beryllium
				sensitization is sufficiently rare in the screened
				population.)
*For some result patterns, split-sample testing may
				be a faster way to arrive at a sensitization determination, which may
				be particularly relevant for workers who are receiving medical
				removal protection benefits while the diagnostic evaluation
				proceeds
*The risk of false-positives is low with either
				algorithm that uses split-sample testing (Middleton et al.
				2006)
Per WAC 296-850-155(3)(b)(v) and (vii), employers
				must make split-sample testing available to workers if requested by
				the provider who is determining whether an employee is sensitized to
				beryllium. In addition, WAC 296-850-155(3)(b)(v) and (vii)  requires
				employers to make multiple rounds of blood BeLPT testing available if
				requested by the provider. Providers need not cease testing if an
				initial abnormal or borderline result is followed by single- instead
				of split-sample testing and a single negative blood BeLPT results,
				for example.
Per WAC 296-850-155(5)(c) and (6)(c) providers may at
				any time choose to refer workers to their choice of either a chronic
				beryllium disease diagnostic center that is mutually agreed upon by
				the employer and the employee, or to a facility recognized by the
				department as a center for research and clinical assessment of
				chemically related illness (see
				RCW
				 51.32.360).
Round one split-sample testing:
Although not required by this rule, providers should
				also consider circumstances under which split-sample testing at the
				time of the initial evaluation may be advantageous:
* This achieves the highest sensitivity (86%) of any
				screening algorithm described in this appendix, while controlling the
				risk of false-positive test results. (Middleton et al. 2006)
*Except in populations where beryllium sensitization
				is sufficiently rare, this increase in sensitivity compared to
				performing the first round of testing with just a single blood BeLPT
				significantly reduces the number of false negative test results
				relative to the increase in false positives.
* Patient-specific considerations include the risk of
				loss-to-follow-up, the expected time to next screening examination,
				provider index of suspicion, and the consequences of sustaining
				ongoing exposure to beryllium in the case of a missed
				diagnosis.
Additional considerations:
The tests used to diagnose beryllium sensitization
				may have been performed at any time following exposure. (L&I
				Clinical Beryllium Guideline) Thus, there may be a need to gather
				additional records of tests that have yielded abnormal or borderline
				results, but that may not be in the possession of the employer or
				provided to the provider at the start of the screening
				examination.
Diagnostic criteria used in the rule anticipate the
				possibility of false-negative testing: If deemed appropriate,
				sensi-tization can be confirmed by bronchoalveolar lavage BeLPT (BAL
				BeLPT). (L&I Clinical Beryllium Guideline)
Diagnosing chronic beryllium disease using the
				secondary diagnostic pathway requires all criteria be met and
				requires the performance of both the blood BeLPT and BAL BeLPT
				(unless medically contraindicated), but does not require
				sensitization be confirmed as described in the primary diagnostic
				pathway. (L&I Clinical Beryllium Guideline)
Concluding recommendations:
Providers should consider providing split-sample
				blood BeLPTs in nearly all circumstances where round two testing is
				indicated or required.
Providers should consider whether patient- and
				population-based considerations warrant using split-sample testing
				for the first round of blood BeLPT testing.
References:
Balmes, J.R., 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
(10): p. e34-59.
Beryllium hearing exhibit 005: National Institute for
				Occupational Safety and Health (NIOSH) Testimony. Docket No.
				OSHA-H005C-2006-0870-1725.
The Clinical Guideline for the Diagnosis of
				Beryllium Sensitization and Chronic Beryllium Disease
, as
				published by the Washington State Department of Labor and
				Industries.
Department of Labor: Occupational Safety and Health
				Administration (OSHA).
Occupational Exposure to
				Beryllium
. Federal Register. Vol. 82, No. 5. Monday, January
				9, 2017. Rules and Regulations. Docket No.
				OSHA-H005C-2006-0870.
Middleton, D.C., et al. The BeLPT: algorithms and
				implications. Am J Ind Med, 2006.
49
(1): p.
				36-44.
Stange, A.W., F.J. Furman, and D.E. Hilmas.
The beryllium lymphocyte proliferation test: Relevant issues
				in beryllium health surveillance
. Am J Ind Med, 2004. 46(5):
				p. 453-62. Middleton et al. 2006.
Welch, L., et al.
Screening for Beryllium
				Disease Among Construction Trade Workers at Department of Energy
				Nuclear Sites
. Am J Ind Med, 2004.
				46:207-218.