To the Editor:
For practitioners treating and preventing chronic beryllium disease (CBD), the recent publication from the Environmental and Occupational Health Sciences Division at National Jewish Medical and Research Center (NJMRC) of their longitudinal experience with beryllium sensitization (BeS) progressing to CBD is a welcome validation of growing efforts to control this epidemic in beryllium workers (1). The total number of workers in the United States with potential for current exposure was recently estimated to be 134,000 (2), and an even larger number of former workers are at risk. The DOE nuclear weapons program has screened over 40,000 production and cleanup workers with the beryllium lymphocyte proliferation test (BeLPT), the largest cohort where the test has been deployed (3). Over 230 cases of CBD have been diagnosed in this cohort with over 750 additional workers sensitized.
CBD, which is preceded by BeS, is a slowly progressive disease. We would therefore expect BeS workers who are closely followed with the BeLPT and invasive diagnostic testing to have disease detection at its earliest stage. In his accompanying commentary, Dr. Cullen suggests that recently diagnosed cases of CBD do not have the "associated clinical manifestations of CBD" (4). However, after follow-up of 4.7 yr (1.6-10) over half showed an average 15.5% decline in DL^sub CO^ and/or similar decline in VO^sub 2^max. Nevertheless, the article by Newman and coworkers (1) does leave open some questions about their clinical findings in CBD. What were the physiologic characteristics of the workers diagnosed with CBD at baseline who are not in their longitudinal study of BeS progression? How many of those CBD cases have required treatment? Are the nine individuals who progressed from BeS to CBD and had physiologic deficits the same workers?
Even in the absence of these data, Newman and coworkers have made a convincing argument for ongoing screening and surveillance of beryllium-exposed workers. Detecting a disease in its early stages before large reductions occur in function is beneficial as identified by Cullen and coworkers, in a previous paper (5). The experience with DOE workers shows that LPT testing provides the benefit of early detection. Longer followup in the DOE group, as with the NJMRC cohort, is likely to yield an increase in those with significant physiologic impairment. Considering the recent confirmation of the risk to workers in industries using low percentage beryllium alloys (6), even workers with relatively low exposures should be tested.
Conflict of Interest Statement: T.K.T. is a medical consultant to the Dept. of Labor Energy Employees Occupational Illness Compensation Program and advises on medical aspects of workers' beryllium claims. He was also paid as an expert on a panel evaluating the use of the beryllium lymphocyte proliferation test convened by Exponent and paid for by Brush Wellman, Inc. LP. was the Chair of the Current Worker Beryllium Surveillance Program for Rocky Flats Workers. The program was managed by the Occupational and Environmental Health Program at National Jewish Medical Center. He received approximately $500-$1,000 per year for 3.5 years as the Panel Chair. He also received travel expenses, and food and lodging. He was a Visiting Professor and Lecturer at National Jewish Medical Center in 1999 and received $500.
TIM K. TAKARO
University of Washington
1. 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.
2. Henneberger PK, Goe SK, Miller WE, Doney B, Groce DW. Industries in the United States with airborne beryllium exposure and estimates of the number of current workers potentially exposed. J Occup Environ Hyg 2004;1:648-659.
3. Stange AW, Furman FJ, Hilmas DE. The beryllium lymphocyte proliferation test: relevant issues in beryllium health surveillance. Am J Ind Med 2004;46:453-462.
4. Cullen MR. Screening for chronic beryllium disease: one hurdle down, two to go. Am J Respir Crit Care Med 2005;171:3-4.
5. Sood A, Beckett WS, Cullen MR. Variable response to long-term corticosteroid therapy in chronic beryllium disease. Chest 2004;126:2000-2007.
6. Schuler CR, Kent MS, Deubner DC, Berakis MT, McCawley M, Henneberger PK, Rossman MD, Kreiss K. Process-related risk of beryllium sensitization and disease in a copper-beryllium alloy facility. Am J Ind Med 2005;47:195-205.
From the Authors:
We thank Drs. Takaro and Pepper for their letter and agree with their conclusions supporting medical surveillance using the BeLPT. The substantial number of cases of CBD and BeS that they report in the DOE cohort supports Dr. Cullen's statement in his editorial accompanying our paper that "the blood BeLPT has now met the first of three critical challenges for a screening test; that those testing positive have a high likelihood of developing CBD" (1). Epidemiologic studies have shown that an average of 50% (range, 14-100%) of individuals with abnormal BeLPTs have CBD on initial clinical evaluation. Our study of surveillance-identified BeS addressed the clinical fate of the remainder: workers who had BeS without evidence of CBD. Those workers progress to CBD at a rate of 6 to 8% per year (2).
We agree with Drs. Takaro and Pepper that Cullen's editorial is wrong to suggest that our subjects lack the "associated clinical manifestations of CBD." They correctly point out that nine patients who progressed to CBD showed a significant decline in DL^sub CO^ and VO^sub 2^max. Only 11 of the 17 patients who progressed to CBD had the opportunity for follow-up evaluations. It is notable that all 11 showed some objective, physiologic decrements over the average 4.7-yr follow-up period, with one patient requiring corticosteroid treatment. These results address the second screening test "hurdle": "showing that patients diagnosed with CBD clinically manifest disease." Drs. Takaro and Pepper inquired about the characteristics of workers diagnosed with CBD at baseline who were not part of this longitudinal study. We have been following more than 150 surveillance-identified patients with CBD and are currently analyzing longitudinal clinical data. This cohort will allow us to determine the progression of physiologic measures in CBD over time.
As Drs. Takaro and Pepper note, a separate publication by Cullen and colleagues (3) snowed that treatment with corticosteroids is beneficial in CBD-a finding that is supported by other case series (4, 5), thus addressing the third hurdle for a screening test: "intervention made after a positive test has the potential to change the natural history."
The letter from Drs. Takaro and Pepper supports the need for continued surveillance with the BeLPT for former and current workers, as well as to clinically follow those diagnosed with BeS and CBD. The case supporting the use of medical surveillance in secondary prevention and in aiding primary prevention strategies is clear.
Conflict of Interest Statement: None of the authors have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
LEE S. NEWMAN
MARGARET M. MROZ
LISA A. MAIER
National Jewish Medical and Research Center
1. Cullen MR. Screening for chronic beryllium disease: one hurdle down, two to go. Am J Respir Crit Care Med 2005;171:3-4.
2. 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.
3. Sood A, Beckett WS, Cullen MR. Variable response to long-term corticosteroids therapy in chronic beryllium disease. Chest 2004;126:2000-2007.
4. Stoeckle JD, Hardy HL, Weber AL. Chronic beryllium disease: long-term follow-up of sixty cases and selective review of the literature. Am J Med 1969;46:545-561.
5. Gaensler EA, Verstraeten JM, Weil WB, Cugell DW, Marks A, Cadigan JB, Jones RH, Ellicott MF. Respiratory pathophysiology in chronic beryllium disease. AMA Arch Ind Health 1958;19:50,132-163,146.
Copyright American Thoracic Society Nov 1, 2005
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