AMERICAN THORACIC SOCIETY DOCUMENTS An Official American Thoracic Society Statement: Diagnosis and Management of Beryllium Sensitivity and Chronic Beryllium Disease John R. Balmes, Jerrold L. Abraham, Raed A. Dweik, Elizabeth Fireman, Andrew P. Fontenot, Lisa A. Maier, Joachim Muller-Quernheim, Gaston Ostiguy, Lewis D. Pepper, Cesare Saltini, Christine R. Schuler, Tim K. Takaro, and Paul F. Wambach; on behalf of the ATS Ad Hoc Committee on Beryllium Sensitivity and Chronic Beryllium Disease THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY (ATS) WAS APPROVED BY THE ATS BOARD OF DIRECTORS, June 2014 Rationale: Beryllium continues to have a wide range of industrial evidence of a granulomatous inflammatory response in the lung is applications. Exposure to beryllium can lead to sensitization (BeS) diagnostic of CBD. The determinants of progression from BeS to and chronic beryllium disease (CBD). CBD are uncertain, but higher exposures and the presence of a genetic variant in the HLA-DP b chain appear to increase the risk. Periodic Objectives: The purpose of this statement is to increase awareness evaluation of affected individuals can detect disease progression and knowledge about beryllium exposure, BeS, and CBD. (from BeS to CBD, or from mild CBD to more severe CBD). Methods: Evidence was identified by a search of MEDLINE. The Corticosteroid therapy is typically administered when a patient with fi committee then summarized the evidence, drew conclusions, and CBD exhibits evidence of signi cant lung function abnormality or described their approach to diagnosis and management. decline. Main Results: The beryllium lymphocyte proliferation test is the Conclusions: Medical surveillance in workplaces that use cornerstone of both medical surveillance and the diagnosis of BeS and beryllium-containing materials can identify individuals with BeS and CBD. A confirmed abnormal beryllium lymphocyte proliferation test at-risk groups of workers, which can help prioritize efforts to reduce without evidence of lung disease is diagnostic of BeS. BeS with inhalational and dermal exposures. Contents Natural History and Management drew conclusions, and described their usual of BeS Overview approach to diagnosis and management. Natural History and Management Introduction of CBD d The beryllium lymphocyte proliferation Methods Prevention test (BeLPT) is used for medical Epidemiology Conclusions surveillance and the diagnosis of BeS and Genetic Susceptibility CBD. A BeLPT is considered “abnormal” Immunopathogenesis if two or more of the six stimulation Pathology indices exceed the normal range. A test is Diagnostic Criteria Overview typically considered “borderline” if only BeLPT one of the six stimulation indices exceeds Diagnostic Criteria for BeS Many workers are exposed to beryllium the normal range. Diagnostic Criteria for CBD throughout the world, and sensitization to d A diagnosis of BeS in beryllium-exposed Evaluation the metal continues to occur. To address this workers undergoing medical surveillance Clinical Manifestations of BeS problem, an international committee of can be based on two abnormal blood and CBD experts was convened to write a statement BeLPTs, one abnormal and one Diagnostic Evaluation for BeS about beryllium sensitization (BeS) and borderline blood BeLPT, or one and CBD chronic beryllium disease (CBD). After abnormal bronchoalveolar lavage (BAL) Natural History and thoroughly reviewing the literature, the BeLPT. Workers identified as having BeS Management committee summarized the relevant evidence, are evaluated for CBD. An Executive Summary of this document is available at http://www.atsjournals.org/doi/suppl/10.1164/rccm.201409-1722ST/suppl_file/Executive_Summary.pdf Am J Respir Crit Care Med Vol 190, Iss 10, pp e34–e59, Nov 15, 2014 Copyright © 2014 by the American Thoracic Society DOI: 10.1164/rccm.201409-1722ST Internet address: www.atsjournals.org e34 American Journal of Respiratory and Critical Care Medicine Volume 190 Number 10 | November 15 2014 AMERICAN THORACIC SOCIETY DOCUMENTS d Pulmonary function testing (PFT) and as machining metal parts, can lead to BeS author directed. They did not conform to the chest imaging (either a chest radiograph and CBD (1). The major applications of standards of a systematic review. Structured or chest computed tomography scan) are beryllium are in automotive electronics, discussions were used to determine the typically performed on any patient whose telecommunications, computers, aerospace, committee members’ usual approach to the BeLPT is diagnostic of BeS. In contrast, and defense equipment (Table 1). One diagnosis and management of BeS and CBD. bronchoscopy with transbronchial biopsy study estimated that as many as 134,000 Variations in clinical practice were infrequent is performed on a case-by-case basis. current U.S. workers may be exposed and minor; therefore, the approach described The following criteria favor performing to beryllium (2), but the number of reflects the committee’s collective clinical bronchoscopy: (1) absence of individuals ever exposed is much greater. experience in occupational health programs. contraindications, (2) evidence of Beryllium exposure is not a problem The committee’s work was partially pulmonary function abnormalities, (3) limited to the United States, as cases of supported by funds from the U.S. evidence of abnormalities on chest imaging, CBD have been reported in many other Department of Energy (DOE) and the and (4) personal preference of the patient. countries (3–10). Beryllium-exposed National Institute for Occupational Safety d The diagnosis of CBD is based on individuals may be unaware of their and Health (NIOSH). the demonstration of both BeS and exposure, and physicians may be unaware granulomatous inflammation on lung of beryllium-related health effects; therefore, Epidemiology biopsy. Depending on the clinical setting, BeS and CBD may not be recognized. feasibility of certain diagnostic tests, and This statement reviews current The first cases of beryllium-related disease degree of diagnostic certainty needed, knowledge about BeS and CBD, including were identified soon after industrial use probable CBD can be diagnosed based its diagnosis, management, and prevention. of beryllium began in the 1930s (11–13). on differing combinations of diagnostic In the mid-1940s, reports of “beryllium criteria, including a clinical presentation poisoning” in the United States appeared consistent with CBD, a history of Methods (14), including cases from the fluorescent beryllium exposure, evidence of BeS (e.g., light industry that had features of sarcoidosis abnormal BeLPT), radiographic findings, The chair of the committee was selected by (15). Additional cases appeared among lung histology, BAL findings, and PFT the leadership of the American Thoracic workers employed in other beryllium-using abnormalities. Society based on expertise and experience. industries as well as among individuals d Periodic evaluation (every 1–3 yr) is The chair invited individuals to participate living near beryllium production facilities performed to determine if an individual in the committee on the basis of their (16–18). The Atomic Energy Commission with BeS has progressed to CBD. It expertise in one or more aspects of BeS established a beryllium case registry for both includes a symptom review, physical and/or CBD. Prospective members of the acute disease and CBD (19, 20). The acute examination, and PFT, followed by committee were required to disclose all cases were observed among workers exposed a chest computed tomography scan if financial interests relevant to the subject to high levels of soluble forms of beryllium; pulmonary function has deteriorated and matter of the statement. Disclosures were however, the distribution of the chronic bronchoscopy on a case-by-case basis. reviewed by the American Thoracic Society disease did not follow a linear exposure– d Corticosteroid therapy is initiated when prior to appointment of the committee, and response model. The high variability of a patient with CBD exhibits significant appointments were made according to disease occurrence in different groups lung function abnormality or decline. American Thoracic Society policies for of workers, disease in workers with short Steroid-sparing agents are considered management of conflicts of interest. In latency, and incident disease in community if significant side effects occur. addition, individuals with conflicts of residents led to the hypothesis that CBD was d Medical surveillance in workplaces that interest related to the subject matter of the immunologically mediated (17). use beryllium-containing materials can statement acknowledged those conflicts in In 1949, the Atomic Energy identify individuals with BeS and at-risk a face-to-face meeting, stated that they Commission proposed a workplace airborne groups of workers, which can help would not bias their participation on the exposure limit of 2 mg/m3 averaged prioritize the efforts to reduce inhalational committee, and were not assigned to work over an 8-hour period (21). After the and dermal exposures. The BeLPT is on sections of the document that addressed implementation of this standard, reports the cornerstone of medical surveillance. issues related to their conflict. of acute beryllium disease ceased, and the Individuals with beryllium exposure who Each member with primary number of new cases of CBD decreased. do not have BeS at the time of initial responsibility for writing a section of the The U.S. Occupational Safety and