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Noninvasive diagnosis of chronic beryllium disease in workers exposed to hazardous dust in Israel
  1. Elizabeth M Fireman1,*,
  2. Oded Mazor1,
  3. Mordechai Kramer2,
  4. Israel Priel3,
  5. Yehuda Lerman4
  1. 1 Tel-Aviv Medical Center, Israel;
  2. 2 Beilinson Medical Center, Campus I. Rabin, Israel;
  3. 3 Edith Wolfson Medical Center, Israel;
  4. 4 Occupational Health Center, Clalit Health Services, Israel
  1. Correspondence to: Elizabeth M Fireman, Pulmonary and Allergic Diseases, Tel-Aviv Medical Center, 6 Weizman St, Tel-Aviv, Israel, Tel-Aviv, 64239, Israel; fireman{at}


Objectives: Chronic beryllium disease (CBD) is caused by prolonged occupational exposure to beryllium and is characterized by a wide variety of clinical presentations, mostly pulmonary. The inflammatory process involves non-caseous granulomas and proliferation of CD4+ cells. CBD is currently diagnosed by a lung biopsy that shows tissue granuloma formation, and by the beryllium lymphocyte proliferation test (BeLPT) which examines past exposure and sensitization to beryllium. The induced sputum (IS) technique was developed in recent years for diagnosing asthma, chronic obstructive pulmonary disease and interstitial lung diseases. A CD4/CD8 ratio >2.5 in T cells from IS is a positive result for granulomatous lung diseases. We had earlier revealed that dental technicians are exposed to excessive levels of beryllium. We now evaluated the efficacy of IS (CD4/CD8 >2.5) and BeLPT in diagnosing CBD in 17 workplaces in which beryllium is known to be present.

Methods: All consecutive patients with a clinical suspicion of CBD who were referred to our institution for diagnosis and management were enrolled. The results of the gold standard lung biopsy + BeLPT were compared to the noninvasive IS + BeLPT. Kappa and McNemar tests evaluated the agreement levels. Correlations between demographic and clinical parameters and a confirmed diagnosis of CBD were analyzed.

Results: The two approaches could be compared in 57 out of 98 suitable study candidates. There was a high level of agreement (Kappa 0.920) between IS + BeLPT and biopsy + BeLPT. IS + BeLPT had a specificity of 97.3% and a sensitivity of 87.5%. Twenty-one of the 87 exposed workers (24%) had CBD, of whom 12 were dental technicians (p = 0.044 dental technicians versus all other occupations).

Conclusions: This study demonstrated that the CD4/CD8 ratio in IS together with positive/negative BeLPT findings are highly suggestive to support the diagnosis of CBD.

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