Shortfalls in imputing sarcoidosis to occupational exposures

Abstract

The cause of sarcoidosis remains elusive. Reports of elevated sarcoidosis incidence in New York City firefighters and World Trade Center disaster responders have been advanced to support a causal relationship. This inference is open to question due to methodological differences in assessing and computing sarcoidosis incidence in populations versus putative occupational exposures. The magnitude of the odds ratio (OR; ca. 1.5) of causal candidates in the ACCESS case-control study of occupational and environmental exposures is sufficiently small that it might easily be attributable to confounders. Additionally, multiplicity of comparisons, difficulty in assembling a valid control population and the potential for recall bias critically limit causal inferences. A possible explanation for etiological elusiveness and multiplicity of elevated OR is that individuals with sarcoidosis, lacking components of efficient cellular immunity, respond with systemic granulomas to a variety of ubiquitous, frequently unidentifiable environmental antigens. Epidemiological methods for the identification of sarcoidosis causal candidates are potentially misleading and are unlikely to prove useful.

Post-9/11 sarcoidosis in WTC-exposed firefighters and emergency medical service workers

“…[24, 25] To address this point, we undertook two sensitivity analyses. The first limited both REP and FDNY cases to persons with symptomatic intra-thoracic involvement at presentation, as we reasoned that these individuals would likely have received a sarcoidosis diagnosis regardless of screening practices.…”

Response

“…Pleurodesis is defined as "fusion of the visceral and parietal pleura to prevent collapse of the lung with pneumothorax or accumulation of pleural fluid with pleural effusions." 2 As stated in our paper, only in animal models it is possible to document the quality and extent of macroscopic pleural adhesions, microscopic pleural inflammation, and collagen deposition after the various forms of pleural interventions used to induce pleurodesis. We would agree that our rabbits did not have complete obliteration of the pleural space after the interventions were performed in a 3-cm area of the apex of the right pleural cavity, mimicking the apical pleurectomy or pleurodesis by abrasion commonly used in clinical practice to control recurrent pneumothorax.…”

A critical analysis of sarcoidosis incidence assessment

“…This inference is weakened by ascertainment bias, lack of an identified putative antigen, the incidence-trebling effect of cohort radiographic surveillance, and the employment of the surveyed, working age cohort as the denominator in the computation [13]. …”