Abstract

Decompression sickness (DCS) develops due to inert gas bubble formation in bodily tissues and in the circulation, leading to a wide range of potentially serious clinical manifestations. Its pathophysiology remains incompletely understood. In this study, we aim to explore changes in the human leukocyte transcriptome in divers with DCS compared to closely matched unaffected controls after uneventful diving. Cases (n = 7) were divers developing the typical cutis marmorata rash after diving with a confirmed clinical diagnosis of DCS. Controls (n = 6) were healthy divers who surfaced from a ≥25 msw dive without decompression violation or evidence of DCS. Blood was sampled at two separate time points—within 8 h of dive completion and 40–44 h later. Transcriptome analysis by RNA-Sequencing followed by bioinformatic analysis was carried out to identify differentially expressed genes and relate their function to biological pathways. In DCS cases, we identified enrichment of transcripts involved in acute inflammation, activation of innate immunity and free radical scavenging pathways, with specific upregulation of transcripts related to neutrophil function and degranulation. DCS-induced transcriptomic events were reversed at the second time point following exposure to hyperbaric oxygen. The observed changes are consistent with findings from animal models of DCS and highlight a continuum between the responses elicited by uneventful diving and diving complicated by DCS. This study sheds light on the inflammatory pathophysiology of DCS and the associated immune response. Such data may potentially be valuable in the search for novel treatments targeting this disease.

Highlights

  • Decompression sickness (DCS) is a potentially fatal condition usually observed after scuba diving

  • One subject presented with limb pain; this was not exclusive limb-pain DCS since it was accompanied by a typical cutis marmorata skin rash and preceded by dyspnea

  • This study describes changes in the peripheral blood leukocyte transcriptome in divers with cutaneous DCS compared to matched controls after uneventful diving

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Summary

Introduction

Decompression sickness (DCS) is a potentially fatal condition usually observed after scuba diving. Cutis marmorata manifesting after diving is pathognomonic of DCS It consists of a patchy, geographical rash usually crossing the midline, commonly involving fatty tissues such as the abdomen, breasts, buttocks, thighs, and the torso and back. It is well-established that this subtype of DCS is associated with arterialization of bubbles via intracardiac right-to-left shunting of venous gas emboli, most commonly due to the presence of a patent foramen ovale (PFO) (Wilmshurst, 2015). Another potential mechanism is through right-toleft shunting via intrapulmonary arteriovenous anastomoses (IPAVA) (Madden et al, 2015). This subtype of DCS is distinct from musculoskeletal DCS, which is thought to be due to the presence of in situ autochthonous bubble formation (Edmonds et al, 2015)

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