Oesophagectomy as a model of the Acute Respiratory Distress Syndrome

Howells, Phillip Alexander (2019). Oesophagectomy as a model of the Acute Respiratory Distress Syndrome. University of Birmingham. M.D.

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Abstract

Acute Respiratory Distress Syndrome (ARDS) is a lifethreatening illness which can follow major surgery, including oesophagectomy. This thesis aimed to confirm the importance of ARDS in this cohort and assess the effects of GSK2862277

Methods

Analysis of previous oesophagectomy trials modelling ARDS sought differences between the studies and identified risk factors. The immunomodulatory effects of oesophagectomy and critical illness and novel therapeutic GSK2862277 on macrophage and neutrophil function were investigated using in vitro assays.

Results

Previous trials showed the harm to patients associated with ARDS, but falling ARDS rates more recently. Active smoking and pre-operative dihydropyridine use were risk factors for ARDS. Oesophagectomy and critical illness modulate neutrophil extracellular trap formation but not phagocytosis. GSK2862277 appears to cause an off-target effect increasing neutrophil extracellular trap formation. GSK2862277 increases alveolar macrophage phagocytosis.

Discussion

Perioperative ARDS has decreased following oesophagectomy although it is harmful to patients who develop it. Oesophagectomy is no longer useful as a model of ARDS. Major surgery and critical illness effect neutrophil function, which may drive complications in these cohorts. Macrophage function was modulated by GSK2862277, suggesting it may have promise in future for preventing or treating ARDS and other post-operative pulmonary complications.

Type of Work:

Thesis (Doctorates > M.D.)

Award Type:

Doctorates > M.D.

Supervisor(s):