T2 Vitamin D supplementation reduces perioperative systemic and alveolar inflammation in patients undergoing oesophagectomy: Results of the Vindaloo Trial

Abstract

Vitamin D deficiency is associated with increased risk of ARDS post-oesophagectomy. We recruited patients to a double-blind, randomised controlled trial of high dose Vitamin D supplementation 3–14 days pre-oesophagectomy.79 patients were randomised to receive placebo or 300,000 IU oral Vitamin D liquid 3–14 days prior to oesophagectomy. Blood samples were collected pre-dose, post-dose (pre-op) and post-op and analysed for 25-OH and 1,25-dOH Vitamin D, inflammatory cells and cytokines. Broncho-alveolar lavage fluid was collected at the end of the operation. PICCO biomarkers of alveolar capillary damage (EVLWI and PVPI) were measured pre- and post-op.Pre-operative supplementation with Vitamin D was well tolerated with no SUSARs and significantly increased circulating 25-OH and 1,25-OH Vitamin D (p < 0.0001). This was associated with reduced systemic inflammation (IL-6 (p = 0.02) and IL-8 (p = 0.002)) and an increase in circulatory Treg (p = 0.027).Changes in PICCO biomarkers were lower in supplemented patients suggesting lower perioperative alveolar oedema (EVLWI p = 0.05, PVPI p = 0.04). This did not result in a significant difference in oxygenation at 24 h.Post-op, systemic and alveolar alarmin (IL-1B, IL-6, IL-8) response was similar in treated and untreated patients but the systemic release of IL-1ra (p = 0.046), sTNFR-1 (p = 0.05) and s-TNFR-2 (p = 0.02) were elevated in treated patients. There was also evidence of decreased alveolar macrophage efferocytosis in patients with Vitamin D deficiency (p = 0.003).Clinical diagnoses of ARDS were significantly lower in this cohort than in previous cohorts, but the study was not powered to detect that outcome. Mortality post-operative was not significantly different at 30 or 90 days but there is a significant difference after 300 days of follow-up (placebo 33% mortality, Vitamin D 8% mortality p = 0.033).In conclusion, vitamin D supplementation was a safe, well tolerated pre-operative intervention that reduced systemic inflammation and biomarkers of alveolar oedema. With evidence of enhanced anti-inflammatory mechanism that may have influenced longer term post-operative survival, Vitamin D deficiency should be identified and treated in patients at risk of ARDS.

Can Optimum Solar Radiation Exposure or Supplemented Vitamin D Intake Reduce the Severity of COVID-19 Symptoms?

“…A murine model study also found that dietary-induced vitamin D deficiency contributes to exaggerated alveolar inflammation, epithelial damage, and hypoxia [ 10 ]. Similar results have emerged from researchers who reported that many esophagectomy patients suffer from ARTI and ARDS in the post-operative environment, and vitamin D supplementation during pre-operative days appears to reduce the risk of ARTI and ARDS in those cohorts [ 60 ]. They also found that vitamin D supplementation increased the concentration of 25-hydroxyvitamin D and 1,25 dihydroxy vitamin D in affected patients, which contributed to reduced lung inflammation [ 60 ].…”

“…Apart from the effects of COVID-19, general respiratory tract infections occur worldwide, causing millions of fatalities annually (2.8 million in 2010) [ 58 ]. There have been several articles published, which have shown the relationship between vitamin D levels in the body and the potential occurrence of ARTI and ARDS [ 10 , 31 , 59 , 60 , 61 , 62 ].…”

Vitamin D to Prevent Lung Injury Following Esophagectomy—A Randomized, Placebo-Controlled Trial*

“…We conducted a phase 2 randomized, placebo-controlled trial to test our hypothesis that high-dose cholecalciferol treatment preoperatively reduces markers of alveolar epithelial lung injury seen post esophagectomy, a high-risk population of developing ARDS. Results of these studies have been previously reported in the form of an abstract ( 26 ).…”

Review of the British Thoracic Society Winter Meeting 2015, 2–4 December, London, UK

“…Her group previously reported that vitamin D deficiency appears to contribute to the development of acute respiratory distress syndrome (ARDS)3 and now demonstrate that vitamin D supplementation reduces perioperative extravascular lung water but not oxygenation 1. The immunomodulatory effects of vitamin D (or the absence of them) have been a recurring theme of our 3 years reporting from the BTS Winter Meeting and we look forward to large confirmatory studies 4 5.…”

“…Dr Rachel Dancer (Birmingham University) received the BLF award for demonstrating that vitamin D supplementation reduces extravascular lung water, a surrogate marker of lung injury, after oesophagectomy in the VINDALOO trial1 (confirming Birmingham as the home of UK Indian Cuisine after the equally delicious BALTI trial!2). Her group previously reported that vitamin D deficiency appears to contribute to the development of acute respiratory distress syndrome (ARDS)3 and now demonstrate that vitamin D supplementation reduces perioperative extravascular lung water but not oxygenation 1.…”