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

Parekh, Dhruv; Dancer, Rachel; Scott, Aaron; D'Souza, Vijay; Howells, Phillip A; Mahida, Rahul; Tang, Jonathan; Cooper, Mark; Fraser, William D.; Tan, LamChin; Gao, Fang; Martineau, Adrian R.; Tucker, Olga; Perkins, Gavin D.; Thickett, David

doi:10.1097/ccm.0000000000003405

Cited by 54 publications

(69 citation statements)

References 48 publications

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“…Oesophagectomy patients were recruited into this trial as they represent a single cause with a reproducible and timed lung injury response that, historically, has been associated with increases in transpulmonary thermodilution-measured postoperative PVPI and EVLWI, inflammation and a high-rate of PPCs, including ARDS. 5 , 21 However, in contrast to previous trials in this population, 3 , 22 minimal postoperative increases in PVPI and EVLWI were observed in the placebo-treated patients, suggesting less lung injury and alveolar capillary leak in patients recruited to this trial.…”

Section: Discussioncontrasting

confidence: 60%

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Ryan

Bayliffe

McAuley

et al. 2020

European Journal of Anaesthesiology

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BACKGROUND Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS Patients randomly received a single nebulised dose (26 mg) of GSK2862277 ( n = 17) or placebo ( n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (−0.23, 0.39) in the placebo and 0.00 (−0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO 2 /F i O 2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION clinicaltrials.gov: NCT02221037.

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Section: Discussioncontrasting

confidence: 60%

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Ryan

Bayliffe

McAuley

et al. 2020

European Journal of Anaesthesiology

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“…This could either reflect an increased risk of developing COVID-19 disease if you have deficiency, or possibly that COVID-19 may have induced vitamin D deficiency, which could be due to dysregulated metabolism as seen in the critically ill where vitamin D levels can fall rapidly. 6 There have been reports of people of BAME ethnicity being disproportionately affected by COVID- 19, and vitamin D deficiency among people of BAME background is well documented. Our data support previous findings of higher vitamin D deficiency in BAME ethnicity, 20 with BAME ethnicity also being an independent predictor of vitamin D deficiency in the multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic

Faniyi

Lugg

Faustini

et al. 2020

Preprint

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Background: It is clear that in UK healthcare workers, COVID-19 infections and deaths were more likely to be in staff who were of BAME origin. This has led to much speculation about the role of vitamin D in healthcare worker COVID-19 infections. We aimed to determine the prevalence of vitamin D deficiency in NHS staff who have isolated with symptoms suggestive of COVID-19 and relate this to vitamin D status. Methods: We recruited NHS healthcare workers between 12th to 22nd May 2020 as part of the COVID-19 convalescent immunity study (COCO). We measured anti-SARS-Cov-2 antibodies using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was determined by measurement of serum 25(OH)D3 using the AB SCIEX Triple Quad 4500 mass spectrometry system. Findings: Of the 392 NHS healthcare workers, 214 (55%) had seroconverted for COVID-19. A total of 61 (15·6%) members of staff were vitamin D deficient (<30 nmol/l) with significantly more staff from BAME backgrounds or in a junior doctor role being deficient. Vitamin D levels were lower in those who were younger, had a higher BMI (>30 kg/m2), and were male. Multivariate analysis revealed that BAME and COVID-19 seroconversion were independent predictors of vitamin D deficiency. Staff who were vitamin D deficient were more likely to self-report symptoms of body aches and pains but importantly not the respiratory symptoms of cough and breathlessness. Vitamin D levels were lower in those COVID-19 positive staff who reported fever, but this did not reach statistical significance. Within the whole cohort there was an increase in seroconversion in staff with vitamin D deficiency compared to those without vitamin D deficiency (n=44/61, 72% vs n=170/331, 51%; p=0· 003); this was particularly marked in the proportion of BAME males who were vitamin D deficient compared to non-vitamin D deficient BAME males (n=17/18, 94% vs n=12/23, 52%; p=0·005). Multivariate analysis revealed that vitamin D deficiency was an independent risk factor for seroconversion (OR 2·6, 95%CI 1·41− 4· 80; p=0·002). Interpretation: In those healthcare workers who have isolated due to symptoms of COVID-19, those of BAME ethnicity are at the highest risk of vitamin D deficiency. Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff.

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“…Vitamin D deficiency is common in critical illness, and has been shown to be associated with poor outcomes 40 like duration of mechanical ventilation in acute respiratory failure, [41][42][43] sepsis and nosocomial infection, [44][45][46] and increased mortality. [47][48][49][50] Many patients admitted to critical care have multiple comorbidities, lack of exposure to sunlight, and are malnourished, leading to a preexisting deficiency.…”

Section: Vitamin D Deficiencymentioning

confidence: 99%

“…62,63 Several preclinical studies have highlighted a role for vitamin D in preventing or treating infections, respiratory failure in particular. 42,46 High-dose vitamin D3 administration has also shown a positive effect in vivo in several fields: contributing to protecting the lung barrier with lower changes in pulmonary vascular permeability index post oesophagectomy, 43 and improving cardiac function in patients with chronic heart failure. 64 Vitamin D can also play a role in atrial fibrillation prevention by negatively regulating the renin-angiotensin-aldosterone system (RAAS), mediating calcium homeostasis, binding to VDR on cardiac myocytes, and having antioxidant properties that can reduce levels of reactive oxygen species, which contribute to inflammation.…”

Section: Mechanistic Rationale In Critical Illnessmentioning

confidence: 99%

Metabolic and Endocrine Challenges

Bonicolini

Parekh

Thein

et al. 2020

Semin Respir Crit Care Med

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This review aims to provide an overview of metabolic and endocrine challenges in the setting of intensive care medicine. These are a group of heterogeneous clinical conditions with a high degree of overlap, as well as nonspecific signs and symptoms. Several diseases involve multiple organ systems, potentially causing catastrophic dysfunction and death. In the majority of cases, endocrine challenges accompany other organ failures or manifest as a complication of prolonged intensive care unit stay and malnutrition. However, when endocrine disorders present as an isolated syndrome, they are a rare and extreme manifestation. As they are uncommon, these can typically challenge both with diagnosis and management. Acute exacerbations may be elicited by triggers such as infections, trauma, surgery, and hemorrhage. In this complex scenario, early diagnosis and prompt treatment require knowledge of the specific endocrine syndrome. Here, we review diabetic coma, hyponatremia, hypercalcemia, thyroid emergencies, pituitary insufficiency, adrenal crisis, and vitamin D deficiency, highlighting diagnostic tools and tricks, and management pathways through defining common clinical presentations.

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

Abstract: Supplemental Digital Content is available in the text.

Cited by 54 publications

References 48 publications

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study

Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic

Metabolic and Endocrine Challenges

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