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Fluid in lung (pleural effusion) associated with low vitamin D – July 2016

Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions. - July 2016

BMC Pulm Med. 2016 Jul 8;16(1):99.
Amado CA1, García-Unzueta MT2, Fariñas MC3, Santos F2, Ortiz M2, Muñoz-Cacho P4, Amado JA5.
.1Division of Pneumology, Universidad de Cantabria, IDIVAL, Santander, Spain. camado at humv.es.
2Clinical Biochemistry, Universidad de Cantabria, IDIVAL, Santander, Spain.
3Infectious Diseases Hospital Universitario Marqués de Valdecilla (HUMV), Universidad de Cantabria, IDIVAL, Santander, Spain.
4Gerencia Atención Primaria, Servicio Cántabro de Salud, Santander, Spain.
5Division of Endocrinology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, Santander, Spain.

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Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and ß-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before.
Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and ß-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis.
Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum ß-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best.
Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of ß-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions.

PMID: 27392908 DOI: 10.1186/s12890-016-0259-4

25-hydroxyvitamin D in malignant pleural disease: A prospective cohort study. - Aug 2016

Clin Respir J. 2016 Aug 9. doi: 10.1111/crj.12540. [Epub ahead of print]
Panagiotou M1, Papaioannou AI1, Kostikas K2, Takou A3, Paraskeva M1, Kalkanis A1, Diamantea F1, Kastanakis E1, Maropoulos G3, Filaditaki V1, Karagianidis N1.
Author information
12rd Respiratory Medicine Department, Sismanoglio General Hospital, 1 Sismanogliou St., 15126, Athens, Greece.
22nd Respiratory Medicine Department, University of Athens Medical School, Attikon Hospital, Rimini St., 12462, Athens, Greece.
3Department of Biochemistry, Laiko General Hospital, 17 Agiou Thoma St., 11527, Athens, Greece.

Growing evidence suggests a role of vitamin D in various cancers but the significance of vitamin D in malignant pleural disease remains unexplored. We sought to investigate the concentration and diagnostic role of 25-hydroxyvitamin D (25(OH)D) in malignant pleural effusions.
Prospective study of consecutive treatment-naïve patients with a new diagnosis of pleural effusion.
Seventy-eight patients were studied, 45 of whom had malignant pleural effusions.
Concentration of 25(OH)D in pleural fluid was significantly higher than serum in both malignant (15.2 ng/ml (9.7, 25.6) versus 10.2 ng/ml (6.4, 17.7), p<0.001) and benign (11.4 ng/ml (8.4, 23.6) versus 7.9 (5.9, 16.1), p<0.001) pleural disease.
Pleural fluid 25(OH)D was almost significantly higher in exudates compared to transudates (p=0.050) but it did not differ significantly between malignant and benign effusions (p=0.217) and it was not diagnostic for malignant pleural disease (AUC 0.58, 95% CI 0.45-0.71).
In subjects with unselected pleural effusions, 25(OH)D in pleural fluid was not diagnostic for malignant pleural disease.
The novel finding of convincingly and consistently higher 25(OH)D in pleural fluid than serum suggests a role for vitamin D in pleural disease and merits further research.

This article is protected by copyright. All rights reserved. © 2016 John Wiley & Sons Ltd. PMID: 27502152

Fluid on the lungs cleared by active vitamin D (mice, shows how) – Jan 2016

1,25-Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Upregulating the Expression of Epithelial Sodium Channels.
J Pharm Sci. 2016 Jan;105(1):333-8. doi: 10.1016/j.xphs.2015.11.022. Epub 2016 Jan 13.
Nie H1, Cui Y2, Wu S3, Ding Y3, Li Y4.

Vitamin D is implicated in the pathogenesis of asthma, acute lung injury, and other respiratory diseases. 1,25-Dihydroxyvitamin D (1,25(OH)2D3), the hormonal form of vitamin D, has been shown to reduce vascular permeability and ameliorate lung edema. Therefore, we speculate that 1,25(OH)2D3 may regulate alveolar Na(+) transport via targeting epithelial Na(+) channels (ENaC), a crucial pathway for alveolar fluid clearance. In vivo total alveolar fluid clearance was 39.4 ± 3.8% in 1,25(OH)2D3-treated mice, significantly greater than vehicle-treated controls (24.7 ± 1.9 %, n = 10, p < 0.05). 1,25(OH)2D3 increased amiloride-sensitive short-circuit currents in H441 monolayers, and whole-cell patch-clamp data confirmed that ENaC currents in single H441 cell were enhanced in 1,25(OH)2D3-treated cells. Western blot showed that the expression of a-ENaC was significantly elevated in 1,25(OH)2D3-treated mouse lungs and 1,25(OH)2D3-treated H441 cells. These observations suggest that vitamin D augments transalveolar fluid clearance, and vitamin D therapy may potentially be used to ameliorate pulmonary edema.

PMID: 26852863 DOI: 10.1016/j.xphs.2015.11.022

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