Vitamin K and cystic fibrosis: A gordian knot that deserves our attention.

Cystic fibrosis (CF) is an inherited genetic disorder with multiorgan involvement. Gastrointestinal tract dysfunction leads to fat and fat-soluble vitamins (A,D,E,K) malabsorption and deficiency of these vitamins. Subclinical vitamin K (VK) deficiency seems to be a common problem in CF patients. However, despite the rest of fat-soluble vitamins being routinely supplemented, this is not a universal clinical practice for VK. Inefficient levels of VK may have significant effects on blood coagulation and bone formation. There are also some data indicating that VK may play a key role on regulation of inflammation. Supplementing CF patients with VK seems rational, but the appropriate dosing regimens are still a matter of debate. This review will try to delineate the problem and communicate the latest opinions on this controversial issue.

Asthma and Allergy "Epidemic" and the Role of Vitamin D Deficiency.

The increase in asthma and allergies prevalence that has been recorded in many countries during the last decades, and the reemergence of vitamin D (VD) deficiency in many populations worldwide, renders fairly plausible the assumption of an underlying association between these two conditions and justifies the research effort invented in this issue. Indeed, there is growing body of evidence from epidemiological, laboratory, and clinical studies, suggesting that such an association does exist. The hypothesis of low levels of VD leading to compromised fetal programming and impairment of various immune functions involved in asthma and allergic disorders, stands as the most credible explanation of this presumed association. However, the evidence is not yet definite and there are some conflicting results among studies. As a consequence, no safe conclusions can be drawn yet, and more research is required in order to fully clarify the involvement of VD deficiency in the pathogenesis of asthma and allergies, and decide if VD has a role to play in the prevention and therapy of these disorders.

Role of vitamin D in cystic fibrosis and non-cystic fibrosis bronchiectasis.

Bronchiectasis is usually classified as cystic fibrosis (CF) related or CF unrelated (non-CF); the latter is not considered an orphan disease any more, even in developed countries. Irrespective of the underlying etiology, bronchiectasis is the result of interaction between host, pathogens, and environment. Vitamin D is known to be involved in a wide spectrum of significant immunomodulatory effects such as down-regulation of pro-inflammatory cytokines and chemokines. Respiratory epithelial cells constitutively express 1α-hydroxylase leading to the local transformation of the inactive 25(OH)-vitamin D to the active 1,25(OH)2-vitamin D. The latter through its autocrine and paracrine functions up-regulates vitamin D dependent genes with important consequences in the local immunity of lungs. Despite the scarcity of direct evidence on the involvement of vitamin D deficiency states in the development of bronchiectasis in either CF or non-CF patients, it is reasonable to postulate that vitamin D may play some role in the pathogenesis of lung diseases and especially bronchiectasis. The potential contribution of vitamin D deficiency in the process of bronchiectasis is of particular clinical importance, taking into consideration the increasing prevalence of vitamin D deficiency worldwide and the significant morbidity of bronchiectasis. Given the well-established association of vitamin D deficiency with increased inflammation, and the indicative evidence for harmful consequences in lungs, it is intriguing to speculate that the administration of vitamin D supplementation could be a reasonable and cost effective supplementary therapeutic approach for children with non-CF bronchiectasis. Regarding CF patients, maybe in the future as more data become available, we have to re-evaluate our policy on the most appropriate dosage scheme for vitamin D.

Does Vitamin D Deficiency Epidemic Parallel with Allergy and Asthma Epidemic?

Vitamin D (VD) deficiency has re-emerged, after more than hundred years, as a public health problem worldwide. Asthma and allergic disorders constitute another major public health problem with studies having recorded increasing prevalences worldwide since the decade of the 60s. Most of the available experimental and epidemiologic evidence point towards a causal association between low levels of VD and the development of asthma and allergic disorders, and imply a role of VD deficiency on the currently high prevalences of asthma and allergic diseases. The proposed, but still largely hypothetical, underlying mechanism is that VD affects the programming of the fetus and it also has a central modulating role in immune functions involved in asthma and allergic disorders. However, the evidence is not yet clear, since there are studies which support that VD supplementation during pregnancy may promote the development of asthma and allergic disorders. More researches, and especially randomized clinical trials, are required in order to draw safe conclusions and define the role of VD in the prevention or even therapy of asthma and allergic disorders.

Bone mass density and associated factors in cystic fibrosis patients of young age.

AIM: To investigate bone mineral status in young cystic fibrosis (CF) patients and determine risk factors related with the development of low bone mineral density (BMD). METHODS: We determined, in 81 patients with CF, 4 to 23-years-old, BMD as well as factors, which are thought to play a role in the development of reduced BMD. RESULTS: BMD Z-score was between -1 and -2.5 in 27 (33%) and lower than -2.5 in 9 (11%). Means of BMD Z-score were lower than the expected value of 0 in the three groups of children, adolescents and young adults (P = 0.004; P < 0.001; P = 0.048, respectively), but they did not differ among them (P = 0.114). Analysis showed that Shwachman-Kulczycki (SK) score, gender and levels of 25-hydroxy-vitamin D were significant predictors of BMD Z-score. Significant also was the interaction between gender and SK score. CONCLUSIONS: Our study supports that BMD may be reduced from a young age in CF patients though this needs to be confirmed using true volumetric measures of BMD. This defect is related to disease severity with males being more vulnerable. Inefficient levels of vitamin D are very common and contribute significantly to impaired bone health. The latter finding underlines the need for higher supplementation doses.

The effect of vitamin K supplementation on biochemical markers of bone formation in children and adolescents with cystic fibrosis.

INTRODUCTION: Impaired vitamin K status in cystic fibrosis (CF) has been considered as a newly emerged pathogenetic factor for reduced bone mineral density (BMD). OBJECTIVES: Our aim was to evaluate the effectiveness of vitamin K supplementation in managing bone formation abnormalities in children and adolescents with CF. MATERIALS AND METHODS: The statuses of vitamins K and D in relation to biochemical markers of bone metabolism and BMD were examined in 20 CF children receiving vitamin D supplements but not vitamin K supplements. Laboratory tests were carried out at the beginning of the study period and after 1 year of vitamin K supplementation (10 mg single oral dose/week) and the results were compared; the results were also compared with those of 25 healthy controls. RESULTS AND DISCUSSION: Ten of the CF patients had BMD z-score