vitamin-k-semiquinone-radical and Pulmonary-Disease--Chronic-Obstructive

Currently, an increasing amount of evidence supports the notion that vitamins C, D and E, carotenoids, and omega-3 fatty acids may protect against the progression of chronic respiratory diseases. Although chronic obstructive pulmonary disease (COPD) primarily affects the lung, it is often accompanied by extrapulmonary manifestations such as weight loss and malnutrition, skeletal muscle dysfunction, and an excess of harmful oxidants, which can lead to a decline in quality of life and possible death. Recently, the role of various vitamins, minerals, and antioxidants in mitigating the effects of environmental pollution and smoking has received significant attention. Therefore, this review evaluates the most relevant and up-to-date evidence on this topic. We conducted a literature review between 15 May 2018 and 15 May 2023, using the electronic database PubMed. Our search keywords included COPD, chronic obstructive pulmonary disease, FEV

Topics: Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Minerals; Pulmonary Disease, Chronic Obstructive; Vitamin A; Vitamin B Complex; Vitamin K

To administer optimal and safe pharmacotherapy, development of stratified and personalized therapy is imperative. Pharmacogenomics (PGx) is useful in elucidating factors causing individual differences in drug efficacy and the emergence of adverse effects. It also helps design accurate drug administration methods by evaluating the effects of patient-related factors, such as genetic factors, that influence pharmacokinetics (PK) and pharmacodynamics (PD). In addition, selection of appropriate therapeutic agents requires the implementation of precision medicine allowing accurate disease diagnosis. To establish precision medicine, it is necessary to uncover the association of pathophysiological factors, which are represented as endotype or genotype, with the pathology of several phenotypes. This review describes two aspects related to realization of individualized medicine, namely the effectiveness of PK/PD/PGx studies and the stratification of pathological conditions. First, we conducted a PK/PD/PGx study with the aim to individualize warfarin treatment. In this study, we elucidated the effect of CYP4F2 polymorphisms associated with vitamin K metabolism by measuring the blood concentrations of warfarin and vitamin K. Then, to develop precision medicine for asthma and chronic obstructive pulmonary disease (COPD), we analyzed not only clinical symptoms but also pathological biomarkers and genes associated with inflammation. The findings may contribute toward better understanding of the pathological conditions of asthma, COPD, and asthma-COPD overlap.

Topics: Asthma; Cytochrome P450 Family 4; Drug Therapy; Humans; Inflammation; Pharmacogenomic Testing; Pharmacokinetics; Polymorphism, Genetic; Precision Medicine; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin

Cardiovascular diseases are prevalent in patients with chronic obstructive pulmonary disease (COPD). Their coexistence implies that many COPD patients require anticoagulation therapy. Although more and more replaced by direct oral anticoagulants, vitamin K antagonists (VKAs) are still widely used. VKAs induce profound deficiency of vitamin K, a key activator in the coagulation pathway. It is recognized however that vitamin K is also an essential cofactor in the activation of other extrahepatic proteins, such as matrix Gla protein (MGP), a potent inhibitor of arterial calcification. No or insufficient MGP activation by the use of VKAs is associated with a rapid progression of vascular calcification, which may enhance the risk for overt cardiovascular disease. Vitamin K consumption, on the other hand, seems to have a protective effect on the mineralization of arteries. Furthermore, vascular calcification mutually relates to elastin degradation, which is accelerated in patients with COPD associating with impaired survival. In this commentary, we hypothesize that vitamin K is a critical determinant to the rate of elastin degradation. We speculate on the potential link between poor vitamin K status and crucial mechanisms of COPD pathogenesis and raise concerns about the use of VKAs in patients with this disease. Future intervention studies are needed to explore if vitamin K supplementation is able to reduce elastin degradation and vascular calcification in COPD patients.

Topics: Animals; Cardiovascular Diseases; Dietary Supplements; Humans; Pulmonary Disease, Chronic Obstructive; Vascular Calcification; Vitamin K; Vitamin K Deficiency

Heart failure (HF) has been associated with an elevated international normalized ratio (INR) in patients on warfarin.. Compare warfarin sensitivity during hospital admission for HF exacerbation and chronic obstructive pulmonary disease (COPD) exacerbation with admissions unrelated to HF or COPD (controls) as well as during disease stability.. We conducted a case-controlled observational study. Patients admitted to a tertiary teaching hospital for HF exacerbation (n = 37), COPD exacerbation (n = 26), and admissions unrelated to HF or COPD (controls, n = 60) were included. Warfarin sensitivity (INR per daily mg dose of warfarin) at admission was compared to periods of disease stability and also compared between the 3 groups.. The increase in warfarin sensitivity at admission was 94% for HF patients (P < 0.0001), 59% for COPD (P = 0.003) patients, and 24% for controls (P = 0.002). HF patients with New York Heart Association (NYHA) class 3 and 4 and NYHA class 1 and 2 experienced changes in warfarin sensitivity of 125% (P = 0.006) and 50% (P = 0.13) at admission. HF patients had higher warfarin sensitivity at admission (mean = 1.62 [SD = 1.27]) compared to the control group (0.91 [0.52], P < 0.0001) and COPD group (1.03 [0.79], P = 0.04). and required greater intervention with vitamin K than controls (14% vs 0%, P = 0.007).. HF and COPD patients were more sensitive to warfarin during disease exacerbation, with HF exacerbation having the largest impact, resulting in clinically significant management implications.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Disease Progression; Female; Heart Failure; Hospitalization; Humans; International Normalized Ratio; Male; Pulmonary Disease, Chronic Obstructive; Vitamin K; Warfarin