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Comparison of the Association between Circulating Vitamin D3 Levels and Clinical Outcomes in Patients with Asthma and Chronic Obstructive Pulmonary Disease: A Prospective Observational Study.
Hirai, K, Shirai, T, Suzuki, Y, Shimomura, T, Itoh, K
Biological & pharmaceutical bulletin. 2019;(11):1861-1866
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Abstract
Vitamin D has an immune-modulating effect, related to the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). However, few studies have focused on the difference between patients with asthma and COPD in the association of circulating vitamin D levels with clinical outcomes. We sought to investigate the associations of circulating vitamin D levels with health-related QOL (HR-QOL), severity, and exacerbations. Subjects included 152 asthma patients and 50 COPD patients. We measured plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3]. HR-QOL was assessed using the EuroQoL 5-Dimension (EQ-5D) and the 12-item Short Form Health Survey (SF-12) scales. Exacerbations were recorded during a one-year follow-up. Associations between plasma 25 (OH)D3 concentrations and outcome variables were evaluated using linear regression. Plasma concentrations of 25(OH)D3 were positively associated with the EQ-5D index value and the SF-12 physical component score in patients with asthma; however, such associations were not observed in patients with COPD. A significant association between severity and plasma concentrations of 25(OH)D3 was found only in patients with COPD. The hazard ratios (95% confidence interval) of plasma 25(OH)D3 concentrations (per 1 ng/mL decrease) for time to first exacerbation was 1.38 (1.10-1.75; p = 0.006) and 0.95 (0.87-1.03; p = 0.179) in patients with COPD and asthma, respectively. Lower concentrations of plasma 25(OH)D3 contributed to lower HR-QOL in patients with asthma, and were associated with severity and risk of future exacerbations in patients with COPD.
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The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention.
Young, RP, Hopkins, RJ
Current molecular pharmacology. 2017;(1):46-59
Abstract
Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A. Smoke exposure activates cell surface proteins which, through the mediating influence of GTPases, then modify the activation of NFkB and its downstream effects on genes underlying innate immunity, neutrophilic inflammation and carcinogenesis. The mevalonate pathway is readily and substantially modified by inhibition of the enzyme 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMGCo-A) reductase. This enzyme controls the rate limiting step of the mevalonate pathway and is subject to inhibition by statin drugs and small chain fatty acids derived from high dietary fibre intake. Thus inhibiting the mevelonate pathway, and dampening the innate immune response to smoking, may play a critical role in modifying pulmonary inflammation and lung remodelling. Such an action might slow the progression of COPD and reduce the tendency to the development of lung cancer. This review examines the pre-clinical and clinical data suggesting that HMGCoA-reductase inhibition and it's modification of the mevalonate pathway, may have a chemo-preventive effect on lung cancer, particularly in patients with COPD where pulmonary inflammation is increased and the risk of lung cancer is greatest.
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Prevention of exacerbations in patients with COPD and vitamin D deficiency through vitamin D supplementation (PRECOVID): a study protocol.
Rafiq, R, Aleva, FE, Schrumpf, JA, Heijdra, YF, Taube, C, Daniels, JM, Lips, P, Bet, PM, Hiemstra, PS, van der Ven, AJ, et al
BMC pulmonary medicine. 2015;:106
Abstract
BACKGROUND Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. METHODS/DESIGN We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. DISCUSSION This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. TRIAL REGISTRATION This trial is registered in ClinicalTrials.gov, ID number NCT02122627 . Date of Registration April 2014.
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Novel Roles for Chloride Channels, Exchangers, and Regulators in Chronic Inflammatory Airway Diseases.
Sala-Rabanal, M, Yurtsever, Z, Berry, KN, Brett, TJ
Mediators of inflammation. 2015;:497387
Abstract
Chloride transport proteins play critical roles in inflammatory airway diseases, contributing to the detrimental aspects of mucus overproduction, mucus secretion, and airway constriction. However, they also play crucial roles in contributing to the innate immune properties of mucus and mucociliary clearance. In this review, we focus on the emerging novel roles for a chloride channel regulator (CLCA1), a calcium-activated chloride channel (TMEM16A), and two chloride exchangers (SLC26A4/pendrin and SLC26A9) in chronic inflammatory airway diseases.
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Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study.
Bourne, S, Cohet, C, Kim, V, Barton, A, Tuck, A, Aris, E, Mesia-Vela, S, Devaster, JM, Ballou, WR, Clarke, SC, et al
BMJ open. 2014;(3):e004546
Abstract
INTRODUCTION The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) remains incompletely understood and strategies for treatment and prevention have not altered significantly for many years. Improved understanding of the role of respiratory pathogens in acute exacerbations of COPD (AECOPD) is required and the use of molecular microbiological techniques may lead to insights into host-pathogen interactions and the development of more targeted therapeutic approaches. METHODS AND ANALYSES Acute Exacerbation and Respiratory InfectionS in COPD (AERIS) is a longitudinal epidemiological study to assess how changes in the COPD airway microbiome contribute to the incidence and severity of AECOPD. Patients with COPD aged 40-85 are followed monthly for 2 years, and reviewed within 72 h of onset of symptoms of AECOPD. Exacerbations are detected using daily electronic diary cards. Blood, sputum, nasopharyngeal and urine samples are collected at prespecified timepoints. Molecular diagnostic and typing techniques are used to describe the dynamics of airway infection during AECOPD and stable disease, and associations with clinical outcome. This study aims to refine the case definition of AECOPD to reflect the possible microbiological aetiology. AERIS will assess the impact of AECOPD on health-related quality of life and healthcare resource utilisation, and the possible interactions between nutritional status, infection and immune responses. ETHICS AND DISSEMINATION AERIS is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, and has been approved by the institutional ethics and review board. All participants must provide written informed consent. The results obtained will be disseminated at international medical conferences and in peer-reviewed publications. DISCUSSION Few other studies have addressed the complexity of the microbiological and systemic components of COPD or employed real-time electronic tracking of symptoms to identify AECOPD and potential aetiological triggers. RESULTS Results of AERIS will increase our understanding of the contribution of pathogens to AECOPD, potentially leading to new targeted therapeutic and preventative interventions. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT01360398.
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[Effects of "reinforcing Qi and activating blood" on stable chronic obstructive pulmonary disease (Qi deficiency and blood stasis syndrome].
Min, J, Mao, B, Jiang, HL, Fan, T, Zhou, W
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2014;(4):601-5
Abstract
OBJECTIVE To study the clinical effects of "Reinforcing Qi and Activating Blood" in the treatment of stable chronic obstructive pulmonary disease (Qi Deficiency and Blood Stasis Syndrome). METHODS This study recruit 50 outpatients with stabe chronic obstructive pulmonary disease (Qi Deficiency and Blood Stasis Syndrome), who were randomly divided into 2 groups, control group and treatment of "Reinforcing Qi and Activating Blood" group. The patients in control group were given conventional treatment, while the patients in treatment group not only received conventional treatment but also the treatment of Yu-Ping-Feng capsules and Fu-Fang-Dan-Shen tablets for 3 months. The duration of follow up was 12 months, and chinese medicine (CM) symptoms, cellular immunity indexes and haemodynamics indexes were assessed every 3 months. RESULTS The total effective rate in treatment group at 3 months treatment and 3 months follow-up were higher than that in control group (P < 0.05). The CM symptoms in treatment group were improved significantly (P < 0.05). In treatment group, the level of CD4 and the ratio of CD4/CD8 after therapy were higher than those before (P < 0.05), and the level of CD8 was lower than that before (P < 0.05). The level of NO was no significant difference (P > 0.05), while the level of endothelin (ET) was significantly different (P < 0.05). The frequency of suffering from cold, the admission due to acute exacerbation and hospital stay in treatment group were all lower than those in control group (P < 0.05). CONCLUSION The "Reinforcing Qi and Activating Blood" therapy can improve the symptoms and clinical curative effect of TCM in the treatment of stable COPD (Qi Deficiency and Blood Stasis Syndrome), with the improvement of their cellular immunological function and vasomotor function.
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Hydrogen peroxide and nitrite reduction in exhaled breath condensate of COPD patients.
Stefanska, J, Sarniak, A, Wlodarczyk, A, Sokolowska, M, Doniec, Z, Bialasiewicz, P, Nowak, D, Pawliczak, R
Pulmonary pharmacology & therapeutics. 2012;(5):343-8
Abstract
Chronic obstructive pulmonary disease (COPD) is predominantly the result of years of cigarette smoking. Increased oxidative stress in COPD derives from the increased burden of inhaled oxidants (cigarette smoke), air pollution and the increase in reactive oxygen and nitrogen species (ROS and RNS), generated by some inflammatory, immune, and structural airways cells. In view of the lack of therapy that might inhibit the progress of the disease, there is an urgent need for a successful therapeutic approach. Apocynin is a molecule inhibiting activation of NADPH oxidase - enzyme generating ROS and RNS precursor. Thus, our aim was to analyze apocynin influence on hydrogen peroxide and nitrite concentrations in EBC of COPD patients. Apocynin reduced concentration of H(2)O(2) in COPD patients 60 and 120 min after apocynin inhalation, in comparison to placebo (0.43 μM vs. 0.59 μM, and 0.4 μM vs. 0.59 μM respectively, p < 0.05). Moreover, apocynin decreased NO(2)(-) ions concentration in airways of COPD patients after apocynin nebulization (3.97 μM vs. 4.48 μM after 30 min, 3.82 μM vs. 4.48 μM after 60 min, and 3.76 μM vs. 4.48 μM after 30 min respectively, p < 0.05). No adverse effects have been observed. The results suggest that apocynin might be considered as anti-inflammatory agent, and, possibly used in therapy of COPD.
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Treatment with the immunomodulator AM3 improves the health-related quality of life of patients with COPD.
Alvarez-Mon, M, Miravitlles, M, Morera, J, Callol, L, Alvarez-Sala, JL
Chest. 2005;(4):1212-8
Abstract
BACKGROUND COPD has a severe impact on patient quality of life. AM3 is an orally effective immunomodulator that can normalize the defective antimicrobial functions of the immune system effector cells of COPD patients. OBJECTIVES We analyzed the effect of AM3 on exacerbation frequency and health-related quality of life (HRQL) of COPD patients with moderate disease. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING Outpatient departments of 21 hospitals. METHODS A total of 253 COPD patients with a mean age of 67.7 years (SD, 8.1 years) and mean FEV(1) percentage of predicted of 49.6% (SD, 10.2%) were evaluated. Patients received (orally) either 3 g/d AM3 or a matched placebo for 180 consecutive days. Patient quality of life was measured using the St. George's Respiratory Questionnaire (SGRQ). RESULTS There were no differences in the exacerbation frequency of the two groups (0.82 episodes per patient in the AM3 arm vs 0.84 in the placebo arm), and 55.3% of patients were exacerbation free in the AM3 arm compared to 48.8% in the placebo arm (p = 0.11). At the end of treatment, quality of life was significantly better in the AM3 arm than in the placebo arm (SGRQ total score, 32.9; SD, 16.4, compared to 37.5; SD, 17.5 [p < 0.05]: activity score, 47.5; SD, 22.4, compared to 54.6; SD, 20.5 [p < 0.05]). The improvements in total SGRQ scores were 8.9 U (SD, 13.4 U) in the AM3 arm and 5.6 U (SD, 15.9 U) in the placebo arm (p = 0.076). Improvements on the symptoms subscale were 15.9 U (SD, 20.7 U) for the AM3 arm and 10.2 U (SD, 21.3 U) for the placebo arm (p < 0.05). Both AM3 and the placebo were clinically, biochemically, and hematologically well tolerated. CONCLUSIONS AM3 is a safe, easily tolerated, effective treatment that improves the quality of life of COPD patients as measured by SGRQ scores. This effect was observed with no significant reduction in the frequency of exacerbations.