beta-carotene and Lung-Diseases

Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review.. To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis.. We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings. Date of most recent search: 16 January 2020. We also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020.. Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis.. Two of the authors independently assessed and extracted data from identified trials.. We identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed β-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA. Three of the interventions measured our primary outcome of pulmonary exacerbations (β-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). β-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome. Respiratory function was measured in all of the included trials. β-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV. We could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.. پیشینه: فیبروز سیستیک یک بیماری چند سیستمی است که مشخصه آن، تولید ترشحات ضخیمی است که باعث عفونت مکرر ریوی، غالبا با باکتری‌های غیرمعمول می‌شود. این وضعیت منجر به تخریب ریه و در نهایت مرگ در اثر نارسایی تنفسی می‌شود. هیچ آنتی‌بیوتیک در حال توسعه‌ای وجود ندارد که دارای یک روش جدید عملکرد باشد و بسیاری از آنتی‌بیوتیک‌های فعلی، در ریشه‌کن کردن باکتری‌ها پس از استقرار عفونت مزمن بی‌اثر هستند. داروهای کمک کننده به آنتی‌بیوتیک ‐ درمان‌هایی که ارگانیسم را با حساس‌تر کردن آن به حمله آنتی‌بیوتیک‌ها یا سیستم ایمنی بدن میزبان، یا با کاهش بیماری‌زایی آن یا کشتن آن با روش‌های دیگر تسلیم می‌کند، پیشرفت درمانی قابل‌توجهی خواهد بود. این یک به‌روزرسانی از مرور منتشر شده قبلی است. اهداف: تعیین اینکه داروهای کمک کننده به آنتی‌بیوتیک باعث بهبود پیامد بالینی و میکروبیولوژیکی عفونت ریوی در افراد مبتلا به فیبروز سیستیک می‌شوند یا خیر. روش‌های جست‌وجو: ما پایگاه ثبت کارآزمایی‌های گروه فیبروز سیستیک در کاکرین را جست‌وجو کردیم که شامل جست‌وجوها در بانک‌های اطلاعاتی و جست‌وجوی دستی در مجلات و کتاب چکیده مقالات کنفرانس‌های مرتبط بود. تاریخ آخرین جست‌وجو: 16 ژانویه 2020. ما همچنین MEDLINE (همه سال‌ها) را در 14 فوریه 2019 و پایگاه‌های ثبت کارآزمایی‌های در حال انجام را در 6 اپریل 2020 جست‌وجو کردیم. معیارهای انتخاب: کارآزمایی‌های تصادفی‌سازی و کنترل شده و کارآزمایی‌های شبه‐تصادفی‌سازی و کنترل شده حاوی استفاده از یک درمان با مکانیسم عملکرد کمک به آنتی‌بیوتیک، در مقایسه با دارونما (placebo) یا عدم درمان برای مبتلایان به فیبروز سیستیک. گردآوری و تجزیه‌وتحلیل داده‌ها: دو نفر از نویسندگان به‌طور مستقل از هم، داده‌های به دست آمده از کارآزمایی‌های شناسایی شده را ارزیابی و استخراج کردند. نتایج اصلی: ما 42 کارآزمایی را شناسایی کردیم که از این میان، هشت (350 شرکت‌کننده) کارآزمایی وارد شدند که درمان‌های کمک کننده به آنتی‌بیوتیک را مورد بررسی قرار دادند. دو کارآزمایی دیگر در حال انجام و پنج مورد در انتظار طبقه‌بندی هستند. کارآزمایی‌های وارد شده به بررسی β‐ کاروتن (یک کارآزمایی، 24 شرکت‌کننده)، سیر (یک کارآزمایی، 34 شرکت‌کننده)، KB001‐A (یک آنتی‌بادی مونوکلونال) (دو کارآزمایی، 196 شرکت‌کننده)، نیتریک اکسید (دو کارآزمایی، 30 شرکت‌کننده) و مکمل زینک (دو کارآزمایی، 66 شرکت‌کننده) پرداختند. کارآزمایی‌های زینک فقط روی کودکان انجام شدند، در حالی که کارآزمایی‌های باقی‌مانده هم بزرگسالان و هم کودکان را جذب کردند. سه کارآزمایی در اروپا، یک مورد در آسیا و چهار مورد در ایالات متحده انجام شدند. سه مورد از مداخلات، پیامد اولیه ما را که تشدیدهای حملات ریوی بودند، اندازه‌گیری کردند (β‐کاروتن، تفاوت میانگین (MD): 8.00‐ (95% فاصله اطمینان (CI): 18.78‐ تا 2.78)؛ KB001‐A، خطر نسبی (RR): 0.25؛ (95% CI؛ 0.03 تا 2.40)؛

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Monoclonal; Bacterial Infections; beta Carotene; Chemotherapy, Adjuvant; Child; Cystic Fibrosis; Disease Progression; Garlic; Humans; Immunoglobulin Fab Fragments; Lung Diseases; Nitric Oxide; Pseudomonas aeruginosa; Pseudomonas Infections; Randomized Controlled Trials as Topic; Vitamins; Young Adult; Zinc

Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, are urgently needed.. To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis.. We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings.Date of most recent search: 26 July 2012.We also searched MEDLINE (all years) on 23 February 2013 and ongoing trials registers on 13 February 2013.. Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis.. The authors independently assessed and extracted data from identified studies.. We identified eighteen studies of which four are included that examined antibiotic adjuvant therapies, three studies are ongoing. The included studies involve the assessment of β-carotene, garlic and zinc supplementation and KB001 (a biological agent). No therapy demonstrated a significant effect upon pulmonary function, pulmonary exacerbations or quality of life. The study of zinc supplementation reports a reduction in the requirement of oral antibiotics but not of intravenous antibiotics, an effect that is difficult to understand. . We could not identify an antibiotic adjuvant therapy that could be recommended for the treatment of lung infection in those with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Bacterial Infections; beta Carotene; Chemotherapy, Adjuvant; Cystic Fibrosis; Garlic; Humans; Lung Diseases; Randomized Controlled Trials as Topic; Vitamins; Zinc

Topics: Administration, Inhalation; Ascorbic Acid; beta Carotene; Cystic Fibrosis; Humans; Lung Diseases; Nitric Oxide; Oxidative Stress; Reactive Oxygen Species; Sulfhydryl Compounds; Trachea

Oxidative stress is thought to play a major role in the pathogenesis of chronic obstructive pulmonary disease, characterized by impaired lung function. A large number (> or =33) of GT repeats (L-allele) in the gene of the powerful antioxidant enzyme heme oxygenase-1 has been associated with susceptibility to accelerated lung function decline. In contrast, beta-carotene may help to protect against accelerated decline. To determine whether high serum levels of beta-carotene might counterbalance the greater susceptibility of L-allele carriers, the authors analyzed the annual decline in forced expiratory volume in 1 second (FEV1) in a general population sample of 523 French subjects (20-44 years, 50% men) examined in 1992 and 2000 as part of the European Community Respiratory Health Survey. Analysis of covariance, adjusted for sex as well as baseline age, body mass index, smoking, and FEV1, showed that, among subjects with low beta-carotene levels, L-allele carriers experienced a steeper mean FEV1 decline than did noncarriers (mean = -58.8, 95% confidence interval: -73.2, -44.5 vs. mean = -34.7, 95% confidence interval: -38.9, -29.8 ml/year) (p = 0.009), whereas among subjects with high beta-carotene levels, the FEV1 decline was not different in L-allele carriers and noncarriers (two-sided p = 0.9). The results suggest that high levels of beta-carotene might counterbalance the effects on FEV1 decline of a genetically determined deficiency in antioxidant response.

Topics: Adult; beta Carotene; Causality; Comorbidity; Female; Forced Expiratory Volume; France; Heme Oxygenase-1; Humans; Longitudinal Studies; Lung Diseases; Male; Polymorphism, Genetic; Smoking

Some studies have indicated that the injury induced by the hepato- and pneumotoxin monocrotaline (MCT) is in part mediated by oxidation. Because beta-carotene is a potent antioxidant, we hypothesized that it would protect the lung and liver parenchyma against MCT-induced injury. Twenty rats were assigned randomly to four groups. All rats were fed a standard AIN93G diet with or without beta-carotene. After 1 week on the purified diets, half of the rats fed the control (standard) diet and half of the rats fed the beta-carotene-supplemented diet were injected subcutaneously with 60 mg MCT/kg body weight or its vehicle (water). All rats were sacrificed at 4 weeks. Histological examination showed that beta-carotene alone did not affect lung or liver structure. On the other hand, lungs of MCT-treated rats had severe focal pneumonia, extensive deposition of collagen in the septa, marked inflammation of the small arteries and arterioles, and arterialization of the small venules. Livers of MCT-treated rats showed some fatty infiltration and diffuse hemorrhages, more prominent sometimes in the centrilobular area and sometimes in the periportal region. Concomitant treatment with beta-carotene protected the lung parenchyma from the inflammatory reaction and the septal fibrosis, but did not prevent cardiac right ventricular hypertrophy and only slightly reduced the thickening of the wall of small arteries and arterioles. Incidence of steatosis and hemorrhages was decreased in the liver. These results indicate that MCT-induced pulmonary vascular remodeling occurs in the absence of inflammatory cell infiltration. Furthermore, beta-carotene prevented inflammation and protected the lung and liver parenchyma of MCT-treated rats.

Topics: Animals; Antidotes; Antioxidants; beta Carotene; Chemical and Drug Induced Liver Injury; Collagen; Diet; Fatty Liver; Hemorrhage; Hypertrophy, Right Ventricular; Liver; Lung; Lung Diseases; Male; Monocrotaline; Poisons; Rats; Rats, Sprague-Dawley

Topics: beta Carotene; Cardiovascular Diseases; Dietary Supplements; Environmental Exposure; Humans; Lung Diseases; Lung Neoplasms; Pneumonectomy; Pulmonary Emphysema; Risk Factors; Sleep Apnea Syndromes; Vitamin A

Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L, all indexes of inflammation were relatively high, whereas those with concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

Topics: Adolescent; Adult; Ascorbic Acid; beta Carotene; Child; Child, Preschool; Cohort Studies; Cystic Fibrosis; Cytokines; Dose-Response Relationship, Drug; Female; Humans; Infant; Inflammation; Interleukin-6; Leukocyte Elastase; Lipid Peroxidation; Lung Diseases; Male; Malondialdehyde; Nutritional Status; Orosomucoid; Seasons; Tumor Necrosis Factor-alpha; Vitamin E

Relationships between plasma levels of beta-carotene (BC) and the numbers and oxidant-generating activities of circulating neutrophils have been investigated in a group of asymptomatic young male cigarette smokers (N = 40) and in a group of nonsmoking control subjects. Plasma BC levels were measured using HPLC, while oxidant generation was measured using a phorbol myristate acetate (PMA) activated whole blood luminol-enhanced chemiluminescence (LECL) method. Relative to nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were increased by 41% (p = 0.0001) and 47% (p = 0.004), respectively, while plasma BC levels were decreased by 24% (p = 0.01). In cigarette smokers, but not in nonsmokers, the numbers of circulating neutrophils, as well as the LECL responses of these cells, were significantly and inversely correlated with plasma BC levels (r = -0.36, p = 0.02; and r = -0.33, P = 0.04 respectively). Diminished plasma levels of BC in cigarette smokers probably reflect the increased numbers and prooxidative activities of circulating neutrophils. Intake of this antioxidant nutrient may be a determinant of susceptibility to smoking-related pulmonary dysfunction mediated by oxidants derived from smoke-activated phagocytes.

Topics: Adult; beta Carotene; Carotenoids; Cholesterol; Chromatography, High Pressure Liquid; Disease Susceptibility; Humans; Leukocyte Count; Luminescent Measurements; Lung Diseases; Male; Neutrophils; Oxidative Stress; Reactive Oxygen Species; Risk Factors; Smoking; Tetradecanoylphorbol Acetate

To determine the relative effects of cigarette smoking and mineral dust exposure on numbers and activity of circulating phagocytes, plasma nutritional antioxidant state, and pulmonary function in South African gold miners.. Pulmonary function was assessed spirometrically, whereas reactive oxidant generation by circulating phagocytes, and plasma concentrations of the nutritional antioxidative nutrients vitamin C and vitamin E and beta carotene were measured with chemiluminescence, spectrophotometry, or high performance liquid chromatography respectively.. Cigarette smoking, but not mineral dust exposure, was associated with increased numbers and pro-oxidative activity of circulating neutrophils and monocytes, decreased plasma concentrations of vitamin C, and pulmonary dysfunction.. In this study group occupational exposure to mineral dust has not been found to promote increases in the numbers or reactivity of circulating phagocytes or to be a significant cause of pulmonary dysfunction, the changes found being due primarily to cigarette smoking.

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Dust; Gold; Humans; Leukocyte Count; Lung; Lung Diseases; Male; Middle Aged; Mining; Occupational Exposure; Phagocytes; Smoking; South Africa; Spirometry; Vitamin E

A case-control study among white women in Los Angeles County was conducted to investigate the role of smoking and other factors in the etiology of lung cancer in women. A total of 149 patients with adenocarcinoma (ADC) and 71 patients with squamous cell carcinoma (SCC) of the lung and their age- and sex-matched controls were interviewed. Personal cigarette smoking accounted for almost all of SCC and about half of ADC in this study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) [RR = 1.2; 95% confidence interval (Cl) = 0.5, 3.3] and at work (RR = 1.3; 95% Cl = 0.5, 3.3). Childhood pneumonia (RR = 2.7; 95% Cl = 1.1, 6.7) and childhood exposure to coal burning (RR = 2.3; 95% Cl = 1.0, 5.5) were additional risk factors for ADC. For both ADC and SCC, increased risks were associated with decreased intake of beta-carotene foods but not for total preformed vitamin A foods and vitamin supplements.

Topics: Adenocarcinoma; beta Carotene; California; Carotenoids; Dairy Products; Diet; Epidemiologic Methods; Female; Humans; Lung Diseases; Lung Neoplasms; Occupations; Population Surveillance; Risk; Smoking; Tobacco Smoke Pollution; Vitamin A