Study to Evaluate the Effects of Weight Loss on Airway Inflammation and Mechanics in Subjects With Asthma (Asthma-Bariatric Surgery Study)
Ключови думи
Резюме
Описание
This study is designed to explain the unexpected effects of obesity on NO bioavailability in the airways of asthmatics: Specifically, that obesity induces systemic oxidative stress in part through increased production of reactive oxygen species (ROS) in adipose tissue and, in parallel (or as a consequence), increased systemic levels of tumor necrosis factor (TNF-α)and 8-isoprostanes. Furthermore, it creates an imbalance in the regulation of protective anti-oxidant thiol/disulfide pairs such as glutathione/glutathione disulfide. We hypothesize that in asthmatics, the lung is a target-organ of this obesity-related systemic oxidative stress. This is manifested as increased oxidation of airway NO into nitrate and reactive nitrogen species (RNS) including peroxynitrate and nitrotyrosine, thereby reducing NO bioavailability and exhaled NO levels. NO has many key physiological properties including bronchodilation, anti-tumoral/bactericidal activity, and anti-inflammatory and anti-oxidative activity. Thus, reduced NO bioavailability in obese asthmatics could favor increased bronchoconstriction and impair the lung's ability to respond to further oxidative or inflammatory challenges. Therefore, we hypothesize that: 1) obesity causes redox stress in the airway, which in turn decreases the bioavailability of NO by shunting it into RNS, 2) that weight loss will decrease systemic oxidative stress and thereby increase NO bioavailability due to decreased oxidation into RNS, and 3) that by decreasing systemic oxidative stress, weight loss will reduce bronchial hyper-reactivity.
Дати
Последна проверка: | 06/30/2013 |
Първо изпратено: | 02/03/2008 |
Очаквано записване подадено: | 02/03/2008 |
Първо публикувано: | 02/13/2008 |
Изпратена последна актуализация: | 07/29/2013 |
Последна актуализация публикувана: | 07/30/2013 |
Действителна начална дата на проучването: | 06/30/2006 |
Приблизителна дата на първично завършване: | 08/31/2008 |
Очаквана дата на завършване на проучването: | 08/31/2008 |
Състояние или заболяване
Фаза
Групи за ръце
Arm | Интервенция / лечение |
---|---|
Surgical cases Subjects who are undergoing bariatric surgery | |
Controls Subjects who qualify for bariatric surgery but do not undergo the procedure |
Критерии за допустимост
Възрасти, отговарящи на условията за проучване | 18 Years Да се 18 Years |
Полове, допустими за проучване | All |
Метод за вземане на проби | Non-Probability Sample |
Приема здрави доброволци | Да |
Критерии | Inclusion Criteria: - Non-smoker, or a limited smoking history - Meet criteria for bariatric surgery according to NIH guidelines Exclusion Criteria: - Illicit drug use - Greater than 10 pack-year history of cigarette smoking - Other significant lung pathology - Other significant non-pulmonary co-morbidities |
Резултат
Първични изходни мерки
1. To measure levels of exhaled nitric oxide, reactive nitrogen species, exhaled biomarkers of lipid peroxidation, asthma quality of life, airway function (spirometry and response to methacholine), and degree of asthma control [Enrollment, 1 month, 6 months, and 1 year]
2. To measure systemic markers of redox stress and inflammation, including plasma levels of adipokines, adiposity-related cytokines (IL-6, TNF-α), GSH/GSSG, 8-isoprostanes, and leukotrienes [Enrollment, 1 month, 6 months, and 1 year]