Journal of pulmonary & respiratory medicine最新文献

Background: Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model.

Methods: Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O₂ (O₂); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O₂ and IR (O₂+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure.

Results: Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O₂ and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group.

Conclusion: We have characterized significant, early and chronic lung c

Purpose: The standard of care in Locally-Advanced Non-Small Cell Lung Cancer (LA-NSCLC) is chemotherapy and radiation; however, Radiation-Induced Lung Injury (RILI), which may be prevented by the anti-inflammatory and anti-oxidant properties of Flaxseed (FS), impedes its maximum benefit.

Materials and methods: Patients with LA-NSCLC requiring definitive RT were randomized to one FS or control muffin daily from start to 2 weeks after RT. Blood and urine were collected to quantify plasma FS metabolites, Enterodione (ED) and Enterolactone (EL), and urinary oxidative stress biomarkers, 8, 12-iso-iPF2a-VI (isoprostane) and 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dGuo). Tolerability was defined as consuming ≥ 75% of the intended muffins and no ≥ grade 3 gastrointestinal toxicities.

Results: Fourteen patients (control,7; FS,7) were enrolled. The tolerability rates were 42.9 versus 71.4% (p=0.59) for FS and control, respectively. Mean percentages of intended number of muffins consumed were 37% versus 73% (p=0.12). ED and EL increased at onset of FS and decreased with discontinuation, confirming bioavailability. Isoprostane and 8-oxo-dGuo were detectable. There was a trend towards decreased rates of pneumonitis in FS.

Conclusions: This is the first study to report FS bioavailability and quantify oxidative stress markers in NSCLC patients. FS in the administered muffin formulation did not meet tolerability criteria. Given the promising mechanism of FS as a radioprotectant, further investigations should focus on the optimal method for administration of FS.

Purpose: Loss of skeletal muscle strength is commonly seen with chronic obstructive pulmonary disease (COPD). The study aim was to determine the effects of comprehensive upper-body resistance training (8 different lifts) and a self-efficacy enhancing intervention in COPD with respect to muscle strength, symptoms, functional status and exercise adherence.

Methods: This randomized trial had 3 groups: upper-body resistance training with an intervention to enhance self-efficacy (UBR + SE), upper-body resistance training and health education (UBR + HE), gentle chair exercises and health education (CE + HE). Subjects performed 16 weeks of supervised training, then 12 months of long-term maintenance at home. Outcomes were: muscle strength, dyspnea, functional status, self-efficacy, and adherence.

Results: Sixty-four subjects completed 16 wks of training: age 71 ± 8 yr, fat-free mass index 19 ± 3 kg/m², forced expiratory volume in one second 58 ± 18 percent predicted. The UBR + SE intervention produced a 46% increase in strength compared to a 36% increase in the UBR + HE group (P = 0.054). The combined UBR + SE and UBR + HE groups produced a 41% increase in strength compared to an 11% increase in the CE+HE (P < 0.001). The combined UBR groups also demonstrated increases in lean arm mass (P = 0.003) and a trend toward decreased dyspnea (P = 0.053). There were no group differences in attrition, attendance and training progression. Fifty subjects completed long-term maintenance and the UBR + SE and UBR + HE groups retained some gains in muscle strength, 24% and 21% respectively, and the CE + HE group lost 3% of muscle strength from baseline.

Conclusion: The study provides strong evidence that comprehensive resistance training increased strength and lean arm mass and that strength can be partially maintained through a simple home program using hand weights. It provides limited evidence that upper-body resistance training improved dyspnea and that the exercise-specific self-efficacy enhancing intervention was beneficial.