Journal of pulmonary & respiratory medicine最新文献

Background: Ample evidence suggests a dose-response relationship between increasing weight and level of asthma risk or reduced asthma control. To establish reversibility, several randomized controlled trials (RCTs) have recently been published to investigate the impact of weight management on asthma. This systematic review synthesizes evidence from these RCTs on the effects of weight management (weight loss, weight maintenance, maintenance of lost weight, or weight gain prevention) interventions on asthma outcomes in both adult and pediatric populations.

Methods: We searched Medline, CINAHL, PsychInfo, and Cochrane for studies published between 1950 and November 2014. Two researchers independently rated the included studies using the quality assessment tool for RCTs as outlined in the 2013 Obesity Treatment Guideline. Discrepancies were resolved by consensus after discussion between the raters and, if needed, with the senior author.

Results: Four RCTs in adults and 3 in children and adolescents were included. The adult studies seem to consistently support the benefit of substantial weight loss, but a threshold effect may exist such that only weight loss beyond a minimal amount will likely lead to clinically important improvement in asthma outcomes. Three of them suggest that the threshold may lie between 5-10% of weight loss. RCTs in youth suggest that modest calorie reductions alone or combined with increased physical activity, or even a healthy normocaloric diet, may lead to improved asthma outcomes. However, most RCTs reviewed were limited by small sample size, short intervention durations, and short follow-up periods.

Conclusion: Trial evidence shows the promise of weight loss interventions for asthma control in adults and youth. More adequately-powered, long-term RCTs are needed to elucidate the role of weight loss and other weight management interventions in asthma control and prevention. Definitive data are needed to guide clinical and public health practice to effectively address the dual epidemic of obesity and asthma.

Background: The molecular mechanisms governing right atrial (RA) and ventricular (RV) hypertrophy and failure in chronic pulmonary hypertension (CPH) remain unclear. The purpose of this investigation was to characterize RA and RV protein changes in CPH and determine their adaptive versus maladaptive role on hypertrophic development.

Methods: Nine dogs underwent sternotomy and RA injection with 3 mg/kg dehydromonocrotaline (DMCT) to induce CPH (n=5) or sternotomy without DMCT (n=4). At 8-10 weeks, RA and RV proteomic analyses were completed after trypsinization of cut 2-D gel electrophoresis spots and peptide sequencing using mass spectrometry.

Results: In the RV, 13 protein spots were significantly altered with DMCT compared to Sham. Downregulated RV proteins included contractile elements: troponin T and C (-1.6 fold change), myosin regulatory light chain 2 (-1.9), cellular energetics modifier: fatty-acid binding protein (-1.5), and (3) ROS scavenger: superoxide dismutase 1 (-1.7). Conversely, beta-myosin heavy chain was upregulated (+1.7). In the RA, 22 proteins spots were altered including the following downregulated proteins contractile elements: tropomyosin 1 alpha chain (-1.9), cellular energetic proteins: ATP synthase (-1.5), fatty-acid binding protein (-2.5), and (3) polyubiquitin (-3.5). Crystallin alpha B (hypertrophy inhibitor) was upregulated in both the RV (+2.2) and RA (+2.6).

Conclusions: In early stage hypertrophy there is adaptive upregulation of major RA and RV contractile substituents and attenuation of the hypertrophic response. However, there are multiple indices of maladaptive pathology including considerable cellular stress associated with aberrancy of actin machinery activity, decreased efficiency of energy utilization, and potentially decreased protein quality control.

Objective: High flow nasal cannula therapy (HFT) has been shown to be similar to nasal continuous positive airway pressure (nCPAP) in neonates with respect to avoiding intubation. The objective of the current study is to determine if there are trends for adverse safety and long-term respiratory outcomes in very low birth weight infants (<1500 g) from centers using HFT as their primary mode of non-invasive respiratory support compared to data from the largest neonatal outcomes database (Vermont Oxford Network; VON).

Methods: A multicenter, retrospective analysis of pulmonary outcomes data was performed for the calendar years 2009, 2010 and 2011. Performance of five HFT centers was compared with population outcomes from the VON database. The five HFT centers routinely use flow rates between 4-8 L/min as described by the mechanistic literature. Weighted average percentages from the five HFT centers were calculated, along with the 95% confidence intervals (CI) to allow for comparison to the VON means.

Results: Patient characteristics between the HFT centers and the VON were not different in any meaningful way, despite the HFT having a greater percentage of smaller infants. The average VON center primarily used nCPAP (69% of all infants) whereas the HFT centers primarily used HFT (73%). A lesser percentage of VLBW infants in the HFT cohort experienced mortality and nosocomial infection. Compared to VON data, an appreciably lesser percent of the HFT cohort were receiving oxygen at 36 weeks and less went home on oxygen.

Conclusions: Considering there was no trend for adverse events, and there was a trend for better outcomes pertaining to long-term oxygen use, these data support claims of safety for HFT as a routine respiratory management strategy in the NICU.

Rationale: Studies in Hispanic/Latino populations have shown ethnicity to be either a predictive or protective factor for COPD mortality and it is unclear whether this disagreement is attributable to ethnic differences in smoking rates, smoking behavior or differences in genetic susceptibility.

Objectives: This study will examine the role of smoking behavior as a means of explaining differences in risk for COPD mortality between Hispanics and non-Hispanic whites.

Methods: Participants were recruited into a cohort study from the San Luis Valley in Colorado beginning in the early 1980's and followed for mortality until 2012. COPD and cardiovascular disease are often comorbid conditions and account for the competing risk of CVD in the analysis of COPD mortality. Mortality searches were conducted regularly and all ICD codes were collected for mortality event. Primary and secondary causes of each event were assessed using appropriate codes.

Results: Hispanic current smokers did not differ from NHW current smokers in years smoked (p=0.6) but Hispanic former smokers accumulated more years smoked compared to NHW former smokers (22 vs. 20, p=0.047). Hispanic ethnicity was significantly protective for COPD mortality adjusting for age, gender, pre-existing emphysema, hypertension and smoking status and accounting for the effect of CVD mortality (RR=0.58, 95% C.I. 0.34-0.99, p=0.035). Further adjustment for smoking behavior mitigated this effect.

Conclusions: The lower COPD mortality seen in Hispanic smokers may be due lower cumulative exposure to tobacco smoke. Thus, smoking behavior may play a key role in explaining differences in COPD mortality as they relate to Hispanic ethnicity.

Recently a great deal of progress has been made in our understanding of pulmonary hypertension (PH). Research from the past 30 years has resulted in newer treatments that provide symptomatic improvements and delayed disease progression. Unfortunately, the cure for patients with this lethal syndrome remains stubbornly elusive. With the relative explosion of scientific literature regarding PH, confusion has arisen regarding animal models of the disease and their correlation to the human condition. This short review uniquely focuses on the clear and present need to better correlate mechanistic insights from existing and emerging animal models of PH to specific etiologies and histopathologies of human PH. A better understanding of the pathologic processes in various animal models and how they relate to the human disease should accelerate the development of newer and more efficacious therapies.

Background: Each year in the United States an estimated 1.5 million people develop pleural effusions and approximately 178,000 thoracenteses (12%) are performed. While it has been established that malignant effusions are associated with increased mortality, the association between mortality and all-cause pleural effusions in a medical population has not been previously evaluated. Our objective was to evaluate associations between 30-day and 12-month all-cause mortality among patients with a pleural effusion.

Methods: All patients admitted to the medical service at Yale-New Haven Hospital during March 2011 were screened for pleural effusion. Pleural effusions were documented by the attending radiologist and the medical record was reviewed for admitting diagnosis, severity of illness and whether a thoracenteses was performed. The outcomes were 30-day and 12-month mortality after identification of the pleural effusion.

Results: One-hundred and four patients admitted to the medical service had pleural effusions documented by the attending radiologist. At 30-days, 15% of these patients had died and by 12-months mortality had increased to 32%. Eleven (10.6%) of the 104 patients underwent a thoracenteses. Severity of illness and malignancy were associated with 30-day mortality. For 12-month mortality, associations were found with age, severity of illness, malignancy, and diagnosis of pulmonary disease. Although sample size precluded statistical significance with mortality, the hazard ratio for thoracenteses and 30-day mortality was protective, suggesting a possible short term survival benefit.

Conclusions: In hospitalized medical patients with a pleural effusion, age, severity of illness and malignancy or pulmonary disease were associated with higher 12-month mortality. Thoracenteses may provide a protective effect in the first 30 days, but larger studies are needed to detect a short-term survival benefit. The presence of a pleural effusion indicates a high risk of death, with 15% of patients dying within 30 days and 32% dead within one-year of hospital admission.

Objective: The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors.

Methods: Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak.

Results: There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak.

Conclusion: Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

Background: Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and 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. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures.

Methods: We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O₂ (O₂); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O₂ and IR (O₂+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals.

Results: At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung.

Conclusion: Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early tissue oxidative damage associated with space exploration.