Plant community composition alters moisture and temperature sensitivity of soil respiration in semi-arid shrubland.

Soil respiration (Rs) is the second largest carbon (C) flux to the atmosphere and our understanding of how Rs and its components shift with plant-community composition remains an important question. We used high-frequency soil respiration measurements and root exclusion to evaluate how Rs, autotrophic respiration (Ra) and heterotrophic respiration (Rh) vary between a semi-arid perennial shrub community and annual invasive community. Over two growing seasons, total Rs was 40% higher under annual vegetation compared to shrubs. Partitioning revealed consistently higher Ra under annual vegetation which accounted for most of the difference in Rs. Under annual vegetation, Ra increased soon after the first rain events and remained high despite cooling temperatures while shrub Ra increased only when soil temperature began to warm up. The Rh rates were similar between vegetation types when daily soil temperatures were lower than 20 °C. As soil temperatures increased and soil moisture dropped below 10%, Rh was consistently higher under annual vegetation than shrubs. Seasonal dynamics of Rs and Rh were best modeled with an interaction term between soil moisture and temperature with significantly different model parameters for each vegetation type. Differences in the timing and magnitude of Rs and Ra between vegetation types are consistent with phenological differences between shrubs and annuals. Under annuals, larger Rh at high temperatures suggests that expansion of annual vegetation and future hotter and drier conditions could lead to greater C losses from this semi-arid shrub system.

Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial.

BACKGROUND: Short-acting ß2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity. This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD. METHODS: The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 µg, once-daily umeclidinium 62.5 µg or twice-daily salmeterol 50 µg for 24 weeks. Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk. A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates. RESULTS: At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206). Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores. By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: - 0.56 [p < 0.001]; low: - 0.10 [p = 0.132]). Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol. Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day. CONCLUSIONS: In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation. SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome. FUNDING: GlaxoSmithKline (study number 201749 [NCT03034915]).

Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-α receptor 1.

PURPOSE: To investigate the impact of a new class of anti-Ig autoantibodies reactive with variable heavy (VH) chain framework sequences (human anti-VH autoantibodies) on the pharmacology and safety of an anti-TNFR1 VH domain antibody (GSK1995057) in healthy human subjects. METHODS: Single-blind, randomised, placebo-controlled dose escalation study in which healthy males (n = 28) received a single GSK1995057 intravenous infusion of 0.0004, 0.002 and 0.01 mg/kg. All enrolled subjects were pre-screened for human anti-VH (HAVH) autoantibody status and prospectively stratified accordingly. Serum samples from drug-naïve, HAVH-positive volunteers were used to investigate the effect of HAVH/GSK1995057 complexes on the activation of TNFR1 and cytokine release in vitro. RESULTS: Human anti-VH autoantibodies were detected in approximately 50 % of drug-naïve healthy human subjects and clinical and in vitro studies were performed to evaluate their impact on the pharmacology and safety of GSK1995057. We demonstrated that formation of HAVH autoantibody/GSK1995057 complexes activated TNFR1 and caused cytokine release in vitro in some, but not all, of the human cell types tested. When GSK1995057 was administered to healthy subjects, clinical and physiological signs of cytokine release were observed in two HAVH autoantibody-positive subjects following GSK1995057 infusion. In vitro, HAVH autoantibody levels correlated with TNFR1-dependent cytokine release and propensity for cytokine release in humans following GSK1995057 dosing. CONCLUSIONS: Our data support a greater focus on the impact of pre-existing, drug-reactive autoantibodies on the development of antibody fragments and biotherapeutics targeting cell surface receptors.

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.

A small animal model of regional alveolar ventilation using HP 3He MRI1.

RATIONALE AND OBJECTIVES: The aim of this study was to establish a standardized procedure for the measurement of regional fractional ventilation in a healthy rat model as a baseline for further studies of pulmonary disorder models. MATERIALS AND METHODS: The lungs of five healthy male Sprague-Dawley rats were imaged using hyperpolarized helium-3 magnetic resonance imaging. From these images, regional fractional ventilation was calculated and maps generated detailing the distribution of fractional ventilation in the lung. The 1.56 mm x 1.56 mm x 4 mm regions of interest were assigned on 5 cm x 5 cm field of view lung maps. Histograms were also generated showing the frequency distribution of fractional ventilation values. To compare fractional ventilation values between animals, the ventilation procedure was standardized to results from individual pulmonary function tests. Each animal's spontaneous tidal volume, respiratory rate, and inspiration percentage (percent of total respiratory cycle in inspiration) were used in their mechanical ventilation settings. RESULTS: Results were similar among all five healthy rats based on examination of ventilation distribution maps and frequency distribution histograms. Mean (0.13) and standard deviation (0.07) were calculated for fractional ventilation in each animal. However, these values were determined to be influenced by slice selection, and therefore the maps and histograms were favored in analysis of results. CONCLUSION: This study shows consistent results in healthy rat lungs and will serve as a baseline study for future measurements in emphysematous rat lungs.

Molecular and metabolic characterization of cold-tolerant alpine soil Pseudomonas sensu stricto.

Alpine soils undergo dramatic temporal changes in their microclimatic properties, suggesting that the bacteria there encounter uncommon shifting selection gradients. Pseudomonads constitute important members of the alpine soil community. In order to characterize the alpine Pseudomonas community and to assess the impact of shifting selection on this community, we examined the ability of cold-tolerant Pseudomonas isolates to grow on a variety of carbon sources, and we determined their phylogenetic relationships based on 16S ribosomal DNA sequencing. We found a high prevalence of Pseudomonas in our soil samples, and isolates from these soils exhibited extensive metabolic diversity. In addition, our data revealed that many of our isolates form a unique cold-adapted clade, representatives of which are also found in the Swedish tundra and Antarctica. Our data also show a lack of concordance between the metabolic properties and 16S phylogeny, indicating that the metabolic diversity of these organisms cannot be predicted by phylogeny.

Changes in soil microbial community structure and function in an alpine dry meadow following spring snow melt.

Previous work in an alpine dry meadow in the Front Range of the Rocky Mountains has shown that microbial biomass is high during winter and declines rapidly as snow melts in the spring, and that this decline is associated with changes in temperature regime and substrate availability. In this study we tested the hypothesis that the summer and winter microbial communities differ in function and composition. Shifts in species composition between pre- and post-snowmelt communities were detected using reciprocal hybridization of community DNA; DNA extracted from soils sampled at different times was significantly less homologous relative to spatial replicates sampled at the same time. Fungal/bacterial ratios, as measured by direct microscopic counts and by substrate-induced respiration experiments with specific inhibitors, were higher in winter soils. Specific activity of cellulase (absolute cellulase activity per unit microbial biomass C) was higher in the winter soils than in summer soils, while specific amylase activity was not different between winter and summer. Based on most-probable number measurements, the use of the phenolic compound vanillic acid was highest in the winter, while the use of the amino acid glycine was lowest in the winter. Winter and summer soil respiration responded differently to temperature; at 0 degrees C, winter soils respired at a higher proportion of the 22 degrees C rate than did summer soils.

Apical perfusion fraction as a predictor of short-term functional outcome following bilateral lung volume reduction surgery.

STUDY OBJECTIVES: To examine whether relative hypoperfusion to the apical one third of the lungs as determined by lung scintigraphy predicts a favorable functional outcome following bilateral lung volume reduction surgery (LVRS). METHODS: We performed a retrospective analysis of 128 patients who underwent bilateral LVRS. An apical perfusion fraction (AP%), defined as the percentage of total lung perfusion to the apical one third of both lungs, was derived for each patient by quantitative scintigraphy technique. Pulmonary function testing and 6-min walk test (6MWT) data were obtained preoperatively and 3 to 6 months postoperatively. RESULTS: The mean (+/- SD) improvement in FEV(1) was 309 +/- 240 mL, 209 +/- 293 mL, and 116 +/- 224 mL for patients with an AP% of 20%, respectively (p = 0.01, analysis of variance [ANOVA]). The likelihood of experiencing an increase in FEV(1) >or= 200 mL was 68% for those with an AP% 20%. Preoperative and postoperative 6MWT data were available for 109 of 128 patients. Improvement was 250 +/- 252 feet, 205 +/- 299 feet, and 77 +/- 200 feet for patients with AP% 20%, respectively (p = 0.04, ANOVA). While 50% of those with an AP% or= 180 feet, only 21% of those with an AP% > 20% did so. CONCLUSION: This retrospective analysis suggests that quantification of apical perfusion by nuclear scintigraphy assists in predicting the likelihood of short-term functional improvement after LVRS.

Dynamic observation of pulmonary perfusion using continuous arterial spin-labeling in a pig model.

The continuous arterial spin-labeling (CASL) method of perfusion MRI is used to observe pulmonary perfusion dynamically in an animal model. Specifically, a respiratory-triggered implementation of the CASL method is used with approximate spatial resolution of 0.9 x 1.8 x 5.0 mm (0.008 cc) and 2-minute temporal resolution. Perfusion MRI is performed dynamically during repeated balloon occlusion of a segmental pulmonary artery, as well as during pharmacological stimulation. A total of three Yorkshire pigs were studied. The results demonstrate the ability of the endogenous spin-labeling method to characterize the dynamic changes in pulmonary perfusion that occur during important physiological alterations.

Detection and localization of pulmonary air leaks using laser-polarized (3)He MRI.

Pulmonary air leaks were created in the lungs of Yorkshire pigs. Dynamic, 3D MRI of laser-polarized (3)He gas was then performed using a gradient-echo pulse sequence. Coronal magnitude images of the helium distribution were acquired during gas inhalation with a voxel resolution of approximately 1.2 x 2.5 x 8 mm, and a time resolution of 5 sec. In each animal, the ventilation images reveal focal high-signal intensity within the pleural cavity at the site of the air leaks. In addition, a wedge-shaped region of increased parenchymal signal intensity was observed adjacent to the site of the air leak in one animal. (3)He MRI may prove helpful in the management of patients with pulmonary air leaks.

Demonstration of a compact compressor for application of metastability-exchange optical pumping of 3He to human lung imaging.

Hyperpolarized gas magnetic resonance imaging has recently emerged as a method to image lungs, sinuses, and the brain. The best lung images to date have been produced using hyperpolarized 3He, which is produced by either spin-exchange or metastability-exchange optical pumping. For hyperpolarized gas MRI, the metastable method has demonstrated higher polarization levels and higher polarizing rates, but it requires compression of the hyperpolarized gas. Prior to this work, compression of hyperpolarized gas had only been accomplished using a large, complex and expensive apparatus. Here, human lung ventilation images are presented that were obtained using a compact compressor that is relatively simple and inexpensive. For this test, 1.1 bar-L of 15% hyperpolarized 3He gas was produced at the National Institute of Standards and Technology using a modified commercial diaphragm pump. The hyperpolarized gas was transported to the University of Pennsylvania in a holding field provided by a portable solenoid.

Tension pneumoperitoneum associated with a pleural-peritoneal shunt.

The differential diagnosis of pneumoperitoneum is broad. We report a case of tension pneumoperitoneum in a patient on mechanical ventilation with initially unrecognized pneumothorax who had an indwelling pleural-peritoneal shunt. The patient developed ventilatory and hemodynamic collapse as air was diverted from the pleural space into the peritoneal cavity. Subsequent abdominal exploration revealed the source of the intra-abdominal air. Placement of a chest thoracostomy tube and removal of the pleural-peritoneal catheter resulted in significant clinical improvement. We suggest that it is important to recognize that pleural-peritoneal catheters may cause tension pneumoperitoneum without obvious concurrent pneumothorax.

Giant gastric ulcers and risk factors for gastroduodenal mucosal disease in orthotopic lung transplant patients.

Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.

GI complications after orthotopic lung transplantation.

OBJECTIVES: Recently, lung transplantation has been performed with increasing frequency and improved outcomes. GI complications have been observed and reported in patients undergoing cardiac and renal transplantations but only recently have been reported in patients after lung transplantation. No large cohort has been systematically analyzed for all GI complications after lung transplantation. The present study describes, categorizes, and assesses risk factors for the development of such GI complications. METHODS: Records of 45 patients who underwent 47 single or bilateral orthotopic lung transplants between November 1991 and January 1994 were reviewed. RESULTS: Twenty-three patients (51%) had 64 GI complications requiring 13 operations on eight patients. The incidence of major abdominal procedures in the entire transplant cohort was 18% (8/45). Their operative mortality rate was 63% (5/8). Eighteen different types of nonoperative complications occurred and were subclassified into major and minor complications. Complications were defined as major if they required medical or surgical intervention and altered patient management. Most GI complications (73%) occurred within 1 month after transplantation. No risk factors were identified to ascertain who will develop GI complications. CONCLUSIONS: GI complications occur in more than one-half of lung transplant recipients early after transplantation and in the absence of identifiable risk factors. Because there are no precedent risk factors to suggest who will develop GI complications, clinicians must be alert to any warning signs and symptoms. The majority of complications are nonoperative, responding to conservative therapy, but there is a higher overall mortality rate for patients requiring operative intervention, necessitating an aggressive search for major, life-threatening complications in these immunosuppressed patients.