Differential proteomic analysis reveals increased cathelicidin expression in porcine bronchoalveolar lavage fluid after an Actinobacillus pleuropneumoniae infection

Accurate definition of respiratory health in pigs is an important problem for swine producers and veterinarians. In an approach to identify potential biomarkers, two-dimensional gel electrophoresis and mass spectrometry on bronchoalveolar lavage fluid (BALF)-derived proteins from pigs experimentally infected with Actinobacillus pleuropneumoniae were performed at different time points post infection. Mock-infected pigs were used as a control. It was shown that the antimicrobial peptides, prophenin-2 and PR-39, and the calcium-binding protein calgranulin C were reproducibly upregulated in BALF of pigs chronically infected with A. pleuropneumoniae. Concentrations of PR-39 were significantly (p < 0.05) increased in BALF (median of 4.8 nM) but not in serum (median of 2.5 nM) on day 21 after infection. A Receiver Operating Characteristics (ROC) plot showed that PR-39 in BALF is an accurate and easily accessible marker to detect clinically healthy pigs convalescent from an experimental A. pleuropneumoniae infection. These results imply that PR-39 might have a potential as a general biomarker to determine porcine respiratory health

Glycoprotein analysis of porcine bronchoalveolar lavage fluid reveals potential biomarkers corresponding to resistance to Actinobacillus pleuropneumoniae infection

Biomarkers facilitating both pathogen-independent diagnosis of respiratory health and breeding selection of pigs with increased resistance to respiratory tract infections would be of considerable interest to the pig industry. Following this concept we performed a comparative glycoproteome analysis of bronchoalveolar lavage fluid (BALF) from healthy pigs and pigs 4 days (acute) and 20 days (chronic) after an experimental infection with Actinobacillus pleuropneumoniae. In order to identify possible differences in BALF glycoprotein patterns we investigated pigs of three different breeding lines (German Landrace, Piétrain, Hampshire). In total, 12 glycosylated proteins (alpha-1-acid glycoprotein, fetuin A, properdin, haptoglobin precursor, haptoglobin, hemoglobin, hyaluronidase, inter-alpha-trypsin inhibitor family heavy chain-related protein, alpha-1-antichymotrypsin 3, pulmonary surfactant-associated protein D (SP-D), transferrin, and alpha-1B-glycoprotein) were identified as being differentially expressed depending on the health status of the animal. Fetuin A levels were consistently low in chronically infected pigs thereby being a potential marker for chronic infection. Hyaluronidase levels were consistently high in all pigs after experimental infection independent on isolation of the pathogen thereby being a potential marker for previous pathogen contact and latent infection. High levels of fetuin A as well as low levels of haptoglobin and pulmonary SP-D correlated with the absence of lung lesions in pigs of the Hampshire breeding line, implying a potential application as selection markers for breeding programmes

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used