The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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Multicenter Study
Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial.
We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. ⋯ The 6MWD increased from 325 ± 96 m at baseline to 351 ± 111 m after 12 weeks. Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.
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The lectin-like domain of thrombomodulin (TM) plays an important regulatory role in sterile inflammatory conditions, but its role in severe Gram-positive infectious disease is unknown. Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. The aim of this study was to determine the role of the lectin-like domain of TM in murine pneumococcal pneumonia. ⋯ Plasma levels of pro-inflammatory cytokines were also reduced in TM(LeD/LeD) mice after exposure to the infection. Deletion of the lectin-like domain of TM improves the host defence in pneumococcal pneumonia. The lectin-like domain of TM may have a differential role in response to Gram-positive or Gram-negative bacteria.
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Community-acquired pneumonia (CAP) represents a major life-threatening infection, but disease course and outcome is highly variable. Major drivers of prognosis are respiratory failure, sepsis-related organ dysfunction and unstable comorbidities. Current risk stratification tools have been primarily designed to predict mortality and identify low risk patients potentially suitable for ambulatory management. ⋯ New cardiovascular or stress-related biomarkers like copeptin, midregional proadrenomedullin and cortisol have been repeatedly linked with outcome and disease course in CAP and improved clinical scoring in observational studies. Thus they represent promising tools for individualised risk stratification. A major task in future CAP research will be the evaluation of their additional value in large interventional trials with control groups incorporating strict management guidance by clinical criteria.
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C(U)RB-65 (confusion, (urea >7 mol · L(-1),) respiratory frequency ≥ 30 breaths · min(-1), systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥ 65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe. In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008-2010, different CRB-age groups (≥ 50 and ≥ 60 years) across the total CAP population and three entities of CAP (younger population aged <65 years, patients aged ≥ 65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death. 660 594 patients were investigated. Mortality was n=93 958 (14.0%). ⋯ Patients with hospitalised CAP aged <65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.
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Vitamin K antagonists are advised in pulmonary arterial hypertension patients despite a lack of safety data. We reviewed major bleeding in three classes of pulmonary hypertension patients, all receiving vitamin K antagonists. Bleeding event rates were 5.4 per 100 patient-years for patients with idiopathic pulmonary arterial hypertension, 19 per 100 patient-years for connective tissue disease related pulmonary arterial hypertension patients and 2.4 per 100 patient-years for chronic thromboembolic pulmonary hypertension patients. ⋯ Major bleeding was independent of age, sex, target international normalised ratio (INR) range, documented INR, vitamin K antagonist type, or right atrial pressure, but was associated with use of prostacyclin analogues. Major bleeding risk during vitamin K antagonist therapy differs among groups of patients with pulmonary hypertension. Further research regarding optimal anticoagulant therapy is needed, as well as risk-benefit analyses for pulmonary hypertension patients with a higher bleeding propensity.