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      ST2 Predicts Mortality In Patients With Acute Hypercapnic Respiratory Failure Treated With Noninvasive Positive Pressure Ventilation

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          Patients with Acute Hypercapnic Respiratory Failure (AHRF) are often treated with Noninvasive Positive Pressure Ventilation (NPPV). In this heterogeneous patient group, there is a lack of clinical tools for predicting mortality and outcome.


          In order to facilitate the choice of treatment in patients with AHRF we evaluated the protein ST2, an established biomarker for cardiac stress, and its role in predicting mortality in patients with AHRF treated with NPPV. We also examined if ST2 baseline levels and changes during the first 12 hrs of treatment were predictive of treatment outcome.


          The study population consisted of 46 patients treated with NPPV for AHRF. Background data and clinical parameters were obtained and blood samples taken at various time points during the treatment. During the follow-up period of 18 months, the prognostic value of ST2 with regards to mortality was evaluated using Cox proportional hazard model.


          Of the 46 patients, there were 3 subgroups in regards to primary diagnosis: Acute Exacerbation of COPD (n=34), Acute Heart Failure (n=8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (n=4). We found that ST2 was an independent predictor of both short-term and long-term mortality during the follow-up period. The Hazard Ratio (HR) per 1-SD increment of ST2 for 28-day mortality was 11.00 (95% CI 1.8–67.2, p 0.009) and for 18-month mortality 2.11 (95% CI 1.4–3.2, p 0.001). The results seem to be driven by the largest subgroup of patients, with Acute Exacerbation of COPD, and deaths within the first 28 days. Furthermore, changes in ST2 values during the first 12 hrs of treatment were not predictive of treatment outcome.


          Our results show that ST2 is a target to explore further as a predictor of short-term mortality in patients with AHRF treated with NPPV.

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          Most cited references 31

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          Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis.

          To determine the effectiveness of non-invasive positive pressure ventilation (NPPV) in the management of respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease. Systematic review of randomised controlled trials that compared NPPV and usual medical care with usual medical care alone in patients admitted to hospital with respiratory failure resulting from an exacerbation of chronic obstructive pulmonary disease and with PaCO2 >6 kPa. The eight studies included in the review showed that, compared with usual care alone, NPPV as an adjunct to usual care was associated with a lower mortality (relative risk 0.41 (95% confidence interval 0.26 to 0.64)), a lower need for intubation (relative risk 0.42 (0.31 to 0.59)), lower likelihood of treatment failure (relative risk 0.51 (0.38 to 0.67)), and greater improvements at 1 hour in pH (weighted mean difference 0.03 (0.02 to 0.04)), PaCO2 (weighted mean difference -0.40 kPa (-0.78 to -0.03)), and respiratory rate (weighted mean difference -3.08 breaths per minute (-4.26 to -1.89)). NPPV resulted in fewer complications associated with treatment (relative risk 0.32 (0.18 to 0.56)) and shorter duration of stay in hospital (weighted mean difference -3.24 days (-4.42 to -2.06)). NPPV should be the first line intervention in addition to usual medical care to manage respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease in all suitable patients. NPPV should be tried early in the course of respiratory failure and before severe acidosis, to reduce mortality, avoid endotracheal intubation, and decrease treatment failure.
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            Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.

            The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.
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              Acute respiratory failure in patients with severe community-acquired pneumonia. A prospective randomized evaluation of noninvasive ventilation.

              In uncontrolled studies, noninvasive positive pressure ventilation (NPPV) was found useful in avoiding endotracheal intubation in patients with acute respiratory failure (ARF) caused by severe community-acquired pneumonia (CAP). We conducted a prospective, randomized study comparing standard treatment plus NPPV delivered through a face mask to standard treatment alone in patients with severe CAP and ARF. Patients fitting the American Thoracic Society criteria for severe CAP were included in presence of ARF (refractory hypoxemia and/or hypercapnia with acidosis). Exclusion criteria were: severe hemodynamic instability, requirement for emergent cardiopulmonary resuscitation, home mechanical ventilation or oxygen long-term supplementation, concomitant severe disease with a low expectation of life, inability to expectorate or contraindications to the use of the mask. Fifty-six consecutive patients (28 in each arm) were enrolled, and the two groups were similar at study entry. The use of NPPV was well tolerated, safe, and associated with a significant reduction in respiratory rate, need for endotracheal intubation (21% versus 50%; p = 0.03), and duration of intensive care unit (ICU) stay (1.8 +/- 0.7 d versus 6 +/- 1.8 d; p = 0.04). The two groups had a similar intensity of nursing care workload, time interval from study entry to endotracheal intubation, duration of hospitalization, and hospital mortality. Among patients with chronic obstructive pulmonary disease (COPD), those randomized to NPPV had a lower intensity of nursing care workload (p = 0.04) and improved 2-mo survival (88.9% versus 37.5%; p = 0.05). We conclude that in selected patients with ARF caused by severe CAP, NPPV was associated with a significant reduction in the rate of endotracheal intubation and duration of ICU stay. A 2-mo survival advantage was seen in patients with COPD.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                23 October 2019
                : 14
                : 2385-2393
                [1 ]Department of Clinical Sciences Malmo, Faculty of Medicine, Lund University , Lund, Sweden
                [2 ]Department of Pulmonary Medicine and Allergology, Skåne University Hospital , Malmö, Sweden
                [3 ]Department of Internal Medicine and Emergency Medicine, Skåne University Hospital , Malmö, Sweden
                [4 ]Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet , Copenhagen, Denmark
                Author notes
                Correspondence: Brynja Jónsdóttir Department of Pulmonary Medicine and Allergology, Skånes Universitetssjukhus Malmö , Södra Förstadsgatan, Malmö20502, Sweden Email
                © 2019 Jónsdóttir et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (

                Page count
                Figures: 2, Tables: 3, References: 38, Pages: 9
                Funded by: Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation
                Funded by: Swedish Heart- and Lung Foundation
                Funded by: Swedish Research Council 10.13039/501100004359
                Funded by: Novo Nordisk Foundation, Region Skåne, Skåne University Hospital
                Funded by: the Swedish Foundation for Strategic Research Dnr
                Award ID: IRC15-0067
                The study was supported by grants from Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation, the Swedish Heart- and Lung Foundation, the Swedish Research Council, the Novo Nordisk Foundation, Region Skåne, Skåne University Hospital and the Swedish Foundation for Strategic Research Dnr IRC15-0067.
                Original Research


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