Publications
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Edvardsen, Elisabeth; Anderssen, Sigmund Alfred; Borchsenius, Fredrik; Holme, Ingar Morten K; Nordsletten, Lars & Skjønsberg, Ole Henning
(2026).
Long-Term Effects of High-Intensity Training following Lung Cancer Surgery - A Five-Year Follow-Up of a Randomized Controlled Trial.
Medicine & Science in Sports & Exercise.
ISSN 0195-9131.
Publish Ahead of Print.
doi:
10.1249/MSS.0000000000003984.
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Allgot, Marte Skogstad; Malone, Joseph Anthony; Kleiven, Anne Louise; Skjønsberg, Ole Henning & Aarrestad, Sigurd
(2025).
Transcutaneous PCO2 Measurements With Long-Term Noninvasive Ventilation.
Respiratory care.
ISSN 0020-1324.
70(11),
p. 1415–1422.
doi:
10.1089/respcare.12855.
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Background: Current guidelines recommend that monitoring of long-term noninvasive ventilation (Long-term NIV) should include measurement of nocturnal transcutaneous PCO2 (PtcCO2). This has previously required an elective hospital admission. However, owing to a growing patient population and advancements in monitoring technology, there is a general trend toward moving specialized health care from the hospital to the home. The aim of this study was to compare the success rate and causes of failure of PtcCO2 monitoring at home versus at the hospital and to discuss the criteria used for the evaluation of nocturnal PtcCO2 monitoring.
Methods: In this real-world observational study, subjects scheduled for long-term NIV follow-up at Oslo University Hospital in the time period January 2020 to December 2022 were prospectively identified. A total of 128 subjects were included, and monitoring occurred either at home or at the hospital. Two physicians, blinded to the location of the monitoring, retrospectively classified the PtcCO2 as successful or unsuccessful and identified the causes of failure for the latter. The evaluation was performed using a predefined set of criteria, and results were divided into successful and unsuccessful recordings based on nontechnical (human) errors, time requirements, and technical errors such as fixed bias, instrumental drift, and artifacts.
Results: A total of 465 recordings of 128 subjects were performed. A 90% success rate was achieved for both groups. The predominant cause of failure in the home group was nontechnical (50% of total failures), whereas the predominant failure in the hospital group was caused by the recordings not meeting the minimum time requirement (38% of total failures).
Conclusions: There was a 90% success rate for PtcCO2 measurements both at home and at the hospital. Our findings suggest that PtcCO2 measurements can successfully be implemented in the regular follow-up of long-term NIV treatment in a home setting.
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Udjus, Camilla; Halvorsen, Bente; Kong, Xiang Yi; Sagen, Ellen Lund; Martinsen, Marita & Yang, Kuan
[Show all 10 contributors for this article]
(2024).
Alveolar hypoxia induces organ-specific inflammasome-related inflammation in male mouse lungs.
Physiological Reports.
12:e16143(14),
p. 1–13.
doi:
10.14814/phy2.16143.
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Inflammation through activation of caspase-1, seems to play a role in pulmonary hypertension induced by alveolar hypoxia. Whether alveolar hypoxia induces caspase-1-mediated inflammation and influx of leukocytes in other organs than the lungs, is not known. Our aim was to explore sites of caspase-1-related inflammation in alveolar hypoxia. Wild type (WT) mice were exposed to environmental hypoxia or room-air, and organs were analyzed. Right heart catheterization was performed after 14 days of alveolar hypoxia in WT mice and mice transplanted with WT or caspase-1−/− bone marrow. Hypoxia induced leukocyte accumulation and increased caspase-1 protein in the lungs, not in other organs. WT mice transplanted with WT or caspase-1−/− bone marrow showed no difference in pulmonary leukocyte accumulation or development of pulmonary hypertension after alveolar hypoxia. Caspase-1 and IL-18 were detected in bronchial epithelium in WT mice, and hypoxia induced IL-18 secretion from bronchial epithelial cells. IL-18 stimulation generated IL-6 mRNA in monocytes. Phosphorylated STAT3 was increased in hypoxic lungs, not in other organs. Alveolar hypoxia induces caspase-1 activation and leukocyte accumulation specific to the lungs, not in other organs. Caspase-1 activation and IL-18 secretion from bronchial epithelial cells might initiate hypoxia-induced inflammation, leading to pulmonary hypertension.
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Barratt-Due, Andreas; Pettersen, Kristin; Dahl, Tuva Børresdatter; Holter, Jan Cato; Grønli, Renathe Henriksen & Dyrhol-Riise, Anne Ma
[Show all 20 contributors for this article]
(2024).
Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients.
Journal of Internal Medicine.
ISSN 0954-6820.
296(1),
p. 80–92.
doi:
10.1111/joim.13783.
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Background: The complement system, an upstream recognition system of innate immunity, is activated upon SARS-CoV-2 infection. To gain a deeper understanding of the extent and duration of this activation, we investigated complement activation profiles during the acute phase of COVID-19, its persistence post-recovery and dynamic changes in relation to disease severity. Methods: Serial blood samples were obtained from two cohorts of hospitalized COVID-19 patients (n = 457). Systemic complement activation products reflecting classical/lectin (C4d), alternative (C3bBbP), common (C3bc) and terminal pathway (TCC and C5a) were measured during hospitalization (admission, days 3–5 and days 7–10), at 3 months and after 1 year. Levels of activation and temporal profiles during hospitalization were related to disease severity defined as respiratory failure (PO2/FiO2 ratio <26.6 kPa) and/or admission to intensive care unit, 60-day total mortality and pulmonary pathology after 3 months. Findings: During hospitalization, TCC, C4d, C3bc, C3bBbP and C5a were significantly elevated compared to healthy controls. Severely ill patients had significantly higher levels of TCC and C4d (p < 0.001), compared to patients with moderate COVID-19. Escalated levels of TCC and C4d during hospitalization were associated with a higher risk of 60-day mortality (p < 0.001), and C4d levels were additionally associated with chest CT changes at 3 months (p < 0.001). At 3 months and 1 year, we observed consistently elevated levels of most complement activation products compared to controls. Conclusion: Hospitalized COVID-19 patients display prominent and long-lasting systemic complement activation. Optimal targeting of the system may be achieved through enhanced risk stratification and closer monitoring of in-hospital changes of complement activation products.
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Aaløkken, Trond Mogens; Ashraf, Haseem; Einvik, Gunnar; Lerum, Tøri Vigeland; Meltzer, Carin & Rivero, Jezabel Rodriguez
[Show all 8 contributors for this article]
(2024).
CT abnormalities 3 and 12 months after hospitalization for COVID-19 and association with disease severity: A prospective cohort study.
PLOS ONE.
19(5).
doi:
10.1371/journal.pone.0302896.
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Objectives To investigate changes in chest CT between 3 and 12 months and associations with disease severity in patients hospitalized for COVID-19 during the first wave in 2020. Materials and methods Longitudinal cohort study of patients hospitalized for COVID-19 in 2020. Chest CT was performed 3 and 12 months after admission. CT images were evaluated using a CT severity score (CSS) (0–12 scale) and recoded to an abbreviated version (0–3 scale). We analyzed determinants of the abbreviated CSS with multivariable mixed effects ordinal regression. Results 242 patients completed CT at 3 months, and 124 (mean age 62.3±13.3, 78 men) also at 12 months. Between 3 and 12 months (n = 124) CSS (0–12 scale) for ground-glass opacities (GGO) decreased from median 3 (25th–75th percentile: 0–12) at 3 months to 0.5 (0–12) at 12 months (p<0.001), but increased for parenchymal bands (p<0.001). In multivariable analysis of GGO, the odds ratio for more severe abbreviated CSS (0–3 scale) at 12 months was 0.11 (95%CI 0.11 0.05 to 0.21, p<0.001) compared to 3 months, for WHO severity category 5–7 (high-flow oxygen/non-invasive ventilation/ventilator) versus 3 (non-oxygen use) 37.16 (1.18 to 43.47, p = 0.032), and for age ≥60 compared to <60 years 4.8 (1.33 to 17.6, p = 0.016). Mosaicism was reduced at 12 compared to 3 months, OR 0.33 (95%CI 0.16 to 0.66, p = 0.002). Conclusions GGO and mosaicism decreased, while parenchymal bands increased from 3 to 12 months. Persistent GGO were associated with initial COVID-19 severity and age ≥60 years.
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Lerum, Tøri Vigeland; Meltzer, Carin; Rivero, Jezabel Rodriguez; Aaløkken, Trond Mogens; Brønstad, Eivind & Aarli, Bernt Bøgvald
[Show all 12 contributors for this article]
(2023).
A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19.
European Respiratory Journal Open Research (ERJ Open Research).
9(2).
doi:
10.1183/23120541.00575-2022.
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COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while DLCO and total lung capacity improved (0.28 mmol·min−1·kPa−1, 95% CI 0.12–0.44, and 0.13 L, 95% CI 0.02–0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, DLCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.
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Murphy, Sarah Louise Mikalsen; Halvorsen, Bente; Holter, Jan Cato; Huse, Camilla; Tveita, Anders & Trøseid, Marius
[Show all 24 contributors for this article]
(2023).
Circulating markers of extracellular matrix remodelling in severe COVID-19 patients.
Journal of Internal Medicine.
ISSN 0954-6820.
294(6),
p. 784–797.
doi:
10.1111/joim.13725.
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Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients.<p> <p>Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. <p>Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. <p>Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19.
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Ueland, Thor; Michelsen, Annika Elisabet; Tveita, Anders; Kåsine, Trine; Dahl, Tuva Børresdatter & Finbråten, Ane-Kristine
[Show all 16 contributors for this article]
(2023).
Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial.
Research and Practice in Thrombosis and Haemostasis (RPTH).
8(1).
doi:
10.1016/j.rpth.2023.102289.
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Background - Several studies have examined parameters of increased thrombogenicity in COVID-19, but studies examining their association with long-term outcome and potential effects of antiviral agents in hospitalized patients with COVID-19 are scarce.<p> <p>Objectives - To evaluate plasma levels of hemostatic proteins during hospitalization in relation to disease severity, treatment modalities, and persistent pulmonary pathology after 3 months.<p> <p>Methods - In 165 patients with COVID-19 recruited into the NOR-Solidarity trial (NCT04321616) and randomized to treatment with hydroxychloroquine, remdesivir, or standard of care, we analyzed plasma levels of hemostatic proteins during the first 10 days of hospitalization (n = 160) and at 3 months of follow-up (n = 100) by enzyme immunoassay.<p> <p>Results - Our main findings were as follows: (i) tissue plasminogen activator (tPA) and tissue factor pathway inhibitor (TFPI) were increased in patients with severe disease (ie, the combined endpoint of respiratory failure [Po2-to-FiO2 ratio, <26.6 kPa] or need for treatment at an intensive care unit) during hospitalization. Compared to patients without severe disease, tPA levels were a median of 42% (P < .001), 29% (P = .002), and 36% (P = .015) higher at baseline, 3 to 5 days, and 7 to 10 days, respectively. For TFPI, median levels were 37% (P = .003), 25% (P < .001), and 10% (P = .13) higher in patients with severe disease at these time points, respectively. No changes in thrombin-antithrombin complex; alpha 2-antiplasmin; a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; or antithrombin were observed in relation to severe disease. (ii) Patients treated with remdesivir had lower levels of TFPI than those in patients treated with standard of care alone. (iii) TFPI levels during hospitalization, but not at 3 months of follow-up, were higher in those with persistent pathology on chest computed tomography imaging 3 months after hospital admission than in those without such pathology. No consistent changes in thrombin-antithrombin complex, alpha 2-antiplasmin, ADAMTS-13, tPA, or antithrombin were observed in relation to pulmonary pathology at 3 months of follow-up.<p> <p>Conclusion - TFPI and tPA are associated with severe disease in hospitalized patients with COVID-19. For TFPI, high levels measured during the first 10 days of hospitalization were also associated with persistent pulmonary pathology even 3 months after hospital admittance.
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Ueland, Thor; Sørvoll, Ingvild Hausberg; Mørtberg, Trude Victoria; Dahl, Tuva Børresdatter; Lerum, Tøri Vigeland & Michelsen, Annika Elisabet
[Show all 16 contributors for this article]
(2022).
Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology.
Platelets.
ISSN 0953-7104.
33(4),
p. 640–644.
doi:
10.1080/09537104.2022.2042238.
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Thromboembolic events are frequent and associated with poor outcome in severe COVID-19 disease. Anti-PF4/polyanion antibodies are related to heparin-induced thrombocytopenia (HIT) and thrombus formation, but data on these antibodies in unselected COVID-19 populations are scarce. We assessed the presence of anti-PF4/polyanion antibodies in prospectively collected serum from an unselected cohort of hospitalized COVID-19 patients and evaluated if elevated levels could give prognostic information on ICU admission and respiratory failure (RF), were associated with markers of inflammation, endothelial activation, platelet activation, coagulation and fibrosis and were associated with long-term pulmonary CT changes. Five out of 65 patients had anti-PF4/polyanion reactivity with OD ≥0.200. These patients had more severe disease as reflected by ICU admission without any evidence of HIT. They also had signs of enhanced inflammation and fibrinogenesis as reflected by elevated ferritin and osteopontin, respectively, during the first 10 days of hospitalization. Increased ferritin and osteopontin persisted in these patients at 3 months follow-up, concomitant with pulmonary CT pathology. Our finding shows that the presence of anti-PF4/polyanion antibodies in unselected hospitalized COVID−19 patients was not related to HIT, but was associated with disease severity, inflammation, and pulmonary pathology after 3 months.
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Tveita, Anders Aune; Murphy, Sarah Louise Mikalsen; Holter, Jan Cato; Kildal, Anders Benjamin; Michelsen, Annika Elisabet & Lerum, Tøri Vigeland
[Show all 28 contributors for this article]
(2022).
High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19.
Journal of Infectious Diseases.
ISSN 0022-1899.
226(12),
p. 2150–2160.
doi:
10.1093/infdis/jiac313.
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Background Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. Methods Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. Results A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. Conclusions Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19.
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Trøseid, Marius; Dahl, Tuva Børresdatter; Holter, Jan Cato; Kildal, Anders Benjamin; Murphy, Sarah Louise Mikalsen & Yang, Kuan
[Show all 28 contributors for this article]
(2022).
Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies.
Journal of Internal Medicine.
ISSN 0954-6820.
292(5),
p. 816–828.
doi:
10.1111/joim.13549.
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Background: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. Objectives: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID-19. Methods: Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID-19 (n = 414) were analyzed for soluble (s) markers of T-cell activation (sCD25) and exhaustion (sTim-3) during hospitalization and follow-up. Results: Both markers were strongly associated with acute respiratory failure, but only sTim-3 was independently associated with 60-day mortality. Levels of sTim-3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months. Conclusion: Our findings suggest prolonged T-cell exhaustion is an important immunological sequela, potentially related to long-term outcomes after severe COVID-19.
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Kleiven, Anne Louise; Markussen, Heidi Øksnes; Skjønsberg, Ole Henning; Janssens, Jean-Paul & Aarrestad, Sigurd
(2022).
Effect of Respiratory Events on Health-Related Quality of Life in Patients Treated with Long-Term Noninvasive Ventilation.
Respiration.
ISSN 0025-7931.
101(12),
p. 1099–1109.
doi:
10.1159/000527066.
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Background: Long-term noninvasive ventilation (NIV) can increase or maintain health-related quality of life (HRQoL) for patients with chronic hypercapnic respiratory failure (CHRF). Evidence from studies systematically assessing how NIV-specific factors influence HRQoL is limited. Objectives: The objective of this study was to describe HRQoL measured by the Severe Respiratory Insufficiency Questionnaire (SRI) in patients with CHRF treated with long-term NIV and to analyze the associations between HRQoL and hypoxemia, hypercapnia, and respiratory events such as apneas, hypopneas (AHI), and patient ventilator asynchrony (PVA) occurring during long-term NIV. Methods: We included sixty-seven stable patients with established long-term NIV due to neuromuscular disease or thoracic cage disorders in a prospective cross-sectional study at Oslo University Hospital. Patients answered the SRI and underwent daytime arterial blood gases, nocturnal pulse oximetry, sleep polygraphy, and nocturnal transcutaneous CO2. Results: The mean global SRI for 62 patients was 64.8 ± 14.5, with the highest score in SRI Social Relationships (79.5 ± 15.6). There were no differences in HRQoL between the different patient groups. Compliant patients had a significantly higher score in SRI Attendant and Sleep. Residual nocturnal hypoxemia affected both the subscale SRI “Respiratory Complaints” and SRI “Attendant Symptoms and Sleep.” Persisting daytime hypercapnia, nocturnal hypoventilation, and high AHI affected the subscale SRI “Anxiety” negatively, while frequent PVA was associated with a lower score in SRI “Physical Function.” Conclusion: In a group of patients with long-term NIV, undesired respiratory events during NIV are associated with lower HRQoL in several of the SRI subscales. We suggest designing interventional studies to confirm the possible relationship between HRQoL and respiratory events during long-term NIV.
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Lekva, Tove; Ueland, Thor; Halvorsen, Bente; Murphy, Sarah Louise Mikalsen; Dyrhol-Riise, Anne Ma & Tveita, Anders Aune
[Show all 14 contributors for this article]
(2022).
Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection.
Infectious Diseases.
ISSN 2374-4235.
54(12),
p. 918–923.
doi:
10.1080/23744235.2022.2113135.
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Background
The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, β-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization.
Methods
Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. β-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months.
Results
We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes.
Conclusions
We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.
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Udjus, Camilla; Sjaastad, Ivar; Hjørnholm, Ulla; Tunestveit, Torbjørn Kinne; Hoffmann, Pavel & Hinojosa, Alexis
[Show all 11 contributors for this article]
(2022).
Extreme altitude induces divergent mass reduction of right and left ventricle in mountain climbers.
Physiological Reports.
10(3).
doi:
10.14814/phy2.15184.
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Mountain climbing at high altitude implies exposure to low levels of oxygen, low temperature, wind, physical and psychological stress, and nutritional insufficiencies. We examined whether right ventricular (RV) and left ventricular (LV) myocardial masses were reversibly altered by exposure to extreme altitude. Magnetic resonance imaging and echocardiography of the heart, dual x-ray absorptiometry scan of body composition, and blood samples were obtained from ten mountain climbers before departure to Mount Everest or Dhaulagiri (baseline), 13.5 ± 1.5 days after peaking the mountain (post-hypoxia), and six weeks and six months after expeditions exceeding 8000 meters above sea level. RV mass was unaltered after extreme altitude, in contrast to a reduction in LV mass by 11.8 ± 3.4 g post-hypoxia (p = 0.001). The reduction in LV mass correlated with a reduction in skeletal muscle mass. After six weeks, LV myocardial mass was restored to baseline values. Extreme altitude induced a reduction in LV end-diastolic volume (20.8 ± 7.7 ml, p = 0.011) and reduced E’, indicating diastolic dysfunction, which were restored after six weeks follow-up. Elevated circulating interleukin-18 after extreme altitude compared to follow-up levels, might have contributed to reduced muscle mass and diastolic dysfunction. In conclusion, the mass of the RV, possibly exposed to elevated afterload, was not changed after extreme altitude, whereas LV mass was reduced. The reduction in LV mass correlated with reduced skeletal muscle mass, indicating a common denominator, and elevated circulating interleukin-18 might be a mechanism for reduced muscle mass after extreme altitude.
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Vestad, Beate; Ueland, Thor; Lerum, Tøri Vigeland; Dahl, Tuva Børresdatter; Holm, Kristian & Barratt-Due, Andreas
[Show all 37 contributors for this article]
(2022).
Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations.
Journal of Internal Medicine.
ISSN 0954-6820.
291(6),
p. 801–812.
doi:
10.1111/joim.13458.
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Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown.
Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene.
Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)
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Lerum, Tøri Vigeland; Maltzahn, Niklas; Aukrust, Pål; Trøseid, Marius; Nezvalova-Henriksen, Katerina & Kåsine, Trine
[Show all 27 contributors for this article]
(2021).
Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9.
Scientific Reports.
11,
p. 1–12.
doi:
10.1038/s41598-021-02547-x.
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The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.
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Tholin, Birgitte; Ghanima, Waleed Khalid; Einvik, Gunnar; Aarli, Bernt Bøgvald; Brønstad, Eivind & Skjønsberg, Ole Henning
[Show all 7 contributors for this article]
(2021).
Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis.
British Journal of Haematology.
ISSN 0007-1048.
194(3),
p. 542–546.
doi:
10.1111/bjh.17522.
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Infection with coronavirus disease-2019 (COVID-19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID-19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID-19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non-hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID-19 was 3·9% [95% confidence interval (CI): 2·1–7·2] during hospitalisation, 0·9% (95% CI: 0·2–3·1) in the three months after discharge and 0·2% (95% CI: 0·00–1·25) in non-hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.
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Torvanger, Ole; Os, Audun; Skjønsberg, Ole Henning & Edvardsen, Elisabeth
(2020).
Cardiorespiratory fitness on a treadmill in an adult cystic fibrosis population.
BMJ Open sport & exercise medicine.
6(1).
doi:
10.1136/bmjsem-2020-000765.
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Objectives: (1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO2peak) and forced expiratory volume in 1 s (FEV1).
Methods: A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO2peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured.
A low CRF was defined as a VO2peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV1 and VO2peak were calculated using linear regression.
Results: The VO2peak was 40.6±11.5 and 35.2±8.9 mL kg−1 min−1, which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO2peak was moderately affected by age, for men (r=−0.36, p<0.001) and women (r=−0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO2peak and FEV1 was r=0.64 (p<0.001). In participants with a low CRF, FEV1 ranged from 20% to 112% of predicted.
Conclusions: The correlation between VO2peak and FEV1 was moderate. The majority of the tests resulted in a VO2peak within normal limits. Interestingly, 44% of the tests with a low VO2peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients.
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Lerum, Tøri Vigeland; Aaløkken, Trond M; Brønstad, Eivind; Aarli, Bernt Bøgvald; Ikdahl, Eirik & Lund, Kristine Marie Aarberg
[Show all 14 contributors for this article]
(2020).
Dyspnoea, lung function and CT findings three months after hospital admission for COVID-19.
European Respiratory Journal.
ISSN 0903-1936.
57.
doi:
10.1183/13993003.03448-2020.
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The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function, and chest CT findings three months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICU), compared with non-ICU patients. Discharged COVID-19-patients from six Norwegian hospitals were consecutively enrolled in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. Modified Medical Research Council dyspnoea scale (mMRC), EuroQol Group's Questionnaire, spirometry, diffusion capacity (DLCO), six-minute walk test, pulse oximetry, and low-dose CT scan were performed three months after discharge. mMRC was >0 in 54% and >1 in 19% of the participants. The median (25th–75th percentile) forced vital capacity and forced expiratory volume in one second were 94% (76, 121) and 92% (84, 106) of predicted, respectively. DLCO was below the lower limit of normal in 24%. Ground-glass opacities (GGO) with >10% distribution in ≥1 of 4 pulmonary zones were present in 25%, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted odds ratio [95% confidence interval] 4.2 [1.1, 15.6]) and performance in lower usual activities. Three months after admission for COVID-19, one fourth of the participants had chest CT opacities and reduced diffusion capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.
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Sæverud, Håvard Andreassen; Falk, Ragnhild Sørum; Dowrick, Adam; Eriksen, Morten; Aarrestad, Sigurd & Skjønsberg, Ole Henning
(2019).
Measuring diaphragm movement and respiratory frequency using a novel ultrasound device in healthy volunteers.
Journal of Ultrasound.
ISSN 1971-3495.
p. 1–8.
doi:
10.1007/s40477-019-00412-2.
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Purpose To evaluate the ability of a novel ultrasound (US) device, DiaMon, to monitor diaphragm movement via its proxy liver movement, and compare it with the respired flow measured with a flowmeter, in awake and healthy volunteers. We wanted to (1) establish the optimal anatomical position for attaching the DiaMon device to the abdominal wall, and (2) evaluate the accuracy of continuous monitoring of respiratory frequency. Methods Thirty healthy subjects were recruited. The DiaMon probe was applied subcostally in four different positions with the subjects in five different postures. The subjects breathed tidal volumes into a spirometer for 30–60 s with the DiaMon recording simultaneously. Results The device detected a readable signal in 83–100% of the position/posture-combinations. The technical correlation between the two signals was highest in the anterior axillary-supine position (mean ± SD: 0.95 ± 0.03), followed by paramidline-supine (0.90 ± 0.09) and midclavicular-supine (0.89 ± 0.12). The frequency measurements yielded a mean difference of 0.03 (95% limits of agreement − 0.11, 0.16) breaths per minute in the anterior axillary-supine position. Conclusion The DiaMon device is able to detect liver movement in most subjects, and it measures breathing frequency accurately.
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Udjus, Camilla; Fadila, Cero; Halvorsen, Bente; Behmen, Dina; Carlson, Cathrine Rein & Bendiksen, Bård Andre
[Show all 14 contributors for this article]
(2019).
Caspase-1 induces smooth muscle cell growth in hypoxia-induced pulmonary hypertension.
American Journal of Physiology - Lung cellular and Molecular Physiology.
316(6),
p. L999–L1012.
doi:
10.1152/ajplung.00322.2018.
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Lung diseases with hypoxia are complicated by pulmonary hypertension, leading to heart failure and death. No pharmacological treatment exists. Increased proinflammatory cytokines are found in hypoxic patients, suggesting an inflammatory pathogenesis. Caspase-1, the effector of the inflammasome, mediates inflammation through activation of the proinflammatory cytokines interleukin (IL)-18 and IL-1β. Here, we investigate inflammasome-related mechanisms that can trigger hypoxia-induced pulmonary hypertension. Our aim was to examine whether caspase-1 induces development of hypoxia-related pulmonary hypertension and is a suitable target for therapy. Wild-type (WT) and caspase-1−/− mice were exposed to 10% oxygen for 14 days. Hypoxic caspase-1−/− mice showed lower pressure and reduced muscularization in pulmonary arteries, as well as reduced right ventricular remodeling compared with WT. Smooth muscle cell (SMC) proliferation was reduced in caspase-1-deficient pulmonary arteries and in WT arteries treated with a caspase-1 inhibitor. Impaired inflammation was shown in hypoxic caspase-1−/− mice by abolished pulmonary influx of immune cells and lower levels of IL-18, IL-1β, and IL-6, which were also reduced in the medium surrounding caspase-1 abrogated pulmonary arteries. By adding IL-18 or IL-1β to caspase-1-deficient pulmonary arteries, SMC proliferation was retained. Furthermore, inhibition of both IL-6 and phosphorylated STAT3 reduced proliferation of SMC in vitro, indicating IL-18, IL-6, and STAT3 as downstream mediators of caspase-1-induced SMC proliferation in pulmonary arteries. Caspase-1 induces SMC proliferation in pulmonary arteries through the caspase-1/IL-18/IL-6/STAT3 pathway, leading to pulmonary hypertension in mice exposed to hypoxia. We propose that caspase-1 inhibition is a potential target for treatment of pulmonary hypertension.
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Aarrestad, Sigurd; Qvarfort, Magnus; Kleiven, Anne Louise; Tollefsen, Elin; Skjønsberg, Ole Henning & Janssens, Jean-Paul
(2018).
Diagnostic accuracy of simple tools in monitoring patients with chronic hypoventilation treated with non-invasive ventilation; a prospective cross-sectional study.
Respiratory Medicine.
ISSN 0954-6111.
144,
p. 30–35.
doi:
10.1016/j.rmed.2018.09.015.
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Objectives To evaluate the sensitivity and specificity of a screening test panel for nocturnal hypoventilation (NH) and other sleep related respiratory events during monitoring of patients with chronic hypercapnic respiratory failure (CRF) treated with NIV. Methods We performed a prospective study at Oslo University Hospital. Eligible for inclusion were consecutive adults with CRF due to neuromuscular diseases or chest walldisorders treated with NIV scheduled for a follow-up visit. All patients underwent the screening test panel (clinical evaluation, daytime arterial blood gas (ABG), nocturnal pulse oximetry (SpO2) and data from ventilator software) and the reference tests; sleep polygraphy and nocturnal transcutaneous CO2. Results Of 67 patients included, NH was confirmed in 23–50 according to the 3 definitions used for NH, apnea-hypopnea index (AHIpolygraphy) ≥ 10 was confirmed in 16 and patient-ventilator asynchrony (PVA) ≥ 10% of total recording time in 14. Sensitivity of the combined screening test panel for NH was 87% (95% confidence interval 66–97), 84% (66–95) and 80% (66–90), for abnormal AHIpolygraphy 91% (59–100) and for PVA 71% (42–92). Sensitivity for NH of SpO2 was 48% (27–69), 39% (22–58) and 38% (24–53) and of daytime ABG 74% (52–90), 74% (55–88) and 68% (53–80). Sensitivity and specificity of AHIsoftware for AHIpolygraphy ≥ 10 was 93% (68–100) and 92% (81–98) respectively. Discussion In patients treated with long term NIV, screening test panel, nocturnal SpO2 and daytime ABG all failed to accurately detect NH, underlining the importance of nocturnal monitoring of CO2. AHIsoftware accurately identified obstructive events and can be used to modify NIV settings.
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Nakstad, Espen Rostrup; Aass, Hans Christian; Opdahl, Helge; Witsø, Anne; Borchsenius, Fredrik & Heyerdahl, Fridtjof
[Show all 7 contributors for this article]
(2017).
Bronchial wheezing predicts inflammation and respiratory failure in fire smoke victims.
Acta Anaesthesiologica Scandinavica.
ISSN 0001-5172.
61(9),
p. 1142–1154.
doi:
10.1111/aas.12962.
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BackgroundAcute fire smoke inhalation injury involves inflammatory mediators whose roles are poorly understood. We carried out a prospective observational study of fire smoke victims to identify clinical and biochemical markers that may predict pulmonary dysfunction and investigated possible correlations between dysfunction and cytokines in bronchoalveolar lavage (BAL) fluid and blood.
MethodsForty patients with respiratory and/or neurological symptoms following acute fire smoke inhalation had pulmonary function tests and blood gas analyses performed on admission, at discharge, and after 3 months. Cytokines were measured using BioPlex/XMap technology.
ResultsOn admission, 30 (75%) patients had dyspnea. Patients presenting with bronchial wheezing (n = 14) had significantly lower PEF (201 l/min, 82-360) than non-wheezing patients (406 l/min, 100-683) (n = 16, P = 0.03). Bronchial wheezing predicted need for ICU treatment with OR = 93.3 at 95% CI (P < 0.001) and was associated with gas exchange impairment, with mean p(a)O(2)/FiO(2) ratio 34.4 (11.8-49.8) kPa on admission and 21.3 (8.3-44.5) kPa 48 h later. Blood HbCO also predicted ICU treatment, with OR = 1.58 at 95% CI (P < 0.001). Serum CRP, IL-6, IL-8, and MCP-1 were significantly higher in wheezing patients after 12-24 h compared with non-wheezing patients and study controls. Cytokine levels were still elevated after 3 months. BAL fluid had significantly higher levels of IL-8, MCP-1, IL-1, and G-CSF compared with healthy controls.
ConclusionIn victims of fire smoke inhalation, pulmonary wheezing predicts inflammation, pulmonary dysfunction, respiratory failure, and need for intensive care.
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Aarrestad, Sigurd; Qvarfort, Magnus; Kleiven, Anne Louise; Tollefsen, Elin; Skjønsberg, Ole Henning & Janssens, Jean-Paul
(2017).
Sleep related respiratory events during non-invasive ventilation of patients with chronic hypoventilation.
Respiratory Medicine.
ISSN 0954-6111.
132,
p. 210–216.
doi:
10.1016/j.rmed.2017.10.025.
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Edvardsen, Elisabeth; Akerø, Aina; Skjønsberg, Ole Henning & Skrede, Bjørn
(2017).
Pre-flight evaluation of adult patients with cystic fibrosis: a cross-sectional study.
BMC Research Notes.
10(84),
p. 1–8.
doi:
10.1186/s13104-017-2386-2.
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Background:
Air travel may imply a health hazard for patients with cystic fibrosis (CF) due to hypobaric environment in the aircraft cabin. The objective was to identify pre-flight variables, which might predict severe hypoxaemia in adult CF patients during air travel.
Methods:
Thirty adult CF-patients underwent pre-flight evaluation with spirometry, arterial oxygen tension (PaO2), pulse oximetry (SpO2) and cardiopulmonary exercise testing (CPET) at sea level (SL). The results were related to the PaO2 obtained during a hypoxia-altitude simulation test (HAST) in which a cabin altitude of 2438 m (8000 ft) was simulated by breathing 15.1% oxygen.
Results:
Four patients fulfilled the criteria for supplemental oxygen during air travel (PaO2 HAST < 6.6 kPa). While walking slowly during HAST, another eleven patients dropped below PaO2 HAST 6.6 kPa. Variables obtained during CPET (PaO2 CPET, SpO2 CPET, minute ventilation/carbon dioxide output, maximal oxygen uptake) showed the strongest correlation to PaO2 HAST.
Conclusions:
Exercise testing might be of value for predicting in-flight hypoxaemia and thus the need for supplemental oxygen during air travel in CF patients.
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Nakstad, Espen Rostrup; Opdahl, Helge; Heyerdahl, Fridtjof; Borchsenius, Fredrik & Skjønsberg, Ole Henning
(2017).
Manual ventilation and open suction procedures contribute to negative pressures in a mechanical lung model.
BMJ Open Respiratory Research.
4:e000176,
p. 1–7.
doi:
10.1136/bmjresp-2016-000176.
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Aarrestad, Sigurd; Tollefsen, Elin; Kleiven, Anne Louise; Qvarfort, Magnus; Janssens, Jean-Paul & Skjønsberg, Ole Henning
(2016).
Validity of transcutaneous PCO2 in monitoring chronic hypoventilation treated with non-invasive ventilation.
Respiratory Medicine.
ISSN 0954-6111.
112,
p. 112–118.
doi:
10.1016/j.rmed.2016.01.017.
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Nakstad, Espen Rostrup; Opdahl, Helge; Heyerdahl, Fridtjof; Borchsenius, Fredrik & Skjønsberg, Ole Henning
(2016).
Can ventilator settings reduce the negative effects of endotracheal suctioning? Investigations in a mechanical lung model.
BMC Anesthesiology.
16:30.
doi:
10.1186/s12871-016-0196-z.
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Edvardsen, Elisabeth; Skjønsberg, Ole Henning; Holme, Ingar Morten K; Nordsletten, Lars; Borchsenius, Fredrik & Anderssen, Sigmund Alfred
(2015).
High-intensity training following lung cancer surgery: a randomised controlled trial.
Thorax.
ISSN 0040-6376.
70(3),
p. 244–250.
doi:
10.1136/thoraxjnl-2014-205944.
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Background: Many patients with lung cancer are deconditioned with poor physical fitness. Lung resection reduces physical fitness further, impairing the patient's ability to function in daily life.
Methods: We conducted a single-blind randomised controlled trial of high-intensity endurance and strength training (60 min, three times a week, 20 weeks), starting 5–7 weeks after surgery. The control group received standard postoperative care. The primary outcome was the change in peak oxygen uptake measured directly during walking until exhaustion. Other outcomes included changes in pulmonary function, muscular strength by one-repetition maximum (1RM), total muscle mass measured by dual energy X-ray absorptiometry, daily physical functioning and quality of life (QoL).
Results: The intention-to-treat analysis of the 61 randomised patients showed that the exercise group had a greater increase in peak oxygen uptake (3.4 mL/kg/min between-group difference, p=0.002), carbon monoxide transfer factor (Tlco) (5.2% predicted, p=0.007), 1RM leg press (29.5 kg, p<0.001), chair stand (2.1 times p<0.001), stair run (4.3 steps, p=0.002) and total muscle mass (1.36 kg, p=0.012) compared with the controls. The mean±SD QoL (SF-36) physical component summary score was 51.8±5.5 and 43.3±11.3 (p=0.006), and the mental component summary score was 55.5±5.3 and 46.6±14.0 (p=0.015) in the exercise and control groups, respectively.
Conclusions: In patients recently operated for lung cancer, high-intensity endurance and strength training was well tolerated and induced clinically significant improvements in peak oxygen uptake, Tlco, muscular strength, total muscle mass, functional fitness and QoL. This study may provide a basis for exercise therapy after lung cancer surgery.
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Edvardsen, Elisabeth; Anderssen, Sigmund Alfred; Borchsenius, Fredrik & Skjønsberg, Ole Henning
(2015).
Reduction in cardiorespiratory fitness after lung resection is not related to the number of lung segments removed.
BMJ Open sport & exercise medicine.
1(1).
doi:
10.1136/bmjsem-2015-000032.
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Sæverud, Håvard Andreassen; Borchsenius, Fredrik; Mellem, Harald; Finstad, Pål Leyell & Skjønsberg, Ole Henning
(2013).
The obstructive siblings; relapsing polychondritis without condritis?
Respiratory Medicine.
ISSN 0954-6111.
10,
p. 4–6.
doi:
10.1016/j.rmcr.2013.04.005.
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Sæverud, Håvard Andreassen; Borchsenius, Fredrik; Mellem, H; Finstad, Pål Leyell & Skjønsberg, Ole Henning
(2013).
the obstructive siblings: Relapsing polychondritis without chondritis.
Respiratory Medicine.
ISSN 0954-6111.
10,
p. 4–6.
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Edvardsen, Anne; Ryg, Morten; Akerø, Aina; Christensen, Carl Christian & Skjønsberg, Ole Henning
(2013).
COPD and air travel: does hypoxia-altitude simulation testing predict in-flight respiratory symptoms?
European Respiratory Journal.
ISSN 0903-1936.
42(5),
p. 1216–1223.
doi:
10.1183/09031936.00157112.
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Fadila, Cero; Hillestad, Vigdis; Løberg, Else Marit; Christensen, Geir Arve; Larsen, Karl-Otto & Skjønsberg, Ole Henning
(2012).
IL-18 and IL-12 synergy induces matrix degrading enzymes in the lung.
Experimental Lung Research.
ISSN 0190-2148.
38(8),
p. 406–419.
doi:
10.3109/01902148.2012.716903.
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Edvardsen, Anne; Akerø, Aina; Christensen, Carl Christian; Ryg, Morten & Skjønsberg, Ole Henning
(2012).
Air travel and chronic obstructive pulmonary disease: a new algorithm for pre-flight evaluation.
Thorax.
ISSN 0040-6376.
67(11),
p. 964–969.
doi:
10.1136/thoraxjnl-2012-201855.
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Nakstad, Espen Rostrup; Opdahl, Helge; Skjønsberg, Ole Henning & Borchsenius, Fredrik
(2011).
Intrabronchial airway pressures in intubated patients during bronchoscopy under volume controlled and pressure controlled ventilation.
Anaesthesia and Intensive Care.
ISSN 0310-057X.
39(3),
p. 431–439.
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Akerø, Aina; Edvardsen, Anne; Christense, Carl C.; Owe, Jan Ove; Ryg, Morten & Skjønsberg, Ole Henning
(2011).
COPD and air travel: Oxygen equipment and pre-flight titration of supplemental oxygen.
Chest.
ISSN 0012-3692.
140(1),
p. 84–90.
doi:
10.1378/chest.10-0965.
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Akerø, Aina; Christensen, Carl C.; Edvardsen, Anne; Ryg, Morten & Skjønsberg, Ole Henning
(2008).
Pulse oximetry in the preflight evaluation of patients with chronic obstructive pulmonary disease.
Aviation, Space and Environmental Medicine.
ISSN 0095-6562.
79,
p. 508–524.
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Nielsen, Hilde Dorthea Grindvik; Skjønsberg, Ole Henning & Lyberg, Torstein
(2008).
Effect of antioxidant supplementation on leucocyte expression of reactive oxygen species in athletes.
Scandinavian Journal of Clinical and Laboratory Investigation.
ISSN 0036-5513.
68(7),
p. 526–533.
doi:
10.1080/00365510701864602.
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Jensen, Torstein; Kierulf, Peter; Sandset, Per Morten; Klingenberg, Olav; Joø, Gun Brit & Godal, Hans Chr
[Show all 7 contributors for this article]
(2007).
Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from peripheral blood mononuclear cells.
Thrombosis and Haemostasis.
ISSN 0340-6245.
97(5),
p. 822–829.
doi:
10.1160/TH07-01-0039.
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Fibrinogen in plasma includes three main fractions; high-molecular-weight (HMW)-fibrinogen, low-molecular-weight (LMW)-fibrinogen, and very-low-molecular-weight (LMW')-fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear. We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6, TNF-alpha and IL-1beta, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep((R)). HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF-alpha in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF-alpha concentrations were 12 (5, 40) pg/ml and 16 (0,61) pg/ml, respectively. Median mRNA quantity was increased 12.3- (6.6, 48.6) and 1.7- (1.5, 6.5) fold for IL-6 and TNF-alpha compared to controls. The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC. The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.
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Jensen, Torstein; Retterstøl, Lars; Sandset, Per Morten; Godal, Hans Chr & Skjønsberg, Ole Henning
(2006).
A daily glass of red wine induces a prolonged reduction in plasma viscosity: a randomized controlled trial.
Blood Coagulation and Fibrinolysis.
ISSN 0957-5235.
17(6),
p. 471–476.
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Moderate red wine consumption has been associated with decreased risk of coronary heart disease. Reduced plasma viscosity and fibrinogen levels have been launched as possible contributors to this risk reduction. The effect of moderate red wine consumption on plasma viscosity, however, has not been investigated in a prospective, randomized trial. We wanted to evaluate the effect of moderate red wine consumption on plasma viscosity, fibrinogen concentration and fibrinogen subfractions. Healthy, nonsmoking volunteers were assigned to consume one glass of red wine daily for 3 weeks in a prospective, randomized cross-over study. In the second 3-week period the volunteers abstained from alcohol use. The plasma viscosity, fibrinogen concentration and the distribution of the main fibrinogen subfractions were determined at inclusion, after wine drinking and after abstention. Plasma viscosity was reduced by 0.026 and 0.024 mPa.s in the two groups following wine intake (95% confidence interval, 0.009-0.043, P = 0.004; 95% confidence interval, 0.0083-0.039, P = 0.003). The decrease in plasma viscosity was maintained following 3 weeks of abstention. The fibrinogen concentration was reduced by 0.17 g/l following wine drinking in the group starting with abstention (95% confidence interval, 0.04-0.29, P = 0.01). The distribution of the fibrinogen subfractions remained unaltered. We conclude that a daily glass of red wine for 3 weeks significantly reduces plasma viscosity. Fibrinogen concentrations are also significantly reduced, when preceded by an abstention period. The decreased viscosity levels are maintained after 3 weeks of abstention, suggesting a sustained viscosity lowering effect of red wine.
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Larsen, Karl-Otto; Sjaastad, Ivar; Svindland, A; Krobert, Kurt Allen; Skjønsberg, Ole Henning & Christensen, Geir Arve
(2006).
Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces phosphorylation of phospholamban in mice.
American Journal of Physiology. Heart and Circulatory Physiology.
ISSN 0363-6135.
291,
p. H507–H516.
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Allgot, Marte Skogstad; Fondenes, Ove; Skjønsberg, Ole Henning & Aarrestad, Sigurd
(2025).
Validating the TriggerCycle Data for the ResMed Lumis 150 ventilator: A Bench Test.
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Allgot, Marte Skogstad; Kleiven, Anne Louise; Malone, Joseph Anthony; Skjønsberg, Ole Henning & Aarrestad, Sigurd
(2024).
Transcutaneous CO2 – from hospital to home monitoring.
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Kleiven, Anne Louise; Markussen, Heidi Øksnes; Skjønsberg, Ole Henning; Janssens, Jean-Paul & Aarrestad, Sigurd
(2023).
Respiratory Events and Health-Related Quality of Life in Long-Term Non-Invasive Ventilation: How Can We Optimize and Prevent Failure?
Respiration.
ISSN 0025-7931.
102(5),
p. 400–401.
doi:
10.1159/000529196.
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Tveiten, Hallgeir; Lehne, Gustav; Aukrust, Pål; Rivero, Jezabel Rodriguez & Skjønsberg, Ole Henning
(2020).
En mann i 40-årene med økendepustevansker.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
140(6),
p. 1–7.
doi:
10.4045/tidsskr.19.0692.
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torvanger, ole; Os, Audun; Skjønsberg, Ole Henning & Edvardsen, Elisabeth
(2018).
Cardiorespiratory Fitness on a Treadmill in an adult Norwegian Cystic Fibrosis Population .
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Edvardsen, Elisabeth; Anderssen, Sigmund Alfred; Borchsenius, Fredrik Charlo & Skjønsberg, Ole Henning
(2018).
Long Term Effects of High-Intensity Exercise Training after Lung Cancer Surgery ~ A Five Year Follow-Up of a Randomized Controlled Trial.
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Udjus, Camilla; Cero, Fadila; Christensen, Geir Arve; Skjønsberg, Ole Henning & Larsen, Karl-Otto
(2015).
The role of caspase-1 in pulmonary hypertension.
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Edvardsen, Anne; Ryg, Morten; Akerø, Aina; Christensen, Carl Christian & Skjønsberg, Ole Henning
(2013).
COPD and air travel: does hypoxia-altitude simulation test predict in-flight respiratory symptoms?
Full text in Research Archive
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Edvardsen, Anne; Akerø, Aina; Christensen, Carl Christian; Ryg, Morten & Skjønsberg, Ole Henning
(2012).
Air Travel and COPD: a new algorithm for pre-flight evaluation.
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Cero, Fadilla; Larsen, Karl Otto; Sandanger, Øystein; Løberg, Else Marit; Christensen, Geir Arve & Skjønsberg, Ole Henning
(2012).
Hypoxia induces IL-18 and neutrophil influx in lung parenchyma possibly mediated by MIP-2.
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Cero, Fadila; Larsen, Karl Otto; Hillestad, Vigdis; Christensen, Geir Arve & Skjønsberg, Ole Henning
(2011).
IL-18 and IL-12 induce inflammatory cytokines, chemokine ligand 9 (CXCL9) and T cell infiltration in pulmonary tissue.
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Hillestad, Vigdis; Larsen, Karl Otto; Sjaastad, Ivar; Nygård, Ståle; Skjønsberg, Ole Henning & Christensen, Geir Arve
(2011).
Neutralization of circulating interleukin-18 reduces diastolic dysfunction.
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Edvardsen, Anne; Akerø, Aina; Christensen, Carl Christian; Ryg, Morten & Skjønsberg, Ole Henning
(2011).
Air travel and COPD: Exercise SpO2 and walking distance as predictors for in-flight desaturation.
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Edvardsen, Anne; Akerø, Aina; Christensen, Carl Christian; Ryg, Morten & Skjønsberg, Ole Henning
(2011).
Hypoxia altitude simulation test (HAST): Arterial blood gases or pulse oximetry?
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Hillestad, Vigdis; Larsen, Karl-Otto; Sjaastad, Ivar; Nygård, Ståle; Skjønsberg, Ole Henning & Christensen, Geir Arve
(2010).
Effects of IL-ı8 neutralization in alveolar hypoxia.
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Akerø, Aina; Edvardsen, Anne; Christensen, Carl C.; Owe, Jan Ove; Ryg, Morten & Skjønsberg, Ole Henning
(2010).
Air travel and COPD: Oxygen equipment and pre-flight titration of supplemental oxygen.
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Nielsen, Hilde Dorthea Grindvik; Skjønsberg, Ole Henning & Lyberg, Torstein
(2009).
Effekten av fire ukers antioksidanttilskudd på produksjon av frie oksygenradikaler i leukocytter hos kvinnelige og mannlige utholdenhetsutøvere.
Norsk idrettsmedisin.
ISSN 0806-9328.
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Edvardsen, Anne; Akerø, Aina; Eagan, Thomas; Hardie, J; Bakke, Per & Skjønsberg, Ole Henning
(2009).
Air travel habits in patients with COPD.
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Edvardsen, Elisabeth; homme, jorunn; Skjønsberg, Ole Henning & Skrede, Bjørn
(2009).
Pre-flight evaluation in adult patients with cystic fibrosis.
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Hillestad, Vigdis; Larsen, Karl-Otto; Sjaastad, Ivar; Nygård, Ståle; Skjønsberg, Ole Henning & Christensen, Geir Arve
(2009).
IL-18BP; a potential therapeutic agent in right ventricular hypertrophy.
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Nielsen, Hilde Grindvik; Skjønsberg, Ole Henning & Lyberg, Torstein
(2009).
Effekten av fire ukers antioksydanttilskudd på produksjon av frie oksygenradikaler i leukocytter hos kvinnelige og mannlige utholdenhetsutøvere.
Idrettsmedisin.
2009(2),
p. 23–25.
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Akerø, Aina; Edvardsen, Anne; Ryg, Morten & Skjønsberg, Ole Henning
(2008).
PaO2 during exerciseas a predictor of in-flight hypoxaemia in COPD patients.
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Larsen, Karl-Otto; Lygren, Birgitte; Sjaastad, Ivar; Krobert, Kurt Allen; Florholmen, Geir & Arnkværn, Kristin
[Show all 10 contributors for this article]
(2007).
Increased PP1 and PP2A mediating reduced Ser16 phosphorylated PLB is a possible mechanism for cardiac dysfunction in alveolar hypoxia.
Journal of Molecular and Cellular Cardiology.
ISSN 0022-2828.
42(6),
p. S245–S245.
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Nakstad, Espen R.; Opdahl, Helge; Borchsenius, Fredrik & Skjønsberg, Ole Henning
(2007).
Intrabronchial airway pressure in intubated patients during bronchoscopy under pressure and volume controlled ventilation.
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Edvardsen, Anne; Christensen, Carl C.; Skjønsberg, Ole Henning & Ryg, Morten
(2007).
Effect of high dose oxygen on dyspnea and exercise tolerance in patients with COPD given LTOT.
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Nakstad, Espen R.; Opdahl, Helge; Borchsenius, Fredrik & Skjønsberg, Ole Henning
(2007).
Intrabronchial airway pressure in intubated patients during bronchoscopy under pressure and volume controlled ventilation.
Full text in Research Archive
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Larsen, Karl-Otto; Lygren, Birgitte; Sjaastad, Ivar; Krobert, Kurt Allen; Florholmen, Geir & Arnkværn, Kristin
[Show all 10 contributors for this article]
(2007).
Alveolar hypoxia induces cardiac dysfunction, possibly mediated through increased amounts of phosphatases, leading to dephosphorylation of calcium regulatory proteins.
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Edvardsen, Elisabeth; Ariansen, Inger; Mellem, Harald; Borchsenius, Fredrik; Gjesdal, Knut & Skjønsberg, Ole Henning
(2006).
Ventilatory limitation may be over-diagnosed in elderly subjects when MVV is calculated instead of measured.
European Respiratory Society.
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Larsen, Karl-Otto; Lygren, Birgitte; Sjaastad, Ivar; Skjønsberg, Ole Henning; Tasken, Kjetil & Christensen, Geir Arve
(2006).
Chronic alveolar hypoxia reduces the phosphorylation of phospholamban in mouse hearts.
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Larsen, Karl-Otto; Lygren, Birgitte; Sjaastad, Ivar; Tasken, Kjetil; Christensen, Geir Arve & Skjønsberg, Ole Henning
(2006).
Alveolar hypoxia induces left ventricular diastolic dysfunction in mice.
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Edvardsen, Elisabeth; Ariansen, h; Mellem, Harald; Borchsenius, Fredrik; Skjønsberg, Ole Henning & Gjesdal, Knut
(2006).
Ventilatory limitation may be over-diagnosed in elderly subjects when MVV is calculated instead of measured;.
Full text in Research Archive
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Akerø, Aina; Christensen, Carl C.; Edvardsen, Anne; Ryg, Morten & Skjønsberg, Ole Henning
(2006).
Pulse oximetry as a screening test in the pre-flight evaluation of COPD patients.
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Jensen, Torstein & Skjønsberg, Ole Henning
(2008).
Studies on subfractions of fibrinogen : With special emphasis on fibrinogen quantification, viscosity and inflammation.
Universitetet i Oslo.
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Show summary
Fibrinogen in plasma is heterogeneous and includes 3 main fractions with different molecular weight, solubility and clottability. 70% is high molecular weight (HMW)-fibrinogen with intact Aα-chains, 25% is low molecular weight (LMW)-fibrinogen, and 5% is very low molecular weight (LMW`)-fibrinogen which has lost the C-terminal end of one or both α-chains, respectively. During acute-phase conditions such as bacterial infections, trauma and major surgery, fibrinogen levels and the HMW-/LMW-fibrinogen ratio in plasma increase rapidly due to increased synthesis of HMW-fibrinogen. Through cleavage by thrombin, fibrinogen is converted to fibrin in the last step of the coagulation cascade, which constitutes its main physiological function. Fibrinogen is also a major determinant of plasma viscosity. Increased fibrinogen levels and plasma viscosity are both markers of increased risk of developing atherothrombotic disease.<br> The aims of our thesis were to investigate the effects of an altered HMW-/LMW fibrinogen ratio on 1) the results of commonly used fibrinogen assays, 2) the viscosity of fibrinogen, and 3) the proinflammatory effects on peripheral blood mononuclear cells. We also wanted to 4) determine the effects of moderate red wine consumption on fibrinogen concentration, fibrinogen subfractions and plasma viscosity.<br> We found that an increased HMW-/LMW fibrinogen ratio resulted in higher fibrinogen levels using a commonly employed clotting rate assay compared to a reference method. The viscosity of the 3 main fibrinogen subfractions did not differ from that of native fibrinogen. A daily glass of red wine significantly reduced plasma viscosity and fibrinogen levels, creating a beneficial profile with regard to atherothrombotic disease. Fibrinogen and fibrin both upregulated mRNA levels and induced synthesis of the proinflammatory cytokines IL-6 and TNF-α in peripheral blood mononuclear cells in a dose dependent manner.
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Published
Apr. 13, 2011 2:54 PM
- Last modified
Nov. 13, 2017 9:13 AM
