Lars C Huber

University of Zurich, Zürich, Zurich, Switzerland

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Publications (90)436.49 Total impact

  • Lars Christian Huber · Hannah Bye · Matthias Brock ·
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    ABSTRACT: Elevation of the mean pulmonary arterial pressure to ≥25 mm Hg within the low-pressure system of the pulmonary circulation is defined as pulmonary hypertension. Pulmonary hypertension may be the consequence of various clinical and pathophysiological entities. Many of these conditions, however, result in a final common pathway of pathogenesis. This pathway is characterised by the triad of excessive vasoconstriction, microthrombosis and remodelling of pulmonary arteries. Remodelling is arguably the most important factor: its complex pathogenesis is not completely understood and no specific treatment directly targets vascular remodelling. This article aims to review the current understanding of the pathogenesis of pulmonary hypertension and to give insights in future developments in this evolving field.
    Schweizerische medizinische Wochenschrift 10/2015; 145:w14202. DOI:10.4414/smw.2015.14202 · 2.09 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA4554. DOI:10.1183/13993003.congress-2015.PA4554 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):OA3526. DOI:10.1183/13993003.congress-2015.OA3526 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2112. DOI:10.1183/13993003.congress-2015.PA2112 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA4906. DOI:10.1183/13993003.congress-2015.PA4906 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):OA2931. DOI:10.1183/13993003.congress-2015.OA2931 · 7.64 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA583. DOI:10.1183/13993003.congress-2015.PA583 · 7.64 Impact Factor
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    ABSTRACT: Cystic fibrosis (CF) is one of the most common genetic disorders. Mutations of the cystic fibrosis transmembrane regulator causes dysfunction of epithelial membranes within the gastrointestinal and respiratory system. Patients with CF are known to be at risk for gastrointestinal malignancies, and lung transplantation further increases this risk. We report a case series of three CF patients who developed adenocarcinoma of the gastrointestinal tract in the posttransplant setting. One of these case histories describes a gastric cancer, which is a novel and to date unreported observation. These data emphasise the importance of checking CF patients for the development of abdominal complications following lung transplantation.
    Schweizerische medizinische Wochenschrift 08/2015; 145:w14165. DOI:10.4414/smw.2015.14165 · 2.09 Impact Factor
  • Urs Bürgi · Lars Christian Huber ·
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    ABSTRACT: The auscultation of the lungs is - among anamnesis - the most important part in the assessment of patients presenting with pulmonary symptoms. The lung auscultation is reproducible, cost efficient and very helpful to distinguish between differential diagnoses, in particular in emergency situations. Detection and description of lung sounds requires experience and should be performed by strict adherence to the internationally accepted terminology. © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 07/2015; 140(14):1078-1082. DOI:10.1055/s-0041-102883 · 0.54 Impact Factor
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    ABSTRACT: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH). To evaluate the long-term efficacy and safety of imatinib. This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated off-label with imatinib 400 mg daily. Pulmonary hypertension-specific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients). After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of 'hemodynamic remission'. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-year survival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years. Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication. © 2015 S. Karger AG, Basel.
    Respiration 06/2015; 89(6). DOI:10.1159/000381923 · 2.59 Impact Factor

  • Pneumologie 05/2015; 69(05). DOI:10.1055/s-0035-1551925
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    ABSTRACT: Vascular remodeling due to excessive proliferation of endothelial and smooth muscle cells is a hallmark feature of pulmonary hypertension. microRNAs (miRNAs) are a class of small, non-coding RNA fragments that have recently been associated with remodeling of pulmonary arteries, in particular by silencing the bone morphogenetic protein receptor type II (BMPR2). Here we identified a novel pathway involving the concerted action of miR-125a, BMPR2 and cyclin-dependent kinase inhibitors (CDKN) that controls a proliferative phenotype of endothelial cells. An in silico approach predicted miR-125a to target BMPR2. Functional inhibition of miR-125a resulted in increased proliferation of these cells, an effect that was found accompanied by upregulation of BMPR2 and reduced expression of the tumor suppressors CDKN1A (p21) and CDKN2A (p16). These data were confirmed in experimental pulmonary hypertension in vivo. Levels of miR-125a were elevated in lung tissue of hypoxic animals that develop pulmonary hypertension. In contrast, circulating levels of miR-125a were found to be lower in mice with pulmonary hypertension as compared to control mice. Similar findings were observed in a small cohort of patients with precapillary pulmonary hypertension. These translational data emphasize the pathogenetic role of miR-125a in pulmonary vascular remodeling. © 2015 by the Society for Experimental Biology and Medicine.
    Experimental Biology and Medicine 04/2015; DOI:10.1177/1535370215579018 · 2.17 Impact Factor
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    ABSTRACT: Levels of microRNAs (miRNAs) are increasingly assessed in biological fluids, for example, in samples obtained by bronchoalveolar lavage (BAL). "Post-collection kinetics" of miRNA expression levels, however, have not been investigated to date. In these experiments, we analyzed the dynamic expression profile of 5 different miRNAs (miR-17, miR-19b, miR-20b, miR-125a, and miR-223-3p) in BAL within the first 24 h following collection by routine bronchoscopy. miRNAs were quantified 0, 1, 4, 8, and 24 h after collection in samples that were kept at 4 °C or at room temperature. The expression of all five miRNAs was found to remain stable between the first 8 h after collection. 24 h after collection miRNAs faced substantial alterations in their expression profile. These data emphasize that BAL samples intended for further miRNA analysis can be handled at room temperature within the first 8 h after bronchoscopy.
    Beiträge zur Klinik der Tuberkulose 03/2015; 193(3). DOI:10.1007/s00408-015-9719-5 · 2.27 Impact Factor
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    ABSTRACT: We investigated the prevalence of bronchial asthma in patients with Tako-Tsubo Syndrome (TTS). This retrospective case-series study was conducted in a primary care hospital in Zurich, Switzerland. Data of all patients with newly diagnosed TTS (2002 - 2012) were assessed electronically by the use of ICD-10. Asthma prevalence was compared to published epidemiologic data. Bronchial asthma is characterized by airway inflammation and, during attack, release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise, catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS. 20 cases of TTS were identified. 90% were female, showed a median age of 70±13y [25y - 90y], an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9% [25% - 55%]. 65% of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45% of patients, 35% were smokers, none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25% vs. 7%, p=0.012). In 30% of the TTS patients an iatrogenic cause for development of TTS was identified. Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age-matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition, we identified other iatrogenic etiologies in patients with TTS.
    The Open Cardiovascular Medicine Journal 02/2015; 9(1):1-4. DOI:10.2174/1874192401509010001
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    ABSTRACT: Excessive proliferation of human pulmonary artery smooth muscle cells (HPASMC) is one of the major factors that trigger vascular remodeling in hypoxia-induced pulmonary hypertension. Several studies have implicated that hypoxia inhibits the tumour suppressor p21 (CDKN1A). However, the precise mechanism is unknown. The mouse model of hypoxia-induced PH and in vitro experiments were used to assess the impact of microRNAs (miRNAs) on the expression of CDKN1A. In these experiments, the miRNA family miR-130 was identified to regulate the expression of CDKN1A. Transfection of HPASMC with miR-130 decreased the expression of CDKN1A and, in turn, significantly increased smooth muscle proliferation. Conversely, inhibition of miR-130 by anti-miRs and seed blockers increased the expression of CDKN1A. Reporter gene analysis proved a direct miR-130-CDKN1A target interaction. Exposure of HPASMC to hypoxia was found to induce the expression of miR-130 with concomitant decrease of CDKN1A. These findings were confirmed in the mouse model of hypoxia-induced pulmonary hypertension showing that the use of seed blockers against miR-130 restored the expression of CDKN1A. These data suggest that miRNA family miR-130 plays an important role in the repression of CDKN1A by hypoxia. miR-130 enhances hypoxia-induced smooth muscle proliferation and might be involved in the development of right ventricular hypertrophy and vascular remodeling in pulmonary hypertension. Copyright © 2015. Published by Elsevier Ltd.
    The International Journal of Biochemistry & Cell Biology 02/2015; 61. DOI:10.1016/j.biocel.2015.02.002 · 4.05 Impact Factor
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    ABSTRACT: Background: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. Objective: To provide long-term data of the Swiss PH registry of 1998-2012. Methods: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. Results: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. Conclusion: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications. © 2015 S. Karger AG, Basel.
    Respiration 02/2015; 89(2). DOI:10.1159/000370125 · 2.59 Impact Factor
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    ABSTRACT: Background: An atherosclerotic disease burden sufficient to put lung transplant candidates at risk for end-organ disease after transplantation is considered to be a relative contraindication for lung transplantation. Objectives: The aim of this study was to assess our current practice of cardiac workup by coronary angiography in lung transplant candidates ≥50 years of age. Methods: We retrospectively analyzed 50 consecutive lung transplant candidates ≥50 years of age in which coronary angiography was performed at the University Hospital Zurich (2009-2013). For every patient, the risk of developing an acute coronary event was estimated by using a recalibrated version of the PROCAM study calculator for the Swiss population. Results: The median estimated risk of developing an acute coronary event within 10 years in the study cohort (n = 50) was 4.2% (interquartile range 1.9-7.6), which is considered to be a low risk. Sixteen percent of patients were considered to be at intermediate risk. In 66% of patients, coronary angiography showed no coronary artery disease (CAD). In 28% of patients, CAD without significant stenosis was diagnosed. In 6% of patients, significant coronary stenosis was detected requiring percutaneous coronary intervention. No correlation between the coronary status and the risk score or cardiovascular risk profile was found. Conclusions: The high prevalence of asymptomatic CAD in lung transplant candidates without correlation to a common clinical risk score supports the important role of coronary angiography for the assessment of coronary artery status. This approach might prevent cardiovascular events and improve long-term survival after transplantation. © 2015 S. Karger AG, Basel.
    Respiration 01/2015; 89(2). DOI:10.1159/000368368 · 2.59 Impact Factor
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    Macé Matthew Schuurmans · Christian Benden · Lars Christian Huber ·
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    ABSTRACT: Lung transplant recipients require life-long profound immunosuppression, making them prone to respiratory tract infections (RTIs), in particular viral infections, during the winter season. Since RTIs may have severe consequences, of which acute or chronic allograft dysfunction is feared most, early diagnosis and treatment are recommended. Patients monitor lung function daily at home and are instructed to contact the transplant center in case of signs and symptoms suspicious of RTIs. We then obtain nasopharyngeal swabs for viral and bacteriological examination and initiate pre-emptive treatment with antivirals, broadband antibiotics, and sometimes intravenous immunoglobulins. Treatment duration is guided by virology sampling results. As preventive measures, we provide vaccination against seasonal influenza for patients and household contacts and recommend specific daily hygiene measures.
    12/2014; 16(3):144-149. DOI:10.5152/ejp.2014.87597
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    Lars C Huber · Bart Vrugt · Mattia Arrigo ·
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    ABSTRACT: Pulmonary hypertension is defined as an increase of the mean pulmonary arterial pressure above 25 mm Hg and, as such, the diagnosis requires invasive haemo­ dynamic measurement by right heart catheterisation. More than just a single disease, pulmonary hyperten­ sion is an umbrella term that includes many different disorders and pathophysiological entities. However, most forms of pulmonary hypertension share a final common pathway, in particular the trias of vasocon­ striction, microthrombosis and vascular remodelling. The classification of pulmonary hypertension has been subjected to many changes within the last decade. At the same time, major achievements in our understand­ ing of the complex pathobiology have been made. Here, these developments are discussed in the light of the re­ cently published report from the fifth World Sympo­ sium on pulmonary hypertension.
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    ABSTRACT: PURPOSE: Pulmonary hypertension (PH) due to COPD has dismal prognosis. We reviewed the long-term effect of PH-target therapy in severe PH-COPD. METHOD: Patients attending our PH-clinic were reviewed for PH-COPD receiving PH-target therapy. Baseline characteristics, death/transplantation until 2014, therapy, NYHA functional class, 6 min walk distance (6MWD) and oxygen saturation (SpO2) at baseline, 3, 6, 12 and 24 months were analysed. RESULTS: Of 48 PH-COPD identified 21 were excluded (insufficient data, comorbidity). 27 patients (7 females, 21 smokers, 23 emphysema) with median (quartiles) baseline age 70 (60; 76) years, FEV1 60 (46; 78) %, FEV1/FVC 57 (51; 64) %, DLCO 42 (36; 59) %, mean pulmonary artery pressure 39 (32;44) mmHg under inhaled iloprost (10), subcutaneous prostanoids (2), intravenous prostanoids (3), endothelin receptor antagonists (15) and phosphodiesterase-5-inhibitors (25) were included. Under therapy, NYHA functional class improved from 3.5 (3; 4) to 3 (2; 4) after 3 months and 3 (2; 3.5) after 6 months (p = .02 and .008). The 6MWD improved from 373 (236; 452) to 395 (339; 472), 414 (285; 492) and 396 (308; 497)m at 3, 6 and 12 months (p = .005, .006 and .011) with unchanged resting-SpO2 but decreased peak-exercise SpO2. During median follow-up of 5.9 (2.3; 8.4) years, 10 died, 2 were transplanted and 2 were lost to follow-up. Transplant-free survival at 1,2,3 years was 92,69,54 % and was similar for GOLD stages 1-4, but worse for patients with mPAP ≥40 mmHg (p = .026), 6MWD <370 m (p = 0.008), resting SpO2 <92 % (p = 0.02) and peak-walk SpO2 <87 % (p = 0.012). CONCLUSION: PH-target vasodilator therapy improved NYHA functional class and 6MWD up to one year in highly selected patients with severe PH-COPD. Poor exercise capacity, low SpO2 and high mean pulmonary artery pressure at baseline but not airflow obstruction were associated with unfavourable outcome.
    Beiträge zur Klinik der Tuberkulose 10/2014; 192(6). DOI:10.1007/s00408-014-9650-1 · 2.27 Impact Factor

Publication Stats

2k Citations
436.49 Total Impact Points


  • 2004-2015
    • University of Zurich
      • • Internal Medicine Unit
      • • Center for Integrative Human Physiology
      Zürich, Zurich, Switzerland
  • 2009
    • University Hospital Zürich
      Zürich, Zurich, Switzerland
  • 2007
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2005
    • Duke University Medical Center
      • Division of Rheumatology and Immunology
      Durham, North Carolina, United States