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Effects of Ambrisentan in a Patient Affected by Combined Pulmonary Fibrosis and Emphysema and by Severe Pulmonary Hypertension: Clinical, Functional, and Biomolecular Findings

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Abstract

Combined pulmonary fibrosis and emphysema (CPFE) is a computed tomography (CT)-defined syndrome of combined pulmonary fibrosis and emphysema, characterized by subnormal spirometry, impairment of gas exchange, and high prevalence of pulmonary hypertension. Although endothelin-1 (ET-1) plays an important role in the development of lung fibrosis as well as in pulmonary hypertension, no ET-1-targeted therapy is currently recommended. Here we report a case of CPFE successfully treated with ambrisentan, an endothelin-A receptor antagonist, and also discuss the biologic mechanisms underlying the observed therapeutic effects. A 79-year-old man with chronic obstructive pulmonary disease (COPD) was referred to our respiratory unit as an outpatient for dyspnea. Clinical, radiologic, and laboratory findings suggested a diagnosis of chronic hypoxemic, type 1 respiratory failure, due to combined pulmonary fibrosis and emphysema, complicated by severe, precapillary pulmonary hypertension. Pharmacologic treatment with ambrisentan induced an initial improvement in clinical symptoms that proved to be very relevant 9 months later. In order to investigate the biologic mechanisms underlying the clinical effects of ambrisentan, we performed an “in vitro” study on primary cultures of fibrotic human lung fibroblasts, as well as on human umbilical vein endothelial cells, incubated for 24 and 48 h with ET-1, in the absence or presence of an overnight treatment with ambrisentan. ET-1 significantly increased cell proliferation and mitogen-activated protein kinase activation (P < 0.01). These effects were significantly (P < 0.01) inhibited by ambrisentan in both cell cultures. In conclusion, we hypothesize that the clinical benefits induced by ambrisentan in this patient with CPFE can be attributed to its vasodilator and anti-proliferative actions, exerted on pulmonary the vascular bed and lung fibroblasts.

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Acknowledgments

All authors have no conflicts of interest to declare and they did not receive funding for this case report.

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy

    Fernando Roccia, Benedetta Campolo, Carmen Spaccarotella, Annalisa Mongiardo, Girolamo Pelaia, Ciro Indolfi & Rosario Maselli

  2. Department of Health Sciences, School of Medicine, University “Magna Graecia” of Catanzaro, Catanzaro, Italy

    Luca Gallelli, Daniela Falcone & Rocco Savino

  3. Clinical Pharmacology Unit, Mater Domini University Hospital, Viale Europa-Germaneto, 88100, Catanzaro, Italy

    Luca Gallelli

Authors
  1. Fernando Roccia
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  2. Benedetta Campolo
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  3. Luca Gallelli
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  4. Carmen Spaccarotella
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  5. Annalisa Mongiardo
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  6. Daniela Falcone
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  7. Rocco Savino
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  8. Girolamo Pelaia
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  9. Ciro Indolfi
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  10. Rosario Maselli
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Correspondence to Luca Gallelli.

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Roccia, F., Campolo, B., Gallelli, L. et al. Effects of Ambrisentan in a Patient Affected by Combined Pulmonary Fibrosis and Emphysema and by Severe Pulmonary Hypertension: Clinical, Functional, and Biomolecular Findings. Clin Drug Investig 33, 451–457 (2013). https://doi.org/10.1007/s40261-013-0083-z

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  • DOI: https://doi.org/10.1007/s40261-013-0083-z

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