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• W2912999677 abstract "Central MessageCorticosteroids may affect lung surfactant expression, with inherited surfactant subtype polymorphisms playing a key role. This may result in unpredictable side effects in lung allograft recipients.See Article page 2109. Corticosteroids may affect lung surfactant expression, with inherited surfactant subtype polymorphisms playing a key role. This may result in unpredictable side effects in lung allograft recipients. See Article page 2109. The use of corticosteroids has become an almost unavoidable aspect of all solid-organ transplantation, including that of the lungs. Steroid-sparing immunosuppression protocols are rarely used today, despite copious data that long-term steroid use is associated with osteoporosis, cataracts, diabetes, hypertension, and hypercholesterolemia.1Baraldo M. Gregoraci G. Livi U. Steroid-free and steroid withdrawal protocols in heart transplantation: the review of literature.Transpl Int. 2014; 27: 515-529Crossref PubMed Scopus (23) Google Scholar All these counterproductive side effects diminish the qualitative and quantitative benefits of solid-organ transplantation. In the current issue of the Journal, Aramini and colleagues2Aramini B. Geraghty P. Lederer D. Costa J. DiAngelo S.L. Floros J. et al.Surfactant proteins A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs.J Thorac Cardiovasc Surg. 2019; 157: 2109-2117Abstract Full Text Full Text PDF Scopus (13) Google Scholar from D'Ovidio's lung transplant program in Columbia University further demonstrate that corticosteroids alter the levels of surfactant proteins in donor lungs. Surfactant levels play a critical role in pulmonary function. This is emphasized by the critical role of surfactant replacement in treating premature neonates.3Polin R.A. Carlo W.A. Committee on Fetus and Newborn; American Academy of Pediatrics. Surfactant replacement therapy for preterm and term neonates with respiratory distress.Pediatrics. 2014; 133: 156-163Crossref PubMed Scopus (245) Google Scholar Surfactant levels also contribute to important aspects of the immunologic defense mechanism in the lung,4Carreto-Binaghi L.E. Aliouat el M. Taylor M.L. Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.Respir Res. 2016; 17: 66Crossref PubMed Scopus (37) Google Scholar a process critical to the already immunosuppressed graft recipient. D'Ovidio's group2Aramini B. Geraghty P. Lederer D. Costa J. DiAngelo S.L. Floros J. et al.Surfactant proteins A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs.J Thorac Cardiovasc Surg. 2019; 157: 2109-2117Abstract Full Text Full Text PDF Scopus (13) Google Scholar demonstrate differential surfactant protein expression according to the genetic polymorphisms, whether in an epithelial cell line with a rare surfactant protein genotype or in human lung tissue. Specifically, they demonstrate, by using the novel method of analysis of precision cut slices of donor lung tissue, that those with the surfactant protein A2 variant 1A0 have increased expression of surfactant when treated with steroids. These in vitro pharmacogenetic findings support previous observations from D'Ovidio's group5D’Ovidio F. Kaneda H. Chaparro C. Mura M. Lederer D. Di Angelo S. et al.Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.Am J Transplant. 2013; 13 (Erratum in: Am J Transplant. 2014;14:496): 2722-2729Crossref PubMed Scopus (26) Google Scholar, 6Aramini B. Kim C. Diangelo S. Petersen E. Lederer D.J. Shah L. et al.Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome.Am J Transplant. 2013; 13: 2130-2136Scopus (20) Google Scholar in the clinical arena, which documented significantly greater surfactant protein A expression in donor lungs carrying the 1A0 variant before implantation when donor organs are under the influence of large steroid treatment. Further, the 1A0 variant within the context of lung transplantation consistently showed a protective effect with better outcomes.5D’Ovidio F. Kaneda H. Chaparro C. Mura M. Lederer D. Di Angelo S. et al.Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.Am J Transplant. 2013; 13 (Erratum in: Am J Transplant. 2014;14:496): 2722-2729Crossref PubMed Scopus (26) Google Scholar, 6Aramini B. Kim C. Diangelo S. Petersen E. Lederer D.J. Shah L. et al.Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome.Am J Transplant. 2013; 13: 2130-2136Scopus (20) Google Scholar Although this issue is not directly explored in the article of Aramini and colleagues,2Aramini B. Geraghty P. Lederer D. Costa J. DiAngelo S.L. Floros J. et al.Surfactant proteins A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs.J Thorac Cardiovasc Surg. 2019; 157: 2109-2117Abstract Full Text Full Text PDF Scopus (13) Google Scholar it is evident to the thoracic surgeon that increased expression of surfactant may in and of itself lead to pathology such as alveolar proteinosis.7Huizar I. Kavuru M.S. Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management.Curr Opin Pulm Med. 2009; 15: 491-498Crossref PubMed Scopus (51) Google Scholar These data thus further confound the role of non–high dose corticosteroid use for both induction and maintenance immunosuppression in the lung allograft recipient. Such data also support the argument for the development of lung-specific immunosuppression that takes advantage of unique inflammatory feedback loops evident in that organ,8Witt C.A. Puri V. Gelman A.E. Krupnick A.S. Kreisel D. Lung transplant immunosuppression—time for a new approach?.Expert Rev Clin Immunol. 2014; 10: 1419-1421Crossref PubMed Scopus (10) Google Scholar, 9Onyema O.O. Guo Y. Wang Q. Stoler M.H. Lau C. Li K. et al.Eosinophils promote inducible NOS-mediated lung allograft acceptance.JCI Insight. 2017; 2: e96455Google Scholar as well as of the donor's specific pharmacogenetics. Surfactant protein A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungsThe Journal of Thoracic and Cardiovascular SurgeryVol. 157Issue 5PreviewSurfactant proteins A and D are important molecules involved in lung allograft innate immunity. Genetic polymorphisms of surfactant proteins A and D are associated with various lung diseases. In this study, surfactant protein A and D expression responses were investigated during pharmacogenetics upon methylprednisolone treatment as observed during lung transplantation. Full-Text PDF Open Archive" @default.
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• W2912999677 title "Commentary: The unknown fact about surfactant" @default.
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