medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-089medsovet-8220Research ArticleПУЛЬМОНОЛОГИЯПрименение экзогенного сурфактанта в пульмонологической практикеThe use of exogenous surfactant in pulmonological practicehttps://orcid.org/0000-0002-0877-6554ИгнатоваГ. Л.IgnatovaG. L.

Игнатова Галина Львовна, д.м.н., профессор, директор Института пульмонологии, заведующая кафедрой терапии института дополнительного профессионального образования

454092, Челябинск, ул. Воровского, д. 64

Galina L. Ignatova, Dr. Sci. (Med.), Professor, Head of the Department of Therapy of the Institute of Additional Professional Education, Director of the Institute of Pulmonology

64, Vorovskiy St., Chelyabinsk, 454092

iglign@mail.ruhttps://orcid.org/0000-0002-3531-3491АнтоновВ. Н.AntonovV. N.

Антонов Владимир Николаевич, д.м.н., профессор кафедры терапии института дополнительного профессионального образования, главный научный сотрудник Института пульмонологии

454092, Челябинск, ул. Воровского, д. 64

Vladimir N. Antonov, Dr. Sci. (Med.), Professor of the Department of Therapy of the Institute of Additional Professional Education, Chief Researcher of the Institute of Pulmonology

64, Vorovskiy St., Chelyabinsk, 454092

ant-vn@yandex.ruhttps://orcid.org/0009-0000-1139-1818ЗахароваИ. А.ZakharovaI. A.

Захарова Инна Александровна, д.м.н., профессор кафедры терапии института дополнительного профессионального образования, научный сотрудник Института пульмонологии

454092, Челябинск, ул. Воровского, д. 64

Inna A. Zakharova, Dr. Sci. (Med.), Professor of the Department of Therapy of the Institute of Additional Professional Education, Researcher of the Institute of Pulmonology

64, Vorovskiy St., Chelyabinsk, 454092

zaharowa.inna2012@yandex.ruЮжно-Уральский государственный медицинский университетРоссияSouth Ural State Medical UniversityRussian Federation202409052024054148Copyright © Игнатова Г.Л., Антонов В.Н., Захарова И.А., 20242024Игнатова Г.Л., Антонов В.Н., Захарова И.А.Ignatova G.L., Antonov V.N., Zakharova I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8220

Легочный сурфактант (ЛС) – это сложная смесь липидов и белков, необходимая для поддержания правильной функции легких. Изменения ЛС играют важную роль при хронических заболеваниях легких, таких как хроническая обструктивная болезнь легких, бронхиальная астма и идиопатический фиброз легких. Целью данной статьи является обоснование применения экзогенного сурфактанта при различных респираторных заболеваниях, на основании анализа публикаций в отечественных и международных медицинских изданиях, а также собственного опыта применения в реальной клинической практике. В данном обзоре в первую очередь обсуждены вклад легочных поверхностно-активных веществ для поддержания гомеостаза респираторной системы; оптимальные пути доставки; отличия натурального и синтетического сурфактанта; заболевания, связанные с нарушением выработки сурфактанта, такие как идиопатический легочный фиброз, хроническая обструктивная болезнь легких, острый респираторный дистресс-синдром, легочный альвеолярный протеиноз, муковисцидоз. Особое внимание обращено на иммунологические свойства специфических белков поверхностно-активных веществ A и D, их влияние на защиту при респираторной вирусной инфекции. Приведены данные о непосредственном влиянии экзогенного сурфактанта на легочную функцию, увеличение постбронходилатационных FEV1 и FVC. Особое внимание уделено применению сурфактанта при новой коронавирусной инфекции COVID-19. Фармакологические и терапевтические стратегии по улучшению дисфункции легочных поверхностно-активных веществ могут предотвратить альвеолярный коллапс, снизить провоспалительную реакцию и ограничить вирусную инфекцию. В настоящее время в нескольких клинических испытаниях изучается использование препаратов поверхностно-активных веществ для лечения различных респираторных заболеваний, что позволит при получении результатов значительно пересмотреть представления о терапевтических возможностях экзогенного сурфактанта и расширить области его применения.

A lung surfactant is a complex mixture of lipids and proteins necessary to maintain proper lung function. Drug changes play an important role in chronic lung diseases such as chronic obstructive pulmonary disease, bronchial asthma and idiopathic pulmonary fibrosis. The purpose of this article is to substantiate the use of exogenous surfactant in various respiratory diseases, based on the analysis of publications in domestic and international medical journals, as well as their own experience of application in real clinical practice. This review primarily discusses the contribution of pulmonary surfactants to maintaining homeostasis of the respiratory system; optimal delivery routes; differences between natural and synthetic surfactant; diseases associated with impaired surfactant production, such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary alveolar proteinosis, cystic fibrosis. Special attention is paid to the immunological properties of specific proteins of surfactants A and D, their effect on protection against respiratory viral infection. Data on the direct effect of exogenous surfactant on pulmonary function, an increase in post-bronchodilation FEV1 and FVC are presented. Special attention is paid to the use of surfactant in the new coronavirus infection COVID-19. Pharmacological and therapeutic strategies to improve pulmonary surfactant dysfunction can prevent alveolar collapse, reduce the proinflammatory response, and limit viral infection. Currently, the use of surfactant preparations for the treatment of various respiratory diseases is being studied in several clinical trials, which will significantly revise the understanding of the therapeutic possibilities of an exogenous surfactant and expand its application areas.

поверхностно-активные веществахронические заболевания легкихспособы доставкиреспираторный дистресс-синдромSP-ASP-Dsurfactantschronic lung diseasesdelivery methodsrespiratory distress syndromeSP-ASP-DReferencesHentschel R, Bohlin K, van Kaam A, Fuchs H, Danhaive O. Surfactant replacement therapy: from biological basis to current clinical practice. Pediatr Res. 2020;88(2):176–183. https://doi.org/10.1038/s41390-020-0750-8.Hentschel R, Bohlin K, van Kaam A, Fuchs H, Danhaive O. Surfactant replacement therapy: from biological basis to current clinical practice. Pediatr Res. 2020;88(2):176–183. https://doi.org/10.1038/s41390-020-0750-8.Garcia MJ, Amarelle L, Malacrida L, Briva A. Novel opportunities from bioimaging to understand the trafficking and maturation of intracellular pulmonary surfactant and its role in lung diseases. Front Immunol. 2023;14:1250350. https://doi.org/10.3389/fimmu.2023.1250350.Garcia MJ, Amarelle L, Malacrida L, Briva A. Novel opportunities from bioimaging to understand the trafficking and maturation of intracellular pulmonary surfactant and its role in lung diseases. Front Immunol. 2023;14:1250350. https://doi.org/10.3389/fimmu.2023.1250350.Milad N, Morissette MC. Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure. Eur Respir Rev. 2021;30(162):210077. https://doi.org/10.1183/16000617.0077-2021.Milad N, Morissette MC. Revisiting the role of pulmonary surfactant in chronic inflammatory lung diseases and environmental exposure. Eur Respir Rev. 2021;30(162):210077. https://doi.org/10.1183/16000617.0077-2021.Echaide M, Autilio C, Arroyo R, Perez-Gil J. Restoring pulmonary surfactant membranes and films at the respiratory surface. Biochim Biophys Acta Biomembr. 2017;1859(9 Pt B):1725–1739. https://doi.org/10.1016/j.bbamem.2017.03.015.Echaide M, Autilio C, Arroyo R, Perez-Gil J. Restoring pulmonary surfactant membranes and films at the respiratory surface. Biochim Biophys Acta Biomembr. 2017;1859(9 Pt B):1725–1739. https://doi.org/10.1016/j.bbamem.2017.03.015.Olmeda B, Martínez-Calle M, Pérez-Gil J. Pulmonary surfactant metabolism in the alveolar airspace: Biogenesis, extracellular conversions, recycling. Ann Anat. 2017;209:78–92. https://doi.org/10.1016/j.aanat.2016.09.008.Olmeda B, Martínez-Calle M, Pérez-Gil J. Pulmonary surfactant metabolism in the alveolar airspace: Biogenesis, extracellular conversions, recycling. Ann Anat. 2017;209:78–92. https://doi.org/10.1016/j.aanat.2016.09.008.Agudelo CW, Samaha G, Garcia-Arcos I. Alveolar lipids in pulmonary disease. A review. Lipids Health Dis. 2020;19(1):122. https://doi.org/10.1186/s12944-020-01278-8.Agudelo CW, Samaha G, Garcia-Arcos I. Alveolar lipids in pulmonary disease. A review. Lipids Health Dis. 2020;19(1):122. https://doi.org/10.1186/s12944-020-01278-8.Numata M, Kandasamy P, Voelker DR. The anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids. Immunol Rev. 2023;317(1):166–186. https://doi.org/10.1111/imr.13207.Numata M, Kandasamy P, Voelker DR. The anti-inflammatory and antiviral properties of anionic pulmonary surfactant phospholipids. Immunol Rev. 2023;317(1):166–186. https://doi.org/10.1111/imr.13207.Voelker DR, Numata M. Phospholipid regulation of innate immunity and respiratory viral infection. J Biol Chem. 2019;294(12):4282–4289. https://doi.org/10.1074/jbc.AW118.003229.Voelker DR, Numata M. Phospholipid regulation of innate immunity and respiratory viral infection. J Biol Chem. 2019;294(12):4282–4289. https://doi.org/10.1074/jbc.AW118.003229.Tlatelpa-Romero B, Cázares-Ordoñez V, Oyarzábal LF, Vázquez-de-Lara LG. The Role of Pulmonary Surfactant Phospholipids in Fibrotic Lung Diseases. Int J Mol Sci. 2022;24(1):326. https://doi.org/10.3390/ijms24010326.Tlatelpa-Romero B, Cázares-Ordoñez V, Oyarzábal LF, Vázquez-de-Lara LG. The Role of Pulmonary Surfactant Phospholipids in Fibrotic Lung Diseases. Int J Mol Sci. 2022;24(1):326. https://doi.org/10.3390/ijms24010326.Walther FJ, Sharma S, Gordon LM, Waring AJ. Structural and functional stability of the sulfur-free surfactant protein B peptide mimic B-YL in synthetic surfactant lipids. BMC Pulm Med. 2021;21(1):330. https://doi.org/10.1186/s12890-021-01695-0.Walther FJ, Sharma S, Gordon LM, Waring AJ. Structural and functional stability of the sulfur-free surfactant protein B peptide mimic B-YL in synthetic surfactant lipids. BMC Pulm Med. 2021;21(1):330. https://doi.org/10.1186/s12890-021-01695-0.Porras-Gómez M, Shoaib T, Steer D, Espinosa-Marzal RM, Leal C. Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes. Biophys J. 2022;121(6):886–896. https://doi.org/10.1016/j.bpj.2022.02.018.Porras-Gómez M, Shoaib T, Steer D, Espinosa-Marzal RM, Leal C. Pathological cardiolipin-promoted membrane hemifusion stiffens pulmonary surfactant membranes. Biophys J. 2022;121(6):886–896. https://doi.org/10.1016/j.bpj.2022.02.018.Numata M, Voelker DR. Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867(6):159139. https://doi.org/10.1016/j.bbalip.2022.159139.Numata M, Voelker DR. Anti-inflammatory and anti-viral actions of anionic pulmonary surfactant phospholipids. Biochim Biophys Acta Mol Cell Biol Lipids. 2022;1867(6):159139. https://doi.org/10.1016/j.bbalip.2022.159139.Pérez-Gil J. A recipe for a good clinical pulmonary surfactant. Biomed J. 2022;45(4):615–628. https://doi.org/10.1016/j.bj.2022.03.001.Pérez-Gil J. A recipe for a good clinical pulmonary surfactant. Biomed J. 2022;45(4):615–628. https://doi.org/10.1016/j.bj.2022.03.001.Hallman M, Herting E. Historical perspective on surfactant therapy: Transforming hyaline membrane disease to respiratory distress syndrome. Semin Fetal Neonatal Med. 2023;28(6):101493. https://doi.org/10.1016/j.siny.2023.101493.Hallman M, Herting E. Historical perspective on surfactant therapy: Transforming hyaline membrane disease to respiratory distress syndrome. Semin Fetal Neonatal Med. 2023;28(6):101493. https://doi.org/10.1016/j.siny.2023.101493.De Luca D, Autilio C. Strategies to protect surfactant and enhance its activity. Biomed J. 2021;44(6):654–662. https://doi.org/10.1016/j.bj.2021.07.011.De Luca D, Autilio C. Strategies to protect surfactant and enhance its activity. Biomed J. 2021;44(6):654–662. https://doi.org/10.1016/j.bj.2021.07.011.Suresh GK, Soll RF. Lung surfactants for neonatal respiratory distress syndrome: animal-derived or synthetic agents?. Paediatr Drugs. 2002;4(8): 485–492. https://doi.org/10.2165/00128072-200204080-00001.Suresh GK, Soll RF. Lung surfactants for neonatal respiratory distress syndrome: animal-derived or synthetic agents?. Paediatr Drugs. 2002;4(8): 485–492. https://doi.org/10.2165/00128072-200204080-00001.Mohanty SS, Koul Y, Varjani S, Pandey A, Ngo HH, Chang JS et al. A critical review on various feedstocks as sustainable substrates for biosurfactants production: a way towards cleaner production. Microb Cell Fact. 2021;20(1):120. https://doi.org/10.1186/s12934-021-01613-3.Mohanty SS, Koul Y, Varjani S, Pandey A, Ngo HH, Chang JS et al. A critical review on various feedstocks as sustainable substrates for biosurfactants production: a way towards cleaner production. Microb Cell Fact. 2021;20(1):120. https://doi.org/10.1186/s12934-021-01613-3.Lv MY, Qiang LX, Wang BC, Zhang YP, Li ZH, Li XS et al. Complex Evaluation of Surfactant Protein A and D as Biomarkers for the Severity of COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1537–1552. https://doi.org/10.2147/COPD.S366988.Lv MY, Qiang LX, Wang BC, Zhang YP, Li ZH, Li XS et al. Complex Evaluation of Surfactant Protein A and D as Biomarkers for the Severity of COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1537–1552. https://doi.org/10.2147/COPD.S366988.Moya F, Curstedt T, Johansson J, Sweet D. Synthetic surfactants. Semin Fetal Neonatal Med. 2023;28(6):101503. https://doi.org/10.1016/j.siny.2023.101503.Moya F, Curstedt T, Johansson J, Sweet D. Synthetic surfactants. Semin Fetal Neonatal Med. 2023;28(6):101503. https://doi.org/10.1016/j.siny.2023.101503.Härtel C, Glaser K, Speer CP. The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs. Neonatology. 2021;118(2):225–234. https://doi.org/10.1159/000516106.Härtel C, Glaser K, Speer CP. The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs. Neonatology. 2021;118(2):225–234. https://doi.org/10.1159/000516106.Ramanathan R, Biniwale M, Sekar K, Hanna N, Golombek S, Bhatia J et al. Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. J Pediatr. 2020;225:90–96.e1. https://doi.org/10.1016/j.jpeds.2020.06.024.Ramanathan R, Biniwale M, Sekar K, Hanna N, Golombek S, Bhatia J et al. Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. J Pediatr. 2020;225:90–96.e1. https://doi.org/10.1016/j.jpeds.2020.06.024.Weaver TE. Synthesis, processing and secretion of surfactant proteins B and C. Biochim Biophys Acta. 1998;1408(2-3):173–179. https://doi.org/10.1016/s0925-4439(98)00066-0.Weaver TE. Synthesis, processing and secretion of surfactant proteins B and C. Biochim Biophys Acta. 1998;1408(2-3):173–179. https://doi.org/10.1016/s0925-4439(98)00066-0.Ghati A, Dam P, Tasdemir D, Kati A, Sellami H, Sezgin GC et al. Exogenous pulmonary surfactant: A review focused on adjunctive therapy for severe acute respiratory syndrome coronavirus 2 including SP-A and SP-D as added clinical marker. Curr Opin Colloid Interface Sci. 2021;51:101413. https://doi.org/10.1016/j.cocis.2020.101413.Ghati A, Dam P, Tasdemir D, Kati A, Sellami H, Sezgin GC et al. Exogenous pulmonary surfactant: A review focused on adjunctive therapy for severe acute respiratory syndrome coronavirus 2 including SP-A and SP-D as added clinical marker. Curr Opin Colloid Interface Sci. 2021;51:101413. https://doi.org/10.1016/j.cocis.2020.101413.Hsieh MH, Chen PC, Hsu HY, Liu JC, Ho YS, Lin YJ et al. Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease. Cell Mol Immunol. 2023;20(1):38–50. https://doi.org/10.1038/s41423-022-00946-2.Hsieh MH, Chen PC, Hsu HY, Liu JC, Ho YS, Lin YJ et al. Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease. Cell Mol Immunol. 2023;20(1):38–50. https://doi.org/10.1038/s41423-022-00946-2.Cavallin F, Bua B, Pasta E, Savio F, Villani PE, Trevisanuto D. Device positioning with LISA vs. INSURE: a crossover randomized controlled manikin trial. J Matern Fetal Neonatal Med. 2022;35(26):10577–10583. https://doi.org/10.1080/14767058.2022.2134774.Cavallin F, Bua B, Pasta E, Savio F, Villani PE, Trevisanuto D. Device positioning with LISA vs. INSURE: a crossover randomized controlled manikin trial. J Matern Fetal Neonatal Med. 2022;35(26):10577–10583. https://doi.org/10.1080/14767058.2022.2134774.Ricci F, Bresesti I, LaVerde PAM, Salomone F, Casiraghi C, Mersanne A et al. Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress. Pediatr Res. 2021;90(3):576–583. https://doi.org/10.1038/s41390-020-01324-2.Ricci F, Bresesti I, LaVerde PAM, Salomone F, Casiraghi C, Mersanne A et al. Surfactant lung delivery with LISA and InSurE in adult rabbits with respiratory distress. Pediatr Res. 2021;90(3):576–583. https://doi.org/10.1038/s41390-020-01324-2.Баутин АЕ, Авдеев СН, Сейлиев АА, Швечкова МВ, Мержоева ЗМ, Трушенко НВ и др. Ингаляционная терапия сурфактантом в комплексном лечении тяжелой формы COVID-19-пневмонии. Туберкулез и болезни легких. 2020;98(9):6–12. https://doi.org/10.21292/2075-1230-2020-98-9-6-12.Bautin AE, Avdeev SN, Seyliev AA, Shvechkova MV, Merzhoeva ZM, Trushenko NV, et al. Inhalation surfactant therapy in the integrated treatment of severe COVID-19 pneumonia. Tuberculosis and Lung Diseases. 2020;98(9):6–12. (In Russ.) https://doi.org/10.21292/2075-1230-2020-98-9-6-12.Ma CC, Ma S. The role of surfactant in respiratory distress syndrome. Open Respir Med J. 2012;6:44–53. https://doi.org/10.2174/1874306401206010044.Ma CC, Ma S. The role of surfactant in respiratory distress syndrome. Open Respir Med J. 2012;6:44–53. https://doi.org/10.2174/1874306401206010044.Li D, Wang X, Liao Y, Wang S, Shan J, Ji J. Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components. Front Immunol. 2022;13:842453. https://doi.org/10.3389/fimmu.2022.842453.Li D, Wang X, Liao Y, Wang S, Shan J, Ji J. Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components. Front Immunol. 2022;13:842453. https://doi.org/10.3389/fimmu.2022.842453.Calabrese F, Pezzuto F, Fortarezza F, Hofman P, Kern I, Panizo A et al. Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Virchows Arch. 2020;477(3):359–372. https://doi.org/10.1007/s00428-020-02886-6.Calabrese F, Pezzuto F, Fortarezza F, Hofman P, Kern I, Panizo A et al. Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Virchows Arch. 2020;477(3):359–372. https://doi.org/10.1007/s00428-020-02886-6.Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122–1127. https://doi.org/10.1126/science.abm8108.Merad M, Blish CA, Sallusto F, Iwasaki A. The immunology and immunopathology of COVID-19. Science. 2022;375(6585):1122–1127. https://doi.org/10.1126/science.abm8108.Zhou R, To KK, Wong YC, Liu L, Zhou B, Li X et al. Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses. Immunity. 2020;53(4):864–877.e5. https://doi.org/10.1016/j.immuni.2020.07.026.Zhou R, To KK, Wong YC, Liu L, Zhou B, Li X et al. Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses. Immunity. 2020;53(4):864–877.e5. https://doi.org/10.1016/j.immuni.2020.07.026.Bos LDJ, Sjoding M, Sinha P, Bhavani SV, Lyons PG, Bewley AF et al. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. Lancet Respir Med. 2021;9(12):1377–1386. https://doi.org/10.1016/S2213-2600(21)00365-9.Bos LDJ, Sjoding M, Sinha P, Bhavani SV, Lyons PG, Bewley AF et al. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. Lancet Respir Med. 2021;9(12):1377–1386. https://doi.org/10.1016/S2213-2600(21)00365-9.Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. https://doi.org/10.1126/science.abd4570.Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4570. https://doi.org/10.1126/science.abd4570.Woods PS, Doolittle LM, Rosas LE, Joseph LM, Calomeni EP, Davis IC. Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome. Am J Physiol Lung Cell Mol Physiol. 2016;311(6): L1160–L1169. https://doi.org/10.1152/ajplung.00339.2016.Woods PS, Doolittle LM, Rosas LE, Joseph LM, Calomeni EP, Davis IC. Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome. Am J Physiol Lung Cell Mol Physiol. 2016;311(6): L1160–L1169. https://doi.org/10.1152/ajplung.00339.2016.Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5(1):16. https://doi.org/10.1038/s41572-019-0066-3.Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5(1):16. https://doi.org/10.1038/s41572-019-0066-3.Salvaterra E, Campo I. Pulmonary alveolar proteinosis: from classification to therapy. Breathe (Sheff). 2020;16(2):200018. https://doi.org/10.1183/20734735.0018-2020.Salvaterra E, Campo I. Pulmonary alveolar proteinosis: from classification to therapy. Breathe (Sheff). 2020;16(2):200018. https://doi.org/10.1183/20734735.0018-2020.Trapnell BC, Whitsett JA. Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense. Annu Rev Physiol. 2002;64:775–802. https://doi.org/10.1146/annurev.physiol.64.090601.113847.Trapnell BC, Whitsett JA. Gm-CSF regulates pulmonary surfactant homeostasis and alveolar macrophage-mediated innate host defense. Annu Rev Physiol. 2002;64:775–802. https://doi.org/10.1146/annurev.physiol.64.090601.113847.Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: what is next? Eur Respir Rev. 2019;28(153):190021. https://doi.org/10.1183/16000617.0021-2019.Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: what is next? Eur Respir Rev. 2019;28(153):190021. https://doi.org/10.1183/16000617.0021-2019.Zhu W, Tan C, Zhang J. Alveolar Epithelial Type 2 Cell Dysfunction in Idiopathic Pulmonary Fibrosis. Lung. 2022;200(5):539–547. https://doi.org/10.1007/s00408-022-00571-w.Zhu W, Tan C, Zhang J. Alveolar Epithelial Type 2 Cell Dysfunction in Idiopathic Pulmonary Fibrosis. Lung. 2022;200(5):539–547. https://doi.org/10.1007/s00408-022-00571-w.Agudelo CW, Kumley BK, Area-Gomez E, Xu Y, Dabo AJ, Geraghty P et al. Decreased surfactant lipids correlate with lung function in chronic obstructive pulmonary disease (COPD). PLoS ONE. 2020;15(2):e0228279. https://doi.org/10.1371/journal.pone.0228279.Agudelo CW, Kumley BK, Area-Gomez E, Xu Y, Dabo AJ, Geraghty P et al. Decreased surfactant lipids correlate with lung function in chronic obstructive pulmonary disease (COPD). PLoS ONE. 2020;15(2):e0228279. https://doi.org/10.1371/journal.pone.0228279.Hohlfeld JM. The role of surfactant in asthma. Respir Res. 2002;3(1):4. https://doi.org/10.1186/rr176.Hohlfeld JM. The role of surfactant in asthma. Respir Res. 2002;3(1):4. https://doi.org/10.1186/rr176.Choi Y, Jang J, Park HS. Pulmonary Surfactants: a New Therapeutic Target in Asthma. Curr Allergy Asthma Rep. 2020;20(11):70. https://doi.org/10.1007/s11882-020-00968-8.Choi Y, Jang J, Park HS. Pulmonary Surfactants: a New Therapeutic Target in Asthma. Curr Allergy Asthma Rep. 2020;20(11):70. https://doi.org/10.1007/s11882-020-00968-8.Ledford JG, Addison KJ, Foster MW, Que LG. Eosinophil-associated lung diseases. A cry for surfactant proteins A and D help? Am J Respir Cell Mol Biol. 2014;51(5):604–614. https://doi.org/10.1165/rcmb.2014-0095TR.Ledford JG, Addison KJ, Foster MW, Que LG. Eosinophil-associated lung diseases. A cry for surfactant proteins A and D help? Am J Respir Cell Mol Biol. 2014;51(5):604–614. https://doi.org/10.1165/rcmb.2014-0095TR.Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G. Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res. 2021;22(1):109. https://doi.org/10.1186/s12931-021-01711-1.Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G. Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res. 2021;22(1):109. https://doi.org/10.1186/s12931-021-01711-1.Griese M, Essl R, Schmidt R, Ballmann M, Paul K, Rietschel E, Ratjen F. Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients. Respir Res. 2005;6(1):133. https://doi.org/10.1186/1465-9921-6-133.Griese M, Essl R, Schmidt R, Ballmann M, Paul K, Rietschel E, Ratjen F. Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients. Respir Res. 2005;6(1):133. https://doi.org/10.1186/1465-9921-6-133.Gunasekara L, Al-Saiedy M, Green F, Pratt R, Bjornson C, Yang A et al. Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug. J Cyst Fibros. 2017;16(5):565–572. https://doi.org/10.1016/j.jcf.2017.04.015.Gunasekara L, Al-Saiedy M, Green F, Pratt R, Bjornson C, Yang A et al. Pulmonary surfactant dysfunction in pediatric cystic fibrosis: Mechanisms and reversal with a lipid-sequestering drug. J Cyst Fibros. 2017;16(5):565–572. https://doi.org/10.1016/j.jcf.2017.04.015.

The authors declare that there are no conflicts of interest present.