{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T23:40:24Z","timestamp":1774050024647,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>In this opinion article, we discuss a serendipitous observation we made in a study investigating survival in aged mice after bacterial infection. This observation involved a non-invasive ventilation approach that led to variable and higher survival in male and female mice with different genetic backgrounds for the innate immune molecule, surfactant protein A (SP-A). We suggest that employing the best ventilatory modality, whether that be HFNC or another method, may augment the role of other factors such as SP-A genetics and sex in a personalized approach, and may ultimately improve the outcome.<\/jats:p>","DOI":"10.3390\/antiox10050640","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Can Prophylactic High Flow of Humidified and Warmed Filtered Air Improve Survival from Bacterial Pneumonia and SARS-CoV-2 in Elderly Individuals? The Role of Surfactant Protein A"],"prefix":"10.3390","volume":"10","author":[{"given":"Ata","family":"Abbasi","sequence":"first","affiliation":[{"name":"Department of Pathology, Urmia University of Medical Sciences, Urmia 5714783734, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Phelps","sequence":"additional","affiliation":[{"name":"Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhika","family":"Ravi","sequence":"additional","affiliation":[{"name":"Division of Anesthesia, Department of Surgery, Veterans Affairs New Jersey Health Care System, 385 Tremont Avenue, East Orange, NJ 07018, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Floros","sequence":"additional","affiliation":[{"name":"Center for Host Defense, Inflammation, and Lung Disease (CHILD) Research, Department of Pediatrics, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"},{"name":"Department of Obstetrics and Gynecology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Thorenoor, N., Phelps, D.S., Kala, P., Ravi, R., Phelps, A.F., Umstead, T.M., Zhang, X., and Floros, J. (2020). Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091276"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12877-018-0787-2","article-title":"The relative burden of community-acquired pneumonia hospitalizations in older adults: A retrospective observational study in the United States","volume":"18","author":"Brown","year":"2018","journal-title":"BMC Geriatr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.vaccine.2019.10.101","article-title":"Rates of hospitalization for community-acquired pneumonia among US adults: A systematic review","volume":"38","author":"McLaughlin","year":"2020","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Del Rio-Pertuz, G., Guti\u00e9rrez, J.F., Triana, A.J., Molinares, J.L., Robledo-Solano, A.B., Meza, J.L., Ariza-Bol\u00edvar, O.M., Acosta-Reyes, J., Garavito, A., and Viasus, D. (2019). Usefulness of sputum gram stain for etiologic diagnosis in community-acquired pneumonia: A systematic review and meta-analysis. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4048-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/MMBR.00078-15","article-title":"Klebsiella pneumoniae: Going on the Offense with a Strong Defense","volume":"80","author":"Paczosa","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1179\/2047773215Y.0000000030","article-title":"Antimicrobial resistance: A global multifaceted phenomenon","volume":"109","author":"Prestinaci","year":"2015","journal-title":"Pathog. Glob. Health"},{"key":"ref_7","first-page":"1","article-title":"Risk factors for carbapenem-resistant Klebsiella pneumoniae infection relative to two types of control patients: A systematic review and meta-analysis","volume":"9","author":"Zhu","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1089\/mdr.2017.0061","article-title":"Risk factors for carbapenem-resistant Klebsiella pneu-moniae infection: A meta-analysis","volume":"24","author":"Liu","year":"2018","journal-title":"Microb. Dug. Resist."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Minozzi, S., Pifferi, S., Brazzi, L., Pecoraro, V., Montrucchio, G., and D\u2019Amico, R. (2021). Topical antibiotic prophylaxis to reduce respir-atory tract infections and mortality in adults receiving mechanical ventilation. Cochrane. Database. Syst. Rev.","DOI":"10.1002\/14651858.CD000022.pub4"},{"key":"ref_10","first-page":"CD000022","article-title":"Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care","volume":"2009","author":"Pifferi","year":"2009","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1165\/ajrcmb.12.1.7811473","article-title":"5\u2032 splicing and allelic variants of the human pulmonary surfactant protein A genes","volume":"12","author":"Karinch","year":"1995","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0925-4439(98)00077-5","article-title":"Genetics of the hydrophilic surfactant proteins A and D","volume":"1408","author":"Floros","year":"1998","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_13","first-page":"87","article-title":"Human surfactant protein A (SP-A) variants: Why so many, why such a complexity?","volume":"131","author":"Floros","year":"2001","journal-title":"Swiss Med Wkly."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1095-6433(01)00325-7","article-title":"A point of view: Quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model","volume":"129","author":"Floros","year":"2001","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1615\/CritRevEukarGeneExpr.v19.i2.30","article-title":"Genetic Complexity of the Human Innate Host Defense Molecules, Surfactant Protein A1 (SP-A1) and SP-A2\u2014Impact on Function","volume":"19","author":"Floros","year":"2009","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1289\/ehp.0211079","article-title":"The effect of ozone exposure on the ability of human sur-factant protein A variants to stimulate cytokine production","volume":"110","author":"Wang","year":"2002","journal-title":"Environ. Health. Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L121","DOI":"10.1152\/ajplung.00288.2007","article-title":"Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants","volume":"294","author":"Mikerov","year":"2008","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1128\/IAI.01341-06","article-title":"Surfactant Protein A2 (SP-A2) Variants Expressed in CHO Cells Stimulate Phagocytosis of Pseudomonas aeruginosa More than Do SP-A1 Variants","volume":"75","author":"Mikerov","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2","DOI":"10.14302\/issn.2326-0793.jpgr-12-207","article-title":"Differences in the alveolar macrophage proteome in transgenic mice expressing human SP-A1 and SP-AJ","volume":"1","author":"Phelps","year":"2013","journal-title":"Proteom. Genom. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jprot.2014.06.007","article-title":"Sex differences in the acute in vivo effects of different human SP-A variants on the mouse alveolar macrophage proteome","volume":"108","author":"Phelps","year":"2014","journal-title":"J. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13293-017-0158-2","article-title":"SP-A2 contributes to miR-NA-mediated sex differences in response to oxidative stress: Pro-inflammatory, anti-apoptotic, and anti-oxidant pathways are involved","volume":"8","author":"Noutsios","year":"2017","journal-title":"Biol. Sex Differ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.3389\/fimmu.2019.01960","article-title":"Differential Impact of Co-expressed SP-A1\/SP-A2 Protein on AM miRNome; Sex Differences","volume":"10","author":"Thorenoor","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"141410","DOI":"10.1172\/jci.insight.141410","article-title":"Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice","volume":"5","author":"Phelps","year":"2020","journal-title":"JCI Insight"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.3389\/fimmu.2018.02404","article-title":"Survival of Surfactant Protein-A1 and SP-A2 Transgenic Mice After Klebsiella pneumoniae Infection, Exhibits Sex-, Gene-, and Variant Specific Differences; Treatment with Surfactant Protein Improves Survival","volume":"9","author":"Thorenoor","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-018-0723-1","article-title":"Differential effects of innate immune variants of surfactant protein-A1 (SFTPA1) and SP-A2 (SFTPA2) in airway function after Klebsiella pneumoniae infection and sex dif-ferences","volume":"19","author":"Thorenoor","year":"2018","journal-title":"Respir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2741\/3935","article-title":"Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury","volume":"17","author":"Silveyra","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev.physiol.60.1.365","article-title":"SURFACTANT PROTEINS: Molecular Genetics of Neonatal Pulmonary Diseases","volume":"60","author":"Floros","year":"1998","journal-title":"Annu. Rev. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1900618","DOI":"10.1183\/13993003.00618-2019","article-title":"Donor surfactant protein A2 polymorphism and lung transplant survival","volume":"55","author":"Floros","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gandhi, C.K., Chen, C., Wu, R., Yang, L., Thorenoor, N., Thomas, N.J., Di Angelo, S.L., Spear, D., Keim, G., and Yehya, N. (2020). As-sociation of SNP\u2013SNP interactions of surfactant protein genes with pediatric acute respiratory failure. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041183"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.3389\/fimmu.2018.02256","article-title":"Genetic asso-ciation of pulmonary surfactant protein genes, SFTPA1, SFTPA2, Sftpb, SFTPC, and Sftpd with cystic fibrosis","volume":"9","author":"Lin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3109\/01902148.2011.654045","article-title":"Gonadal hormones and oxidative stress in-teraction differentially affects survival of male and female mice after lung Klebsiella pneumoniae infection","volume":"38","author":"Durrani","year":"2012","journal-title":"Exp. Lung. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.bpj.2021.02.002","article-title":"Hydrating the respiratory tract: An alternative explanation why masks lower severity of COVID-19","volume":"120","author":"Courtney","year":"2021","journal-title":"Biophys. J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Reiman, J.M., Das, B., Sindberg, G.M., Urban, M.D., Hammerlund, M.E.M., Lee, H.B., Spring, K.M., Lyman-Gingerich, J., Generous, A.R., and Koep, T.H. (2018). Humidity as a non-pharmaceutical intervention for influenza A. PLoS ONE, 13.","DOI":"10.1101\/273870"},{"key":"ref_34","first-page":"1043","article-title":"SNP and haplotype interaction models reveal association of surfactant protein gene polymorphisms with hypersensitivity pneu-monitis of Mexican population","volume":"7","author":"Gandhi","year":"2020","journal-title":"Front. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Fainardi, V., Abelli, L., Muscar\u00e0, M., Pisi, G., Principi, N., and Esposito, S. (2021). Update on the Role of High-Flow Nasal Cannula in Infants with Bronchiolitis. Children, 8.","DOI":"10.3390\/children8020066"},{"key":"ref_36","first-page":"3433","article-title":"Clinical Characteristics and Prognosis of COPD Patients Hospitalized with SARS-CoV-Int","volume":"15","author":"Estrada","year":"2020","journal-title":"J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Winck, J., and Scala, R. (2021). Non-invasive respiratory support paths in hospitalized patients with COVID-19: Proposal of an algorithm. Pulmonol.","DOI":"10.1016\/j.pulmoe.2020.12.005"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"529","DOI":"10.4187\/respcare.04577","article-title":"High-Flow Nasal Cannula Oxygen Therapy in Adults: Physiological Benefits, Indication, Clinical Benefits, and Adverse Effects","volume":"61","author":"Nishimura","year":"2016","journal-title":"Respir. Care"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1016\/j.chest.2020.07.013","article-title":"High Flow, Non-invasive ventilation and Awake (non-intubation) Proning in Covid-19 Patients with Respiratory Failure","volume":"158","author":"Raoof","year":"2020","journal-title":"Chest"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1001\/jama.2016.2711","article-title":"Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: A randomized clinical trial","volume":"315","author":"Vaquero","year":"2016","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/S2213-2600(16)30093-5","article-title":"Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: A post-hoc analysis of a randomised trial","volume":"4","author":"Frat","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"168","DOI":"10.5578\/tt.69807","article-title":"High flow nasal cannula in COVID-19: A literature review","volume":"68","year":"2020","journal-title":"Tuberk. Toraks."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s12630-020-01740-2","article-title":"High-flow nasal cannula for acute hypoxemic respiratory failure in patients with COVID-19: Systematic reviews of effec-tiveness and its risks of aerosolization, dispersion, and infection transmission","volume":"67","author":"Agarwal","year":"2020","journal-title":"Can. J. Anesth."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1753466620963016","DOI":"10.1177\/1753466620963016","article-title":"Oxygen therapy via high flow nasal cannula in severe respiratory failure caused by Sars-Cov-2 infection: A real-life observa-tional study","volume":"14","author":"Procopio","year":"2020","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1056\/NEJMoa1503326","article-title":"High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure","volume":"372","author":"Frat","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1152\/japplphysiol.00584.2016","article-title":"Nasal high flow reduces dead space","volume":"122","author":"Feng","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1152\/japplphysiol.00934.2014","article-title":"Nasal high flow clears ana-tomical dead space in upper airway models","volume":"118","author":"Celik","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.4187\/respcare.04028","article-title":"Effect of Very-High-Flow Nasal Therapy on Airway Pressure and End-Expiratory Lung Impedance in Healthy Volunteers","volume":"60","author":"Parke","year":"2015","journal-title":"Respir. Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4187\/respcare.01963","article-title":"Hyperoxic Acute Lung Injury","volume":"58","author":"Kallet","year":"2013","journal-title":"Respir. Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"196","DOI":"10.4187\/respcare.02239","article-title":"Oxygen in Respiratory Care: A Personal Perspective from 40 Years in the Field","volume":"58","author":"Pierson","year":"2012","journal-title":"Respir. Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1001\/jama.2020.6266","article-title":"Rates of co-infection between SARS-CoV-2 and other respiratory patho-gens","volume":"323","author":"Kim","year":"2020","journal-title":"JAMA"},{"key":"ref_52","first-page":"1","article-title":"Is the role of lung innate immune molecules, SP-A1 and SP-A2, and of the alveolar macrophage being overlooked in COVID-19 diverse outcomes","volume":"33","author":"Floros","year":"2020","journal-title":"Pneumon"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Tekos, F., Skaperda, Z., Goutzourelas, N., Phelps, D.S., Floros, J., and Kouretas, D. (2020). The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection. 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