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1. A toxicology study of Csf2ra complementation and pulmonary macrophage transplantation therapy of hereditary PAP in mice

Author

Arumugam, Paritha, Carey, Brenna C., Wikenheiser-Brokamp, Kathryn A., Krischer, Jeffrey, Wessendarp, Matthew, Shima, Kenjiro, Chalk, Claudia, Stock, Jennifer, Ma, Yan, Black, Diane, Imbrogno, Michelle, Collins, Margaret, Kalenda Yombo, Dan Justin, Sakthivel, Haripriya, Suzuki, Takuji, Lutzko, Carolyn, Cancelas, Jose A., Adams, Michelle, Hoskins, Elizabeth, Lowe-Daniels, Dawn, Reeves, Lilith, Kaiser, Anne, and Trapnell, Bruce C.

Published
2024
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3. Human inherited CCR2 deficiency underlies progressive polycystic lung disease

Author

Neehus, Anna-Lena, Carey, Brenna, Landekic, Marija, Panikulam, Patricia, Deutsch, Gail, Ogishi, Masato, Arango-Franco, Carlos A., Philippot, Quentin, Modaresi, Mohammadreza, Mohammadzadeh, Iraj, Corcini Berndt, Melissa, Rinchai, Darawan, Le Voyer, Tom, Rosain, Jérémie, Momenilandi, Mana, Martin-Fernandez, Marta, Khan, Taushif, Bohlen, Jonathan, Han, Ji Eun, Deslys, Alexandre, Bernard, Mathilde, Gajardo-Carrasco, Tania, Soudée, Camille, Le Floc’h, Corentin, Migaud, Mélanie, Seeleuthner, Yoann, Jang, Mi-Sun, Nikolouli, Eirini, Seyedpour, Simin, Begueret, Hugues, Emile, Jean-François, Le Guen, Pierre, Tavazzi, Guido, Colombo, Costanza Natalia Julia, Marzani, Federico Capra, Angelini, Micol, Trespidi, Francesca, Ghirardello, Stefano, Alipour, Nasrin, Molitor, Anne, Carapito, Raphael, Mazloomrezaei, Mohsen, Rokni-Zadeh, Hassan, Changi-Ashtiani, Majid, Brouzes, Chantal, Vargas, Pablo, Borghesi, Alessandro, Lachmann, Nico, Bahram, Seiamak, Crestani, Bruno, Fayon, Michael, Galode, François, Pahari, Susanta, Schlesinger, Larry S., Marr, Nico, Bogunovic, Dusan, Boisson-Dupuis, Stéphanie, Béziat, Vivien, Abel, Laurent, Borie, Raphael, Young, Lisa R., Deterding, Robin, Shahrooei, Mohammad, Rezaei, Nima, Parvaneh, Nima, Craven, Daniel, Gros, Philippe, Malo, Danielle, Sepulveda, Fernando E., Nogee, Lawrence M., Aladjidi, Nathalie, Trapnell, Bruce C., Casanova, Jean-Laurent, and Bustamante, Jacinta

Published
2024
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4. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial

Author

Cremer, Paul C, Abbate, Antonio, Hudock, Kristin, McWilliams, Carla, Mehta, Jinesh, Chang, Steven Y, Sheng, Calvin C, Van Tassell, Benjamin, Bonaventura, Aldo, Vecchié, Alessandra, Carey, Brenna, Wang, Qiuqing, Wolski, Katherine E, Rajendram, Prabalini, Duggal, Abhijit, Wang, Tisha S, Paolini, John F, Trapnell, Bruce C, group, MASH-COVID study, Gladish, Deborah, Myers, Karen, Kuramochi, Yuki, Sewell, Christina, Balog, Craig, Sweeny, Denise Kosty, Kandrac, Jill, Spencer, Stephanie, Goyanes, Alice, Sahoo, Debasis, Dugar, Siddharth, Prada, Robier Aguillon, Nichols, Dave, Celiberti, Jeannie, Partisano, Annie, Fang, Fang, Coehlo, Jennifer, Perrin, Randy, Mandell, Brian, Gordon, Steven, Wiedemann, Herbert, Young, James, Greer, Joan, Ho, Ai-Chen, Ladd, Any, Mihalick, Virginia, Montpetit, Alison, O'Brine, Joyce, Owen, Catherine, Pal, Mary, Priday, Anna, Sedhai, Yub Raj, Wohlford, George, Hummel, Nicole, and Korbee, Leslie

Subjects
Lung, Pneumonia, Pneumonia & Influenza, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, MASH-COVID study group
Abstract

BackgroundIn patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation.MethodsThis investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514.FindingsBetween May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups.InterpretationThere was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed.FundingKiniksa Pharmaceuticals.

Published
2021

6. MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn’s Disease

Author

Dillman, Jonathan R, primary, Tkach, Jean A, additional, Fletcher, Joel G, additional, Bruining, David H, additional, Lu, Aiming, additional, Kugathasan, Subra, additional, Alazraki, Adina L, additional, Knight-Scott, Jack, additional, Stidham, Ryan W, additional, Adler, Jeremy, additional, Trapnell, Bruce C, additional, Swanson, Scott D, additional, Fei, Lin, additional, Qian, Lucia, additional, Towbin, Alexander J, additional, Kocaoglu, Murat, additional, Anton, Christopher G, additional, Imbus, Rebecca A, additional, Dudley, Jonathan A, additional, and Denson, Lee A, additional

Published
2024
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8. Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis.

Author

McCarthy, Cormac, Lee, Elinor, Bridges, James P, Sallese, Anthony, Suzuki, Takuji, Woods, Jason C, Bartholmai, Brian J, Wang, Tisha, Chalk, Claudia, Carey, Brenna C, Arumugam, Paritha, Shima, Kenjiro, Tarling, Elizabeth J, and Trapnell, Bruce C

Subjects
Macrophages, Alveolar, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, Lung Diseases, Pulmonary Alveolar Proteinosis, Cholesterol, Lipids, Pulmonary Surfactants, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Surface-Active Agents, Tomography, X-Ray Computed, Gene Expression Profiling, Bronchoalveolar Lavage, Aged, Middle Aged, Female, Cytokine Receptor Common beta Subunit, Macrophages, Alveolar, Inbred C57BL, Knockout, Tomography, X-Ray Computed, Lung, Rare Diseases, Autoimmune Disease, Clinical Research, 2.1 Biological and endogenous factors, Respiratory, Cardiovascular
Abstract

Pulmonary alveolar proteinosis (PAP) is a syndrome of reduced GM-CSF-dependent, macrophage-mediated surfactant clearance, dysfunctional foamy alveolar macrophages, alveolar surfactant accumulation, and hypoxemic respiratory failure for which the pathogenetic mechanism is unknown. Here, we examine the lipids accumulating in alveolar macrophages and surfactant to define the pathogenesis of PAP and evaluate a novel pharmacotherapeutic approach. In PAP patients, alveolar macrophages have a marked increase in cholesterol but only a minor increase in phospholipids, and pulmonary surfactant has an increase in the ratio of cholesterol to phospholipids. Oral statin therapy is associated with clinical, physiological, and radiological improvement in autoimmune PAP patients, and ex vivo statin treatment reduces cholesterol levels in explanted alveolar macrophages. In Csf2rb-/- mice, statin therapy reduces cholesterol accumulation in alveolar macrophages and ameliorates PAP, and ex vivo statin treatment increases cholesterol efflux from macrophages. These results support the feasibility of statin as a novel pathogenesis-based pharmacotherapy of PAP.

Published
2018

9. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial

Author

Gladish, Deborah, Myers, Karen, Kuramochi, Yuki, Sewell, Christina, Balog, Craig, Kosty Sweeny, Denise, Kandrac, Jill, Spencer, Stephanie, Goyanes, Alice, Sahoo, Debasis, Dugar, Siddharth, Aguillon Prada, Robier, Nichols, Dave, Celiberti, Jeannie, Partisano, Annie, Fang, Fang, Coehlo, Jennifer, Perrin, Randy, Mandell, Brian, Gordon, Steven, Wiedemann, Herbert, Young, James, Greer, Joan, Ho, Ai-Chen, Ladd, Any, Mihalick, Virginia, Montpetit, Alison, O'Brine, Joyce, Owen, Catherine, Pal, Mary, Priday, Anna, Raj Sedhai, Yub, Wohlford, George, Hummel, Nicole, Korbee, Leslie, Cremer, Paul C, Abbate, Antonio, Hudock, Kristin, McWilliams, Carla, Mehta, Jinesh, Chang, Steven Y, Sheng, Calvin C, Van Tassell, Benjamin, Bonaventura, Aldo, Vecchié, Alessandra, Carey, Brenna, Wang, Qiuqing, Wolski, Katherine E, Rajendram, Prabalini, Duggal, Abhijit, Wang, Tisha S, Paolini, John F, and Trapnell, Bruce C

Published
2021
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10. Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study

Author

Kugathasan, Subra, Denson, Lee A, Walters, Thomas D, Kim, Mi-Ok, Marigorta, Urko M, Schirmer, Melanie, Mondal, Kajari, Liu, Chunyan, Griffiths, Anne, Noe, Joshua D, Crandall, Wallace V, Snapper, Scott, Rabizadeh, Shervin, Rosh, Joel R, Shapiro, Jason M, Guthery, Stephen, Mack, David R, Kellermayer, Richard, Kappelman, Michael D, Steiner, Steven, Moulton, Dedrick E, Keljo, David, Cohen, Stanley, Oliva-Hemker, Maria, Heyman, Melvin B, Otley, Anthony R, Baker, Susan S, Evans, Jonathan S, Kirschner, Barbara S, Patel, Ashish S, Ziring, David, Trapnell, Bruce C, Sylvester, Francisco A, Stephens, Michael C, Baldassano, Robert N, Markowitz, James F, Cho, Judy, Xavier, Ramnik J, Huttenhower, Curtis, Aronow, Bruce J, Gibson, Greg, Hyams, Jeffrey S, and Dubinsky, Marla C

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Inflammatory Bowel Disease, Prevention, Autoimmune Disease, Clinical Research, Digestive Diseases, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Adalimumab, Adolescent, Anti-Inflammatory Agents, Non-Steroidal, Child, Cohort Studies, Crohn Disease, Disease Progression, Female, Gastrointestinal Microbiome, Humans, Infliximab, Intestinal Obstruction, Male, Prognosis, Propensity Score, Prospective Studies, Risk Assessment, Severity of Illness Index, Tumor Necrosis Factor-alpha, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundStricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown.MethodsWe did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk.FindingsBetween Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%.InterpretationOur findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy.FundingCrohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.

Published
2017

11. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study

Author

De Luca, Giacomo, Cavalli, Giulio, Campochiaro, Corrado, Della-Torre, Emanuel, Angelillo, Piera, Tomelleri, Alessandro, Boffini, Nicola, Tentori, Stefano, Mette, Francesca, Farina, Nicola, Rovere-Querini, Patrizia, Ruggeri, Annalisa, D'Aliberti, Teresa, Scarpellini, Paolo, Landoni, Giovanni, De Cobelli, Francesco, Paolini, John F, Zangrillo, Alberto, Tresoldi, Moreno, Trapnell, Bruce C, Ciceri, Fabio, and Dagna, Lorenzo

Published
2020
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12. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients

Author

Campo, Ilaria, primary, Carey, Brenna C., additional, Paracchini, Elena, additional, Kadija, Zamir, additional, De Silvestri, Annalisa, additional, Rodi, Giuseppe, additional, De Amici, Mara, additional, Torre, Cristina, additional, Zorzetto, Michele, additional, Griese, Matthias, additional, Meloni, Federica, additional, Corsico, Angelo Guido, additional, Trapnell, Bruce C., additional, and Mariani, Francesca, additional

Published
2023
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13. Inhaled molgramostim therapy for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP): a plain language summary of the IMPALA trial

Author

Trapnell, Bruce C.

Abstract

Plain Language SummaryWhat is this summary about?This is a plain language summary of a late-stage clinical trial called IMPALA, originally reported in The New England Journal of Medicine. The IMPALA trial studied a drug called molgramostim nebulizer solution (molgramostim) to see how well it worked and how safe it was in patients with autoimmune pulmonary alveolar proteinosis (aPAP). Normally, tiny air sacs (alveoli) in the lungs are covered by a thin layer of an oily substance called surfactant that helps to keep them open. In aPAP, surfactant builds up and clogs alveoli making it difficult to breathe. Inhaled molgramostim helps to reduce the amount of surfactant clogging the alveoli.What were the results of the trial?After 24 weeks of treatment, patients who received molgramostim every day had better oxygen transfer into blood than patients who received an inactive substance (placebo). Patients’ sense of well-being and quality of life was improved more with daily molgramostim than placebo. The amount of surfactant in the lungs measured using scans and the number of whole-lung lavages (lung washes) patients required were lower with daily molgramostim than placebo. The number of medical problems (adverse events) was similar in patients who received molgramostim and placebo except for chest pain, which was more common with molgramostim.What do the results of the trial mean?The IMPALA trial demonstrated that molgramostim is a promising treatment option for people with aPAP.

Published
2024
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17. Cell Therapy for Lung Diseases. Report from an NIH–NHLBI Workshop, November 13–14, 2012

Author

Matthay, Michael A, Anversa, Piero, Bhattacharya, Jahar, Burnett, Bruce K, Chapman, Harold A, Hare, Joshua M, Hei, Derek J, Hoffman, Andrew M, Kourembanas, Stella, McKenna, David H, Ortiz, Luis A, Ott, Harald C, Tente, William, Thébaud, Bernard, Trapnell, Bruce C, Weiss, Daniel J, Yuan, Jason X-J, and Blaisdell, Carol J

Subjects
Rare Diseases, Cardiovascular, Cancer, Heart Disease, Lung, Lung Cancer, Respiratory, Good Health and Well Being, Biomedical Research, Cell- and Tissue-Based Therapy, Humans, Lung Diseases, National Heart, Lung, and Blood Institute (U.S.), United States, mesenchymal stromal (stem) cells, epithelial and endothelial progenitor cells, lung stem cells, Medical and Health Sciences, Respiratory System
Abstract

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13-14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy.

Published
2013

18. Contributors

Author

Abel, Robin, primary, Abman, Steven H., additional, Alton, Eric, additional, Ambruso, Daniel R., additional, Anderson, William Carl, additional, Balakrishnan, Karthik, additional, Balfour-Lynn, Ian Michael, additional, Bamford, Anna, additional, Bar-Yoseph, Ronen, additional, Berman-Rosenzweig, Erika, additional, Bhatla, Deepika, additional, Blatter, Joshua A., additional, Boesch, R. Paul, additional, Bruzoni, Matias, additional, Bush, Andrew, additional, Bye, Michael, additional, Carlsen, Kai Håkon, additional, Chang, Anne B., additional, Chao, Stephanie D., additional, Chatwin, Michelle, additional, Chaudhari, Bimal Pankaj, additional, Chitty, Lyn, additional, Collins, Nicola, additional, Cooper, Dan M., additional, Corren, Jonathan, additional, Cotton, Robin T., additional, Coverstone, Andrea, additional, Crowley, Suzanne, additional, Cunningham, Steve, additional, Cutting, Garry R., additional, Czovek, Dorottya, additional, Daley, Charles L., additional, Davies, Gwyneth, additional, Davies, Jane C., additional, de Alarcòn, Alessandro, additional, DeBoer, Emily M., additional, De Guzman, Marietta Morales, additional, Dell, Sharon D., additional, Deterding, Robin, additional, Deutsch, Gail H., additional, Devadason, Sunalene, additional, Fox Ditcham, William Graham, additional, Dorsey, Jill, additional, Ducharme, Francine M., additional, Engelhardt, John, additional, Everard, Mark L., additional, Fan, Leland L., additional, Faro, Albert, additional, Ferkol, Thomas, additional, Fleming, Louise, additional, Fonceca, Angela Mary, additional, Ganatra, Hammad A., additional, Garcia, Amy Michelle, additional, Gozal, David, additional, Gray, Diane, additional, Greenough, Anne, additional, Griesenbach, Uta, additional, Grigg, Jonathan, additional, Hagood, James S., additional, Hammer, Jürg, additional, Hamvas, Aaron, additional, Harcourt, Jonny, additional, Hauk, Pia J., additional, Heininger, Ulrich, additional, Henderson, Alexander John, additional, Henry, Marianna M., additional, Hewitt, Richard J., additional, Highsmith, Heather Young, additional, Hillman, Noah H., additional, Hoch, Heather Ellen, additional, Hyun, Jeong S., additional, Isa, Mas Suhaila, additional, Jaffé, Adam, additional, Jennings, Lance C., additional, Jobe, Alan H., additional, Kamdar, Ankur A., additional, Katira, Bhushan, additional, Kavanagh, Brian P., additional, Kemp, James, additional, Kercsmar, Carolyn M., additional, Kheirandish-Gozal, Leila, additional, King, Wilson, additional, Kingma, Paul, additional, Knight-Madden, Jennifer, additional, Knutsen, Alan Paul, additional, Kornecki, Alik, additional, Krishnan, Usha, additional, Kurland, Geoffrey, additional, Simon Lam, Hugh, additional, Langston, Claire, additional, Lee, Ada, additional, Leigh, Margaret W., additional, Lesser, Daniel, additional, Lloyd, Clare M., additional, Mandalakas, Anna Maria, additional, Marostica, Paulo J.C., additional, Martiniano, Stacey L., additional, Maybee, Jennifer, additional, McDowell, Karen M., additional, Michelson, Peter, additional, Miller, Aaron Samuel, additional, Miller, Claire Kane, additional, Mirza, Ayesha, additional, Murdoch, David R., additional, Newth, Christopher J.L., additional, Nicholson, Andrew Gordon, additional, Nick, Jerry A., additional, Nicolais, Christina J., additional, Noah, Terry L., additional, Nogee, Lawrence M., additional, Noyes, Blakeslee, additional, Numa, Andrew H., additional, Nyquist, Ann-Christine, additional, O'Brodovich, Hugh, additional, Ochs, Matthias, additional, Olin, J. Tod, additional, Olsen, Øystein, additional, Owens, Catherine, additional, Panitch, Howard B., additional, Pasterkamp, Hans, additional, Payne, Donald, additional, Pentiuk, Scott, additional, Prager, Jeremy, additional, Praud, Jean-Paul, additional, Prayle, Andrew P., additional, Prentice, Bernadette, additional, Putnam, Philip E., additional, Quittner, Alexandra L., additional, Radom-Aizik, Shlomit, additional, Rao, Suchitra, additional, Rathore, Mobeen, additional, Redding, Gregory J., additional, Rutter, Michael, additional, Saez-Flores, Estefany, additional, Saglani, Sejal, additional, Schneider, Rayfel, additional, Schowengerdt, Kenneth O., additional, Scotta, Marcelo C., additional, Semple, Thomas, additional, Sherlock, Laurie, additional, Singh, Ram N., additional, Slavin, Raymond G., additional, Sly, Peter, additional, Smevik, Bjarne, additional, Smith, Keely Garrett, additional, Spahr, Jonathan, additional, Stark, James M., additional, Starke, Jeffrey R., additional, Stein, Renato T., additional, Stillwell, Paul C., additional, Stokes, Dennis C., additional, Swarr, Daniel T., additional, Sweet, Stuart Charles, additional, Szefler, Stanley James, additional, Tambyah, Paul, additional, Tan, Christelle Xian-Ting, additional, Temprano, James, additional, Thorson, Chad M., additional, Trapnell, Bruce C., additional, Varisco, Brian Michael, additional, Vece, Timothy J., additional, Vyas, Harish G., additional, Wakeman, Ruth, additional, Wallis, Colin, additional, Wambach, Jennifer, additional, Weiner, Daniel J., additional, Werno, Anja M., additional, Wert, Susan E., additional, Whitsett, Jeffrey A., additional, Wilmott, Robert William, additional, Wood, Robert E., additional, Wootten, Christopher Todd, additional, Wright, Marie, additional, Wright, Sarah, additional, Yeung, Rae S.M., additional, Yoshida, Takeshi, additional, Young, Carolyn, additional, Young, Lisa R., additional, Zar, Heather J., additional, Zeitlin, Pamela Leslie, additional, and Zielinski, David, additional

Published
2019
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21. Pulmonary alveolar proteinosis

Author

Trapnell, Bruce C., Nakata, Koh, Bonella, Francesco, Campo, Ilaria, Griese, Matthias, Hamilton, John, Wang, Tisha, Morgan, Cliff, Cottin, Vincent, and McCarthy, Cormac

Published
2019
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28. A Peer-to-Peer Blacklisting Strategy Inspired by Leukocyte-Endothelium Interaction

Author

Trapnell, Bruce C., Jr., Hutchison, David, editor, Kanade, Takeo, editor, Kittler, Josef, editor, Kleinberg, Jon M., editor, Mattern, Friedemann, editor, Mitchell, John C., editor, Naor, Moni, editor, Nierstrasz, Oscar, editor, Pandu Rangan, C., editor, Steffen, Bernhard, editor, Sudan, Madhu, editor, Terzopoulos, Demetri, editor, Tygar, Dough, editor, Vardi, Moshe Y., editor, Weikum, Gerhard, editor, Jacob, Christian, editor, Pilat, Marcin L., editor, Bentley, Peter J., editor, and Timmis, Jonathan I., editor

Published
2005
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34. Pulmonary macrophage transplantation therapy

Author

Suzuki, Takuji, Arumugam, Paritha, Sakagami, Takuro, Lachmann, Nico, Chalk, Claudia, Sallese, Anthony, Abe, Shuichi, Trapnell, Cole, Carey, Brenna, Moritz, Thomas, Malik, Punam, Lutzko, Carolyn, Wood, Robert E., and Trapnell, Bruce C.

Subjects
Bone marrow -- Transplantation, Pulmonary alveolar proteinosis -- Development and progression -- Care and treatment, Macrophages -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Bone-marrow transplantation is an effective cell therapy but requires myeloablation, which increases infection risk and mortality. Recent lineage-tracing studies documenting that resident macrophage populations self-maintain independently of haematological progenitors prompted us to consider organ-targeted, cell- specific therapy. Here, using granulocytemacrophage colony-stimulating factor (GM-CSF) receptor -β- deficient ([Csf2rb.sup.-/-]) mice that develop a myeloid cell disorder identical to hereditary pulmonary alveolar proteinosis (hPAP) in children with CSF2RA or CSF2RB mutations, we show that pulmonary macrophage transplantation (PMT) of either wild-type or Csf2rb-gene-corrected macrophages without myeloablation was safe and well- tolerated and that one administration corrected the lung disease, secondary systemic manifestations and normalized disease-related biomarkers, and prevented disease-specific mortality. PMT-derived alveolar macrophages persisted for at least one year as did therapeutic effects. Our findings identify mechanisms regulating alveolar macrophage population size in health and disease, indicate that GM-CSF is required for phenotypic determination of alveolar macrophages, and support translation of PMT as the first specific therapy for children with hPAP., Mutations in CSF2RA or CSF2RB, encoding GM-CSF receptor α or β, respectively, cause hPAP by impairing GM-CSF-dependent surfactant clearance by alveolar macrophages, resulting in progressive surfactant accumulation in alveoli and [...]

Published
2014
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35. Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial

Author

Cid, Maria C, primary, Unizony, Sebastian H, additional, Blockmans, Daniel, additional, Brouwer, Elisabeth, additional, Dagna, Lorenzo, additional, Dasgupta, Bhaskar, additional, Hellmich, Bernhard, additional, Molloy, Eamonn, additional, Salvarani, Carlo, additional, Trapnell, Bruce C, additional, Warrington, Kenneth J, additional, Wicks, Ian, additional, Samant, Manoj, additional, Zhou, Teresa, additional, Pupim, Lara, additional, and Paolini, John F, additional

Published
2022
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36. A murine model of hereditary pulmonary alveolar proteinosis caused by homozygous Csf2ra gene disruption

Author

Shima, Kenjiro, primary, Arumugam, Paritha, additional, Sallese, Anthony, additional, Horio, Yuko, additional, Ma, Yan, additional, Trapnell, Cole, additional, Wessendarp, Matthew, additional, Chalk, Claudia, additional, McCarthy, Cormac, additional, Carey, Brenna C., additional, Trapnell, Bruce C., additional, and Suzuki, Takuji, additional

Published
2022
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37. Contributors

Author

Adams, Lewis, primary, Adler, Dan Elie, additional, Agusti, Alvar, additional, Akoumianaki, Evangelia, additional, Alberg, Anthony J., additional, Albertine, Kurt H., additional, Alexander, Barbara D., additional, Alfille, Paul H., additional, Anantham, Devanand, additional, Arenberg, Douglas A., additional, Ayas, Najib T., additional, Bagchi, Aranya, additional, Balmes, John Randolph, additional, Banaei, Niaz, additional, Barnett, Christopher F., additional, Baughman, Robert P., additional, Becklake, Margaret R., additional, Benditt, Joshua O., additional, Benowitz, Neal L., additional, Bhakta, Nirav R., additional, Bhave, Anant D., additional, Blanc, Paul D., additional, Bleecker, Eugene R., additional, Bove, Alfred A., additional, Bradley, T. Douglas, additional, Brambilla, Elisabeth, additional, Broaddus, V. Courtney, additional, Brochard, Laurent, additional, Brock, Malcolm V., additional, Brown, Kevin K., additional, Brunetta, Paul G., additional, Cadranel, Jacques, additional, Celli, Bartolome, additional, Chan, Edward D., additional, Channick, Richard N., additional, Chastre, Jean, additional, Cheng, Guang-Shing, additional, Chin, Kelly, additional, Chung, Kian Fan, additional, Clerici, Christine, additional, Colby, Thomas V., additional, Collard, Harold R., additional, Cool, Carlyne D., additional, Cordier, Jean-François, additional, Cordioli, Ricardo Luiz, additional, Corte, Tamera J., additional, Cottin, Vincent, additional, Courey, Mark S., additional, Cowie, Robert L., additional, Crothers, Kristina, additional, Curley, Gerard F., additional, Daley, Charles L., additional, Davis, J. Lucian, additional, De Marco, Teresa, additional, Deresinski, Stanley C., additional, Deroose, Christophe, additional, Dobbs, Leland G., additional, Dooms, Christophe, additional, Downey, Gregory P., additional, du Bois, Roland M., additional, Dulohery, Megan M., additional, Effros, Richard M., additional, Eisner, Mark D., additional, Elicker, Brett M., additional, Ernst, Armin, additional, Ernst, Joel D., additional, Fahy, John V., additional, Fedullo, Peter F., additional, Feller-Kopman, David, additional, Fenster, Brett E., additional, Fingerlin, Tasha E., additional, Fontenot, Andrew P., additional, Frankel, Stephen K., additional, Garcia, Joe G.N., additional, Gebhart, G.F., additional, Gilstrap, Daniel Lee, additional, Girard, Nicolas, additional, Gladwin, Mark T., additional, Glenny, Robb W., additional, Gold, Warren M., additional, Gotway, Michael B., additional, Grasselli, Giacomo, additional, Greenberg, James M., additional, Griffith, David E., additional, Gruden, James F., additional, Han, MeiLan King, additional, Henderson, William, additional, Hill, Nicholas S., additional, Hoover, Wynton, additional, Hopewell, Philip C., additional, Horan-Saullo, Jennifer L., additional, Horner, Richard L., additional, Huang, Laurence, additional, Huchon, Gérard, additional, Inoue, Yoshikazu, additional, Iseman, Michael D., additional, Jackson, James E., additional, Jakubzick, Claudia V., additional, Janssen, Julius P., additional, Jett, James R., additional, Jones, Kirk, additional, Judson, Marc A., additional, Kato-Maeda, Midori, additional, Kavanagh, Brian P., additional, Keshavjee, Shaf, additional, Kim, Kami, additional, Kimoff, R. John, additional, King, Talmadge E., additional, Klein, Jeffrey S., additional, Koth, Laura L., additional, Kotloff, Robert M., additional, Kraft, Monica, additional, Küpeli, Elif, additional, Laffey, John G., additional, Lapinsky, Stephen E., additional, Lazarus, Stephen C., additional, Lee, Frances Eun-Hyung, additional, Lee, Jarone, additional, Lee, Y.C. 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Published
2016
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44. Human treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression

Author

Mueller, Christian, Chulay, Jeffrey D., Trapnell, Bruce C., Humphries, Margaret, Carey, Brenna, Sandhaus, Robert A., McElvaney, Noel G., Messina, Louis, Tang, Qiushi, Rouhani, Farshid N., Campbell-Thompson, Martha, Fu, Ann Dongtao, Yachnis, Anthony, Knop, David R., Ye, Guo-jie, Brantly, Mark, Calcedo, Roberto, Somanathan, Suryanarayan, Richman, Lee P., Vonderheide, Robert H., Hulme, Maigan A., Brusko, Todd M., Wilson, James M., and Flotte, Terence R.

Subjects
Gene expression -- Research, Gene therapy -- Research, Virus diseases -- Genetic aspects, Health care industry
Abstract

Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss [...]

Published
2013

48. The Alveolar Lipidome in Pulmonary Alveolar Proteinosis. A New Target for Therapeutic Development?

Author

Trapnell, Bruce C. and McCarthy, Cormac

Subjects
Male, Pathology, Vesicular Transport Proteins, Apoptosis, Critical Care and Intensive Care Medicine, 0302 clinical medicine, Medicine, Child, 0303 health sciences, Pulmonary Surfactant-Associated Protein B, Pulmonary Surfactant-Associated Protein A, Genetic Diseases, X-Linked, Middle Aged, Lipidome, Pulmonary Surfactant-Associated Protein C, Cholesterol, Leukemia, Myeloid, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Child, Preschool, Phosphatidylcholines, Female, Cholesterol Esters, Pulmonary alveolar proteinosis, Bronchoalveolar Lavage Fluid, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary Surfactant-Associated Proteins, Adolescent, Methionine-tRNA Ligase, Phosphatidylserines, Pulmonary Alveolar Proteinosis, Ceramides, Autoimmune Diseases, Young Adult, 03 medical and health sciences, Humans, 030304 developmental biology, Sphingolipids, business.industry, Phosphatidylethanolamines, Editorials, Infant, Lipid Metabolism, medicine.disease, 030228 respiratory system, Case-Control Studies, Lipidomics, Phenylalanine-tRNA Ligase, business
Published
2019

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