1,265 results on '"Lederer, David"'
Search Results
2. Sociology’s “One Law”: Moral Statistics, Modernity, Religion, and German Nationalism in the Suicide Studies of Adolf Wagner and Alexander von Oettingen
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Lederer, David
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- 2013
3. The Politics of Suicide: Historical Perspectives on Suicidology before Durkheim. An Introduction
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Brancaccio, Maria Teresa, Engstrom, Eric J., and Lederer, David
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- 2013
4. Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.
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Peljto, Anna L, Blumhagen, Rachel Z, Walts, Avram D, Cardwell, Jonathan, Powers, Julia, Corte, Tamera J, Dickinson, Joanne L, Glaspole, Ian, Moodley, Yuben P, Vasakova, Martina Koziar, Bendstrup, Elisabeth, Davidsen, Jesper R, Borie, Raphael, Crestani, Bruno, Dieude, Philippe, Bonella, Francesco, Costabel, Ulrich, Gudmundsson, Gunnar, Donnelly, Seamas C, Egan, Jim, Henry, Michael T, Keane, Michael P, Kennedy, Marcus P, McCarthy, Cormac, McElroy, Aoife N, Olaniyi, Joshua A, O'Reilly, Katherine MA, Richeldi, Luca, Leone, Paolo M, Poletti, Venerino, Puppo, Francesco, Tomassetti, Sara, Luzzi, Valentina, Kokturk, Nurdan, Mogulkoc, Nesrin, Fiddler, Christine A, Hirani, Nikhil, Jenkins, R Gisli, Maher, Toby M, Molyneaux, Philip L, Parfrey, Helen, Braybrooke, Rebecca, Blackwell, Timothy S, Jackson, Peter D, Nathan, Steven D, Porteous, Mary K, Brown, Kevin K, Christie, Jason D, Collard, Harold R, Eickelberg, Oliver, Foster, Elena E, Gibson, Kevin F, Glassberg, Marilyn, Kass, Daniel J, Kropski, Jonathan A, Lederer, David, Linderholm, Angela L, Loyd, Jim, Mathai, Susan K, Montesi, Sydney B, Noth, Imre, Oldham, Justin M, Palmisciano, Amy J, Reichner, Cristina A, Rojas, Mauricio, Roman, Jesse, Schluger, Neil, Shea, Barry S, Swigris, Jeffrey J, Wolters, Paul J, Zhang, Yingze, Prele, Cecilia MA, Enghelmayer, Juan I, Otaola, Maria, Ryerson, Christopher J, Salinas, Mauricio, Sterclova, Martina, Gebremariam, Tewodros H, Myllärniemi, Marjukka, Carbone, Roberto G, Furusawa, Haruhiko, Hirose, Masaki, Inoue, Yoshikazu, Miyazaki, Yasunari, Ohta, Ken, Ohta, Shin, Okamoto, Tsukasa, Kim, Dong Soon, Pardo, Annie, Selman, Moises, Aranda, Alvaro U, Park, Moo Suk, Park, Jong Sun, Song, Jin Woo, Molina-Molina, Maria, Planas-Cerezales, Lurdes, Westergren-Thorsson, Gunilla, Smith, Albert V, Manichaikul, Ani W, and Kim, John S
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Autoimmune Disease ,Lung ,Rare Diseases ,Genetics ,Human Genome ,Prevention ,Precision Medicine ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Humans ,Idiopathic Pulmonary Fibrosis ,Whole Genome Sequencing ,Exome ,whole-genome sequencing ,interstitial lung disease ,TOPMed ,genetic association studies ,telomerase ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
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- 2023
5. Subphenotypes of frailty in lung transplant candidates.
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Diamond, Joshua, Anderson, Michaela, Benvenuto, Luke, Gao, Ying, Wang, Ping, Arcasoy, Selim, Lederer, David, Hays, Steven, Venado, Aida, Kolaitis, Nicholas, Leard, Lorianna, Shah, Rupal, Kleinhenz, Mary, Golden, Jeffrey, Betancourt, Legna, Oyster, Michelle, Brown, Melanie, Zaleski, Derek, Medikonda, Nikhila, Kalman, Laurel, Balar, Priya, Patel, Shreena, Calabrese, Daniel, Christie, Jason, Calfee, Carolyn, Kukreja, Jasleen, Singer, Jonathan, Delucchi, Kevin, and Greenland, John
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clinical research/practice ,epidemiology ,lung transplantation/pulmonology ,patient survival ,recipient selection ,Humans ,Frailty ,Pilot Projects ,Cohort Studies ,Biomarkers ,Lung Transplantation - Abstract
Heterogeneous frailty pathobiology might explain the inconsistent associations observed between frailty and lung transplant outcomes. A Subphenotype analysis could refine frailty measurement. In a 3-center pilot cohort study, we measured frailty by the Short Physical Performance Battery, body composition, and serum biomarkers reflecting causes of frailty. We applied latent class modeling for these baseline data. Next, we tested class construct validity with disability, waitlist delisting/death, and early postoperative complications. Among 422 lung transplant candidates, 2 class model fit the best (P = .01). Compared with Subphenotype 1 (n = 333), Subphenotype 2 (n = 89) was characterized by systemic and innate inflammation (higher IL-6, CRP, PTX3, TNF-R1, and IL-1RA); mitochondrial stress (higher GDF-15 and FGF-21); sarcopenia; malnutrition; and lower hemoglobin and walk distance. Subphenotype 2 had a worse disability and higher risk of waitlist delisting or death (hazards ratio: 4.0; 95% confidence interval: 1.8-9.1). Of the total cohort, 257 underwent transplant (Subphenotype 1: 196; Subphenotype 2: 61). Subphenotype 2 had a higher need for take back to the operating room (48% vs 28%; P = .005) and longer posttransplant hospital length of stay (21 days [interquartile range: 14-33] vs 18 days [14-28]; P = .04). Subphenotype 2 trended toward fewer ventilator-free days, needing more postoperative extracorporeal membrane oxygenation and dialysis, and higher need for discharge to rehabilitation facilities (P ≤ .20). In this early phase study, we identified biological frailty Subphenotypes in lung transplant candidates. A hyperinflammatory, sarcopenic Subphenotype seems to be associated with worse clinical outcomes.
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- 2023
6. The Origins of Sectarianism in Early Modern Ireland (review)
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Lederer, David
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- 2007
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7. Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study
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Bacharier, Leonard B., Maspero, Jorge F., Katelaris, Constance H., Fiocchi, Alessandro G., Gagnon, Remi, De Mir, Ines, Guilbert, Theresa W., Jackson, Daniel J., Staudinger, Heribert W., Laws, Elizabeth, Mannent, Leda P., Akinlade, Bolanle, Maloney, Jennifer, Tawo, Kelsey, Khokhar, Faisal A., Li, Ning, Hardin, Megan, Abdulai, Raolat M., Lederer, David J., Robinson, Lacey B., Bacharier, Leonard B, Maspero, Jorge F, Katelaris, Constance H, Fiocchi, Alessandro G, de Mir, Ines, Guilbert, Theresa W, Jackson, Daniel J, Staudinger, Heribert W, Mannent, Leda P, Khokhar, Faisal A, Abdulai, Raolat M, Lederer, David J, and Robinson, Lacey B
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- 2024
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8. Witchcraft and Inquisition in Early Modern Venice by Jonathan Seitz (review)
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Lederer, David
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- 2014
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9. Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma
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Bacharier, Leonard B., Pavord, Ian D., Maspero, Jorge F., Jackson, Daniel J., Fiocchi, Alessandro G., Mao, Xuezhou, Jacob-Nara, Juby A., Deniz, Yamo, Laws, Elizabeth, Mannent, Leda P., Amin, Nikhil, Akinlade, Bolanle, Staudinger, Heribert W., Lederer, David J., and Hardin, Megan
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- 2024
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10. Rare coding variants in CHRNB2 reduce the likelihood of smoking
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Rajagopal, Veera M., Watanabe, Kyoko, Mbatchou, Joelle, Ayer, Ariane, Quon, Peter, Sharma, Deepika, Kessler, Michael D., Praveen, Kavita, Gelfman, Sahar, Parikshak, Neelroop, Otto, Jacqueline M., Bao, Suying, Chim, Shek Man, Pavlopoulos, Elias, Avbersek, Andreja, Kapoor, Manav, Chen, Esteban, Jones, Marcus B., Leblanc, Michelle, Emberson, Jonathan, Collins, Rory, Torres, Jason, Morales, Pablo Kuri, Tapia-Conyer, Roberto, Alegre, Jesus, Berumen, Jaime, Shuldiner, Alan R., Balasubramanian, Suganthi, Abecasis, Gonçalo R., Kang, Hyun M., Marchini, Jonathan, Stahl, Eli A., Jorgenson, Eric, Sanchez, Robert, Liedtke, Wolfgang, Anderson, Matthew, Cantor, Michael, Lederer, David, Baras, Aris, and Coppola, Giovanni
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- 2023
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11. Reformation and the German Territorial State: Upper Franconia, 1300–1630 (review)
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Lederer, David
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- 2011
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12. German Histories in the Age of Reformations, 1400–1650 (review)
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Lederer, David
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- 2011
13. Dupilumab sustains lung function improvements in patients with moderate-to-severe asthma
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Papi, Alberto, Castro, Mario, Corren, Jonathan, Pavord, Ian D., Tohda, Yuji, Altincatal, Arman, Pandit-Abid, Nami, Laws, Elizabeth, Akinlade, Bolanle, Mannent, Leda P., Gall, Rebecca, Jacob-Nara, Juby A., Deniz, Yamo, Rowe, Paul J., Lederer, David J., and Hardin, Megan
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- 2024
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14. Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE Study
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Bacharier, Leonard B., Guilbert, Theresa W., Katelaris, Constance H., Deschildre, Antoine, Phipatanakul, Wanda, Liu, Dongfang, Altincatal, Arman, Mannent, Leda P., Amin, Nikhil, Laws, Elizabeth, Akinlade, Bolanle, Jacob-Nara, Juby A., Deniz, Yamo, Rowe, Paul J., Lederer, David J., and Hardin, Megan
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- 2024
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15. Madness in Seventeenth-Century Autobiography (review)
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Lederer, David
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- 2009
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16. Die doppelte Konfessionalisierung in Irland: Konflikt und Koexistenz im 16. Jahrhundert und in der ersten Halfte des 17. Jahrhunderts (review)
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Lederer, David
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- 2004
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17. Development of the Lung Transplant Frailty Scale (LT-FS)
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Singer, Jonathan P., Christie, Jason D., Diamond, Joshua M., Anderson, Michaela A., Benvenuto, Luke A., Gao, Ying, Arcasoy, Selim M., Lederer, David J., Calabrese, Daniel, Wang, Ping, Hays, Steven R., Kukreja, Jasleen, Venado, Aida, Kolaitis, Nicholas A., Leard, Lorriana E., Shah, Rupal J., Kleinhenz, Mary Ellen, Golden, Jeffrey, Betancourt, Legna, Oyster, Michelle, Zaleski, Derek, Adler, Joe, Kalman, Laurel, Balar, Priya, Patel, Shreena, Medikonda, Nikhila, Koons, Brittany, Tevald, Michael, Covinsky, Kenneth E., Greenland, John R., and Katz, Patti K.
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- 2023
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18. Dupilumab pharmacokinetics and effect on type 2 biomarkers in children with moderate-to-severe asthma
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Jackson, Daniel J., Bacharier, Leonard B., Phipatanakul, Wanda, Sher, Lawrence, Domingo, Christian, Papadopoulos, Nikolaos, Modena, Brian, Li, Ning, Xia, Changming, Kamal, Mohamed A., Dillon, Myles, Wolfe, Kelley, Gall, Rebecca, Amin, Nikhil, Mannent, Leda P., Laws, Elizabeth, Rowe, Paul J., Jacob-Nara, Juby A., Deniz, Yamo, Lederer, David J., Hardin, Megan, and Xu, Christine
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- 2023
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19. Skeletal muscle adiposity and outcomes in candidates for lung transplantation: a lung transplant body composition cohort study.
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Anderson, Michaela R, Easthausen, Imaani, Gallagher, Grace, Udupa, Jayaram, Tong, Yubing, Torigian, Drew, Diamond, Joshua Matthew, Porteous, Mary Katherine, Palmer, Scott M, Snyder, Laurie D, Benvenuto, Luke, Aversa, Meghan, Arcasoy, Selim, Greenland, John R, Hays, Steven R, Kukreja, Jasleen, Cantu, Edward, Kim, John Shinn, Gallagher, Dympna, Baldwin, Matthew R, Barr, R Graham, Lederer, David J, Christie, Jason D, and Singer, Jonathan Paul
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Abdominal Wall ,Thigh ,Muscle ,Skeletal ,Humans ,Lung Diseases ,Tomography ,X-Ray Computed ,Treatment Outcome ,Lung Transplantation ,Survival Rate ,Risk Assessment ,Cohort Studies ,Aged ,Middle Aged ,Waiting Lists ,Female ,Male ,Adiposity ,Walk Test ,clinical epidemiology ,imaging/CT MRI etc ,lung transplantation ,Transplantation ,Organ Transplantation ,Lung ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,imaging ,CT MRI etc ,Clinical Sciences ,Respiratory System - Abstract
CT measurement of body composition may improve lung transplant candidate selection. We assessed whether skeletal muscle adipose deposition on abdominal and thigh CT scans was associated with 6 min walk distance (6MWD) and wait-list survival in lung transplant candidates. Each ½-SD decrease in abdominal muscle attenuation (indicating greater lipid content) was associated with 14 m decrease in 6MWD (95% CI -20 to -8) and 20% increased risk of death or delisting (95% CI 10% to 40%). Each ½-standard deviation decrease in thigh muscle attenuation was associated with 15 m decrease in 6MWD (95% CI -21 to -10). CT imaging may improve candidate risk stratification.
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- 2020
20. Subphenotypes of frailty in lung transplant candidates
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Singer, Jonathan P., Calfee, Carolyn S., Delucchi, Kevin, Diamond, Joshua M., Anderson, Michaela A., Benvenuto, Luke A., Gao, Ying, Wang, Ping, Arcasoy, Selim M., Lederer, David J., Hays, Steven R., Kukreja, Jasleen, Venado, Aida, Kolaitis, Nicholas A., Leard, Lorianna E., Shah, Rupal J., Kleinhenz, Mary Ellen, Golden, Jeffrey, Betancourt, Legna, Oyster, Michelle, Brown, Melanie, Zaleski, Derek, Medikonda, Nikhila, Kalman, Laurel, Balar, Priya, Patel, Shreena, Calabrese, Daniel R., Greenland, John R., and Christie, Jason D.
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- 2023
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21. A Systematically Derived Exposure Assessment Instrument for Chronic Hypersensitivity Pneumonitis
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Barnes, Hayley, Morisset, Julie, Molyneaux, Philip, Westall, Glen, Glaspole, Ian, Collard, Harold R, Collaborators, CHP Exposure Assessment, Antoniou, Katerina M, Barber, Christopher M, Behr, Jürgen, Bonella, Francesco, Corte, Tamera, Costabel, Ulrich, Cottin, Vincent, Crestani, Bruno, Dalphin, Jean-Charles, Flaherty, Kevin R, Goh, Nicole, Johannson, Kerri A, Kondoh, Yasuhiro, Lederer, David, Lee, Joyce, Maher, Toby M, Martinez, Fernando J, Morell, Ferran, Noth, Imre, Raghu, Ganesh, Renzoni, Elisabetta, Richeldi, Luca, Ryerson, Christopher J, Ryu, Jay H, Salisbury, Margaret L, Singh, Sheetu, Selman, Moises, Strek, Mary E, Tarlo, Susan M, Tomassetti, Sara, Vancheri, Carlo, Vasakova, Martina, Wolters, Paul, and Wells, Athol
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Management of diseases and conditions ,7.3 Management and decision making ,Alveolitis ,Extrinsic Allergic ,Chronic Disease ,Consensus ,Humans ,Lung ,Tomography ,X-Ray Computed ,extrinsic allergic alveolitis ,hypersensitivity pneumonitis ,interstitial lung diseases ,CHP Exposure Assessment Collaborators ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundChronic hypersensitivity pneumonitis (CHP) is an immune-mediated interstitial lung disease (ILD) caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis.MethodsA list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, interquartile range = 0 on a 5-point Likert scale (1, strongly agree; 2, tend to agree; 3, neither agree nor disagree; 4, disagree; 5, strongly disagree).ResultsIn two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by patients with ILD for readability and usability.ConclusionsThis Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.
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- 2020
22. Associations of Serum Adipokines With Subclinical Interstitial Lung Disease Among Community-Dwelling Adults The Multi-Ethnic Study of Atherosclerosis (MESA)
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Kim, John S, Anderson, Michaela R, Podolanczuk, Anna J, Kawut, Steven M, Allison, Matthew A, Raghu, Ganesh, Hinckley-Stuckovsky, Karen, Hoffman, Eric A, Tracy, Russell P, Barr, R Graham, Lederer, David J, and Giles, Jon T
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Atherosclerosis ,Prevention ,Clinical Research ,Lung ,Aetiology ,2.1 Biological and endogenous factors ,Adipokines ,Adiponectin ,Aged ,Asymptomatic Diseases ,Body Mass Index ,Cohort Studies ,Female ,Humans ,Independent Living ,Leptin ,Lung Diseases ,Interstitial ,Male ,Middle Aged ,Obesity ,Resistin ,Smoking ,Tomography ,X-Ray Computed ,Vital Capacity ,adipokine ,chest imaging ,epidemiology ,interstitial lung disease ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundAdipokines have inflammatory and fibrotic properties that may be critical in interstitial lung disease (ILD). We examined associations of serum adipokine levels with CT imaging-based measures of subclinical ILD and lung function among community-dwelling adults.MethodsA subset of the original Multi-Ethnic Study of Atherosclerosis cohort (n = 1,968) had adiponectin, leptin, and resistin measured during follow-up visits (2002-2005). We used regression models to examine associations of adiponectin, leptin, and resistin levels with (1) high-attenuation areas (HAAs) from CT scans (2004-2005, n = 1,144), (2) interstitial lung abnormalities (ILAs) from CT scans (2010-2012, n = 872), and (3) FVC from spirometry (2004-2006, n = 1,446). We used -(1/HAA2), which we denoted with H, to model HAA as our outcome to meet model assumptions.ResultsHigher adiponectin was associated with lower HAA on CT imaging among adults with a BMI ≥ 25 kg/m2 (P for BMI interaction = .07). Leptin was more strongly associated with ILA among never smokers compared with ever smokers (P for smoking interaction = .004). For every 1-SD increment of log-transformed leptin, the percent predicted FVC was 3.8% lower (95% CI, -5.0 to -2.5). Higher serum resistin levels were associated with greater HAA on CT in a fully adjusted model. For every 1-SD increment of log-transformed resistin there was an increase in H of 14.8 (95% CI, 3.4-26.3).ConclusionsHigher adiponectin levels were associated with lower HAA on CT imaging among adults with a higher BMI. Higher leptin and resistin levels were associated with lower FVC and greater HAA, respectively.
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- 2020
23. Efficiency in Lung Transplant Allocation Strategies
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Zou, Jingjing, Lederer, David J., and Rabinowitz, Daniel
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Statistics - Applications ,Statistics - Methodology - Abstract
Currently in the United States, lung transplantations are allocated to candidates according to the candidates' Lung Allocation Score (LAS). The LAS is an ad-hoc ranking system for patients' priorities of transplantation. The goal of this study is to develop a framework for improving patients' life expectancy over the LAS based on a comprehensive modeling of the lung transplantation waiting list. Patients and organs are modeled as arriving according to Poisson processes, patients' health status evolving a waiting time inhomogeneous Markov process until death or transplantation, with organ recipient's expected post-transplant residual life depending on waiting time and health status at transplantation. Under allocation rules satisfying minimal fairness requirements, the long-term average expected life converges, and its limit is a natural standard for comparing allocation strategies. Via the Hamilton-Jacobi-Bellman equations, upper bounds for the limiting average expected life are derived as a function of organ availability. Corresponding to each upper bound is an allocable set of (time, state) pairs at which patients would be optimally transplanted. The allocable set expands monotonically as organ availability increases, which motivates the development of an allocation strategy that leads to long-term expected life close to the upper bound. Simulation studies are conducted with model parameters estimated from national lung transplantation data. Results suggest that compared to the LAS, the proposed allocation strategy could provide a 7.7% increase in average total life. We further extended the results to the the allocation and matching of multiple organ types., Comment: 36 pages of main text, 10 figures
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- 2018
24. Adipose tissue quantification and primary graft dysfunction after lung transplantation: The Lung Transplant Body Composition study.
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Anderson, Michaela R, Udupa, Jayaram K, Edwin, Ethan, Diamond, Joshua M, Singer, Jonathan P, Kukreja, Jasleen, Hays, Steven R, Greenland, John R, Ferrante, Anthony, Lippel, Matthew, Blue, Tatiana, McBurnie, Amika, Oyster, Michelle, Kalman, Laurel, Rushefski, Melanie, Wu, Caiyun, Pednekar, Gargi, Liu, Wen, Arcasoy, Selim, Sonett, Joshua, D'Ovidio, Frank, Bacchetta, Matthew, Newell, John D, Torigian, Drew, Cantu, Edward, Farber, Donna L, Giles, Jon T, Tong, Yubing, Palmer, Scott, Ware, Lorraine B, Hancock, Wayne W, Christie, Jason D, and Lederer, David J
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Adipose Tissue ,Humans ,Obesity ,Tomography ,X-Ray Computed ,Organ Size ,Lung Transplantation ,Risk Assessment ,Prospective Studies ,Body Composition ,Aged ,Middle Aged ,Female ,Male ,Primary Graft Dysfunction ,adipose tissue ,inflammation ,lung transplantation ,obesity ,primary graft dysfunction ,Clinical Research ,Organ Transplantation ,Nutrition ,Rare Diseases ,Lung ,Transplantation ,Prevention ,Cancer ,Cardiovascular ,Cardiorespiratory Medicine and Haematology ,Surgery - Abstract
BackgroundObesity is associated with an increased risk of primary graft dysfunction (PGD) after lung transplantation. The contribution of specific adipose tissue depots is unknown.MethodsWe performed a prospective cohort study of adult lung transplant recipients at 4 U.S. transplant centers. We measured cross-sectional areas of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on chest and abdominal computed tomography (CT) scans and indexed each measurement to height.2 We used logistic regression to examine the associations of adipose indices and adipose classes with grade 3 PGD at 48 or 72 hours, and Cox proportional hazards models to examine survival. We used latent class analyses to identify the patterns of adipose distribution. We examined the associations of adipose indices with plasma biomarkers of obesity and PGD.ResultsA total of 262 and 117 subjects had available chest CT scans and underwent protocol abdominal CT scans, respectively. In the adjusted models, a greater abdominal SAT index was associated with an increased risk of PGD (odds ratio 1.9, 95% CI 1.02-3.4, p = 0.04) but not with survival time. VAT indices were not associated with PGD risk or survival time. A greater abdominal SAT index correlated with greater pre- and post-transplant leptin (r = 0.61, p < 0.001, and r = 0.44, p < 0.001), pre-transplant IL-1RA (r = 0.25, p = 0.04), and post-transplant ICAM-1 (r = 0.25, p = 0.04). We identified 3 latent patterns of adiposity. The class defined by high thoracic and abdominal SAT had the greatest risk of PGD.ConclusionsSubcutaneous, but not visceral, adiposity is associated with an increased risk of PGD after lung transplantation.
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- 2019
25. Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis.
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Hobbs, Brian D, Putman, Rachel K, Araki, Tetsuro, Nishino, Mizuki, Gudmundsson, Gunnar, Gudnason, Vilmundur, Eiriksdottir, Gudny, Zilhao Nogueira, Nuno Rodrigues, Dupuis, Josée, Xu, Hanfei, O'Connor, George T, Manichaikul, Ani, Nguyen, Jennifer, Podolanczuk, Anna J, Madahar, Purnema, Rotter, Jerome I, Lederer, David J, Barr, R Graham, Rich, Stephen S, Ampleford, Elizabeth J, Ortega, Victor E, Peters, Stephen P, O'Neal, Wanda K, Newell, John D, Bleecker, Eugene R, Meyers, Deborah A, Allen, Richard J, Oldham, Justin M, Ma, Shwu-Fan, Noth, Imre, Jenkins, R Gisli, Maher, Toby M, Hubbard, Richard B, Wain, Louise V, Fingerlin, Tasha E, Schwartz, David A, Washko, George R, Rosas, Ivan O, Silverman, Edwin K, Hatabu, Hiroto, Cho, Michael H, and Hunninghake, Gary M
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Humans ,Lung Diseases ,Interstitial ,Genetic Predisposition to Disease ,beta Karyopherins ,TATA Box Binding Protein-Like Proteins ,Case-Control Studies ,Polymorphism ,Single Nucleotide ,Aged ,Middle Aged ,Female ,Male ,Promoter Regions ,Genetic ,Idiopathic Pulmonary Fibrosis ,Genome-Wide Association Study ,Mucin-5B ,Genetic Loci ,SNP ,genetics ,genome-wide association study ,idiopathic pulmonary fibrosis ,interstitial lung abnormalities ,Genetics ,Lung ,Rare Diseases ,Chronic Obstructive Pulmonary Disease ,Clinical Research ,Prevention ,Human Genome ,Autoimmune Disease ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Respiratory ,Medical and Health Sciences ,Respiratory System - Abstract
Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P
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- 2019
26. A nonlinear relationship between visceral adipose tissue and frailty in adult lung transplant candidates.
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Anderson, Michaela R, Kolaitis, Nicholas A, Gao, Ying, Kukreja, Jasleen, Greenland, John, Hays, Steven, Wolters, Paul, Golden, Jeff, Diamond, Joshua, Palmer, Scott, Arcasoy, Selim, Udupa, Jayaram, Christie, Jason D, Lederer, David J, and Singer, Jonathan P
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Humans ,Tomography ,X-Ray Computed ,Body Mass Index ,Prognosis ,Lung Transplantation ,Incidence ,Risk Factors ,Follow-Up Studies ,Prospective Studies ,Cross-Sectional Studies ,Adult ,Aged ,Middle Aged ,United States ,Female ,Male ,Subcutaneous Fat ,Intra-Abdominal Fat ,Obesity ,Abdominal ,Frailty ,clinical research/practice ,lung transplantation/pulmonology ,obesity ,quality of life ,Lung ,Clinical Research ,Organ Transplantation ,Obesity ,Aging ,Prevention ,Transplantation ,clinical research ,practice ,lung transplantation ,pulmonology ,Medical and Health Sciences ,Surgery - Abstract
Frailty is a state of decreased physiologic reserve associated with poor outcomes before and after lung transplantation. Obesity, particularly central obesity characterized by excess proinflammatory visceral adipose tissue (VAT), is associated with incident frailty in middle-aged and older adults. The association between VAT and frailty in advanced lung disease, however, is unknown. In two, nonoverlapping multicenter cohorts of adults listed for lung transplantation, we measured VAT area on bioelectrical impedance assay (BIA) in one cohort and cross-sectional VAT and subcutaneous adipose tissue (SAT) areas on abdominal computed tomography (CT) in the other. We identified a nonlinear relationship between greater VAT by BIA and frailty. In fully adjusted piecewise regression models, every 20 cm2 increase in VAT area was associated with 50% increased odds of frailty in subjects with high VAT (95% CI 1.2-1.9, P
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- 2019
27. Low Dose Carbon Monoxide Exposure in Idiopathic Pulmonary Fibrosis Produces a CO Signature Comprised of Oxidative Phosphorylation Genes.
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Casanova, Nancy, Zhou, Tong, Gonzalez-Garay, Manuel, Rosas, Ivan, Goldberg, Hilary, Ryter, Stefan, Collard, Harold, El-Chemaly, Souheil, Flaherty, Kevin, Hunninghake, Gary, Lasky, Joseph, Lederer, David, Machado, Roberto, Martinez, Fernando, Noth, Imre, Raghu, Ganesh, Choi, Augustine, and Garcia, Joe
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Administration ,Inhalation ,Aged ,Carbon Monoxide ,Case-Control Studies ,Dose-Response Relationship ,Drug ,Female ,Gene Expression Profiling ,Gene Expression Regulation ,Genetic Markers ,Humans ,Idiopathic Pulmonary Fibrosis ,Leukocytes ,Mononuclear ,Male ,Middle Aged ,Oligonucleotide Array Sequence Analysis ,Oxidative Phosphorylation ,Precision Medicine ,Transcriptome ,Treatment Outcome ,Up-Regulation - Abstract
Compelling preclinical studies indicate that low-dose carbon monoxide (CO) abrogates experimental lung fibrosis. We recently reported the results of a multicenter, double-blinded, clinical trial of inhaled CO in patients with idiopathic pulmonary fibrosis (IPF). Identifying no significantly changes in metalloproteinase-7 (MMP7) serum concentration, or secondary endpoints of physiologic measurements, hospitalization, death, or patient-reported outcomes. In the present study, we evaluated the effect of low dose CO exposure (100-200 ppm) for 12 weeks on genome-wide gene expression in peripheral blood mononuclear cells (PBMC) derived from these IPF study subjects. We conducted transcriptome profiling on 38 IPF subjects with time points available at 0, 12, and 24 weeks. Total RNA isolated from PBMCs was hybridized onto the Affymetrix Human Gene 2.0 ST Array. We identified 621 genes significantly upregulated in the 24-week CO exposed group compared with the 12-week. Pathway analysis demonstrated association with Oxidative Phosphorylation (adjusted P
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- 2019
28. Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction
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Hanania, Nicola A., Castro, Mario, Bateman, Eric, Pavord, Ian D., Papi, Alberto, FitzGerald, J. Mark, Maspero, Jorge F., Katelaris, Constance H., Singh, Dave, Daizadeh, Nadia, Altincatal, Arman, Pandit-Abid, Nami, Soler, Xavier, Siddiqui, Shahid, Laws, Elizabeth, Jacob-Nara, Juby A., Rowe, Paul J., Lederer, David J., Hardin, Megan, and Deniz, Yamo
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- 2023
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29. AERIFY-1/-2: 2 phase 3 randomised controlled trials of itepekimab in former smokers with moderate-to-severe COPD
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Rabe, Klaus F., primary, Martinez, Fernando J., additional, Bhatt, Surya P., additional, Kawayama, Tomotaka, additional, Cosio, Borja G., additional, Mroz, Robert M., additional, Boomsma, Maarten M., additional, Goulaouic, Helene, additional, Nivens, Michael C., additional, Djandji, Michel, additional, Soler, Xavier, additional, Liu, Ying, additional, Kosloski, Matthew P., additional, Xu, Christine R., additional, Amin, Nikhil, additional, Staudinger, Heribert, additional, Lederer, David J., additional, and Abdulai, Raolat M., additional
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- 2024
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30. Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis
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Moore, Camille, Blumhagen, Rachel Z, Yang, Ivana V, Walts, Avram, Powers, Julie, Walker, Tarik, Bishop, Makenna, Russell, Pamela, Vestal, Brian, Cardwell, Jonathan, Markin, Cheryl R, Mathai, Susan K, Schwarz, Marvin I, Steele, Mark P, Lee, Joyce, Brown, Kevin K, Loyd, James E, Crapo, James D, Silverman, Edwin K, Cho, Michael H, James, Judith A, Guthridge, Joel M, Cogan, Joy D, Kropski, Jonathan A, Swigris, Jeffrey J, Bair, Carol, Kim, Dong Soon, Ji, Wonjun, Kim, Hocheol, Song, Jin Woo, Maier, Lisa A, Pacheco, Karin A, Hirani, Nikhil, Poon, Azin S, Li, Feng, Jenkins, R Gisli, Braybrooke, Rebecca, Saini, Gauri, Maher, Toby M, Molyneaux, Philip L, Saunders, Peter, Zhang, Yingze, Gibson, Kevin F, Kass, Daniel J, Rojas, Mauricio, Sembrat, John, Wolters, Paul J, Collard, Harold R, Sundy, John S, O’Riordan, Thomas, Strek, Mary E, Noth, Imre, Ma, Shwu-Fan, Porteous, Mary K, Kreider, Maryl E, Patel, Namrata B, Inoue, Yoshikazu, Hirose, Masaki, Arai, Toru, Akagawa, Shinobu, Eickelberg, Oliver, Fernandez, Isis Enlil, Behr, Jürgen, Mogulkoc, Nesrin, Corte, Tamera J, Glaspole, Ian, Tomassetti, Sara, Ravaglia, Claudia, Poletti, Venerino, Crestani, Bruno, Borie, Raphael, Kannengiesser, Caroline, Parfrey, Helen, Fiddler, Christine, Rassl, Doris, Molina-Molina, Maria, Machahua, Carlos, Worboys, Ana Montes, Gudmundsson, Gunnar, Isaksson, Helgi J, Lederer, David J, Podolanczuk, Anna J, Montesi, Sydney B, Bendstrup, Elisabeth, Danchel, Vivi, Selman, Moises, Pardo, Annie, Henry, Michael T, Keane, Michael P, Doran, Peter, Vašáková, Martina, Sterclova, Martina, Ryerson, Christopher J, Wilcox, Pearce G, Okamoto, Tsukasa, Furusawa, Haruhiko, Miyazaki, Yasunari, Laurent, Geoffrey, Baltic, Svetlana, and Prele, Cecilia
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Human Genome ,Autoimmune Disease ,Clinical Research ,Lung ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,ATP-Binding Cassette Transporters ,Case-Control Studies ,Cellular Senescence ,DNA Helicases ,Exoribonucleases ,Female ,GTPase-Activating Proteins ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,High-Throughput Nucleotide Sequencing ,Host-Pathogen Interactions ,Humans ,Idiopathic Pulmonary Fibrosis ,Logistic Models ,Male ,Mucin-5B ,Promoter Regions ,Genetic ,Pulmonary Surfactant-Associated Protein A ,Pulmonary Surfactant-Associated Protein C ,RNA ,Sequence Analysis ,DNA ,Telomerase ,Telomere-Binding Proteins ,targeted resequencing ,idiopathic pulmonary fibrosis ,genetic variants ,rare variants ,disease risk alleles ,Medical and Health Sciences ,Respiratory System - Abstract
Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.
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- 2019
31. Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep
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Cade, Brian E, Chen, Han, Stilp, Adrienne M, Louie, Tin, Ancoli-Israel, Sonia, Arens, Raanan, Barfield, Richard, Below, Jennifer E, Cai, Jianwen, Conomos, Matthew P, Evans, Daniel S, Frazier-Wood, Alexis C, Gharib, Sina A, Gleason, Kevin J, Gottlieb, Daniel J, Hillman, David R, Johnson, W Craig, Lederer, David J, Lee, Jiwon, Loredo, Jose S, Mei, Hao, Mukherjee, Sutapa, Patel, Sanjay R, Post, Wendy S, Purcell, Shaun M, Ramos, Alberto R, Reid, Kathryn J, Rice, Ken, Shah, Neomi A, Sofer, Tamar, Taylor, Kent D, Thornton, Timothy A, Wang, Heming, Yaffe, Kristine, Zee, Phyllis C, Hanis, Craig L, Palmer, Lyle J, Rotter, Jerome I, Stone, Katie L, Tranah, Gregory J, Wilson, James G, Sunyaev, Shamil R, Laurie, Cathy C, Zhu, Xiaofeng, Saxena, Richa, Lin, Xihong, and Redline, Susan
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Genetics ,Lung ,Sleep Research ,Clinical Research ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Cell Adhesion Molecules ,Neuronal ,Computational Biology ,Extracellular Matrix Proteins ,Female ,Gene Regulatory Networks ,Genetic Variation ,Genome-Wide Association Study ,Hexokinase ,Humans ,Hypoxia ,Interleukin-18 Receptor alpha Subunit ,Male ,Middle Aged ,NLR Family ,Pyrin Domain-Containing 3 Protein ,Nerve Tissue Proteins ,Oxygen ,Oxyhemoglobins ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Reelin Protein ,Serine Endopeptidases ,Sleep ,Sleep Apnea Syndromes ,Young Adult ,Developmental Biology - Abstract
Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
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- 2019
32. Dupilumab Reduces Oral Corticosteroid Use in Patients With Corticosteroid-Dependent Severe Asthma: An Analysis of the Phase 3, Open-Label Extension TRAVERSE Trial
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Sher, Lawrence D., Wechsler, Michael E., Rabe, Klaus F., Maspero, Jorge F., Daizadeh, Nadia, Mao, Xuezhou, Ortiz, Benjamin, Mannent, Leda P., Laws, Elizabeth, Ruddy, Marcella, Pandit-Abid, Nami, Jacob-Nara, Juby A., Gall, Rebecca, Rowe, Paul J., Deniz, Yamo, Lederer, David J., and Hardin, Megan
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- 2022
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33. EFFICIENCY IN LUNG TRANSPLANT ALLOCATION STRATEGIES
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Zou, Jingjing, Lederer, David J., and Rabinowitz, Daniel
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- 2020
34. Frailty phenotypes and mortality after lung transplantation: A prospective cohort study.
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Singer, Jonathan P, Diamond, Joshua M, Anderson, Michaela R, Katz, Patricia P, Covinsky, Ken, Oyster, Michelle, Blue, Tatiana, Soong, Allison, Kalman, Laurel, Shrestha, Pavan, Arcasoy, Selim M, Greenland, John R, Shah, Lori, Kukreja, Jasleen, Blumenthal, Nancy P, Easthausen, Imaani, Golden, Jeffrey A, McBurnie, Amika, Cantu, Ed, Sonett, Joshua, Hays, Steven, Robbins, Hilary, Raza, Kashif, Bacchetta, Matthew, Shah, Rupal J, D'Ovidio, Frank, Venado, Aida, Christie, Jason D, and Lederer, David J
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Humans ,Lung Diseases ,Postoperative Complications ,Prognosis ,Lung Transplantation ,Severity of Illness Index ,Survival Rate ,Risk Factors ,Follow-Up Studies ,Prospective Studies ,Phenotype ,Quality of Life ,Aged ,Middle Aged ,Female ,Male ,Frailty ,clinical research/practice ,lung transplantation/pulmonology ,patient survival ,recipient selection ,Lung ,Organ Transplantation ,Clinical Research ,Transplantation ,Good Health and Well Being ,clinical research ,practice ,lung transplantation ,pulmonology ,Medical and Health Sciences ,Surgery - Abstract
Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score-adjusted Cox models. We calculated postestimation marginalized standardized risks for 1-year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1- and 4-year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6-36.0 and aHR 3.8; 95%CI: 1.8-8.0, respectively). Each 1-point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08-1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%-21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1-13.2) but not over longer follow-up. Preoperative frailty is associated with an increased risk of death after lung transplantation.
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- 2018
35. Identification of Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis. An International Modified Delphi Survey
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Morisset, Julie, Johannson, Kerri A, Jones, Kirk D, Wolters, Paul J, Collard, Harold R, Walsh, Simon LF, Ley, Brett, Antoniou, Katerina M, Assayag, Deborah, Behr, Juergen, Bonella, Francesco, Brown, Kevin K, Collins, Bridget F, Cormier, Yvon, Corte, Tamera J, Costabel, Ulrich, Danoff, Sonye K, de Boer, Kaïssa, Fernandez Perez, Evans R, Flaherty, Kevin R, Goh, Nicole SL, Glaspole, Ian, Jones, Mark G, Kondoh, Yasuhiro, Kreuter, Michael, Lacasse, Yves, Lancaster, Lisa H, Lederer, David J, Lee, Joyce S, Maher, Toby M, Martinez, Fernando J, Meyer, Keith C, Mooney, Joshua J, Gall, Xavier Muñoz, Noble, Paul W, Noth, Imre, Oldham, Justin M, Alberto de Castro Pereira, Carlos, Poletti, Venerino, Selman, Moises, Spagnolo, Paolo, Renzoni, Elisabetta, Richeldi, Luca, Ryerson, Christopher J, Ryu, Jay H, Salisbury, Margaret L, Strek, Mary E, Tomassetti, Sara, Valeyre, Dominique, Vancheri, Carlo, Wijsenbeek, Marlies S, and Wuyts, Wim
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Biomedical and Clinical Sciences ,Clinical Sciences ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Alveolitis ,Extrinsic Allergic ,Chronic Disease ,Consensus ,Delphi Technique ,Female ,Humans ,Internationality ,Male ,Surveys and Questionnaires ,hypersensitivity pneumonitis ,interstitial lung disease ,diagnosis ,Delphi ,HP Delphi Collaborators ,Diagnosis ,Hypersensitivity pneumonitis ,Interstitial Lung Disease ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
RationaleCurrent diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers.ObjectivesWe aimed to identify diagnostic criteria for cHP that reach consensus among international experts.MethodsA 3-round modified Delphi survey was conducted between April and August 2017. Forty-five experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5-point Likert scale. The a priori threshold of consensus was ≥ 75% of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios.Measurements and main resultsConsensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed non-necrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items.ConclusionThis consensus-based approach for the diagnosis of cHP represents a first step towards the development of international guidelines for the diagnosis of cHP.
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- 2018
36. Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant
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Cantu, Edward, Diamond, Joshua M, Suzuki, Yoshikazu, Lasky, Jared, Schaufler, Christian, Lim, Brian, Shah, Rupal, Porteous, Mary, Lederer, David J, Kawut, Steven M, Palmer, Scott M, Snyder, Laurie D, Hartwig, Matthew G, Lama, Vibha N, Bhorade, Sangeeta, Bermudez, Christian, Crespo, Maria, McDyer, John, Wille, Keith, Orens, Jonathan, Shah, Pali D, Weinacker, Ann, Weill, David, Wilkes, David, Roe, David, Hage, Chadi, Ware, Lorraine B, Bellamy, Scarlett L, and Christie, Jason D
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Transplantation ,Acute Respiratory Distress Syndrome ,Rare Diseases ,Organ Transplantation ,Lung ,Good Health and Well Being ,Adult ,Biomarkers ,Cause of Death ,Cohort Studies ,Consensus ,Female ,Graft Rejection ,Graft Survival ,Humans ,Kaplan-Meier Estimate ,Logistic Models ,Lung Transplantation ,Male ,Middle Aged ,Primary Graft Dysfunction ,Proportional Hazards Models ,Reproducibility of Results ,Retrospective Studies ,Risk Assessment ,Severity of Illness Index ,Survival Rate ,Time Factors ,United States ,Young Adult ,Lung Transplant Outcomes Group ,lung transplant ,lung transplant outcomes ,primary graft dysfunction ,Medical and Health Sciences ,Respiratory System - Abstract
RationalePrimary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted.ObjectivesWe sought to determine whether refinements to the 2005 consensus definition could further improve construct validity.MethodsData from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination.Measurements and main resultsA total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P
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- 2018
37. A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis
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Rosas, Ivan O, Goldberg, Hilary J, Collard, Harold R, El-Chemaly, Souheil, Flaherty, Kevin, Hunninghake, Gary M, Lasky, Joseph A, Lederer, David J, Machado, Roberto, Martinez, Fernando J, Maurer, Rie, Teller, Danielle, Noth, Imre, Peters, Elizabeth, Raghu, Ganesh, Garcia, Joe GN, and Choi, Augustine MK
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Autoimmune Disease ,Lung ,Rare Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Respiratory ,Administration ,Inhalation ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Carbon Monoxide ,Carboxyhemoglobin ,Double-Blind Method ,Female ,Forced Expiratory Volume ,Humans ,Idiopathic Pulmonary Fibrosis ,Male ,Middle Aged ,Patient Reported Outcome Measures ,Treatment Outcome ,Vital Capacity ,Young Adult ,carbon monoxide ,idiopathic pulmonary fibrosis ,inhaled therapy ,IPF ,MMP7 ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundPreclinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF).MethodsWe conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. Patients with IPF were randomized to treatment with inhaled CO at 100 to 200 parts per million or to inhaled 21% oxygen for 2 h daily, twice weekly, for 12 weeks. The primary study end point was the difference in change in matrix metalloproteinase-7 (MMP7) serum concentration after 12 weeks of treatment. Secondary end points included pulmonary function test measures, 6-min walk distance, rates of adverse events, acute exacerbation, hospitalization and death, and quality of life measures.ResultsFifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations after 12 weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12, -0.90 ng/mL; 95% CI, -4.18 to 2.38 ng/mL). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death, or patient-reported outcomes. Importantly, no differences in distribution of adverse events were noted between the treatment arms.ConclusionsInhaled CO is well tolerated and can be safely administered to patients with IPF in the ambulatory setting; however, inhaled CO did not result in significant changes in study end points. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials.Trial registryClinicalTrials.gov; No.: NCT01214187; URL: www.clinicaltrials.gov.
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- 2018
38. Clinical Risk Factors and Prognostic Model for Primary Graft Dysfunction after Lung Transplantation in Patients with Pulmonary Hypertension.
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Porteous, Mary K, Lee, James C, Lederer, David J, Palmer, Scott M, Cantu, Edward, Shah, Rupal J, Bellamy, Scarlett L, Lama, Vibha N, Bhorade, Sangeeta M, Crespo, Maria M, McDyer, John F, Wille, Keith M, Localio, A Russell, Orens, Jonathan B, Shah, Pali D, Weinacker, Ann B, Arcasoy, Selim, Wilkes, David S, Ware, Lorraine B, Christie, Jason D, Kawut, Steven M, Diamond, Joshua M, and Lung Transplant Outcomes Group
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Lung Transplant Outcomes Group ,Lung ,Humans ,Hypertension ,Pulmonary ,Obesity ,Body Mass Index ,Prognosis ,Lung Transplantation ,Linear Models ,Logistic Models ,Risk Factors ,Retrospective Studies ,Time Factors ,Adult ,Middle Aged ,Tissue Donors ,United States ,Female ,Male ,Primary Graft Dysfunction ,Young Adult ,lung transplantation ,primary graft dysfunction ,pulmonary hypertension ,Rare Diseases ,Clinical Research ,Cardiovascular ,Transplantation ,Organ Transplantation ,Respiratory ,Good Health and Well Being - Abstract
RationalePulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation.ObjectiveWe evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.MethodsWe conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaO2/FiO2 ≤200 with allograft infiltrates at 48 or 72 hours after transplantation. Donor, recipient, and operative characteristics were evaluated in a multivariable explanatory model. A prognostic model derived using donor and recipient characteristics was then validated in a separate cohort.ResultsIn the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion fraction of inspired oxygen were associated with primary graft dysfunction. Donor obesity was associated with a lower risk for primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1% [95% confidence interval, 85.3-92.8] and 83.3% [95% confidence interval, 78.5-88.2], respectively), but low positive predictive value.ConclusionsSeveral recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value, to rule out high risk for primary graft dysfunction.
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- 2017
39. Blood eosinophils and FeNO are prognostic and predictive biomarkers in childhood asthma
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Bacharier, Leonard B., primary, Pavord, Ian D., additional, Maspero, Jorge F., additional, Jackson, Daniel J., additional, Fiocchi, Alessandro G., additional, Mao, Xuezhou, additional, Jacob-Nara, Juby A., additional, Deniz, Yamo, additional, Laws, Elizabeth, additional, Mannent, Leda P., additional, Amin, Nikhil, additional, Akinlade, Bolanle, additional, Staudinger, Heribert W., additional, Lederer, David J., additional, and Hardin, Megan, additional
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- 2024
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40. Dupilumab Improves Lung Function Parameters in Pediatric Type 2 Asthma: VOYAGE study
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Bacharier, Leonard B., primary, Guilbert, Theresa W., additional, Katelaris, Constance H., additional, Deschildre, Antoine, additional, Phipatanakul, Wanda, additional, Liu, Dongfang, additional, Altincatal, Arman, additional, Mannent, Leda P., additional, Amin, Nikhil, additional, Laws, Elizabeth, additional, Akinlade, Bolanle, additional, Jacob-Nara, Juby A., additional, Deniz, Yamo, additional, Rowe, Paul J., additional, Lederer, David J., additional, and Hardin, Megan, additional
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- 2023
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41. Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study
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Bacharier, Leonard B, primary, Maspero, Jorge F, additional, Katelaris, Constance H, additional, Fiocchi, Alessandro G, additional, Gagnon, Remi, additional, de Mir, Ines, additional, Guilbert, Theresa W, additional, Jackson, Daniel J, additional, Staudinger, Heribert W, additional, Laws, Elizabeth, additional, Mannent, Leda P, additional, Akinlade, Bolanle, additional, Maloney, Jennifer, additional, Tawo, Kelsey, additional, Khokhar, Faisal A, additional, Li, Ning, additional, Hardin, Megan, additional, Abdulai, Raolat M, additional, Lederer, David J, additional, Robinson, Lacey B, additional, Bacharier, Leonard B., additional, Maspero, Jorge F., additional, Katelaris, Constance H., additional, Fiocchi, Alessandro G., additional, De Mir, Ines, additional, Guilbert, Theresa W., additional, Jackson, Daniel J., additional, Staudinger, Heribert W., additional, Mannent, Leda P., additional, Khokhar, Faisal A., additional, Abdulai, Raolat M., additional, Lederer, David J., additional, and Robinson, Lacey B., additional
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- 2023
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42. Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness
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Baldwin, Matthew R, Singer, Jonathan P, Huang, Debbie, Sell, Jessica, Gonzalez, Wendy C, Pollack, Lauren R, Maurer, Mathew S, D'Ovidio, Frank F, Bacchetta, Matthew, Sonett, Joshua R, Arcasoy, Selim M, Shah, Lori, Robbins, Hilary, Hays, Steven R, Kukreja, Jasleen, Greenland, John R, Shah, Rupal J, Leard, Lorriana, Morrell, Matthew, Gries, Cynthia, Katz, Patricia P, Christie, Jason D, Diamond, Joshua M, and Lederer, David J
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Aging ,Clinical Research ,Lung ,Rehabilitation ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,7.1 Individual care needs ,Management of diseases and conditions ,Respiratory ,Aged ,Critical Illness ,Disability Evaluation ,Exercise ,Female ,Frailty ,Humans ,Intensive Care Units ,Kaplan-Meier Estimate ,Linear Models ,Lung Diseases ,Lung Transplantation ,Male ,Middle Aged ,Multivariate Analysis ,Prospective Studies ,Risk Assessment ,Severity of Illness Index ,Surveys and Questionnaires ,Survivors ,United States ,frailty ,motor activity ,disability ,lung transplantation ,critical illness ,Clinical Sciences ,Respiratory System - Abstract
RationaleThe frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients.ObjectivesTo test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument.MethodsIn separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors.ResultsAmong 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3).ConclusionsThe DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.
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- 2017
43. 12.1 The Humane Society in Eighteenth-Century Europe and the Newly United States: A Research Agenda for the Atlantic Maritime World
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Bell, Richard, primary, Brancaccio, Maria Teresa, additional, Kästner, Alexander, additional, and Lederer, David, additional
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- 2021
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44. Extended post ex-vivo lung perfusion cold preservation predicts primary graft dysfunction and mortality: Results from a multicentric study
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Leiva-Juárez, Miguel M., Urso, Andreacarola, Arango Tomás, Elisabet, Lederer, David J., Sanchez, Pablo, Griffith, Bartley, Davis, R. Duane, Daneshmand, Mani, Hartwig, Matthew, Cantu, Edward, Weyant, Michael J., Bermudez, Christian, D'Cunha, Jonathan, Machuca, Tiago, Wozniak, Thomas, Lynch, William, Nemeh, Hassan, Mulligan, Michael, Song, Tae, Jessen, Michael, Camp, Phillip C., Caldeira, Christiano, Whitson, Bryan, Kreisel, Daniel, Ramzy, Danny, and D'Ovidio, Frank
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- 2020
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45. Lung Transplantation for Idiopathic Pulmonary Fibrosis
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Lamas, Daniela J., Lederer, David J., Rounds, Sharon I.S., Series Editor, Dixon, Anne, Series Editor, Schnapp, Lynn M., Series Editor, Meyer, Keith C., editor, and Nathan, Steven D., editor
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- 2019
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46. The prognostic value of peripheral retinal nonperfusion in diabetic retinopathy using ultra-widefield fluorescein angiography
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Antaki, Fares, Coussa, Razek Georges, Mikhail, Mikel, Archambault, Cyril, and Lederer, David E.
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- 2020
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47. A Systematically Derived Exposure Assessment Instrument for Chronic Hypersensitivity Pneumonitis
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Antoniou, Katerina M., Barber, Christopher M., Behr, Jürgen, Bonella, Francesco, Corte, Tamera, Costabel, Ulrich, Cottin, Vincent, Crestani, Bruno, Dalphin, Jean-Charles, Flaherty, Kevin R., Goh, Nicole, Johannson, Kerri A., Kondoh, Yasuhiro, Lederer, David, Lee, Joyce, Maher, Toby M., Martinez, Fernando J., Morell, Ferran, Noth, Imre, Raghu, Ganesh, Renzoni, Elisabetta, Richeldi, Luca, Ryerson, Christopher J., Ryu, Jay H., Salisbury, Margaret L., Singh, Sheetu, Selman, Moises, Strek, Mary E., Tarlo, Susan M., Tomassetti, Sara, Vancheri, Carlo, Vasakova, Martina, Wolters, Paul, Wells, Athol, Barnes, Hayley, Morisset, Julie, Molyneaux, Philip, Westall, Glen, Glaspole, Ian, and Collard, Harold R.
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- 2020
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48. Disease Severity and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A Cross-Sectional Analysis of the IPF-PRO Registry
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Asi, Wael, Baker, Albert, Beegle, Scott, Belperio, John A., Condos, Rany, Cordova, Francis, Culver, Daniel A., de Andrade, Joao A.M., Dilling, Daniel, Flaherty, Kevin R., Glassberg, Marilyn, Gulati, Mridu, Guntupalli, Kalpalatha, Gupta, Nishant, Hajari Case, Amy, Hotchkin, David, Huie, Tristan, Kaner, Robert, Kim, Hyun, Kreider, Maryl, Lancaster, Lisa, Lasky, Joseph, Lederer, David, Lee, Doug, Liesching, Timothy, Lipchik, Randolph, Lobo, Jason, Mageto, Yolanda, Menon, Prema, Morrison, Lake, Namen, Andrew, Oldham, Justin, Raj, Rishi, Ramaswamy, Murali, Russell, Tonya, Sachs, Paul, Safdar, Zeenat, Sigal, Barry, Silhan, Leann, Strek, Mary, Suliman, Sally, Tabak, Jeremy, Walia, Rajat, Whelan, Timothy P., O’Brien, Emily C., Hellkamp, Anne S., Neely, Megan L., Swaminathan, Aparna, Bender, Shaun, Snyder, Laurie D., Conoscenti, Craig S., Todd, Jamie L., Palmer, Scott M., and Leonard, Thomas B.
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- 2020
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49. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial
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Maher, Toby M, Corte, Tamera J, Fischer, Aryeh, Kreuter, Michael, Lederer, David J, Molina-Molina, Maria, Axmann, Judit, Kirchgaessler, Klaus-Uwe, Samara, Katerina, Gilberg, Frank, and Cottin, Vincent
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- 2020
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50. Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial
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Richeldi, Luca, Fernández Pérez, Evans R, Costabel, Ulrich, Albera, Carlo, Lederer, David J, Flaherty, Kevin R, Ettinger, Neil, Perez, Rafael, Scholand, Mary Beth, Goldin, Jonathan, Peony Yu, Kin-Hung, Neff, Thomas, Porter, Seth, Zhong, Ming, Gorina, Eduard, Kouchakji, Elias, and Raghu, Ganesh
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- 2020
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