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214. Diagnostic Likelihood Thresholds That Define a Working Diagnosis of Idiopathic Pulmonary Fibrosis

Author

Walsh, Simon L. F., primary, Lederer, David J., additional, Ryerson, Christopher J., additional, Kolb, Martin, additional, Maher, Toby M., additional, Nusser, Richard, additional, Poletti, Venerino, additional, Richeldi, Luca, additional, Vancheri, Carlo, additional, Wilsher, Margaret L., additional, Antoniou, Katerina M., additional, Behr, Juergen, additional, Bendstrup, Elisabeth, additional, Brown, Kevin K., additional, Corte, Tamera J., additional, Cottin, Vincent, additional, Crestani, Bruno, additional, Flaherty, Kevin R., additional, Glaspole, Ian N., additional, Grutters, Jan, additional, Inoue, Yoshikazu, additional, Kondoh, Yasuhiro, additional, Kreuter, Michael, additional, Johannson, Kerri A., additional, Ley, Brett, additional, Martinez, Fernando J., additional, Molina-Molina, Maria, additional, Morais, Antonio, additional, Nunes, Hilario, additional, Raghu, Ganesh, additional, Selman, Moises, additional, Spagnolo, Paolo, additional, Taniguchi, Hiroyuki, additional, Tomassetti, Sara, additional, Valeyre, Dominique, additional, Wijsenbeek, Marlies, additional, Wuyts, Wim A., additional, and Wells, Athol U., additional

Published
2019
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215. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases

Author

Flaherty, Kevin R., primary, Wells, Athol U., additional, Cottin, Vincent, additional, Devaraj, Anand, additional, Walsh, Simon L.F., additional, Inoue, Yoshikazu, additional, Richeldi, Luca, additional, Kolb, Martin, additional, Tetzlaff, Kay, additional, Stowasser, Susanne, additional, Coeck, Carl, additional, Clerisme-Beaty, Emmanuelle, additional, Rosenstock, Bernd, additional, Quaresma, Manuel, additional, Haeufel, Thomas, additional, Goeldner, Rainer-Georg, additional, Schlenker-Herceg, Rozsa, additional, and Brown, Kevin K., additional

Published
2019
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217. The circulating metabolome in idiopathic pulmonary fibrosis (IPF)

Author

Hesslinger, Christian, primary, Overton, Robert, additional, Keller, Sascha, additional, Neely, Megan L, additional, Belperio, John A, additional, Vinisko, Richard, additional, Leonard, Thomas, additional, Flaherty, Kevin R, additional, Noth, Imre, additional, Palmer, Scott M, additional, and Todd, Jamie L, additional

Published
2019
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218. Nintedanib in patients with chronic fibrosing interstitial lung diseases with progressive phenotype: the INBUILD trial

Author

Flaherty, Kevin R., primary, Wells, Athol U., additional, Cottin, Vincent, additional, Devaraj, Anand, additional, Inoue, Yoshikazu, additional, Richeldi, Luca, additional, Walsh, Simon, additional, Stowasser, Susanne, additional, Coeck, Carl, additional, Goeldner, Rainer-Georg, additional, Clerisme-Beaty, Emmanuelle, additional, Schlenker-Herceg, Rozsa, additional, and Brown, Kevin K., additional

Published
2019
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219. Patient Registries in Idiopathic Pulmonary Fibrosis

Author

Culver, Daniel A., primary, Behr, Jürgen, additional, Belperio, John A., additional, Corte, Tamera J., additional, de Andrade, Joao A., additional, Flaherty, Kevin R., additional, Gulati, Mridu, additional, Huie, Tristan J., additional, Lancaster, Lisa H., additional, Roman, Jesse, additional, Ryerson, Christopher J., additional, and Kim, Hyun J., additional

Published
2019
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220. Lung Microbiota Contribute to Pulmonary Inflammation and Disease Progression in Pulmonary Fibrosis

Author

O’Dwyer, David N., primary, Ashley, Shanna L., additional, Gurczynski, Stephen J., additional, Xia, Meng, additional, Wilke, Carol, additional, Falkowski, Nicole R., additional, Norman, Katy C., additional, Arnold, Kelly B., additional, Huffnagle, Gary B., additional, Salisbury, Margaret L., additional, Han, MeiLan K., additional, Flaherty, Kevin R., additional, White, Eric S., additional, Martinez, Fernando J., additional, Erb-Downward, John R., additional, Murray, Susan, additional, Moore, Bethany B., additional, and Dickson, Robert P., additional

Published
2019
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222. Hypersensitivity Pneumonitis

Author

Salisbury, Margaret L., primary, Gu, Tian, additional, Murray, Susan, additional, Gross, Barry H., additional, Chughtai, Aamer, additional, Sayyouh, Mohamed, additional, Kazerooni, Ella A., additional, Myers, Jeffrey L., additional, Lagstein, Amir, additional, Konopka, Kristine E., additional, Belloli, Elizabeth A., additional, Sheth, Jamie S., additional, White, Eric S., additional, Holtze, Colin, additional, Martinez, Fernando J., additional, and Flaherty, Kevin R., additional

Published
2019
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225. Computed Tomographic Biomarkers in Idiopathic Pulmonary Fibrosis. The Future of Quantitative Analysis

Author

Wu, Xiaoping, primary, Kim, Grace H., additional, Salisbury, Margaret L., additional, Barber, David, additional, Bartholmai, Brian J., additional, Brown, Kevin K., additional, Conoscenti, Craig S., additional, De Backer, Jan, additional, Flaherty, Kevin R., additional, Gruden, James F., additional, Hoffman, Eric A., additional, Humphries, Stephen M., additional, Jacob, Joseph, additional, Maher, Toby M., additional, Raghu, Ganesh, additional, Richeldi, Luca, additional, Ross, Brian D., additional, Schlenker-Herceg, Rozsa, additional, Sverzellati, Nicola, additional, Wells, Athol U., additional, Martinez, Fernando J., additional, Lynch, David A., additional, Goldin, Jonathan, additional, and Walsh, Simon L. F., additional

Published
2019
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226. Pamrevlumab (FG-3019), an Anti-Connective Tissue Growth Factor Therapy for Idiopathic Pulmonary Fibrosis: A Randomized, Double-Blind, Placebo-Controlled Trial

Author

Richeldi, Luca, primary, Fernández Pérez, Evans R., additional, Costabel, Ulrich, additional, Albera, Carlo, additional, Lederer, David J., additional, Flaherty, Kevin R., additional, Ettinger, Neil, additional, Perez, Rafael, additional, Scholand, Mary Beth, additional, Goldin, Jonathan, additional, Yu, Kin-Hung Peony, additional, Neff, Thomas, additional, Porter, Seth, additional, Zhong, Ming, additional, Gorina, Eduard, additional, Kouchakji, Elias, additional, and Raghu, Ganesh, additional

Published
2019
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227. Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial.

Author

Martinez, Fernando J., Yow, Eric, Flaherty, Kevin R., Snyder, Laurie D., Durheim, Michael T., Wisniewski, Stephen R., Sciurba, Frank C., Raghu, Ganesh, Brooks, Maria M., Kim, Dong-Yun, Dilling, Daniel F., Criner, Gerard J., Kim, Hyun, Belloli, Elizabeth A., Nambiar, Anoop M., Scholand, Mary Beth, Anstrom, Kevin J., Noth, Imre, and CleanUP-IPF Investigators of the Pulmonary Trials Cooperative

Subjects
IDIOPATHIC pulmonary fibrosis, CO-trimoxazole, DOXYCYCLINE, ANTI-infective agents, CLINICAL trials, LUNG microbiology, ANTIBIOTICS, RESEARCH, RESEARCH methodology, RESPIRATORY infections, MEDICAL cooperation, EVALUATION research, TREATMENT effectiveness, COMPARATIVE studies, RANDOMIZED controlled trials, PULMONARY function tests, HOSPITAL care, RESEARCH funding
Abstract

Importance: Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis.Objective: To assess the effect of antimicrobial therapy on clinical outcomes.Design, Setting, and Participants: Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020).Interventions: Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if ≥50 kg, n = 126). No placebo was administered in the usual care alone group.Main Outcomes and Measures: The primary end point was time to first nonelective respiratory hospitalization or all-cause mortality.Results: Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%).Conclusions and Relevance: Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease.Trial Registration: ClinicalTrials.gov Identifier: NCT02759120. [ABSTRACT FROM AUTHOR]

Published
2021
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229. Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort.

Author

Todd, Jamie L., Vinisko, Richard, Liu, Yi, Neely, Megan L., Overton, Robert, Flaherty, Kevin R., Noth, Imre, Newby, L. Kristin, Lasky, Joseph A., Olman, Mitchell A., Hesslinger, Christian, Leonard, Thomas B., Palmer, Scott M., Belperio, John A., on behalf of the IPF-PRO Registry investigators, Asi, Wael, Baker, Albert, Beegle, Scott, Condos, Rany, and Cordova, Francis

Subjects
IDIOPATHIC pulmonary fibrosis, TISSUE inhibitors of metalloproteinases, MATRIX metalloproteinases, CARBOXYHEMOGLOBIN, CARBON monoxide, EXTRACELLULAR matrix
Abstract

Background: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.Methods: The IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.Results: All the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.Conclusions: Circulating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers. [ABSTRACT FROM AUTHOR]

Published
2020
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230. Predictors of death or transplant in patients with idiopathic pulmonary fibrosis in the IPF-PRO Registry

Author

Snyder, Laurie, primary, Neely, Megan L, additional, Hellkamp, Anne, additional, O'Brien, Emily, additional, Flaherty, Kevin R, additional, De Andrade, Joao, additional, Conoscenti, Craig, additional, Leonard, Thomas, additional, Bender, Shaun, additional, Gulati, Mridu, additional, Culver, Daniel A, additional, Kaner, Robert J, additional, Palmer, Scott, additional, and Kim, Hyun J, additional

Published
2018
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231. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline

Author

Raghu, Ganesh, primary, Remy-Jardin, Martine, additional, Myers, Jeffrey L., additional, Richeldi, Luca, additional, Ryerson, Christopher J., additional, Lederer, David J., additional, Behr, Juergen, additional, Cottin, Vincent, additional, Danoff, Sonye K., additional, Morell, Ferran, additional, Flaherty, Kevin R., additional, Wells, Athol, additional, Martinez, Fernando J., additional, Azuma, Arata, additional, Bice, Thomas J., additional, Bouros, Demosthenes, additional, Brown, Kevin K., additional, Collard, Harold R., additional, Duggal, Abhijit, additional, Galvin, Liam, additional, Inoue, Yoshikazu, additional, Jenkins, R. Gisli, additional, Johkoh, Takeshi, additional, Kazerooni, Ella A., additional, Kitaichi, Masanori, additional, Knight, Shandra L., additional, Mansour, George, additional, Nicholson, Andrew G., additional, Pipavath, Sudhakar N. J., additional, Buendía-Roldán, Ivette, additional, Selman, Moisés, additional, Travis, William D., additional, Walsh, Simon L. F., additional, and Wilson, Kevin C., additional

Published
2018
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232. Quantitative high-resolution computed tomography fibrosis score: performance characteristics in idiopathic pulmonary fibrosis

Author

Humphries, Stephen M., primary, Swigris, Jeffrey J., additional, Brown, Kevin K., additional, Strand, Matthew, additional, Gong, Qi, additional, Sundy, John S., additional, Raghu, Ganesh, additional, Schwarz, Marvin I., additional, Flaherty, Kevin R., additional, Sood, Rohit, additional, O'Riordan, Thomas G., additional, and Lynch, David A., additional

Published
2018
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234. Development and validation of a radiological diagnosis model for hypersensitivity pneumonitis

Author

Salisbury, Margaret L., primary, Gross, Barry H., additional, Chughtai, Aamer, additional, Sayyouh, Mohamed, additional, Kazerooni, Ella A., additional, Bartholmai, Brian J., additional, Xia, Meng, additional, Murray, Susan, additional, Myers, Jeffrey L., additional, Lagstein, Amir, additional, Konopka, Kristine E., additional, Belloli, Elizabeth A., additional, Sheth, Jamie S., additional, White, Eric S., additional, Holtze, Colin, additional, Martinez, Fernando J., additional, and Flaherty, Kevin R., additional

Published
2018
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238. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches.

Author

Martinez, Fernando J, Martinez, Fernando J, Chisholm, Alison, Collard, Harold R, Flaherty, Kevin R, Myers, Jeffrey, Raghu, Ganesh, Walsh, Simon LF, White, Eric S, Richeldi, Luca, Martinez, Fernando J, Martinez, Fernando J, Chisholm, Alison, Collard, Harold R, Flaherty, Kevin R, Myers, Jeffrey, Raghu, Ganesh, Walsh, Simon LF, White, Eric S, and Richeldi, Luca

Abstract

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients.

Published
2017

241. A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease. An International Working Group Perspective

Author

Ryerson, Christopher J., primary, Corte, Tamera J., additional, Lee, Joyce S., additional, Richeldi, Luca, additional, Walsh, Simon L. F., additional, Myers, Jeffrey L., additional, Behr, Jürgen, additional, Cottin, Vincent, additional, Danoff, Sonye K., additional, Flaherty, Kevin R., additional, Lederer, David J., additional, Lynch, David A., additional, Martinez, Fernando J., additional, Raghu, Ganesh, additional, Travis, William D., additional, Udwadia, Zarir, additional, Wells, Athol U., additional, and Collard, Harold R., additional

Published
2017
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242. Usual Interstitial Pneumonia Can Be Detected in Transbronchial Biopsies Using Machine Learning

Author

Pankratz, Daniel G., primary, Choi, Yoonha, additional, Imtiaz, Urooj, additional, Fedorowicz, Grażyna M., additional, Anderson, Jessica D., additional, Colby, Thomas V., additional, Myers, Jeffrey L., additional, Lynch, David A., additional, Brown, Kevin K., additional, Flaherty, Kevin R., additional, Steele, Mark P., additional, Groshong, Steve D., additional, Raghu, Ganesh, additional, Barth, Neil M., additional, Walsh, P. Sean, additional, Huang, Jing, additional, Kennedy, Giulia C., additional, and Martinez, Fernando J., additional

Published
2017
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243. Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients

Author

Salisbury, Margaret L., primary, Tolle, Leslie B., additional, Xia, Meng, additional, Murray, Susan, additional, Tayob, Nabihah, additional, Nambiar, Anoop M., additional, Schmidt, Shelley L., additional, Lagstein, Amir, additional, Myers, Jeffery L., additional, Gross, Barry H., additional, Kazerooni, Ella A., additional, Sundaram, Baskaran, additional, Chughtai, Aamer R., additional, Martinez, Fernando J., additional, and Flaherty, Kevin R., additional

Published
2017
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244. Idiopathic Pulmonary Fibrosis: Data-driven Textural Analysis of Extent of Fibrosis at Baseline and 15-Month Follow-up

Author

Humphries, Stephen M., primary, Yagihashi, Kunihiro, additional, Huckleberry, Jason, additional, Rho, Byung-Hak, additional, Schroeder, Joyce D., additional, Strand, Matthew, additional, Schwarz, Marvin I., additional, Flaherty, Kevin R., additional, Kazerooni, Ella A., additional, van Beek, Edwin J. R., additional, and Lynch, David A., additional

Published
2017
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248. Design of the PF-ILD trial: a double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease

Author

Flaherty, Kevin R, primary, Brown, Kevin K, additional, Wells, Athol U, additional, Clerisme-Beaty, Emmanuelle, additional, Collard, Harold R, additional, Cottin, Vincent, additional, Devaraj, Anand, additional, Inoue, Yoshikazu, additional, Le Maulf, Florence, additional, Richeldi, Luca, additional, Schmidt, Hendrik, additional, Walsh, Simon, additional, Mezzanotte, William, additional, and Schlenker-Herceg, Rozsa, additional

Published
2017
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250. Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis

Author

Huang, Yong, primary, Ma, Shwu-Fan, additional, Espindola, Milena S., additional, Vij, Rekha, additional, Oldham, Justin M., additional, Huffnagle, Gary B., additional, Erb-Downward, John R., additional, Flaherty, Kevin R., additional, Moore, Beth B., additional, White, Eric S., additional, Zhou, Tong, additional, Li, Jianrong, additional, Lussier, Yves A., additional, Han, MeiLan K., additional, Kaminski, Naftali, additional, Garcia, Joe G. N., additional, Hogaboam, Cory M., additional, Martinez, Fernando J., additional, and Noth, Imre, additional

Published
2017
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