941 results on '"Flaherty, Kevin R."'
Search Results
2. Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults
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Adegunsoye, Ayodeji, Freiheit, Elizabeth, White, Emily N, Kaul, Bhavika, Newton, Chad A, Oldham, Justin M, Lee, Cathryn T, Chung, Jonathan, Garcia, Nicole, Ghodrati, Sahand, Vij, Rekha, Jablonski, Renea, Flaherty, Kevin R, Wolters, Paul J, Garcia, Christine Kim, and Strek, Mary E
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Rare Diseases ,Lung ,Clinical Research ,Aging ,Clinical Trials and Supportive Activities ,Respiratory ,Good Health and Well Being ,Humans ,Male ,Adult ,Child ,Aged ,Female ,Ethnicity ,Cohort Studies ,Prospective Studies ,Pulmonary Fibrosis ,Minority Groups ,Biomedical and clinical sciences ,Health sciences - Abstract
ImportancePulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown.ObjectiveTo compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants.Design, setting, and participantsThis cohort study included adult patients with a PF diagnosis and used data from prospective clinical registries: the Pulmonary Fibrosis Foundation Registry (PFFR) for the primary cohort and registries from 4 geographically distinct tertiary hospitals in the US for the external multicenter validation (EMV) cohort. Patients were followed between January 2003 and April 2021.ExposuresRace and ethnicity comparisons between Black, Hispanic, and White participants with PF.Main outcomes and measuresAge and sex distribution of participants were measured at the time of study enrollment. All-cause mortality and age at PF diagnosis, hospitalization, lung transplant, and death were assessed in participants over 14 389 person-years. Differences between racial and ethnic groups were compared using Wilcoxon rank sum tests, Bartlett 1-way analysis of variance, and χ2 tests, and crude mortality rates and rate ratios were assessed across racial and ethnic categories using Cox proportional hazards regression models.ResultsIn total, 4792 participants with PF were assessed (mean [SD] age, 66.1 [11.2] years; 2779 [58.0%] male; 488 [10.2%] Black, 319 [6.7%] Hispanic, and 3985 [83.2%] White); 1904 were in the PFFR and 2888 in the EMV cohort. Black patients with PF were consistently younger than White patients (mean [SD] age at baseline, 57.9 [12.0] vs 68.6 [9.6] years; P
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- 2023
3. Impact of Pirfenidone on Patient-Reported Outcomes in Patients With Idiopathic Pulmonary Fibrosis From the Pulmonary Fibrosis Foundation Patient Registry
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Kang, Mohleen, Gupta, Sachin, Tu, Yi-Hsuan, Raimundo, Karina, Patel, Anisha M., and Flaherty, Kevin R.
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- 2024
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4. Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study)
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Combs, Michael P., Belloli, Elizabeth A., Gargurevich, Nicolas, Flaherty, Kevin R., Murray, Susan, Galbán, Craig J., and Lama, Vibha N.
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- 2024
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5. A multidimensional classifier to support lung transplant referral in patients with pulmonary fibrosis
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Pugashetti, Janelle Vu, Kim, John S., Combs, Michael P., Ma, Shwu-Fan, Adegunsoye, Ayodeji, Linderholm, Angela L., Strek, Mary E., Chen, Ching-Hsien, Dilling, Daniel F., Whelan, Timothy P.M., Flaherty, Kevin R., Martinez, Fernando J., Noth, Imre, and Oldham, Justin M.
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- 2024
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6. Effect of Nintedanib in Patients with Progressive Pulmonary Fibrosis in Subgroups with Differing Baseline Characteristics
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Kolb, Martin, Flaherty, Kevin R., Silva, Rafael S., Prasse, Antje, Vancheri, Carlo, Mueller, Heiko, Sroka-Saidi, Kamila, and Wells, Athol U.
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- 2023
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7. Comparison of Pirfenidone and Nintedanib: Post Hoc Analysis of the CleanUP-IPF Study
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Kim, John S., Murray, Susan, Yow, Eric, Anstrom, Kevin J., Kim, Hyun J., Flaherty, Kevin R., Martinez, Fernando J., and Noth, Imre
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- 2024
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8. Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial
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Podolanczuk, Anna J, Kim, John S, Cooper, Christopher B, Lasky, Joseph A, Murray, Susan, Oldham, Justin M, Raghu, Ganesh, Flaherty, Kevin R, Spino, Cathie, Noth, Imre, and Martinez, Fernando J
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Rare Diseases ,Clinical Trials and Supportive Activities ,Genetics ,Lung ,Complementary and Integrative Health ,Clinical Research ,Autoimmune Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Respiratory ,Good Health and Well Being ,Humans ,Acetylcysteine ,Double-Blind Method ,Genotype ,Idiopathic Pulmonary Fibrosis ,Treatment Outcome ,Vital Capacity ,Randomized Controlled Trials as Topic ,Multicenter Studies as Topic ,Clinical Trials ,Phase III as Topic ,IPF ,Clinical trial ,Protocol ,N-acetylcysteine ,PRECISIONS Study Team ,Cardiorespiratory Medicine and Haematology ,Respiratory System - Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. N-acetylcysteine (NAC) is a well-tolerated, inexpensive treatment with antioxidant and anti-fibrotic properties. The National Heart, Lung, and Blood Institute (NHLBI)-sponsored PANTHER (Prednisone Azathioprine and NAC therapy in IPF) trial confirmed the harmful effects of immunosuppression in IPF, and did not show a benefit to treatment with NAC. However, a post hoc analysis revealed a potential beneficial effect of NAC in a subgroup of individuals carrying a specific genetic variant, TOLLIP rs3750920 TT genotype, present in about 25% of patients with IPF. Here, we present the design and rationale for the Phase III, multi-center, randomized, double-blind, placebo-controlled Prospective Treatment Efficacy in IPF Using Genotype for NAC Selection (PRECISIONS) clinical trial.MethodsThe PRECISIONS trial will randomize 200 patients with IPF and the TOLLIP rs3750920 TT genotype 1:1 to oral N-acetylcysteine (600 mg tablets taken three times a day) or placebo for a 24-month duration. The primary endpoint is the composite of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or death from any cause. Secondary endpoints include change in patient-reported outcome scores and proportion of participants with treatment-emergent adverse events. Biospecimens, including blood, buccal, and fecal will be collected longitudinally for future research purposes. Study participants will be offered enrollment in a home spirometry substudy, which explores time to 10% relative FVC decline measured at home, and its comparison with study visit FVC.DiscussionThe sentinel observation of a potential pharmacogenetic interaction between NAC and TOLLIP polymorphism highlights the urgent, unmet need for better, molecularly focused, and precise therapeutic strategies in IPF. The PRECISIONS clinical trial is the first study to use molecularly-focused techniques to identify patients with IPF most likely to benefit from treatment. PRECISIONS has the potential to shift the paradigm in how trials in this condition are designed and executed, and is the first step toward personalized medicine for patients with IPF. Trial Registration ClinicalTrials.gov identifier: NCT04300920. Registered March 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04300920.
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- 2022
9. Nonspecific, Unclassifiable, and Rare Idiopathic Interstitial Pneumonia: Acute Interstitial Pneumonia, Respiratory Bronchiolitis Interstitial Pneumonia, Desquamative Interstitial Pneumonia, Nonspecific Interstitial Pneumonia
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Ntiamoah, Prince, Purpura, Russell, Vehar, Susan, Coley, Curtis J., II, Hasvold, Jennifer, Schmidt, Lindsay A., Flaherty, Kevin R., Tolle, Leslie B., Cottin, Vincent, editor, Richeldi, Luca, editor, Brown, Kevin, editor, and McCormack, Francis X., editor
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- 2023
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10. Associations of Plasma Omega-3 Fatty Acids With Progression and Survival in Pulmonary Fibrosis
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Kim, John S., Ma, Shwu-Fan, Ma, Jennie Z., Huang, Yong, Bonham, Catherine A., Oldham, Justin M., Adegunsoye, Ayodeji, Strek, Mary E., Flaherty, Kevin R., Strickland, Emma, Udofia, Inemesit, Mooney, Joshua J., Ghosh, Shrestha, Maddipati, Krishnarao, and Noth, Imre
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- 2024
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11. Expert consensus on the management of systemic sclerosis-associated interstitial lung disease
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Rahaghi, Franck F., Hsu, Vivien M., Kaner, Robert J., Mayes, Maureen D., Rosas, Ivan O., Saggar, Rajan, Steen, Virginia D., Strek, Mary E., Bernstein, Elana J., Bhatt, Nitin, Castelino, Flavia V., Chung, Lorinda, Domsic, Robyn T., Flaherty, Kevin R., Gupta, Nishant, Kahaleh, Bashar, Martinez, Fernando J., Morrow, Lee E., Moua, Teng, Patel, Nina, Shlobin, Oksana A., Southern, Brian D., Volkmann, Elizabeth R., and Khanna, Dinesh
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- 2023
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12. Factors associated with listing for lung transplantation in IPF patients: An analysis of the pulmonary fibrosis foundation registry
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King, Christopher S., White, Emily, Aryal, Shambhu, Shlobin, Oksana A., Singhal, Anju, Brown, A. Whitney, Thomas, Christopher, Khangoora, Vikramjit, Nyquist, Alan, Flaherty, Kevin R., Nathan, Steven D., and Mooney, Joshua J.
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- 2023
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13. 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
14. Safety, tolerability, and efficacy of pirfenidone in patients with rheumatoid arthritis-associated interstitial lung disease: a randomised, double-blind, placebo-controlled, phase 2 study
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Haynes-Harp, Shana, Poli, Fernando, Vidya, Coimbatore Sree, Baron, Rebecca R., Clouser, Timothy, Doyle, Tracy, Maeda, Anthony, Highland, Kristin B., Albayda, Jemima F., Collins, Sarah E., Suresh, Karthik S., Davis, John M., Limper, Andrew H., Amigues, Isabel, Eliopoulos, Kristina, Swigris, Jeffery J., Humphries, Stephen, Huntwork, John C., Glynn, Chris, Duncan, Steve R., Danila, Maria I., Glassberg, Marilyn K., Oberstein, Elana M., Belloli, Elizabeth A., Briggs, Linda, Nagaraja, Vivek, Cholewa, Linda, DiFranco, Donna, Green, Edward, Liffick, Christie, Naik, Tanvi, Montas, Genevieve, Lebiedz-Odrobina, Dorota, Bissell, Reba, Wener, Mark, Lancaster, Lisa H., Crawford, Leslie J., Chan, Karmela, Kaner, Robert J., Morris, Alicia, Wu, Xiaoping, Khalidi, Nader A., Ryerson, Christopher J., Wong, Alyson W., Fell, Charlene D., LeClercq, Sharon A., Hyman, Mark, Shapera, Shane, Mittoo, Shikha, Shaffu, Shireen, Gaffney, Karl, Wilson, Andrew M., Barratt, Shaney, Gunawardena, Harsha, Hoyles, Rachel K., David, Joel, Kewalramani, Namrata, Maher, Toby M., Molyneaux, Philip L., Kokosi, Maria A., Cates, Matthew J., Mandizha, Mandizha, Ashish, Abdul, Chelliah, Gladstone, Parfrey, Helen, Thillai, Muhunthan, Vila, Josephine, Fletcher, Sophie V., Beirne, Paul, Favager, Clair, Brown, Jo, Dawson, Julie K., Ortega, Pilar Rivera, Haque, Sahena, Watson, Pippa, Khoo, Jun K., Symons, Karen, Youssef, Peter, Mackintosh, John A., Solomon, Joshua J, Danoff, Sonye K, Woodhead, Felix A, Hurwitz, Shelley, Maurer, Rie, Glaspole, Ian, Dellaripa, Paul F, Gooptu, Bibek, Vassallo, Robert, Cox, P Gerard, Flaherty, Kevin R, Adamali, Huzaifa I, Gibbons, Michael A, Troy, Lauren, Forrest, Ian A, Lasky, Joseph A, Spencer, Lisa G, Golden, Jeffrey, Scholand, Mary Beth, Chaudhuri, Nazia, Perrella, Mark A, Lynch, David A, Chambers, Daniel C, Kolb, Martin, Spino, Cathie, Raghu, Ganesh, Goldberg, Hilary J, and Rosas, Ivan O
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- 2023
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15. Screening Strategies for Pulmonary Hypertension in Patients With Interstitial Lung Disease: A Multidisciplinary Delphi Study
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Rahaghi, Franck F., Kolaitis, Nicholas A., Adegunsoye, Ayodeji, de Andrade, Joao A., Flaherty, Kevin R., Lancaster, Lisa H., Lee, Joyce S., Levine, Deborah J., Preston, Ioana R., Safdar, Zeenat, Saggar, Rajan, Sahay, Sandeep, Scholand, Mary Beth, Shlobin, Oksana A., Zisman, David A., and Nathan, Steven D.
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- 2022
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16. Inhaled Nitric Oxide in Fibrotic Lung Disease: A Randomized, Double-Blind, Placebo-controlled Trial.
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Nathan, Steven D., Rajicic, Natasa, Dudenhofer, Rosemarie, Hussain, Rahat, Argula, Rahul, Bandyopadhyay, Debabrata, Luckhardt, Tracy, Muehlemann, Natalia, Flaherty, Kevin R., Glassberg, Marilyn K., Lancaster, Lisa, Raghu, Ganesh, and Fernandes, Peter
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PULMONARY fibrosis ,INTERSTITIAL lung diseases ,RESPIRATORY infections ,PULMONARY hypertension ,OXYGEN therapy - Abstract
Rationale: Inhaled nitric oxide (iNO) has been shown to result in benefits in moderate to vigorous physical activity (MVPA) in patients with fibrotic interstitial lung disease (f-ILD) receiving supplemental oxygen in two independent trials. Objective: This phase III randomized, double-blind, placebo-controlled study sought to validate the benefit of ambulatory iNO in patients with f-ILD requiring supplemental oxygen. Methods: Patients with f-ILD receiving supplemental long-term oxygen were randomized in a 1:1 fashion to iNO at 45 μg/kg ideal body weight per hour or placebo for 16 weeks. The primary outcome was the change from baseline to Week 16 in MVPA assessed by accelerometry. Secondary outcomes included overall activity, 6-minute-walk distance and patient-reported outcomes. Results: 145 patients were enrolled; 75 were assigned to receive iNO and 70 placebo. The changes from baseline in MVPA at 16 weeks were −9.2 min/d (standard error, 3.51) in the iNO45 group and −3.7 min/d (3.76) in the placebo group (difference, 5.5; P = 0.265). No statistically significant differences between the two treatment arms were found for any of the secondary outcomes. A subgroup analysis of patients with an intermediate or high probability of pulmonary hypertension on echocardiography did not demonstrate any benefit. The most common adverse events reported were respiratory tract infections, but the therapy was generally very well tolerated. Conclusions: There was no demonstrable benefit to iNO in patients with f-ILD receiving supplemental oxygen in daily physical activity assessed by actigraphy, a potential novel clinical trial endpoint. Clinical trial registered with (NCT 03267108). [ABSTRACT FROM AUTHOR]
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- 2024
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17. Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.
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Lancaster, Lisa, Cottin, Vincent, Ramaswamy, Murali, Wuyts, Wim A., Jenkins, R. Gisli, Scholand, Mary Beth, Kreuter, Michael, Valenzuela, Claudia, Ryerson, Christopher J., Goldin, Jonathan, Kim, Grace Hyun J., Jurek, Marzena, Decaris, Martin, Clark, Annie, Turner, Scott M., Barnes, Chris N., Achneck, Hardean E., Cosgrove, Gregory P., Lefebvre, Éric A., and Flaherty, Kevin R.
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IDIOPATHIC pulmonary fibrosis ,CRITICAL care medicine ,LUNG diseases ,DISEASE progression ,PLACEBOS - Abstract
What is this summary about? This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the American Journal of Respiratory and Critical Care Medicine in 2024. This study looked at a medicine called bexotegrast (beck-so-teh-grast) as a possible treatment for idiopathic pulmonary fibrosis (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). Bexotegrast is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment. IPF is a chronic, progressive lung disease that makes it hard to breathe and gets worse over time. There is no cure for IPF, treatment includes symptom management and consideration for the use of nintedanib or pirfenidone, which may decrease the pace of disease progression. The study compared bexotegrast to a placebo (a treatment that looks identical to the medicine but has no medicinal effect) to look at how well it works and how safe it is in treating people with IPF. Most people in the study also took one of two medicines that are already approved by the FDA for IPF, pirfenidone or nintedanib. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort
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Todd, Jamie L., Neely, Megan L., Overton, Robert, Mulder, Hillary, Roman, Jesse, Lasky, Joseph A., de Andrade, Joao A., Gulati, Mridu, Huang, Howard, Leonard, Thomas B., Hesslinger, Christian, Noth, Imre, Belperio, John A., Flaherty, Kevin R., and Palmer, Scott M.
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- 2022
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19. 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
20. Biological Age, Chronological Age and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis
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Pugashetti, Janelle Vu, primary, Kim, John S., additional, Bose, Swaraj, additional, Adegunsoye, Ayodeji, additional, Linderholm, Angela L, additional, Chen, Ching-Hsien, additional, Strek, Mary E., additional, Flaherty, Kevin R., additional, Murray, Susan, additional, Newton, Chad A., additional, Alqalyoobi, Shehabaldin, additional, Ma, Shwu-Fan, additional, Mychaleckyj, Josyf C., additional, Bowler, Russell P., additional, Han, MeiLan K., additional, Curtis, Jeffrey L., additional, Martinez, Fernando J., additional, Smith, Jennifer A, additional, Noth, Imre, additional, and Oldham, Justin M., additional
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- 2024
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21. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Study
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Lancaster, Lisa, primary, Cottin, Vincent, additional, Ramaswamy, Murali, additional, Wuyts, Wim A., additional, Jenkins, R. Gisli, additional, Scholand, Mary Beth, additional, Kreuter, Michael, additional, Valenzuela, Claudia, additional, Ryerson, Christopher J, additional, Goldin, Jonathan, additional, Kim, Grace Hyun J, additional, Jurek, Marzena, additional, Decaris, Martin, additional, Clark, Annie, additional, Turner, Scott, additional, Barnes, Chris N., additional, Achneck, Hardean E, additional, Cosgrove, Gregory, additional, Lefebvre, Éric A, additional, and Flaherty, Kevin R., additional
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- 2024
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22. Optimising the approach to ILD diagnosis: the balance of procedural complications against diagnostic accuracy
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Salisbury, Margaret L, primary and Flaherty, Kevin R, additional
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- 2024
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23. Organizing Pneumonia
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Wang, Bonnie R., primary and Flaherty, Kevin R., additional
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- 2022
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24. Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Patient Registry
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King, Christopher S., Freiheit, Elizabeth, Brown, A. Whitney, Shlobin, Oksana A., Aryal, Shambhu, Ahmad, Kareem, Khangoora, Vikramjit, Flaherty, Kevin R., Venuto, Drew, and Nathan, Steven D.
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- 2021
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25. 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
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Flaherty, Kevin R, Brown, Kevin K, Wells, Athol U, Clerisme-Beaty, Emmanuelle, Collard, Harold R, Cottin, Vincent, Devaraj, Anand, Inoue, Yoshikazu, Le Maulf, Florence, Richeldi, Luca, Schmidt, Hendrik, Walsh, Simon, Mezzanotte, William, and Schlenker-Herceg, Rozsa
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Lung ,Autoimmune Disease ,Clinical Trials and Supportive Activities ,Clinical Research ,Rare Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Respiratory ,Good Health and Well Being ,interstitial fibrosis ,rare lung diseases - Abstract
600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King's Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks.Ethics and disseminationThe trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations.Trial registration numberNCT02999178.
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- 2017
26. Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis
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Huang, Yong, Ma, Shwu-Fan, Espindola, Milena S, Vij, Rekha, Oldham, Justin M, Huffnagle, Gary B, Erb-Downward, John R, Flaherty, Kevin R, Moore, Beth B, White, Eric S, Zhou, Tong, Li, Jianrong, Lussier, Yves A, Han, MeiLan K, Kaminski, Naftali, Garcia, Joe GN, Hogaboam, Cory M, Martinez, Fernando J, and Noth, Imre
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Autoimmune Disease ,Rare Diseases ,Genetics ,Human Genome ,Clinical Research ,Lung ,Aetiology ,2.1 Biological and endogenous factors ,Respiratory ,Life Below Water ,Bronchoalveolar Lavage ,Disease-Free Survival ,Down-Regulation ,Female ,Flow Cytometry ,Gene Expression ,Humans ,Idiopathic Pulmonary Fibrosis ,Immunity ,Innate ,Male ,Microarray Analysis ,Microbiota ,Middle Aged ,host immune response and microbial interaction ,peripheral blood mononuclear cell transcriptome ,bronchoalveolar lavage microbiome ,CpG-oligodeoxynucleotide response ,pattern recognition receptors ,COMET-IPF Investigators ,Medical and Health Sciences ,Respiratory System - Abstract
RationaleDifferences in the lung microbial community influence idiopathic pulmonary fibrosis (IPF) progression. Whether the lung microbiome influences IPF host defense remains unknown.ObjectivesTo explore the host immune response and microbial interaction in IPF as they relate to progression-free survival (PFS), fibroblast function, and leukocyte phenotypes.MethodsPaired microarray gene expression data derived from peripheral blood mononuclear cells as well as 16S ribosomal RNA sequencing data from bronchoalveolar lavage obtained as part of the COMET-IPF (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in Idiopathic Pulmonary Fibrosis) study were used to conduct association pathway analyses. The responsiveness of paired lung fibroblasts to Toll-like receptor 9 (TLR9) stimulation by CpG-oligodeoxynucleotide (CpG-ODN) was integrated into microbiome-gene expression association analyses for a subset of individuals. The relationship between associated pathways and circulating leukocyte phenotypes was explored by flow cytometry.Measurements and main resultsDown-regulation of immune response pathways, including nucleotide-binding oligomerization domain (NOD)-, Toll-, and RIG1-like receptor pathways, was associated with worse PFS. Ten of the 11 PFS-associated pathways correlated with microbial diversity and individual genus, with species accumulation curve richness as a hub. Higher species accumulation curve richness was significantly associated with inhibition of NODs and TLRs, whereas increased abundance of Streptococcus correlated with increased NOD-like receptor signaling. In a network analysis, expression of up-regulated signaling pathways was strongly associated with decreased abundance of operational taxonomic unit 1341 (OTU1341; Prevotella) among individuals with fibroblasts responsive to CpG-ODN stimulation. The expression of TLR signaling pathways was also linked to CpG-ODN responsive fibroblasts, OTU1341 (Prevotella), and Shannon index of microbial diversity in a network analysis. Lymphocytes expressing C-X-C chemokine receptor 3 CD8 significantly correlated with OTU1348 (Staphylococcus).ConclusionsThese findings suggest that host-microbiome interactions influence PFS and fibroblast responsiveness.
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- 2017
27. The diagnosis of idiopathic pulmonary fibrosis: current and future approaches
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Martinez, Fernando J, Chisholm, Alison, Collard, Harold R, Flaherty, Kevin R, Myers, Jeffrey, Raghu, Ganesh, Walsh, Simon LF, White, Eric S, and Richeldi, Luca
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Biomedical Imaging ,Lung ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Respiratory ,Biopsy ,Diagnosis ,Differential ,Humans ,Idiopathic Pulmonary Fibrosis ,Symptom Assessment ,Tomography ,X-Ray Computed ,Public Health and Health Services ,Other Medical and Health Sciences ,Cardiovascular medicine and haematology ,Clinical sciences - 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.
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- 2017
28. Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis
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Wijsenbeek, Marlies, Swigris, Jeffrey J., Inoue, Yoshikazu, Kreuter, Michael, Maher, Toby M., Suda, Takafumi, Baldwin, Michael, Mueller, Heiko, Rohr, Klaus B., Flaherty, Kevin R., Wijsenbeek, Marlies, Swigris, Jeffrey J., Inoue, Yoshikazu, Kreuter, Michael, Maher, Toby M., Suda, Takafumi, Baldwin, Michael, Mueller, Heiko, Rohr, Klaus B., and Flaherty, Kevin R.
- Abstract
BACKGROUND: Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. METHODS: Patients had a fibrosing interstitial lung disease (ILD) (other than idiopathic pulmonary fibrosis) of >10% extent on high-resolution computed tomography (HRCT) and met criteria for ILD progression within the prior 24 months. Patients were randomised 1:1 to receive nintedanib or placebo. Changes in L-PF questionnaire scores from baseline to week 52 were assessed using mixed models for repeated measures. RESULTS:In total, 663 patients were treated. Compared with placebo, there were significantly smaller increases (worsenings) in adjusted mean L-PF questionnaire total (0.5 versus 5.1), symptoms (1.3 versus 5.3), dyspnoea (4.3 versus 7.8) and fatigue (0.7 versus 4.0) scores in the nintedanib group at week 52. L-PF questionnaire cough score decreased in the nintedanib group and increased in the placebo group (-1.8 versus 4.3). L-PF questionnaire impacts score decreased slightly in the nintedanib group and increased in the placebo group (-0.2 versus 4.6). Similar findings were observed in patients with a usual interstitial pneumonia-like fibrotic pattern on HRCT and in patients with other fibrotic patterns on HRCT.CONCLUSION: Based on changes in L-PF questionnaire scores, nintedanib reduced worsening of dyspnoea, fatigue and cough and the impacts of ILD over 52 weeks in patients with PPF.
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- 2024
29. Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'
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Raghu, Ganesh, Ghazipura, Marya, Fleming, Thomas R., Aronson, Kerri I, Behr, Jürgen, Brown, Kevin K, Flaherty, Kevin R., Kazerooni, Ella A, Maher, Toby M, Richeldi, Luca, Lasky, Joseph A., Swigris, Jeffrey J, Busch, Robert, Garrard, Lili, Ahn, Dong-Hyun, Li, Ji, Puthawala, Khalid, Rodal, Gabriela, Seymour, Sally, Weir, Nargue, Danoff, Sonye K., Ettinger, Neil, Goldin, Jonathan, Glassberg, Marilyn K, Kawano-Dourado, Leticia, Khalil, Nasreen, Lancaster, Lisa, Lynch, David A., Mageto, Yolanda, Noth, Imre, Shore, Jessica E, Wijsenbeek, Marlie, Brown, Robert, Grogan, Daniel, Ivey, Dorothy, Golinska, Patrycja, Karimi-Shah, Banu A., Martinez, Fernando J., Richeldi, Luca (ORCID:0000-0001-8594-1448), Raghu, Ganesh, Ghazipura, Marya, Fleming, Thomas R., Aronson, Kerri I, Behr, Jürgen, Brown, Kevin K, Flaherty, Kevin R., Kazerooni, Ella A, Maher, Toby M, Richeldi, Luca, Lasky, Joseph A., Swigris, Jeffrey J, Busch, Robert, Garrard, Lili, Ahn, Dong-Hyun, Li, Ji, Puthawala, Khalid, Rodal, Gabriela, Seymour, Sally, Weir, Nargue, Danoff, Sonye K., Ettinger, Neil, Goldin, Jonathan, Glassberg, Marilyn K, Kawano-Dourado, Leticia, Khalil, Nasreen, Lancaster, Lisa, Lynch, David A., Mageto, Yolanda, Noth, Imre, Shore, Jessica E, Wijsenbeek, Marlie, Brown, Robert, Grogan, Daniel, Ivey, Dorothy, Golinska, Patrycja, Karimi-Shah, Banu A., Martinez, Fernando J., and Richeldi, Luca (ORCID:0000-0001-8594-1448)
- Abstract
Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinical care in IPF. Methods: A landmark in-person symposium in June 2023 assembled 43 participants from the US and internationally, including patients with IPF, investigators, and regulatory representatives, to discuss the immediate future of IPF clinical trial endpoints. Patient advocates were central to discussions, which evaluated endpoints according to regulatory standards and the FDA's "feels, functions, survives" criteria. Results: Three themes emerged: 1) consensus on endpoints mirroring the lived experiences of patients with IPF; 2) consideration of replacing forced vital capacity (FVC) as the primary endpoint, potentially by composite endpoints that include 'feels, functions, survives' measures or FVC as components; 3) support for simplified, user-friendly patient-reported outcomes (PROs) as either components of primary composite endpoints or key secondary endpoints, supplemented by functional tests as secondary endpoints and novel biomarkers as supportive measures . Conclusion: This report, detailing the proceedings of this pivotal symposium, suggests a potential turning point in designing future IPF clinical trials more attuned to outcomes meaningful to patients, and documents the collective agreement across multidisciplinary stakeholders on the importance of anchoring IPF trial endpoints on real patient experiences-namely, how they feel, function, and survive. There is considerable optimism that clinical care in IPF will progress through trials focused on patient-centric insights, ultimately guiding transformative treatment strategies to enhance patients' quality of life and survival.
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- 2024
30. Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.
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Lancaster, Lisa, Cottin, Vincent, Ramaswamy, Murali, Wuyts, Wim A., Jenkins, R. Gisli, Scholand, Mary Beth, Kreuter, Michael, Valenzuela, Claudia, Ryerson, Christopher J., Goldin, Jonathan, Kim, Grace Hyun J., Jurek, Marzena, Decaris, Martin, Clark, Annie, Turner, Scott, Barnes, Chris N., Achneck, Hardean E., Cosgrove, Gregory P., Lefebvre, Éric A., and Flaherty, Kevin R.
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IDIOPATHIC pulmonary fibrosis ,COUGH ,CLINICAL trials ,PULMONARY fibrosis ,INVESTIGATIONAL drugs ,DRUG development - Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Objectives: Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. Methods: This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in fibrosis-related biomarkers. Measurements and Main Results: Bexotegrast was well tolerated, with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Participants who were treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those who received placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging, and a decrease in fibrosis-associated biomarkers was observed with bexotegrast versus placebo. Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registered with (NCT04396756). [ABSTRACT FROM AUTHOR]
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- 2024
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31. Use of Race-Specific Equations in Pulmonary Function Tests Impedes Potential Eligibility for Care and Treatment of Pulmonary Fibrosis.
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Adegunsoye, Ayodeji, Bachman, Wendi Mason, Flaherty, Kevin R., Li, Zhongze, and Gupta, Sachin
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LUNGS ,PULMONARY function tests ,PULMONARY fibrosis ,VITAL capacity (Respiration) ,BLACK people ,INTERSTITIAL lung diseases - Abstract
Rationale: The use of race-specific reference values to evaluate pulmonary function has long been embedded into clinical practice; however, there is a growing consensus that this practice may be inappropriate and that the use of race-neutral equations should be adopted to improve access to health care. Objectives: To evaluate whether the use of race-neutral equations to assess percent predicted forced vital capacity (FVC%
pred ) impacts eligibility for clinical trials, antifibrotic therapy, and referral for lung transplantation in Black, Hispanic/Latino, and White patients with interstitial lung disease (ILD). Methods: FVC%pred values for patients from the Pulmonary Fibrosis Foundation Patient Registry were calculated using race-specific (Hankinson and colleagues, 1999), race-agnostic (Global Lung Function Initiative [GLI]-2012), and race-neutral (GLI-2022 or GLI-Global) equations. Eligibility for ILD clinical trials (FVC%pred >45% and <90%), antifibrotic therapy (FVC%pred >55% and <82%), and lung transplantation referral (FVC%pred <70%) based on GLI-2022 and GLI-2012 equations were compared with those based on the Hankinson 1999 equation. Results: Baseline characteristics were available for 1,882 patients (Black, n = 104; Hispanic/Latino, n = 103; White, n = 1,675), and outcomes were evaluated in 1,531 patients with FVC%pred within ±90 days of registry enrollment (Black, n = 78; Hispanic/Latino, n = 72; White, n = 1,381). Black patients were younger at the time of consent and more likely to be female compared with Hispanic/Latino or White patients. Compared with GLI-2022, the Hankinson 1999 equation misclassified 22% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for ILD clinical trial eligibility; 21% of Black patients, 17% of Hispanic/Latino patients, and 19% of White patients for antifibrotic therapy eligibility; and 6% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for lung transplantation referral. Similar trends were observed when comparing the GLI-2012 and Hankinson 1999 equations. Conclusions: Misclassification of patients for critical interventions is highly prevalent when using the Hankinson 1999 equation and highlights the need to consider adopting the race-neutral GLI-2022 equation for enhanced accuracy and more equitable representation in pulmonary health care. Our results make a compelling case for reevaluating the use of race as a physiological variable and emphasize the pressing need for continuous innovation to ensure equal and optimal care for all patients regardless of their race or ethnicity. Clinical trial registered with (NCT 02758808). [ABSTRACT FROM AUTHOR]- Published
- 2024
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32. The Keys to Making a Confident Diagnosis of IPF
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Sheth, Jamie, Wadhwa, Anish, Flaherty, Kevin R., 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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33. 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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34. Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial
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Abe, S., Aburto, M., Acosta, O., Andrews, C., Antin-Ozerkis, D., Arce, G., Arias, M., Avdeev, S., Barczyk, A., Bascom, R., Bazdyrev, E., Beirne, P., Belloli, E., Bergna, M.A., Bergot, E., Bhatt, N., Blaas, S., Bondue, B., Bonella, F., Britt, E., Buch, K., Burk, J., Cai, H., Cantin, A., Castillo Villegas, D.M., Cazaux, A., Cerri, S., Chaaban, S., Chaudhuri, N., Cottin, V., Crestani, B., Criner, G., Dahlqvist, C., Danoff, S., Dematte D'Amico, J., Dilling, D., Elias, P., Ettinger, N., Falk, J., Fernández Pérez, E.R., Gamez-Dubuis, A., Giessel, G., Gifford, A., Glassberg, M., Glazer, C., Golden, J., Gómez Carrera, L., Guiot, J., Hallowell, R., Hayashi, H., Hetzel, J., Hirani, N., Homik, L., Hope-Gill, B., Hotchkin, D., Ichikado, K., Ilkovich, M., Inoue, Y., Izumi, S., Jassem, E., Jones, L., Jouneau, S., Kaner, R., Kang, J., Kawamura, T., Kessler, R., Kim, Y., Kishi, K., Kitamura, H., Kolb, M., Kondoh, Y., Kono, C., Koschel, D., Kreuter, M., Kulkarni, T., Kus, J., Lebargy, F., León Jiménez, A., Luo, Q., Mageto, Y., Maher, T.M., Makino, S., Marchand-Adam, S., Marquette, C., Martinez, R., Martínez, M., Maturana Rozas, R., Miyazaki, Y., Moiseev, S., Molina-Molina, M., Morrison, L., Morrow, L., Moua, T., Nambiar, A., Nishioka, Y., Nunes, H., Okamoto, M., Oldham, J., Otaola, M., Padilla, M., Park, J.S., Patel, N., Pesci, A., Piotrowski, W., Pitts, L., Poonyagariyagorn, H., Prasse, A., Quadrelli, S., Randerath, W., Refini, R., Reynaud-Gaubert, M., Riviere, F., Rodríguez Portal, J.A., Rosas, I., Rossman, M., Safdar, Z., Saito, T., Sakamoto, N., Salinas Fénero, M., Sauleda, J., Schmidt, S., Scholand, M.B., Schwartz, M., Shapera, S., Shlobin, O., Sigal, B., Silva Orellana, A., Skowasch, D., Song, J.W., Stieglitz, S., Stone, H., Strek, M., Suda, T., Sugiura, H., Takahashi, H., Takaya, H., Takeuchi, T., Thavarajah, K., Tolle, L., Tomassetti, S., Tomii, K., Valenzuela, C., Vancheri, C., Varone, F., Veeraraghavan, S., Villar, A., Weigt, S., Wemeau, L., Wuyts, W., Xu, Z., Yakusevich, V., Yamada, Y., Yamauchi, H., Ziora, D., Wells, Athol U, Flaherty, Kevin R, Brown, Kevin K, Inoue, Yoshikazu, Devaraj, Anand, Richeldi, Luca, Moua, Teng, Crestani, Bruno, Wuyts, Wim A, Stowasser, Susanne, Quaresma, Manuel, Goeldner, Rainer-Georg, Schlenker-Herceg, Rozsa, and Kolb, Martin
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- 2020
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35. 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.
- Published
- 2020
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36. 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
- Published
- 2020
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37. Computational Deconvolution of Cell Type-Specific Gene Expression in COPD and IPF Lungs Reveals Disease Severity Associations
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Ryu, Min Hyung, primary, Yun, Jeong H., additional, Kim, Kangjin, additional, Gentili, Michele, additional, Ghosh, Auyon, additional, Sciurba, Frank, additional, Barwick, Lucas, additional, Limper, Andrew, additional, Criner, Gerard, additional, Brown, Kevin K., additional, Wise, Robert, additional, Martinez, Fernando J., additional, Flaherty, Kevin R., additional, Cho, Michael H., additional, Castaldi, Peter J., additional, DeMeo, Dawn L., additional, Silverman, Edwin K., additional, Hersh, Craig P., additional, and Morrow, Jarrett D., additional
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- 2024
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38. Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on ‘Feels, Functions, Survives’. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a Patient Advocacy Organization, and a Regulatory Agency
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Raghu, Ganesh, primary, Ghazipura, Marya, additional, Fleming, Thomas R., additional, Aronson, Kerri I., additional, Behr, Jürgen, additional, Brown, Kevin K., additional, Flaherty, Kevin R., additional, Kazerooni, Ella A., additional, Maher, Toby M., additional, Richeldi, Luca, additional, Lasky, Joseph A., additional, Swigris, Jeffrey J., additional, Busch, Robert, additional, Garrard, Lili, additional, Ahn, Dong-Hyun, additional, Li, Ji, additional, Puthawala, Khalid, additional, Rodal, Gabriela, additional, Seymour, Sally, additional, Weir, Nargues, additional, Danoff, Sonye K., additional, Ettinger, Neil, additional, Goldin, Jonathan, additional, Glassberg, Marilyn K., additional, Kawano-Dourado, Leticia, additional, Khalil, Nasreen, additional, Lancaster, Lisa, additional, Lynch, David A., additional, Mageto, Yolanda, additional, Noth, Imre, additional, Shore, Jessica E., additional, Wijsenbeek, Marlies, additional, Brown, Robert, additional, Grogan, Daniel, additional, Ivey, Dorothy, additional, Golinska, Patrycja, additional, Karimi-Shah, Banu, additional, and Martinez, Fernando J., additional
- Published
- 2024
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39. A Multi-dimensional Classifier to Support Lung Transplant Referral in Patients with Pulmonary Fibrosis
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Vu Pugashetti, Janelle, primary, Kim, John S., additional, Combs, Michael P., additional, Ma, Shwu-Fan, additional, Adegunsoye, Ayodeji, additional, Linderholm, Angela L., additional, Strek, Mary E., additional, Chen, Ching-Hsien, additional, Dilling, Daniel F., additional, Whelan, Timothy P.M., additional, Flaherty, Kevin R., additional, Martinez, Fernando J., additional, Noth, Imre, additional, and Oldham, Justin M., additional
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- 2024
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40. Association of hospital admission and forced vital capacity endpoints with survival in patients with idiopathic pulmonary fibrosis: analysis of a pooled cohort from three clinical trials
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Durheim, Michael T, Collard, Harold R, Roberts, Rhonda S, Brown, Kevin K, Flaherty, Kevin R, King, Talmadge E, Palmer, Scott M, Raghu, Ganesh, Snyder, Laurie D, Anstrom, Kevin J, Martinez, Fernando J, and investigators, for the IPFnet
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Rare Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Respiratory ,Good Health and Well Being ,Aged ,Cohort Studies ,Female ,Hospitalization ,Humans ,Idiopathic Pulmonary Fibrosis ,Male ,Middle Aged ,Proportional Hazards Models ,Risk ,Survival Analysis ,United States ,Vital Capacity ,IPFnet investigators ,Public Health and Health Services ,Other Medical and Health Sciences ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundMortality is an impractical primary endpoint for clinical trials in patients with idiopathic pulmonary fibrosis who have mild-to-moderate physiological impairment because event rates are low. Change in forced vital capacity (FVC) is widely accepted as a surrogate for mortality and is the most common primary endpoint in clinical trials for this disorder. Use of hospital admission as a predictor for mortality, independent of FVC decline, has not been well defined. We aimed to ascertain the independent and combined association of hospital admission and at least a 10% decrease in FVC with all-cause mortality.MethodsWe did a pooled cohort study of 517 patients with idiopathic pulmonary fibrosis from three IPFnet multicentre randomised controlled trials. We compared the incidence of non-elective hospital admission and a 10% or greater reduction in FVC across strata of baseline physiological impairment. We used Cox proportional-hazards models to assess the risk of all-cause mortality associated with these surrogate events, occurring up to a predefined landmark timepoint. The three studies are registered at ClinicalTrials.gov, numbers NCT00650091, NCT00517933, and NCT00957242.FindingsSeven patients died before the landmark timepoint. Of the 510 patients remaining, 38 (7%) were admitted to hospital up to the predefined timepoint and 58 (11%) had a categorical decrease in FVC of at least 10%. Most patients admitted to hospital did not have a 10% or greater decrease in FVC (30 vs eight). Both surrogate events were associated with subsequent time to death from any cause (hazard ratio [HR] for admission 4·05, 95% CI 1·36-12·11 vs HR for 10% or greater decline in FVC 4·68, 1·83-11·99). When causes of hospital admission were considered, only respiratory events were associated with mortality (5·97, 1·81-19·74).InterpretationHospital admission might be an appropriate component of a clinically meaningful composite endpoint that improves the feasibility of clinical trials in idiopathic pulmonary fibrosis. Further studies are needed to refine the most appropriate definition of hospital admission for future trials.FundingUS National Heart, Lung, and Blood Institute (NHLBI), and The Cowlin Family Fund at the Chicago Community Trust.
- Published
- 2015
41. Use of a molecular classifier to identify usual interstitial pneumonia in conventional transbronchial lung biopsy samples: a prospective validation study
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Raghu, Ganesh, Flaherty, Kevin R, Lederer, David J, Lynch, David A, Colby, Thomas V, Myers, Jeffrey L, Groshong, Steve D, Larsen, Brandon T, Chung, Jonathan H, Steele, Mark P, Benzaquen, Sadia, Calero, Karel, Case, Amy H, Criner, Gerard J, Nathan, Steven D, Rai, Navdeep S, Ramaswamy, Murali, Hagmeyer, Lars, Davis, J Russell, Gauhar, Umair A, Pankratz, Daniel G, Choi, Yoonha, Huang, Jing, Walsh, P Sean, Neville, Hannah, Lofaro, Lori R, Barth, Neil M, Kennedy, Giulia C, Brown, Kevin K, and Martinez, Fernando J
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- 2019
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42. Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory
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Salisbury, Margaret L., Gu, Tian, Murray, Susan, Gross, Barry H., Chughtai, Aamer, Sayyouh, Mohamed, Kazerooni, Ella A., Myers, Jeffrey L., Lagstein, Amir, Konopka, Kristine E., Belloli, Elizabeth A., Sheth, Jamie S., White, Eric S., Holtze, Colin, Martinez, Fernando J., and Flaherty, Kevin R.
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- 2019
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43. Frailty and geriatric conditions in older patients with idiopathic pulmonary fibrosis
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Sheth, Jamie S., Xia, Meng, Murray, Susan, Martinez, Carlos H., Meldrum, Catherine A., Belloli, Elizabeth A., Salisbury, Margaret L., White, Eric S., Holtze, Colin H., and Flaherty, Kevin R.
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- 2019
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44. Lung function outcomes in the INPULSIS® trials of nintedanib in idiopathic pulmonary fibrosis
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Brown, Kevin K., Flaherty, Kevin R., Cottin, Vincent, Raghu, Ganesh, Inoue, Yoshikazu, Azuma, Arata, Huggins, John T., Richeldi, Luca, Stowasser, Susanne, Stansen, Wibke, Schlenker-Herceg, Rozsa, Maher, Toby M., and Wells, Athol U.
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- 2019
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45. Open-Access Biorepository for Idiopathic Pulmonary Fibrosis. The Way Forward
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White, Eric S, Brown, Kevin K, Collard, Harold R, Conoscenti, Craig S, Cosgrove, Gregory P, Flaherty, Kevin R, Leff, Jonathan A, Martinez, Fernando J, Roman, Jesse, Rose, Dan, Violette, Shelia, and Kaminski, Naftali
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Biomedical and Clinical Sciences ,Clinical Sciences ,Rare Diseases ,Lung ,Autoimmune Disease ,Clinical Research ,4.5 Resources and infrastructure (detection) ,Detection ,screening and diagnosis ,Respiratory ,Biomedical Research ,Humans ,Idiopathic Pulmonary Fibrosis ,Informatics ,Specimen Handling ,Tissue Banks ,biological specimen banks ,humans ,lung ,research priorities ,respiratory tract diseases ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Although widespread use of animal modeling has transformed pulmonary research, the overarching goal of biomedical research is to enhance our understanding of human physiology and pathology. Thus, we believe that future gains in understanding human lung disease will be enhanced when studying patient-derived samples becomes an integral part of the investigational process. For idiopathic pulmonary fibrosis (IPF), investigators need quality human specimens, collected in a standardized fashion, along with carefully annotated, long-term clinical and outcomes data to address current knowledge gaps. Access to human lung tissues through commercial entities or the Lung Tissue Resource Consortium, an NHLBI-funded consortium, has demonstrated the feasibility of this approach. However, these samples are not always well annotated or collected uniformly and are limited in their breadth to address future IPF research needs. Therefore, we propose leveraging ongoing and future studies in IPF to establish a biorepository that will meet current and future needs of IPF investigations. Specifically, we propose that blood, cell, and lung samples, linked to robust longitudinal clinical phenotyping generated from future industry, federally sponsored, and investigator-initiated clinical studies be prospectively and uniformly collected and stored in a biorepository and linked registry. Here we outline standardized methodologies that would allow specimens and clinical data collected from different studies to be integrated and accessible to the IPF research community for investigations that will inform future basic and translational research in IPF. Such a biorepository needs the combined efforts of all stakeholders, to be driven by projected future scientific needs and to be available to all qualified researchers. We believe this infrastructure is crucial, is feasible, and would accelerate research in IPF.
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- 2014
46. Smoking-related idiopathic interstitial pneumonia
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Flaherty, Kevin R, Fell, Charlene, Aubry, Marie-Christine, Brown, Kevin, Colby, Thomas, Costabel, Ulrich, Franks, Teri J, Gross, Barry H, Hansell, David M, Kazerooni, Ella, Kim, Dong Soon, King, Talmadge E, Kitachi, Masanori, Lynch, David, Myers, Jeff, Nagai, Sonoko, Nicholson, Andrew G, Poletti, Venerino, Raghu, Ganesh, Selman, Moises, Toews, Galen, Travis, William, Wells, Athol U, Vassallo, Robert, and Martinez, Fernando J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Pneumonia & Influenza ,Clinical Research ,Tobacco Smoke and Health ,Prevention ,Tobacco ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Pneumonia ,Respiratory ,Adult ,Aged ,Carbon Monoxide ,Female ,Humans ,Idiopathic Interstitial Pneumonias ,International Cooperation ,Male ,Mental Recall ,Mexico ,Middle Aged ,Models ,Organizational ,Prognosis ,Pulmonary Medicine ,Radiology ,Republic of Korea ,Retrospective Studies ,Smoking ,Tobacco Smoke Pollution ,United Kingdom ,United States ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.
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- 2014
47. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.
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Saketkoo, Lesley Ann, Mittoo, Shikha, Huscher, Dörte, Khanna, Dinesh, Dellaripa, Paul F, Distler, Oliver, Flaherty, Kevin R, Frankel, Sid, Oddis, Chester V, Denton, Christopher P, Fischer, Aryeh, Kowal-Bielecka, Otylia M, LeSage, Daphne, Merkel, Peter A, Phillips, Kristine, Pittrow, David, Swigris, Jeffrey, Antoniou, Katerina, Baughman, Robert P, Castelino, Flavia V, Christmann, Romy B, Christopher-Stine, Lisa, Collard, Harold R, Cottin, Vincent, Danoff, Sonye, Highland, Kristin B, Hummers, Laura, Shah, Ami A, Kim, Dong Soon, Lynch, David A, Miller, Frederick W, Proudman, Susanna M, Richeldi, Luca, Ryu, Jay H, Sandorfi, Nora, Sarver, Catherine, Wells, Athol U, Strand, Vibeke, Matteson, Eric L, Brown, Kevin K, Seibold, James R, and CTD-ILD Special Interest Group
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CTD-ILD Special Interest Group ,Humans ,Lung Diseases ,Interstitial ,Connective Tissue Diseases ,Registries ,Consensus ,International Cooperation ,Societies ,Medical ,Congresses as Topic ,Randomized Controlled Trials as Topic ,Idiopathic Pulmonary Fibrosis ,Connective tissue disease associated lung disease ,Idiopathic pulmonary fibrosis ,Interstitial Fibrosis ,Rheumatoid lung disease ,Systemic disease and lungs ,Lung Diseases ,Interstitial ,Societies ,Medical ,Respiratory System ,Clinical Sciences - Abstract
RationaleClinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.MethodsThe Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).ResultsA core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.ConclusionIdentification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
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- 2014
48. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report
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Blackwell, Timothy S, Tager, Andrew M, Borok, Zea, Moore, Bethany B, Schwartz, David A, Anstrom, Kevin J, Bar-Joseph, Ziv, Bitterman, Peter, Blackburn, Michael R, Bradford, William, Brown, Kevin K, Chapman, Harold A, Collard, Harold R, Cosgrove, Gregory P, Deterding, Robin, Doyle, Ramona, Flaherty, Kevin R, Garcia, Christine Kim, Hagood, James S, Henke, Craig A, Herzog, Erica, Hogaboam, Cory M, Horowitz, Jeffrey C, King, Talmadge E, Loyd, James E, Lawson, William E, Marsh, Clay B, Noble, Paul W, Noth, Imre, Sheppard, Dean, Olsson, Julie, Ortiz, Luis A, O’Riordan, Thomas G, Oury, Tim D, Raghu, Ganesh, Roman, Jesse, Sime, Patricia J, Sisson, Thomas H, Tschumperlin, Daniel, Violette, Shelia M, Weaver, Timothy E, Wells, Rebecca G, White, Eric S, Kaminski, Naftali, Martinez, Fernando J, Wynn, Thomas A, Thannickal, Victor J, and Eu, Jerry P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Orphan Drug ,Rare Diseases ,Lung ,Autoimmune Disease ,Respiratory ,Good Health and Well Being ,Animals ,Biomedical Research ,Disease Models ,Animal ,Extracellular Matrix ,Genetic Predisposition to Disease ,Humans ,Idiopathic Pulmonary Fibrosis ,Inflammation ,Mice ,Pulmonary Alveoli ,Respiratory Mucosa ,idiopathic pulmonary fibrosis ,alveolar epithelial cells ,extracellular matrix ,interstitial lung disease ,inflammation ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI.
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- 2014
49. Deep Learning Classification of Usual Interstitial Pneumonia Predicts Outcomes.
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Humphries, Stephen M., Thieke, Devlin, Baraghoshi, David, Strand, Matthew J., Swigris, Jeffrey J., Chae, Kum Ju, Hwang, Hye Jeon, Oh, Andrea S., Flaherty, Kevin R., Adegunsoye, Ayodeji, Jablonski, Renea, Lee, Cathryn T., Husain, Aliya N., Chung, Jonathan H., Strek, Mary E., and Lynch, David A.
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IDIOPATHIC pulmonary fibrosis ,DEEP learning ,MACHINE learning ,INTERSTITIAL lung diseases ,PULMONARY fibrosis ,RECEIVER operating characteristic curves ,NONINVASIVE diagnostic tests ,DICOM (Computer network protocol) - Abstract
Rationale: Computed tomography (CT) enables noninvasive diagnosis of usual interstitial pneumonia (UIP), but enhanced image analyses are needed to overcome the limitations of visual assessment. Objectives: Apply multiple instance learning (MIL) to develop an explainable deep learning algorithm for prediction of UIP from CT and validate its performance in independent cohorts. Methods: We trained an MIL algorithm using a pooled dataset (n = 2,143) and tested it in three independent populations: data from a prior publication (n = 127), a single-institution clinical cohort (n = 239), and a national registry of patients with pulmonary fibrosis (n = 979). We tested UIP classification performance using receiver operating characteristic analysis, with histologic UIP as ground truth. Cox proportional hazards and linear mixed-effects models were used to examine associations between MIL predictions and survival or longitudinal FVC. Measurements and Main Results: In two cohorts with biopsy data, MIL improved accuracy for histologic UIP (area under the curve, 0.77 [n = 127] and 0.79 [n = 239]) compared with visual assessment (area under the curve, 0.65 and 0.71). In cohorts with survival data, MIL-UIP classifications were significant for mortality (n = 239, mortality to April 2021: unadjusted hazard ratio, 3.1; 95% confidence interval [CI], 1.96–4.91; P < 0.001; and n = 979, mortality to July 2022: unadjusted hazard ratio, 3.64; 95% CI, 2.66–4.97; P < 0.001). Individuals classified as UIP positive by the algorithm had a significantly greater annual decline in FVC than those classified as UIP negative (−88 ml/yr vs. −45 ml/yr; n = 979; P < 0.01), adjusting for extent of lung fibrosis. Conclusions: Computerized assessment using MIL identifies clinically significant features of UIP on CT. Such a method could improve confidence in radiologic assessment of patients with interstitial lung disease, potentially enabling earlier and more precise diagnosis. [ABSTRACT FROM AUTHOR]
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- 2024
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50. Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis.
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Oldham, Justin M., Huang, Yong, Bose, Swaraj, Ma, Shwu-Fan, Kim, John S., Schwab, Alexandra, Ting, Christopher, Mou, Kaniz, Lee, Cathryn T., Adegunsoye, Ayodeji, Ghodrati, Sahand, Pugashetti, Janelle Vu, Nazemi, Nazanin, Strek, Mary E., Linderholm, Angela L., Chen, Ching-Hsien, Murray, Susan, Zemans, Rachel L., Flaherty, Kevin R., and Martinez, Fernando J.
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IDIOPATHIC pulmonary fibrosis ,PROTEOMICS ,BIOMARKERS ,PULMONARY fibrosis ,MEDICAL registries - Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) causes progressive lung scarring and high mortality. Reliable and accurate prognostic biomarkers are urgently needed. Objectives: To identify and validate circulating protein biomarkers of IPF survival. Methods: High-throughput proteomic data were generated using prospectively collected plasma samples from patients with IPF from the Pulmonary Fibrosis Foundation Patient Registry (discovery cohort) and the Universities of California, Davis; Chicago; and Virginia (validation cohort). Proteins associated with three-year transplant-free survival (TFS) were identified using multivariable Cox proportional hazards regression. Those associated with TFS after adjustment for false discovery in the discovery cohort were advanced for testing in the validation cohort, with proteins maintaining TFS association with consistent effect direction considered validated. After combining cohorts, functional analyses were performed, and machine learning was used to derive a proteomic signature of TFS. Measurements and Main Results: Of 2,921 proteins tested in the discovery cohort (n = 871), 231 were associated with differential TFS. Of these, 140 maintained TFS association with consistent effect direction in the validation cohort (n = 355). After cohorts were combined, the validated proteins with the strongest TFS association were latent-transforming growth factor β-binding protein 2 (hazard ratio [HR], 2.43; 95% confidence interval [CI] = 2.09–2.82), collagen α-1(XXIV) chain (HR, 2.21; 95% CI = 1.86–2.39), and keratin 19 (HR, 1.60; 95% CI = 1.47–1.74). In decision curve analysis, a proteomic signature of TFS outperformed a similarly derived clinical prediction model. Conclusions: In the largest proteomic investigation of IPF outcomes performed to date, we identified and validated 140 protein biomarkers of TFS. These results shed important light on potential drivers of IPF progression. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
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