202 results on '"Martinez, Fernando J."'
Search Results
2. Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases
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Kawano-Dourado, Leticia, Kulkarni, Tejaswini, Ryerson, Christopher J, Rivera-Ortega, Pilar, Baldi, Bruno Guedes, Chaudhuri, Nazia, Funke-Chambour, Manuela, Hoffmann-Vold, Anna-Maria, Johannson, Kerri A, Khor, Yet Hong, Montesi, Sydney B, Piccari, Lucilla, Prosch, Helmut, Molina-Molina, María, Sellares Torres, Jacobo, Bauer-Ventura, Iazsmin, Rajan, Sujeet, Jacob, Joseph, Richards, Duncan, Spencer, Lisa G, Wendelberger, Barbara, Jensen, Tom, Quintana, Melanie, Kreuter, Michael, Gordon, Anthony C, Martinez, Fernando J, Kaminski, Naftali, Cornelius, Victoria, Lewis, Roger, Adams, Wendy, and Jenkins, Gisli
- Abstract
BackgroundFibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD).MethodsDescription of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure.ResultsThe target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results.ConclusionBy using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.
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- 2024
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3. IMPORTANCE OF PRE- AND POSTBRONCHODILATOR SPIROMETRY RESULTS IN INTERPRETATIONS
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YAWN, BARBARA P, MAKE, BARRY J, MANNINO, DAVID M, JOO, MIN J, THOMASHOW, BYRON M, HAN, MEILAN K, MARTINEZ, FERNANDO J, MELDRUM, CATHERINE A, ANGULO, DANIELA, and MURRAY, SUSAN
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- 2024
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4. Predicting severe chronic obstructive pulmonary disease exacerbations using quantitative CT: a retrospective model development and external validation study
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Chaudhary, Muhammad F A, Hoffman, Eric A, Guo, Junfeng, Comellas, Alejandro P, Newell, John D, Nagpal, Prashant, Fortis, Spyridon, Christensen, Gary E, Gerard, Sarah E, Pan, Yue, Wang, Di, Abtin, Fereidoun, Barjaktarevic, Igor Z, Barr, R Graham, Bhatt, Surya P, Bodduluri, Sandeep, Cooper, Christopher B, Gravens-Mueller, Lisa, Han, MeiLan K, Kazerooni, Ella A, Martinez, Fernando J, Menchaca, Martha G, Ortega, Victor E, III, Robert Paine, Schroeder, Joyce D, Woodruff, Prescott G, and Reinhardt, Joseph M
- Abstract
Quantitative CT is becoming increasingly common for the characterisation of lung disease; however, its added potential as a clinical tool for predicting severe exacerbations remains understudied. We aimed to develop and validate quantitative CT-based models for predicting severe chronic obstructive pulmonary disease (COPD) exacerbations.
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- 2023
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5. Quantitative Interstitial Abnormality Progression and Outcomes in the Genetic Epidemiology of COPD and Pittsburgh Lung Screening Study Cohorts
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Choi, Bina, Adan, Najma, Doyle, Tracy J., San José Estépar, Ruben, Harmouche, Rola, Humphries, Stephen M., Moll, Matthew, Cho, Michael H., Putman, Rachel K., Hunninghake, Gary M., Kalhan, Ravi, Liu, Gabrielle Y., Diaz, Alejandro A., Mason, Stefanie E., Rahaghi, Farbod N., Pistenmaa, Carrie L., Enzer, Nicholas, Poynton, Clare, Sánchez-Ferrero, Gonzalo Vegas, Ross, James C., Lynch, David A., Martinez, Fernando J., Han, MeiLan K., Bowler, Russell P., Wilson, David O., Rosas, Ivan O., Washko, George R., San José Estépar, Raúl, and Ash, Samuel Y.
- Abstract
The risk factors and clinical outcomes of quantitative interstitial abnormality progression over time have not been characterized.
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- 2023
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6. Longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis: a genome-wide association study
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Allen, Richard J, Oldham, Justin M, Jenkins, David A, Leavy, Olivia C, Guillen-Guio, Beatriz, Melbourne, Carl A, Ma, Shwu-Fan, Jou, Jonathan, Kim, John S, Fahy, William A, Oballa, Eunice, Hubbard, Richard B, Navaratnam, Vidya, Braybrooke, Rebecca, Saini, Gauri, Roach, Katy M, Tobin, Martin D, Hirani, Nik, Whyte, Moira K B, Kaminski, Naftali, Zhang, Yingze, Martinez, Fernando J, Linderholm, Angela L, Adegunsoye, Ayodeji, Strek, Mary E, Maher, Toby M, Molyneaux, Philip L, Flores, Carlos, Noth, Imre, Gisli Jenkins, R, and Wain, Louise V
- Abstract
Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease characterised by progressive scarring leading to alveolar stiffness, reduced lung capacity, and impeded gas transfer. We aimed to identify genetic variants associated with declining lung capacity or declining gas transfer after diagnosis of IPF.
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- 2023
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7. Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans
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Angelini, Elsa D, Yang, Jie, Balte, Pallavi P, Hoffman, Eric A, Manichaikul, Ani W, Sun, Yifei, Shen, Wei, Austin, John H M, Allen, Norrina B, Bleecker, Eugene R, Bowler, Russell, Cho, Michael H, Cooper, Christopher S, Couper, David, Dransfield, Mark T, Garcia, Christine Kim, Han, MeiLan K, Hansel, Nadia N, Hughes, Emlyn, Jacobs, David R, Kasela, Silva, Kaufman, Joel Daniel, Kim, John Shinn, Lappalainen, Tuuli, Lima, Joao, Malinsky, Daniel, Martinez, Fernando J, Oelsner, Elizabeth C, Ortega, Victor E, Paine, Robert, Post, Wendy, Pottinger, Tess D, Prince, Martin R, Rich, Stephen S, Silverman, Edwin K, Smith, Benjamin M, Swift, Andrew J, Watson, Karol E, Woodruff, Prescott G, Laine, Andrew F, and Barr, R Graham
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BackgroundTreatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.MethodsNew CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case–control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined.ResultsThe algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91–1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1, which is implicated in mucin hypersecretion (p=1.1 ×10−8). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome.ConclusionLarge-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.
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- 2023
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8. Risk of COPD exacerbation is increased by poor sleep quality and modified by social adversity.
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Baugh, Aaron, Buhr, Russell G, Quibrera, Pedro, Barjaktarevic, Igor, Barr, R Graham, Bowler, Russell, Han, Meilan King, Kaufman, Joel D, Koch, Abigail L, Krishnan, Jerry, Labaki, Wassim, Martinez, Fernando J, Mkorombindo, Takudzwa, Namen, Andrew, Ortega, Victor, Paine, Robert, Peters, Stephen P, Schotland, Helena, Sundar, Krishna, and Zeidler, Michelle R
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- 2022
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9. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort.
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Radicioni, Giorgia, Ceppe, Agathe, Ford, Amina A, Alexis, Neil E, Barr, R Graham, Bleecker, Eugene R, Christenson, Stephanie A, Cooper, Christopher B, Han, MeiLan K, Hansel, Nadia N, Hastie, Annette T, Hoffman, Eric A, Kanner, Richard E, Martinez, Fernando J, Ozkan, Esin, Paine III, Robert, Woodruff, Prescott G, O'Neal, Wanda K, Boucher, Richard C, and Kesimer, Mehmet
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OBSTRUCTIVE lung diseases ,CHRONIC bronchitis ,PULMONARY function tests ,RESPIRATORY obstructions ,PANEL analysis ,MUCINS - Abstract
We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD. SPIROMICS was a multicentre, observational study in patients aged 40–80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV 1 , forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF 25–75%). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344). This analysis included 331 participants (mean age 63 years [SEM 9·40]), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV 1 and FEF 25–75% , and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04–1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV 1 , FEV 1 /FVC, FEF 25–75% , and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years. These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents. National Institutes of Health; National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Significance of FEV3/FEV6in Recognition of Early Airway Disease in Smokers at Risk of Development of COPD
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Yee, Nathan, Markovic, Daniela, Buhr, Russell G., Fortis, Spyridon, Arjomandi, Mehrdad, Couper, David, Anderson, Wayne H., Paine, Robert, Woodruff, Prescott G., Han, Meilan K., Martinez, Fernando J., Barr, R. Graham, Wells, James M., Ortega, Victor E., Hoffman, Eric A., Kim, Victor, Drummond, M. Bradley, Bowler, Russell P., Curtis, Jeffrey L., Cooper, Christopher B., Tashkin, Donald P., and Barjaktarevic, Igor Z.
- Abstract
Small airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease.
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- 2022
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11. Serum proteomic profiling of rheumatoid arthritis–interstitial lung disease with a comparison to idiopathic pulmonary fibrosis
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Wu, Xiaoping, Jeong, Yunju, Poli de Frías, Sergio, Easthausen, Imaani, Hoffman, Katherine, Oromendia, Clara, Taheri, Shahrad, Esposito, Anthony J, Quesada Arias, Luisa, Ayaub, Ehab A, Maurer, Rie, Gill, Ritu R, Hatabu, Hiroto, Nishino, Mizuki, Frits, Michelle L, Iannaccone, Christine K, Weinblatt, Michael E, Shadick, Nancy A, Dellaripa, Paul F, Choi, Augustine M K, Kim, Edy Y, Rosas, Ivan O, Martinez, Fernando J, and Doyle, Tracy J
- Abstract
Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.
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- 2022
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12. Association of circulating cell-free double-stranded DNA and metabolic derangements in idiopathic pulmonary fibrosis
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Whalen, William, Buyukozkan, Mustafa, Moore, Bethany, Moon, Jong-Seok, Dela Cruz, Charles S, Martinez, Fernando J, Choi, Augustine M K, Krumsiek, Jan, Stout-Delgado, Heather, and Cho, Soo Jung
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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with unclear aetiology and poorly understood pathophysiology. Although plasma levels of circulating cell-free DNA (ccf-DNA) and metabolomic changes have been reported in IPF, the associations between ccf-DNA levels and metabolic derangements in lung fibrosis are unclear. Here, we demonstrate that ccf-double-stranded DNA (dsDNA) is increased in patients with IPF with rapid progression of disease compared with slow progressors and healthy controls and that ccf-dsDNA associates with amino acid metabolism, energy metabolism and lipid metabolism pathways in patients with IPF.
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- 2022
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13. Screening for idiopathic pulmonary fibrosis using comorbidity signatures in electronic health records
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Onishchenko, Dmytro, Marlowe, Robert J., Ngufor, Che G., Faust, Louis J., Limper, Andrew H., Hunninghake, Gary M., Martinez, Fernando J., and Chattopadhyay, Ishanu
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Idiopathic pulmonary fibrosis (IPF) is a lethal fibrosing interstitial lung disease with a mean survival time of less than 5 years. Nonspecific presentation, a lack of effective early screening tools, unclear pathobiology of early-stage IPF and the need for invasive and expensive procedures for diagnostic confirmation hinder early diagnosis. In this study, we introduce a new screening tool for IPF in primary care settings that requires no new laboratory tests and does not require recognition of early symptoms. Using subtle comorbidity signatures identified from the history of medical encounters of individuals, we developed an algorithm, called the zero-burden comorbidity risk score for IPF (ZCoR-IPF), to predict the future risk of an IPF diagnosis. ZCoR-IPF was trained on a national insurance claims database and validated on three independent databases, comprising a total of 2,983,215 participants, with 54,247 positive cases. The algorithm achieved positive likelihood ratios greater than 30 at a specificity of 0.99 across different cohorts, for both sexes, and for participants with different risk states and history of confounding diseases. The area under the receiver-operating characteristic curve for ZCoR-IPF in predicting IPF exceeded 0.88 and was approximately 0.84 at 1 and 4 years before a conventional diagnosis, respectively. Thus, if adopted, ZCoR-IPF can potentially enable earlier diagnosis of IPF and improve outcomes of disease-modifying therapies and other interventions.
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- 2022
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14. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
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Radicioni, Giorgia, Ceppe, Agathe, Ford, Amina A, Alexis, Neil E, Barr, R Graham, Bleecker, Eugene R, Christenson, Stephanie A, Cooper, Christopher B, Han, MeiLan K, Hansel, Nadia N, Hastie, Annette T, Hoffman, Eric A, Kanner, Richard E, Martinez, Fernando J, Ozkan, Esin, Paine, Robert, Woodruff, Prescott G, O'Neal, Wanda K, Boucher, Richard C, and Kesimer, Mehmet
- Abstract
We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD.
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- 2021
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15. Triple Versus Dual Combination Therapy in Chronic Obstructive Pulmonary Disease in Asian Countries: Analysis of the IMPACT Trial
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Halpin, David M. G., Criner, Gerard J., Dransfield, Mark T., Han, MeiLan K., Hartley, Benjamin, Harvey, Catherine, Jones, C. Elaine, Kato, Motokazu, Lange, Peter, Lettis, Sally, Lomas, David A., Martinez, Fernando J., Martin, Neil, Singh, Dave, Wise, Robert, Zheng, Jinping, and Lipson, David A.
- Abstract
Introduction: In the IMPACT trial, single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) reduced moderate/severe exacerbation rates versus FF/VI or UMEC/VI dual therapy in patients with chronic obstructive pulmonary disease (COPD); however, pneumonia incidence was higher in FF-containing arms. As COPD is a growing problem in Asia, we compared the efficacy and safety of FF/UMEC/VI in Asia versus non-Asia regions. Methods: IMPACT was a double-blind, 52-week trial in symptomatic COPD patients with ≥ 1 moderate/severe exacerbation in the prior year. This pre-specified analysis evaluated the annual rate of moderate/severe exacerbations, change from baseline in trough forced expiratory volume in 1 s, and St George’s Respiratory Questionnaire total score, mortality, and safety (including pneumonia) in Asia versus non-Asia regions. Results: The intent-to-treat population comprised 10,355 patients (Asia n= 1644 [16%]). Rate ratios (95% confidence intervals) for moderate/severe exacerbations with FF/UMEC/VI were 0.89 (0.76–1.05) versus FF/VI and 0.86 (0.71–1.04) versus UMEC/VI in Asia, and 0.84 (0.79–0.90) and 0.74 (0.68–0.80) in non-Asia. Efficacy of FF/UMEC/VI on other endpoints was similar in both regions. There was an increased incidence of investigator-reported pneumonia in patients in Asia (FF/UMEC/VI: 13%; FF/VI: 14%; UMEC/VI: 6%) compared with non-Asia (FF/UMEC/VI: 6%; FF/VI: 5%; UMEC/VI: 4%). The increased risk of pneumonia in patients in Asia was most marked in patients with lower body mass index, lower lung function, and taking inhaled corticosteroids. In post hoc analysis of adjudicated on-treatment all-cause mortality, probabilities of death were numerically lower in both regions with FF/UMEC/VI (Asia: 1.16%; non-Asia: 1.35%) and FF/VI (Asia: 1.77%; non-Asia: 1.21%) versus UMEC/VI (Asia: 1.91%; non-Asia: 2.23%). Conclusions: FF/UMEC/VI provides similar benefits in COPD patients in Asia and non-Asia regions. Clinical benefits of treatment, including reduction in mortality risk, should be weighed against risk of pneumonia, taking account of all known risk factors. Trial Registration: ClinicalTrials.gov identification, NCT02164513.
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- 2021
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16. Moving beyond usual interstitial pneumonia to define progressive fibrotic interstitial lung disease.
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Podolanczuk, Anna J and Martinez, Fernando J
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INTERSTITIAL lung diseases ,IDIOPATHIC pulmonary fibrosis - Published
- 2021
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17. Study design of BI 1015550 for idiopathic pulmonary fibrosis and progressive pulmonary fibrosis: a plain language summary
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Maher, Toby M, Azuma, Arata, Cottin, Vincent, Assassi, Shervin, Hoffmann-Vold, Anna-Maria, Kreuter, Michael, Martinez, Fernando J, Oldham, Justin M, Valenzuela, Claudia, Wijsenbeek, Marlies S, Liu, Yi, Wachtlin, Daniel, Stowasser, Susanne, Zoz, Donald F, and Richeldi, Luca
- Abstract
What is this summary about?Two ongoing clinical studies are part of a programme called FIBRONEER. The FIBRONEER studies are testing the drug BI 1015550 as a treatment for people with idiopathic pulmonary fibrosis (IPF) and people with progressive pulmonary fibrosis (PPF).IPF is a severe lung disease where scar tissue builds up in the lungs. The ‘idiopathic’ part means that doctors do not know the cause of the lung scarring. PPF is a general term to describe the worsening of lung scarring in any disease where scar tissue forms in the lungs, both from known causes such as other underlying diseases and for unknown reasons. While IPF can be considered to be a typical form of worsening lung scarring, in clinical studies, IPF and PPF are usually considered separately. In both IPF and PPF, scar tissue builds up in the lungs, making them smaller and no longer able to take in oxygen well. This leads to difficulty in breathing and getting oxygen to the tissues, making it difficult to perform daily activities and reducing the patient's quality of life.The symptoms and outcomes of PPF are often similar to IPF.What study drug is being investigated?BI 1015550 is a new study drug being developed to reduce scarring in the lungs in IPF and PPF. In the FIBRONEER studies, some participants are taking BI 1015550 and others are taking placebo. The placebo looks identical to BI 1015550 but does not contain any medicine. Researchers will compare the study drug to placebo to find out how well the study drug works. Participants may also take another approved medicine to treat their lung scarring. The FIBRONEER studies are investigating the effects of BI 1015550 alone and in combination with any existing medicines the participants are taking. The goal is to see whether BI 1015550 can slow down or stop a decline in lung function in people with IPF and PPF, and how well it is tolerated.
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- 2024
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18. Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD
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Hanania, Nicola A., Mannino, David M., Criner, Gerard J., Dransfield, Mark T., Han, MeiLan K., Jones, C. Elaine, Kilbride, Sally, Lomas, David A., Martin, Neil, Martinez, Fernando J., Singh, Dave, Wise, Robert A., Halpin, David M.G., Lima, Robson, and Lipson, David A.
- Abstract
In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile.
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- 2021
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19. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial
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Martinez, Fernando J., Afzal, Amna Sadaf, Smith, Jaclyn A., Ford, Anthony P., Li, Jerry Jing, Li, Yuping, and Kitt, Michael M.
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Introduction: Chronic cough is a highly problematic symptom for patients with idiopathic pulmonary fibrosis (IPF); limited therapeutic options are available. We evaluated gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough in IPF. Methods: This randomized, double-blind, placebo-controlled, crossover study included subjects with IPF. Sequence A included gefapixant 50 mg BID (period 1; 14 days) followed by placebo (period 2; 14 days); sequence B had the opposite sequence of treatments. This regimen was specified in a protocol amendment that modified the original active treatment regimen of gefapixant 50 mg BID for 10 days and 150 mg BID for 4 days. Patients randomized to the original treatment regimen were excluded from efficacy analyses but included in safety assessments. The primary efficacy endpoint was change from baseline in awake cough frequency (coughs/hour) from periods 1 and 2 combined. Adverse events (AEs) were monitored throughout the study. Results: A total of 51 subjects were randomized, 44 of whom were randomized to treatment sequences evaluated in the primary efficacy analysis (i.e., 22 subjects in sequence A and 22 subjects in sequence B); seven subjects received the treatment assigned before the protocol amendment and were excluded from efficacy analyses. The change from baseline in awake cough frequency from periods 1 and 2 combined (mixed model for repeated measures analysis) did not demonstrate a significant reduction versus placebo in cough at day 14 (p= 0.90); in a post hoc analysis of log-transformed data pvalue for reduction versus placebo at day 14 was 0.07. The most common AEs were related to taste (dysgeusia and ageusia). Conclusions: Gefapixant was generally well tolerated but was not associated with a significant improvement in chronic cough in subjects with IPF as defined by the primary endpoint in this study. Trial Registration: NCT02502097.
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- 2021
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20. Clinical Phenotypes of Atopy and Asthma in COPD
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Putcha, Nirupama, Fawzy, Ashraf, Matsui, Elizabeth C., Liu, Mark C., Bowler, Russ P., Woodruff, Prescott G., O’Neal, Wanda K., Comellas, Alejandro P., Han, MeiLan K., Dransfield, Mark T., Wells, J. Michael, Lugogo, Njira, Gao, Li, Talbot, C. Conover, Hoffman, Eric A., Cooper, Christopher B., Paulin, Laura M., Kanner, Richard E., Criner, Gerard, Ortega, Victor E., Barr, R. Graham, Krishnan, Jerry A., Martinez, Fernando J., Drummond, M. Bradley, Wise, Robert A., Diette, Gregory B., Hersh, Craig P., and Hansel, Nadia N.
- Abstract
Little is known about the concordance of atopy with asthma COPD overlap. Among individuals with COPD, a better understanding of the phenotypes characterized by asthma overlap and atopy is needed to better target therapies.
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- 2020
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21. Serum IgG Levels and Risk of COPD Hospitalization
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Leitao Filho, Fernando Sergio, Mattman, Andre, Schellenberg, Robert, Criner, Gerard J., Woodruff, Prescott, Lazarus, Stephen C., Albert, Richard K., Connett, John, Han, Meilan K., Gay, Steven E., Martinez, Fernando J., Fuhlbrigge, Anne L., Stoller, James K., MacIntyre, Neil R., Casaburi, Richard, Diaz, Philip, Panos, Ralph J., Cooper, J. Allen, Bailey, William C., LaFon, David C., Sciurba, Frank C., Kanner, Richard E., Yusen, Roger D., Au, David H., Pike, Kenneth C., Fan, Vincent S., Leung, Janice M., Man, Shu-Fan Paul, Aaron, Shawn D., Reed, Robert M., and Sin, Don D.
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Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.
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- 2020
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22. Host, Gender, and Early-Life Factors as Risks for Chronic Obstructive Pulmonary Disease
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Han, MeiLan K. and Martinez, Fernando J.
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Although smoking results in lung pathology in many, still not all smokers develop chronic obstructive pulmonary disease (COPD). Roughly a quarter of patients with COPD have never smoked. An understanding of both host and environmental factors beyond smoking that contribute to disease development remain critical to understanding disease prevention and ultimately effectively intervene. In this article, we summarize host factors, including genetics and gender, as well as early-life events that contribute to the development of COPD.
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- 2020
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23. Progressive fibrosing interstitial lung disease: clinical uncertainties, consensus recommendations, and research priorities
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George, Peter M, Spagnolo, Paolo, Kreuter, Michael, Altinisik, Goksel, Bonifazi, Martina, Martinez, Fernando J, Molyneaux, Philip L, Renzoni, Elisabetta A, Richeldi, Luca, Tomassetti, Sara, Valenzuela, Claudia, Vancheri, Carlo, Varone, Francesco, Cottin, Vincent, and Costabel, Ulrich
- Abstract
Within the spectrum of fibrosing interstitial lung diseases (ILDs) is a subset of patients who have inexorable progression of pulmonary fibrosis despite treatment, which is known as the progressive fibrotic phenotype. Although the concept of progressive fibrosing ILD has been applied largely to patients with idiopathic pulmonary fibrosis (IPF), there is now an increasing focus on irreversible progressive fibrosis in a proportion of patients with a range of underlying ILD diagnoses. Evidence has emerged to support a possible role for antifibrotic therapy in these patients. In this Position Paper, we discuss the importance of retaining diagnostic scrutiny within the multidisciplinary team and suggest a multidomain definition for progressive fibrosis. We consider the potential role of antifibrotic drugs as second-line therapy in the treatment algorithm for patients with progressive non-IPF ILD. We highlight risk factors that might predispose individuals to developing progressive fibrosis. Finally, we discuss key uncertainties and future directions for research and clinical practice.
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- 2020
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24. Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life
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Keller, Thomas, Spece, Laura J., Donovan, Lucas M., Udris, Edmunds, Coggeshall, Scott S., Griffith, Matthew, Bryant, Alexander D., Casaburi, Richard, Cooper, J. Allen, Criner, Gerard J., Diaz, Philip T., Fuhlbrigge, Anne L., Gay, Steven E., Kanner, Richard E., Martinez, Fernando J., Panos, Ralph J., Shade, David, Sternberg, Alice, Stibolt, Thomas, Stoller, James K., Tonascia, James, Wise, Robert, Yusen, Roger D., Au, David H., and Feemster, Laura C.
- Abstract
Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear.
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- 2020
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25. 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., 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
- Abstract
Chronic 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.
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- 2020
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26. Associations Among 25-Hydroxyvitamin D Levels, Lung Function, and Exacerbation Outcomes in COPD
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Burkes, Robert M., Ceppe, Agathe S., Doerschuk, Claire M., Couper, David, Hoffman, Eric A., Comellas, Alejandro P., Barr, R. Graham, Krishnan, Jerry A., Cooper, Christopher, Labaki, Wassim W., Ortega, Victor E., Wells, J. Michael, Criner, Gerard J., Woodruff, Prescott G., Bowler, Russell P., Pirozzi, Cheryl S., Hansel, Nadia N., Wise, Robert A., Brown, Todd T., Drummond, M. Bradley, Alexis, Neil E., Anderson, Wayne H., Arjomandi, Mehrdad, Barjaktarevic, Igor, Barr, R. Graham, Bateman, Lori A., Bhatt, Surya P., Bleecker, Eugene R., Boucher, Richard C., Bowler, Russell P., Christenson, Stephanie A., Comellas, Alejandro P., Cooper, Christopher B., Couper, David J., Criner, Gerard J., Crystal, Ronald G., Curtis, Jeffrey L., Doerschuk, Claire M., Dransfield, Mark T., Drummond, Brad, Freeman, Christine M., Galban, Craig, Han, MeiLan K., Hansel, Nadia N., Hastie, Annette T., Hoffman, Eric A., Huang, Yvonne, Kaner, Robert J., Kanner, Richard E., Kleerup, Eric C., Krishnan, Jerry A., LaVange, Lisa M., Lazarus, Stephen C., Martinez, Fernando J., Meyers, Deborah A., Moore, Wendy C., Newell, John D., Paine, Robert, Paulin, Laura, Peters, Stephen P., Pirozzi, Cheryl, Putcha, Nirupama, Oelsner, Elizabeth C., O’Neal, Wanda K., Ortega, Victor E., Raman, Sanjeev, Rennard, Stephen I., Tashkin, Donald P., Wells, J. Michael, Wise, Robert A., Woodruff, Prescott G., Postow, Lisa, and Viviano, Lisa
- Abstract
The relationship between 25-hydroxyvitamin D (25-OH-vitamin D) and COPD outcomes remains unclear. Using the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), we determined associations among baseline 25-OH-vitamin D and cross-sectional and longitudinal lung function and COPD exacerbations.
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- 2020
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27. Association of Long-term Ambient Ozone Exposure With Respiratory Morbidity in Smokers
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Paulin, Laura M., Gassett, Amanda J., Alexis, Neil E., Kirwa, Kipruto, Kanner, Richard E., Peters, Stephen, Krishnan, Jerry A., Paine, Robert, Dransfield, Mark, Woodruff, Prescott G., Cooper, Christopher B., Barr, R. Graham, Comellas, Alejandro P., Pirozzi, Cheryl S., Han, MeiLan, Hoffman, Eric A., Martinez, Fernando J., Woo, Han, Peng, Roger D., Fawzy, Ashraf, Putcha, Nirupama, Breysse, Patrick N., Kaufman, Joel D., and Hansel, Nadia N.
- Abstract
IMPORTANCE: Few studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history. OBJECTIVE: To investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (≥20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis. EXPOSURES: The 10-year mean historical ambient ozone concentration at participants’ residences estimated by cohort-specific spatiotemporal modeling. MAIN OUTCOMES AND MEASURES: Spirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure. RESULTS: A total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (β = 0.94; 95% CI, 0.25-1.64; P = .007) and percentage of air trapping (β = 1.60; 95% CI, 0.16-3.04; P = .03); worse scores for the mMRC Dyspnea Scale (β = 0.10; 95% CI, 0.03-0.17; P = .008), CAT (β = 0.65; 95% CI, 0.05-1.26; P = .04), and SGRQ (β = 1.47; 95% CI, 0.01-2.93; P = .048); lower FEV1% predicted value (β = −2.50; 95% CI, −4.42 to −0.59; P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66; P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76; P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result. CONCLUSIONS AND RELEVANCE: This study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.
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- 2020
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28. Maintenance inhaler therapy preferences of patients with asthma or chronic obstructive pulmonary disease: a discrete choice experiment
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Tervonen, Tommi, Hawken, Natalia, Hanania, Nicola A, Martinez, Fernando J, Heidenreich, Sebastian, and Gilbert, Ileen
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BackgroundA variety of maintenance inhaler therapies are available to treat asthma and COPD. Patient-centric treatment choices require understanding patient preferences for the alternative therapies.MethodsA self-completed web-based discrete choice experiment was conducted to elicit patient preferences for inhaler device and medication attributes. Selection of attributes was informed by patient focus groups and literature review.ResultsThe discrete choice experiment was completed by 810 patients with asthma and 1147 patients with COPD. Patients with asthma most valued decreasing the onset of action from 30 to 5 min, followed by reducing yearly exacerbations from 3 to 1. Patients with COPD most and equally valued decreasing the onset of action from 30 to 5 min and reducing yearly exacerbations from 3 to 1. Both patients with asthma and patients with COPD were willing to accept an additional exacerbation in exchange for a 15 min decrease in onset of action and a longer onset of action in exchange for a lower risk of adverse effects from inhaled corticosteroids. Patients with asthma and COPD valued once-daily over twice-daily dosing, pressurised inhalers over dry powder inhalers and non-capsule priming over single-use capsules, although these attributes were not valued as highly as faster onset of action or reduced exacerbations.ConclusionsThe most important maintenance inhaler attributes for patients with asthma and COPD were fast onset of symptom relief and a lower rate of exacerbations. Concerns about safety of inhaled corticosteroids and device convenience also affected patient preferences but were less important.
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- 2020
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29. Objectively Measured Chronic Lung Injury on Chest CT
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Harmouche, Rola, Ash, Samuel Y., Putman, Rachel K., Hunninghake, Gary M., San Jose Estepar, Ruben, Martinez, Fernando J., Choi, Augustine M., Lynch, David A., Hatabu, Hiroto, Han, MeiLan K., Bowler, Russell P., Kalhan, Ravi, Rosas, Ivan O., Washko, George R., and San Jose Estepar, Raul
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Tobacco smoke exposure is associated with emphysema and pulmonary fibrosis, both of which are irreversible. We have developed a new objective CT analysis tool that combines densitometry with machine learning to detect high attenuation changes in visually normal appearing lung (NormHA) that may precede these diseases.
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- 2019
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30. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study.
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Nathan, Steven D, Behr, Jürgen, Collard, Harold R, Cottin, Vincent, Hoeper, Marius M, Martinez, Fernando J, Corte, Tamera J, Keogh, Anne M, Leuchte, Hanno, Mogulkoc, Nesrin, Ulrich, Silvia, Wuyts, Wim A, Yao, Zhen, Boateng, Francis, and Wells, Athol U
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IDIOPATHIC interstitial pneumonias ,PULMONARY hypertension ,INTERACTIVE voice response (Telecommunication) ,INTERSTITIAL lung diseases ,SYSTOLIC blood pressure ,SYMPTOMS - Abstract
Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP. RISE-IIP was a double-blind, randomised, placebo-controlled study done at 65 pulmonary hypertension and interstitial lung disease centres in 19 countries to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Eligible patients were adults (aged 18–80 years) diagnosed with idiopathic interstitial pneumonia (as per American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines), forced vital capacity (FVC) of at least 45%, 6MWD of 150–450 m, WHO functional classes II–IV, precapillary pulmonary hypertension confirmed by right heart catheterisation, systolic blood pressure of at least 95 mm Hg, and no signs or symptoms of hypotension. Patients were randomly allocated (1:1) using an interactive voice and web response system to riociguat (0·5–2·5 mg three times daily) or placebo for 26 weeks (main study), after which they could enter an open-label extension in which all patients received riociguat. The primary endpoint was change in 6-min walking distance (6MWD) in the intention-to-treat population. Prespecified safety variables included adverse events and serious adverse events, laboratory parameters, and adverse events of special interest (haemoptysis and symptomatic hypotension), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov , number NCT02138825. Between June 4, 2014, and May 5, 2016, we enrolled 229 participants. After the exclusion of 82 participants, 147 were randomly allocated to treatment (73 to riociguat, 74 to placebo). The study was terminated early (median treatment duration 157 days [range 6–203]) at the request of the data monitoring committee owing to increased serious adverse events (main study: 27 [37%] of 73 participants in the riociguat group vs 17 [23%] of 74 in the placebo group) and mortality in patients receiving riociguat, and the absence of efficacy signals in the riociguat group. 11 patients died in the main study (eight in the riociguat group, three in the placebo group), and nine died in the extension phase (one in the riociguat group, eight in the former placebo group; all received riociguat). In the main study, the most common adverse events were peripheral oedema (16 [22%] of 73 in the riociguat group vs seven [9%] of 74 in the placebo group) and diarrhoea (11 [15%] vs seven [9%]). The most common serious adverse events were worsening of interstitial lung disease (main study: six [8%] of 73 in the riociguat group vs five [7%] of 74 in the placebo group) and pneumonia (four [5%] vs one [1%]). Riociguat did not improve 6MWD versus placebo at 26 weeks (least-squares mean difference 21 m; 95% CI −9 to 52). In patients with PH-IIP, riociguat was associated with increased serious adverse events and mortality, and an unfavourable risk–benefit profile. Riociguat should not be used in patients with PH-IIP. Bayer AG and Merck & Co. [ABSTRACT FROM AUTHOR]
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- 2019
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31. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.
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Pascoe, Steven, Barnes, Neil, Brusselle, Guy, Compton, Chris, Criner, Gerard J, Dransfield, Mark T, Halpin, David M G, Han, MeiLan K, Hartley, Benjamin, Lange, Peter, Lettis, Sally, Lipson, David A, Lomas, David A, Martinez, Fernando J, Papi, Alberto, Roche, Nicolas, van der Valk, Ralf J P, Wise, Robert, and Singh, Dave
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OBSTRUCTIVE lung diseases ,EOSINOPHILS - Abstract
Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS. We aimed to model these relationships and their interactions, including outcomes other than exacerbations. IMPACT was a phase 3, randomised, double-blind, parallel-group, 52-week global study comparing once-daily single-inhaler triple therapy (fluticasone furoate–umeclidinium–vilanterol) with dual inhaled therapy (fluticasone furoate–vilanterol or umeclidinium–vilanterol). Eligible patients had moderate-to-very-severe COPD and at least one moderate or severe exacerbation in the previous year. We used fractional polynomials to model continuous blood eosinophil counts. We used negative binomial regression for numbers of moderate and severe exacerbations, severe exacerbations, and pneumonia. We modelled differences at week 52 in trough FEV 1 , St George's Respiratory Questionnaire (SGRQ) total score, and Transition Dyspnoea Index using repeated measurements mixed effect models. IMPACT was registered with ClinicalTrials.gov , number NCT02164513. The magnitude of benefit of regimens containing ICS (fluticasone furoate–umeclidinium–vilanterol n=4151 and fluticasone furoate–vilanterol n=4134) in reducing rates of moderate and severe exacerbations increased in proportion with blood eosinophil count, compared with a non-ICS dual long-acting bronchodilator (umeclidinium–vilanterol n=2070). The moderate and severe exacerbation rate ratio for triple therapy versus umeclidinium–vilanterol was 0·88 (95% CI 0·74 to 1·04) at blood eosinophil count less than 90 cells per μL and 0·56 (0·47 to 0·66) at counts of 310 cells per μL or more; the corresponding rate ratio for fluticasone furoate–vilanterol versus umeclidinium–vilanterol was 1·09 (0·91 to 1·29) and 0·56 (0·47 to 0·66), respectively. Similar results were observed for FEV 1 , Transition Dyspnoea Index, and SGRQ total score; however, the relationship with FEV 1 was less marked. At blood eosinophil counts less than 90 cells per μL and at counts of 310 cells per μL or more, the triple therapy versus umeclidinium–vilanterol treatment difference was 40 mL (95% CI 10 to 70) and 60 mL (20 to 100) for trough FEV 1 , −0·01 (–0·68 to 0·66) and 0·30 (–0·37 to 0·97) for Transition Dyspnoea Index score, and −0·01 (–1·81 to 1·78) and −2·78 (–4·64 to −0·92) for SGRQ total score, respectively. Smoking status modified the relationship between observed efficacy and blood eosinophil count for moderate or severe exacerbations, Transition Dyspnoea Index, and FEV 1 , with former smokers being more corticosteroid responsive at any eosinophil count than current smokers. This analysis of the IMPACT trial shows that assessment of blood eosinophil count and smoking status has the potential to optimise ICS use in clinical practice in patients with COPD and a history of exacerbations. GlaxoSmithKline. [ABSTRACT FROM AUTHOR]
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- 2019
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32. Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study.
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Scott, Madeleine K D, Quinn, Katie, Li, Qin, Carroll, Robert, Warsinske, Hayley, Vallania, Francesco, Chen, Shirley, Carns, Mary A, Aren, Kathleen, Sun, Jiehuan, Koloms, Kimberly, Lee, Jungwha, Baral, Jessika, Kropski, Jonathan, Zhao, Hongyu, Herzog, Erica, Martinez, Fernando J, Moore, Bethany B, Hinchcliff, Monique, and Denny, Joshua
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MYELOFIBROSIS ,PULMONARY fibrosis ,IDIOPATHIC pulmonary fibrosis ,BLOOD cell count ,SYSTEMIC scleroderma ,ELECTRONIC health records ,HYPERTROPHIC cardiomyopathy - Abstract
There is an urgent need for biomarkers to better stratify patients with idiopathic pulmonary fibrosis by risk for lung transplantation allocation who have the same clinical presentation. We aimed to investigate whether a specific immune cell type from patients with idiopathic pulmonary fibrosis could identify those at higher risk of poor outcomes. We then sought to validate our findings using cytometry and electronic health records. We first did a discovery analysis with transcriptome data from the Gene Expression Omnibus at the National Center for Biotechnology Information for 120 peripheral blood mononuclear cell (PBMC) samples of patients with idiopathic pulmonary fibrosis. We estimated percentages of 13 immune cell types using statistical deconvolution, and investigated the association of these cell types with transplant-free survival. We validated these results using PBMC samples from patients with idiopathic pulmonary fibrosis in two independent cohorts (COMET and Yale). COMET profiled monocyte counts in 45 patients with idiopathic pulmonary fibrosis from March 12, 2010, to March 10, 2011, using flow cytometry; we tested if increased monocyte count was associated with the primary outcome of disease progression. In the Yale cohort, 15 patients with idiopathic pulmonary fibrosis (with five healthy controls) were classed as high risk or low risk from April 28, 2014, to Aug 20, 2015, using a 52-gene signature, and we assessed whether monocyte percentage (measured by cytometry by time of flight) was higher in high-risk patients. We then examined complete blood count values in the electronic health records (EHR) of 45 068 patients with idiopathic pulmonary fibrosis, systemic sclerosis, hypertrophic cardiomyopathy, or myelofibrosis from Stanford (Jan 01, 2008, to Dec 31, 2015), Northwestern (Feb 15, 2001 to July 31, 2017), Vanderbilt (Jan 01, 2008, to Dec 31, 2016), and Optum Clinformatics DataMart (Jan 01, 2004, to Dec 31, 2016) cohorts, and examined whether absolute monocyte counts of 0·95 K/μL or greater were associated with all-cause mortality in these patients. In the discovery analysis, estimated CD14+ classical monocyte percentages above the mean were associated with shorter transplant-free survival times (hazard ratio [HR] 1·82, 95% CI 1·05–3·14), whereas higher percentages of T cells and B cells were not (0·97, 0·59–1·66; and 0·78, 0·45–1·34 respectively). In two validation cohorts (COMET trial and the Yale cohort), patients with higher monocyte counts were at higher risk for poor outcomes (COMET Wilcoxon p=0·025; Yale Wilcoxon p=0·049). Monocyte counts of 0·95 K/μL or greater were associated with mortality after adjusting for forced vital capacity (HR 2·47, 95% CI 1·48–4·15; p=0·0063), and the gender, age, and physiology index (HR 2·06, 95% CI 1·22–3·47; p=0·0068) across the COMET, Stanford, and Northwestern datasets). Analysis of medical records of 7459 patients with idiopathic pulmonary fibrosis showed that patients with monocyte counts of 0·95 K/μL or greater were at increased risk of mortality with lung transplantation as a censoring event, after adjusting for age at diagnosis and sex (Stanford HR=2·30, 95% CI 0·94–5·63; Vanderbilt 1·52, 1·21–1·89; Optum 1·74, 1·33–2·27). Likewise, higher absolute monocyte count was associated with shortened survival in patients with hypertrophic cardiomyopathy across all three cohorts, and in patients with systemic sclerosis or myelofibrosis in two of the three cohorts. Monocyte count could be incorporated into the clinical assessment of patients with idiopathic pulmonary fibrosis and other fibrotic disorders. Further investigation into the mechanistic role of monocytes in fibrosis might lead to insights that assist the development of new therapies. Bill & Melinda Gates Foundation, US National Institute of Allergy and Infectious Diseases, and US National Library of Medicine. [ABSTRACT FROM AUTHOR]
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- 2019
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33. Reprint of: Voxel-Wise Longitudinal Parametric Response Mapping Analysis of Chest Computed Tomography in Smokers.
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Labaki, Wassim W., Gu, Tian, Murray, Susan, Hatt, Charles R., Galbán, Craig J., Ross, Brian D., Martinez, Carlos H., Curtis, Jeffrey L., Hoffman, Eric A., Pompe, Esther, Lynch, David A., Kazerooni, Ella A., Martinez, Fernando J., and Han, MeiLan K.
- Abstract
Rationale and Objectives: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and Methods: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).Results: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.Conclusion: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]- Published
- 2019
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34. Voxel-Wise Longitudinal Parametric Response Mapping Analysis of Chest Computed Tomography in Smokers.
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Labaki, Wassim W., Gu, Tian, Murray, Susan, Hatt, Charles R., Galbán, Craig J., Ross, Brian D., Martinez, Carlos H., Curtis, Jeffrey L., Hoffman, Eric A., Pompe, Esther, Lynch, David A., Kazerooni, Ella A., Martinez, Fernando J., and Han, MeiLan K.
- Abstract
Rationale and Objectives: Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers.Materials and Methods: We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH).Results: Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH.Conclusion: A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]- Published
- 2019
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35. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised...
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Ferguson, Gary T, Rabe, Klaus F, Martinez, Fernando J, Fabbri, Leonardo M, Wang, Chen, Ichinose, Masakazu, Bourne, Eric, Ballal, Shaila, Darken, Patrick, DeAngelis, Kiernan, Aurivillius, Magnus, Dorinsky, Paul, and Reisner, Colin
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ADRENOCORTICAL hormones ,OBSTRUCTIVE lung diseases patients ,BUDESONIDE ,HOSPITAL care ,OCCUPATIONAL diseases - Abstract
Summary Background Inhaled corticosteroids have been used in patients with chronic obstructive pulmonary disease (COPD), but the potential benefits of their use in triple therapy are not well known. We aimed to compare the efficacy of a triple therapy with corresponding dual therapies in symptomatic patients with moderate to very severe COPD, without a requirement for a history of exacerbations. Methods In this double-blind, parallel-group, multicentre phase 3 randomised controlled trial, we recruited patients from hospitals and care centres in Canada, China, Japan, and the USA. Eligible patients were 40–80 years of age, were current or former smokers (with a smoking history of ≥10 pack-years), had an established clinical history of COPD, and were symptomatic for COPD, despite receiving two or more inhaled maintenance therapies for at least 6 weeks before screening. We randomly assigned patients (2:2:1:1) using an interactive web response system to receive budesonide/glycopyrrolate/formoterol fumarate metered-dose inhaler 320/18/9·6 μg (BGF MDI), glycopyrrolate/ formoterol fumarate metered-dose inhaler 18/9·6 μg (GFF MDI), budesonide/formoterol fumarate metered-dose inhaler 320/9·6 μg (BFF MDI), or open-label budesonide/formoterol fumarate dry-powder inhaler 400/12 μg (BUD/ FORM DPI). Primary endpoints for the Europe/Canada statistical analysis approach were FEV 1 area under the curve from 0–4 h (AUC 0–4) for BGF MDI versus BFF MDI and BGF MDI versus BUD/FORM DPI over 24 weeks; and change from baseline in morning pre-dose trough FEV 1 for BGF MDI versus GFF MDI and non-inferiority of BFF MDI versus BUD/FORM DPI (margin of −50 mL from lower bound of 95% CI) over 24 weeks. Comparisons with BUD/FORM DPI were made for the Europe/Canada statistical analysis approach only. This study is registered with ClinicalTrials.gov , number NCT02497001. Findings Between Aug 20, 2015, and Jan 5, 2018, 3047 patients were screened from 215 sites, and 1902 were randomly assigned to receive BGF MDI (n=640), GFF MDI (n=627), BFF MDI (n=316), or BUD/FORM DPI (n=319). Over 24 weeks, BGF MDI significantly improved FEV 1 AUC 0–4 versus BFF MDI (least squares mean difference 104 mL, 95% CI 77 to 131; p<0·0001) and BUD/FORM DPI (91 mL, 64 to 117; p<0·0001). BGF MDI also significantly improved pre-dose trough FEV 1 versus GFF MDI (22 mL, 4 to 39; p=0·0139) and was non-inferior to BUD/FORM DPI (−10 mL, −36 to 16; p=0·4390). At week 24, patients in the BGF MDI group had a significantly improved FEV 1 AUC 0–4 compared with patients receiving BFF MDI (116 mL, 95% CI 80 to 152; p<0·0001); there was a non-significant improvement in the change from baseline in morning pre-dose trough FEV 1 at week 24 versus GFF MDI (13 mL, −9 to 36 mL; p=0·2375). The most common treatment-emergent adverse events were nasopharyngitis (n=49 [8%] in the BGF MDI group; n=41 [7%] in the GFF MDI group; n=26 [8%] in the BFF MDI group; and n=30 [9%] in the BUD/FORM DPI group) and upper respiratory tract infection (n=65 [10%]; n=38 [6%]; n=18 [6%]; and n=22 [7%]). Pneumonia incidence was low (<2%) and similar across treatments. There were two treatment-related deaths, both in the GFF MDI group. Interpretation BGF MDI was efficacious, well tolerated, and could be a more appropriate treatment than the corresponding dual therapies for symptomatic patients with moderate to very severe COPD, irrespective of exacerbation history. Funding Pearl—a member of the AstraZeneca Group. [ABSTRACT FROM AUTHOR]
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- 2018
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36. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort
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Hastie, Annette T, Martinez, Fernando J, Curtis, Jeffrey L, Doerschuk, Claire M, Hansel, Nadia N, Christenson, Stephanie, Putcha, Nirupama, Ortega, Victor E, Li, Xingnan, Barr, R Graham, Carretta, Elizabeth E, Couper, David J, Cooper, Christopher B, Hoffman, Eric A, Kanner, Richard E, Kleerup, Eric, O'Neal, Wanda K, Paine, Richard, Peters, Stephen P, Alexis, Neil E, Woodruff, Prescott G, Han, MeiLan K, Meyers, Deborah A, Bleecker, Eugene R, Alexis, Neil E, Anderson, Wayne H, Barr, R Graham, Bleecker, Eugene R, Boucher, Richard C, Bowler, Russell P, Carretta, Elizabeth E, Christenson, Stephanie A, Comellas, Alejandro P, Cooper, Christopher B, Couper, David J, Criner, Gerard J, Crystal, Ronald G, Curtis, Jeffrey L, Doerschuk, Claire M, Dransfield, Mark T, Freeman, Christine M, Han, MeiLan K, Hansel, Nadia N, Hastie, Annette T, Hoffman, Eric A, Kaner, Robert J, Kanner, Richard E, Kleerup, Eric C, Krishnan, Jerry A, LaVange, Lisa M, Lazarus, Stephen C, Martinez, Fernando J, Meyers, Deborah A, Newell, John D, Oelsner, Elizabeth C, O'Neal, Wanda K, Paine, Robert, Putcha, Nirupama, Rennard, Stephen I., Tashkin, Donald P, Scholand, Mary Beth, Wells, J Michael, Wise, Robert A, and Woodruff, Prescott G
- Abstract
Increased concentrations of eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with increased frequency of exacerbations, reduced lung function, and corticosteroid responsiveness. We aimed to assess whether high eosinophil concentrations in either sputum or blood are associated with a severe COPD phenotype, including greater exacerbation frequency, and whether blood eosinophils are predictive of sputum eosinophils.
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- 2017
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37. Letter to editor – a response to: ‘efficacy and safety of triple combination therapy for treating chronic obstructive pulmonary disease: an expert review’
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Barnes, Neil C., Jones, Paul, Lipson, David A., Singh, Dave, and Martinez, Fernando J.
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- 2021
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38. Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
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Han, MeiLan K, Quibrera, Pedro M, Carretta, Elizabeth E, Barr, R Graham, Bleecker, Eugene R, Bowler, Russell P, Cooper, Christopher B, Comellas, Alejandro, Couper, David J, Curtis, Jeffrey L, Criner, Gerard, Dransfield, Mark T, Hansel, Nadia N, Hoffman, Eric A, Kanner, Richard E, Krishnan, Jerry A, Martinez, Carlos H, Pirozzi, Cheryl B, O'Neal, Wanda K, Rennard, Stephen, Tashkin, Donald P, Wedzicha, Jadwiga A, Woodruff, Prescott, Paine, Robert, Martinez, Fernando J, Alexis, Neil E, Anderson, Wayne H, Barr, R Graham, Bleecker, Eugene R, Boucher, Richard C, Bowler, Russell P, Carretta, Elizabeth E, Christenson, Stephanie A, Comellas, Alejandro P, Cooper, Christopher B, Couper, David J, Criner, Gerard J, Crystal, Ronald G, Curtis, Jeffrey L, Doerschuk, Claire M, Dransfield, Mark T, Freeman, Christine M, Han, MeiLan K, Hansel, Nadia N, Hastie, Annette T, Hoffman, Eric A, Kaner, Robert J, Kanner, Richard E, Kleerup, Eric C, Krishnan, Jerry A, LaVange, Lisa M, Lazarus, Stephen C, Martinez, Fernando J, Meyers, Deborah A, Newell, John D, Oelsner, Elizabeth C, O'Neal, Wanda K, Paine, Robert, Putcha, Nirupama, Rennard, Stephen I., Tashkin, Donald P, Scholand, Mary Beth, Wells, J Michael, Wise, Robert A, and Woodruff, Prescott G
- Abstract
Present treatment strategies to stratify exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) rely on a history of two or more events in the previous year. We aimed to understand year to year variability in exacerbations and factors associated with consistent exacerbations over time.
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- 2017
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39. Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD
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Fortis, Spyridon, Quibrera, Pedro M., Comellas, Alejandro P., Bhatt, Surya P., Tashkin, Donald P., Hoffman, Eric A., Criner, Gerard J., Han, MeiLan K., Barr, R. Graham, Arjomandi, Mehrdad, Dransfield, Mark B., Peters, Stephen P., Dolezal, Brett A., Kim, Victor, Putcha, Nirupama, Rennard, Stephen I., Paine, Robert, Kanner, Richard E., Curtis, Jeffrey L., Bowler, Russell P., Martinez, Fernando J., Hansel, Nadia N., Krishnan, Jerry A., Woodruff, Prescott G., Barjaktarevic, Igor Z., Couper, David, Anderson, Wayne H., Cooper, Christopher B., Alexis, Neil E., Anderson, Wayne H., Arjomandi, Mehrdad, Barjaktarevic, Igor, Barr, R. Graham, Basta, Patricia, Bateman, Lori A., Bhatt, Surya P., Bleecker, Eugene R., Boucher, Richard C., Bowler, Russell P., Christenson, Stephanie A., Comellas, Alejandro P., Cooper, Christopher B., Couper, David J., Criner, Gerard J., Crystal, Ronald G., Curtis, Jeffrey L., Doerschuk, Claire M., Dransfield, Mark T., Drummond, Brad, Freeman, Christine M., Galban, Craig, Han, MeiLan K., Hansel, Nadia N., Hastie, Annette T., Hoffman, Eric A., Huang, Yvonne, Kaner, Robert J., Kanner, Richard E., Kleerup, Eric C., Krishnan, Jerry A., LaVange, Lisa M., Lazarus, Stephen C., Martinez, Fernando J., Meyers, Deborah A., Moore, Wendy C., Newell, John D., Paine, Robert, Paulin, Laura, Peters, Stephen P., Pirozzi, Cheryl, Putcha, Nirupama, Oelsner, Elizabeth C., O’Neal, Wanda K., Ortega, Victor E., Raman, Sanjeev, Rennard, Stephen I., Tashkin, Donald P., Wells, J. Michael, Wise, Robert A., and Woodruff, Prescott G.
- Abstract
Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features.
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- 2023
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40. Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial.
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Raghu, Ganesh, Pellegrini, Carlos A, Yow, Eric, Flaherty, Kevin R, Meyer, Keith, Noth, Imre, Scholand, Mary Beth, Cello, John, Ho, Lawrence A, Pipavath, Sudhakar, Lee, Joyce S, Lin, Jules, Maloney, James, Martinez, Fernando J, Morrow, Ellen, Patti, Marco G, Rogers, Stan, Wolters, Paul J, Yates, Robert, and Anstrom, Kevin J
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LAPAROSCOPIC surgery ,PULMONARY fibrosis ,PULMONARY fibrosis treatment ,PULMONARY hypertension ,CLINICAL trials ,DEGLUTITION disorders - Abstract
Summary Background Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to determine whether treatment of abnormal acid GER with laparoscopic anti-reflux surgery reduces the rate of disease progression. Methods The WRAP-IPF trial was a randomised controlled trial of laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER recruited from six academic centres in the USA. We enrolled patients with IPF, abnormal acid GER (DeMeester score of ≥14·7; measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We excluded patients with a FVC below 50% predicted, a FEV 1 /FVC ratio of less than 0·65, a history of acute respiratory illness in the past 12 weeks, a body-mass index greater than 35, and known severe pulmonary hypertension. Concomitant therapy with nintedanib and pirfenidone was allowed. The primary endpoint was change in FVC from randomisation to week 48, in the intention-to-treat population with mixed-effects models for repeated measures. This trial is registered with ClinicalTrials.gov , number NCT01982968. Findings Between June 1, 2014, and Sept 30, 2016, we screened 72 patients and randomly assigned 58 patients to receive surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20 patients in the no surgery group had an FVC measurement at 48 weeks (p=0·041). Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated the adjusted rate of change in FVC over 48 weeks was −0·05 L (95% CI −0·15 to 0·05) in the surgery group and −0·13 L (−0·23 to −0·02) in the non-surgery group (p=0·28). Acute exacerbation, respiratory-related hospitalisation, and death was less common in the surgery group without statistical significance. Dysphagia (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most common adverse events after surgery. There was one death in the surgery group and four deaths in the non-surgery group. Interpretation Laparoscopic anti-reflux surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A larger, well powered, randomised controlled study of anti-reflux surgery is needed in this population. Funding US National Institutes of Health National Heart, Lung and Blood Institute. [ABSTRACT FROM AUTHOR]
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- 2018
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41. Alveolar eosinophilia in current smokers with chronic obstructive pulmonary disease in the SPIROMICS cohort.
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Martinez, Carlos H., Li, Sara X., Hirzel, Andrew J., Stolberg, Valerie R., Alexis, Neil E., Barr, R. Graham, Bleecker, Eugene R., Carretta, Elizabeth E., Christenson, Stephanie A., Cooper, Christopher B., Couper, David J., Doerschuk, Claire M., Han, MeiLan K., Hansel, Nadia N., Hastie, Annette T., Hoffman, Eric A., Kaner, Robert J., Martinez, Fernando J., Meyers, Deborah A., and O'Neal, Wanda K.
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- 2018
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42. Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial
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Pascoe, Steven, Barnes, Neil, Brusselle, Guy, Compton, Chris, Criner, Gerard J, Dransfield, Mark T, Halpin, David M G, Han, MeiLan K, Hartley, Benjamin, Lange, Peter, Lettis, Sally, Lipson, David A, Lomas, David A, Martinez, Fernando J, Papi, Alberto, Roche, Nicolas, van der Valk, Ralf J P, Wise, Robert, and Singh, Dave
- Abstract
Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS. We aimed to model these relationships and their interactions, including outcomes other than exacerbations.
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- 2019
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43. Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study
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Nathan, Steven D, Behr, Jürgen, Collard, Harold R, Cottin, Vincent, Hoeper, Marius M, Martinez, Fernando J, Corte, Tamera J, Keogh, Anne M, Leuchte, Hanno, Mogulkoc, Nesrin, Ulrich, Silvia, Wuyts, Wim A, Yao, Zhen, Boateng, Francis, and Wells, Athol U
- Abstract
Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP.
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- 2019
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44. Increased monocyte count as a cellular biomarker for poor outcomes in fibrotic diseases: a retrospective, multicentre cohort study
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Scott, Madeleine K D, Quinn, Katie, Li, Qin, Carroll, Robert, Warsinske, Hayley, Vallania, Francesco, Chen, Shirley, Carns, Mary A, Aren, Kathleen, Sun, Jiehuan, Koloms, Kimberly, Lee, Jungwha, Baral, Jessika, Kropski, Jonathan, Zhao, Hongyu, Herzog, Erica, Martinez, Fernando J, Moore, Bethany B, Hinchcliff, Monique, Denny, Joshua, Kaminski, Naftali, Herazo-Maya, Jose D, Shah, Nigam H, and Khatri, Purvesh
- Abstract
There is an urgent need for biomarkers to better stratify patients with idiopathic pulmonary fibrosis by risk for lung transplantation allocation who have the same clinical presentation. We aimed to investigate whether a specific immune cell type from patients with idiopathic pulmonary fibrosis could identify those at higher risk of poor outcomes. We then sought to validate our findings using cytometry and electronic health records.
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- 2019
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45. 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
- Abstract
In the appropriate clinical setting, the diagnosis of idiopathic pulmonary fibrosis (IPF) requires a pattern of usual interstitial pneumonia to be present on high-resolution chest CT (HRCT) or surgical lung biopsy. A molecular usual interstitial pneumonia signature can be identified by a machine learning algorithm in less-invasive transbronchial lung biopsy samples. We report prospective findings for the clinical validity and utility of this molecular test.
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- 2019
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46. Systemic Markers of Inflammation in Smokers With Symptoms Despite Preserved Spirometry in SPIROMICS
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Garudadri, Suresh, Woodruff, Prescott G., Han, MeiLan K., Curtis, Jeffrey L., Barr, R. Graham, Bleecker, Eugene R., Bowler, Russell P., Comellas, Alejandro, Cooper, Christopher B., Criner, Gerard, Dransfield, Mark T., Hansel, Nadia N., Paine, Robert, Krishnan, Jerry A., Peters, Stephen P., Hastie, Annette T., Martinez, Fernando J., O'Neal, Wanda K., Couper, David J., Alexis, Neil E., and Christenson, Stephanie A.
- Abstract
Chronic respiratory symptoms and exacerbation-like events are common among ever-smokers without airflow limitation on spirometry. The pathobiology of respiratory disease in this subgroup remains poorly defined, but may be due to underlying inflammation that overlaps with COPD or asthma. We hypothesized that symptoms, exacerbations, and functional measures of disease severity among smokers with preserved spirometry would be associated with markers of systemic inflammation, similar to what is reported in bone fide COPD, rather than elevated type 2 inflammation, which is often present in asthma.
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- 2019
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47. Hypersensitivity Pneumonitis
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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.
- Abstract
Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype.
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- 2019
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48. Aspirin Use and Respiratory Morbidity in COPD
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Fawzy, Ashraf, Putcha, Nirupama, Aaron, Carrie P., Bowler, Russell P., Comellas, Alejandro P., Cooper, Christopher B., Dransfield, Mark T., Han, MeiLan K., Hoffman, Eric A., Kanner, Richard E., Krishnan, Jerry A., Labaki, Wassim W., Paine, Robert, Paulin, Laura M., Peters, Stephen P., Wise, Robert, Barr, R. Graham, Hansel, Nadia N., Alexis, Neil E., Anderson, Wayne H., Barjaktarevic, Igor, Barr, R. Graham, Bleecker, Eugene R., Boucher, Richard C., Bowler, Russell P., Carretta, Elizabeth E., Christenson, Stephanie A., Comellas, Alejandro P., Cooper, Christopher B., Couper, David J., Criner, Gerard J., Crystal, Ronald G., Curtis, Jeffrey L., Doerschuk, Claire M., Dransfield, Mark T., Freeman, Christine M., Han, MeiLan K., Hansel, Nadia N., Hastie, Annette T., Hoffman, Eric A., Kaner, Robert J., Kanner, Richard E., Kleerup, Eric C., Krishnan, Jerry A., LaVange, Lisa M., Lazarus, Stephen C., Martinez, Fernando J., Meyers, Deborah A., Moore, Wendy C., Newell, John D., Paulin, Laura, Peters, Stephen, Pirozzi, Cheryl, Oelsner, Elizabeth C., O’Neal, Wanda K., Ortega, Victor E., Paine, Robert, Putcha, Nirupama, Raman, Sanjeev, Rennard, Stephen I., Tashkin, Donald P., Wells, J. Michael, Wise, Robert A., and Woodruff, Prescott G.
- Abstract
Aspirin use in COPD has been associated with reduced all-cause mortality in meta-regression analysis with few equivocal studies. However, the effect of aspirin on COPD morbidity is unknown.
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- 2019
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49. Clinical Approach to the Therapy of Asthma-COPD Overlap
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Maselli, Diego J., Hardin, Megan, Christenson, Stephanie A., Hanania, Nicola A., Hersh, Craig P., Adams, Sandra G., Anzueto, Antonio, Peters, Jay I., Han, MeiLan K., and Martinez, Fernando J.
- Abstract
Over the last few years, there has been a renewed interest in patients with characteristics of both asthma and COPD. Although the precise definition of asthma-COPD overlap (ACO) is still controversial, patients with overlapping features are frequently encountered in clinical practice, and may indeed have worse clinical outcomes and increased health-care utilization than those with asthma or COPD. Therefore, there is a critical need to set a framework for the therapeutic approach of such patients. There are key distinctions in the therapy between asthma and COPD, particularly regarding the initial choice of therapy. However, there is considerable overlap in the use of existing medications for both diseases. Furthermore, novel therapies approved for asthma, such as monoclonal antibodies, may have a role in patients with COPD and ACO. The use of biomarkers, such as peripheral blood eosinophils, exhaled nitric oxide, and serum IgE, may help in selecting appropriate therapies for ACO. In this review, we provide an overview of available treatments for both asthma and COPD and explore their potential role in the treatment of patients with ACO.
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- 2019
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50. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial
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Ferguson, Gary T, Rabe, Klaus F, Martinez, Fernando J, Fabbri, Leonardo M, Wang, Chen, Ichinose, Masakazu, Bourne, Eric, Ballal, Shaila, Darken, Patrick, DeAngelis, Kiernan, Aurivillius, Magnus, Dorinsky, Paul, and Reisner, Colin
- Abstract
Inhaled corticosteroids have been used in patients with chronic obstructive pulmonary disease (COPD), but the potential benefits of their use in triple therapy are not well known. We aimed to compare the efficacy of a triple therapy with corresponding dual therapies in symptomatic patients with moderate to very severe COPD, without a requirement for a history of exacerbations.
- Published
- 2018
- Full Text
- View/download PDF
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