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1. Current and future developments in the pharmacology of asthma and COPD: ERS seminar, Naples 2022

Author

Daiana Stolz, Maria Gabriella Matera, Paola Rogliani, Maarten van den Berge, Eleni Papakonstantinou, Reinoud Gosens, Dave Singh, Nicola Hanania, Mario Cazzola, Anke-Hilse Maitland-van der Zee, Laura Fregonese, Alexander G. Mathioudakis, Jørgen Vestbo, Maia Rukhadze, and Clive P. Page

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Pharmacological management of airway obstructive diseases is a fast-evolving field. Several advances in unravelling disease mechanisms as well as intracellular and molecular pathways of drug action have been accomplished. While the clinical translation and implementation of in vitro results to the bedside remains challenging, advances in comprehending the mechanisms of respiratory medication are expected to assist clinicians and scientists in identifying meaningful read-outs and designing clinical studies. This European Respiratory Society Research Seminar, held in Naples, Italy, 5–6 May 2022, focused on current and future developments of the drugs used to treat asthma and COPD; on mechanisms of drug action, steroid resistance, comorbidities and drug interactions; on prognostic and therapeutic biomarkers; on developing novel drug targets based on tissue remodelling and regeneration; and on pharmacogenomics and emerging biosimilars. Related European Medicines Agency regulations are also discussed, as well as the seminar's position on the above aspects.

Published
2023
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2. Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation

Author

Premranjan Kumar, Ob Osahon, David B. Vides, Nicola Hanania, Charles G. Minard, and Rajagopal V. Sekhar

Subjects
COVID-19, glutathione, oxidative stress, oxidant damage, GlyNAC, Therapeutics. Pharmacology, RM1-950
Abstract

Humanity is battling a respiratory pandemic pneumonia named COVID-19 which has resulted in millions of hospitalizations and deaths. COVID-19 exacerbations occur in waves that continually challenge healthcare systems globally. Therefore, there is an urgent need to understand all mechanisms by which COVID-19 results in health deterioration to facilitate the development of protective strategies. Oxidative stress (OxS) is a harmful condition caused by excess reactive-oxygen species (ROS) and is normally neutralized by antioxidants among which Glutathione (GSH) is the most abundant. GSH deficiency results in amplified OxS due to compromised antioxidant defenses. Because little is known about GSH or OxS in COVID-19 infection, we measured GSH, TBARS (a marker of OxS) and F2-isoprostane (marker of oxidant damage) concentrations in 60 adult patients hospitalized with COVID-19. Compared to uninfected controls, COVID-19 patients of all age groups had severe GSH deficiency, increased OxS and elevated oxidant damage which worsened with advancing age. These defects were also present in younger age groups, where they do not normally occur. Because GlyNAC (combination of glycine and N-acetylcysteine) supplementation has been shown in clinical trials to rapidly improve GSH deficiency, OxS and oxidant damage, GlyNAC supplementation has implications for combating these defects in COVID-19 infected patients and warrants urgent investigation.

Published
2021
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3. Review: The potential role of natural agents in treatment of airway inflammation

Author

Amir Sharafkhaneh, Suryakanta Velamuri, Vladimir Badmaev, Charlie Lan, and Nicola Hanania

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Obstructive airway diseases including asthma, chronic obstructive pulmonary disease and cystic fibrosis present with dyspnea and variety of other symptoms. Physiologically, they are characterized by maximal expiratory flow limitation and pathologically, by inflammation of the airways and the lung parenchyma. Inflammation plays a major role in the gradual worsening of the lung function resulting in worsening symptoms. For many years, scientists focused their efforts in identifying various pathways involved in the chronic inflammation present in these diseases. Further, studies are underway to identify various molecular targets in these pathways for the purpose of developing novel therapeutic agents. Natural agents have been used for thousands of years in various cultures for the treatment of several medical conditions and have mostly proven to be safe. Recent in vivo and in vitro studies show potential anti-inflammatory role for some of the existing natural agents. This review provides an overview of the literature related to the anti-inflammatory effects of some of the natural agents which have potential value in the treatment of inflammatory lung diseases.

Published
2007
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4. Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

Author

Auyon J. Ghosh, Brian D. Hobbs, Matthew Moll, Aabida Saferali, Adel Boueiz, Jeong H. Yun, Frank Sciurba, Lucas Barwick, Andrew H. Limper, Kevin Flaherty, Gerard Criner, Kevin K. Brown, Robert Wise, Fernando J. Martinez, David Lomas, Peter J. Castaldi, Vincent J. Carey, Dawn L. DeMeo, Michael H. Cho, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri H. Beaty, Adel El-Boueiz, Marilyn G. Foreman, Lystra P. Hayden, Jacqueline Hetmanski, John E. Hokanson, Wonji Kim, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dmitry Prokopenko, Jarrett Morrow, Dandi Qiao, Phuwanat Sakornsakolpat, Emily S. Wan, Juan Pablo Centeno, Jean-Paul Charbonnier, Harvey O. Coxson, Craig J. Galban, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, Pietro Nardelli, John D. Newell, Aleena Notary, Andrea Oh, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, Gonzalo Vegas Sanchez-Ferrero, Lucas Veitel, George R. Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Katherine Pratte, Matt Strand, Erin Austin, Gregory Kinney, Kendra A. Young, Surya P. Bhatt, Jessica Bon, Alejandro A. Diaz, Barry Make, Susan Murray, Elizabeth Regan, Xavier Soler, Russell P. Bowler, Katerina Kechris, Farnoush Banaei-Kashani, Jeffrey L. Curtis, Perry G. Pernicano, Nicola Hanania, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Craig Hersh, George Washko, R. Graham Barr, John Austin, Belinda D’Souza, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Brown, Nadia N. Hansel, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Ken M. Kunisaki, Eric L. Flenaugh, Hirut Gebrekristos, Mario Ponce, Silanath Terpenning, Gloria Westney, Richard Rosiello, David Pace, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Anand Iyer, Hrudaya Nath, J. Michael Wells, Douglas Conrad, Andrew Yen, Alejandro P. Comellas, Karin F. Hoth, John Newell, Brad Thompson, Ella Kazerooni, Wassim Labaki, Craig Galban, Dharshan Vummidi, Joanne Billings, Abbie Begnaud, Tadashi Allen, Divay Chandra, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, and Harjinder Singh

Subjects
Male, Endotype, Respiratory System, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Gastroenterology, Loss of heterozygosity, Pulmonary Disease, Chronic Obstructive, Genotype, 80 and over, 2.1 Biological and endogenous factors, Medicine, Longitudinal Studies, Aetiology, Lung, Aged, 80 and over, COPD, RNA sequencing, Middle Aged, Respiratory Function Tests, medicine.anatomical_structure, Phenotype, Meta-analysis, Respiratory, Female, alpha-1 antitrypsin, Genetic Markers, Adult, Pulmonary and Respiratory Medicine, Chronic Obstructive, Heterozygote, medicine.medical_specialty, Chronic Obstructive Pulmonary Disease, Pulmonary disease, Pulmonary Disease, Clinical Research, Internal medicine, alpha 1-Antitrypsin Deficiency, Humans, Allele, Aged, Emphysema, COPDGene Investigators, Whole Genome Sequencing, business.industry, Original Articles, medicine.disease, Survival Analysis, respiratory tract diseases, meta-analysis, alpha 1-Antitrypsin, Case-Control Studies, business
Abstract

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Published
2021

5. Spirometric Volumes and Breathlessness across Levels of Airflow Limitation: The COPDGene Study

Author

Magnus Ekström, Anna Bornefalk-Hermansson, Nicholas Wysham, David C. Currow, Neil MacIntyre, James D. Crapo, Edwin K. Silverman, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Peter J. Castaldi, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Craig P. Hersh, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Margaret M. Parker, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D’Souza, Gregory D. N. Pearson, Anna Rozenshtein, Byron Thomashow, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D’Alonzo, Parag Desai, Michael Jacobs Pharm.D, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, and Mario E. Ruiz

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, business.industry, Airflow, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, Correspondence, Cardiology, Medicine, business, Lung function
Abstract

Spirometric Volumes and Breathlessness Across Levels of Airflow Limitation : The COPDGene Study.

Published
2018

6. Blood eosinophil count thresholds and exacerbations in patients with chronic obstructive pulmonary disease

Author

Jeong H. Yun, Andrew Lamb, Robert Chase, Dave Singh, Margaret M. Parker, Aabida Saferali, Jørgen Vestbo, Ruth Tal-Singer, Peter J. Castaldi, Edwin K. Silverman, Craig P. Hersh, James D. Crapo, Barry J. Make, Elizabeth A. Regan, Terri Beaty, Ferdouse Begum, Robert Busch, Michael Cho, Dawn L. DeMeo, Adel R. Boueiz, Marilyn G. Foreman, Eitan Halper-Stromberg, Nadia N. Hansel, Megan E. Hardin, Lystra P. Hayden, Jacqueline Hetmanski, Brian D. Hobbs, John E. Hokanson, Nan Laird, Christoph Lange, Sharon M. Lutz, Merry-Lynn McDonald, Dandi Qiao, Stephanie Santorico, Emily S. Wan, Sungho Won, Mustafa Al Qaisi, Harvey O. Coxson, Teresa Gray, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, Alex Kluiber, David A. Lynch, John D. Newell, James C. Ross, Raul San Jose Estepar, Joyce Schroeder, Jered Sieren, Douglas Stinson, Berend C. Stoel, Juerg Tschirren, Edwin Van Beek, Bram van Ginneken, Eva van Rikxoort, George Washko, Carla G. Wilson, Robert Jensen, Douglas Everett, Jim Crooks, Camille Moore, Matt Strand, John Hughes, Gregory Kinney, Katherine Pratte, Kendra A. Young, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Mustafa Atik, Venkata Bandi, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Arun Nachiappan, Amit Parulekar, Craig Hersh, R. Graham Barr, John Austin, Belinda D'Souza, Gregory D.N. Pearson, Anna Rozenshtein, Byron Thomashow, Neil MacIntyre, H. Page McAdams, Lacey Washington, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Allison Lambert, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Matthew Budoff, Hans Fischer, Janos Porszasz, Harry Rossiter, William Stringer, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Eugene Berkowitz, Gloria Westney, Russell Bowler, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, Surya Bhatt, Anand Iyer, Hrudaya Nath, J. Michael Wells, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro P. Comellas, John Newell, Brad Thompson, Ella Kazerooni, Joanne Billings, Abbie Begnaud, Tadashi Allen, Frank Sciurba, Jessica Bon, Divay Chandra, Carl Fuhrman, Joel Weissfeld, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, P. de Mallorca, Y. Feschenko, V. Gavrisyuk, L. Yashina Kiev, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, and MUMC+: MA Longziekten (3)

Subjects
Male, Exacerbation, Allergy, AIRWAY INFLAMMATION, INHALED CORTICOSTEROIDS, Rate ratio, Leukocyte Count, 0302 clinical medicine, exacerbation, CLINICAL CHARACTERISTICS, Immunology and Allergy, 030212 general & internal medicine, Longitudinal Studies, Lung, COPD, medicine.diagnostic_test, Chronic obstructive pulmonary disease, Complete blood count, Middle Aged, RANDOMIZED CONTROLLED-TRIAL, Observational Studies as Topic, medicine.anatomical_structure, Disease Progression, Respiratory, Female, SHORT-TERM RESPONSE, medicine.medical_specialty, Chronic Obstructive, Chronic Obstructive Pulmonary Disease, Immunology, Pulmonary Disease, 03 medical and health sciences, FEV1/FVC ratio, Clinical Research, Internal medicine, White blood cell, medicine, Humans, eosinophil, Asthma, Aged, business.industry, COPDGene and ECLIPSE Investigators, Eosinophil, asthma, medicine.disease, Eosinophils, 030228 respiratory system, SPUTUM-EOSINOPHILIA, OVERLAP SYNDROME, business, COPENHAGEN GENERAL-POPULATION
Abstract

BACKGROUND:Eosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk. OBJECTIVE:We sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD. METHODS:Blood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n=1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n=1,895). Asubset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time. RESULTS:COPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies. CONCLUSIONS:Patients with moderate-to-severe COPD and blood eosinophil counts of 300cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.

Published
2018

7. Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects

Author

Robert Busch, Brian D. Hobbs, Jin Zhou, Peter J. Castaldi, Michael J. McGeachie, Megan E. Hardin, Iwona Hawrylkiewicz, Pawel Sliwinski, Jae-Joon Yim, Woo Jin Kim, Deog K. Kim, Alvar Agusti, Barry J. Make, James D. Crapo, Peter M. Calverley, Claudio F. Donner, David A. Lomas, Emiel F. Wouters, Jørgen Vestbo, Ruth Tal-Singer, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Peter D. Paré, Robert D. Levy, Stephen I. Rennard, Terri H. Beaty, John Hokanson, Edwin K. Silverman, Michael H. Cho, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, Dawn DeMeo, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Adel El-Bouiez, Dandi Qiao, Eitan Halper-Stromberg, Ferdouse Begum, Sungho Won, Sharon Lutz, David A. Lynch, Harvey O. Coxson, MeiLan K. Han, Eric A. Hoffman, Stephen Humphries, Francine L. Jacobson, Philip F. Judy, Ella A. Kazerooni, John D. Newell, James C. Ross, Raul San Jose Estepar, Berend C. Stoel, Juerg Tschirren, Eva van Rikxoort, Bram van Ginneken, George Washko, Carla G. Wilson, Mustafa Al Qaisi, Teresa Gray, Alex Kluiber, Tanya Mann, Jered Sieren, Douglas Stinson, Joyce Schroeder, Edwin Van Beek, Robert Jensen, Douglas Everett, Anna Faino, Matt Strand, Carla Wilson, John E. Hokanson, Gregory Kinney, Kendra Young, Katherine Pratte, Lindsey Duca, Jeffrey L. Curtis, Carlos H. Martinez, Perry G. Pernicano, Nicola Hanania, Philip Alapat, Venkata Bandi, Mustafa Atik, Aladin Boriek, Kalpatha Guntupalli, Elizabeth Guy, Amit Parulekar, Arun Nachiappan, Francine Jacobson, R. Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D. N. Pearson, Anna Rozenshtein, Neil MacIntyre, Lacey Washington, H. Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Robert Brown, Karen Horton, Nirupama Putcha, Richard Casaburi, Alessandra Adami, Janos Porszasz, Hans Fischer, Matthew Budoff, Harry Rossiter, Amir Sharafkhaneh, Charlie Lan, Christine Wendt, Brian Bell, Gloria Westney, Eugene Berkowitz, Russell Bowler, David Lynch, Richard Rosiello, David Pace, Gerard Criner, David Ciccolella, Francis Cordova, Chandra Dass, Gilbert D'Alonzo, Parag Desai, Michael Jacobs, Steven Kelsen, Victor Kim, A. James Mamary, Nathaniel Marchetti, Aditi Satti, Kartik Shenoy, Robert M. Steiner, Alex Swift, Irene Swift, Maria Elena Vega-Sanchez, Mark Dransfield, William Bailey, J. Michael Wells, Surya Bhatt, Hrudaya Nath, Joe Ramsdell, Paul Friedman, Xavier Soler, Andrew Yen, Alejandro Comellas, John Newell, Brad Thompson, MeiLan Han, Ella Kazerooni, Carlos Martinez, Joanne Billings, Tadashi Allen, Frank Sciurba, Divay Chandra, Joel Weissfeld, Carl Fuhrman, Jessica Bon, Antonio Anzueto, Sandra Adams, Diego Maselli-Caceres, Mario E. Ruiz, Jaume Sauleda, Peter M. A. Calverley, Stephen Rennard, Y. Ivanov, K. Kostov, J. Bourbeau, M. Fitzgerald, P. Hernandez, K. Killian, R. Levy, F. Maltais, D. O'Donnell, J. Krepelka, J. Vestbo, E. Wouters, D. Quinn, P. Bakke, M. Kosnik, A. Agusti, J. Sauleda, Y. Feschenko, V. Gavrisyuk, L. Yashina, N. Monogarova, P. Calverley, D. Lomas, W. MacNee, D. Singh, J. Wedzicha, A. Anzueto, S. Braman, R. Casaburi, B. Celli, G. Giessel, M. Gotfried, G. Greenwald, N. Hanania, D. Mahler, B. Make, S. Rennard, C. Rochester, P. Scanlon, D. Schuller, F. Sciurba, A. Sharafkhaneh, T. Siler, E. Silverman, A. Wanner, R. Wise, R. ZuWallack, H. Coxson, C. Crim, L. Edwards, R. Tal Singer, J. Yates, B. Miller, R. Tal-Singer, J. Benditt, G. Criner, M. DeCamp, P. Diaz, M. Ginsburg, L. Kaiser, M. Katz, M. Krasna, N. MacIntyre, R. McKenna, F. Martinez, Z. Mosenifar, J. Reilly, A. Ries, J. Utz, RS: NUTRIM - R3 - Respiratory & Age-related Health, Pulmonologie, MUMC+: MA Longziekten (3), and RS: NUTRIM - R3 - Chronic inflammatory disease and wasting

Subjects
0301 basic medicine, Male, Clinical Biochemistry, EMPHYSEMA, SUSCEPTIBILITY, AIR-FLOW OBSTRUCTION, Pulmonary Disease, Chronic Obstructive, Risk Factors, Medicine, EPIDEMIOLOGY, Genetic epidemiology, Original Research, COPD, COMPLEX DISEASE, RECLASSIFICATION, Chronic obstructive pulmonary disease, Middle Aged, Genetic risk score, Respiratory Function Tests, LUNG-FUNCTION, Genetic risk factors, alpha-1 antitrypsin, Meta-analysis, Female, SMOKING, Pulmonary and Respiratory Medicine, medicine.medical_specialty, genetic epidemiology, Pulmonary disease, Single-nucleotide polymorphism, genetic risk score, chronic obstructive pulmonary disease, 03 medical and health sciences, Internal medicine, Genetic variation, genetic risk factors, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Genetic association, Aged, business.industry, Cell Biology, Heritability, medicine.disease, respiratory tract diseases, 030104 developmental biology, Physical therapy, business, Genome-Wide Association Study
Abstract

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

Published
2017

8. COPD in the Elderly Patient.

Author

Nicola Hanania

Subjects
*OBSTRUCTIVE lung disease diagnosis, *OLDER patients, *SPIROMETRY, *PHARMACOLOGY, *POLYPHARMACY, *COMORBIDITY, *PATIENT compliance
Abstract

The elderly are especially prone to the adverse health effects of chronic obstructive pulmonary disease (COPD), which is a common disorder in that population. While the prevalence and morbidity of COPD in the elderly are high, it is often undiagnosed and thus undertreated. The diagnosis of COPD is primarily based on the physiological documentation of airflow limitation using spirometry. However, several controversies exist as to the range of predicted normal values for these measurements in the elderly population, and the clinical presentation of COPD in the elderly may be complicated by the presence of several comorbidities. Many nonpharmcological and pharmacological interventions are available for managing COPD. However, management of COPD in the elderly population may be challenged by the "polypharmacy" of medications that these patients often take, which can interfere with compliance with therapy. Additionally, the elderly often suffer from physical or cognitive disabilities that can prevent compliance with prescribed medications. Lastly, adverse effects from medications prescribed for treatment of COPD may be more pervasive in elderly patients. [ABSTRACT FROM AUTHOR]

Published
2010
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