Risk factors for COPD exacerbations in inhaled medication users: the COPDGene study biannual longitudinal follow-up prospective cohort

Robert Busch, MeiLan K Han, Russell P Bowler, Mark T Dransfield, J Michael Wells, Elizabeth A Regan, Craig P Hersh, COPDGene Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Robert Busch, Adel El-Boueiz, Peter Castaldi, Megan Hardin, Dandi Qiao, Elizabeth Regan, 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 Jr, Elizabeth Regan, 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, Sharon Lutz, 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, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D N Pearson, Anna Rozenshtein, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, 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, Marilyn Foreman, 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, 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 Cornellas, John Newell Jr, 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, Robert Busch, MeiLan K Han, Russell P Bowler, Mark T Dransfield, J Michael Wells, Elizabeth A Regan, Craig P Hersh, COPDGene Investigators, James Crapo, Edwin Silverman, Barry Make, Elizabeth Regan, Terri Beaty, Nan Laird, Christoph Lange, Michael Cho, Stephanie Santorico, John Hokanson, Nadia Hansel, Craig Hersh, Peter Castaldi, Merry-Lynn McDonald, Emily Wan, Megan Hardin, Jacqueline Hetmanski, Margaret Parker, Marilyn Foreman, Brian Hobbs, Robert Busch, Adel El-Boueiz, Peter Castaldi, Megan Hardin, Dandi Qiao, Elizabeth Regan, 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 Jr, Elizabeth Regan, 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, Sharon Lutz, 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, Dawn DeMeo, Craig Hersh, George Washko, Francine Jacobson, R Graham Barr, Byron Thomashow, John Austin, Belinda D'Souza, Gregory D N Pearson, Anna Rozenshtein, Neil MacIntyre Jr, Lacey Washington, H Page McAdams, Charlene McEvoy, Joseph Tashjian, Robert Wise, Nadia Hansel, 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, Marilyn Foreman, 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, 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 Cornellas, John Newell Jr, 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

Abstract

Background: Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications.

Methods: 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta-agonist/inhaled-corticosteroid (ICS ± LABA), tiotropium alone, ICS ± LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS ± LABA.

Results: In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS ± LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS ± LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05).

Conclusions: Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS ± LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma.

Trial registration: ClinicalTrials.gov NCT00608764, first received 1/28/2008.

Figures

Fig. 1
Fig. 1
Study subjects. The COPDGene cohort was narrowed to those with LFU data available, then narrowed to subjects with a diagnosis of COPD by GOLD criteria, then to those taking medications. These subjects were divided into four exclusive groups based on medication use, as defined in the Methods section. Exacerbators had one or more exacerbations per year, non-exacerbators had zero exacerbations per year, subjects with between 0 and 1 exacerbations per year were not classified. LFU = Longitudinal follow-up; FEV1/FVC = ratio of forced expiratory volume in one second to forced vital capacity
Fig. 2
Fig. 2
Frequency of COPD exacerbations within the four medication groups. Medication groups are mutually exclusive. TIO/LABA/ICS indicates triple therapy with tiotropium, long-acting beta-agonist/inhaled corticosteroid, TIO indicates tiotropium alone, ICS ± LABA indicates long-acting beta-agonist/inhaled corticosteroid combination therapy, and SAB indicates short-acting bronchodilators alone

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