Characteristics of Alpha-1 Antitrypsin-Deficient Individuals in the Long-term Oxygen Treatment Trial and Comparison with Other Subjects with Chronic Obstructive Pulmonary Disease
James K Stoller, Loutfi S Aboussouan, Richard E Kanner, Laura A Wilson, Phil Diaz, Robert Wise, LOTT Research Group, William C Bailey, Anne L Fuhlbrigge, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, James K Stoller, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Richard K Albert, Jennifer Underwood, Barry Make, Jennifer Underwood, Neil MacIntyre, John Davies, Thomas Stibolt, Richard Mularski, Allison Naleway, Sarah Vertrees, Richard Casaburi, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Philip Diaz, Janice Drake, Mahasti Rittinger, Rachael Compton, Ralph Panos, Laura A Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J Allen Cooper Jr, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, J Allen Cooper Jr, Patti Smith, Peruvemba Sriram, Katherine Herring, Steven Gay, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K P Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Frank Sciurba, Benjamin Kelly, Richard Kanner, Mary Beth Scholand, G Martin Villegas, Judy Carle, David Au, Edmunds Udris, Randall Curtis, David Au, Laura C Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Edmunds Udris, Moira Aitken, Bruce Culver, Roger Yusen, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, James Tonascia, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Steven Piantadosi, Girlie Reyes, David Shade, Michael Smith, Alice L Sternberg, Laura Wilson, Annette Wagoner, Robert Wise, Katherine P Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, Kevin Weiss, James K Stoller, Loutfi S Aboussouan, Richard E Kanner, Laura A Wilson, Phil Diaz, Robert Wise, LOTT Research Group, William C Bailey, Anne L Fuhlbrigge, Ernestina Sampong, Karin Sloan, Ashley Wagner, Susan Anderson, Marilyn Moy, Osarenoma Okunbor, James K Stoller, Scott Marlow, Yvonne Meli, Richard Rice, Loutfi S Aboussouan, Robert Castele, Joseph Parambil, Sumita Khatri, Aman Pande, Joe Zein, Thomas Olbrych, Stephan Alkins, Christine Jocko, Franck Rahaghi, Jean Barton, Richard K Albert, Jennifer Underwood, Barry Make, Jennifer Underwood, Neil MacIntyre, John Davies, Thomas Stibolt, Richard Mularski, Allison Naleway, Sarah Vertrees, Richard Casaburi, Janos Porszasz, Peggy Walker, Renee Indelicato, Lennard Specht, Kathleen Ellstrom, Jamie Portillo, David Horak, Brian Tiep, Mary Barnett, Philip Diaz, Janice Drake, Mahasti Rittinger, Rachael Compton, Ralph Panos, Laura A Lach, Gerard Criner, Carla Grabianowski, Francis Cordova, Parag Desai, Samuel Krachman, James Mamary, Nathaniel Marchetti, Aditi Satti, Eileen Mumm, Michelle Vega-Olivo, Jenny Hua, Vanna Tauch, Lii-Yoong Criner, Michael Jacobs, Peter Rising, Paul Simonelli, Michele Mitchell, Matthew Lammi, Connie Romaine, Howard Lee, Mary Ianacone, Steven Scharf, Wanda Bell-Farrell, M Jeffery Mador, Ayesha Rahman, Mumtaz Zaman, Lisa Hill, Alec Platt, J Allen Cooper Jr, Kathleen Harrington, Mark Dransfield, Patti Smith, Donald Davis, J Allen Cooper Jr, Patti Smith, Peruvemba Sriram, Katherine Herring, Steven Gay, Fernando Martinez, Meilan Han, Kelly Rysso, Catherine Meldrum, K P Ravikrishnan, Daniel Keena, Jennifer DeRidder, Beth Kring, Antonio Anzueto, Alex Aguilera, Timothy Houlihan, Reda Girgis, Jennifer Cannestra, Frank Sciurba, Benjamin Kelly, Richard Kanner, Mary Beth Scholand, G Martin Villegas, Judy Carle, David Au, Edmunds Udris, Randall Curtis, David Au, Laura C Feemster, Richard Goodman, Brianna Moss, Lynn Reinke, Edmunds Udris, Moira Aitken, Bruce Culver, Roger Yusen, Mario Castro, Brigitte Mittler, Jeanne Heaghney, Myron Jacobs, Min Joo, Nina Bracken, Edward Diamond, Mary K Joseph, Xavier Soler, Arianna Villa, Daniel Layish, Edwin Silverman, Roxanne Kelly, Daniel Cossette, James Tonascia, Patricia Belt, Amanda Blackford, Betty Collison, John Dodge, Michele Donithan, Cathleen Ewing, Rosetta Jackson, K Patrick May, Jill Meinert, Steven Piantadosi, Girlie Reyes, David Shade, Michael Smith, Alice L Sternberg, Laura Wilson, Annette Wagoner, Robert Wise, Katherine P Yates, Rosemarie Hakim, Antonello Punturieri, Julie Bamdad, Thomas Croxton, Joanne Deshler, Pamela McCord-Reynolds, Mario Stylianou, Gail Weinmann, Gordon Bernard, James Anderson, Bernard Lo, Andrew Ries, Stuart Stoloff, Byron Thomashow, Barbara Tilley, Kevin Weiss
Abstract
Rationale: Alpha-1 antitrypsin deficiency (AATD) predisposes to chronic obstructive pulmonary disease, but is underrecognized. Oxygenation and exercise desaturation in individuals with AATD-associated chronic obstructive pulmonary disease has been sparsely studied. The Long-term Oxygen Treatment Trial (LOTT) permits comparing these features of individuals with AATD with alpha-1 antitrypsin-replete (called "usual chronic obstructive pulmonary disease") LOTT participants.
Objectives: Compare demographic, clinical, baseline oxygenation, and exercise desaturation features in participating AATD subjects with those of other LOTT subjects.
Methods: LOTT is a multicenter randomized controlled trial comparing use of supplemental oxygen versus not in subjects with chronic obstructive pulmonary disease and moderate hypoxemia (resting oxygen saturation as measured by pulse oximetry, 89-93%) or normal oxygen saturation at rest and significant exercise desaturation.
Measurement and main results: Among the 597 LOTT participants with nonmissing alpha-1 antitrypsin levels, 11 (1.8%) had severe AATD and 44 (7.4%) had mild/moderate AATD. Comparison of the 11 severely AAT-deficient individuals with the 542 LOTT participants with usual chronic obstructive pulmonary disease showed that the AATD subjects were younger and despite less smoking, had lower FEV1/FVC (mean post-bronchodilator FEV1/FVC, 0.38 ± 0.06 vs. 0.46 ± 0.13; P = 0.002). Comparison with 27 age-, sex-, and FEV1-matched alpha-1 antitrypsin-normal LOTT participants showed no baseline difference in resting room air pulse oximetry saturation (AATD, 93.6% ± 2.3% vs. 92.7% ± 2.2%; P = 0.64). Exercise-related desaturation was more severe in the individuals with AATD based on desaturation to 88% or less sooner during a 6-minute-walk test, having a higher percentage of desaturation points (e.g., <90%) during exercise, and having a higher distance-saturation product (defined as the distance walked in 6 min multiplied by the nadir saturation achieved during the 6-minute-walk test).
Conclusions: These data suggest that individuals with AATD experience more profound desaturation with exercise than age-, sex-, race-, and FEV1-matched control subjects with usual chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00692198).
Trial registration: ClinicalTrials.gov NCT00692198.
Keywords: Long-term Oxygen Treatment Trial; alpha-1 antitrypsin deficiency; desaturation; oxygenation.
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Source: PubMed