Submitted on March 23, 2007
Accepted on November 7, 2007
Lung Function in Adults with Stable but Severe Asthma: Air Trapping and Incomplete Reversal of Obstruction with Bronchodilation
Ronald L. Sorkness1*, Eugene R. Bleecker2, William W. Busse3, William J. Calhoun4, Mario Castro5, Kian Fan Chung6, Douglas Curran-Everett7, Serpil C. Erzurum8, Benjamin M. Gaston9, Elliot Israel10, Nizar N. Jarjour11, Wendy C. Moore12, Stephen P. Peters12, W. Gerald Teague13, and Sally E. Wenzel14
1 Department of Pharmacy Medicine & Pediatrics, University of Wisconsin, Madison, Wisconsin, United States
2 Center for Human Genomics, Wake Forest University, Winston-Salem, United States; Section on Pulmonary, Critical Care, Allergy & Immunologic Diseases, United States
3 Allergy, U Wisconsin Medical School, Madison, Wisconsin, United States
4 Medicine-APICS, UTMB, 5.132 JSA Rt 0561, Galveston, Texas, 77555-0561, United States; Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
5 Medicine, Washington University, St. Louis, Missouri, United States
6 Department of Thoracic Medicine, National Heart & Lung Institute, London, United Kingdom
7 Biostatistics, M222, National Jewish Med Research Center, Denver, Colorado, United States
8 Pathobiology, Cleveland Clinic, Cleveland, Ohio, United States
9 Pediatrics, UVA Sch Med, Charlottesville, Virginia, United States
10 Medicine, Brigham & Women's Hospital, Boston, Massachusetts, United States
11 Medicine, University of Wisconsin, Madison, Wisconsin, United States
12 Center for Human Genomics, Wake Forest University, Winston-Salem, United States
13 Pediatrics, Emory University, Atlanta, Georgia, United States
14 National Jewish Medical & Research Center, Denver, Colorado, United States
* To whom correspondence should be addressed. E-mail: rlsorkne{at}wisc.edu.
5-10% of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 non-severe asthma subjects from the Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping (indicated by FVC) and airflow limitation (indicated by FEV1/FVC). Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV1/FVC. This pattern was confirmed with measures of RV/TLC in a subgroup. In contrast, non-severe asthma did not exhibit prominent air trapping, even at FEV1/FVC<75% predicted. Air trapping also was associated with increases in total lung capacity and functional reserve capacity. After maximal bronchodilation, FEV1 reversed similarly from baseline in severe and non-severe asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV1 after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV1 when baseline FEV1 was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.
