David A Kaminsky1, David G Chapman1,2,3, Janet T Holbrook4, Robert J Henderson4, Elizabeth A Sugar4, John Mastronarde5, William G Teague6, Michael Busk7, Kaharu Sumino8, Anne E Dixon1, Robert A Wise9, Charles G Irvin1. 1. Pulmonary and Critical Care, University of Vermont Larner College of Medicine, Burlington, VT, USA. 2. Translational Airways Group, School of Life Sciences, University of Technology Sydney, Sydney, NSW, Australia. 3. Airway Physiology and Imaging Group, Woolcock Institute of Medical Research, Sydney, NSW, Australia. 4. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. 5. Division of Pulmonary Medicine, Providence Portland Medical Center, Portland, OR, USA. 6. Division of Pediatric Respiratory Medicine and Allergy, University of Virginia, Charlottesville, VA, USA. 7. Division of Pulmonary Medicine, St. Vincent Hospital and Health Care Center, Inc., Indianapolis, IN, USA. 8. Division of Pulmonary and Critical Care Medicine, Washington University, St. Louis, MO, USA. 9. Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract
BACKGROUND AND OBJECTIVE: The reduction of forced expiratory volume in 1 s (FEV1 ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV1 /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC). METHODS: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV1 , and calculated as %ΔFVC/%ΔFEV1 . RESULTS: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control. CONCLUSION: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.
BACKGROUND AND OBJECTIVE: The reduction of forced expiratory volume in 1 s (FEV1 ) in response to methacholine challenge in asthma may reflect two components: airway narrowing, assessed by the change in FEV1 /forced vital capacity (FVC), and airway closure, assessed by the change in FVC. The purpose of this study was to determine the degree and determinants of airway closure in response to methacholine in a large group of asthmatic patients participating in studies conducted by the American Lung Association-Airways Clinical Research Centers (ALA-ACRC). METHODS: We used the methacholine challenge data from participants in five studies of the ALA-ACRC to determine the closing index, defined as the contribution of airway closure to the decrease in FEV1 , and calculated as %ΔFVC/%ΔFEV1 . RESULTS: There were a total of 936 participants with asthma, among whom the median closing index was 0.67 relative to that of a published healthy population of 0.54. A higher closing index was associated with increased age (10-year increments) (0.04, 95% CI = 0.02, 0.05, P < 0.005) and obesity (0.07, 95% CI = 0.03, 0.10, P < 0.001). There was no association between the closing index and asthma control. CONCLUSION: Our findings confirm that airway closure in response to methacholine occurs in a large, diverse population of asthmatic participants, and that increased airway closure is associated with older age and obesity. These findings suggest that therapies targeting airway closure may be important in patients with a high closing index.
Authors: Brittany Duchene; Sarah Caffry; David A Kaminsky; Loretta G Que; Matthew E Poynter; Anne E Dixon Journal: Respir Med Date: 2021-06-09 Impact factor: 4.582