Surya P Bhatt1, James M Wells2, Victor Kim3, Gerard J Criner3, Craig P Hersh4, Megan Hardin4, William C Bailey2, Hrudaya Nath5, Young-Il Kim6, Marilyn G Foreman7, Douglas S Stinson8, Carla G Wilson9, Stephen I Rennard10, Edwin K Silverman4, Barry J Make11, Mark T Dransfield2. 1. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, Birmingham, AL, USA; Lung Health Center, University of Alabama, Birmingham, AL, USA. Electronic address: spbhatt@uab.edu. 2. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama, Birmingham, AL, USA; Lung Health Center, University of Alabama, Birmingham, AL, USA. 3. Division of Pulmonary and Critical Care, Temple University Hospital, Philadelphia, PA, USA. 4. Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 5. Department of Radiology, University of Alabama, Birmingham, AL, USA. 6. Department of Preventive Medicine, University of Alabama, Birmingham, AL, USA. 7. Morehouse School of Medicine, Atlanta, GA, USA. 8. Quantitative Imaging Laboratory, National Jewish Health, Denver, CO, USA. 9. Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO, USA. 10. Division of Pulmonary, Critical Care, Sleep and Allergy, University of Nebraska Medical Center, Omaha, NE, USA. 11. Division of Pulmonary and Critical Care Medicine, National Jewish Health, Denver, CO, USA.
Abstract
BACKGROUND: Bronchodilator response has been noted in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to β₂ agonists resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely to be far more common than is symptomatic bronchoconstriction with β₂ agonists, but no systematic studies have been done. We assessed the prevalence of paradoxical response in current and former smokers with and without COPD, and its radiological correlates and clinical implications. METHODS: Non-Hispanic white and African-American patients (aged 45-80 years) from a large multicentre study COPDGene were classified into two groups on the basis of a paradoxical response, defined as at least a 12% and 200 mL reduction in forced expiratory volume in 1 sec (FEV₁) or forced vital capacity (FVC), or both, after administration of a shortacting β₂ agonist (180 μg salbutamol). FINDINGS: Patients were recruited from January, 2008, to June, 2011. 9986 (96%) of 10,364 patients enrolled in the COPDGene study were included in the analysis population (mean age 59·6 years [SD 9·0]). Paradoxical response was noted in 453 (5%) of 9986 patients and the frequency was similar in patients with COPD (198 [4%] of 4439) and smokers without airflow obstruction (255 [5%] of 5547). Compared with white patients, a paradoxical response was twice as common in African-American patients (227 [7%] of 3282 vs 226 [3%] of 6704; p<0·0001). In the multivariate analyses, African-American ethnic origin (adjusted odds ratio 1·89, 95% CI 1·50-2·39; p<0·0001), less emphysema (0·96, 0·92-0·99; p=0·023), and increased wall-area percentage of the segmental airways (1·04, 1·01-1·08; p=0·023) were independently associated with a paradoxical response. A paradoxical response was independently associated with worse dyspnoea (adjusted β for Modified Medical Research Council Dyspnoea Scale 0·12 [95% CI 0·00 to 0·24]; p=0·05), lower 6 min walk distance (-45·8 [-78·5 to -13·2]; p=0·006), higher Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index (0·31 [0·19 to 0·43]; p<0·0001), and a greater frequency of severe exacerbations (increased by a factor of 1·35, 1·00-1·81; p=0·048). INTERPRETATION: Paradoxical response to β₂ agonists is associated with respiratory morbidity and is more common in African-Americans. These findings might have implications for the use of β2agonists in some patients. FUNDING: National Institutes of Health.
BACKGROUND: Bronchodilator response has been noted in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to β₂ agonists resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely to be far more common than is symptomatic bronchoconstriction with β₂ agonists, but no systematic studies have been done. We assessed the prevalence of paradoxical response in current and former smokers with and without COPD, and its radiological correlates and clinical implications. METHODS: Non-Hispanic white and African-American patients (aged 45-80 years) from a large multicentre study COPDGene were classified into two groups on the basis of a paradoxical response, defined as at least a 12% and 200 mL reduction in forced expiratory volume in 1 sec (FEV₁) or forced vital capacity (FVC), or both, after administration of a shortacting β₂ agonist (180 μg salbutamol). FINDINGS:Patients were recruited from January, 2008, to June, 2011. 9986 (96%) of 10,364 patients enrolled in the COPDGene study were included in the analysis population (mean age 59·6 years [SD 9·0]). Paradoxical response was noted in 453 (5%) of 9986 patients and the frequency was similar in patients with COPD (198 [4%] of 4439) and smokers without airflow obstruction (255 [5%] of 5547). Compared with white patients, a paradoxical response was twice as common in African-American patients (227 [7%] of 3282 vs 226 [3%] of 6704; p<0·0001). In the multivariate analyses, African-American ethnic origin (adjusted odds ratio 1·89, 95% CI 1·50-2·39; p<0·0001), less emphysema (0·96, 0·92-0·99; p=0·023), and increased wall-area percentage of the segmental airways (1·04, 1·01-1·08; p=0·023) were independently associated with a paradoxical response. A paradoxical response was independently associated with worse dyspnoea (adjusted β for Modified Medical Research Council Dyspnoea Scale 0·12 [95% CI 0·00 to 0·24]; p=0·05), lower 6 min walk distance (-45·8 [-78·5 to -13·2]; p=0·006), higher Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index (0·31 [0·19 to 0·43]; p<0·0001), and a greater frequency of severe exacerbations (increased by a factor of 1·35, 1·00-1·81; p=0·048). INTERPRETATION: Paradoxical response to β₂ agonists is associated with respiratory morbidity and is more common in African-Americans. These findings might have implications for the use of β2agonists in some patients. FUNDING: National Institutes of Health.
Authors: Andrei Schwartz; Nicholas Arnold; Becky Skinner; Jacob Simmering; Michael Eberlein; Alejandro P Comellas; Spyridon Fortis Journal: Respir Care Date: 2020-09-01 Impact factor: 2.258
Authors: Surya P Bhatt; George R Washko; Eric A Hoffman; John D Newell; Sandeep Bodduluri; Alejandro A Diaz; Craig J Galban; Edwin K Silverman; Raúl San José Estépar; David A Lynch Journal: Am J Respir Crit Care Med Date: 2019-02-01 Impact factor: 21.405
Authors: James E Hansen; Asli G Dilektasli; Janos Porszasz; William W Stringer; Youngju Pak; Harry B Rossiter; Richard Casaburi Journal: Ann Am Thorac Soc Date: 2019-12
Authors: Maud Koopman; Frits M E Franssen; Swetlana Gaffron; Henrik Watz; Thierry Troosters; Judith Garcia-Aymerich; Pierluigi Paggiaro; Eduard Molins; Miguel Moya; Lindy van Burk; Dieter Maier; Esther Garcia Gil; Emiel F M Wouters; Lowie E G W Vanfleteren; Martijn A Spruit Journal: Int J Chron Obstruct Pulmon Dis Date: 2022-03-08