Loren C Denlinger1, Brenda R Phillips2, Ronald L Sorkness1, Eugene R Bleecker3, Mario Castro4, Mark D DeBoer5, Anne M Fitzpatrick6, Annette T Hastie7, Jonathan M Gaffin8, Wendy C Moore7, Michael C Peters9, Stephen P Peters7, Wanda Phipatanakul8, Juan Carlos Cardet8, Serpil C Erzurum10, John V Fahy9, Merritt L Fajt11, Benjamin Gaston12, Bruce D Levy8, Deborah A Meyers7, Kristie Ross13, W Gerald Teague5, Sally E Wenzel11, Prescott G Woodruff9, Joe Zein10, Nizar N Jarjour1, David T Mauger2, Elliot Israel14. 1. Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. 2. Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, The Pennsylvania State University, Hershey, Pennsylvania. 3. Division of Genetics, Genomics and Precision Medicine, Department of Medicine, College of Medicine, The University of Arizona, Tucson, Arizona. 4. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, KU School of Medicine, The University of Kansas, Kansas City, Kansas. 5. Divisions of Pediatric Diabetes and Endocrinology and Pediatric Respiratory Medicine, Allergy, Immunology and Sleep, Department of Pediatrics, School of Medicine, University of Virginia, Charlottesville, Virginia. 6. Division of Pulmonary, Allergy and Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia. 7. Section of Pulmonary, Critical Care, Allergy and Immunologic Disease, Department of Internal Medicine, School of Medicine, Wake Forest University, Winston-Salem, North Carolina. 8. Divisions of Pulmonary Medicine and Allergy and Immunology, Department of Pediatrics, Boston Children's Hospital, and. 9. Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, UCSF School of Medicine, University of California, San Francisco, San Francisco, California. 10. Lerner Research Institute and the Respiratory Institute, The Cleveland Clinic, Cleveland, Ohio. 11. Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. 12. Division of Pediatric Pulmonary, Allergy and Sleep Medicine, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana; and. 13. Division of Pediatric Pulmonology and Sleep Medicine, Department of Pediatrics, UH Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Case Western Reserve University, Cleveland, Ohio. 14. Divisions of Pulmonary and Critical Care and of Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard University, Boston, Massachusetts.
Abstract
Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline.Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models (P < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and body mass index.Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.
Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline.Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models (P < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and body mass index.Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.
Entities:
Keywords:
corticosteroid sensitivity; exacerbations; longitudinal; lung function; severe asthma
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