@article{6438c89feadf4197885b5697dbf3756d,
title = "Responsiveness to parenteral corticosteroids and lung function trajectory in adults with moderate-to-severe asthma",
abstract = "Rationale: It is unclear why select patients with moderate-tosevere 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 postbronchodilator 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.",
keywords = "Corticosteroid sensitivity, Exacerbations, Longitudinal, Lung function, Severe asthma",
author = "Denlinger, {Loren C.} and Phillips, {Brenda R.} and Sorkness, {Ronald L.} and Bleecker, {Eugene R.} and Mario Castro and DeBoer, {Mark D.} and Fitzpatrick, {Anne M.} and Hastie, {Annette T.} and Gaffin, {Jonathan M.} and Moore, {Wendy C.} and Peters, {Michael C.} and Peters, {Stephen P.} and Wanda Phipatanakul and Cardet, {Juan Carlos} and Erzurum, {Serpil C.} and Fahy, {John V.} and Fajt, {Merritt L.} and Benjamin Gaston and Levy, {Bruce D.} and Meyers, {Deborah A.} and Kristie Ross and Teague, {W. Gerald} and Wenzel, {Sally E.} and Woodruff, {Prescott G.} and Joe Zein and Jarjour, {Nizar N.} and Mauger, {David T.}",
note = "Funding Information: Supported by the following NHLBI grants to the SARP III (Severe Asthma Research Program III) principal investigators, clinical centers, and data coordinating center: U10 HL109164 (E.R.B., W.C.M., and D.A.M.), U10 HL109257 (M.C.), U10 HL109250 (S.C.E.), U10 HL109146 (J.V.F.), U10 HL109250 (B.G.), U10 HL109172 (B.D.L. and E.I.), U10 HL109168 (N.N.J.), U10 HL109250 (W.G.T.), U10 HL109152 (S.E.W.), and U10 HL109086-04 (D.T.M.). In addition, this program is supported through the following NIH National Center for Advancing Translational Sciences awards: UL1 TR001420 (Wake Forest University), UL1 TR000427 (University of Wisconsin), UL1 TR001102 (Harvard University), and UL1 TR000454 (Emory University). Support for visits occurring beyond the third year of follow-up came from the following partnerships. AstraZeneca supported visits at the Brigham and Women{\textquoteright}s Hospital, Boston Children{\textquoteright}s Hospital, University of Wisconsin, University of Virginia, and Case Western Reserve University–Rainbow Babies and Children{\textquoteright}s Hospital. Boehringer-Ingelheim supported visits at the University of Pittsburgh and University of California, San Francisco. Genentech supported visits at the Wake Forest School of Medicine. GlaxoSmithKline supported core activities occurring at Pennsylvania State University and the Wake Forest School of Medicine. Sanofi–Genzyme–Regeneron supported visits at Washington University and Emory University. The Cleveland Clinic did not participate in these industry partnerships and used internal funds for visits after the third year. Finally, this work was supported in part by funds provided by the William W. and Judith H. Busse Endowed Professorship in Allergy and Asthma Research (L.C.D.). Publisher Copyright: {\textcopyright} 2021 by the American Thoracic Society.",
year = "2021",
month = apr,
day = "1",
doi = "10.1164/rccm.202002-0454OC",
language = "English (US)",
volume = "203",
pages = "841--852",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "7",
}