• Loren C Denlinger, Brenda R Phillips, Ronald L Sorkness, Eugene R Bleecker, Mario Castro, Mark D DeBoer, Anne M Fitzpatrick, Annette T Hastie, Jonathan M Gaffin, Wendy C Moore, Michael C Peters, Stephen P Peters, Wanda Phipatanakul, Juan Carlos Cardet, Serpil C Erzurum, John V Fahy, Merritt L Fajt, Benjamin Gaston, Bruce D Levy, Deborah A Meyers, Kristie Ross, W Gerald Teague, Sally E Wenzel, Prescott G Woodruff, Joe Zein, Nizar N Jarjour, David T Mauger, and Elliot Israel.
• Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
• Am. J. Respir. Crit. Care Med. 2021 Apr 1; 203 (7): 841-852.

AbstractRationale: 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.

27 keywords...

hide…