Responsiveness to parenteral corticosteroids and lung function trajectory in adults with moderate-to-severe asthma

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. MeyersKristie Ross, W. Gerald Teague, Sally E. Wenzel, Prescott G. Woodruff, Joe Zein, Nizar N. Jarjour, David T. Mauger

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)841-852
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Volume203
Issue number7
DOIs
StatePublished - Apr 1 2021

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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