Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate-to-Severe Asthma.

Abstract

<b>Rationale:</b> 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.<b>Objectives:</b> To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline.<b>Methods:</b> 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.<b>Measurements and Main Results:</b> 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 (<i>P</i> < 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.<b>Conclusions:</b> 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.