TY - JOUR
T1 - Biomarkers of Type 2 Airway Inflammation as Predictors of Loss of Asthma Control During Step-Down Therapy for Well-Controlled Disease
T2 - The Long-Acting Beta-Agonist Step-Down Study (LASST)
AU - American Lung Association Airways Clinical Research Centers
AU - Bose, Sonali
AU - Bime, Christian
AU - Henderson, Robert J.
AU - Blake, Kathryn V.
AU - Castro, Mario
AU - DiMango, Emily
AU - Hanania, Nicola A.
AU - Holbrook, Janet T.
AU - Irvin, Charles G.
AU - Kraft, Monica
AU - Peters, Stephen P.
AU - Reibman, Joan
AU - Sugar, Elizabeth A.
AU - Sumino, Kaharu
AU - Wise, Robert A.
AU - Rogers, Linda
N1 - Funding Information:
This work was funded by The American Lung Association Airways Clinical Research Centers . The parent clinical trial (LASST) used for this analysis was funded by an unrestricted grant from Glaxo Smith Kline to the American Lung Association.
Funding Information:
This work was funded by The American Lung Association Airways Clinical Research Centers. The parent clinical trial (LASST) used for this analysis was funded by an unrestricted grant from Glaxo Smith Kline to the American Lung Association.Conflicts of interest: M. Castro receives university grant funding from the National Institutes of Health, the American Lung Association, and Patient Centered Outcomes Research Institute; pharmaceutical grant funding from AstraZeneca, Chiesi, Novartis, GlaxoSmithKline (GSK), and Sanofi-Aventis; is a consultant for Genentech, Theravance, VIDA, Teva, Sanofi-Aventis, and Novartis; is a speaker for AstraZeneca, Genentech, GSK, Regeneron, Sanofi, and Teva; and receives royalties from Elsevier. E. DiMango reports receiving consulting fees from Astra Zeneca. N. A. Hanania has received honoraria for serving on advisory boards or as consultant with GSK, Boehringer Ingelheim (BI), Novartis, Sanofi Genzyme, Regeneron, Astra Zeneca, and Genentech. His institution has received research support on his behalf from GSK, BI, Astra Zeneca, Novartis, and Sanofi. J. T. Holbrook receives research support from the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, the Food and Drug Administration, and the American Lung Association and is a Data Safety and Monitoring Committee member for Gilead Sciences. M. Kraft has received support from AstraZeneca, Sanofi, Gossamer, Ionis, and Elsevier. Her institution has received research support from the NIH, American Lung Association, AstraZeneca, Chiesi, and Sanofi. S. P. Peters has received support from PRIME, Elsevier, the NIH, the National Institute of Allergy and Infectious Diseases, UpToDate, the American College of Allergy, Asthma & Immunology, the American Lung Association, AstraZeneca, Novartis, Regeneron-Sanofi, Teva, and the National Heart, Lung, and Blood Institute for research in AsthmaNet, SARP, and SPIROMICS. J. Reibman has served on the advisory boards of Astra Zeneca and Novartis, and Genentech; has been a consultant for Astra Zeneca; received an investigator grant from Novartis; and performed clinical trials with AstraZeneca, Novartis, and Teva. E. A. Sugar receives salary support from the American Lung Association. L. Rogers has received support from Sanofi and AstraZeneca, and is an advisory board member for Astra Zeneca, Sanofi, and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.
Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Background: Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking. Objective: To evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (FENO) predict loss of asthma control as therapy is stepped down. Methods: In subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial FENO measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator). Results: Four hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of FENO were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P = .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, FENO levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers. Conclusions: In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of FENO are strong predictors of treatment failure.
AB - Background: Biomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking. Objective: To evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (FENO) predict loss of asthma control as therapy is stepped down. Methods: In subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial FENO measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator). Results: Four hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of FENO were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P = .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, FENO levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers. Conclusions: In patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of FENO are strong predictors of treatment failure.
KW - Asthma
KW - Biomarkers
KW - Eosinophil peroxidase
KW - Fractional exhaled nitric oxide
KW - IgE
KW - Step-down therapy
UR - http://www.scopus.com/inward/record.url?scp=85089198319&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2020.06.067
DO - 10.1016/j.jaip.2020.06.067
M3 - Article
C2 - 32693214
AN - SCOPUS:85089198319
SN - 2213-2198
VL - 8
SP - 3474
EP - 3481
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 10
ER -