Sputum eosinophil counts predict asthma control after discontinuation of inhaled corticosteroids - 18/08/11
, Stephen C. Lazarus, MD c, John V. Fahy, MD, ChB c, Michael E. Wechsler, MD, MMSc a, Homer A. Boushey, MD c, Vernon M. Chinchilli, PhD b, Timothy J. Craig, DO b, Emily Dimango, MD e, Monica Kraft, MD f, Frank Leone, MD g, Robert F. Lemanske, MD d, Richard J. Martin, MD f, Gene R. Pesola, MD, MPH e, Stephen P. Peters, MD, PhD h, Christine A. Sorkness, PharmD d, Stanley J. Szefler, MD f, Elliot Israel, MD afor the National Heart, Lung, And Blood Institute's Asthma Clinical Research Network
Reprint requests: Aaron Deykin, MD, Pulmonary Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115.Boston, Mass, Hershey and Philadelphia, Pa, San Francisco, Calif, New York, NY, Denver, Colo, and Winston-Salem, NC
Abstract |
Background |
Although inhaled corticosteroids (ICSs) are effective in preventing deterioration in asthma control, at least half of subjects with mild-to-moderate asthma will remain stable when these agents are discontinued.
Objective |
We sought to determine whether noninvasive markers of inflammation predict which individuals maintain asthma control after discontinuation of ICSs.
Methods |
We analyzed data obtained from 164 subjects with mild-to-moderate asthma who participated in a 16-week trial comparing the effects of continued ICS use with the effects of a switch to salmeterol or placebo.
Results |
In comparison with continued ICS use, a switch to salmeterol or placebo was associated with increased rates of asthma deterioration over 16 weeks (9.3% vs 24.1% and 37.5%, respectively; P=.04 and P < .001, respectively). We found that neither exhaled nitric oxide nor methacholine PC20, when measured at randomization or 2 weeks after randomization, were significant predictors of subsequent asthma control in subjects who discontinued ICSs. However, both induced sputum eosinophil counts measured 2 weeks after a switch from ICS to placebo and changes in sputum eosinophil counts from before cessation of ICSs to after a switch to placebo predicted subsequent asthma deterioration (area under the receiver-operating characteristic curve, 0.771 [P < .001] and 0.825 [P < .001], respectively).
Conclusion |
On the basis of a model treatment strategy, we estimate that allocating subjects to ICS therapy on the basis of changes in sputum eosinophil counts after a trial discontinuation could allow 48% of subjects with mild-to-moderate asthma to discontinue ICS therapy without an increased risk of asthma deterioration over a period of at least 14 weeks.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, exacerbation, sputum, eosinophils, inhaled corticosteroids, methacholine, nitric oxide
Abbreviations used : ECP, Feno, ICS, ROC, SOCS trial, TAA
Plan
| Funding information: U10-HL51810, U10-HL51834, U10-HL51831, U10-Hl51823, U10-HL51845, U10-HL51843, U10-HL56443, U10-HL, and M01-RR03186. Disclosure of potential conflict of interest: Aaron Deykin has served as a consultant for Aerocrine US. Stephen C. Lazarus has served as a consultant for Aventis, Fujisawa, GlaxoSmithKline, Immunex, Merck, and Novartis and has received research funding and/or honoraria from Abbott, Astra, Boehringer Ingelheim, Genentech, Merck Frosst, Pfizer, Pharmacia-Upjohn, and Zeneca. John V. Fahy has served as a consultant for Xoma, Tularik, Bayer, Amgen, Dynavax, Boehringer, and Roche; has received honoraria from Merck; and has received research grants from GlaxoSmithKline and AstraZeneca. Homer Boushey has received consultancy fees and honoraria from GlaxoSmithKline, and GlaxoSmithKline has made payment to the Regents of the University of California for support of a clinical research project on which he was the Principal Investigator. Vernon M. Chinchilli has served as a biostatistical consultant for BristolMyersSquibb and Wyeth-Ayerst. Monica Kraft has served on the speakers' bureau for Novartis, Genentach, Merck, GlaxoSmithKline, Forest, and Aventis and as a consultant for Novartis, Genentech, Merck, and Forest. Frank T. Leone has received commercial research grants or contracts from Pfizer, Merck, Ono, GlaxoSmithKline, and Ortho Biotech. Robert F. Lemanske has served as a consultant for Aventis and AstraZeneca. Richard J. Martin has served as a consultant and has received honoraria from GlaxoSmithKline Aventis, Forest, Schering, Merck, AstraZeneca, IVAX, Novartis, and Genentech. Stephen P. Peters has received a basic research grant from Merck; has participated in clinical trials supported by Abaris, AstraZeneca, Altana, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, and Pfizer; has served as a consultant for the National Institutes of Health, Adelphi, AstraZeneca, Aventis, Genentech, RAND Corporation, and Novartis; and has participated in physical education programs (including speakers' bureaus) sponsored by the American Lung Association, the American Academy of Allergy, Asthma & Immunology, AstraZeneca, Merck, Genentech, and Novartis. Christine A. Sorkness has served on the advisory board and speaker's bureau of GlaxoSmithKline. Stanley J. Szefler has served as an ad hoc consultant for and has received honoraria from GlaxoSmithKline and has served as an ad hoc consultant and as the Principal Investigator for the Denver site of a clinical trial sponsored by AstraZeneca. None of the remaining authors have relevant conflicts of interest to disclose. |
Vol 115 - N° 4
P. 720-727 - avril 2005 Retour au numéro
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