0
Clinical Investigations: ASTHMA |

Dose-Response Relationship and Reproducibility of the Fall in Exhaled Nitric Oxide After Inhaled Beclomethasone Dipropionate Therapy in Asthma Patients*

Philip E. Silkoff, MD; Patricia McClean, MSc; Michael Spino, PharmD; LuAnn Erlich, PhD; Arthur S. Slutsky, MD, FCCP; Noe Zamel, MD, FCCP
Author and Funding Information

*From the Toronto Hospital, Toronto, Ontario, Canada.

Correspondence to: Philip E. Silkoff, MD, 1400 Jackson St, Denver, CO 80206; e-mail: silkoffp@njc.org



Chest. 2001;119(5):1322-1328. doi:10.1378/chest.119.5.1322
Text Size: A A A
Published online

Study objectives: The fractional concentration of exhaled nitric oxide (Feno) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the Feno fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients.

Study design: Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 μg/d of iBDP; period 3, 400 μg/D of iBDP; and period 4, 800 μg/d of iBDP. Spirometry, Feno, and provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 μg/d of iBDP for 14 days (period 2), washout on placebo treatment until the Feno was within 15% of baseline (period 3), and 200 μg/d of iBDP for 14 days (period 4).

Results: Study A: Mean FEV1 rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV1 rise compared to placebo treatment, but with no significant separation of doses using FEV1. Feno geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in Feno from placebo treatment, but with significant separation of only the 100-μg and 800-μg doses by Feno. Geometric mean (95% confidence limits) PC20 rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC20 from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC20. Study B: Feno fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between Feno in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220).

Conclusions: Feno was superior to FEV1 and PC20 in separating doses of iBDP. The fall in Feno after two identical administrations of iBDP separated by placebo washout was highly reproducible.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543