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Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge.
Respiration. 2007; 74(4):411-7.R

Abstract

BACKGROUND

Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma.

OBJECTIVES

This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge.

METHODS

In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) <or=9 h after allergen challenge. AHR to histamine provocation was measured before and repeated 24 h after allergen provocation. Patients inhaled histamine in doubling concentrations until attaining a decrease in FEV(1) of <or=20% (PC(20)FEV(1)).

RESULTS

Roflumilast had no detectable bronchodilator activity 60 min after administration. Roflumilast significantly attenuated AHR compared with placebo, with a mean change in pre- to postallergen challenge PC(20)FEV(1) ratio of 1.23 +/- 2.75 and 2.51 +/- 2.95 for roflumilast and placebo, respectively (p = 0.002). During the late asthmatic response, roflumilast reduced the mean maximum decrease in FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV(1) at 9 h after challenge was significantly higher in patients treated with roflumilast (p = 0.03). Early asthmatic responses to allergen challenge were not significantly reduced by the single dose of roflumilast.

CONCLUSIONS

Roflumilast attenuated allergen-induced AHR in patients with mild asthma. These results support further investigation of roflumilast as an anti-inflammatory treatment of asthma.

Authors+Show Affiliations

Internal Medicine, Lung and Allergy Unit, University of Stellenbosch, School of Medicine, Cape Town, South Africa.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16954654

Citation

Louw, C, et al. "Roflumilast, a Phosphodiesterase 4 Inhibitor, Reduces Airway Hyperresponsiveness After Allergen Challenge." Respiration; International Review of Thoracic Diseases, vol. 74, no. 4, 2007, pp. 411-7.
Louw C, Williams Z, Venter L, et al. Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge. Respiration. 2007;74(4):411-7.
Louw, C., Williams, Z., Venter, L., Leichtl, S., Schmid-Wirlitsch, C., Bredenbroker, D., & Bardin, P. G. (2007). Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge. Respiration; International Review of Thoracic Diseases, 74(4), 411-7.
Louw C, et al. Roflumilast, a Phosphodiesterase 4 Inhibitor, Reduces Airway Hyperresponsiveness After Allergen Challenge. Respiration. 2007;74(4):411-7. PubMed PMID: 16954654.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roflumilast, a phosphodiesterase 4 inhibitor, reduces airway hyperresponsiveness after allergen challenge. AU - Louw,C, AU - Williams,Z, AU - Venter,L, AU - Leichtl,S, AU - Schmid-Wirlitsch,C, AU - Bredenbroker,D, AU - Bardin,P G, Y1 - 2006/09/05/ PY - 2005/11/07/received PY - 2006/06/19/accepted PY - 2006/9/7/pubmed PY - 2007/9/28/medline PY - 2006/9/7/entrez SP - 411 EP - 7 JF - Respiration; international review of thoracic diseases JO - Respiration VL - 74 IS - 4 N2 - BACKGROUND: Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, is currently in clinical development for the treatment of asthma. OBJECTIVES: This pilot study examined the effect of roflumilast on allergen-induced airway hyperresponsiveness (AHR) to histamine challenge and asthmatic response to allergen challenge. METHODS: In a randomized, double-blind, 2-period, crossover trial, 13 patients with mild allergic asthma [mean forced expiratory volume in 1 s (FEV(1)) % predicted = 86%] received a single dose of oral roflumilast 1,000 microg or placebo. Patients were administered roflumilast 60 min before allergen challenge, and asthmatic responses were assessed via change in FEV(1) <or=9 h after allergen challenge. AHR to histamine provocation was measured before and repeated 24 h after allergen provocation. Patients inhaled histamine in doubling concentrations until attaining a decrease in FEV(1) of <or=20% (PC(20)FEV(1)). RESULTS: Roflumilast had no detectable bronchodilator activity 60 min after administration. Roflumilast significantly attenuated AHR compared with placebo, with a mean change in pre- to postallergen challenge PC(20)FEV(1) ratio of 1.23 +/- 2.75 and 2.51 +/- 2.95 for roflumilast and placebo, respectively (p = 0.002). During the late asthmatic response, roflumilast reduced the mean maximum decrease in FEV(1) from 2 to 9 h after allergen challenge compared with placebo (p = 0.005). Additionally, FEV(1) at 9 h after challenge was significantly higher in patients treated with roflumilast (p = 0.03). Early asthmatic responses to allergen challenge were not significantly reduced by the single dose of roflumilast. CONCLUSIONS: Roflumilast attenuated allergen-induced AHR in patients with mild asthma. These results support further investigation of roflumilast as an anti-inflammatory treatment of asthma. SN - 0025-7931 UR - https://www.unboundmedicine.com/medline/citation/16954654/Roflumilast_a_phosphodiesterase_4_inhibitor_reduces_airway_hyperresponsiveness_after_allergen_challenge_ L2 - https://www.karger.com?DOI=10.1159/000095677 DB - PRIME DP - Unbound Medicine ER -