Tags

Type your tag names separated by a space and hit enter

Effects of theophylline on tolerance to the bronchoprotective actions of salmeterol in asthmatics in vivo.
Am J Respir Crit Care Med. 1998 Sep; 158(3):792-6.AJ

Abstract

Long-term treatment with salmeterol produces tolerance for its protective effects against bronchoconstrictor stimuli in patients with asthma. There is human in vitro evidence that theophylline may prevent beta2-adrenoceptor downregulation. Therefore, we investigated the effect of theophylline on the tolerance to the protective effect of salmeterol against histamine challenge in asthma in vivo. In a parallel 6-wk study, 25 asthmatics were treated with theophylline (mean serum level +/- SEM: 9.9 +/- 1.1 mg/L, Days 1 to 40) or placebo, combined with inhaled salmeterol (50 microgram twice daily, Days 8 to 36). Histamine challenges were carried out by tidal breathing method at entry, and at Days 4, 8, 22, 36, and 40. The response was measured by PC20. There was no significant change in PC20 after 4 d monotherapy with theophylline or placebo (mean difference +/- SEM: 0.54 +/- 0.39 and -0.02 +/- 0.41 doubling dose [DD], respectively; p > 0.15). One hour after the first dose, salmeterol afforded significant protection against histamine, as shown by an increase in PC20 in both the theophylline and placebo group (by 3.49 +/- 0.28 and 3.36 +/- 0.32 DD, respectively; p < 0. 001). However, after 2 and 4 wk salmeterol treatment, the improvements in PC20 by salmeterol were significantly reduced to 1. 80 +/- 0.35 and 1.69 +/- 0.36 DD, respectively, in the theophylline group (p < 0.001), and to 1.55 +/- 0.47 and 1.52 +/- 0.56 DD, respectively, in the placebo group (p < 0.002). These changes were not significantly different between the groups (p > 0.80). After cessation of salmeterol treatment, PC20 was not significantly different from the values at entry in either group (p > 0.90). We conclude that regular theophylline treatment neither prevents, nor worsens, the development of tolerance to the bronchoprotective effect of salmeterol in asthmatics in vivo.

Authors+Show Affiliations

Department of Pulmonology, Leiden University Medical Centre, Red Cross Hospital, The Hague, The Netherlands. dcheung@pulmonology.azl.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9731006

Citation

Cheung, D, et al. "Effects of Theophylline On Tolerance to the Bronchoprotective Actions of Salmeterol in Asthmatics in Vivo." American Journal of Respiratory and Critical Care Medicine, vol. 158, no. 3, 1998, pp. 792-6.
Cheung D, Wever AM, de GOEIJ JA, et al. Effects of theophylline on tolerance to the bronchoprotective actions of salmeterol in asthmatics in vivo. Am J Respir Crit Care Med. 1998;158(3):792-6.
Cheung, D., Wever, A. M., de GOEIJ, J. A., de GRAAFF, C. S., Steen, H., & Sterk, P. J. (1998). Effects of theophylline on tolerance to the bronchoprotective actions of salmeterol in asthmatics in vivo. American Journal of Respiratory and Critical Care Medicine, 158(3), 792-6.
Cheung D, et al. Effects of Theophylline On Tolerance to the Bronchoprotective Actions of Salmeterol in Asthmatics in Vivo. Am J Respir Crit Care Med. 1998;158(3):792-6. PubMed PMID: 9731006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of theophylline on tolerance to the bronchoprotective actions of salmeterol in asthmatics in vivo. AU - Cheung,D, AU - Wever,A M, AU - de GOEIJ,J A, AU - de GRAAFF,C S, AU - Steen,H, AU - Sterk,P J, PY - 1998/9/10/pubmed PY - 1998/9/10/medline PY - 1998/9/10/entrez SP - 792 EP - 6 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 158 IS - 3 N2 - Long-term treatment with salmeterol produces tolerance for its protective effects against bronchoconstrictor stimuli in patients with asthma. There is human in vitro evidence that theophylline may prevent beta2-adrenoceptor downregulation. Therefore, we investigated the effect of theophylline on the tolerance to the protective effect of salmeterol against histamine challenge in asthma in vivo. In a parallel 6-wk study, 25 asthmatics were treated with theophylline (mean serum level +/- SEM: 9.9 +/- 1.1 mg/L, Days 1 to 40) or placebo, combined with inhaled salmeterol (50 microgram twice daily, Days 8 to 36). Histamine challenges were carried out by tidal breathing method at entry, and at Days 4, 8, 22, 36, and 40. The response was measured by PC20. There was no significant change in PC20 after 4 d monotherapy with theophylline or placebo (mean difference +/- SEM: 0.54 +/- 0.39 and -0.02 +/- 0.41 doubling dose [DD], respectively; p > 0.15). One hour after the first dose, salmeterol afforded significant protection against histamine, as shown by an increase in PC20 in both the theophylline and placebo group (by 3.49 +/- 0.28 and 3.36 +/- 0.32 DD, respectively; p < 0. 001). However, after 2 and 4 wk salmeterol treatment, the improvements in PC20 by salmeterol were significantly reduced to 1. 80 +/- 0.35 and 1.69 +/- 0.36 DD, respectively, in the theophylline group (p < 0.001), and to 1.55 +/- 0.47 and 1.52 +/- 0.56 DD, respectively, in the placebo group (p < 0.002). These changes were not significantly different between the groups (p > 0.80). After cessation of salmeterol treatment, PC20 was not significantly different from the values at entry in either group (p > 0.90). We conclude that regular theophylline treatment neither prevents, nor worsens, the development of tolerance to the bronchoprotective effect of salmeterol in asthmatics in vivo. SN - 1073-449X UR - https://www.unboundmedicine.com/medline/citation/9731006/Effects_of_theophylline_on_tolerance_to_the_bronchoprotective_actions_of_salmeterol_in_asthmatics_in_vivo_ L2 - https://www.atsjournals.org/doi/10.1164/ajrccm.158.3.9801036?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -