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The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma.
Clin Exp Allergy. 1999 Jan; 29(1):42-51.CE

Abstract

BACKGROUND

Cysteinyl leukotrienes are capable of inducing chemotaxis of eosinophils in vitro and within the airways of animals and humans in vivo.

OBJECTIVE

We hypothesized that montelukast (MK-0476), a potent cysLT1 receptor antagonist, would protect against allergen-induced early (EAR) and late (LAR) asthmatic responses by virtue of anti-inflammatory properties. Hence, we studied the effect of pretreatment with oral montelukast on allergen-induced airway responses. As an exploratory endpoint, changes in inflammatory cell differentials and eosinophil cationic protein (ECP) were evaluated in hypertonic saline-induced sputum.

METHODS

Twelve asthmatic men (20-34 years, FEV1 79-109% predicted, histamine PC20FEV1 <4 mg/mL) with dual responses to inhaled house dust mite extract participated in a two-period, double-blind, placebo-controlled, crossover study. Three oral doses of montelukast (10 mg) or matching placebo were administered 36 and 12 h before, and 12 h post-allergen. The airway response to allergen was measured by FEV1, and the EAR and LAR were expressed as the corresponding areas under the time-response curves (AUC0-3 h and AUC3-8h, respectively). During each study period, sputum was induced with 4.5% NaCl 24 h before and 24 h after a standardized allergen challenge. Processed whole sputum cytospins were stained with Giemsa, and cell counts expressed as percentage nonsquamous cells. ECP was measured by FEIA in sputum supernatants.

RESULTS

All subjects completed the study. The changes in baseline FEV1 were not significantly different between the two pretreatments (P = 0.183). Montelukast significantly inhibited the EAR and LAR, reducing the AUC0-3h by 75.4% (P<0.001) and the AUC3-8h by 56.9% (P = 0.003) as compared with placebo. Sputa of nine subjects could be included in the analysis (<80% squamous cells). Allergen challenge significantly increased sputum eosinophils after placebo (mean change +/- SD: 4.8 +/- 5.8%, P = 0.038), with a similar trend after montelukast (mean change +/- SD: 4.1 +/- 5.4%; P = 0.056). The allergen-induced changes in sputum eosinophils and ECP, however, were not significantly different between the two pretreatments (P = 0.652 and P = 0.506, respectively).

CONCLUSION

We conclude that oral montelukast protects against allergen-induced early and late airway responses in asthma. However, using the present dosing and sample size, this protection was not accompanied with changes in sputum eosinophil percentage or activity, which may require more prolonged pretreatment with cysLT1 receptor antagonists.

Authors+Show Affiliations

Department of Pulmonology, Leiden University Medical Center, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

Language

eng

PubMed ID

10051701

Citation

Diamant, Z, et al. "The Effect of Montelukast (MK-0476), a Cysteinyl Leukotriene Receptor Antagonist, On Allergen-induced Airway Responses and Sputum Cell Counts in Asthma." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 29, no. 1, 1999, pp. 42-51.
Diamant Z, Grootendorst DC, Veselic-Charvat M, et al. The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy. 1999;29(1):42-51.
Diamant, Z., Grootendorst, D. C., Veselic-Charvat, M., Timmers, M. C., De Smet, M., Leff, J. A., Seidenberg, B. C., Zwinderman, A. H., Peszek, I., & Sterk, P. J. (1999). The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 29(1), 42-51.
Diamant Z, et al. The Effect of Montelukast (MK-0476), a Cysteinyl Leukotriene Receptor Antagonist, On Allergen-induced Airway Responses and Sputum Cell Counts in Asthma. Clin Exp Allergy. 1999;29(1):42-51. PubMed PMID: 10051701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. AU - Diamant,Z, AU - Grootendorst,D C, AU - Veselic-Charvat,M, AU - Timmers,M C, AU - De Smet,M, AU - Leff,J A, AU - Seidenberg,B C, AU - Zwinderman,A H, AU - Peszek,I, AU - Sterk,P J, PY - 1999/3/3/pubmed PY - 1999/3/3/medline PY - 1999/3/3/entrez SP - 42 EP - 51 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 29 IS - 1 N2 - BACKGROUND: Cysteinyl leukotrienes are capable of inducing chemotaxis of eosinophils in vitro and within the airways of animals and humans in vivo. OBJECTIVE: We hypothesized that montelukast (MK-0476), a potent cysLT1 receptor antagonist, would protect against allergen-induced early (EAR) and late (LAR) asthmatic responses by virtue of anti-inflammatory properties. Hence, we studied the effect of pretreatment with oral montelukast on allergen-induced airway responses. As an exploratory endpoint, changes in inflammatory cell differentials and eosinophil cationic protein (ECP) were evaluated in hypertonic saline-induced sputum. METHODS: Twelve asthmatic men (20-34 years, FEV1 79-109% predicted, histamine PC20FEV1 <4 mg/mL) with dual responses to inhaled house dust mite extract participated in a two-period, double-blind, placebo-controlled, crossover study. Three oral doses of montelukast (10 mg) or matching placebo were administered 36 and 12 h before, and 12 h post-allergen. The airway response to allergen was measured by FEV1, and the EAR and LAR were expressed as the corresponding areas under the time-response curves (AUC0-3 h and AUC3-8h, respectively). During each study period, sputum was induced with 4.5% NaCl 24 h before and 24 h after a standardized allergen challenge. Processed whole sputum cytospins were stained with Giemsa, and cell counts expressed as percentage nonsquamous cells. ECP was measured by FEIA in sputum supernatants. RESULTS: All subjects completed the study. The changes in baseline FEV1 were not significantly different between the two pretreatments (P = 0.183). Montelukast significantly inhibited the EAR and LAR, reducing the AUC0-3h by 75.4% (P<0.001) and the AUC3-8h by 56.9% (P = 0.003) as compared with placebo. Sputa of nine subjects could be included in the analysis (<80% squamous cells). Allergen challenge significantly increased sputum eosinophils after placebo (mean change +/- SD: 4.8 +/- 5.8%, P = 0.038), with a similar trend after montelukast (mean change +/- SD: 4.1 +/- 5.4%; P = 0.056). The allergen-induced changes in sputum eosinophils and ECP, however, were not significantly different between the two pretreatments (P = 0.652 and P = 0.506, respectively). CONCLUSION: We conclude that oral montelukast protects against allergen-induced early and late airway responses in asthma. However, using the present dosing and sample size, this protection was not accompanied with changes in sputum eosinophil percentage or activity, which may require more prolonged pretreatment with cysLT1 receptor antagonists. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/10051701/The_effect_of_montelukast__MK_0476__a_cysteinyl_leukotriene_receptor_antagonist_on_allergen_induced_airway_responses_and_sputum_cell_counts_in_asthma_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0954-7894&amp;date=1999&amp;volume=29&amp;issue=1&amp;spage=42 DB - PRIME DP - Unbound Medicine ER -