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Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases.
Free Radic Biol Med 1998; 24(6):952-8FR

Abstract

Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness. It is thought that these two effects of ozone are linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the effect of recombinant antileukoprotease (rALP), one of the major serine proteinase inhibitors in the lung, on ozone-induced changes in airway hyperresponsiveness in this model. We observed that 16 h after exposure to ozone, airway hyperresponsiveness to methacholine was increased both following placebo and rALP treatment. There was no significant difference between placebo and rALP treatment (change in area under the dose-response curve to methacholine: 117.3+/-59.0 vs 193.6+/-59.6 % fall x DD; p=.12). Moreover, the immediate decrease in FEV1 after ozone exposure was not significantly different between the two groups (placebo: -29.6+/-6.7%; rALP: -20.9+/-3.8%; p=.11). In addition, no significant differences were observed in plasma levels of fibrinogen degradation products generated by neutrophil serine proteinases before and after exposure to ozone. We conclude that neutrophil-derived serine proteinases are not important mediators for ozone-induced hyperresponsiveness.

Authors+Show Affiliations

Department of Pulmonology, Leiden University Hospital, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

9607605

Citation

Hiltermann, T J., et al. "Ozone-induced Airway Hyperresponsiveness in Patients With Asthma: Role of Neutrophil-derived Serine Proteinases." Free Radical Biology & Medicine, vol. 24, no. 6, 1998, pp. 952-8.
Hiltermann TJ, Peters EA, Alberts B, et al. Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases. Free Radic Biol Med. 1998;24(6):952-8.
Hiltermann, T. J., Peters, E. A., Alberts, B., Kwikkers, K., Borggreven, P. A., Hiemstra, P. S., ... Stolk, J. (1998). Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases. Free Radical Biology & Medicine, 24(6), pp. 952-8.
Hiltermann TJ, et al. Ozone-induced Airway Hyperresponsiveness in Patients With Asthma: Role of Neutrophil-derived Serine Proteinases. Free Radic Biol Med. 1998;24(6):952-8. PubMed PMID: 9607605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ozone-induced airway hyperresponsiveness in patients with asthma: role of neutrophil-derived serine proteinases. AU - Hiltermann,T J, AU - Peters,E A, AU - Alberts,B, AU - Kwikkers,K, AU - Borggreven,P A, AU - Hiemstra,P S, AU - Dijkman,J H, AU - van Bree,L A, AU - Stolk,J, PY - 1998/6/2/pubmed PY - 1998/6/2/medline PY - 1998/6/2/entrez SP - 952 EP - 8 JF - Free radical biology & medicine JO - Free Radic. Biol. Med. VL - 24 IS - 6 N2 - Proteinase inhibitors may be of potential therapeutic value in the treatment of respiratory diseases such as chronic obstructive pulmonary disease (COPD) or asthma. Our aim was to study the role of neutrophils, and neutrophil-derived serine proteinases in an acute model in patients with asthma. Exposure to ozone induces an acute neutrophilic inflammatory reaction accompanied by an increase in airway hyperresponsiveness. It is thought that these two effects of ozone are linked, and that neutrophil-derived serine proteinases (i.e. elastase) may play a role in the ozone-induced airway hyperresponsiveness. Therefore, we examined the effect of recombinant antileukoprotease (rALP), one of the major serine proteinase inhibitors in the lung, on ozone-induced changes in airway hyperresponsiveness in this model. We observed that 16 h after exposure to ozone, airway hyperresponsiveness to methacholine was increased both following placebo and rALP treatment. There was no significant difference between placebo and rALP treatment (change in area under the dose-response curve to methacholine: 117.3+/-59.0 vs 193.6+/-59.6 % fall x DD; p=.12). Moreover, the immediate decrease in FEV1 after ozone exposure was not significantly different between the two groups (placebo: -29.6+/-6.7%; rALP: -20.9+/-3.8%; p=.11). In addition, no significant differences were observed in plasma levels of fibrinogen degradation products generated by neutrophil serine proteinases before and after exposure to ozone. We conclude that neutrophil-derived serine proteinases are not important mediators for ozone-induced hyperresponsiveness. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/9607605/Ozone_induced_airway_hyperresponsiveness_in_patients_with_asthma:_role_of_neutrophil_derived_serine_proteinases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(97)00381-X DB - PRIME DP - Unbound Medicine ER -