Effects of Nedocromil Sodium on Changes in Bronchial Hyperreactivity in Non-Asthmatic Atopic Rhinitic Subjects during the Grass Pollen Season

Altounyan, R. E. C.; Cole, Milton B.; Lee, T. B.

doi:10.1159/000411458

Cited by 15 publications

(10 citation statements)

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“…It has been demonstrated that nedocromil sodium impairs the release of inflammatory mediators from activated mast cells (Riley et al, 1987), and accordingly its efficacy has been attributed to this ability. It has also been shown that nedocromil sodium prevents early and late allergic reactions and allergeninduced bronchial hyperresponsiveness in experimental animals and man (Altounyan et al, 1986;Hutson et al, 1988;Pretolani et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Nedocromil sodium prevents in vivo generation of the eosinophilotactic substance induced by PAF but fails to antagonize its effects

Silva

Martins

Castro‐Faria‐Neto

et al. 1992

British J Pharmacology

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IThe intrathoracic injection of platelet activating factor (PAF) into rats induced a decrease in the pleural leucocyte numbers within 15 min, accompanied by a marked exudation, maximal 1 h later. After 6 h, concomitantly with the reduction of exudation, a marked increase in the number of mononuclear cells, neutrophils and eosinophils was observed. Within 24 h, the pleural eosinophil accumulation peaked and persisted up to 96 h. 2 Topical treatment with nedocromil sodium affected pleural exudation by PAF under conditions where systemic meclizine was ineffective. Nedocromil sodium blocked, dose-dependently, the increase in the pleural content of mononuclear cells, neutrophils and eosinophils, observed 6 h after PAF administration, as well as the eosinophilia 24 h later. Moreover, the co-incubation of peritoneal eosinophils with nedocromil sodium did not interfere with the migration triggered by PAF. 3 The transfer of the 6 h-PAF pleural washings from donor to recipient rats caused a selective pleural eosinophilia, which was clearly inhibited when nedocromil sodium was administered to donor, but not to recipient animals, showing that this drug interferes with the generation rather than with the expression of the eosinophilotactic activity(ies). 4 These findings indicate that the nedocromil sodium interferes with PAF-induced exudation and leucocyte accumulation, by a mechanism other than its ability to reduce the local effects of histamine and which may relate to suppression of the eosinophilotactic principle generation.

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Section: Discussionmentioning

confidence: 99%

Nedocromil sodium prevents in vivo generation of the eosinophilotactic substance induced by PAF but fails to antagonize its effects

Silva

Martins

Castro‐Faria‐Neto

et al. 1992

British J Pharmacology

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“…In addi tion to protecting against bronchoconstriction after aller gen challenge and exercise-induced asthma in man [24], NS also reduces the bronchial reactivity of asthmatics dur ing the pollen season [25], NS was previously found to de crease LTC4 generated by stimulated eosinophils [26], Thus, the aim of the present study was to determine whether NS was able to decrease LTB4 and 5-HETE syn thesis in A23187-stimulated PMN.…”

Section: Introductionmentioning

confidence: 88%

Arachidonate 5-Lipoxygenase Metabolism in Human Neutrophils from Patients with Asthma: In vitro Effect of Nedocromil Sodium

Radeau

Chavis

Godard

et al. 1992

Int Arch Allergy Immunol

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Among the cells which participate in amplification of the local inflammatory reaction in asthma, neutrophils (PMN) are pro-inflammatory cells that can generate inflammatory mediators and arachidonic acid derivatives in particular. In asthmatic patients (AP) with attacks, the capacity of blood PMN to produce 5-lipoxygenase metabolites was investigated and compared to the response in healthy subjects (HS). PMN from 6 AP and from 6 HS were stimulated by calcium ionophore A23187 and arachidonate 5-lipoxygenase metabolites were analyzed by reverse-phase HPLC. LTB₄, 6-trans LTB₄, ωOH-LTB₄ and 5-HETE were identified. In AP, total LTB₄ synthesis was enhanced as compared to synthesis with PMN in HS. But the total 5-HETE synthesis by PMN from AP was decreased. Thus, the inflammatory potential of PMN from AP was enhanced in comparison to HS. The anti-inflammatory effect of nedocromil sodium (NS) was studied in the 5-lipoxygenase metabolism of arachidonic acid. NS (10^––⁴ mol/l) inhibited total LTB₄ synthesized by PMN in AP but not in HS. We conclude that NS affects leukotriene synthesis only in cells with enhanced inflammatory potential.

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“…In addition, nedocromil sodium has inhibitory effects on the activation of neutrophils and eosin ophils from peripheral blood [15,16]. In atopic patients it reduces the seasonal in crease in nonspecific bronchial hyperreac tivity that accompanies the influx of these inflammatory cells into the airways [17][18][19][20], These properties suggest that nedocromil sodium has activity against inflamma tory reactions in the lung and should have a place in the management of chronic asthma. The present study was carried out to assess the efficacy of nedocromil so dium as an addition to existing mainte nance therapy of patients with chronic asthma.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Nedocromil Sodium versus Placebo as Additions to Routine Asthma Maintenance Therapy: a Multicentre, Double-Blind, Group Comparative Trial

Bianco¹,

Bono

Grassi

et al. 1989

Respiration

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A total of 117 subjects took part in a double-blind, placebo-controlled trial of nedocromil sodium (4 × 4 mg daily by inhalation) in the management of patients with moderately severe bronchial asthma. Treatment was randomly allocated and was continued for 12 weeks following a 2-week baseline period on routine asthma therapy.Statistically significant differences for nedocromil sodium versus placebo were found for diary card asthma severity scores, morning and evening peak flow measurements and daily bronchodilator usage. The clinicians’ assessments of asthma severity and global opinions of treatment efficacy were also significantly in favour of nedocromil sodium. Overall, the clinical status of these asthmatic patients was improved by adding nedocromil sodium onto their existing therapy.

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Effects of Nedocromil Sodium on Changes in Bronchial Hyperreactivity in Non-Asthmatic Atopic Rhinitic Subjects during the Grass Pollen Season

Cited by 15 publications

References 0 publications

Nedocromil sodium prevents in vivo generation of the eosinophilotactic substance induced by PAF but fails to antagonize its effects

Nedocromil sodium prevents in vivo generation of the eosinophilotactic substance induced by PAF but fails to antagonize its effects

Arachidonate 5-Lipoxygenase Metabolism in Human Neutrophils from Patients with Asthma: In vitro Effect of Nedocromil Sodium

Effectiveness of Nedocromil Sodium versus Placebo as Additions to Routine Asthma Maintenance Therapy: a Multicentre, Double-Blind, Group Comparative Trial

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