Inhaled nedocromil sodium reduces histamine release from isolated large airway segments of asthmatic subjects in vivo.
Placement of an intrabronchial single balloon catheter provides the possibility of measuring histamine release in isolated large airway segments in vivo. We wanted to assess the protective effect of nedocromil sodium on intrabronchial histamine release after hyperosmolar challenge. Six mild asthmatics were bronchoscoped 30 min after inhalation of 4 mg nedocromil sodium or placebo, given via a metered dose inhaler in a randomized, double-blind, cross-over study. Lavage of the left main bronchus was carried out proximal to a balloon catheter inflated at its bifurcation, and specimens were assayed for histamine and prostaglandin D2 (PGD2) by radioimmunoassay. The rise in histamine concentration in bronchial epithelial fluid following hyperosmolar saline challenge was significantly greater following placebo than following nedocromil sodium (mean +/- SEM prechallenge histamine concentration on placebo day 6.9 +/- 2.9 nM; post-challenge: 25.3 +/- 8.0 nM; mean +/- SEM prechallenge histamine concentration on the day nedocromil sodium was given: 3.7 +/- 0.7 nM; post-challenge 5.8 +/- 1.7 nM). Changes in PGD2 levels reflected the changes in histamine, but the variability of response was large, and there were no significant differences between the effects of placebo and nedocromil sodium. The procedure caused significantly greater falls in peak expiratory flow rates following placebo (mean +/- SEM percentage fall 20.2 +/- 4.4%) than following nedocromil sodium (0.9 +/- 5.8%, p < 0.02). We conclude that there is tonic basal histamine release within asthmatic airways, and that nedocromil sodium inhibits histamine release from mediator cells in vivo.
Maxwell
D L
DL
Dept of Allergy and Allied Respiratory Disorders, UMDS, Guy's Hospital, London, UK.
Hawksworth
R J
RJ
Lee
T H
TH
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects; D001999:Bronchoscopy; D002404:Catheterization; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008297:Male; D017835:Nedocromil / Q000008:administration & dosage / Q000627:therapeutic use*; D015230:Prostaglandin D2 / Q000032:analysis; D011863:Radioimmunoassay
D000336:Aerosols; D017835:Nedocromil; D006632:Histamine; D015230:Prostaglandin D2