The pathophysiology of obstructive airways disease involves, in varying degree, components of reversible bronchoconstriction,
inflammation and
bronchial hyperreactivity. This multifactorial aetiology is the probable reason why no single animal model exists which is predictive of therapeutic efficacy in airway diseases, including
asthma.
Nedocromil sodium has therefore been profiled in a number of systems ranging from simple in vitro tests and in vivo models of passive
anaphylaxis to complex models of anaphylactic bronchoconstriction in actively sensitized primates.
Nedocromil sodium possesses efficacy and potency similar to those of
sodium cromoglycate in classical passive models of
immediate hypersensitivity in the rat. Preliminary studies have also shown that
nedocromil sodium, like
sodium cromoglycate, attenuates non-specific
bronchial hyperreactivity in dogs exposed to sulphur dioxide. Extensive studies have been carried out in a model of airway disease in the primate Macaca arctoides infected with the nematode Ascaris suum. Bronchoalveolar cells obtained from these animals by lung lavage release substantial quantities of the inflammatory mediators
histamine,
leukotriene C4 (
LTC4) and
prostaglandin D2 (
PGD2) on immunological activation.
Nedocromil sodium significantly inhibits the release of
histamine,
LTC4 and
PGD2 from these cells in response to stimulation with
antigen or antibody to human
IgE. Under identical conditions,
sodium cromoglycate has less than 1/200th the potency of
nedocromil sodium, producing only insignificant inhibition of mediator release even at concentrations greater than 10(-4) M. A similar difference between the two drugs has been observed in vivo, where
nedocromil sodium produced significant inhibition of
antigen-induced bronchoconstriction in the Ascaris-sensitized macaque but
sodium cromoglycate did not.(ABSTRACT TRUNCATED AT 250 WORDS)