Transcutaneous O₂ and CO₂ Monitoring of Bronchial Responsiveness in FEV₁ Non-Responder Asthmatics during Ketotifen and Placebo Treatment

Abstract

Effects of ultrasonically nebulized distilled water (UNDW) on PtcO₂ and PtcCO₂ time courses were studied in 26 mild asthmatics (FEV₁ non-responders) in basal conditions and monitored after 2,6,12 and 18 weeks of randomly allocated treatment with ketotifen 1 mg b.i.d. or placebo. Magnitude and duration of both PtcO₂ and PtcCO₂ changes due to UNDW inhalation were progressively normalized only by ketotifen. Partial but significant protection against UNDW-induced hyperventilation was achieved after 2 weeks of treatment, complete protection (also against UNDW-induced hypoxia) being achieved later. In view of the CO₂ dependency of respiratory drive and the primary structural targets of the hypo-osmotic bronchial challenge employed, these results suggest that ketotifen may affect the mucosal structures of the bronchial airways, thereby acting as a mucosal protective drug.

A partial involvement of histamine in ultrasonically nebulized distilled water‐induced bronchoconstriction in guinea‐pigs

“…Inhibitory effect of anti‐histamines on UNDW‐IB in our animal model is compatible with the previous studies in asthmatic subjects (Azevedo et al , 1990; Allegra et al , 1993). However, the partial inhibition of anti‐histamines shown both in asthmatics and in our animal model suggests that the mechanisms of UNDW‐IB may involve not only histamine release but also release of other mediators such as sensory neuropeptides, lipid mediators excluding TXA 2 (Fujimura et al , 1997a) and so on.…”

“…Azevedo et al (1990) have reported that the decrease in FEV 1 induced by UNDW inhalation is significantly reduced with terfenadine. Allegra et al (1993) have also shown that the magnitude and duration of both PtcO 2 and PtcCO 2 changes due to UNDW inhalation are progressively normalized by ketotifen. Sodium cromoglycate is a well‐established prophylactic drug for asthma and this substance has been shown to inhibit the mediator release from mast cells (Goose et al , 1969).…”

“…Some investigators (Allegra & Bianco, 1980; Allegra et al , 1993; Anderson et al , 1983; Kaliner et al , 1974; Azevedo et al , 1990; Goose & Blair, 1969; Wells et al , 1986; Robuschi et al , 1987; del Bufalo et al , 1989) have reported that histamine, one of the mediators in allergic response, may play a role in UNDW‐IB of asthmatics. The purpose of the present study was to examine whether histamine is involved in the UNDW‐IB of our animal model.…”