Plasma Histamine and Bronchial Reactivity in Allergic Asthma

in Allergy (1993), 48(7), 547-9

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic ... [more ▼]

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic asthmatic patients have yielded controversial results. We therefore measured plasma histamine and bronchial reactivity in 30 nonsmoker volunteers taking no medication. Eleven were normal subjects; 19 were stable, mildly allergic asthmatic patients. Venous blood was taken to measure blood cells and basal plasma histamine by radioimmunoassay. After blood sampling, all subjects underwent a measurement of PC20M (concentration of methacholine causing a 20% fall in FEV1). Mean plasma histamine levels were 0.21 +/- 0.1 ng/ml and 0.44 +/- 0.3 ng/ml in normal and asthmatic subjects, respectively (P < 0.05). We found a significant increase of blood eosinophils and basophils in asthmatic patients, and a positive correlation between plasma histamine and circulating basophils. PC20M was greater than 16 mg in normal volunteers, and mean PC20M was 2.1 +/- 2 mg/ml in asthmatic patients. PC20M did not correlate with plasma histamine levels, but it did so negatively with blood eosinophils. The increased plasma histamine concentration in mildly atopic asthmatic patients might be a consequence of the high basophil releasability of atopics and the higher basophil counts in allergic asthma. Plasma histamine is thus unlikely to be a determinant of BHR in asthma. [less ▲]

No Increase in Plasma Histamine During Paf-Induced Airway Obstruction in Allergic Asthmatics

in CHEST (1993), 104(3), 806-10

To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single ... [more ▼]

To investigate the possible role of mast cell or basophil histamine release in mediating platelet-activating factor (PAF) airway obstruction, we studied the effect of inhaled PAF (30 micrograms, single dose) on plasma histamine, bronchial caliber, and leukocyte and platelet counts in six patients with mild or moderate allergic asthma (mean age, 27 +/- 1.3 years; mean FEV1, 95 +/- 5 percent of predicted; mean PC20 methacholine, 1.46 +/- 0.36 mg/ml). Specific conductance (SGaw) FEV1, FEF25-75 percent, differential leukocyte and platelet counts, and plasma histamine (radioimmunoassay) were measured before and 5, 10, 15, and 20 min after PAF inhalation. Mean basal plasma histamine level was 0.28 +/- 0.04 ng/ml. Inhalation of PAF caused a fall in SGaw peaking at 5 min (43 +/- 9 percent) and a fall in FEV1 and FEF25-75 peaking at 10 min (19 +/- 10 percent and 30 +/- 13 percent, respectively). There was also a rapid and transient fall in circulating neutrophils at 5 min (from 3,096 +/- 204/mm3 to 2,551 +/- 158/mm3, p < 0.05) followed by a rebound neutrophilia. In contrast, plasma histamine level did not change significantly at any time measured. Conversely in the same asthmatics, a rapid rise in plasma histamine level (from 0.29 +/- 0.03 ng/ml at baseline to 0.53 +/- 0.06 ng/ml at 5 min; p < 0.01) was observed after an allergenic challenge (Dermatophagoides pteronyssinus) causing a fall in FEV1 peaking at 10 min (22 +/- 4 percent). Thus, inhaled PAF may induce airway obstruction and neutropenia in asthmatics without any significant change of plasma histamine level. These results indicate that it is unlikely that lung mast cells or basophils degranulate during PAF-induced bronchoconstriction. [less ▲]

Chylothorax: a rare complication of endoscopic variceal sclerotherapy.

in European Journal of Gastroenterology & Hepatology (1993), 5

Ly 186655, a Phosphodiesterase Inhibitor, Inhibits Histamine Release from Human Basophils, Lung and Skin Fragments

in International Journal of Immunopharmacology (1992), 14(2), 191-4

LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived from the xanthine, possessing bronchodilating activity in animals. The aim of this work was to study the effect of LY 186655 ... [more ▼]

LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived from the xanthine, possessing bronchodilating activity in animals. The aim of this work was to study the effect of LY 186655 and theophylline on histamine release from human leukocytes, skin and lung fragments. Histamine was measured using a spectrofluorometric method. Both drugs (3 x 10(-5)-3 x 10(-3) M) exhibited a dose-dependent inhibition on anti-IgE (1/2000)-induced histamine release from human leukocytes. At 3 x 10(-3) M, theophylline was significantly more effective than LY 186655 (mean inhibition 94 and 42%, respectively). On lung fragments, theophylline and LY 186655 (3 x 10(-5)-3 x 10(-3) M) caused strong and comparable inhibitory effects on anti-IgE (1/500)-induced histamine release with a mean inhibition reaching maximally 65%. Histamine release induced by compound 48/80 (1 mg/ml) on sliced human foreskin was reduced with both drugs (3 x 10(-3) M) by about 37%. We conclude that LY 186655 inhibits in vitro immunological histamine release from human lung and cutaneous mast cells as well as basophils with a similar pattern of activity to theophylline. [less ▲]

L'hyperréactivité bronchique non spécifique : son déterminisme et son traitement.

in Médecine et Hygiène (1991), 49