This work studies the temporal development of the acute anaphylactic bronchoconstriction in guinea-pigs sensitized to ovalbumin by different regimens, including IgE-antibody promoting ones. The results show that guinea-pigs sensitized with low amounts (1-10 micrograms) of ovalbumin together with alum produce the most pronounced bronchospasm when challenged with an intravenous injection of a low dose of antigen. Examination of the antibody classes by PCA technique shows that guinea-pigs sensitized with small amounts of antigen together with alum produced IgE and IgG1 antibodies. However, in sera from animals immunized with large amounts of antigen, only IgG1 antibodies could be detected.

A method is presented for the objective monitoring of the inflammatory response of the nasal mucosa to natural allergen exposure through measurements of biochemical markers such as TAME-esterase activity in a daily nasal lavage. Nine patients with strictly seasonal allergic rhinitis caused by birch pollen and five healthy nonatopic control subjects participated in the present study, which started 1 wk before the birch pollen season and continued throughout the entire pollen season. A diary card was used to assess daily nasal symptoms, and a daily nasal lavage was performed once every afternoon. The degree of pollen exposure was assessed by daily pollen counts. The TAME-esterase activity in the lavage fluid from the allergic patients, but not in that from the nonallergic control subjects, increased significantly during pollen exposure despite low pollen counts and was found to correlate with daily nasal symptoms (r = 0.36; p less than 0.05) and the degree of pollen exposure (r = 0.45; p less than 0.01). The area under the curve for the daily TAME-esterase measurements thus differed significantly (p less than 0.02) between allergic patients (158 +/- 28) and control subjects (74 +/- 9). This approach for the monitoring of patients with hay fever during natural allergen exposure will make further objective studies on the pathophysiology and pharmacology of hay fever possible. We also provide support for the validity of previous findings obtained in allergen challenge situations utilizing the lavage approach.

Tritiated budesonide and beclomethasone 17 alpha,21-dipropionate (BDP) were incubated with the 9000g supernatant of human liver homogenate. BDP was immediately hydrolysed to beclomethasone 17 alpha-propionate (BMP). BMP was then further biotransformed to polar metabolites. Budesonide was rapidly biotransformed (2-4 times more rapidly than BMP) to metabolites of low glucocorticoid potency. The compounds were also incubated with the 1000g supernatant of human lung homogenate. BDP was rapidly hydrolysed to BMP and then more slowly to beclomethasone. Budesonide was not biotransformed in the lung.

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The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.