Lavage Fluid Levels Of Alpha2-macroglobulin Research Articles

Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses

Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).

Steroid‐sensitive indices of airway inflammation in children with seasonal allergic rhinitis

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 microg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and alpha2-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of alpha2-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in alpha2-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.

Allergen challenge-induced acute exudation of IL-8, ECP and alpha2-macroglobulin in human rhinovirus-induced common colds.

Rhinovirus infections cause exacerbations of eosinophilic airway disease. The acute effects of allergen-challenge on nasal interleukin-8 (IL-8), eosinophil cationic protein (ECP), and alpha2-macroglobulin were examined in atopic subjects with common cold symptoms. Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 outside the pollen season. Diluent and allergen challenges, followed by nasal lavages, were carried out about 3 months before and 4 days after virus inoculation. Seventeen patients developed significant common cold symptoms with increased nasal lavage fluid levels of alpha2-macroglobulin, IL-8, and ECP at baseline (p<0.001-0.05 versus before inoculation), and were further increased by allergen challenge (p< 0.001-0.05); IL-8 and ECP levels were correlated (r = 0.63, p<0.001). Before inoculation, the six patients who later did not develop common cold symptoms had high levels of IL-8 and myeloperoxidase (MPO), and exhibited strong allergen-induced plasma exudation responses (alpha2-macroglobulin). After inoculation, IL-8 and ECP did not increase in these symptomless subjects. In conclusion, high nasal interleukin-8 and myeloperoxidase levels and exudative hyperresponsiveness may protect against infection. The association between nasal interleukin-8 and eosinophil cationic protein in common cold, particularly that observed in nasal lavage fluids after allergen-induced acute exudation of plasma, suggests the involvement of interleukin-8 in exacerbation of airway mucosal eosinophil activity.

Effects of two weeks of topical budesonide treatment on microvascular exudative responsiveness in healthy human nasal airways

Extravasation and luminal entry of plasma (mucosal exudation) is not only a key feature of airway inflammation in rhinitis and asthma but also a major first-line respiratory defence mechanism. Topical steroids are effective antiexudative agents in disease but, so far, little is known about the direct effects of these drugs on the responsiveness of the microcirculation in human airways. In this study, the effects of prolonged budesonide treatment on histamine-induced mucosal exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were carried out before and late in the treatment periods. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation of bulk plasma. Histamine produced concentration-dependent mucosal exudation of plasma before as well as after treatment with either placebo or budesonide. The topical steroid treatment only marginally (1.8 fold) decreased the response to the low concentration histamine (40 microg x mL(-1)) and, although it was significantly (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant mucosal exudation of plasma in the budesonide group. If the present observations are extrapolated to inflammatory conditions, the antiexudative effects of topical steroids in rhinitis (and asthma) may reflect only a small degree of microvascular antipermeability effects. We suggest that topical steroid treatment may not impede mucosal exudation responses when called for in acute human airway defence reactions.

Topical azelastine has a 12‐hour duration of action as assessed by histamine challenge‐induced exudation of α2‐macroglobulin into human nasal airways

Oral anti-histamine drugs are widely used in the treatment of seasonal allergic rhinitis. Recently, anti-histamines have become available also for topical treatment. The present study, involving healthy subjects, examined the effect of topical azelastine on luminal entry of alpha 2-macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The effect was compared to a clinical dose of the oral anti-histamine cetirizine and to placebo treatments. Placebo and azelastine (0.254 mg per nasal cavity) were delivered as two consecutive actuations per nasal cavity using a nasal spray device. Oral placebo and cetirizine (10 mg) were given as single doses in a placebo-controlled (double-dummy), double-blind, and cross-over design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12, and 24 h after each treatment. The nasal mucosal surface was lavaged after each challenge. The lavage-fluid levels of alpha 2-macroglobulin were determined to assess mucosal exudation of bulk plasma, and nasal symptoms were scored. Histamine (40-400 micrograms/mL) produced dose-dependent exudation and symptoms. Compared between each treatment and placebo, azelastine and cetirizine reduced the 40 and/or 400 micrograms/mL histamine-induced mucosal exudation of plasma from 1-12 h after treatment. In addition, cetirizine reduced the 40 micrograms/mL histamine-induced mucosal exudation of plasma 24 h after treatment. Differences between the two treatments were not evident regarding nasal symptoms. Histamine challenge-induced mucosal exudation of plasma appears to be a useful method for studies of the duration of action of antihistamines. We conclude that topical azelastine is suited for b.i.d. therapy and that neither the exudative process nor watery secretion may impede the efficacy or the duration of action of this nasal drug.