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Studies of tile nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15 000 (approx. 14700 Da), to predict the mucosal permeation of inhalational allergens. PS 15 000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15 000 (50 μg/ml: 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15 000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15 000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens. [ABSTRACT FROM AUTHOR]

The article focuses on the new aspects of the allergic airway in vivo namely epithelium, microcirculation and eosinophils. Current research paradigms may give the impression that gross airway mucosal processes in vivo in allergy, inflammation, and repair are already well known. The widely acknowledged reductionist in vitro and cellular approaches, thus appear to be very justified. This review deals with one inflammatory cell, the eosinophil, and two airway end organs, the epithelium and the microvasculature. Three events are focused: epithelial shedding-restitution processes, micro vascular-mucosal exudation of bulk plasma, and generation of free extra cellular eosinophilic granules in airway tissue.

Background: In view of recent observations demonstrating that rhinovirus infections are associated with increased local activity of eosinophils, we hypothesized that eotaxin, a selective eosinophil chemoattractant, may be involved in eosinophil recruitment/activation in common cold infections., Methods: Twenty-three patients with seasonal allergic rhinitis were inoculated with human rhinovirus 16 (HRV 16) outside the pollen season. Sequential diluent and allergen (10(3) SQ-U) challenges, each followed by nasal lavage, were carried out about 3 months before and 4 days after virus inoculation., Results: Seventeen patients developed common cold and were further analyzed. Lavage fluid levels of eotaxin were increased at the height of active common cold (day 4 after inoculation) both at baseline (after diluent challenge) (P<0.01) and acutely after allergen challenge (P<0.05)., Conclusions: Common cold symptoms after nasal HRV 16 inoculation are associated with increased nasal mucosal output of eotaxin, suggesting that this chemokine is partly responsible for recruitment/activation of airway mucosal eosinophils in common cold infections.

Studies of the nasal permeation of small molecules (< 1000 Da) have yielded important information about the integrity of the human airway mucosa in health and disease. In this study, we used a much larger tracer molecule, polysucrose (PS) 15,000 (approx. 14,700 Da), to predict the mucosal permeation of inhalational allergens. PS 15,000 (50 mg/ml; 15 ml), with or without a detergent type of permeation enhancer (dioctyl sodium sulfosuccinate 10 mg/ml), was maintained for 15 min in one nasal cavity of 12 healthy nonatopic subjects by employment of a nasal-pool device. Permeation as determined by the 24-h urine recovery of PS (micro-ELISA analysis assay) was expressed as percentage of nasal instillate. Mean baseline permeation was 0.044% (range 0.009-0.250%). In the presence of the detergent, permeation increased to 0.600% (range 0.007-2.260%) (P < 0.01). After oral intake of 750 mg of PS 15,000 (50 micrograms/ml; 15 ml), the 24-h urinary recovery was 0.013% (range 0.004-0.023%). Our study thus demonstrates a measurable baseline permeation of PS 15,000, an elevated permeation rate in the presence of an epithelium-damaging detergent molecule, and a negligible permeation by the oral route. These properties support the utility of PS 15,000 as a nasal airway permeation tracer. Its size further suggests that its permeation may reflect mucosal perviousness to many allergens.