Hyperosmolar environments induce histamine release from mast cells and basophils in vitro. To assess whether the same stimulus induces mediator release in vivo, 15 healthy human volunteers underwent nasal challenges with instilled solutions of differing osmolalities: lactated Ringer's solution (257 +/- 3 mOsm/kg), isosmolar mannitol (277 +/- 6 mOsm/kg), and hyperosmolar mannitol (869 +/- 8 mOsm/kg). The effect of these challenges on the volume, osmolality, and inflammatory mediator content of subsequent 5-ml isosmolar lavages was determined. The volumes of lavages returned after hyperosmolar challenges were significantly greater than those after isosmolar challenges (5.5 +/- 0.2 ml versus 4.2 +/- 0.1 ml; p less than 0.01) and these lavage solutions had higher osmolalities. Even when corrected for increased volumes, the lavages after hyperosmolar challenges contained significantly higher quantities of inflammatory mediators such as histamine (29.0 versus 10.1 ng; p less than 0.01), TAME-esterase activity (32.7 versus 11.1 cpm x 10(-3); p less than 0.01), and immunoreactive leukotrienes (9.9 versus 3.4 ng; p less than 0.01). The changes in mediators were dose dependent in that incremental increase in challenge osmolality were associated with incremental increases in histamine release. Therefore, when exposed to hyperosmolar stimuli in vivo, the nasal respiratory airway releases inflammatory mediators and fluid rapidly shifts into the airway lumen. It has been suggested that the mediator release observed on breathing cold and dry air is due to increased osmolality of airway secretions; the present data confirm that osmotic variations at the airway surface can provide an adequate stimulus for cell activation.

The findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use.

In order to compare results of allergen immunotherapy in paediatric and adult populations, 22 children with a history of ragweed hay fever were matched with an equal number of adults for skin sensitivity to ragweed and all were given a 1-year course of immunotherapy with a partially purified ragweed extract. Biological responses were measured by nasal challenges with ragweed before therapy was started, after 12 weekly injections and when the maintenance dose had been reached and also by methacholine bronchoprovocation tests before and after 12 months of therapy. Skin-test sensitivity to ragweed and control allergens, and ragweed-specific IgE and IgG antibody responses were measured at the same intervals as the challenges and at the end of the study. The effect of the therapy on clinical symptoms was not evaluated. Before therapy the groups of adults and children were comparable by all indices, except for TAME esterase activity in nasal washes during ragweed nasal challenge which was significantly lower in children. During treatment, mediators released during sequential nasal challenges declined to undetectable levels in most patients and changes in nasal ragweed sensitivity were comparable in both groups. Ragweed IgE increases after 12 weeks of therapy and IgG levels at maintenance therapy tended to be higher in the children, but neither difference was statistically significant. At the end of the study IgE and IgG antibody levels were comparable in both groups. Results of methacholine inhalation tests did not change significantly in either group. The decrease in skin sensitivity to ragweed was similar in both groups. We conclude that ragweed immunotherapy leads to immunological and biological consequences that are comparable in children and adults.

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