Physiologic Manifestations of Human Anapf is

A B S T R A C T In the course of a controlled study to evaluate different forms of immunotherapy for subjects with insect-sting hypersensitivity, we observed 11 subjects who had systemic cutaneous urticarial reactions and 3 subjects who experienced systemic anaphylaxis. With the exception of tachyeardia, there were no cardiopulmonary changes in the subjects with urticaria, whereas the major manifestation of anaphylactic shock in the other three subjects was severe hypotension that was probably secondary to peripheral vasodilation. Significant abnormalities in gas exchange developed in two subjects. In one, bronchospasm precipitated a respiratory arrest followed by endotracheal intubation with mechanical ventilation. Although plasma histamine levels were not related to the development of cutaneous reactions, the plasma histamine levels correlated with the severity and duration of the cardiopulmonary changes observed during anaphylactic shock. The two subjects with the most severe shock showed evidence of intravascular coagulation characterized by a diminution of Factor V, Factor VIII, fibrinogen, and high molecular weight kininogen, as well as changes in components of the complement system. Standard therapy with epinephrine and fluids, usually recommended for the treatment of systemic anaphylaxis, did not immediately reverse either the hemodynamic or the respiratory abnormalities in the two subjects with the most sever

Inhaled Corticosteroids and the Beneficial Effect of Deep Inspiration in Asthma

Deep inspiration–induced bronchoprotection and bronchodilation are impaired in asthma. We evaluated the effect of inhaled glucocorticosteroids on these phenomena. Two groups of subjects with asthma, 9 with moderate/severe hyperresponsiveness to methacholine, and 12 with mild/borderline hyperresponsiveness to methacholine, received inhaled fluticasone (880 μg daily) for 12 weeks. Serial bronchoprovocations were performed at Weeks 0, 6, and 12. The impact of deep inspirations on the airway response to methacholine was evaluated on the basis of inspiratory vital capacity and FEV1. Fluticasone produced a wide spectrum of changes in the beneficial effects of deep inspiration, but the mean changes were not significant. The magnitude of the steroid-induced changes in bronchoprotection by deep inspiration correlated with baseline log PC20 (the provocative concentration of methacholine causing a 20% fall in FEV1; higher log PC20 predicted improvement of the deep inspiration effect). The steroid-induced changes led to the emergence of strong positive correlations between the effects of deep inspiration and the methacholine log PC20 that did not exist at baseline. We conclude that deep inspiration–induced bronchoprotection can be restored by inhaled glucocorticosteroids only in individuals with mild hyperresponsiveness. After steroid treatment, the beneficial effects of deep inspiration become significant determinants of the magnitude of airway hyperresponsiveness