Airway Responsiveness to Leukotrienes C4 and D4 and to Methacholine in Patients with Asthma and Normal Controls

Leukotrienes C₄ and D₄ may serve as chemical mediators in asthma. Although patients with asthma are known to be hyperresponsive to the bronchoconstrictive effects of histamine and methacholine, whether the same is true for the leukotrienes is controversial. We compared the airway responses to methacholine and to leukotrienes C₄ and D₄ in 12 asthmatic patients and 6 controls. We found that the patients were more responsive to the leukotrienes than the controls, and we observed a linear correlation between airway response to methacholine and that to leukotriene C₄ (r = 0.68, P<0.01) and D₄ (r = 0.79, P<0.001). However, relative to the airway response to methacholine, the response to the leukotrienes was much greater in the controls than in the patients. Furthermore, the asthmatic subjects who were most responsive to methacholine had the lowest relative airway response to both leukotrienes. Thus, the patients with the greatest airway responsiveness to methacholine paradoxically showed the lowest relative airway response to the leukotrienes. In contrast, this difference in relative airway responses has not been observed between methacholine and other bronchoconstrictor mediators, such as histamine. Although no adequate explanation for these observations has yet emerged, our data suggest that leukotrienes C₄ and D₄ are unique bronchoconstrictors with a possible role in the pathogenesis of asthma. (N Engl J Med 1986; 315:480–4.), It has been suggested that the sulfidopeptide leukotrienes C₄, D₄, and E₄ are important mediators in asthma. These leukotrienes are thought to be released from mast cells that have been activated by an allergen,¹ and leukotrienes C₄ and D₄ have been shown to be potent bronchoconstricting agents both in animals^2,3 and in normal and asthmatic humans.^{4 5 6 7} The bronchoconstriction induced by these mediators has a slower onset and a more prolonged action than that produced by inhaled histamine.⁸ Hyperresponsiveness of the airways to inhaled bronchoconstrictors is a cardinal feature of asthma.⁹ Thus, patients with.