TY - JOUR
T1 - The effects of inhaled leukotriene E4 on the airway responsiveness to histamine in subjects with asthma and normal subjects
AU - Arm, Jonathan P.
AU - Spur, Bernd W.
AU - Lee, Tak H.
PY - 1988/10
Y1 - 1988/10
N2 - Eight subjects with asthma inhaled on separate occasions leukotriene E4 (LTE4) (6.1 nmol, geometric mean), methacholine, and diluent, which produced an average 41.0%, 37.0%, and 3.3% decrease in specific airway conductance (SGaw), respectively. When the SGaw had recovered to baseline levels at 60 minutes after challenge, the provocative dose of inhaled histamine that produced a 35% decrease in SGaw (PD35) was determined. The histamine PD35 observed after inhalation of LTE4 was 0.46 μmol, and this was significantly less than the histamine PD35, observed after inhalation of methacholine (0.88 μmol; p < 10-4) and diluent (0.97 μmol; p < 10-5). Histamine responsiveness was also enhanced by a fiftyfold lower dose of LTE4 (p = 0.005), and the enhancement was less than that elicited by the higher dose of LTE4 in the same individuals (p = 0.02). The changes in histamine PD35 during a 1-week period after LTE4 and methacholine challenges were compared in four subjects with asthma. There was a time-dependent enhancement in histamine responsiveness that reached a maximal of 3.5-fold at 7 hours after LTE4. The enhancement had disappeared by 1 week. Similar changes were not observed after methacholine challenge, which elicited the same degree of bronchoconstriction as LTE4. Inhalation of LTE4 in five normal subjects that produced a mean 37.6% decrease in SGaw did not change histamine responsiveness for up to 7 hours. These findings suggest that LTE4 may play a role in the perpetuation of nonspecific airway hyperresponsiveness in bronchial asthma.
AB - Eight subjects with asthma inhaled on separate occasions leukotriene E4 (LTE4) (6.1 nmol, geometric mean), methacholine, and diluent, which produced an average 41.0%, 37.0%, and 3.3% decrease in specific airway conductance (SGaw), respectively. When the SGaw had recovered to baseline levels at 60 minutes after challenge, the provocative dose of inhaled histamine that produced a 35% decrease in SGaw (PD35) was determined. The histamine PD35 observed after inhalation of LTE4 was 0.46 μmol, and this was significantly less than the histamine PD35, observed after inhalation of methacholine (0.88 μmol; p < 10-4) and diluent (0.97 μmol; p < 10-5). Histamine responsiveness was also enhanced by a fiftyfold lower dose of LTE4 (p = 0.005), and the enhancement was less than that elicited by the higher dose of LTE4 in the same individuals (p = 0.02). The changes in histamine PD35 during a 1-week period after LTE4 and methacholine challenges were compared in four subjects with asthma. There was a time-dependent enhancement in histamine responsiveness that reached a maximal of 3.5-fold at 7 hours after LTE4. The enhancement had disappeared by 1 week. Similar changes were not observed after methacholine challenge, which elicited the same degree of bronchoconstriction as LTE4. Inhalation of LTE4 in five normal subjects that produced a mean 37.6% decrease in SGaw did not change histamine responsiveness for up to 7 hours. These findings suggest that LTE4 may play a role in the perpetuation of nonspecific airway hyperresponsiveness in bronchial asthma.
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U2 - 10.1016/0091-6749(88)90979-7
DO - 10.1016/0091-6749(88)90979-7
M3 - Article
C2 - 2844876
AN - SCOPUS:0023745152
SN - 0091-6749
VL - 82
SP - 654
EP - 660
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -