Localization of the site of the bronchoconstrictor effects of leukotriene C4 compared with that of histamine in asthmatic subjects.
Although the sulfidopeptide leukotrienes are known to be potent bronchoconstrictors, the relative aerodynamic site of response to these compounds is controversial. We determined the decrease in maximal expiratory flow rates (Vmax) from partial and maximal flow-volume curves in seven asthmatic subjects after inhalation of aerosols of histamine or leukotriene C4 (LTC4) while breathing air or a mixture of 80% helium and 20% oxygen (He/O2). Density dependence (DD) of maximal expiratory flow was determined from partial expiratory flow volume curves by an isovolumic comparison of maximal expiratory flows with subjects breathing He/O2 with those obtained while breathing air. Measurements were made before and after inhalation of aerosols generated from graded concentrations of each constrictor agent. An aerodynamic site of response to LTC4 more central than for histamine was indicated by a significant (p less than 0.02) increase in DD with the former but not with the latter agonist. The ratio of Vmax at 30% vital capacity determined from maximal and partial maneuvers (M/P) was routinely higher at baseline while breathing He/O2 compared to the corresponding values with air, suggesting a degree of peripheral obstruction that was reversed by a deep inhalation. Obstruction induced by LTC4 inhalation resulted in a greater increase in M/P compared with baseline when air was the test gas (p less than 0.02). This was not observed when He/O2 was the test gas. Similar effects on M/P were not induced by histamine aerosol inhalation, consistent with a central airway response to LTC4 that was not affected by volume history.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Brigham and Women's Hospital, MA.
B M
BM
Pichurko
R H
RH
Ingram
R I
RI
Sperling
J E
JE
Lafleur
E J
EJ
Corey
K F
KF
Austen
J M
JM
Drazen
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D003250:Constriction; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008448:Maximal Expiratory Flow Rate; D013189:SRS-A / Q000008:administration & dosage / Q000494:pharmacology*
D000336:Aerosols; D013189:SRS-A; D006632:Histamine