Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma.
Histamine and certain cyclooxygenase products of arachidonic acid have been implicated as mediators of inflammation and are potent constrictors of human airways. Because asthma may represent manifestations of chronic inflammation of the airways, the levels of histamine and six prostanoid mediators were measured in airway fluids obtained by bronchoalveolar lavage (BAL) of 12 normal, 11 allergic rhinitic, and 15 asymptomatic, allergic asthmatic subjects. Simultaneous profiling of prostanoid mediators in individual samples was performed using gas chromatography-mass spectrometry. Levels of PGD2, 9 alpha,11 beta-PGF2 and PGF2 alpha were 12 to 22 times higher in asthmatic than in normal subjects (p less than 0.01), with concentrations in airway fluids of asthmatic subjects after correction for dilution of 3.8, 0.5, and 1.4 nanomolar, respectively. Levels of PGD2 and 9 alpha,11 beta-PGF2 were increased nearly tenfold in asthmatic subjects compared with those in rhinitic subjects (p less than 0.01), distinguishing the subjects with lower airway disease from those with another atopic condition. Histamine levels were increased fourfold in asthmatic subjects compared with those in normal subjects (p less than 0.001); however, similar increases were found in rhinitic subjects. We conclude that elevated levels of multiple mediators with potent bronchoconstricting activity are present in the airways of subjects with mild asthma, indicating that even mild disease is associated with evidence of airway inflammation. The interactions of bronchoconstricting mediators and airway inflammation may play important roles in the pathogenesis of asthma.
Liu
M C
MC
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Bleecker
E R
ER
Lichtenstein
L M
LM
Kagey-Sobotka
A
A
Niv
Y
Y
McLemore
T L
TL
Permutt
S
S
Proud
D
D
Hubbard
W C
WC
D000328:Adult; D001249:Asthma / Q000209:etiology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006632:Histamine / Q000032:analysis*; D006801:Humans; D008297:Male; D015230:Prostaglandin D2 / Q000032:analysis*; D011453:Prostaglandins / Q000032:analysis; D012221:Rhinitis, Allergic, Perennial / Q000378:metabolism; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism
D011453:Prostaglandins; D006632:Histamine; D015230:Prostaglandin D2