Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction.
Bronchoalveolar lavage (BAL) of canine peripheral airways was performed at various times after hyperventilation, and BAL fluid (BALF) cell and mediator data were used to evaluate two hypotheses: 1) hyperventilation-induced mucosal injury stimulates mediator production, and 2) mucosal damage is correlated with the magnitude of hyperventilation-induced bronchoconstriction. We found that epithelial cells increased in BALF immediately after a 2- and a 5-min dry air challenge (DAC). Prostaglandins D(2) and F(2alpha) and thromboxane B(2) were unchanged immediately after a 2-min DAC but were significantly increased after a 5-min DAC. Leukotriene C(4), D(4), and E(4) did not increase until 5 min after DAC. Hyperventilation with warm moist air did not alter BALF cells or mediators and caused less airway obstruction that occurred earlier than DAC. BALF epithelial cells were correlated with mediator release, and mediator release and epithelial cells were correlated with hyperventilation-induced bronchoconstriction. These observations are consistent with the hypothesis that hyperventilation-induced mucosal damage initiates peripheral airway constriction via the release of biochemical mediators.
Freed
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AN
Department of Environmental Health Sciences, The Johns Hopkins University, Baltimore, Maryland 21205, USA. afreed@jhsph.edu
Wang
Y
Y
McCulloch
S
S
Myers
T
T
Suzuki
R
R
D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D016084:Bronchoconstriction / Q000502:physiology*; D002452:Cell Count; D004285:Dogs; D015777:Eicosanoids / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D006813:Humidity; D006985:Hyperventilation / Q000503:physiopathology*; D007700:Kinetics; D015289:Leukotrienes / Q000378:metabolism / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000502:physiology; D020545:Respiratory Mucosa / Q000293:injuries*
D015777:Eicosanoids; D015289:Leukotrienes; D018727:Muscarinic Antagonists; D011453:Prostaglandins; D001285:Atropine