Increased neutrophil numbers and IL-8 levels in airway secretions in acutesevere asthma clinical and biologic significance

The inflammatory events in the airways at the time of acute respiratory fai lure from acute severe asthma are poorly understood. To determine the patte rns of cellular inflammation in the airways in acute severe asthma, we anal yzed tracheal aspirates collected within 12 h of intubation from patients i ntubated emergently for acute severe asthma (n = 10) and from patients intu bated electively for nonpulmonary surgery (n = 14). The number of neutrophi ls in tracheal aspirates from asthma patients was 10 times higher than norm al (4.2 [0.6 to 335.0] [median, range] versus 0.4 [0.009 to 9.4] x 10(6)/ml , p = 0.001), and there was a strong trend for a positive relationship betw een neutrophil number and duration of intubation (r(s) = 0.64, p = 0.06). A lthough eosinophil numbers were also significantly higher than normal (0.5 [0.0 to 23.3] versus 0.0 [0.0 to 0.1] x 10(6)/ml, p = 0.003), the numbers o f eosinophils were 8-fold less than neutrophils, and there was no significa nt correlation between eosinophil number and duration of intubation (r(s) = 0.4 p = 0.26). Interleukin-8 (IL-8), a chemoattraction for neutrophils, wa s 19 times higher than normal in tracheal aspirates from asthmatic patients (75.0 [9.0 to 168.0] versus 4.0 [0.08 to 24.0] ng/ml, p < 0.05) and correl ated significantly with the neutrophil number (r(s) = 0.77, p = 0.03). Furt hermore, the IL-8 levels correlated positively with the duration of mechani cal ventilation (r(s) = 0.74 p = 0.03). Surprisingly, the number of neutrop hils increased significantly during the period of intubation in the asthmat ic subjects, possibly because of intravenous corticosteroid treatment. We c onclude that neutrophils are the dominant inflammatory leukocyte characteri zing airway inflammation in acute severe asthma that requires mechanical ve ntilation, and that IL-8 is an important mediator of this neutrophilia.