PROMINENT NEUTROPHILIC INFLAMMATION IN SPUTUM FROM SUBJECTS WITH ASTHMA EXACERBATION

To infer possible mechanisms of acute airway inflammation and mucus hy persecretion in acute severe asthma, we performed cellular and biochem ical analysis on sputum from 18 adults with acute severe asthma and co mpared the results with results of analysis of sputum from 12 adults w ith cystic fibrosis (CF). We found that in subjects with asthma neutro phils made up more than 75% of sputum cells in 10 samples whereas eosi nophils made up more than 75% of cells in only three samples. Fifty pe rcent of the subjects with asthma reported that their asthma exacerbat ion was precipitated by a respiratory tract infection, and these subje cts had a significantly higher percentage of neutrophils in their sput um (85% +/- 6% vs 57% +/- 12%, p = 0.05). In the CF samples neutrophil s made up more than 95% and eosinophils less than 1% of cells in all s amples analyzed. Analysis of fluid phase chemicals in asthmatic and CF sputum samples showed that despite overall lower mean values of neutr ophil elastase (27 +/- 11 mu g/ml vs 466 +/- 121 mu g/ml, p = 0.0001) and interleukin-8 (IL-8) (55 +/- 25 ng/ml vs 186 +/- 24 ng/ml, p = 0.0 002), some of the asthmatic samples had values for these variables tha t overlapped those in the CF samples. In addition, the asthmatic sampl es were distinguished by the presence of higher tryptase (10 +/- 7 U/L vs 0.9 +/- 0.9 U/L, p = 0.0001) and interleukin-6 (1166 +/- 447 ng/ml vs 186 +/- 24 ng/ml; p = 0.0001) levels and by a higher ratio of albu min to mucin-like glycoprotein (0.8 +/- 0.5 vs 0.1 +/- 0.002, p = 0.02 ). DNA levels were lower in the asthmatic samples (0.5 +/- 0.3 mg/ml v s 3.5 +/- 1.2 mg/ml, p = 0.05). We conclude that neutrophils predomina te more frequently than eosinophils as the major inflammatory cell in sputum from patients with asthma in acute exacerbation. We speculate t hat this may be because respiratory tract infections are a frequent pr ecipitant of acute asthma. In addition, the high IL-8 levels and free neutrophil elastase activity observed in asthmatic sputum suggests tha t IL-8 may mediate airway neutrophilia in acute asthma and that neutro phil elastase may mediate mucin glycoprotein hypersecretion in acute a sthma, as has been proposed for the mucin hypersecretion in CF.