Neutrophil Chemotactic Activity in Acute Severe Asthma (Status Asthmaticus)

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Abstract
Serum neutrophil chemotactic activity (NCA) was measured in patients with acute severe asthma (status asthmaticus) and compared with that in control subjects (mild asthma, stable chronic irreversible air-flow obstruction, allergic rhinitis, noninfective lung conditions, or asymptomatic). There were 9 subjects in each group. Statistically significant elevations (p < 0.002) in NCA were detected in acute severe asthma when compared with each control groups. Serial measurements of NCA were subsequently undertaken in 12 patients with acute asthma, at the time of admission to hospital, after 3 days of treatment, and on discharge after approximately 7 days. A highly significant(p < 0.001) reduction in serum NCA activity on Day 7 compared with that on Day 0 was observed, and this correlated inversely with the improvement in lung function (PEFR). Gel filtration by fast protein liquid chromatography (FPLC) using Superose 6 prep grade (6PG) indicated that NCA in acute severe asthma was heterogeneous and consisted of at least 4 peaks of activity associated with proteins with molecular weights of approximately 800, 600, 150, and < 20 kD. The 800- and 150-kD peaks were also observed in control subjects, but to a lesser degree. The 600- and < 20-kD activities were virtually confined to the patients with acute severe asthma. FPLC chromatofocusing of the 600-MW peak from the acute asthmatics, using a Mono-P column and a pH gradient from 8.3 to 5.0, revealed considerable activity in fractions eluting between pH 6.0 and 7.0, which was not observed in the normal control subjects. A second peak, associated with pl of > 7.0, was observed in acute asthma, mild asthma, and in normal subjects. These observations indicate (1) that the asthma-associated high molecular weight neutrophil chemotactic activity (HMW-NCA) is present in serum in the acute form of the natural disease, (2) that this activity significantly decreases with treatment, (3) that HMW-NCA of severe asthma (and some control groups) is heterogeneous, and (4) that the peak of chemotactic activity is associated with a molecular size of 600 kD and an isoelectric point between pI 6.0 and 7.0, and is therefore comparable in these respects with the activity previously described in association with allergen- and exercise-induced early- and late-phase asthmatic reactions.