We have investigated whether IL-8 is present in airway secretions from patients with asthma and chronic obstructive pulmonary disease (COPD) to obtain information on its possible role in airway inflammation in obstructive airways disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable patients with asthma the levels of IL-8 were increased compared to 10 healthy subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p<0.005). In the patients with asthma the levels of IL-8 correlated with the percentage neutrophils in the BALF (r = 0.81; p<0.001) and with a parameter of the permeability of the respiratory membrane, the quotient (α₂-macroglobulin in BALF)/(α₂-macroglobulin in serum) (r = 0.66; p<0.025). In the sputum sol phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in 9 patients with COPD (asthma: 6.4ng/ml; COPD: 16.3 ng/ml; p<0.02) and significantly correlated with those of neutrophilic myeloperoxidase (MPO; r = 0.85; p<0.005). The increased levels of IL-8 in the airway secretions from both patients with asthma and COPD may be markers of an ongoing inflammatory process, which is more pronounced in patients with COPD. In patients with asthma the strong correlation between the levels of IL-8 and the percentage neutrophils and/or the levels of MPO points to a role of IL-8 in the recruitment and activation of neutrophils in the airway lumen.

Background: Segmental allergen challenge is a powerful tool to study inflammatory reactions in asthmatic airways. There is little information on the early events at 5 min and 4 h after allergen challenge with respect to the cell influx and the chemokine interleukin–8 (IL–8). Methods: Seven mild to moderate allergic asthmatics (AA group), 5 allergic nonasthmatics (ANA group) and 5 nonallergic controls underwent segmental allergen challenge, with allergen doses based upon skin reactivity. Bronchoalveolar lavage (BAL) samples were obtained before, 5 min and 4 h postchallenge, and were analyzed for cell numbers and differential counts, eosinophil and neutrophil chemotactic activity, and levels of IL–8. Results: At 5 min postchallenge, no changes were observed compared to baseline. At 4 h postchallenge, an increase was found in the number of neutrophils and the levels of IL–8, which was dependent on the dose of allergen in the AA and ANA group. At the same allergen dose, the increases in neutrophils and levels of IL–8 were calculated to be 91 and 67 times higher, respectively, in AA than in ANA. Levels of IL–8 correlated with the number of neutrophils and with the in vitro neutrophil chemotactic activities in BAL fluid. Conclusions: Neutrophil chemotactic activity is increased in BAL fluid at 4 h after segmental allergen challenge. We suggest that apart from IgE–mediated mast cell degranulation, additional local factors in the airways determine the degree of IL–8 increase and neutrophil influx.

Plasma protein exudation into the airways is an important pathophysiological event in asthma. The effect of 12 wk of treatment with inhaled fluticasone propionate (FP; 250 microgram twice a day) or salbutamol (Sb; 400 microgram twice a day) on plasma protein leakage was compared in a double-blind, randomized parallel-group study of 30 patients with asthma. Primary outcomes were plasma protein leakage and size selectivity of the blood-airway lumen barrier, cell differentials in BAL fluid, and bronchial responsiveness to histamine (PC20histamine). Two independent procedures to account for the effect of variable dilution of BAL on the levels of albumin (Alb) and alpha2-macroglobulin (A2M) in BAL fluid consisted of correction based on urea levels and on the application of the relative coefficient of excretion [RCE = ([A2M] in BAL fluid/[A2M] in serum)/([Alb] in BAL fluid/[Alb] in serum)]. In the FP group a significant decrease was found in the A2M level and the RCE, and in the percentage of eosinophils in BAL fluid. The PC20histamine increased significantly (mean increase, 2.4 doubling doses), whereas PC20histamine decreased in the Sb group. Differences between groups were significant except for the decrease in eosinophils. We conclude that 12 wk of FP (250 microgram twice a day) decreased the permeability of the blood-airway lumen barrier, in particular for high molecular weight proteins.