Plasma protein leakage and local secretion of proteins assessed in sputum in asthma and COPD. The effect of inhaled corticosteroids.

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by chronic airway inflammation with cell infiltration, increased plasma exudation and abnormal local secretion of proteins. We have analysed whether sputum differs in this respect between asthma (n = 9) and COPD (n = 9), and whether inflammatory markers in sputum are affected by treatment. In non-smoking asthma patients there was more plasma protein leakage, based on the relative coefficient of excretion Q alpha 2macroglobulin/QIgG (P = 0.03). There was less local secretion of sIgA and lactoferrin than in COPD (P < 0.05). Tryptase was slightly higher in sputum from asthma than from COPD (P < 0.05), whereas eosinophil cationic protein and myeloperoxidase were similar. After treatment with glucocorticosteroids, there was a reduction in the Q alpha 2macroglobulin/Qalbumin (P < 0.015), but no effect was seen on the levels of products from local cells. We conclude that sputum analysis is useful to study the local inflammatory process in asthma and COPD.

Analysis of plasma-protein leakage and local secretion in sputum from patients with asthma and chronic obstructive pulmonary disease.

In order to assess the usefulness of sputum analysis in studying plasma-protein exudation and local secretion of proteins in the airways, we measured specific proteins in the sputum sol phase (SSP) and sputum gel phase (SGP) from patients with stable asthma or chronic obstructive pulmonary disease (COPD). Protein levels in SSP showed relatively small variations between two subsequent visits of each patient (n = 22), as also reflected by intraclass correlation coefficients above 0.79. Protein levels differed between SSP and SGP, but inclusion of the SGP data did not affect the variation of protein levels in sputum. The degree of plasma-protein leakage was estimated from the relative coefficients of excretion (RCE) of alpha 2-macroglobulin and albumin (QA2M/QALB), and of alpha 2-macroglobulin and ceruloplasmin (QA2M/QCP), which do not depend on variable dilution of sputum. Despite the heterogeneity of the study group of 26 patients with asthma (atopic [13] smokers [13], including five patients using inhaled steroids), QA2M/QALB and QA2M/QCP correlated both with bronchial hyperreactivity (Spearman rank: r = -0.45 and r = -0.36, p < 0.05) and with blood eosinophil counts (r = 0.37 and 0.56, p < 0.05). We conclude that protein levels in SSP are relatively constant in patients with stable asthma or COPD; in patients with asthma, the plasma-protein leakage, as measured with the RCE in SSP, appears to correlate with indirect indices of airway inflammation.

Nedocromil sodium in obstructive airways disease: effect on symptoms and plasma protein leakage in sputum.

In patients with asthma or chronic obstructive pulmonary disease, there is chronic airway inflammation with increased leakage of plasma proteins into the airway lumen, which can be reduced by inhaled glucocorticosteroids. Nedocromil sodium is an anti-inflammatory drug, and we questioned whether it also affects the leakage of plasma proteins. In a double-blind placebo-controlled study we investigated the effect of 12 weeks of treatment with nedocromil on forced expiratory volume in one second (FEV1), provocative concentration of histamine causing a 20% fall in FEV1 (PC20), peak flow, symptom scores, and plasma protein leakage in sputum, in 31 patients with obstructive airways disease and sputum production (mean (range) FEV1 61% of predicted (42-87%); geometric mean (range) PC20 0.39 (0.04-2.9) mg x mL(-1)). As a measure for plasma protein leakage we calculated the relative coefficients of excretion (RCE) of proteins from serum to the soluble phase of sputum. There was a small increase in morning and evening peak flow (p<0.05) and a decrease in night-time bronchodilator use (p<0.02) in favour of nedocromil. The RCE of alpha2-macroglobulin to albumin significantly decreased after treatment with nedocromil (p=0.03). The results show limited clinical efficacy of nedocromil in our study group. They further suggest that the anti-inflammatory properties of nedocromil extend to inhibition of plasma protein leakage into the airways.

Importance of total serum IgE for improvement in airways hyperresponsiveness with inhaled corticosteroids in asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 < or = 8 mg/ml and FEV1 < 95% confidence interval of predicted normal. They were followed for 2.5 yr, during which one-third received inhaled corticosteroids. The independent influences of baseline FEV1/IVC, bronchodilator response, PC20, smoking habits, allergy, age, and sex on the improvement in airways hyperresponsiveness with inhaled corticosteroids were analyzed. Total serum IgE was taken as a parameter of allergy, next to specific IgE for house dust mite, skin tests, and blood eosinophils. Total serum IgE was found to be the most important and single independent predictor of change in PC20 with inhaled corticosteroids: patients with a higher IgE had a greater increase in PC20 when administered inhaled corticosteroids than those with lower IgE levels. Alternatively, patients with a higher IgE who did not receive corticosteroids had a decrease in PC20 compared with patients with a lower IgE. This effect was most prominent in asthma but was inconsistent in asthmatic bronchitis and COPD. The level of IgE cannot be used to predict the response to inhaled corticosteroids in individuals accurately. Total serum IgE is the single most important predictor of change in PC20 with and without inhaled corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease.

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 (alpha 2-macroglobulin in BALF)/(alpha 2-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: 6.4 ng/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.