Do sputum eosinophils and ECP relate to the severity of asthma?

Abstract

There is much evidence that eosinophils play an important role in bronchial epithelial damage in asthma by releasing cationic proteins. However, the extent to which eosinophil inflammation relates to indices of asthma severity in chronic stable asthma is still a matter of debate.We studied 46 clinically stable patients with mild to severe chronic asthma (forced expiratory volume in one second (FEV1) 50-126% of predicted value). The clinical severity of asthma was graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects were also studied as controls. Induction of sputum was performed by hypertonic saline to determine differential cell count, and eosinophil cationic protein (ECP) by the so-called "plug technique". The concentration of ECP was measured by a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling progressive concentrations of histamine, and the concentration that caused a 20% decrease in FEV1 (PC20) was calculated.Sputum eosinophils (range 0-61%), sputum ECP (range 24-10,800 µg·L -1 ) and serum ECP (range 4-61 µg·L -1 ) were significantly greater in asthmatics than in normal subjects, and distinguished the most severe group with the highest Aas score from the others. Sputum eosinophils and sputum ECP were strongly related to each other. The relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg·mL -1 ), and between sputum ECP and FEV1 were found to be weak.In conclusion, sputum outcomes of eosinophil activation and serum eosinophilic cationic protein appear to be useful indicators of disease. They do not accurately reflect current clinical or functional indices of asthma severity in chronic stable patients, and might therefore provide complementary data disease monitoring.

Sputum analysis, bronchial hyperresponsiveness, and airway function in asthma: Results of a factor analysis

“…29 Moreover, sputum examination has been demonstrated to be a more accurate diagnostic test than measurement of blood eosinophils or serum ECP in detecting airway eosinophilic inflammation, 29 suggesting a relevant role of sputum analysis in the identification and monitoring of airway inflammation in asthma. 12,14,30 Our results demonstrate that sputum eosinophils and ECP provide another unique dimension related to the status of patients with chronic bronchial asthma that was independent of both lung function and baseline BHR. These data confirm the results of previous studies in which the relationships between sputum outcomes and baseline airway obstruction were not clinically meaningful.…”

“…These data confirm the results of previous studies in which the relationships between sputum outcomes and baseline airway obstruction were not clinically meaningful. 12 Recent studies have found a relatively good correlation between sputum eosinophils and BHR when both normal subjects and smokers with bronchitis 13 or patients with rhinitis 31 were included in the correlation. Pizzichini et al 13 argue that the high significance of the correlations between sputum markers and hyperresponsiveness partially reflects the significant differences between asthmatic and healthy subjects or smokers with bronchitis.…”

“…The levels of these relationships were somewhat consistent with the clinical irrelevance reported in other studies. 12,16,[18][19][20] The level of correlations we found indicates that physiologic and inflammatory outcome measures are not overlapping characteristics of asthma. In this investigation we used factor analysis to examine the independence of respiratory function, BHR, and bronchial inflammation in the assessment of patients with chronic, stable asthma.…”

“…Every 5 minutes subjects were asked to try to cough sputum into a Petri dish and to collect saliva in a separate container. Cytologic analysis and ECP measurement were performed according to the method of Ronchi et al 12 Two or 3 plugs free of salivary contamination were suspended in dithiothreitol solution (0.1%) and incubated for 30 minutes at 37°C for slide making. Cells were centrifuged at 1500 rpm for 10 minutes and then resuspended in saline.…”

“…Recent studies have indicated that eosinophilic inflammation (both number and activation of eosinophils) is an important outcome measure in the diagnosis and management of asthma. [12][13][14][15] In many studies, however, the level of significance of the interrelations among all these outcome measures has been found to be clinically irrelevant. [16][17][18][19][20] In this regard we have recently found that sputum measurements of eosinophilic inflammation do not accurately reflect current clinical indices of asthma severity in patients with chronic, stable asthma 12 and might therefore provide complementary data for monitoring of the disease.…”