Measurement Of Eosinophil Cationic Protein Research Articles

Serum Eosinophilic Cationic Protein as a Useful Noninvasive Marker of Eosinophilic Gastrointestinal Disease in Children.

Recently, the prevalence of eosinophilic gastrointestinal disease (EGID) has shown an increasing trend worldwide. As the diagnosis of EGID requires invasive endoscopy with biopsy, noninvasive markers for detecting EGID in suspected patients, particularly children, are urgently needed. Therefore, this study aimed to evaluate the diagnostic accuracy of serum eosinophil cationic protein (ECP) beyond peripheral eosinophil counts in pediatric patients with EGID. Overall, 156 children diagnosed with EGID were enrolled and 150 children with functional abdominal pain disorder (FAPD) were recruited as controls. All participants underwent endoscopic biopsy in each segment of the gastrointestinal (GI) tract and serum ECP measurement, as well as peripheral eosinophil percent and absolute eosinophil count. Comparing EGID (n=156) with FAPD (n=150) patients, serum ECP levels were significantly higher in pediatric patients with EGID than in those with FAPD (25.8±28.6 µg/L vs. 19.5±21.0 µg/L, p=0.007), while there was no significant difference in peripheral eosinophil percent and absolute eosinophil counts between the two groups. Serum ECP levels were correlated with peripheral eosinophil percent (r=0.593, p<0.001) and the absolute eosinophil count (r=0.660, p<0.001). The optimal cutoff value of serum ECP for pediatric EGID was 10.5 µg/mL, with a sensitivity of 69.9% and a specificity of 43.4% with an area under the receiver operating characteristic curve of 0.562. The combination of serum ECP levels and peripheral eosinophil counts, when employed with appropriated thresholds, could serve as a valuable noninvasive biomarker to distinguish between EGID and FAPD in pediatric patients manifesting GI symptoms.

Predictive Value of Eosinophil Cationic Protein in Nasal Secretions in Eosinophilic Chronic Rhinosinusitis.

To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions. Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions. Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS. 3 Laryngoscope, 133:3304-3312, 2023.

Diagnostic value of myeloperoxidase and eosinophil cationic protein in nasal secretions for endotypes of chronic rhinosinusitis.

To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.

Eosinophil cationic protein (ECP) correlates with eosinophil cell counts in the induced sputum of elite swimmers.

Swimming practice has been associated with eosinophilic inflammation, however, the underlying mechanisms are not fully understood. The eosinophil cationic protein (ECP) in induced sputum may be used as a potential biomarker to assess airway eosinophilic inflammation among elite swimmers. The objective of this study is to characterize ECP levels in sputum supernatant in elite swimmers and evaluate ECP as an eosinophilic inflammatory marker. Elite swimmers annually screened in our department (n = 27) were invited to participate in this cross-sectional study. Swimmers who agreed to participate (n = 24, 46% girls) performed lung function and skin-prick tests. Induced sputum was also collected and analyzed for differential cell counts and ECP measurements in sputum supernatant (ImmunoCAPTM 100, ECP, Thermo Fisher Scientific, Uppsala, Sweden). The median ECP level was 15.60 μg/L (6.02-38.75 μg/L) and higher levels were found among boys (27.90 (11.20-46.30) μg/L vs 6.65 (2.82-22.80) μg/L, P = .02). In addition, ECP levels in the sputum supernatant were positively correlated with eosinophil cell counts in the induced sputum (r = 0.583, P = .08). ECP levels correlated positively with eosinophil counts in the induced sputum in elite swimmers. The measurement of ECP in sputum supernatant may be a useful marker to assess and manage eosinophilic inflammatory changes in the airways of elite swimmers.

Eosinophil-related markers and total immunoglobulin E as a predictive marker for antibiotic response in chronic rhinosinusitis.

BACKGROUND AND OBJECTIVESChronic rhinosinusitis (CRS) is a commonly diagnosed disease that has a significant impact on a child’s quality of life. However, no useful biomarker is available to identify antibiotic-responsive CRS. We determined the significance of eosinophil-related markers and total IgE levels in childhood CRS with regard to antibiotic response.DESIGN AND SETTINGThis was a case-control study of patients admitted to Uijeongbu St. Mary’s Hospital between November 2010 and November 2011 and diagnosed with CRS.PATIENTS AND METHODSIn this analytical cross-sectional study, we identified children whose symptoms and radiologic abnormalities did not resolve after 12 weeks despite appropriate antibiotics (non-responder CRS group), children whose symptoms and radiologic abnormalities resolved after 12 weeks with appropriate antibiotics (responder CRS group), and healthy controls selected from clinic patients. Skin prick tests were performed along with serum total IgE, total eosinophil count (TEC), serum eosinophil cationic protein (ECP) level, and ImmunoCAP analysis for common allergens.RESULTSThis study included 36 responders, 22 nonresponders and 22 healthy controls. The prevalence of allergic diseases, atopy, and a family history of allergic diseases were significantly higher in the non-responder group than in the responder and control groups. TEC, ECP, and total IgE levels were significantly higher in the non-responder group than in the responder and control groups (all P<.05). Multiple linear regression analysis showed that no response to appropriate antibiotics and TEC was positively associated with ECP concentration.CONCLUSIONThese findings suggest that there is a high prevalence of allergic diseases in the non-responder group, that the TEC and ECP levels in the non-responder group are significantly higher than those in the responder group and controls, and that no response to antibiotics may be due to eosinophilic inflammation. The measurement of serum ECP may be useful in monitoring the progress of childhood CRS with regard to antibiotic response.

Inflammatory activity at school age in very low birth weight bronchopulmonary dysplasia survivors

Airway inflammation is involved in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of the study was to evaluate the inflammatory activity in plasma and exhaled air in very low birth weight (VLBW) BPD survivors at school age. Twenty-one 6-14-year-old former VLBW (birth weight ≤1,500 g) children with severe radiographic BPD (radBPD), 19 without radBPD (nonBPD group) and 19 non-asthmatic term controls underwent measurement of eosinophil cationic protein, IL-6, IL-8, adiponectin, adipsin, leptin, and resistin in plasma, leukotriene B4 and 8-isoprostane in exhaled breath condensate, and NO in exhaled breath. Background data were obtained from patient records, clinical examination and parental questionnaire. Both univariate and multivariate models were applied in the statistical analysis. There were no significant differences between the groups in any of the inflammatory markers measured. Five (25%) radBPD and 2 (11%) nonBPD children reported asthma (P = 0.058). In logistic regression analysis, exposure to chorioamnionitis was associated with low IL-8 (OR 29.0, 95% CI 3.27-258) and postnatal corticosteroid therapy with high adiponectin (OR 32.0, 95% CI 1.29-793). High body mass index standard deviation score (BMI-SDS) was associated with high plasma adipsin (OR 2.47, 95% CI 1.07-5.75) and leptin (OR 5.76, 95%CI 1.83-18.2) levels. The inflammatory activity seems to decrease by school age in VLBW BPD survivors. Chorioamnionitis and postnatal corticosteroid treatment may modulate the inflammatory responsiveness in VLBW subjects even up to school age. The respiratory outcome in VLBW infants might be improved by preventing excessive weight gain.

Placebo-controlled study with OHIO chamber of prophylactic pranlukast for children with Japanese cedar pollinosis: TOPIC-J III study

Objective:This double-blind, placebo-controlled comparative study was designed to investigate whether pranlukast dry syrup, a leukotriene receptor antagonist, has a protective effect against priming, controlled pollen exposure, and natural pollen exposure in children with Japanese cedar pollinosis.Research design and methods:Thirty children aged 12–15 years with Japanese cedar pollinosis (positive skin test for Japanese cedar pollen), who had suffered from pollinosis for at least 2 years and developed severe nasal obstruction when exposed to Japanese cedar pollen, were enrolled in this study. They were randomly allocated to treatment with pranlukast or placebo orally after breakfast and dinner for 8 weeks during the Japanese cedar pollen season. Soon after the start of the pollen season, all subjects underwent a challenge by exposure for 3 h to Japanese cedar pollen (8000 grains/m3) in an artificial exposure chamber (OHIO chamber).Clinical trial registration:The University Hospital Medical Information Network in Japan (UMIN000009840).Main outcome measures:The effect of pranlukast was evaluated using self-rating of nasal symptoms by the subjects and measurement of eosinophil cationic protein in nasal discharge specimens.Results:Scores for the symptoms of pollinosis were lower in the pranlukast group than in the placebo group during treatment in the priming state, as well as after controlled pollen exposure and natural pollen exposure. Pranlukast significantly improved the score for nasal obstruction, compared with placebo. A correlation was found between changes of the scores for symptoms of pollinosis and changes of the eosinophil cationic protein level.Conclusions:These results confirm a protective effect of pranlukast against both priming and challenge (controlled and natural) with Japanese cedar pollen. The present findings suggested that pranlukast dry syrup may be useful for prophylaxis against pollinosis in children.

Downregulation of IL-8, ECP, and total IgE in the tears of patients with atopic keratoconjunctivitis treated with rebamipide eyedrops.

Rebamipide eyedrops are approved in Japan for the treatment of dry eye disease. Some patients with allergic conjunctival diseases also manifest dry eye. Earlier we reported that rebamipide suppressed polyI:C-induced inflammatory cytokines in human conjunctival epithelial cells. In the current study we examined the effect of rebamipide eyedrops on the level of interleukin-8 (IL-8), eosinophil cationic protein (ECP), and total IgE on the ocular surface.We prescribed rebamipide eyedrops to patients with atopic keratoconjunctivitis (AKC) who presented with dry eye (6 eyes in 4 AKC patients) and measured the IL-8, ECP, and total IgE levels in their tears before- and 2, and 4–6 weeks after the start of rebamipide treatment. To measure the IL-8 and total IgE levels in their tears we used BD™ CBA Flex sets; ECP measurements were with ELISA. The level of IL-8, ECP, and total IgE in the tears of AKC patients was reduced significantly 4–6 weeks after the start of rebamipide treatment. We also recorded subjective symptoms associated with AKC, e.g. itching, foreign body sensation, and eye mucus discharge, by using a patient questionnaire. Their subjective symptoms associated with AKC were also significantly ameliorated at 2 and 4–6 weeks.Our observations suggest that the anti-inflammatory effects of rebamipide eyedrops help to combat human ocular surface inflammation and that they may be a new effective therapy in patients with AKC.Electronic supplementary materialThe online version of this article (doi:10.1186/2045-7022-4-40) contains supplementary material, which is available to authorized users.

Activity and turnover of eosinophil and neutrophil granulocytes are altered in visceral leishmaniasis

Visceral leishmaniasis (VL) is a health issue in Sudan. Our aim was to investigate the involvement of eosinophils and neutrophils in VL by serum and plasma measurements of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) and some key cytokines and chemokines. Blood was collected from 125 VL patients and 181 healthy Sudanese controls from the same rural area. Results showed reduced eosinophil and neutrophil counts in the VL group (P=0.0001and P=0.002, respectively). Serum-ECP levels were higher in the controls (P<0.0001), while plasma MPO levels were higher in the VL group (P<0.0001). Levels of IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-17 were increased among the VL group (P<0.0001, P=0.017 and P=0.03, respectively), whereas eotaxin and IL-8 levels were reduced (P<0.0001 and P=0.002, respectively). Positive correlations were found between IL-8 and ECP/MPO (P<0.0001). We conclude that eosinophil and neutrophil turnover and activity are increased in subjects in rural areas of Sudan. In VL the turnover was further increased, but the relatively low secretory activity of eosinophils and neutrophils in VL may relate to the reduced production and availability of the chemokines eotaxin and IL-8. The combined assay of ECP and MPO in serum and plasma provides further insight into the mechanisms of eosinophil and neutrophil involvement in disease and constitutes a novel approach to the study of disease processes.

スギ花粉症に対するアレグラの初期治療効果

Cedar pollinosis is prevalent in Japan with a growing number of patients reporting increasingly severe symptoms each year. This study evaluated the clinical effect of treating patients with fexofenadine early in the cedar pollinosis season. Patients were divided into two treatment groups: early pollen season patients who consulted the clinic before the pollen season (Group 1); full pollen season patients who consulted the clinic after the start of the pollen season (Group 2). Both groups received fexofenadine HCI 60mg bid from the date of arrival in the clinic until pollen season end. Mean duration of treatment was 55.2 days (Group 1), 19.2 days (Group 2). Clinical efficacy was assessed based on changes in patient-reported symptoms [collected in daily diaries] and concurrent usage of other medications. Other assessments included measurement of eosinophil cationic protein (ECP), vascular endothelial growth factor (VEGF) and eotaxin concentrations in the nasal wash. Forty-nine patients were included in this study (Group 1: N=26; Group 2: N=23). Symptom and symptom-medication scores for Group 1 at weeks 2 and 4 (peak pollen season) were significantly lower (p<0.05) than those of Group 2. While both groups showed elevation of ECP, VEGF and eotaxin in the nasal wash during the peak pollen season, the elevation was lower in Group 1 (p=NS). This study showed that fexofenadine treatment prior to the pollen season reduced cedar pollinosis symptoms to a greater extent than commencing treatment after the start of the pollen season. This difference in efficacy may be linked to the inhibition of ECP and VEGF by fexofenadine.

Eosinophil chemoattractants in the middle ear of patients with eosinophilic otitis media

Patients with intractable otitis media associated with bronchial asthma have an extensive accumulation of eosinophils in the effusion and mucosa of the middle ear; this condition is called eosinophilic otitis media (EOM). It remained to be determined how eosinophils accumulate in the middle ear. To clarify the pathogenesis of middle ear diseases, we measured the concentration of eosinophil chemoattractants in middle ear effusion (MEE), and carried out immunohistochemical studies of middle ear mucosa specimens to demonstrate the expression of eosinophil chemoattractants. Middle ear effusion samples were obtained from 15 EOM patients with bronchial asthma and from six controls for the measurement of eosinophil cationic protein (ECP), IL-5, eotaxin and regulated on activation, normal T expressed and secreted concentrations. Middle ear mucosa samples were also taken from 14 EOM patients and 16 controls for immunohistochemical study. In 10 EOM patients, the numbers of immunoreactive cells as well as apoptotic cells were determined before and after the topical application of triamcinolone acetonide into the middle ear. In EOM, significantly higher ECP and IL-5 concentrations were detected in MEE than in serum, and ECP, IL-5 and eotaxin concentrations in MEE were higher in the EOM patients than in the controls. ECP concentration positively correlated with that of IL-5. Immunohistochemically, the numbers of cells positive for EG2 and ecalectin were significantly higher in the EOM patients than in the controls. After the topical application of triamcinolone acetonide, the numbers of infiltrating cells and immunoreactive cells distinctly decreased, whereas the number of apoptotic cells significantly increased. In EOM, locally produced IL-5 may play a crucial role in the accumulation of eosinophils in the middle ear. Chemokines such as ecalectin and eotaxin are also produced in the middle ear, and help activate and enhance the survival of eosinophils to induce the intractable condition in the middle ear. The topical application of triamcinolone acetonide induces the apoptosis of not only eosinophils but also eosinophil chemoattractant-producing cells, thereby improving the middle ear condition.

Effects of montelukast treatment on clinical and inflammatory variables in patients with cystic fibrosis

In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects. To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF. Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels. Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all). Montelukast may have measurable anti-inflammatory properties in patients with CF.

Bronchial responsiveness and serum eosinophil cationic protein levels in preschool children with recurrent wheezing

Bronchial hyperresponsiveness is a universally recognized phenomenon of asthma, and increased levels of eosinophil cationic protein (ECP) have been identified in the serum of patients with asthma. To investigate whether enhanced bronchial responsiveness and elevated serum ECP levels are associated with recurrent wheezing in preschool children and to examine the possible relationship between these 2 variables. We recruited 130 children aged 4 to 6 years: 59 with at least 3 episodes of wheezing in the previous year (current wheezers), 38 with a documented history of wheezing before 3 years of age but no subsequent wheezing episodes (past wheezers), and 33 who had never experienced wheezing (nonwheezers). The children underwent methacholine bronchial provocation tests using a modified auscultation method and blood sampling for the measurement of ECP levels. Current wheezers showed greater bronchial responsiveness than past wheezers and nonwheezers, as demonstrated by lower provocation concentrations that caused audible wheeze and lower provocation concentrations that caused a decline in oxygen saturation of at least 5% from baseline. Likewise, current wheezers had higher serum ECP levels than the other 2 groups. Among current wheezers, ECP levels showed a significant negative correlation with provocation concentrations that caused oxygen desaturation and a marginally significant correlation with provocation concentrations that caused audible wheeze. Enhanced bronchial responsiveness and elevated serum ECP levels are associated with recurrent wheezing in 4- to 6-year-old children. These results suggest that wheezing during preschool years may be phenotypically similar to wheezing in older children.

Macrolides in the treatment of asthma and cystic fibrosis

Asthma and cystic fibrosis are two respiratory diseases characterized by chronic inflammation, leading to remodelling of the airways. Macrolides are widely used antibiotics, with a peculiar anti-inflammatory effect. On the basis of the methodologies used by the Cochrane collaboration, this review discusses the evidence for their long-term use as anti-inflammatory agents in these two diseases. Three randomized-controlled trials (RCTs) were identified for both asthma and cystic fibrosis. A positive effect of macrolides on reducing eosinophil numbers and markers of eosinophilic inflammation was demonstrated in patients with asthma. Data on cystic fibrosis demonstrated an effect on lung function with an increase of 5.4% in forced vital capacity (FVC) in patients treated with macrolide vs. placebo, but without a significant effect on FEV1. Side-effects were rare, mild and reversible on withdrawal of treatment. Although preliminary data from small studies are promising, the role of macrolides in the treatment of these chronic disorders needs to be more firmly established with larger, well-designed trials, targeted to investigate major clinical outcomes.

Do tryptase, ECP and specific IgE measurement by nasal incubation increase the specific nasal provocation test sensitivity?

The specific Nasal Provocation Test (sNPT) is a third level diagnostic tool. Fitted to reproduce natural exposure condition to pick the responsible allergen for nasal symptoms out, it is applied when prick test and RAST responses are doubtful. SNPT results have been evaluated measuring nasal resistance (anterior rhinomanometry) and nasal symptoms (clinical score), reaching 50% of sensitivity. This study focused on the determination of allergic response markers, triggered by nasal challenge: tryptase levels in the nose, specific IgE and ECP (Eosinophil Cationic Protein). The aim was to increase sNPT sensitivity. Twenty patients suffering from allergic rhinitis and 16 age-matched-nonallergic subjects were enrolled in the study. Tryptase, specific IgE and ECP were determined in nasal mucosa applying a new method, based on in situ incubation, before and after sNPT. The latter was performed following a standardized method. Tryptase levels increased in 13 patients (65%), were unchanged in four patients (20%), and slightly decreased in three patients (15%). The increase recorded was significant in mite allergic patients (p=0.005), but not significant (p> 0.05) in pollen allergic patients. ECP values increased in 13 patients (65%), were unchanged in two patients (10%), and highly decreased in five patients (25%). ECP increase was not significant (p> 0.05). Specific IgE levels increased in seven patients (35%), were unchanged in 11 patients (55%) and decreased in two patients (10%). The IgE increase was significant in pollen-allergic patients (p<0.05), while it was not significant in mite-allergic patients (p>0.05). Tryptase, ECP, and specific IgE were not detected in the control group. The data obtained showed a positive sNPT response in 12 patients (60%). Comparing our results with those derived from classical-parameter employment, we gathered an improvement of 10%. On the basis of the usual parameters, in fact, we recorded 50% positivity, while the use of mediators provided an additional 10% improvement in sNPT sensitivity: taking together the usual parameters and nasal allergic mediators values, we reached an sNPT over-all sensitivity of 85%.

Eosinophil Cationic Protein Concentration in Saliva Does Not Correlate With Eosinophil Cationic Protein Concentration in Sputum

Eosinophilic infiltration is a prominent component of the inflammation characteristic of asthma. Measurement of eosinophils and eosinophil cationic protein (ECP) in induced sputum is a noninvasive indicator of changes in airways inflammation. Recently, Schmekel and colleagues 1 Schmekel B Ahlner J Malmstrom M et al. Eosinophil cationic protein (ECP) in saliva: a new marker of disease activity in bronchial asthma. Respir Med. 2001; 95: 670-675 Abstract Full Text PDF PubMed Scopus (31) Google Scholar reported that salivary ECP was elevated in subjects with asthma and was correlated with disease activity. The measurement of salivary ECP as a surrogate for sputum ECP is attractive because it can be done rapidly, requires less cooperation on the part of the subject, and is devoid of the potential adverse effects of sputum induction. We examined the correlation of sputum ECP and salivary ECP in 26 paired samples from 14 nonsmoking asthmatic subjects not receiving corticosteroids (12 subjects had specimens collected 4 weeks apart). Asthma severity ranged from mild intermittent to moderate persistent. After mouth rinsing, 3 mL of saliva was collected by repetitive expectoration. Sputum was then induced by inhalation of 3% saline solution and collected over 20 min. Specimens were collected on ice and processed within 60 min. ECP in sputum and saliva was measured by radio-immunoassay (Kabi Pharmacia Diagnostics; Uppsala, Sweden). Mean (± SD) values for sputum and salivary ECP were 88 ± 141 μg/L and 43 ± 20 μg/L, respectively. Following acid acetate extraction, as reported by Schmekel and colleagues, 1 Schmekel B Ahlner J Malmstrom M et al. Eosinophil cationic protein (ECP) in saliva: a new marker of disease activity in bronchial asthma. Respir Med. 2001; 95: 670-675 Abstract Full Text PDF PubMed Scopus (31) Google Scholar there was an increase in salivary ECP to 201 ± 189, likely reflecting lysis of cells. There was no correlation between sputum and saliva ECP (r2 = 0.00). After acetate extraction, the correlation was better (r2 = 0.26, p = .029) though not strong. Hence, while salivary ECP may be elevated in subjects with asthma compared to normal subjects, it is not useful as a surrogate marker for sputum ECP.

Treatment of asthma patients with herbal medicine TJ-96: a randomized controlled trial

Alternative medicine use has increased at a remarkable pace all over the world in recent years. Although herbal medicine for the treatment of asthma is becoming the focus of public attention, randomized studies had not been performed, even in Eastern countries including Japan. This study was designed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to (TJ-96) is effective for the treatment of atopic asthma, and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation. A double-blind, randomized, crossover design was used. Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine. Furthermore, eosinophil counts and measurement of eosinophilic cationic protein (ECP) were performed. After 4 weeks of treatment with TJ-96, values of PC20-methacholine significantly improved in the treatment with TJ-96. Also, patients' symptoms, blood eosinophils, serum ECP, sputum eosinophils, and sputum ECP were significantly decreased. Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration. This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma.

Clinical characteristics of so called eosinophilic otitis media

Objective: Although ‘eosinophilic otitis media’ is not as uncommon a condition as was previously believed, its cause and pathogenesis are not yet fully understood. The purpose of this study was to describe the clinical characteristics in patients with ‘eosinophilic otitis media’ to clarify its pathogenesis. Methods: Seven adult patients with persistent and intractable otitis media with viscous middle ear effusion containing many eosinophils, who were also under treatment for bronchial asthma, were studied. The following examinations were conducted: nasopharyngeal endoscopy, pure-tone audiometry, eustachian tube function test, temporal bone CT scan, blood analysis, bacterial and fungal culture of middle ear effusion, histological study of the middle ear and nasal specimens, and measurement of eosinophilic cationic protein (ECP) in middle ear effusion. Results: Some patients had persistent perforation with papillomatous granulation tissue arising from the mesotympanic mucosa, and all the patients had nasal polyposis. The pure-tone audiometry showed the mixed-type of hearing loss in all the patients, and the hearing level deteriorated progressively during the course in some patients. The eustachian tube function was not always poor but was patulous in some cases. The most severely diseased areas were in the eustachian tube and mesotympanum by temporal bone CT images. All the seven patients had the high levels of total serum IgE, but the RAST scores were negative in three patients and low grade in three patients. The accumulation of eosinophils was observed in middle ear effusion, middle ear mucosa and nasal polyps, and the eosinophils were highly activated with degranulation. High level of ECP was also recovered from middle ear effusion. Conclusions: Active eosinophilic inflammation occurs in the entire respiratory tract, including the middle ear in these patients. From our present investigation, we propose the criteria and clinical characteristics of ‘eosinophilic otitis media’.

Changes in inflammatory markers following treatment of acute exacerbations of obstructive pulmonary disease

The aim of the study was to investigate changes in inflammatory markers following emergency treatment of obstructive pulmonary disease. The study comprised 43 patients. After acute treatment, they were given either 30 mg of prednisolone p.o. or 1600 μ g of inhaled budesonide daily for 1 week. Over the following 3 weeks, all the patients were given 1600μ g of inhaled budesonide daily. Blood samples for measurements of eosinophil cationic protein (S-ECP), eosinophil peroxidase (S-EPO), total eosinophil count (B-Eos), myeloperoxidase (S-MPO) and human neutrophil lipocaline (HNL) were taken and spirometry was performed before emergency treatment and after 1 and 4 weeks. There was no difference in the improvement in forced expiratory volume in 1 sec (FEV1) between patients given prednisolone or budesonide. Patients with an improvement in FEV1of ⩾20% of baseline after 1 and 4 weeks displayed a larger decrease in eosinophil markers. The correlation between ΔFEV1and ΔS-ECP was r=−0·37, P<0·05, ΔS-EPO −0·40, P<0·01 and ΔB-Eos −0·44, P<0·01, after 4 weeks. This correlation was highly significant in patients who had smoked ⩽5 pack-years, while the correlation was not significant in patients with a longer smoking history and chronic airflow limitation (best FEV1<80% of predicted). We conclude that the change in eosinophil markers is correlated to the improvement in lung function in non-smokers or short-term smokers following the emergency treatment of obstructive pulmonary disease. This study indicates that following eosinophil markers is more useful in patients with asthma than patients with COPD.

Cromolyn sodium suppresses eosinophilic inflammation in patients with aspirin-intolerant asthma

Although administration of cromolyn sodium is one of the most useful drugs for the treatment of aspirin-intolerant asthma (AIA), both its pharmacologic mechanism of action and association with the pathogenesis remain obscure. This study was designed to investigate the protective effect of cromolyn sodium on airway responsiveness to the sulpyrine provocation test, and to examine whether its activity is associated with a reduction in eosinophilic inflammation. Patients were randomly assigned to receive cromolyn sodium (20 mg/2 mL, or 1 ampoule; Fujisawa, Osaka, Japan) or matching placebo (2 mL of saline) four times daily for 1 week. We evaluated the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of sulpyrine in 16 adult patients with mild or moderate AIA; those who were in stable clinical condition were allocated to this study. A double-blind, randomized, crossover design was used. Blood and sputum samples were taken in the morning on the sulpyrine provocation testing day. Eosinophil counting and measurement of eosinophilic cationic protein (ECP) were performed. Inhaled cromolyn sodium protect against aspirin-induced attacks of asthma through mechanisms not related to the bronchodilator property, but related to the improvement of the bronchial hypersensitivity, almost completely in all patients (P < 0.001). After 1 week's treatment with cromolyn sodium, patients' symptoms, blood and sputum eosinophils counts, and sputum ECP levels were significantly decreased compared with both placebo and baseline. Cromolyn sodium has a bronchial anti-inflammatory effect associated with decreased eosinophilic infiltration. This is the first report that cromolyn sodium reduces blood and sputum eosinophils counts and sputum ECP levels in AIA.