Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease.

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.     

PGE2 and PGF2 alpha content in bronchoalveolar lavage fluid obtained from patients with eosinophilic pneumonia

Cell differential, prostaglandins (PGs) E2 and F2 alpha in the bronchoalveolar lavage fluid (BALF) in two patients with eosinophilic pneumonia were measured at different times in the course of the disease. Results showed markedly increased numbers of eosinophils and increased content of prostaglandin (PG) E2 in BALF obtained from the patients with eosinophilic pneumonia compared to that of normal volunteers. Interestingly, the increased content of PGE2 in BALF obtained from the patients reverted to normal range with corticosteroid treatment. This change in PGE2 content in BALF was accompanied by normalization of number and percentage of eosinophils in BALF. These findings indicated that PGE2 level in lower respiratory tract of patients with eosinophilic pneumonia may be related to an increased number of eosinophils.     

嗜酸粒细胞性支气管炎患者气道炎症细胞及介质特征的探讨

目的观察嗜酸粒细胞性支气管炎(EB)诱导痰和支气管肺泡灌洗液(BALF)中细胞分类和炎症介质浓度,探讨EB的气道炎症特征。方法对43例EB(EB组)患者行诱导痰检查,将20例咳嗽变异型哮喘(CVA)患者(CVA组)、16例典型支气管哮喘(哮喘组)患者和21名健康人(健康对照组)行对照诱导痰检查,并对部分EB(11例)和CVA患者(10例)行支气管肺泡灌洗(BAL)。观察检测诱导痰、BALF中的细胞分类、嗜酸粒细胞阳离子蛋白(ECP)、白三烯C4(LTC4)和组胺的浓度。结果EB组患者诱导痰中嗜酸粒细胞(EOS)百分比为0.1130±0.1470,CVA组为0.1900±0.1800,哮喘组为0.3860±0.2670,与健康对照组(0.0020±0.0050)比较差异有统计学意义(P均<0.01);哮喘组与CVA组、CVA组与EB组比较差异均有统计学意义(P均<0.05);EB组BALF中EOS为0.011±0.016,CVA组为0.053±0.040,两组比较差异有统计学意义(P<0.05);EB组诱导痰中的ECP浓度为(0.62±0.66)mg/L、CVA组为(1.27±1.74)mg/L,对照组为(0.07±0.10)mg/L,3组间比较差异有统计学意义(P<0.01);CVA组诱导痰中的LTC4浓度为(0.65±0.62)μg/L,EB组为(0.39±0.61)μg/L,对照组为(0.15±0.11)μg/L,3组间比较差异有统计学意义(P分别<0.05、0.01);CVA组BALF中组胺浓度为(3.4±1.4)μg/L,EB组为(1.6±1.5)μg/L,两组比较差异有统计学意义(P<0.05)。结论EB组EOS炎症主要局限于中心气道,部分气道炎性介质水平低于CVA组。上述气道炎性特征可能是EB患者无非特异性气道高反应性的重要机制。     

Clinical Significance of Interleukin 33 (IL-33) in Patients with Eosinophilic Pneumonia

Background: Interleukin 33 (IL-33) works as a functional mediator in allergic disease by enhancing the activity of eosinophils and inducing expression of T helper 2 (Th2)-associated cytokines. However, the role of IL-33 in pulmonary eosinophilia has not been elucidated. We investigated the levels of IL-33 in eosinophilic pneumonia (EP) together with associated cytokines, and discussed the clinical significance of IL-33 in EP.Methods: Sera and bronchoalveolar lavage fluid (BALF) were obtained from 16 patients with EP, including acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Twelve patients with acute respiratory distress syndrome (ARDS) were also included for comparison. The concentration of IL-33 and Th2 cytokines (IL-4, IL-5, IL-13) were measured by enzyme-linked immunosorbent assay (ELISA).Results: The concentration of serum IL-33 was significantly higher in patients with AEP than in CEP. In CEP, only patients with atopic factors showed mild increase of serum IL-33. The concentration of BALF IL-33 was also significantly elevated in AEP, however, it remained quite low in CEP. Among Th2 cytokines, IL-5 was significantly increased in both serum and BALF in AEP, and the level of IL-5 was positively correlated with that of IL-33. ARDS showed no increase of serum and BALF IL-33.Conclusions: The remarkable increase of BALF IL-33 in AEP indicated the local production of IL-33 in lungs. IL-33 is considered to be a local key molecule for triggering pulmonary eosinophilia, together with IL-5. BALF IL-33 appears to be a useful marker for discriminating AEP from CEP and ARDS.     

Clinical significance of eosinophilic cationic protein in serum and bronchoalveolar lavage fluid of adult patients with mycoplasmal pneumonia

Pathogenic mechanisms of mycoplasmal pneumonia is not fully understood at present though some kind of cell-mediated hypersensitivity is closely related to its mechanisms. Though eosinophilia in peripheral blood are sometimes revealed in patient with mycoplasmal pneumonia, it is not unclear whether eosinophils related to its pathogenesis, or not. We evaluated the clinical significance of ECP in serum and BAL fluid in patients with mycoplasmal pneumonia. The diagnosis of mycoplasmal pneumonia was confirmed both by serological diagnosis from paired serum and by the polymerase chain reaction (PCR) methods using specific primers of the Mycoplasma pneumoniae for detecting specific DNA from bronchial washing fluids. ECP level in serum were measured in 27 patients (11 male, 16 female, average age 31.7 yo) with mycoplasmal pneumonia by ELISA methods. ECP level in BALF were also measured in ten of all patients. The level of ECP in serum was high in 17 cases (63%) of the total cases. In addition the level of ECP in BALF was also high in all tested patients (10 cases). There was a correlation between serum ECP level and days from onset. There was also a correlation between serum ECP level and WBC counts, the degree of PaO2. These results suggested that ECP derived from activated eosinophils in the lung might in part play a role in the pathogenesis of mycoplasmal pneumonia.     

Increased macrophage inflammatory protein-1alpha and -1beta in BAL fluid of bronchiolitis obliterans organizing pneumonia

OBJECTIVE: CC chemokines are mainly chemotactic for monocytes and lymphocytes. The aim of this study was to evaluate the involvement of the CC chemokines, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, in the pathogenesis of bronchiolitis obliterans organizing pneumonia (BOOP). METHODOLOGY: The concentrations of MIP-1alpha and MIP-1beta in BAL fluid (BALF) obtained from patients with BOOP (n = 13) and control patients (CP, n= 18) were measured by enzyme-linked immunosorbent assay. RESULTS: MIP-1alpha in BALF was significantly higher in patients with BOOP (mean +/- SD; 123.8 +/- 98.0 pg/mL) than in CP (62.5 +/- 46.1 pg/mL). Significantly higher MIP-1beta was also detected in patients with BOOP (51.6 +/- 72.5 pg/mL) than in CP (6.4 +/- 3.7 pg/mL). The concentration of MIP-1alpha significantly correlated with the percentage of lymphocytes in BALF, and the concentration of MIP-1beta significantly correlated with the numbers of lymphocytes, neutrophils and eosinophils in BALF. Both MIP-1alpha and MIP-1beta in BALF were decreased after corticosteroid therapy and this was accompanied by decreased lymphocytes in BALF. CONCLUSION: This study suggests that MIP-1alpha and MIP-1beta may play important roles in the recruitment of immuno-inflammatory cells into the lungs, and may contribute to the pathogenesis of BOOP.     

Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia

Purpose

Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP.

Methods

IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis.

Results

The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP.

Conclusions

Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

     

BALF N-acetylglucosaminidase and beta-galactosidase activities in idiopathic pulmonary fibrosis

The lysosomal enzymes N-acetylglucosaminidase (N-ACGA) and beta-galactosidase (beta-gal) are involved in cellular collagen metabolism and may, therefore, be markers of fibrosis in idiopathic interstitial pneumonias, such as idiopathic pulmonary fibrosis (IPF). N-ACGA and beta-gal were analyzed in the bronchoalveolar lavage fluid (BALF) of patients with the histologic pattern of usual interstitial pneumonia (UIP, n=10) and controls (n=9). Cellular distribution in BALF as well as the concentration of TGF-beta a well-known mediator of fibroblast matrix deposition were correlated to the enzyme activities in both groups of patients. We found that both, N-ACGA (UIP: 25.2 nmol/l s +/- 3.4; controls: 73 nmol/l s +/- 1.3) and beta-gal (UIP: 4.7 nmol/l s +/- 0.5; controls: 2.4 nmol/l s +/- 0.3) were elevated significantly in BALF of patients with IPF compared to that of control patients (P<0.003). This increase was paralleled by an increase in neutrophils (IPF: 17.9% +/- 21.8; controls: 5.4% +/- 6.3; P=0.03) and eosinophils (IPF: 2.0% +/- 1.5; controls: 0.2% +/- 0.45; P=0.002) in BALF fluid. In addition, N-ACGA activity correlated closely with lung function (FVC, TLC, and DLCO), transforming growth factor-beta (TGF-beta) in BALF (r=0.77, P=0.008) and activated lymphocytes (r=0.66, P=0.0021). Our findings suggest that measurement of lysosomal enzymes such as N-ACGA may represent a useful indicator of fibrotic activity in IPF.     

Immunohistochemically stained activated eosinophils in sputum in patients with asthma

BACKGROUND: Eosinophils play an important role in asthmatic airway inflammation. Monoclonal antibody EG2 has been considered to identify activated eosinophils. OBJECTIVE: The present study was aimed to investigate whether immunohistochemically stained EG2+ eosinophils in sputum reflect the severity of asthma. METHODS: Sputum was obtained in 23 asthmatic patients, of whom 13 patients were examined before and after antiasthma treatment including steroid preparations. We used immunohistochemical staining to detect EG2+ (activation marker) eosinophils and fluoroimmunoassay to detect eosinophil cationic protein (ECP). RESULTS: Moderate to severe asthmatics had a significantly higher proportion of eosinophils and EG2+ eosinophils and higher levels of ECP compared to mild asthmatics (40.9 +/- 5.8 vs. 6.4 +/- 1.2%, 35.5 +/- 5.6 vs. 2.7 +/- 1.0%, 1.470.2 +/- 251.5 vs. 210.6 +/- 52.0 microgram/l, respectively; p < 0.01). Significant increases in proportions of eosinophils, EG2+ eosinophils and ECP in the sputum from patients with exacerbated asthma were evident. The proportions of eosinophils, EG2+ eosinophils, and the levels of ECP were reduced following treatment with antiasthmatic drugs. FEV(1) and FEV(1)/FVC were significantly correlated with EG2+ eosinophils. CONCLUSION: These findings demonstrate that EG2+ eosinophils in sputum are closely related to the clinical status in patients with asthma.     

Osteopontin levels are elevated in patients with eosinophilic pneumonia

Background and objective: Osteopontin is a key cytokine involved in pro‐inflammatory T helper type 1 (Th1)‐associated immune responses, which has recently been implicated in allergic diseases. We investigated the pathogenic role of osteopontin in eosinophilic pneumonia. Methods: The concentrations of osteopontin and Th1‐ or Th2‐associated cytokines were measured in BAL fluid (BALF) from 41 patients with eosinophilic pneumonia, including those with acute (AEP, n = 12), chronic (CEP, n = 16), or drug‐induced eosinophilic pneumonia (DEP, n = 13). The results were compared with those from patients with other interstitial lung diseases. Immunocytochemistry and double immunofluorescence labelling were performed to determine the cellular source of osteopontin. Results: Osteopontin was significantly elevated in BALF from patients with eosinophilic pneumonia as compared with BALF from patients with drug‐induced interstitial pneumonia, hypersensitivity pneumonitis, idiopathic interstitial pneumonia, or sarcoidosis, and also compared with BALF from healthy volunteers. Osteopontin concentrations elevated at the time of exacerbation decreased during clinical improvement, either spontaneously or as a result of corticosteroid therapy. Elevated concentrations of CXCL10, CCL17 and IL‐10 were also detected in BALF from patients with eosinophilic pneumonia. Osteopontin concentrations in BALF of AEP patients were correlated with IL‐5, as well as IL‐10, CCL11, CCL17 and CXCL10 concentrations. In AEP and DEP patients, serum osteopontin concentrations were also elevated. Double immunofluorescence labelling showed that in patients with eosinophilic pneumonia, osteopontin was expressed in lung eosinophils. Conclusions: Osteopontin is likely to contribute to the development of inflammation in patients with eosinophilic pneumonia.     

Elevated levels of antimicrobial peptides in bronchoalveolar lavage fluid in patients with chronic eosinophilic pneumonia

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is an idiopathic pulmonary disease. As the lung is in direct communication with the environment, inhaled antigen may activate immune mechanisms in the airway that may participate in the pathogenesis of idiopathic pulmonary diseases. Defensins are antimicrobial peptides that consist of alpha-defensin (HAD) in neutrophils and beta-defensin (HBD) in epithelial cells. Defensins act as innate immunity against pathogens acquired from the environment and as mediators to induce local inflammation. OBJECTIVES: The aim of the present study was to determine whether immune mechanisms in the airway are induced in CEP patients. METHODS: We measured BALF defensin levels in patients with CEP, acute EP (AEP) and drug-induced eosinophilic pneumonia (drug-EP). We also measured BALF levels of IL-5, GM-CSF, eotaxin and RANTES. These substances can recruit eosinophils. RESULTS: BALF HAD levels were higher in patients with CEP than in those with drug-EP and normal controls. HBD-2 was detected in BALF of 10 of 11 CEP patients and in 3 of 5 AEP patients while its level was below detection in drug-EP patients and normal controls. BALF HBD-2 levels correlated with the proportion of lymphocytes in CEP patients. CONCLUSION: The defensin-linked immune system is activated in CEP but not in drug-EP. This suggests that inhaled antigen(s) may be involved in the pathogenesis of CEP.     

The eosinophil component of the alveolitis in idiopathic pulmonary fibrosis. Signs of eosinophil activation in the lung are related to impaired lung function

The number of eosinophils and the concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients (n = 22) with idiopathic pulmonary fibrosis (IPF). The median recovery of eosinophils during lavage performance was 4% (range, zero to 49) of the nonepithelial cells and significantly increased compared with the recovery in healthy control subjects (less than 1%) and in control patients with sarcoidosis (1%; range, zero to 7). The median BAL fluid concentration of ECP was in IPF 13.3 micrograms/L (range, 2 to 118) and significantly increased compared with the concentrations in healthy control subjects (2.7 micrograms/L; range, less than 2 to 8) and in control patients (6.6 micrograms/L; range, less than 2 to 64). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in IPF, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. BAL fluid eosinophils and ECP correlated with the reduced diffusion capacity of the lung but not with vital capacity or forced expiratory volume. It is concluded that eosinophil activation is part of the inflammatory process in IPF. ECP and other cytotoxic eosinophil products may play a pathophysiologic role for the lung damage in this disease.     

Eosinophil activation in the lung is related to lung damage in adult respiratory distress syndrome

The concentrations of eosinophil cationic protein (ECP), a specific granule constituent of eosinophil granulocytes, were measured in bronchoalveolar lavage (BAL) fluid from patients with adult respiratory distress syndrome (ARDS). The mean level was 163 +/- 85 (SD) micrograms/L and significantly increased (p less than 0.001) compared with the levels in control subjects (19 +/- 18 micrograms/L). The BAL fluid concentrations of myeloperoxidase (MPO) were also significantly increased in ARDS, indicating a local neutrophil activation. A significant correlation was found between BAL fluid ECP and MPO, suggesting a common activator of eosinophils and neutrophils. No relation was seen between BAL fluid ECP or MPO and degree of complement consumption, suggesting that other mechanisms besides complement activation may underlie granulocyte activation in ARDS. Lavage ECP levels correlated strongly with the severity of lung damage defined by pulmonary oxygenation index (PaO2/inspired fraction of O2). Activation of eosinophils, neutrophils, and the complement system is not specific for ARDS but was also observed in patients after major surgery, but at a significantly lower level (p less than 0.001). It is concluded that eosinophil activation is part of the inflammatory process in the lung in ARDS. The association observed between elevated lavage fluid levels of ECP and reduced pulmonary function in ARDS might reflect a pathophysiologic role for ECP and other cytotoxic eosinophil products in this syndrome and should be evaluated.     

哮喘和慢性阻塞性肺疾病患者糖皮质激素治疗前后痰液炎性标志物 …

探讨哮喘和慢性阻塞性疾病患者吸入糖皮质激素治疗后痰液中细菌因子和嗜酸细胞阳离子蛋白浓度及糖皮质激素对其影响。方法采用荧光酶联免疫法检测糖皮质激素治疗前后痰液中白细胞介素（ＩＬ）－５、ＩＬ－８、ＥＣＰ浓度及嗜酸细胞和嗜中性粒细胞计数。     

Ratio of serum eosinophil cationic protein/blood eosinophil counts in children with asthma: comparison between acute exacerbation and clinical remission.

Serum eosinophil (Eo) cationic protein (ECP) concentrations during acute exacerbations in asthma patients are significantly elevated compared with those during clinical remission. We measured the ratio of serum ECP concentration to peripheral blood Eo counts (ECP/Eo ratio), to determine whether the ECP release from Eo differs between the two clinical asthma situations. Forty-six children with asthma underwent spirometric assessment and blood sampling at the times of acute exacerbation and clinical remission. Twenty healthy children also were studied as a control group. The peripheral blood Eo count (468 +/- 262 per microL, mean +/- SD), the serum ECP concentration (41.7 +/- 16.9 micrograms/L), and the ECP/Eo ratio (0.104 +/- 0.049) during acute asthma exacerbations were significantly higher than the respective values during clinical remission (383 +/- 191 per microL, 27.4 +/- 11.5 micrograms/L, 0.084 +/- 0.041, all p < 0.05). The ECP/Eo ratio as well as the serum ECP concentration during acute exacerbations correlated significantly with the degree of airflow obstruction (both, p < 0.01). Both the increased peripheral blood Eo counts and the possible enhanced Eo activation may account for the elevated serum ECP concentration observed during acute exacerbations compared with that during clinical remission. Our results suggest a differential release of ECP by the Eo, depending on the disease status and asthma exacerbation severity.     

One-year evaluation of the preventative effect of hydrofluoroalkane-beclomethasone dipropionate on eosinophilic inflammation of asthmatic peripheral airways

BACKGROUND: In asthmatic patients with eosinophilic inflammation of the peripheral airways, appropriate drug delivery to the affected area is required. OBJECTIVE: It was the aim of this study to assess persistent eosinophilic inflammation of the peripheral airways in asthmatic patients, stabilized by the long-term use of dry powder type inhaled steroids, and to evaluate the clinical efficacy of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) over 1 year. METHODS: Seventy-four outpatients with moderate stable asthma were studied for at least 6 months, 37 treated with fluticasone propionate Diskus (FP-DK) and 37 with budesonide Turbuhaler (BUD-TH). The eosinophil count, eosinophil cationic protein (ECP), eotaxin and RANTES levels in 10% hypertonic saline-induced sputum were examined before treatment, as well as 4 weeks, 8 weeks, 6 months and 1 year after switching patients to HFA-BDP. RESULTS: Fifteen patients (40.5%) in the FP-DK group and 12 (32.4%) in the BUD-TH group had eosinophils in induced sputum. The sputum ECP in the eosinophil-positive and the eosinophil-negative groups was 1,510.1 +/- 2,009.3 versus 426.6 +/- 464.1 microg/l (p = 0.037) in the FP-DK group, and 3,850.0 +/- 5,486.2 versus 492.0 +/- 1,150.7 microg/l (p = 0.011) in the BUD-TH group, respectively. Four weeks after the switch to HFA-BDP, the number of eosinophil-positive patients decreased in both groups. Significant reductions in sputum ECP and eotaxin were observed at 8 weeks, and their concentrations continued decreasing for 1 year. CONCLUSION: There is a certain proportion of asthmatic patients for whom long-term treatment with dry powder type steroids may not be suitable; however, their peripheral airway inflammation improved after switching them to HFA-BDP, suggesting its excellent delivery.     

Reproducibility in induced sputum in children with asthma

In asthmatic children sputum-induction with hypertonic saline is useful to quantify the eosinophilic inflammation. However, only few data are available about feasibility and safety of the procedure in children. Therefore, taking 9 non-atopic healthy control children (mean age 11.8 years) and 34 asthmatic children (mean age 11.4 years), inhaling n = 25 Budesonid (400-1200 micrograms/die) and n = 9 DNCG (60 mg/die), sputum induction was performed twice within 6 weeks. Briefly, 10 minutes after inhalation of 200 micrograms salbutamol subjects inhaled hypertonic saline (3, 4 and 5%) for in all 30 minutes, while all 5 minutes lung function was checked and expectoration of sputum was supported. Adequate sputum plugs were separated from contaminating saliva and processed immediately employing native chamber and cytospin cell count as well as measurement of eosinophilic cationic protein (ECP). Sputum-induction could be performed in 84 out of 86 planed tests (97.7%) without any objective clinical adverse effects. The mean fall in FEV1 was 3.0%, the maximum 11.0%. The reproducibility of eosinophil, neutrophil and lymphocyte differential cell count (5-95%-values Test1: 0.0-4.2%, 0.8-11.4%, and 3.2-35.1%, respectively) was moderate for eosinophils and neutrophils (Intraclass-Correlation-Coefficient (ICC) 0.41) as well as for lymphocytes (ICC = 0.49). For ECP 5-95%-values Test1: 39.8-8000.0 micrograms/l) only a fair reproducibility (ICC = 0.24) was found. The ICC levels for total cell count (ICC = 0.31) and for weight of the sputum plug (ICC = 0.30) were also fair. Based on the procedure presented induced sputum is a feasible and safe method in childhood. The differential sputum cell count of eosinophils, neutrophils and lymphocytes can be recommended as parameters with moderate reproducibility.     

Eosinophil degranulation status in allergic rhinitis: observations before and during seasonal allergen exposure.

Despite the fact that extensive degranulation is a likely prerequisite for a pathogenic role of eosinophils, little is known about the degranulation status of these cells in eosinophilic conditions. The present study of the ultrastructure of tissue eosinophils explores eosinophil degranulation in allergic rhinitis before and during seasonal allergen exposure. A total of 23 patients scored symptoms q.d., prior to and during the pollen season. The numbers of mucosal eosinophils and their degranulation status were determined in nasal biopsies. Furthermore, nasal lavage fluid levels of eosinophil cationic protein (ECP) and alpha2-macroglobulin were assessed as indices of eosinophil activity and plasma exudation, respectively. Seasonal allergen exposure was associated with increased nasal symptoms, increased lavage fluid levels of ECP and alpha2-macroglobulin, and increased numbers of tissue eosinophils. In the tissue, transmission electron microscopy revealed a moderate piecemeal degranulation already prior to the season (mean+/-sd 37+/-2.7% altered granules). Seasonal allergen exposure increased this degranulation (87+/-1.8%), and produced local areas with extensive deposition of granule proteins. The degree of eosinophil degranulation correlated with levels of ECP in lavage fluids obtained at histamine challenge. In conclusion, this study demonstrated that the nasal mucosa in allergic rhinitis features moderately degranulated eosinophils already at nonsymptomatic baseline conditions. In association with the development of symptomatic seasonal allergic rhinitis, the tissue deposition of eosinophil granule proteins is dramatically elevated through increased eosinophil numbers, together with markedly augmented degranulation of individual cells.     

哮喘患者痰液细胞因子和哮嗜酸细胞阳离子蛋白水平及意义

目的 探讨痰中细胞因子、嗜酸细胞阳离子蛋白（ＥＣＰ）水平与哮喘严重程度的关系。方法 采用酶联免疫法及荧光光免疫法对轻（Ｍ组１０例）中、重度（ＭＳ组１５例）哮喘２痰液白细胞介素（ＩＬ）５、肿瘤坏死因子α（ＴＮＦ－α）、可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）、ＥＣＰ水平进行检测。结果 中、重度哮喘患溶液ＩＬ－５（３５ｎｇ／Ｌ以上）、ＴＮＦ－α（Ｍ组为１４９±５９ｎｇ／Ｌ，ＭＳ组为２６７±１４７ｇ／Ｌ