Sputum Eosinophil Cationic Protein Research Articles

Effect of Benralizumab on Mucus Plugs in Severe Eosinophilic Asthma

Introduction: Mucus plugs are associated with airway obstruction in severe asthma and are involved in the formation of activated eosinophils. Benralizumab, an anti-interleukin-5 receptor antibody, markedly reduces not only peripheral blood eosinophils but also airway eosinophils; however, its effects on mucus plugs have not been clarified. In this study, we examined the efficacy of benralizumab on mucus plugs using computed tomography (CT) imaging. Methods: Twelve patients who were administered benralizumab and underwent CT before and approximately 4 months after the introduction of benralizumab were included in this study, and the number of mucus plugs before and after benralizumab administration was compared. The correlation between the clinical background and treatment effect was also examined. Results: The number of mucus plugs significantly decreased after the introduction of benralizumab. The number of mucus plugs was correlated with sputum eosinophil percentage and eosinophil cationic protein in the sputum supernatants and inversely correlated with forced expiratory volume in 1 s (FEV1). Benralizumab induction resulted in a marked decrease in blood and sputum eosinophil levels and a significant improvement in asthma symptoms, quality of life scores, FEV1, and exacerbation frequency. Furthermore, there was a significant correlation between the reduction in mucus plugs and changes in the symptom score or FEV1. Discussion/Conclusion: These data suggest that benralizumab may have the potential to improve symptoms and respiratory function in patients with severe eosinophilic asthma by reducing mucus plugs.

Macrolides versus placebo for chronic asthma.

Macrolides versus placebo for chronic asthma.

Clinical value of IL-13 and ECP in the serum and sputum of eosinophilic AECOPD patients.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an inevitable trend in the development of the disease and eosinophils (EOS) participate in inflammation process. It is important to explore some relatively simple biomarkers in AECOPD which are useful to recognize the disease. In the present study, 108 hospitalized patients with AECOPD were collected and the levels of IL-13 and ECP in the serum and sputum were measured. The levels of IL-13 and ECP in sputum in the eosinophilic group were higher than those in the noneosinophilic group. Moreover, the noneosinophilic group had a higher rate of rehospitalization due to acute exacerbation during the one-year follow-up. The results show that eosinophils in peripheral blood are a simple, convenient, and inexpensive index for assessing the condition and prognosis of AECOPD patients. IL-13 and ECP are involved in the pathogenesis of eosinophilic AECOPD and may be the new targeted anti-inflammatory therapies.

Correlation between expressions of myeloperoxidase and eosinophil cationic protein in sputum and clinical features of asthma-chronic obstructive pulmonary disease overlap

To observe the role of myeloperoxidase(MPO)and eosinophilic cationic protein(ECP)in the airway inflammation and their correlation with clinical feature in asthma-COPD overlap (ACO) patients. Twenty patients with COPD, 20 with asthma, 20 with ACO and 20 control subjects underwent pulmonary function test for measurement of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and maximum midexpiratory flow (MMF25/75). COPD assessment test (CAT) was used to evaluate the clinical symptoms of the patients with COPD and ACO. The asthma control test (ACT) was used to evaluate the asthma control in the patients with asthma and ACO. Induced sputum samples were collected from the subjects for analysis of neutrophil and eosinophil ratios, and enzyme-linked immunosorbent assay was used to determine the expression levels of MPO and ECP in the sputum. No significant difference was observed in the CAT scores between ACO group and COPD group (P> 0.05). Compared with the asthma group, the patients with ACO had significantly lower ACT scores and lower FEV1, PEF and MMF25/75 (P < 0.05). The patients with ACO had significantly higher FVC and sputum eosinophil ratio than those with COPD (P < 0.05), and a higher sputum neutrophil ratio than those with asthma (P < 0.01). In ACO group, the MPO level in sputum was significantly higher than that in the asthma group (P < 0.05), while sputum ECP level was significantly higher than that in both the asthma group and COPD group (P < 0.05 or 0.01). In ACO group, sputum MPO level was positively correlated with sputum neutrophil ratio (r=0.8358, P < 0.01) but was not correlated with CAT score or FEV1 (P> 0.05); sputum ECP level was positively correlated with sputum eosinophil ratio (r=0.4666, P < 0.05) and was inversely correlated with ACT score (r=-0.4966, P < 0.05) and FEV1 (r=-0.4610, P < 0.05). Both neutrophilic and eosinophilic inflammations occur in the airway of patients with ACO, and their sputum ECP level is negatively correlated with asthma control and obstructive airflow limitation.

Absence of airway inflammation in a large proportion of adolescents with asthma.

Neutrophilic inflammation has been implicated in non-eosinophilic asthma (NEA) in adults, but little is known about NEA in children/adolescents. We assessed clinical and inflammatory characteristics of NEA in adolescent asthma. Airway inflammation, sputum endotoxin, airway hyper-reactivity, atopy and lung function were assessed in 77 adolescents with asthma and 68 without asthma (12-17 years). Asthma was identified on the basis of wheeze and asthma history. The proportion of NEA (sputum eosinophils <2.5%) was 54%. In this group, atopy, sputum neutrophil, eosinophil, eosinophil cationic protein (ECP), endotoxin, neutrophil elastase and IL-8 levels were not different from those without asthma. In contrast, eosinophilic asthma (EA) was associated with atopy and sputum ECP and IL-8. The majority of NEA had no evidence of inflammation; only 14% had neutrophilia (≥61% neutrophils), compared with 11% of EA, and 15% of those without asthma. Small differences in FEV1 (NS) were found between EA and NEA, but symptom prevalence and severity was not different (63% of EA and 52% of NEA were classified moderate to severe). NEA is common in adolescent asthma and has similar clinical characteristics as EA. Neutrophils do not appear to play a role in NEA in adolescents, and underlying mechanisms may not involve airway inflammation.

P45 Sputum And Nasal Markers Of Inflammation In Severe Asthma - A Pilot Study

Introduction and objectives The Manchester Severe Asthma Team has successfully been using sputum eosinophil monitoring for several years to help tailor steroid medication. Whilst very useful for patients able to produce a sputum sample, some patients cannot produce a sample. As a result we looked at developing an alternative method of monitoring using nasal lavage samples to study the intra-individual changes in inflammation in severe asthma. Methods Patients requiring sputum monitoring as part of their clinical management were invited to take part in this pilot and to provide an additional nasal lavage sample obtained using an olive method. Participants were clear of infection at time of sampling. Sputum was either spontaneous or induced using the traditional 3%-4%-5% nebulised sodium chloride procedure. ECP (Eosinophil Cationic Protein) was measured in sputum and nasal supernatants using a commercial ELISA kit (Mesacup, MBL). Differential cell count (DCC) was attempted for both sputum and nasal sample types. Results This abstract show the results obtained for the first 32 consecutive patients. Our patient population is described in Table 1, 69% female, 69% atopic (as defined by positive RAST of elevated total IgE), and 50% were non-smokers, 7.6 current smokers and 42.4% ex-smokers. No patient was immunosuppressed or on IM Triamcinolone. ECP levels were as follows: Sputum: median 2650 (min:20.76–28603 ng/ml), 100% of samples had detectable levels. Nasal lavage: 0(0–7.6), 20%. DCC were as follows: Sputum: 38% patients were eosinophil positive (as defined by >3%), Nasal lavage: no eosinophil was detected, 38.5% of samples had a DCC but interpretation was hindered by low cell yield. Sputum DCC/ECP did not correlate significantly with nasal ECP (Pearson R=0.168, p = 0.374 and R=-0.048, p = 0.807 respectively). Nasal DCC data could not be computed as no patient was found to be eosinophil positive. Sputum DTT and sputum ECP correlated significantly (Pearson R=0.607, p = 0.001) as reported in the literature. Conclusions At this stage of our pilot, intermediate data analysis shows that nasal sampling does not appear to be a successful alternative to sputum monitoring in severe asthma.

Effects of regular treatment with combination of salmeterol/fluticasone propionate and salmeterol alone in cough variant asthma

Objective: Cough variant asthma (CVA) is an important cause of chronic cough, and pathophysiological features of the disease appear to be similar to typical asthma. Because CVA is recognized as a precursor of asthma, early intervention with long-term anti-inflammatory agents may be recommended. However, the role of combination therapy with inhaled corticosteroid and β2-agonist in the treatment of CVA has not been elucidated. To evaluate the effectiveness of the combination therapy, we investigated the clinical impact of regular treatment with salmeterol/fliticasone propionate combination (SFC) and inhaled salmeterol (SAL) alone in patients with CVA. Methods: The study was a randomized, controlled, parallel-group multi-center trial. Forty-three CVA patients were assigned to SFC (50/100 µg once daily) or SAL (50 µg twice daily) for 12 weeks. Then, these medications were stopped for the next 24 weeks. Main outcome measures were cough symptoms, pulmonary function and airway inflammation. Results: Treatment with each of SFC and SAL significantly decreased cough scores and increased FEV1 and PEF, where the efficacy was more pronounced with SFC than SAL. SFC also decreased sputum eosinophil counts and eosinophil cationic protein contents, whereas SAL had no effect. After discontinuation of the treatment, cough scores increased, pulmonary function and eosinophilic airway inflammation were aggravated and returned to the baseline levels. Conclusions: Maintenance therapy with SFC provides further improvements in cough symptoms, pulmonary function and airway inflammation, and discontinuation of the therapy causes worsening of the disease, indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with CVA.

Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis. METHODS: We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV1-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV1. RESULTS: The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (↓8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (↓83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (↓267.60 µg/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV1 (↑8.09%; 95% CI: 5.35-10.83; p < 0.001). CONCLUSIONS: In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV1.

Investigating the spill-over hypothesis: Analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma

Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis.Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables.Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥−0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin.In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.

CCL11 as a potential diagnostic marker for asthma?

Objective: Asthma is an inflammatory airway disease characterized by airway eosinophilia, in which CCL11 (eotaxin) plays a crucial role. The aim of study is to determine the elevation of CCL11 levels in bronchoalveolar lavage fluid (BALF), blood, exhaled breath condensate (EBC) and sputum in asthma patients and to identify which medium yields the most significant change in CCL11 level. Methods: The databases of PubMed, Embase and Cochrane Centre Register of Controlled Trials were systematically searched from inception to September 2013. Controlled clinical trials that focused on CCL11 concentrations in asthma patients and controls, and their correlations with other asthma indicators were obtained. Data were analysed using Stata 12.0. Results: Thirty studies were included in this investigation. CCL11 levels in blood, EBC and sputum were significantly higher in asthma patients than in healthy subjects. Sputum CCL11 concentrations were significantly elevated in unstable asthma patients versus stable asthma patients and in uncontrolled asthma patients versus partially controlled asthma patients. CCL11 levels in sputum and blood were negatively correlated with the lung function as measured by FEV1% predicted, and were positively correlated with BALF, EBC and sputum eosinophil counts. Similarly, CCL11 concentrations were positively correlated with eosinophil cationic protein in EBC, blood and sputum as well as with interleukin-5 in sputum and fractional exhaled nitric oxide in EBC. Steroid treatment had no significant effect on CCL11 levels. Conclusions: CCL11 is a potentially useful biomarker for the diagnosis and assessment of asthma severity and control, especially in sputum. CCL11 is crucial in eosinophil chemoattraction and activation in asthma pathogenesis. Further studies using anti-CCL11 approaches are needed to confirm a role for CCL11 in asthma pathogenesis particularly in patients with more severe disease.

Exhaled nitric oxide predicts eosinophilic airway inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation may represent a unique phenotype, possibly with shared features of COPD and asthma. The role of exhaled nitric oxide (eNO) in identifying COPD patients with sputum eosinophilia was examined in this study. Ninety COPD patients without past medical history of asthma or allergic diseases were prospectively enrolled, and their eNO, lung function, and cellular profile of induced sputum were measured. Eosinophil cationic protein and IgE in sputum and venous blood also were determined. Subjects with and without sputum eosinophilia (>3 %) were compared. The role of eNO in the prediction of sputum eosinophilia was assessed in a logistic regression model. Patients with sputum eosinophilia had significantly higher levels of eNO (29 vs. 18 ppb, p = 0.01) than those without. The difference in serum total IgE (168 vs. 84.9 IU/ml, p = 0.057) and percentages of positive allergen test results (48.3 vs. 29.5 %, p = 0.082) showed a trend toward significance. The sputum eosinophil level was significantly correlated to the eNO level (r = 0.485, p < 0.001). The eNO level at the cutoff of 23.5 ppb had the maximum sum of sensitivity (62.1 %) and specificity (70.5 %). The unadjusted and adjusted odds ratios of a higher eNO level (>23.5 ppb) in the prediction of sputum eosinophilia were 3.909 (confidence interval (CI) 1.542-9.91, p = 0.004) and 4.329 (CI 1.306-14.356, p = 0.017), respectively. eNO is a good marker to identify COPD patients with eosinophilic airway inflammation.

Are sputum eosinophil cationic protein and eosinophils differently associated with clinical and functional findings of asthma?

Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation. To assess whether sputum eosinophils and ECP were differently related to functional and clinical parameters of asthma in a large number of steroid-naïve asthmatic patients, taking into account several potential determinants of activity and chronicity of asthma. One hundred and twenty-nine patients with mild-moderate asthma were studied. Sputum was induced by hypertonic saline inhalation and processed using the whole sample method. Sputum eosinophils and ECP significantly correlated with each other (r=0.41, P<0.001). When patients were grouped on the basis of high/low sputum eosinophils and high/low sputum ECP levels, significant differences were observed among groups, with patients with high sputum eosinophils and ECP showing the greatest asthma severity. In the overall sample, disease duration inversely correlated with sputum eosinophils, whereas FEV1 and peak expiratory flow (PEF) inversely correlated with sputum ECP. Rescue β2 -agonist use and total symptom score positively correlated with both eosinophil counts and sputum ECP. Stepwise regression analysis showed that symptom score and disease duration accounted for 17.6% of sputum eosinophil variance, whereas symptom score and FEV1 accounted for 14.7% of sputum ECP variance. Both sputum eosinophils and ECP are weakly related to clinical markers of asthma severity. However, ECP was more closely related to lung function parameters than eosinophil counts.

Association between Eosinophilic Airway Inflammation and Persistent Airflow Limitation

Objective. We aimed to evaluate the association between eosinophilic inflammation in induced sputum and pulmonary function and persistent airflow limitation in children. Methods. A total of 92 asthmatic children and 72 controls were enrolled in this study. Eosinophil count (%) and eosinophil cationic protein (ECP) levels were measured in induced sputum. We performed spirometry and a methacholine challenge test, and measured total eosinophil count, total serum IgE, and serum ECP in all subjects. Results. Asthmatic children had significantly higher levels of sputum eosinophils (9% vs. 0%; P < 0.001) and sputum ECP (2.3 ± 0.7 vs. 1.6 ± 0.6 log µg/L, p < .001) than controls. Sputum ECP levels showed a significant negative correlation with post-bronchodilator (post-BD) FEV1 (r = –0.307; p = .001) and post-BD FEV1/FVC (r = –0.286; p = .002), whereas sputum eosinophils showed no correlation with post-BD FEV1 and post-BD FEV1/FVC. However, no significant differences in sputum ECP and sputum eosinophil counts were observed in asthmatic children with and without persistent airflow limitation. Conclusions. Our findings suggest that sputum eosinophilic inflammation, especially ECP, is associated with pulmonary function and persistent airflow limitation, which is manifested by low post-BD FEV1/FVC.

The Usefulness of Job Relocation and Serum Eosinophil Cationic Protein in Baker's Asthma

Background: Although the most widely recommended treatment for occupational asthma is to completely avoid the causative agents, job relocation within the same company is often substituted for a complete career change. However, there is not much data on the efficacy of job relocation within the workplace and appropriate follow-up parameters. We investigated baker's asthma patients to validate the efficacy of job relocation and follow-up markers. Methods: Twelve bakery plant workers diagnosed with baker's asthma were enrolled in the study. Asthma-related symptoms and methacholine provocation test were followed up 6 months after a job relocation. Skin prick test and ELISA to detect wheat flour-specific IgE and eosinophil cationic protein (ECP) in sputum and serum were also followed up to evaluate the status of allergic inflammation. Results: After a 6-month job relocation, all 12 workers showed an improvement in symptoms, and airway hyperresponsiveness to methacholine was negatively converted in 9 of them. There were no significant differences in skin reactivity and serum flour-specific IgE levels before and after the relocation. While sputum ECP levels did not show a significant difference (338.3 ± 93.0 μg/l vs. 175.0 ± 78.9 μg/l, p = 0.118), there was a remarkable difference in serum ECP levels before and after the relocation (12.2 ± 3.0 μg/l vs. 2.8 ± 3.1 μg/l, p = 0.004). Conclusions: Job relocation was effective in managing baker's asthma. Serum ECP level was a useful follow-up marker of baker's asthma.

Salt chamber treatment is ineffective in treating eosinophilic inflammation in asthma

We have shown that salt chamber treatment reduces airway hyper-responsiveness as an add-on therapy in adult asthmatics on inhaled corticosteroids. We assessed whether this effect is due to the suppression of eosinophilic airway inflammation. Thirty-nine adult asthmatics on inhaled corticosteroids were randomized to receive active salt chamber treatment with low-salt treatment 6.6mg/m(3) (n=14), high-salt treatment 10.8mg/m(3) (n=15) or placebo 0.3mg/m(3) (n=10) 10 times in a 2weeks' period in a double-blind manner. The level of induced sputum eosinophilic cationic protein μg/l, was 3070 before and 4651 after the low-salt treatment period, on average. In the high-salt treatment group, it was 12192μg/l vs 11803 and in the placebo group 3942 vs 4144, respectively. Salt chamber treatment had no effect on sputum eosinophil or neutrophil cell numbers. The reduction in hyper-responsiveness observed in the previous study is probably not due to the effect on eosinophilic inflammation.

Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects

BackgroundPhosphodiesterase 4 (PDE4) inhibitors increase intracellular cyclic adenosine monophosphate (cAMP), leading to regulation of inflammatory cell functions. Roflumilast is a potent and targeted PDE4 inhibitor. The objective of this study was to evaluate the effects of roflumilast on bronchoconstriction, airway hyperresponsiveness (AHR), and airway inflammation in mild asthmatic patients undergoing allergen inhalation challenge.Methods25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15.ResultsRoflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen.ConclusionsThis study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR.Trial RegistrationClinicalTrials.gov: NCT01365533

Level of Eosinophil Cationic Protein in Sputum of Chemical Warfare Victims

Objective(s) Considering fair response to inhaled corticosteroids and reports of severe air way hyper responsiveness in chemical warfare victims (CWV), a role for eosinophilic inflammation (i.e. asthma) was postulated. The objective of this study was to determine the presence of eosinophilic inflammation in CWV by evaluation of Sputum cellularity and eosinophil cationic protein (ECP). Materials and Methods Forty CWV and 15 control subjects entered this cross sectional study. Demographic data, dyspnea severity scale, spirometry results and 6 min walk test were determined. Sputum was collected with inducing by nebulizing hypertonic saline and analyzed for total inflammatory cell count, the cellular differential count and ECP level. Control group was normal volunteers with PC20 more than 8 mg/ml. Results Mean±SD of eosinophil percentage (11.7±11.1%) and ECP level in sputum of CWV (46.1±19.5 ng/ml) were significantly more than control group. Regression analysis showed significant correlation between ECP level and percentage of eosinophils in sputum (r= +0.43, P< 0.01). ECP level of CWV subjects with obstructive pattern did not show any significant difference from CWV with normal spirometry. ECP level in CWV subjects who revealed more than 12% improvement in forced expiratory volume in one second (FEV1) was significantly higher than CWV who had improvement less than 12% (P= 0.01). BO and asthma as final clinical diagnosis of CWV did not show any significant difference of sputum ECP. Conclusion Bronchial inflammation in different types of pulmonary complication of CWV is eosinophil dependent. ECP level of sputum in CWV could guide physician to select CWV who would respond to corticosteroids.

Increased levels of osteopontin in sputum supernatant in severe refractory asthma

BackgroundOsteopontin (OPN) is a glycoprotein that has been associated with inflammation and fibrosis. Severe refractory asthma (SRA) is characterised by an intense inflammatory and remodelling process. The aim of this...

The roles of a Th2 cytokine and CC chemokine in children with stable asthma: Potential implication in eosinophil degranulation

Th2 cytokine IL-5 and CC chemokine eotaxin are thought to be key regulators of eosinophils in bronchial asthma. However, their involvement in children with stable asthma (SA) has not been determined. We investigated the roles of IL-5 and eotaxin in eosinophil degranulation in children with SA. Induced sputum was obtained from 30 SA, 21 allergic rhinitis (AR), and 22 non-atopic healthy control (HC) children. We measured sputum levels of IL-5, eotaxin, and eosinophil indices [percentage eosinophils, eosinophil-derived neurotoxin (EDN), and eosinophil-cationic protein (ECP)]. We also examined correlations of IL-5 and eotaxin with eosinophil indices. Sputum percentage eosinophils and EDN and ECP levels were significantly higher in the SA group than in the HC group, while only the sputum EDN and ECP levels were significantly higher in the AR group than in the HC group. Unexpectedly, sputum levels of IL-5 were not significantly different among the three groups; however, the levels of eotaxin were higher in the SA group when compared to the HC group. No significant correlations were found between IL-5 and percentage eosinophils, EDN, or ECP levels; in contrast, eotaxin levels correlated significantly with percentage eosinophils (R(s) = 0.638; p = 0.0001), EDN (R(s) = 0.522; p = 0.003), and ECP levels (R(s) = 0.630 and p = 0.0002). The elevated levels and good correlations of eotaxin with sputum eosinophil indices, and no elevation or correlation of IL-5 with these indices, suggest that CC chemokine eotaxin may play a more important role in eosinophil degranulation in children with SA.

Increased B cell-activating factor (BAFF) level in the sputum of children with asthma

PurposeB cell-activating factor (BAFF) is a tumor-necrosis factor (TNF) superfamily member best known for its role in the survival and maturation of B cells. BAFF activity is observed in naïve cells as well as in effector/memory T cells. We aimed to explore whether BAFF in sputum is expressed at elevated levels in asthmatic airways and associated with eosinophilic inflammation, pulmonary function, and bronchial hyperresponsiveness in children.MethodsOne hundred and fifty-four asthmatic children and 98 healthy children were enrolled in the study. Sputum supernatants were collected and sputum BAFF and eosinophil cationic protein (ECP) levels were measured. We performed pulmonary function tests and methacholine challenge tests, while measuring total eosinophil count, total serum IgE, and serum ECP in all subjects.ResultsAsthmatic children had significantly higher levels of BAFF in induced sputum [26.50 (10.50-100.27) pg/mL] compared to healthy children [18.32 (7.68-44.63) pg/mL; P=0.011]. Sputum BAFF positively correlated with sputum eosinophils (γ=0.406, P<0.001) and sputum ECP (γ=0.789, P<0.001). Significant negative correlations were found between sputum BAFF and FEV1 (γ=-0.291, P<0.001) or post-bronchodilator FEV1 (γ=-0.334, P<0.001), whereas nonsignificant correlations were found between sputum BAFF and bronchial hyperresponsiveness, serum eosinophil count, and serum ECP.ConclusionThese findings suggest that BAFF may play a role in childhood asthma, and BAFF levels in sputum could be a supportive marker that represents airway inflammation, especially eosinophilic inflammation.