Leukotriene B4 in exhaled breath condensate and sputum supernatant in patients with COPD and asthma

STUDY OBJECTIVES: Some patients with COPD present with significant reversibility of airflow limitation after receiving bronchodilation therapy. Leukotriene B(4) (LTB(4)) has been implicated in the pathophysiology of both COPD and asthma. We tested the hypothesis that COPD patients with airflow reversibility and asthmatic patients who smoke might have similar levels of LTB(4) in exhaled breath condensate (EBC) and sputum supernatant. The repeatability and stability of LTB(4) measurements were additionally studied. DESIGN: Prospective, cross-sectional study. PATIENTS OR PARTICIPANTS: We studied 30 patients with COPD (15 smokers [FEV(1), 56% predicted; SD, 6% predicted]; 15 patients with significant reversibility in airway obstruction after bronchodilation [FEV(1), 14% predicted; SD, 2% predicted]). Fifteen asthmatic patients who smoked, with similar FEV(1) and reversibility were also studied. Ten healthy smokers served as control subjects. SETTING: A hospital research laboratory. INTERVENTIONS: Spirometry and reversibility testing were performed on the first visit. On the following day, EBC was collected for the measurement of LTB(4), and induced sputum was collected for differential cell counts and LTB(4) measurement in the sputum supernatant. MEASUREMENTS AND RESULTS: LTB(4) levels in EBC [mean (SD)] were increased in COPD patients (mean, 86.7 pg/mL; SD, 19 pg/mL) and asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL) compared to control subjects (mean, 32.3 pg/mL; SD, 10 pg/mL; p < 0.0001 for both groups). COPD patients with airflow reversibility (mean, 99.8 pg/mL; SD, 12 pg/mL) had values similar to those of asthmatic patients (mean, 97.5 pg/mL; SD, 15 pg/mL; p = 0.2) and higher than those of COPD patients without airflow reversibility (mean, 73.7 pg/mL; SD, 17 pg/mL; p = 0.002). Similar results were observed in the sputum supernatant. Measurements of LTB(4) in EBC and sputum were repeatable on two consecutive days, but measurements in the frozen samples of EBC and sputum were not stable after 3 weeks. CONCLUSIONS: Patients with asthma and reversible COPD presented with higher LTB(4) values compared to patients with nonreversible COPD and healthy smokers. This difference may be mainly attributed to the presence of reversibility in airway obstruction, probably as part of a common underlying inflammatory process.     

Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.     

诱导痰嗜酸粒细胞检测在支气管哮喘-慢性阻塞性肺疾病重叠综合征中的应用

目的：本研究旨在探讨支气管哮喘(简称哮喘)-慢性阻塞性肺疾病重叠综合征(ACOS)患者诱导痰嗜酸粒细胞水平及其与吸入糖皮质激素(inhaled corticosteroid,ICS)治疗效果的关系,为 ACOS 的诊断及治疗提供依据。方法选择2012年6月至2014年6月广东省江门市中心医院诊治的稳定期 ACOS 患者60例(ACOS 组),同期在广东省江门市中心医院诊治的无合并哮喘的稳定期 COPD 患者60例(单纯 COPD 组)。所有受试者均接受单纯 ICS 治疗,治疗前后进行肺通气功能检查,支气管舒张试验,动脉血气分析,血嗜酸粒细胞计数及诱导痰中炎性细胞的分析。结果外周血嗜酸粒细胞计数和诱导痰嗜酸粒细胞计数 ACOS 组均显著高于单纯 COPD 组。ROC 曲线分析显示以2.5%为截点,诱导痰嗜酸粒细胞计数诊断 ACOS 的敏感性为82.4%,特异性为84.8%。ICS 治疗后的 FEV1值增幅 ACOS 组亦显著高于单纯 COPD 组。ACOS 组 ICS 治疗后的 FEV1值增幅与诱导痰嗜酸粒细胞计数呈显著正相关。结论诱导痰嗜酸粒细胞检测可以作为 ACOS 和 COPD 鉴别诊断的指标之一,且能较好的预测 ACOS 对 ICS 治疗的反应性。     

诱导痰炎性标志物对支气管哮喘和慢性阻塞性肺疾病稳定期的鉴别诊断价值

目的 探讨诱导痰中嗜酸细胞（Eos）和嗜酸细胞阳离子蛋白（ECP）水平对支气管哮喘与慢性阻塞性肺疾病（COPD）稳定期的鉴别诊断价值.方法 选择支气管哮喘患者62例,检测肺功能并分别采用瑞氏染色及荧光免疫法检测高渗盐水诱导痰中Eos数量和ECP水平.选择51例慢性阻塞性肺疾病稳定期患者和30名健康人作为对照.结果 支气管哮喘患者诱导痰中Eos数量[（14.4±6.3）%]和ECP水平[（413±199）μg/L]显著高于COPD稳定期组[（3.2±1.5）%、（54±35）μg/L,P〈0.01]和对照组[（1.1±0.6）%、（46±23）μg/L,P〈0.01].以诱导痰中Eos≥7%和ECP≥100μg/L作为与稳定期COPD鉴别的标准,诊断哮喘的敏感性分别为79.3%和81.2%,特异性分别为81.0%和83.0%.联合检测两者的敏感性和特异性分别为85.2%和86.0%.结论 检测诱导痰Eos和ECP水平有助于支气管哮喘与COPD稳定期的鉴别.     

Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease

To determine whether patients with fixed airflow obstruction have distinct pathologic and functional characteristics depending on a history of either asthma or chronic obstructive pulmonary disease (COPD), we characterized 46 consecutive outpatients presenting with fixed airflow obstruction by clinical history, pulmonary function tests, exhaled nitric oxide, sputum analysis, bronchoalveolar lavage, bronchial biopsy, and high-resolution computed tomography chest scans. Subjects with a history of COPD (n = 27) and subjects with a history of asthma (n = 19) had a similar degree of fixed airflow obstruction (FEV1: 56 +/- 2 versus 56 +/- 3% predicted) and airway hyperresponsiveness (PC20FEV1: 2.81 [3.1] versus 1.17 [3.3]). Subjects with a history of asthma had significantly more eosinophils in peripheral blood, sputum, bronchoalveolar lavage, and airway mucosa; fewer neutrophils in sputum and bronchoalveolar lavage fluid; a higher CD4+/CD8+ ratio of T cells infiltrating the airway mucosa; and a thicker reticular layer of the epithelial basement membrane. They also had significantly lower residual volume, higher diffusing capacity, higher exhaled nitric oxide, lower high-resolution computed tomography scan emphysema score, and greater reversibility to bronchodilator and steroids. In conclusion, despite similar fixed airflow obstruction, subjects with a history of asthma have distinct characteristics compared with subjects with a history of COPD and should be properly identified and treated.     

诱导痰炎性标志物检测在判定哮喘严重程度和鉴别诊断中的应用

目的探讨哮喘患者诱导痰中嗜酸性粒细胞(Eos)和嗜酸细胞阳离子蛋白(ECP)与其哮喘严重程度的关系及鉴别诊断价值。方法选择武汉大学人民医院2002-07~2004-06的门诊哮喘患者59例,检测其肺功能并分别采用瑞氏染色及荧光免疫法检测高渗盐水诱导痰中Eos数量和ECP质量浓度。选择同期20例慢性阻塞性肺疾病患者和10名健康人作为对照。结果哮喘患者诱导痰中Eos数量与患者第1秒用力呼气容积/用力肺活量(FEV1%)呈显著负相关(r=-0·65,P<0·01);ECP质量浓度与患者FEV1%呈显著负相关(r=-0·59,P<0·01)。随病情加重哮喘患者诱导痰中Eos数量和ECP质量浓度逐渐升高,且轻度、中度和重度患者之间比较差异有统计学意义(P<0·05)。哮喘患者诱导痰中Eos数量和ECP质量浓度显著高于慢性阻塞性肺疾病组和健康组(P<0·01)。结论诱导痰中Eos和ECP质量浓度可了解哮喘的严重程度,并有助于与慢性阻塞性肺疾病的鉴别。     

Characteristics of airway inflammation and bronchodilator reversibility in COPD: a potential guide to treatment

STUDY OBJECTIVES: The management of stable patients with COPD depends on the severity of symptoms and airflow limitation. Regarding inflammation, corticosteroids are the only medications that are recommended for use, and only under restricted circumstances. Corticosteroids tend to undertreat or overtreat patients with COPD when only clinical manifestations and the findings of simple spirometry are considered. Accordingly, our aim was to survey the characteristics of airway inflammation in stable COPD patients, and to assess the interrelations among inflammatory cells, inflammatory mediators, bronchodilator reversibility, and pulmonary function. Factors related to airway inflammation and bronchodilator reversibility may be important in the management of stable COPD patients. METHODS: A total of 88 stable patients with smoking-related COPD were recruited into the study. All patients were steroid-free, and had been treated with theophylline, oral beta(2)-agonist agents, anticholinergic agents, and possibly mucolytic agents. Bronchodilator tests and sputum induction were performed to evaluate bronchodilator reversibility, and numbers of inflammatory cells and mediators (eg, interleukin [IL]-8, eotaxin, and regulated on activation, normal T cells expressed and secreted [RANTES]). RESULTS: Thirty-one of 48 patients (64.6%) who had bronchodilator reversibility, and 19 of 40 patients (47.5%) without bronchodilator reversibility had sputum eosinophilia (median, 8.0% and 7.0%, respectively). FEV(1) showed a significant inverse correlation with the number of sputum neutrophils. The correlation coefficient for postbronchodilator FEV(1) vs the percentage of neutrophils in patients with nonreversible COPD was higher than that in those with reversible COPD. The levels of IL-8 were closely associated with the percentage of neutrophils. The sputum concentrations of IL-8 and albumin were significantly higher in patients with nonreversible COPD than in those with reversible COPD. A significant inverse correlation was found between bronchodilator response (ie, DeltaFEV(1) and DeltaFVC) and prebronchodilator FEV(1). CONCLUSIONS: Eosinophilic inflammation may play a substantial role in COPD, while neutrophils and IL-8 may have a great influence on nonreversible obstructive airways. The assessment of airway inflammation and bronchodilator responses can help the selection of specific therapies and the prediction of clinical outcomes for COPD patients.     

Long-term effects of budesonide on inflammatory status in COPD

A beneficial effect of long-term corticosteroid treatment in patients with COPD may be linked to suppressing inflammation, in particular neutrophilic inflammation. Effects on neutrophilic and eosinophilic inflammation and on lung function of long-term inhaled budesonide treatment (800 microg daily, 6 months, double-blind, randomised, cross-over versus placebo) were studied and compared to the effects of 3 weeks oral prednisolone (30 mg daily) in 19 patients with COPD (mean age 63 y, FEV(1) 65% of predicted). Neither treatment influenced neutrophilic inflammation. Inhaled budesonide compared to placebo significantly reduced sputum % eosinophils at 3 months (-42%, p = 0.036), but not significantly at 6 months (-31%, p = 0.78). Eosinophil count per g sputum was decreased with 30% at 3 months (p = 0.09) and with 9% at 6 months (p = 0.78). FEV(1) was slightly higher after 6 months budesonide (+2.5% predicted, p = 0.09). Prednisolone significantly reduced sputum % eosinophils (-87%, p = 0.007), but did not affect eosinophil count per g sputum and did not improve FEV(1) (-0.6% predicted, p = 0.40). A higher baseline FEV(1) (%) correlated with effects of budesonide on FEV(1) (p < 0.001), effects on sputum interleukin-8 and eosinophil cationic protein (both p < 0.05) and tended to correlate with effects on sputum % eosinophils (p = 0.056). Baseline inflammatory data and effects of prednisolone did not correlate with effects of budesonide. Effects of inhaled budesonide in COPD are not restricted to patients with severe disease and may be linked to a suppression of eosinophilic inflammation. Investigating effects of prednisolone has no predictive value for long-term treatment.     

Inhaled Fluticasone and Salmeterol Suppress Eosinophilic Airway Inflammation in Chronic Obstructive Pulmonary Disease: Relations with Lung Function and Bronchodilator Reversibility

The aim of this study was to determine whether combined inhaled corticosteroids and long-acting β₂ agonists can suppress eosinophilic inflammation in chronic dostructive plumonary disease (COPD) and to investigate the association between the level of eosinophilia and the degree of bronchodilator reversibility. Sixty-two patients with stable COPD (forced expiratory volume in 1 [FEV₁] of 30%–70% predicted before bronchodilation) were enrolled from our outpatient clinic. Patients received inhaled fluticasone (100 μg)/salmeterol (50 μg) twice daily for two months. Lung function measurements, bronchodilator tests, and sputum induction were performed. The number of inflammatory cells and mediators, including interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and eosinophilic cationic protein (ECP), were measured. Treatment with inhaled fluticasone and salmeterol significantly suppressed eosinophilic inflammation in COPD patients with sputum eosinophilia (mean 8.9% ± 2.0% vs. 1.6% ± 0.5%, p = 0.003), but insignificant differences in FEV₁ and FVC between patients with and without eosinophilia suggested that suppression of eosinophilic inflammation had no effect on FEV₁ or FVC. Reduction in the percentage of eosinophils was significantly correlated with decreased levels of ECP (r = 0.48, p < 0.001). Levels of neutrophils, IL-8, and TNF-α were not affected. Sputum eosinophilia was not related to the degree of bronchodilator reversibility. The degree of bronchodilator reversibility did not predict the increase in FEV₁ and FVC after treatment with inhaled corticosteroids/long-acting β₂ agonists. Suppression of eosinophilic inflammation and bronchodilator responsiveness indices were not correlated with clinical outcomes in COPD patients treated with inhaled corticosteroids/long-acting β₂ agonists. Diahn-Warng Perng and Cheng-Che Wu contributed equally to this work.     

Comparison of Sputum and Serum Eosinophil Cationic Protein (ECP) Levels in Nonatopic Asthma and Chronic Obstructive Pulmonary Disease

The aim of the present study was to investigate whether sputum eosinophil cationic protein (ECP) concentrations could be a useful marker in the differential diagnosis between intrinsic asthma and chronic obstructive pulmonary disease (COPD). For this purpose total blood eosinophil counts were obtained and concentrations of serum and sputum ECP from 10 nonatopic asthmatics with a mild attack and 9 COPD patients with acute exacerbation were measured by radioimmunoassay. Mean serum ECP concentration was 54.3 ± 23.0 g/L in the asthmatic group and 83.3 ± 79.2 g/L in the COPD group (p: n.s.). In the group of asthmatics mean sputum ECP level was 984.5 ± 1245.5 mg/L/g sputum and in the COPD group it was 417.5 ± 363.5 mg/L/g sputum. There was no significant difference in sputum ECP levels between patients with asthma and COPD. We conclude that neither sputum nor serum ECP levels are useful markers in differential diagnosis of asthma attack and acute exacerbation of COPD.     

Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiologic, and pathologic presentation. We aimed to evaluate whether airflow limitation, airway responsiveness, and airway inflammation are separate entities underlying the pathophysiology of COPD by using factor analysis. A total of 114 patients (99 males/15 females, age 62 +/- 8 years, 42 pack-years smoking, no inhaled or oral steroids > 6 months) with irreversible airflow limitation (postbronchodilator FEV(1) 63 +/- 9% predicted, FEV(1)/inspiratory vital capacity [IVC] 48 +/- 9%) and symptoms of chronic bronchitis or dyspnea were studied in a cross-sectional design. Postbronchodilator FEV(1) and FEV(1)/IVC, reversibility to inhaled beta(2)-agonists, diffusing capacity, provocative concentration of methacholine required to produce a 20% drop in FEV(1), total serum IgE, exhaled nitric oxide, and induced sputum cell counts (% eosinophils, % neutrophils) were collected. Factor analysis yielded 4 separate factors that accounted for 63.6% of the total variance. Factor 1 was comprised of FEV(1), FEV(1)/IVC, and residual volume/total lung capacity. Factor 2 included reversibility, IgE, provocative concentration of methacholine required to produce a 20% drop in FEV(1,) and diffusing capacity. Factor 3 contained exhaled nitric oxide and factor 4 included sputum % neutrophils and % eosinophils. We conclude that airflow limitation, airway inflammation, and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD.     

Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation

BACKGROUND: Interest in airways inflammatory disease has increasingly focused on innate immunity. We investigated several components of innate immunity in induced sputum of patients with cystic fibrosis (CF), COPD, and asthma, and healthy control subjects. METHODS: Twenty eight patients with mild CF lung disease (age > or = 12 years; FEV1, 74 +/- 3% predicted [mean +/- SE]), 74 adults with COPD (FEV1, 55 +/- 2% of predicted), 34 adults with persistent asthma (FEV1, 66 +/- 2% of predicted), and 44 adult control subjects (FEV1, 85 +/- 1% of predicted) were studied while in stable clinical condition. Levels of sputum interleukin (IL)-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, human cationic antimicrobial protein 18 (CAP18), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 were determined. Cell sources were investigated by flow cytometry and immunohistochemistry. Spirometry was performed prior to sputum induction. RESULTS: CF patient sputum showed greatest increase in IL-8 compared to that of patients with COPD and asthma (which were also greater than control subjects), and elevated levels of TNF-alpha and IL-10 compared to other groups. There were no differences in IFN-gamma. CAP18 levels were elevated in CF and COPD patients compared to control subjects, while asthma patients had reduced CAP18 levels. uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients, while PAI-1 levels were elevated in all three disease groups. CAP18 localized to neutrophil secondary granules; neutrophils were also sources of IL-8 and PAI-1. CAP18 and PAI-1 negatively correlated with pulmonary function. CONCLUSION: Induced-sputum innate immune factor levels discriminate inflammatory changes in CF, COPD, and asthma, suggesting potential roles in pathophysiology and as well as providing disease-specific biomarker patterns.     

Similarity and differences in elderly patients with fixed airflow obstruction by asthma and by chronic obstructive pulmonary disease

BACKGROUND: Epidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD). METHODS: We studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum. RESULTS: The age was not different in patients with COPD (n=28) and asthma (n=21) (70.2+/-3.9 years vs. 69.6+/-3.7 years), also the degree of fixed airflow obstruction was similar (FEV1: 58.3+/-1.5% vs. 59.0+/-1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43+/-0.05x10(-3)microL vs. 0.27+/-0.1x10(-3)microL, P<0.0001), and in induced sputum (5.0% [(p25th and p75th) 5.0-6.0%] vs. 1.0% [(p25th and p75th) 0.01-1.0%]; P<0.0001), as well as serum ECP (18.6+/-4.9ng/mL vs. 7.7+/-4.7ng/mL, P<0.0001) and ECP in the induced sputum (31.6+/-2.9ng/mL vs. 5.6+/-4.9ng/mL, P<0.0001). Finally, in induced sputum the eosinophils EG2+ were higher in patients with asthma than in patients with COPD (40.5 [(p25th and p75th) 39.3-44.3] MFI vs. 3.9 [(p25th and p75th) 0-11.4] MFI, P<0.0001). They also had significantly higher diffusing capacity, and a greater reversibility to steroids, after 14-day course of therapy, whereas the reversibility to 400microg of salbutamol was similar. CONCLUSION: Despite similar fixed airflow obstruction, elderly patients with asthma have distinct characteristics compared with patients with COPD.     

The characteristics of different diagnostic tests in adult mild asthmatic patients: comparison with patients with asthma-like symptoms by gastro-oesophageal reflux

BACKGROUND: Diagnosing asthma cannot be always easy. It is important to consider the validity of the diagnostic tests, and/or how much more commonly they are positive in patients with asthma compared to healthy subjects and, particularly, to patients with asthma-like symptoms. OBJECTIVE: To evaluate the validity of diagnostic tests for asthma, in terms of sensitivity, specificity, positive and negative predictive values, in patients with bronchial asthma compared to patients affected by gastro-oesophageal reflux disease (GERD) with asthma-like symptoms, and healthy control subjects without asthma and gastro-oesophageal reflux (GER). DESIGN: Single-center, cross-sectional, observational study. PATIENTS: We studied 60 patients with mild asthma, 30 patients with GERD and asthma-like symptoms and 25 healthy control subjects. MEASUREMENTS: We measured provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in 1s (MCh PC(20)/FEV(1)), the amplitude percent mean of peak expiratory flow (A%M of PEF), derived from twice-daily readings for >2 weeks, the FEV(1)/forced vital capacity (FEV(1)/FVC) ratio, the eosinophil count in blood and in induced sputum and the serum eosinophil cationic protein (ECP) levels. RESULTS: FEV(1)/FVC ratio, A%M of PEF, blood eosinophils counts and serum ECP levels were less sensitive and specific when the reference population was composed of patients with asthma-like symptoms by GER. While, MCh PC(20)/FEV(1) and induced sputum eosinophils count were the most sensitive (both 90%) and specific (89% and 92%, respectively) tests. CONCLUSION: Our findings demonstrate that MCh PC(20)/FEV(1) and the induced sputum eosinophil count are the most useful objective tests in patients with mild asthma. All patients with asthma presented both an MCh PC(20)/FEV(1) <1500 microg and eosinophils count in the induced sputum >1%.     

Leukotriene E(4) in urine in patients with asthma and COPD--the effect of smoking habit

Leukotriene E(4) (LTE(4)) is implicated in asthma pathophysiology and possibly in chronic obstructive pulmonary disease (COPD) as one of the causes of persistent bronchoconstriction and mucus hypersecretion. Cigarette smoking stimulates cysteinyl leukotrienes (CysLTs) production. We investigated whether LTE(4) is equally increased in asthma and COPD and whether smoking significantly affects LTE(4) levels. Secondary outcomes involved correlations with inflammatory and functional parameters. We studied 40 patients with COPD [20 smokers], 40 asthmatics [20 smokers] and 30 healthy subjects [15 smokers]. Spirometry (FEV(1)% pred., FEV(1)/FVC) was performed, urine was collected for measurement of LTE(4) and creatinine, induced sputum was collected for differential cell counts and serum for ECP. LTE(4)/creatinine levels (pg/mg) [mean (sd)] were increased in asthmatic patients compared to COPD and controls, [125.6(54.5) vs. 54.5(19) vs. 55.9(18.9)pg/mg, respectively, P<0.0001 for asthma]. Smoking significantly affects LTE(4) levels only in asthmatic patients [164 (48) vs. 87 (26.3), P<0.0001 for smokers]. The only significant correlation was between eosinophils in induced sputum and LTE(4)/creatinine levels in asthmatics. In conclusion, patients with asthma presented higher LTE(4) values compared to normals and patients with COPD. Smoking significantly affects LTE(4) values only in asthmatics indicating a different underlying CysLTs inflammatory process in this condition.     

Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity.

This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma. Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12-18 yrs of age, FEV1 65-110% of predicted, on 500-2,000 microg inhaled steroids daily). FEV1 was reversible by 13.3-2.3% pred. After sputum induction, FEV1 was still increased by 9.0+/-2.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4-59.5)% squamous cells, 47.3 (6.8-84.0)% macrophages, 39.0 (4.6-84.8)% neutrophils, 4.8 (1.0-12.4)% lymphocytes, 0.4 (0-10.8)% eosinophils and 3.6 (0-23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03). In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with beta2-agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma.     

Mild exacerbations and eosinophilic inflammation in patients with stable, well-controlled asthma after 1 year of follow-up

OBJECTIVES: To determine the time to exacerbation and probability of a mild exacerbation of asthma, and the impact of eosinophilic inflammation on these parameters in patients with stable, well-controlled asthma. PATIENTS AND METHODS: A cohort of 31 patients with stable, well-controlled asthma receiving inhaled steroid treatment regularly were followed up for 1 year or until a mild exacerbation occurred. Mild exacerbation was defined as symptoms of asthma lasting > 48 h with a fall in peak expiratory flow > 20%. FEV(1), provocative concentration of methacholine causing a 20% fall in FEV(1), eosinophil count, and eosinophilic cationic protein (ECP) levels in blood and in sputum were measured at the first visit and every 2 months. RESULTS: At baseline, the mean (SD) eosinophil count was 0.39 x 10(9)/L (0.21 x 10(9)/L) in blood and 13% (14%) in sputum; ECP was 30 microg/L (28 microg/L) in blood and 75 microg/L (85 microg/L) in sputum. Thirteen subjects experienced a mild exacerbation during the 1-year follow-up period. The mean time to mild exacerbation was 293 days (95% confidence interval [CI], 248 to 337 days), and the cumulative probability of not experiencing a mild exacerbation in 1 year was 49% (95% CI, 39 to 59%). An increased risk of mild exacerbation was associated with blood eosinophil count > 0.4 x 10(9)/L (relative risk 4.5; 95% CI of relative risk, 1.8 to 38.0), blood ECP > 20 microg/L (relative risk, 2.1; 95% CI of relative risk, 1.0 to 9.2), and sputum ECP > 40 microg/L (relative risk, 2.5; 95% CI of relative risk, 1.2 to 11.2), but was unassociated with other variables. CONCLUSIONS: Patient with stable, well-controlled asthma are at risk of mild exacerbation during 1 year of follow-up despite regular inhaled steroid treatment. Eosinophilic inflammation expressed as eosinophil count and ECP is associated with higher risk of mild exacerbation.     

Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children.

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.     

Analysis of sputum cell counts during spontaneous moderate exacerbations of asthma in comparison to the stable phase.

BACKGROUND: Acute airway inflammation is considered to characterize asthma exacerbations, but its specific cellular pattern has not yet been completely evaluated. AIM: To evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations of moderate severity, compared with a stable phase of the disease, and to assess the concordance between changes in pulmonary function and sputum eosinophilia in the period between exacerbation and post exacerbation. METHODS: We compared sputum and blood inflammatory cell counts in 29 asthmatic subjects during a spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell counts measured 4 weeks after the resolution of asthma exacerbation (visit 2). At visit 1, all subjects required an appropriate 1 week treatment with oral corticosteroids. RESULTS: At visit 1, all subjects were able to collect spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist pretreatment. Asthma exacerbation was accompanied by a significant increase in sputum eosinophil percentages compared with levels after exacerbation [25% (1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum eosinophil percentages during exacerbation, and these showed no differences in main clinical findings with respect to subjects with sputum eosinophilia. At visit 2, the stability of asthma was assessed on the basis of PEF, FEV1, symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21 out of 29 subjects. Sputum eosinophil percentages fell significantly between visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum eosinophil percentages were still high in subjects with unstable asthma. In patients who proved to be stable at visit 2, there was a significant correlation between the changes recorded in sputum eosinophil percentages and in FEV1 between the two visits (rho: 0.723, p<0.001). CONCLUSION: Sputum cosinophil but not neutrophil percentages increase in most asthmatic subjects during moderate exacerbation of asthma. Changes in the degree of airway eosinophilic inflammation are related to changes in the severity of airway obstruction during asthma exacerbation.     

慢性阻塞性肺疾病和哮喘患者痰中降钙素基因相关肽的变化

目的 探讨慢性阻塞性肺疾病（ＣＯＰＤ）和支气管哮喘患气道分泌物中,感觉神经肽降钙素基因相关肽（ＣＧＲＰ）释放在气道慢性炎症性疾病发病中的作用。方法 选择稳定期ＣＯＰＤ患１９例,支气管哮喘患１４例,正常对照组１０名,通过面罩吸入超声雾化的４％向张盐水诱导痰液,将获得的诱导痰涂片进行瑞氏－姬姆萨染色计数细胞成分的变化,用放射免疫方法测定诱导痰中ＣＧＲＰ免疫反应性物质（ＣＧＲＰ－ＬＩ）的含量改变,