Long-term observations of the clinical course after step down of corticosteroid inhalation therapy in adult chronic asthmatics: correlation with serum levels of eosinophil cationic protein

BACKGROUND: Symptoms often deteriorate in well-controlled asthmatics after a step down in inhaled beclomethasone dipropionate (iBDP) therapy if the serum concentration of eosinophil cationic protein (sECP) is high. This deterioration is significantly abrogated by pranlukast, a leukotriene receptor antagonist, or by seratrodast, a thromboxane A2 receptor antagonist. However, these results were based on short-term (less than 6 months) observations. METHODS: We studied 35 well-controlled adult asthmatics. We assigned the patients into different groups according to their sECP levels before the step down: (i) group A, sECP < 25 microg/L; (ii) group B, sECP > or = 25 microg/L; and (iii) group C, sECP > or = 25 microg/L but patients treated with pranlukast or seratrodast. We began the study with a step down in iBDP therapy (initial step down), then followed the clinical course of the asthma for 2 years. During the study period, we decreased, increased or maintained the iBDP dose on the basis of the stepwise approach described in the National Institutes of Health guidelines. We monitored the time and frequency of exacerbation and evaluated the iBDP dose required to control the asthma symptoms. RESULTS: The rates of exacerbation after the step down were high in groups A and B. In group A, the conditions were again qualified for the step down in all patients, but this was not the case for most group B patients. From 15 to 21 months after the initial step down, the average dose of iBDP required to control symptoms was significantly higher in group B than in group A patients (P = 0.0127-0.0373). The exacerbation rate in group C after 12 months tended to be lower than in the other two patient groups (P = 0.0743). In group C, the average dose of iBDP from 9 to 24 months after the initial step down was significantly lower than before the step down (P < 0.0001) and was not significantly different from the mean dose of iBDP in groups A or B. CONCLUSIONS: High sECP in well-controlled asthma may indicate the necessity for a higher iBDP dose over a long period than when the sECP concentration is not high. Even if sECP is high, pranlukast or seratrodast help to prevent exacerbation of asthma and enable successful step down in iBDP therapy for at least 2 years thereafter.     

Effects of inhaled fluticasone propionate on CTLA-4-positive CD4+CD25+ cells in induced sputum in mild asthmatics

Background and objective: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects. Methods: Eleven mild, stable asthmatic subjects completed a double-blind, randomized, cross-over, placebo-controlled study to compare the effects of 14 days 200 µg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-β Results: FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-β Conclusions: The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness. Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease.     

Evaluation of switching low-dose inhaled corticosteroid to pranlukast for step-down therapy in well-controlled patients with mild persistent asthma

Objective: Treatment guidelines for asthma recommend step-down therapy for well-controlled asthma patients. However, the precise strategy for step-down therapy has not been well defined. We investigated whether well-controlled patients with mild persistent asthma can tolerate a step-down therapy of either a reduced dose of inhaled corticosteroid (ICS) or a switch to a leukotriene receptor antagonist (LTRA), pranlukast hydrate. Methods: We recruited 40 adult patients with mild persistent asthma who were well-controlled for at least 3 months with a low-dose ICS therapy. The patients were randomly assigned to either an ICS dose reduction or a switch to pranlukast for 6 months. Results: FeNO levels in the pranlukast group were significantly increased over that in the ICS group. There were no significant differences between the two groups for lung function, FOT, at the endpoint. The percentage of patients with controlled asthma was 72.2% in the pranlukast group and 90% in the ICS group. No statistically significant difference between the two groups in the percentages of patients with treatment failure was observed. Conclusions: Patients with mild persistent asthma that is well-controlled by a low dose of ICS can be switched to pranlukast safely for at least 6 months. However, 27.8% of the pranlukast group failed to maintain well-control, and FeNO levels increased with the switch to pranlukast at 6 months. This study was been limited by the small sample size and should therefore be considered preliminary. Further studies are needed to investigate the therapeutic efficacy of LTRA monotherapy as a step-down therapy.     

Induced sputum eosinophils in the assessment of asthma and chronic cough

OBJECTIVE: To evaluate induced sputum eosinophils in asthma and chronic cough. DESIGN: This was an analytical, cross-sectional study set in an ambulatory respiratory clinic. SUBJECTS: Subjects (n=75) referred for evaluation of symptomatic asthma or episodic respiratory symptoms had a clinical assessment, spirometry, hypertonic saline challenge and induced sputum. Two diagnostic groups were identified. The first group comprised subjects with symptomatic asthma and variable airway obstruction (VAO) (n=32). The second group included subjects with episodic respiratory symptoms and no VAO (n=43). RESULTS: The prevalence of eosinophilic bronchitis (eosinophils >2.75%) was greatest in asthma (n=14, 44%), compared to the episodic respiratory symptoms group (n=9, 21%, P = 0.02). Clinical variables did not predict increased eosinophils (P > 0.05). Sputum eosinophils were highest in asthmatics not using inhaled corticosteroids (6.5% vs 0.5%, P = 0.02). Sputum neutrophils were higher in subjects using inhaled corticosteroid (53% vs 25%, P = 0.04). CONCLUSION: Airway inflammation with eosinophilia was common among patients presenting to a respiratory clinic, especially those with asthma who were not using inhaled corticosteroids. Induced sputum also identified eosinophilic bronchitis in those without asthma. It was not possible to detect the presence or absence of airway eosinophilia by routine clinical assessment. The results in this study imply that the assessment of induced sputum eosinophils may be a useful guide to therapy, especially in the assessment of persistent symptoms in asthmatics on corticosteroids, and in the assessment of non-asthmatic subjects with symptoms.     

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.     

支气管哮喘患者不同时期诱导痰及血嗜酸粒细胞水平的观察

目的探讨诱导痰及末梢血嗜酸粒细胞(EOS)比例、诱导痰嗜酸粒细胞阳离子蛋白(ECP)水平在支气管哮喘（简称哮喘）发病不同时期的变化及应用价值。方法检测哮喘发作期40例（发作组）、哮喘缓解期48例（缓解组）、40名正常健康体检者（对照组）的诱导痰及末梢血EOS占白细胞百分比,同时分别测定痰ECP。结果 ①末梢血中EOS比...     

重度哮喘缓解期患者吸入高渗盐水诱导痰的安全性和副反应评价

目的探讨重度哮喘缓解期患者吸人高渗盐水诱导痰前后的肺功能、血氧饱和度和生命征心率和呼吸次数的变化,并评价其安全性及副反应。方法预防性吸人沙丁胺醇气雾剂15分钟后,吸入3%高渗盐水诱导痰。观察30例重度哮喘缓解期患者诱导痰前后最大呼气流量（PEF）、血氧饱和度（SaO2）的改变和生命征心率和呼吸次数的变化。结果诱导痰前后PEF、SaO2、心率（HR）、呼吸频率（RR）等均无显著变化（P〉0.05）。有1例患者轻度气促,发生率为6.66%（1/30）。有12.5%患者出现胸闷,但程度较轻。结论对于重度哮喘缓解期患者,预防性吸人沙丁胺醇气雾剂后,进行高渗盐水诱导痰是一种安全的方法。     

哮喘患者呼出气冷凝液及诱导痰中超敏C反应蛋白相关性研究

目的探讨哮喘患者呼出气冷凝液和诱导痰中超敏C反应蛋白含量相关性。方法随机选择60位哮喘患者,分别在急性期和缓解期检测超敏C反应蛋白在呼出气冷凝液(exhaled breath condensate,EBC)及诱导痰(induced sputum,IS)中含量,研究两者相关性。结果急性期哮喘患者EBC中hs-CRP的含量(重度组0.32±0.02 mg/L,中度组0.28±0.04 mg/L)均高于缓解期含量(重度组0.20±0.04 mg/L,中度组0.18±0.02 mg/L;均P0.05)及健康对照组0.08±0.01 mg/L(P0.05);急性期哮喘患者IS中hs-CRP含量(重度组2.7±0.1 mg/L,中度组2.0±0.16 mg/L)也均高于缓解期(重度组1.2±0.15 mg/L,中度组1.4±0.12 mg/L;均P0.05)及健康对照组0.4±0.05 mg/L(P0.05);中、重度组EBC和诱导痰中hs-CRP含量在治疗前、后均具有显著正相关性。结论哮喘患者EBC中超敏C反应蛋白检测可用于评价气道炎症水平,其临床价值可与诱导痰中超敏C反应蛋白检测相媲美。     

CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling

Objectives: Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. Methods: We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). Results: The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. Conclusions: The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.     

Effects of single-dose fluticasone on exercise-induced asthma in asthmatic children: a pilot study

A single high dose of inhaled corticosteroid (ICS) can increase airway caliber in children with asthma attacks and laryngitis subglottica. Presumably the effect is due to the vasoconstrictive and antiedematous properties of topical steroids. Enlarged vessels have been suggested to play a role in the pathophysiology of exercise-induced bronchial obstruction (EIB). To investigate this, we evaluated the effect of a single high dose of fluticasone propionate (FP) on EIB in asthmatic children. Nine children aged 8-16 years with mild to moderate asthma were included. All children had a history of EIB, which was confirmed by an exercise test. None was taking ICS maintenance therapy. The children inhaled either a single dose of 1 mg FP or placebo on 2 separate days within 7-14 days. After inhalation, airway caliber (FEV(1)) was assessed for 4 hr before exercise. Then an exercise challenge was performed on a treadmill to assess EIB (% fall FEV(1)). A significant increase in FEV(1) was observed 1 hr after inhalation of FP compared to placebo. Response to exercise was expressed as maximal % fall in FEV(1) from baseline (% fall) and as area under the curve (AUC) of the 30-min time/response curve. The % fall FEV(1) after exercise and the AUC were significantly reduced when FP was inhaled compared to placebo inhalation (% fall 9.7% vs. 19.2%, respectively, P = 0.038 and AUC 92.0%.min vs. 205.7%.min, respectively, P = 0.03). There was considerable individual variability in reduction of EIB, with 5 out of 9 children having a clinically significant response. We conclude that a single high dose of inhaled FP has an acute protective effect on the bronchial response to exercise in a substantial proportion of asthmatic children.     

哮喘患者吸入表面激素减量后哮喘症状变化与诱导痰嗜酸性粒细胞比例的关系

目的 探讨吸入表面激素（ICS）减量后哮喘症状变化与诱导痰嗜酸性粒细胞（EOS）比例的关系.方法 选择专科门诊已使用ICS治疗的39例缓解期哮喘患者,进行诱导痰检查.根据减量时间分为两组,一组16例为缓解1个月后ICS剂量减半（减量1组16例）,另一组23例为缓解3个月后ICS剂量减半（减量2组）,予诱导痰检查.分别予目前使用ICS剂量减半,并于ICS减量后1个月、2个月、3个月及6个月复诊,复查诱导痰,观察气道炎症变化,对所得数据应用SPSS15.0软件分析.结果 两组患者ICS减量后3个月（43.8％ vs.21.7％）及6个月（43.8％ vs.43.5％）内哮喘症状复发率无显著差异（P ＞0.05）;ICS减量后3个月复发组与未复发组患者减量前诱导痰EOS比例存在显著差异（10.3％ vs.2.5％,P＜0.05）.ICS减量后6个月复发组与未复发组患者减量前诱导痰EOS比例也存在显著差异（11.5％ vs.2.5％,P＜0.05）.结论 诱导痰EOS比例对判断缓解期患者ICS减量后症状复发具有重要参考价值,临床症状缓解后,参考诱导痰EOS比例进行ICS减量,有可能减少哮喘的复发.     

Effects of a Short Course of Pranlukast Combined with Systemic Corticosteroid on Acute Asthma Exacerbation Induced by Upper Respiratory Tract Infection

Background. Upper respiratory tract infections (URIs) represent the most frequent cause of acute asthma exacerbation. Systemic corticosteroid (CS) is presently recommended for URI-induced asthma exacerbation, although it might inhibit cellular immunity against respiratory virus infection. Objectives. To determine the effects of adding a short course (2 weeks) of a leukotriene receptor antagonist (LTRA) to systemic CS on URI-induced acute asthma exacerbation. Methods. Twenty-three adult asthmatics (mean age, 42.8 ± 9.8 y; Male:Female, 10:13) with URI-induced acute asthma exacerbation confirmed by a questionnaire and physical findings were randomly assigned to receive either oral prednisolone (PSL) alone or oral PSL plus the LTRA pranlukast (PRL) for 2 weeks (PSL + PRL). The cumulative doses of PSL and the amount of time required to clear asthma-related symptoms were determined. Levels of respiratory syncytial virus (RSV) RNA and influenza viral (IV) antigen in nasopharyngeal swabs were also determined. Results. Adding PRL significantly reduced the cumulative dose of PSL and tended to reduce the time required to clear asthma-related symptoms. Either RSV or IV was detected in about one-third of the patients. Conclusion. The combination of an LTRA and CS might be more useful than CS alone for treating URI-induced acute exacerbation of asthma and reducing the cumulative CS dose.     

Agreement in surfactant measurements of sputum induced with hypertonic and normal saline

OBJECTIVE: The contribution of surfactant to the airway epithelial barrier is increasingly being recognized. Dipalmitoyl phosphatidycholine (DPPC), the major constituent of surfactant, is affected by lung injury. Hypertonic saline-induced sputum is a convenient and reliable method of assessing airway cells and mediators. However, the influence of hypertonic saline on DPPC content of sputum is unknown. In this study the level of DPPC in induced sputum obtained using hypertonic saline is examined and compared with that obtained using normal saline. METHODOLOGY: Sputum was induced on two occasions using nebulized hypertonic saline and normal saline, in 15 well non-smoking adults, in random order on different days. DPPC content (microg/mL of sputum) was measured using a standard spectrophotometric method. RESULTS: The mean of log10 DPPC level in sputum obtained using hypertonic saline was 1.88 microg/mL sputum (95% CI 1.53, 2.13) and that obtained using normal saline was 1.83 (95% CI 1.62, 2.14). The mean difference of the two methods was -0.03 (95% CI -0.27, 0.33). Bland and Altman plot showed an equal distribution around the mean and all points were within the mean +/- 2 SD. CONCLUSION: We conclude that DPPC concentration of sputum can be easily measured in induced sputum and that the use of hypertonic saline does not influence the DPPC levels.     

Clinical and inflammatory features of asthma with dissociation between fractional exhaled nitric oxide and eosinophils in induced sputum

Background: Measurement of the fractional exhaled nitric oxide (FeNO) and eosinophils in induced sputum are noninvasive markers for assessing airway inflammation in asthma. The clinical usefulness of the correlation between raised FeNO and sputum eosinophilia is controversial. We aimed to examine dissociation between FeNO and sputum eosinophils in a clinical series of asthma patients and to determine whether dissociation between these noninvasive markers was associated with clinical and inflammatory differences in these patients. Methods and findings: A total of 110 patients with asthma were included in a cross-sectional study. All of them were on maintenance treatment for asthma. All patients underwent the following on the same day: FeNO, induced sputum, spirometry, serum total IgE levels and skin prick test. The level of asthma control was determined by the Asthma control Test Questionnaire. In 46 (41.8%) patients, a discrepancy between FeNO and sputum eosinophil count was observed, of those, 34 (73.9%) had a FeNO <50?ppb and high eosinophil count, and were characterized by having a predominance of nonallergic asthma with bronchial eosinophilic inflammatory phenotype. Also, 12 (26.1%) patients had FeNO ≥50?ppb and sputum eosinophilia within the normal reference values, and were characterized by having a predominance of atopy with a paucigranulocytic inflammatory phenotype. Conclusions: A high percentage of patients with dissociation between results of FeNO and sputum eosinophils was observed. These patients showed differential clinical and inflammatory features.     

哮喘控制水平、肺功能下降与诱导痰IL-6表达水平的相关性分析

目的 通过对比哮喘不同控制水平患者诱导痰IL-6表达水平,探究哮喘控制水平、患者肺功能与诱导痰IL-6表达水平的相关性.方法 研究纳入2019年1月至2020年12月就诊于我院门诊的哮喘患者159例,其中哮喘良好控制水平患者42例,处于哮喘部分控制水平患者49例,处于哮喘未控制水平患者68例.收集各患者诱导痰标本,使用...