Atopic features of cough variant asthma and classic asthma with wheezing

Background Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. Objective To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Methods Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Results Patients with classic asthma had higher total IgE (P<0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate‐to‐severe disease (n=55), as reported previously. Conclusions Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.     

Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non-productive cough

BACKGROUND: We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have global atopic tendency and airway cough hypersensitivity without non-specific bronchial hyperresponsiveness, abbreviated as atopic cough. The cough is successfully treated with histamine H1-antagonists and/or glucocorticoids. OBJECTIVE: This prospective study was conducted to elucidate the histological feature of atopic cough. METHODS: Tracheal and bronchial mucosa obtained by transbronchoscopic biopsy and bronchoalveolar lavage (BAL) cell component were studied with special emphasis on eosinophils in eight non-smokers diagnosed with atopic cough, all of whom had increased sensitivity of cough response to inhaled capsaicin, normal lung function and bronchial responsiveness to methacholine and normal chest roentgenogram. Their cough completely resolved on histamine H1-antagonists and/or glucocorticoids. Transbronchoscopic tracheal and bronchial biopsy and BAL were also performed in healthy non-smokers as a control. RESULTS: A small number of eosinophils was detected in subepithelium of trachea in six of seven patients and in subepithelium of bronchi in seven of eight cough patients. The numbers of eosinophils in subepithelium of trachea and bronchi were significantly increased in the patients compared with control subjects. There was no BAL eosinophilia in any patients. CONCLUSION: It is concluded that eosinophilic tracheobronchitis and cough hypersensitivity are pathological and physiological characteristics of atopic cough.     

口服白三烯受体拮抗剂与吸入糖皮质激素治疗小儿咳嗽变异型哮喘合并变应性鼻炎的对比研究

目的对比研究口服白三烯受体拮抗剂（LTRA）与吸入糖皮质激素（ICS）对dxJL咳嗽变异型哮喘合并变应性鼻炎的防治效果。方法54例2-5岁患儿随机分为LTRA组（27例）和ICS组（27例）。LTRA组口服孟鲁司特钠，每次4mg，睡前服用1次；ICS组患儿规律吸入布地奈德气雾剂，每日200-400μg，采用储雾罐辅助吸入。药物治疗3个月后继续随访观察15个月。结果LTRA组与ICS组比较．控制症状所需的平均天数为（8．31±3．69）d和（7．20±2．78）d；症状缓解率为92．6％和96．3％，差异无统计学意义（P〉0．05）。在病程的18个月LTRA组复发率（36．0％）显著高于ICM组（15．4％）。转化为典型哮喘者。LTRA组7例（28．0％），ICS组2例（7．7％），差异有统计学意义（P〈0．05）。结论口服LTRA控制小儿咳嗽变异型哮喘合并变应性鼻炎的近期疗效与ICS相当。可作为一线药物使用。但接受LTRA治疗的患儿远期复发率或者转化为典型哮喘的比率高于ICS治疗的患儿。     

Induced sputum: comparison of postinfectious cough with allergic asthma in children

BACKGROUND: Cough persisting after a respiratory infection is common in children and is often managed as asthma. However, little is known about the pathophysiologic mechanisms of such cough and how it compares with asthma. OBJECTIVE: We used the technique of induced sputum to examine the inflammatory index values associated with persistent cough or allergic asthma in children. We hypothesized that the sputum from children with persistent postinfectious cough would differ from that of children with allergic asthma in that the former would lack eosinophils compared with the latter.Study design: Sputum production was induced with hypertonic saline solution in 34 children: 12 with cough persisting for 1 month or more after an apparent respiratory tract infection, not treated with corticosteroid; 11 with untreated atopic asthma, not using inhaled corticosteroid; and 11 with treated atopic asthma using inhaled corticosteroid. RESULTS: The percentage of eosinophils in the sputum of children with cough was significantly lower than in the sputum of children with untreated allergic asthma (median 0.5% vs 14.5%, P <.0001). Similarly, the percentage of eosinophils in the sputum of children with asthma treated with inhaled steroids was significantly lower compared with untreated asthmatic children (1.5% vs 14.5%, P <.0001). The peripheral blood eosinophils, serum eosinophil cationic protein, and nasal percent eosinophils of the patients with cough were also significantly lower than those from patients with untreated asthma. Methacholine challenge in 6 of the 11 cough patients tested showed mild-to-moderate hyperresponsiveness, whereas the other 5 had a negative methacholine challenge. CONCLUSIONS: Children with persistent postinfectious cough do not have airway eosinophilia typical of untreated asthma. Despite the absence of eosinophilic inflammation, some of the patients with chronic cough had reactive airways. These results suggest that postinfectious cough in children has different pathophysiologic features than allergic asthma and probably represents a different disease.     

温州地区儿童慢性咳嗽病因构成比研究

目的分析温州地区慢性咳嗽患儿的常见病因分布,为临床诊治提供依据。方法选取2008年1月至2010年12月温州医学院附属育英儿童医院呼吸科门诊就诊的慢性咳嗽初诊患儿,依据年龄分为-3岁、-6岁和-14岁组,在初诊后2周、1个月和3个月门诊或电话随访,根据随访治疗效果得出最终诊断结果。分析各病因的构成比,初诊和最终诊断的符合率。结果研究期间共纳入739例慢性咳嗽患儿,年龄8个月至14岁,其中-3岁组174例（23.5%）,-6岁组288例（39.0%）,-14岁组277例（37.5%）。咳嗽病程4周至5年。1-4季度分别纳入103例（13.9%）、247例（33.4%）、96例（13.0%）和293例（39.7%）。①739例慢性咳嗽患儿中,单病因680例（92.0%）,单病因依次为上气道咳嗽综合征237例（32.1%）,咳嗽变异性哮喘219例（29.6%）,感染后咳嗽109例（14.8%）,变应性咳嗽76例（10.3%）,心因性咳嗽25例（3.4%）,胃食管反流性咳嗽9例（1.2%）,其他5例（0.7%）;双病因45例（6.1%）;病因不明14例（1.9%）。②-3岁组最常见病因为感染后咳嗽（58例,33.3%）,-6岁组为上气道咳嗽综合征（114例,39.6%）,-14岁组为咳嗽变异性哮喘（103例,37.2%）,上述3种主要病因的各年龄组构成比差异有统计学意义（P〈0.05）。③上气道咳嗽综合征、咳嗽变异性哮喘、感染后咳嗽、变应性咳嗽、心因性咳嗽和胃食管反流性咳嗽所致慢性咳嗽共675例,其中496例初诊和最终诊断相符,初诊准确率为73.5%。结论温州地区儿童慢性咳嗽主要病因为上气道咳嗽综合征、咳嗽变异性哮喘、感染后咳嗽和变应性咳嗽;不同年龄组儿童慢性咳嗽的病因构成比有所不同。     

Enhanced cough response to hyperpnea with cold air challenge in chronic cough patients showing increased cough sensitivity to inhaled capsaicin

BACKGROUND: Although many chronic cough patients have complained of an induced cough by cold air contact, the clinical relevance of cold air to inducing a cough and the diagnostic value of a hyperpnea with cold air (HCA) challenge to detect a hyperreactive cough reflex have not yet been investigated. METHODS: Recordings of cough counts after a 2-min HCA challenge were performed in 49 chronic cough patients and 15 healthy controls. Capsaicin cough provocation tests, which determine the threshold concentration of capsaicin that induces five or more consecutive coughs (C5), were also administered. RESULTS: After comparing the results from the capsaicin cough provocation tests of the patients and the controls, the chronic cough patients were divided into two groups: an increased cough sensitivity (ICS) group (n = 28) (C5 < 32 micromol/l) and a normal cough sensitivity (NCS) group (n = 21) (C5 >or= 32 micromol/l). The median value of induced cough counts after a HCA challenge was 11 coughs in patients with ICS and was a significantly enhanced cough response compared to that of the patients with NCS and healthy controls (four coughs, respectively). CONCLUSIONS: A simple cough provocation test using a HCA challenge may be useful for detecting ICS. It also suggests that hyperreactive cough reflexes may be one of the mechanisms of inducing chronic cough.     

Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients.

BACKGROUND: Bronchial reactivity and exhaled nitric oxide (eNO) are not often used to monitor control and severity of asthma in clinical practice. OBJECTIVE: To evaluate the relationship among different physiologic measures (pulmonary function, nonspecific bronchial reactivity, and eNO) in asthmatic patients. METHODS: Cross-sectional, hospital-based study conducted in patients with varied asthma severity. RESULTS: A total of 392 patients participated in the study. There was no difference in eNO levels between patients taking inhaled corticosteroids (ICS group) and patients not receiving inhaled corticosteroids (NICS group). However, the percentage of predicted forced expiratory volume in 1 second (FEV1) and the provocative dose of methacholine causing a 20% decrease in FEV1 were significantly lower in the ICS group compared with the NICS group (mean, 83.2%; 95% confidence interval [CI], 80.4%-86.0%; vs mean, 94.1%; 95% CI, 91.1%-97.1%; P = .001; and geometric mean, 0.32 mg; 95% CI, 0.23-0.45 mg; vs geometric mean, 0.58 mg; 95% CI, 0.42-0.81 mg; P = .01; respectively). Patients with more severe bronchial hyperresponsiveness had a lower percentage of predicted FEV1 values (P < .001) and levels of eNO were significantly increased with increasing bronchial hyperresponsiveness (P < .001). There was no relationship between the percentage of predicted FEV1 and eNO. Atopic patients had significantly higher eNO levels than nonatopic patients (geometric mean, 11.21 ppb; 95% CI, 10.07-12.49 ppb; vs geometric mean, 7.76 ppb; 95% CI, 6.11-9.85 ppb; P = .006; respectively). CONCLUSIONS: eNO values are not related to the degree of airway obstruction but are related to airway reactivity and atopic status independent of inhaled corticosteroid use. Higher values of eNO are seen with increased airway reactivity.     

Effectiveness of montelukast in the treatment of cough variant asthma.

BACKGROUND: Antileukotriene agents have been shown to be beneficial in chronic asthma. Although patients with cough variant asthma have cough with minimal wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism. OBJECTIVE: To evaluate the effectiveness of montelukast, a leukotriene receptor antagonist, in the treatment of cough variant asthma. METHODS: Fourteen patients with cough variant asthma participated in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo daily. Inclusion criteria were (1) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in 1 second of 50% to 85% of predicted and reversibility of 12% with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and positive methacholine challenge results. Patients fulfilled the minimum criteria for cough frequency and symptom scores for randomization. RESULTS: Eight patients received montelukast and 6 received placebo. The primary efficacy variable, mean percentage change from baseline in cough frequency, was significantly improved by the second week, and by the fourth week the mean percentage change from baseline was 75.7% for the treatment group and 20.7% for the placebo group. CONCLUSIONS: The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma. Larger studies are recommended to confirm this effect.     

Exhaled nitric oxide of childhood asthma]

Chronic airway inflammation is a central feature of pathology of bronchial asthma. In order to evaluate inflammatory status in asthma, examinations such as bronchoscope or induced sputum test can be done. Because of difficulty of those examinations we need non-invasive and simple measures for childhood asthma. Here we investigated eNO in childhood asthma. Twenty-six of atopic asthma, 13 non-asthmatic atopic children and 12 normal children were enrolled in this study. eNO was measured by chemiluminescence analyzer. eNO was significantly collerated with % FEV 1.0 and blood eosinophil counts (R = -0.494, R = 0.416, respectively). Geometrical mean of eNO in normal, non-asthmatic atopic, asthma without inhaled corticosteroid (ICS) and asthma with ICS was 16.3, 23.7, 71.6, 43.6 ppb, respectively. eNO was significantly higher in asthma than in normals. eNO in patients without ICS were significantly higher than in non-asthmatic atopic. We concluded that eNO might be useful marker for evaluation of airway inflammation in asthmatic children.     

Effect of inhaled corticosteroids on symptom severity and sputum mediator levels in chronic persistent cough

BACKGROUND: Chronic cough often lasts for more than 1 year and is associated with airway inflammation. The effect of inhaled corticosteroids on symptom severity and inflammatory mediator levels in these patients is unknown. OBJECTIVE: We sought to determine whether inhaled corticosteroids reduce cough severity and sputum mediator concentrations in patients with chronic persistent cough. METHODS: We performed a double-blind, randomized, placebo-controlled crossover study with inhaled fluticasone, 500 microg twice daily, and placebo for 14 days in 88 patients with cough for more than 1 year, with normal chest radiography and spirometry results. Outcome measures were a daily cough visual analogue scale and induced sputum concentrations of eosinophilic cationic protein (ECP), myeloperoxidase, leukotriene B(4) (LTB(4)), leukotrienes C(4)/D(4)/E(4) (cysteinyl leukotrienes [Cys-LTs]), prostaglandin E(2) (PGE(2)), IL-8, and TNF-alpha. Sputum cell counts, exhaled nitric oxide levels, and carbon monoxide levels were also measured. RESULTS: There was a significant improvement in the cough visual analogue scale after inhaled fluticasone compared with placebo (mean difference, 1.0; 95% CI, 0.4-1.5; P <.001). LTB(4), Cys-LT, and PGE(2) levels were increased in all causes of cough. Sputum ECP counts, exhaled nitric oxide levels, and carbon monoxide levels decreased significantly after inhaled fluticasone. There was no change in sputum cell counts and other mediator concentrations. CONCLUSION: Cough severity and sputum ECP levels are modestly reduced by inhaled corticosteroids in patients with chronic cough persisting for more than 1 year. LTB(4), Cys-LT, PGE(2), IL-8, myeloperoxidase, and TNF-alpha levels are unaltered by this therapy. This raises the possibility that drugs targeted to reduce the effects of these mediators might be of benefit in chronic persistent cough.     

The role of the methacholine challenge in children with chronic cough

Thirty-nine male and 35 female subjects, aged 6 to 20 years, with chronic cough were studied with spirometry and standard methacholine (MCH) challenge. The duration of their cough before the MCH challenge ranged from 2 months to 13 years. Their FEV1 ranged 62% to 132% predicted. Thirty-six (49%) patients had a positive MCH challenge. The MCH concentration inhaled to decrease the FEV1 by 20% ranged from 0.55 to 25 mg/ml. Follow-up data (mean 14 months) were available on all 74 patients. Fifty-four patients received asthma medications, and 93% improved in mean 3.6 weeks. At the end of the follow-up, 22 (30%) were asymptomatic, 39 (53%) were improved, and 13 patients (17%) were symptomatic. We were unable to predict bronchial hyperreactivity in this population on the basis of duration of the cough, personal or family history of allergies, or baseline spirometry. Thus, MCH challenge is helpful in evaluating children with chronic cough and in guiding therapy. Follow-up of children with chronic cough is important. Eleven percent of this study population progressed to develop bronchial asthma. Forty percent of these patients, initially doing well, were asymptomatic at the end of the follow-up period.     

Evidence of ongoing mast cell and eosinophil degranulation in symptomatic asthma airway.

To assess whether mast cell and eosinophil (EOS) degranulation occurs in the airway of subjects with moderately symptomatic asthma, we have measured levels of preformed mast cell-derived mediators (histamine and tryptase) and EOS-derived mediators (major basic protein and EOS-derived neurotoxin) in bronchoalveolar lavage fluid (BALF) obtained from patients with symptomatic (N = 14) and asymptomatic asthma (N = 9) and patients without asthma (N = 6). Both the FEV1 (1.52 +/- 0.33 L:55% +/- 15% of predicted FEV1) and the forced expiratory flow at 50% (FEF50) (1.11 +/- 0.62 L/sec:26% +/- 14% of predicted FEF50) in the patients with symptomatic asthma were significantly lower than the corresponding values for FEV1 (3.16 +/- 0.45 L:86% +/- 10% of predicted FEV1) and the FEF50 (4.04 +/- 1.54 L/sec:71% +/- 25% of predicted FEF50) in the patients with asymptomatic asthma. Levels of histamine (4.8 +/- 5.0 ng/ml versus 0.2 +/- 0.2 ng/ml) (p = 0.05), EOS-derived neurotoxin (420.6 +/- 959.4 ng/ml versus 12.6 +/- 7.7 ng/ml) (p = 0.05), major basic protein (31.4 +/- 46.6 ng/ml versus less than 9 ng/ml) (p = 0.05), and percent EOSs (10.6% +/- 7.0% versus 1.1% +/- 0.9% of BAL cells) (p = 0.0006) were all significantly elevated in BALF from symptomatic compared to asymptomatic patients with asthma. The elevated levels of tryptase (13.2 +/- 14.8 ng/ml versus 3.9 +/- 3.9 ng/ml) in BALF from symptomatic compared to asymptomatic patients with asthma approximated, but did not reach, statistical significance. Spontaneous histamine release from BAL mast cells of symptomatic patients with asthma was 46% +/- 5% compared to 5% +/- 2% in asymptomatic patients with asthma. In response to antihuman IgE, histamine release from BAL mast cells recovered from asymptomatic patients with asthma increased to 25% +/- 10%, whereas in BAL mast cells of symptomatic patients with asthma, no anti-IgE potentiation of histamine release occurred. This study suggests that mast cell and EOS degranulation is ongoing in the airway of patients with moderately symptomatic asthma.     

Efficacy and safety of fluticasone propionate 250 microg administered once daily in patients with persistent asthma treated with or without inhaled corticosteroids.

BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS.     

Respiratory muscle strength and cough capacity in patients with Duchenne muscular dystrophy

The function of inspiratory muscles is crucial for effective cough as well as expiratory muscles in patients with Duchenne muscular dystrophy (DMD). However, there is no report on the correlation between cough and inspiratory muscle strength. To investigate the relationships of voluntary cough capacity, assisted cough techniques, and inspiratory muscle strength as well as expiratory muscle strength in patients with DMD (n= 32). The vital capacity (VC), maximum insufflation capacity (MIC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured. Unassisted peak cough flow (UPCF) and three different techniques of assisted PCF were evaluated. The mean value of MICs (1918 +/- 586 mL) was higher than that of VCs (1474 +/- 632 mL) (p < 0.001). All three assisted cough methods showed significantly higher value than unassisted method (212 +/- 52 L/min) (F = 66.13, p < 0.001). Combined assisted cough technique (both manual and volume assisted PCF; 286 +/- 41 L/min) significantly exceeded manual assisted PCF (MPCF; 246 +/- 49 L/ min) and volume assisted PCF (VPCF; 252 +/- 45 L/min) (F = 66.13, p < 0.001). MIP (34 +/- 13 cmH2O) correlated significantly with both UPCF and all three assisted PCFs as well as MEP (27 +/- 10 cmH2O) (p < 0.001). Both MEP and MIP, which are the markers of respiratory muscle weakness, should be taken into account in the study of cough effectiveness.     

Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE

BACKGROUND: Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. OBJECTIVE: To evaluate whether prolonged treatment with ICSs is associated with FEV(1) decline in adults with asthma. METHODS: An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV(1) decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. RESULTS: As ICS use increased, the decline in FEV(1) was lower (P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction (P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV(1) decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. CONCLUSION: Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. CLINICAL IMPLICATIONS: This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management.     

慢性咳嗽患者咳嗽敏感性的影响因素

目的探讨慢性咳嗽患者咳嗽敏感性的影响因素.方法按照慢性咳嗽病因诊断程序,人选并诊断慢性咳嗽患者.通过辣椒素咳嗽激发试验测定慢性咳嗽患者(治疗前)的气道咳嗽敏感性,以最先诱发5次或以上咳嗽的辣椒素溶液浓度(C5)的对数作为咳嗽阈值.分析咳嗽阈值与咳嗽积分、年龄、性别、病程、肺通气功能与诱导痰炎性细胞分类间的相关性.结果入选并获得明确诊断的不同病因慢性咳嗽患者共计150例.单因素相关分析显示,慢性咳嗽患者的咳嗽阈值与日间咳嗽积分、性别、年龄、咳嗽病程及诱导痰嗜酸细胞百分比有相关,r分别为-0.175、-0.305、-0.297、-0.238及0.173,P均<0.05;咳嗽阈值与夜间咳嗽积分、痰中性粒细胞百分比、痰巨噬细胞百分比、痰淋巴细胞百分比及肺通气功能[第1秒用力呼气容积占预计值的百分比(FEV1/pred%)、用力呼气中段流速占预计值的百分比(MMEF/pred%)]均不相关,P均>0.05.多元线性回归分析显示,咳嗽阈值仅与性别、咳嗽病程有关(P均<0.01).结论咳嗽敏感性与咳嗽症状积分反映咳嗽程度的不同特征,性别与咳嗽病程可能影响慢性咳嗽患者的咳嗽敏感性.     

The influence oc glycocorticoid therapy on sputum ECP concentration in symptomatic patients with bronchial asthma

ECP released from the granules of activated eosinophils is regarded to be a marker of airway inflammation in asthma. The study was performed to compare the usefulness of measuring serum and sputum ECP for monitoring the asthma treatment. 29 subjects with mild to moderate asthma (mean age 41 +/- 17) were admitted in exacerbation (FEV1 55.54 +/- 87.49% N). 10 subjects with grass pollen asymptomatic asthma and 10 healthy subjects were also enrolled in the study. Patients with symptomatic asthma were ordered 30 mg prednisone for 2 weeks and they continued during next 2 weeks inhaled budesonide therapy. The concentrations of ECP (mcg/L) were determined by CAP-system (Pharmacia). The total eosinophil count and serum ECP in all subjects treated orally and next by inhaled GKS didn't differ statistically. The highest sputum ECP concentration was determined in exacerbation of asthma 84.5 +/- 78 mcg/L and statistically were reduced after 2-weeks of prednisone treatment 24.4 +/- 12.1 mcg/L (p = 0.05). In following 2 weeks of budesonide treatment sputum ECP concentration was statistically negligible in relation to previous treatment in spite of increasing tendency (50 +/- 61.3 mcg/L (p = 0.2394). In asymptomatic grass pollen asthma sputum ECP concentration was 19.7 +/- 9.4 mcg/L, higher than in controls 12 +/- 5.8 mcg/L (p = 0.04). There were a significant correlations between total eosinophil count and serum (r = 0.6396) and sputum ECP(r = 0.4683) in exacerbation. CONCLUSIONS: 1. In asthma exacerbation elevated sputum ECP concentration was observed. 2. In consequence of prednisone treatment the sputum ECP concentration was reduced. 3. Sputum ECP measurement is more accurate than serum ECP for monitoring the effectiveness of treatment. 4. Sputum ECP concentration is a sensitive parameter which discriminate asymptomatic patients with asthma from healthy subjects.     

Sensory neuropeptides induce histamine release from bronchoalveolar lavage cells in both nonasthmatic coughers and cough variant asthmatics

BACKGROUND: Sensory neuropeptides have been suggested to play a role in the pathogenesis of a number of respiratory diseases including asthma and chronic non-productive cough. OBJECTIVES: To investigate the action of sensory neuropeptides on airway mast cells obtained by bronchoalveolar lavage (BAL). METHODS: BAL was performed on 23 nonasthmatic patients with cough (NAC), 11 patients with cough variant asthma (CVA) and 10 nonatopic controls. Washed lavage cells were stimulated (20 min, 37 degrees C) with calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and substance P (25 and 50 micromol/L). RESULTS: The neuropeptides tested induced histamine release in all groups studied. Only CGRP (50 micromol/L) induced significantly more histamine release from both NAC and CVA patients compared with control subjects (P = 0.038 and 0.045, respectively). CONCLUSION: Regardless of aetiology, mast cells from patients with chronic cough appear to have an increased responsiveness to CGRP compared with controls. The results of the present study suggest that the role of CGRP in chronic cough should be further investigated.     

Th1/Th2 profile in peripheral blood in atopic cough and atopic asthma

BACKGROUND: Eosinophilic tracheobronchitis with cough hypersensitivity, abbreviated as atopic cough, is an important cause of chronic cough. The reason for the absence of airway hyper-responsiveness is unknown, differing from asthma, a Th2 cytokine-mediated disorder. OBJECTIVE: To compare the type 1 helper T cell (Th1)/Th2 balance in the peripheral blood from subjects with atopic cough and atopic asthma, we assessed the intracellular cytokine production at the single-cell level. METHODS: Thirty-six subjects (10 patients with atopic cough, 18 with atopic asthma, and eight control subjects) were included. Intracellular IL-4 and IFN-gamma were detected in CD4+ T cells by flow cytometry. RESULTS: A significantly lower ratio of IFN-gamma-/IL-4-producing CD4+ T cells after phorbol 12-myristate acetate/ionomycin stimulation was found in patients with atopic cough and atopic asthma compared with normal subjects. In comparison between atopic patients, the ratio of IFN-gamma-/IL-4-producing cells was significantly higher in atopic cough than in atopic asthma. However, the proportion of IL-4-producing CD4+ T cells was significantly higher in patients with atopic asthma than in normal control subjects and no significant difference was detected between patients with atopic cough and normal subjects. No significant difference in the proportion of IFN-gamma-producing cells was found between the subjects. Overall, the total IgE levels were positively correlated to the IL-4-producing cells and inversely correlated to the ratio of IFN-gamma-/IL-4-producing cells. CONCLUSION: These results show the lower degree of Th2 cytokine predominance in atopic cough compared with atopic asthma and suggest the relation between the Th1/Th2 balance and atopic status.     

Relationship of airway symptoms from chemicals to capsaicin cough sensitivity in atopic subjects

BACKGROUND: It is well known that some patients with allergy complain of airway symptoms from chemicals (ASCs) and strong odours. However, the importance of such information for the treatment of allergic disease is not known. Such symptoms in non-allergic patients have previously been shown to be related to increased sensory nerve reactivity, which is expressed as increased cough sensitivity to inhaled capsaicin. OBJECTIVE: The aim of this study was to examine ASC in atopic patients and relate it to cough reaction to capsaicin inhalation. MATERIALS AND METHODS: Fifty-seven consecutively chosen, skin prick-positive patients with symptoms of the upper and/or lower airways completed a questionnaire concerning ASC. The patients were then divided into two groups, those with and those without such symptoms. Both groups were provoked with inhaled capsaicin in three increments and compared with 73 healthy control subjects. RESULTS: Out of 57 atopic patients, 34 reported ASC agents and 23 did not. The patients with ASC were older (P<0.01) and coughed significantly more on capsaicin provocation (P<0.001), but did not differ from them with respect to the allergic disease or its treatment or to smoking habits. Patients with atopy but without ASC did not differ from healthy controls with regard to sensitivity to capsaicin inhalation. The scored degree of ASC was directly related to the number of coughs during the capsaicin provocation. CONCLUSION: ASC in atopic patients are related to increased airway sensory nerve reactivity. There is still no explanation for this in certain patients with atopy, but age may be a confounding factor.