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.     

Attenuating effect of H+K+ATPase inhibitors on airway cough hypersensitivity induced by allergic airway inflammation in guinea-pigs

BACKGROUND: Gastrooesophageal reflux (GER) is a frequent cause of chronic cough. Several investigators have indicated that inhibitors of H(+)K(+)ATPase (proton pump inhibitors; PPIs) could relieve coughing via inhibition of acid reflux. However, we considered that PPIs might directly inhibit increased cough reflex sensitivity. OBJECTIVE: The present study was designed to examine whether PPIs directly inhibit antigen-induced increase in cough reflex sensitivity and to elucidate the mechanism. METHODS: Actively sensitized guinea-pigs were challenged with aerosol antigen (ovalbumin, OVA) and cough reflex sensitivity to inhaled capsaicin was measured 24 h later. The PPIs (omeprazole and rabeprazole) or the histamine H(2) blocker cimetidine were administered intraperitoneally 1 h before OVA challenge and before measuring cough reflex sensitivity, then bronchoalveolar lavage fluid (BALF) was immediately collected. The pH of the fluid obtained by bronchial washing was determined after examining the effect of rabeprazole on the cough response to capsaicin. RESULTS: The number of coughs elicited by capsaicin was significantly increased 24 h after challenge with OVA compared with saline, indicating antigen-induced increase in cough reflex sensitivity. Both PPIs dose dependently and significantly inhibited antigen-induced cough hypersensitivity. Omeprazole did not influence the antigen-induced increase in the total number of cells or ratio (%) of eosinophils in BALF. Cimetidine did not affect the antigen-induced cough hypersensitivity or cellular components of BALF. The pH of the bronchial washing fluid was significantly decreased in antigen-challenged animals. Rabeprazole did not affect the antigen-induced decrease in the pH of bronchial washing fluid. CONCLUSION: These findings show that PPIs, but not histamine H(2) blockers, can directly decrease antigen-induced cough reflex hypersensitivity, while the mechanism remains unclear.     

Effects of suplatast tosilate, a new type of anti-allergic agent, on airway cough hypersensitivity induced by airway allergy in guinea-pigs

BACKGROUND: Cough receptor hypersensitivity is a fundamental feature of some conditions presenting with chronic non-productive cough. Suplatast tosilate, an anti-allergic agent, is a T helper (Th)2 cytokine inhibitor that inhibits the synthesis of interleukin (IL)-4, IL-5, immunoglobulin (Ig)E production, and local eosinophil accumulation. OBJECTIVE: The purpose of this study was to investigate the effect of suplatast on antigen-induced airway cough hypersensitivity and eosinophil infiltration into the airway. METHODS: Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an antigen challenge in conscious guinea-pigs and then bronchoalveolar lavage was performed. We investigated the effect of single (before antigen challenge or capsaicin provocation) or repetitive treatment with intraperitoneal suplatast at a dose of 10 or 30 mg/kg on antigen-induced cough hypersensitivity. RESULTS: Twenty-four hours after antigen challenge, guinea-pigs developed an increase in cough receptor sensitivity to inhaled capsaicin and eosinophil infiltration in the airways. After a 2-week treatment with suplatast, but not after only a single treatment before antigen challenge or capsaicin provocation, the antigen-induced early phase bronchoconstriction, cough hypersensitivity, and airway eosinophilia were inhibited in a dose-dependent manner. CONCLUSION: These results indicate that suplatast inhibits airway cough hypersensitivity underlying allergic eosinophilic inflammation.     

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.     

Serum and sputum neurotrophin levels in chronic persistent cough

BACKGROUND: Neurotrophins (NTs) are a family of growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin3 (NT-3) that are involved in inflammation. Serum and induced sputum NT levels are increased in asthma and in cough because of idiopathic pulmonary fibrosis, respectively. Neurogenic inflammation is implicated in the pathogenesis of chronic cough in individuals with normal chest radiography, but the role of NTs in this condition is unknown. OBJECTIVE: To assess if NT levels are elevated in the serum and airways in subjects with chronic persistent cough. METHODS: Eighty-one subjects with chronic cough persistent for over 1 year; with normal chest radiography and spirometry were included. Thirty healthy subjects were controls. Serum NGF, BDNF and NT-3 were measured by enzyme immunoassay. In a subset, NGF was measured in induced sputum. Sputum cell counts and allergen-specific serum IgE were measured and all patients received specific sequential treatment trials to achieve a final diagnosis for the cough. RESULTS: There was no significant difference either in the levels of serum or sputum NTs in chronic cough subjects compared with controls or between the most common causes of cough: post-nasal drip syndrome, gastro-oesophageal reflux disease, asthma and bronchiectasis. The median (inter-quartile range) for sputum NGF (pg/mL) was 516 (296-772) in healthy controls and 580 (312-880) in subjects with chronic cough (P=0.284). There was no correlation between NT levels and sputum cell counts. Sputum NGF levels correlated with duration of cough (r=0.34, P=0.002). CONCLUSION: NTs are not elevated in induced sputum or serum of subjects with chronic persistent cough. This implies that NTs do not have a central role in perpetuating airway inflammation in chronic persistent cough.     

Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma

Background: Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine – MCh) or indirect (adenosine 5′‐monophosphate – AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). Objective: We designed a randomized, single‐blind, cross‐over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. Methods: Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV₁) value (PD₂₀MCh); (ii) a provocative dose producing a 25% fall in the maximal mid‐inspiratory flow (FIF₅₀) from baseline (PD₂₅MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV₁ value (PC₂₀AMP) and (iv) a provocative concentration producing a 25% fall in the FIF₅₀ from baseline (PC₂₅AMP) for AMP. Results: All 113 patients with CVA responded to PD₂₀MCh and 96% and 69% responded to PC₂₀AMP, if we used PC₂₀ ≤ 200 mg/ml or PC₂₀ ≤ 100 mg/ml, respectively, with an excellent correlation between these two tests (r = 0.87 and 0.76, respectively). Extrathoracic AHR associated with AHR was found in 10% in MCh challenge and in 11% with AMP challenge and no patients had EAHR alone. Conclusion: Adenosine challenges correlate well with MCh in patients with CVA. A minority (c. 10%) of CVA patients have EAHR as measured by these tests, while most had AHR as assessed with each of the challenge agents.     

Longitudinal decline in pulmonary function in atopic cough and cough variant asthma

OBJECTIVE: Cough variant asthma and atopic cough are different clinical manifestations of eosinophilic airway inflammation presenting with isolated chronic non-productive cough. The aim of this study was to examine the longitudinal change in pulmonary function in cough variant asthma and atopic cough. METHODS: Longitudinal change in FEV1 was prospectively examined in 20 patients with cough variant asthma, 14 patients with atopic cough and 271 asymptomatic healthy subjects. All were lifetime non-smokers. Of the 20 cough variant asthma patients, 13 were taking long-term inhaled corticosteroid therapy (ICS) (beclomethasone dipropionate 615 +/- 58 micro g/day) and the other seven were not. Spirometry was taken at first visit, after cough was almost completely relieved on therapy, and at least once every year for 5 or more years afterwards. RESULTS: The slope of longitudinal change in FEV1 was not significantly different among cough variant asthma patients (- 0.029 +/- 0.007/year), atopic cough patients (- 0.021 +/- 0.022/year) and asymptomatic subjects (- 0.028 +/- 0.002 L/year). In patients with cough variant asthma, the slope in patients not taking inhaled corticosteroids (ICS) was 0.032 +/- 0.007 L/year, which was not significantly different from that in patients taking ICS (- 0.027 +/- 0.010 L/year). CONCLUSION: Pulmonary function decline is not greater in cough variant asthma than atopic cough and the normal population, and long-term ICS has no effect on the decline in cough variant asthma.     

Inflammatory cells and eicosanoid mediators in subjects with late asthmatic responses and increases in airway responsiveness

To determine the relationship of inflammatory cells and eicosanoid mediators to the pathogenesis of the late asthmatic response (LAR) and increases in nonspecific airway responsiveness, we studied bronchoalveolar lavage (BAL) cells and fluid in 27 subjects 12 hours after inhaled antigen challenge. Methacholine challenge was performed before antigen challenge and 24 hours later (12 hours after BAL). Eight subjects had no LAR (-LAR, less than or equal to 10% fall in FEV1), nine subjects had an equivocal LAR (+/- LAR, 11% 25% fall in FEV1), and 10 subjects had a definite LAR (+LAR, greater than 25% fall in FEV1). Subjects developing +LAR had increased airway responsiveness at baseline compared with that of subjects developing an +/- LAR, but not with subjects having -LAR. If airway responsiveness was markedly increased at baseline, further increases after antigen challenge were often not observed. We found that both percent neutrophils and eosinophils increased in BAL as the severity of the LAR increased, but significant differences between the groups with -LAR and +LAR were only observed when both cell types were considered together. In addition, there was a significant correlation between the combined cell percentages and the severity of the LAR as determined by fall in FEV1. Likewise, increases in airway responsiveness were associated with significant increases in both neutrophil and eosinophil numbers, but only neutrophils correlated with the change in airway responsiveness after antigen challenge. However, despite the significant physiologic and cellular differences that we found between our groups, no significant differences could be found in BAL eicosanoid-mediator concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing

BACKGROUND: Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown. OBJECTIVE: To determine the test accuracy of serum ECP and blood eosinophil percentage as noninvasive markers of eosinophilic airways inflammation. METHODS: Bronchoalveolar lavage (BAL) fluid and peripheral blood samples for eosinophil percentages and serum ECP were obtained from children undergoing elective surgery and who gave a history of wheezing in the previous year. Sensitivity, specificity and likelihood ratios (LH) and the area under the curve (AUC) for the receiver operator characteristic (ROC) curve were calculated for each blood marker for the prediction of airways inflammation defined by a BAL eosinophil percentage > 0.86. Data were analysed on the basis of how recently symptoms had occurred. RESULTS: Seventy-seven children (median age 6.75 years) were studied. An AUC of 0.75 (log serum ECP concentration) and 0.76 (log blood eosinophil percentage) was obtained for predicting airways inflammation. A serum ECP > 13 microg/L yielded a LH of 4.4, whereas using a cutoff blood eosinophils > 4% yielded a LH of 1.9, for the prediction of elevated eosinophils in BAL. Serum ECP and eosinophil percentages in BAL and blood were lowest (not statistically significant) when last symptoms had occurred more than 12 weeks previously. CONCLUSIONS: Serum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.     

Asthma, smoking and chronic cough in rural and urban adult communities in The Gambia

BACKGROUND: Asthma is reported to be rare in traditional rural communities, but is thought to be increasing as lifestyles become more urbanized or 'western'. OBJECTIVES: A community-based survey of non-communicable diseases was conducted from October 1996 to June 1997, and included comparison of the prevalence of asthma, smoking and chronic cough in rural and urban Gambia. METHODS: A cluster sample survey was conducted in a random sample of rural and urban adults (> or = 15 years of age). Subjects were asked about respiratory symptoms using a locally adapted version based on the IULTD questionnaire. Spirometry (basal, methacholine provocation and reversibility with a bronchodilator) and skin prick tests were performed on a randomly selected subsample of all subjects and those who, when interviewed, said they wheezed or had been diagnosed as asthmatic by a doctor. RESULTS: Out of 2166 participants in the urban population, 4.1% reported having had wheezing or whistling in the chest in the previous 12 months, 3.6% reported doctor-diagnosed asthma, and 0.6% chronic cough. In the rural population with 3223 participants these figures were 3.3%, 0.7% and 1.2%, respectively. Wheeze was more common in women, cough for 3 months of the year was more common in the age-groups 45+. Those who reported that they currently smoked accounted for 34% in urban and 42% in rural men. Figures were much lower for women (1.5% and 6.0%). Seven out of 574 randomly selected subjects (1.4%) exhibited bronchial hyper-responsiveness to methacholine challenge. Four of 133 (3.0%) people with self-reported wheeze and 3/69 (4.3%) participants with doctor-diagnosed asthma reacted positively on bronchial provocation with methacholine. There was a remarkably high prevalence of positive skin prick tests to aeroallergens: 38% in participants with a history of wheeze and 27% in those without. CONCLUSION: The prevalence of wheeze (particularly in association with bronchial hyper-responsiveness) was low in both rural and urban Gambia. This is in contrast to the relatively high prevalence of positive skin prick tests to aeroallergens (in both wheezers and non-wheezers), questioning the mechanisms of interaction between allergy and asthma and the presence of protective factors against asthma in this West African population. The high smoking rates justify international concern about tobacco marketing in developing societies.     

Late respiratory response and associated eosinophilic inflammation induced by repeated exposure to toluene diisocyanate in guinea pigs

OBJECTIVE: The study was designed to establish an animal model of toluene diisocyanate (TDI)–induced late respiratory response and to investigate airway inflammatory cell dynamics in this model. METHODS: Guinea pigs were exposed to 2,4-TDI dissolved in ethyl acetate by nasal application according to three schedules. Schedule 1 consisted of sensitization and multiple challenge (n = 58): 10% TDI was applied once daily for 7 days (sensitization) followed by challenges with 5% TDI once weekly for 4 weeks. Schedule 2 consisted of sensitization only (n = 5): 10% TDI was applied once daily for 7 days. Schedule 3 consisted of single challenge only (n = 12): 5% TDI was applied only once. As controls, ethyl acetate was applied according to the three schedules described above. Each animal was premedicated with metyrapone before each challenge. Bronchoalveolar lavage and histologic examination were performed at various times after the last challenge. RESULTS: Schedule 1 induced immediate and late respiratory responses at a prevalence of 63% and 56%, respectively. Schedules 2 and 3 induced an immediate response in some animals but no late response. Neither immediate nor late response was observed in control animals. All of the subgroups of schedule 1 that developed late responses (examined at 2, 3, 6, 24 and 168 hours) showed a significant increase of eosinophils in bronchoalveolar lavage fluid and tissue compared with the corresponding control of each (examined at the same time points). Two of the subgroups with late responses (examined at 3 and 6 hours) were compared with their corresponding subgroups, which were given the same treatment, failed to develop late response, and were examined at the same time points; they again proved to have a significant increase of eosinophils in both samples. Subgroups of schedule 1 without late response (30 minutes, 3 and 6 hours), schedule 2 (6 hours), or schedule 3 (2 and 6 hours) did not show significant changes in lavage or tissue cell composition, except for the schedule 1 subgroup examined at 6 hours, which showed a significant increase of eosinophils only in the tissue compared with its control. CONCLUSIONS: Sensitization and multiple challenge with TDI induced immediate and/or late respiratory responses at a high prevalence in guinea pigs. Eosinophilic but not neutrophilic inflammation was involved in the late response. (J ALLERGY CLIN IMMUNOL 1996;97:1308-19.)     

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.     

下丘脑室旁核对胃食管反流豚鼠咳嗽敏感性的调控机制

目的:探究下丘脑室旁核(paraventricular nucleus,PVN)在胃食管反流(gastro-esophageal reflux,GER)豚鼠咳嗽敏感性增高中的作用及其可能的调控途径。方法:利用健康雄性白化Hartley豚鼠制备GER模型,并通过柠檬酸咳嗽激发试验测定咳嗽敏感性;应用免疫荧光组织化学染色方法分别观察PVN内Fos蛋白和P物质(SP)的表达情况,以及Fos/SP双标神经元的分布;利用假狂犬病毒(PRV)示踪剂进行气管壁逆行神经束路追踪,并结合免疫荧光组织化学染色方法观察追踪剂的分布情况。结果:模型组与对照组相比,咳嗽敏感性明显增高。免疫荧光染色结果显示:Fos表达于PVN神经元的细胞核内,SP免疫阳性物质主要表达于PVN神经元的细胞浆内,模型组Fos和SP的表达显著增多(P0.05),且PVN内部分Fos阳性神经元同时呈SP免疫阳性,这些Fos/SP免疫双标神经元大约占SP单标神经元数量的77.25%。神经束路追踪结果显示:气管壁内注射PRV 48 h后,在延髓迷走复合体(dorsal vagal complex,DVC)内可观察到PRV标记的神经元胞体,72 h后PRV标记的神经元胞体可见于PVN内。结论:PVN在GER豚鼠咳嗽敏感性增高中发挥重要作用,可能是PVN内SP能神经元通过PVN-DVC-气道神经通路调控实现的。     

Characterization of increased cough sensitivity after antigen challenge in guinea pigs

Increased sensitivity of cough reflex is a fundamental feature of bronchodilator resistant non-productive cough associated with eosinophilic tracheobronchitis. Our hypothesis is that cough sensitivity is increased by airway allergic reaction characterized by airway eosinophilic inflammation. The aim of this study was to elucidate the hypothesis and clarify the characteristics of the increased cough sensitivity. Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an aerosolized antigen or saline in actively sensitized or non-sensitized (naive) conscious guinea pigs and then bronchoalveolar lavage was performed. The cough response was also measured 1 day before and 1, 2, 3, 5 and 7 days after an aerosolized antigen challenge in sensitized or naive animals. In addition, effect of procaterol (0.1 mg/kg), atropine (1 or 10 mg/kg), phosphoramidon (2.5 mg/kg) given intraperitoneally 30 min before the capsaicin challenge or capsaicin desensitization on the cough response was examined. Furthermore, the thromboxane A2 (TXA2) receptor antagonist S-1452 in a dose of 0.01 or 0.1 mg/kg or vehicle (saline) was given intraperitoneally at 24 and 1 h before the measurement of cough response. Number of coughs caused by capsaicin was extremely increased 24 h after an antigen challenge in sensitized guinea pigs compared with a saline or an antigen challenge in naive animals or a saline challenge in sensitized animals. The increased cough response disappeared at 3-7 days after the antigen challenge. Eosinophils in bronchoalveolar lavage fluid obtained after the measurement of capsaicin-induced coughs, which was performed 24 h after the antigen challenge, were significantly increased in sensitized guinea pigs. The eosinophil count was significantly correlated to the number of capsaicin-induced coughs. Procaterol or atropine did not alter the antigen-induced increase of cough sensitivity, whereas atropine did reduce the cough response in naive animals. Phosphoramidon increased the number of capsaicin-induced coughs in naive guinea pigs but not in sensitized and antigen-challenged animals. Capsaicin desensitization decreased the cough response in both antigen-challenged sensitized guinea pigs and naive animals. S-1452 reduced the antigen-induced increase of cough response in sensitized guinea pigs, but not in naive animals. Airway allergy accompanied with airway eosinophilia induces transient increase in cough sensitivity, which is not mediated by bronchoconstriction. The increased cough sensitivity may result in part from inactivation of neutral endopeptidase and TXA2, one of the inflammatory mediators.     

A new tool to assess and monitor the burden of chronic cough on quality of life: Chronic Cough Impact Questionnaire

INTRODUCTION: Chronic cough, one of the most frequent causes for a patient to consult a medical practitioner, limits the course of normal activities in everyday life of the patient affected (work, physical activities, social relations, night sleep). By now, there are few validated questionnaires for the evaluation of the impact of this symptom in the patient's quality of life (QoL). For this reason, we created a new questionnaire for the assessment of QoL in patients affected by chronic cough (Chronic Cough Impact Questionnaire, CCIQ). MATERIALS AND METHODS: In the development procedure of CCIQ an initial questionnaire of 40 items was compiled and given to a first pool of 170 patients, each coming to our attention because of chronic cough; then the 25 most significant items were detected and converted into questions evaluating the answers on a Likert scale of five steps. Consequently, this final questionnaire underwent a validation procedure to assess its construct validity, internal consistency, reliability, and responsiveness. 95 patients (44.2% F, 55.8% M) were evaluated (age 53.69 +/- 11.7 years). RESULTS: Following a statistical analysis, CCIQ showed a four-dimensional structure and good levels of internal consistency for the extracted factors: sleep/concentration (79.98), relationship (86.98), daily life impact (69.04), and mood (65.41). In stable conditions CCIQ showed a good reliability, ranged between 0.67 and 0.88. Responsiveness to clinical changes was accomplished. DISCUSSION: These results provide evidence that CCIQ has specificity enough for being a valid tool for detecting the relative burden of cough on subjective well-being, and for obtaining a global evaluation both of chronic cough impact and of treatments for it, taking into account the patient's point of view. The CCIQ was easily and quickly filled in by the patients while waiting, and it was accepted by the patients.     

Different inflammatory cell pattern and macrophage phenotype in chronic obstructive pulmonary disease patients, smokers and non-smokers

Smokers exhibit airway inflammation and increased number of alveolar macrophages (AM), but not all develop chronic obstructive pulmonary disease (COPD). We hypothesized that AMs in COPD patients have an altered functional capacity mirrored in a different phenotype. Sixteen steroid-naive COPD patients [forced expiratory volume in 1 s (FEV(1)) < 70% of predicted] underwent bronchoalveolar lavage (BAL). Age- and smoking-matched non-obstructive smokers (n = 10) and healthy non-smokers (n = 9) served as controls. Nine COPD patients had a BAL cell yield sufficient for flow cytometry analysis, where expression of AM cell surface markers reflecting various functions was determined. AMs from COPD patients showed decreased expression of CD86 (co-stimulation) and CD11a (adhesion) compared to smokers' AMs (P < 0.05). Furthermore, smokers' AMs showed lower (P < 0.05) expression of CD11a compared to non-smokers. AM expression of CD11c was higher in the COPD and smokers groups compared to non-smokers (P < 0.05). The expression of CD54 (adhesion) was lower in smokers' AMs compared to non-smokers (P < 0.05), whereas CD16 was lower (P < 0.05) in COPD patients compared to non-smokers. The AM expression of CD11b, CD14, CD58, CD71, CD80 and human leucocyte antigen (HLA) Class II did not differ between the three groups. The AM phenotype is altered in COPD and further research may develop disease markers. The lower AM expression of CD86 and CD11a in COPD implies a reduced antigen-presenting function. Some alterations were found in smokers compared to non-smokers, thus indicating that changes in AM phenotype may be associated with smoking per se. The functional relevance of our findings remains to be elucidated.