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.     

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.     

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.     

Effects of Bakumondo-to (Mai-Men-Dong-Tang) on cough sensitivity to capsaicin in asthmatic patients with cough hypersensitivity]

Some patients with bronchial asthma have increased cough sensitivity. In such patients coughing may be an inducer of wheeze. The aim of the present study was to investigate the effect of Bakumondo-to on the cough sensitivity and respiratory tract inflammation in asthmatic patients with increased cough sensitivity. In addition influences of intensity of respiratory tract inflammation, gender, type of asthma, and disease period on the effect of Bakumondo-to on the cough sensitivity were examined. Twenty-one bronchial asthmatics whose cough thresholds to capsaicin were less than 3.9 microM were examined. METHODS: Cough thresholds to capsaicin (concentration of inhaled capsaicin solution causing 5 or more coughs) was measured before and after 2 months or more treatment with Bakumondo-to (9 g/day, TJ-29). Number of eosinophils in peripheral blood, sputum eosinophil ratio, and ECP level in the serum were also measured before and after treatment. RESULTS: Bakumondo-to significantly increased the cough threshold. Although respiratory tract inflammation was not significantly improved, number of eosinophils in peripheral blood, sputum eosinophil ratio and ECP level in the serum were remarkably decreased more than the half. And Bakumondo-to was more effective in asthmatic subjects with severe airway inflammation. Furthermore, a greater effect of it was observed in women. A greater effect was also observed in patients having a disease duration of less than 1 year. CONCLUSION: Our results suggest that Bakumondo-to may be an effective therapeutic preparation for coughing in asthmatic patients with cough hypersensitivity.     

Inflammatory mediators in bronchoalveolar lavage samples from children with and without asthma

BACKGROUND: We investigated whether eosinophils and mast cells, found in the airways of children with wheeze, were activated during relatively asymptomatic periods. METHODS: A nonbronchoscopic bronchoalveolar lavage (BAL) procedure was performed on children presenting for an elective surgical procedure. Eosinophil-derived (eosinophil cationic protein, ECP) and mast cell-derived (histamine/tryptase) mediator concentrations were measured in the BAL fluid. A detailed history and serum immunoglobulin E were used to classify the children into four groups: atopic with and without asthma, viral-associated wheeze and normal controls. RESULTS: The ECP concentrations in BAL from atopic asthmatic subjects were significantly higher than those measured in BAL from normal controls (P < 0.01), no other groups differed significantly. Histamine concentrations were elevated in both the atopic asthmatic and viral-associated wheeze groups compared with controls (P < 0.02) and additionally higher concentrations were obtained in atopics with asthma compared with atopics without asthma (P < 0.03). Tryptase concentrations did not differ between groups, although the tryptase and histamine concentrations correlated significantly (r = 0.78, P < 0.0001). CONCLUSIONS: Elevated histamine concentrations were found in children with wheeze regardless of the aetiology, whereas ECP was only elevated in those asthmatics with atopy. This suggests that even in relatively quiescent periods, there is some on going activation of airway eosinophils in children with atopic asthma.     

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects: Comparison with bronchial challenge and skin test responses

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV₁ decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.     

Chronic non-asthmatic cough is not affected by inhaled beclomethasone dipropionate

Thirty-one patients with a dry cough for at least 1 h duration in more than half of the last 30 days and with no recent respiratory infection participated in a clinical trial to evaluate the effect of inhaled beclomethasone dipropionate (BDP). Lung function was normal and reversibility was excluded by spirometry before and after bronchodilator and by no diurnal variation in home peak flow monitoring. Only one had significant eosinophilia and only three were mildly hyperreactive by bronchial provocation with histamine. After a 1-week run-in period the patients were randomly allocated to receive either BDP 4 puffs of 50 micrograms b.i.d., or placebo. After 2 weeks the patients were crossed over and received the alternative treatment for another 2-week period. The degree of cough, disturbance of night sleep and peak expiratory flow morning and evening were recorded daily in a diary. Spirometry was performed at each control visit. A significant period effect from run-in to period 1 and/or from period 1 to period 2 was demonstrated for cough and disturbance at night but not for peak flow or spirometry. However, no significant treatment effect was found for any of the measured variables.     

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.     

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.     

Airway inflammation and cough sensitivity in cough-variant asthma

BACKGROUND: Mechanisms underlying cough and bronchoconstriction in patients with cough-variant asthma (CVA) are not well established. Differences in location or degree of activation of eosinophils and allergic cytokines have been suggested as the likely causes. To address this issue, we have carried out a comparative study of airway inflammatory markers between patients with CVA and classic asthma (CA). The relationship between these markers with airway hyperresponsiveness (AHR) and cough sensitivity has also been studied. METHODS: Twenty-seven non-smokers and steroid-naive patients with CVA (12) and CA (15) were examined. Capsaicin challenge, histamine bronchoprovocation test, nitric oxide levels in exhaled air and sputum induction were performed in all of them. Differential cell sputum recount and supernatant concentrations of eosinophil granule-derived cationic proteins (ECP), interleukin (IL)5, IL8 and tumour necrosis factor (TNF)-alpha were also measured. RESULTS: There were no significant differences in either the inflammatory pattern of soluble markers or differential cell counts between CA and CVA. Histamine PC20 was correlated with IL-5 in CVA, whereas it was associated with sputum eosinophilia in CA. Cough sensitivity (log C5) and histamine PC20 were inversely related in CA. CONCLUSIONS: Although the pattern of inflammatory sputum markers in patients with asthma and cough-variant asthma is similar, its relation with bronchial hyperreactivity and cough sensitivity is different in each group.     

Local release of eosinophil peroxidase following segmental allergen provocation in asthma

BACKGROUND: Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma. OBJECTIVE: As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma. METHODS: Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils. RESULTS: In asthmatic patients a large increase in BAL eosinophils--total cells: median 9.5 x 10(6) (range: 0.5 to 455.0 x 10(6)); relative: 38% (1 to 91%)--was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 microg/L (1.0 to 6.8 microg/L) to 42 microg/L (5.6 to 379.6 microg/L; P < 0.01) after allergen but not after saline challenge (1.5 microg/L; 1.0 to 21.9 microg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 microg/L (3.0 to 56.8 microg/L) to 27 microg/L (3.8 to 133.9 microg/L; P < 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P < 0.01) after allergen challenge. CONCLUSION: The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space.     

IgE-Fc receptor expressions on bronchoalveolar lavage (BAL) cells in a patient with eosinophilic pneumonia accompanied with bronchial asthma--the effect of ketotifen on their expression

In this study, IgE-Fc receptor expressions on each type of BAL cells (lymphocytes, macrophages and eosinophils) in a patients with eosinophilic pneumonia accompanied by bronchial asthma were examined by indirect immunofluorescent method using monoclonal antibody (H107). BAL cell findings showed marked increases of total BAL cell counts and eosinophils, an increased number of lymphocytes and the presence of basophilic cells. These results match those of our previous report. Furthermore, IgE-Fc receptor expressions on lymphocytes, macrophages and eosinophils were markedly increased as compared to those in the peripheral blood and normal control subjects. These findings suggest that IgE production in the lung plays the main role in the pathogenesis of eosinophilic pneumonia and bronchial asthma. On the other hand, during ketotifen administration, decreases of peripheral blood eosinophilia, of eosinophilia in the sputum and of serum IgE level and an improvement in chest X-ray findings were observed. Furthermore not only normalization of total BAL cell counts but also decreases of IgE-Fc receptor expressions on BAL cells were observed.     

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.     

Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma

BACKGROUND: We have previously shown increased expression of the CD4(+) cell chemoattractant IL-16 in bronchial mucosa of patients with asthma. We investigated the effects of allergen challenge on airway IL-16 expression. METHODS: We investigated the expression of IL-16 immunoreactivity in bronchial biopsy samples obtained from atopic asthmatic subjects (n = 19) and normal subjects (n = 6) 24 hours after segmental allergen challenge. Control biopsy samples were obtained either at baseline or after diluent challenge. IL-16 expression was correlated to numbers of CD4(+) cells, CD25(+) cells, and activated eosinophils. IL-16 bioactivity was assessed in bronchoalveolar fluid obtained from patients with asthma. RESULTS: IL-16 expression was higher in control biopsy specimens obtained from subjects with asthma compared with normal subjects (P<.05). In patients with asthma, numbers of IL-16 immunoreactive cells were significantly higher in biopsy specimens obtained after allergen challenge compared with control biopsy specimens (P<.001). Allergen provocation was associated with release of IL-16 in bronchoalveolar fluid in patients with asthma. In normal subjects, there was no difference in the number of IL-16-immunoreactive cells in biopsy specimens obtained after allergen challenge compared with biopsy specimens obtained after diluent challenge. Allergen challenge was associated with an increase in the numbers of EG2(+) eosinophils in patients with asthma but not in normal subjects. IL-16 expression correlated with the numbers of CD4(+) cells and CD25(+) cells after allergen challenge in asthmatic subjects with a provocative concentration required to decrease the FEV(1) by 20% of its baseline value (PC(20)FEV(1)) < 4 mg/mL. IL-16-immunoreactive cells were identified mainly as T cells and eosinophils in asthmatic subjects after allergen challenge. CONCLUSION: Endobronchial allergen provocation in atopic asthmatic patients resulted in increased airway expression of IL-16 and release of bioactive IL-16 in airways. IL-16 may contribute to the immunoregulation of the inflammatory infiltrate in the airways in response to antigen.     

Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients

Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.     

Plasma histamine and bronchial reactivity in allergic asthma

Histamine is an important mediator of allergic inflammation and bronchial hyperresponsiveness (BHR), a hallmark of asthma. Studies on the relationship between plasma histamine and BHR in allergic asthmatic patients have yielded controversial results. We therefore measured plasma histamine and bronchial reactivity in 30 nonsmoker volunteers taking no medication. Eleven were normal subjects; 19 were stable, mildly allergic asthmatic patients. Venous blood was taken to measure blood cells and basal plasma histamine by radioimmunoassay. After blood sampling, all subjects underwent a measurement of PC₂₀M (concentration of methacholine causing a 20% fall in FEV₁). Mean plasma histamine levels were 0.21 ± 0.1 ng/ml and 0.44 ± 0.3 ng/ml in normal and asthmatic subjects, respectively (P<0.05). We found a significant increase of blood eosinophils and basophils in asthmatic patients, and a positive correlation between plasma histamine and circulating basophils. PC₂₀M was greater than 16 mg in normal volunteers, and mean PC₂₀M was 2.1 ± 2 mg/ml in asthmatic patients. PC₂₀M did not correlate with plasma histamine levels, but it did so negatively with blood eosinophils. The increased plasma histamine concentration in mildly atopic asthmatic patients might be a consequence of the high basophil releasability of atopies and the higher basophil counts in allergic asthma. Plasma histamine is thus unlikely to be a determinant of BHR in asthma.     

Interleukin-5 receptors on human lung eosinophils after segmental allergen challenge

BACKGROUND: IL-5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge. OBJECTIVE: The action of IL-5 is mediated via the specific IL-5 receptor-alpha (IL-5Ralpha). Although in vitro data suggest that IL-5R expression is regulated by cytokines such as IL-3, IL-5 and GM-CSF, IL-5R regulation in vivo and its kinetics following allergen provocation are incompletely understood. METHODS: We investigated IL-5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL-5Ralpha was measured by flow cytometry and IL-5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA. RESULTS: IL-5Ralpha expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL-5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL-5 concentrations in serum 18 or 42 h after allergen exposure. CONCLUSIONS: Although there was no correlation between IL-5 concentrations and IL-5Ralpha expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL-5 concentrations and IL-5Ralpha expression on eosinophils.     

Serum IgE levels in normal subjects and allergy patients among the Chinese in Singapore.

Serum IgE was determined in four groups of Singapore Chinese consisting of 292 normal subjects, 15 patients with atopic dermatitis, 39 with drug allergy and 14 with bronchial asthma. The results were compared with the findings of similar groups in western countries. In the normal subjects the range and means (numerical and geometrical) of serum IgE were four to seven times higher in the Singapore Chinese than reported in the western countries. However, the circulating levels in atopic dermatitis and bronchial asthma patients were comparable. In drug allergy moderate IgE elevation was noted. The serum IgE levels of the normal subjects and patients with atopic dermatitis and bronchial asthma were markedly lower than those found in nearby Papua New Guinea. The significance of these observations is discussed.     

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.