Airway inflammatory response to ozone in subjects with different asthma severity.
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The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity. Two groups of asthmatic subjects were studied: seven with intermittent mild asthma not requiring regular treatment (group A); and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting beta2-agonists (group B). All subjects were exposed, in a randomized cross-over design, to air or O3 (0.26 parts per million (ppm) for 2 h with intermittent exercise); subjects in group B withdrew from regular treatment 72 h before each exposure. Before the exposure, and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test, and a questionnaire was completed to obtain a total symptom score (TSS). Six hours after the end of the exposure, hypertonic saline (HS) sputum induction was conducted. Sputum cell percentages, eosinophil cationic protein (ECP) and interleukin (IL)-8 concentrations in the sputum supernatant were measured. TSS significantly increased and forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) significantly decreased after O3 exposure in comparison with air exposure in group A, whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O3 exposure. Sputum neutrophil percentage was significantly higher after O3 exposure than after air exposure in both groups (Group A: 70.2% (28-87) versus 26.6% (8.6-73.2); Group B: 62.1% (25-82.4) versus 27.9% (14.4-54)). IL-8 was higher in sputum supernatant collected 6 h after O3 exposure than after air, only in group A. No change due to O3 has been found in sputum eosinophil percentage and ECP concentration in both groups. In conclusion, the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity. The available data do not allow elucidation of whether this difference depends on the severity of the disease or on the regular anti-inflammatory treatment. (+info)
Inflammatory response after inhalation of bacterial endotoxin assessed by the induced sputum technique.
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BACKGROUND: Organic dusts may cause inflammation in the airways. This study was performed to assess the usefulness of the induced sputum technique for evaluating the presence of airways inflammation using inhaled endotoxin (lipopolysaccharide) as the inducer of inflammation. METHODS: To characterise the inflammatory response after inhalation of endotoxin, 21 healthy subjects inhaled 40 micrograms lipopolysaccharide and were examined before and 24 hours after exposure. Examinations consisted of a questionnaire for symptoms, spirometric testing, blood sampling, and collection of induced sputum using hypertonic saline. Eleven of the subjects inhaled hypertonic saline without endotoxin exposure as controls. Cell counts, eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) were determined in blood and sputum. RESULTS: A significantly higher proportion of subjects reported respiratory and general symptoms after endotoxin inhalation. MPO and the number of neutrophils in the blood were higher and spirometric values were decreased after the lipopolysaccharide challenge. In the sputum MPO, ECP, and the numbers of neutrophils and lymphocytes were higher after the lipopolysaccharide challenge. No significant differences were found after the inhalation of hypertonic saline compared with before, except for a significantly lower number of lymphocytes in the sputum. CONCLUSIONS: The results support previous studies that inhaled endotoxin causes an inflammation at the exposure site itself, as well as general effects. Sampling of sputum seems to be a useful tool for assessing the presence of airways inflammation, and the inhalation of hypertonic saline used to induce sputum did not significantly interfere with the results found after inhalation of lipopolysaccharide. (+info)
Suppression of airway inflammation by theophylline in adult bronchial asthma.
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BACKGROUND: Chronic continuous airway inflammation caused by eosinophils has been noted to play critical roles in the pathophysiology of bronchial asthma, in addition to reversible obstruction and hypersensitivity of the respiratory tract. Therefore, suppression of chronic airway inflammation has become more important in asthma treatment. Although theophylline has been a conventionally used bronchodilator, it has been recently reported to have concurrent anti-inflammatory effects. OBJECTIVE: Accordingly, we studied the effects of a slow-release theophylline preparation, Theolong, on airway inflammation. METHODS: Administration of Theolong 400 mg/day to 24 patients with mild or moderate asthma and measuring eosinophil cationic protein (ECP), a marker of airway inflammation, and eosinophils in sputum and peripheral blood at 4 and 8 weeks. RESULTS: As a result, sputum ECP, serum ECP and sputum eosinophil count (%) were significantly lowered after 4 and 8 weeks. CONCLUSION: Thus, in the theophylline-administered group, slow-release theophylline, Theolong, was effective in treating asthma, with anti-inflammatory effects on inflammatory cells besides its bronchodilator action. (+info)
Adhesive explant culture of allergic nasal mucosa: effect of emedastine difumarate, an anti-allergic drug.
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Allergic reaction of the nose comprises of an immediate and a late reaction. To evaluate nasal allergic reactions, many experiments have been performed by investigators. In this study, we performed a new tissue culture technique (adhesive explant culture) to analyze the migration of cells into the culture medium from the cultured allergic nasal mucosa in response to an allergen. Basophilic cells (mast cells and basophils) and eosinophils, which were released into the culture medium after the allergen challenge, were evaluated by the analysis of histamine and eosinophil cationic protein (ECP) content in the culture medium. Histamine and basophilic cells in the culture medium were more abundant in the immediate phase (within 30 min) after challenge than in the late phase (from 30 min to 10 hr). On the other hand, ECP and eosinophils in the culture medium were more abundant in the late phase than in the immediate phase. The increase of histamine content in both phases were not inhibited by pre-treatment of emedastine difumarate (EME), an anti-allergic drug. However, the increase of ECP in the late phase was inhibited by pre-treatment with EME. Moreover, the number of EG2-positive cells was also decreased by pre-treatment with EME. These results suggest that EME might lower the activation of eosinophils in the late phase of the allergic reaction. The present study also indicates that this adhesive explant culture system is useful model for studying the cellular allergic responses to drugs ex vivo. (+info)
Diagnosing occupational asthma: use of induced sputum.
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The diagnosis of occupational asthma (OA) needs to be made with as much objective evidence as possible. If there is airway inflammation, measurement of this should be an asset. The objective of this study was to investigate whether there is an increase in induced sputum and blood eosinophils and eosinophil cationic protein (ECP) in OA after work exposure. Patients were assessed after a 2-4 week period at work and away from work with cell counts and ECP assays performed blind to the clinical data. They were considered to have OA if symptoms were worse at work and there was a fall in forced expiratory volume in one second (FEV1) > or =20% or in the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) of four-fold or more compared with away from work. Patients whose symptoms were worse at work but had a change in FEV1 of <20% and in methacholine PC20 of less than four-fold were considered as controls. Sixteen patients were studied. Ten had OA and six were controls. Patients with OA had a significant increase in median (interquartile range) sputum eosinophils and ECP when at work compared with the periods out of work, 10.0 (17.05) versus 0.8 (1.6)% (p=0.007) and 3,840 (6,076) versus 116 (180) microg x L(-1) (p=0.01). They also had a higher blood eosinophil count, 0.3 (0.5) x 10(9) versus 0.2 (0.1) x 10(9) x L(-1) (p=0.013), and a trend towards higher serum ECP levels, 44.0 (20.0) versus 32.0 (18.5) microg x L(-1) (p=0.07). In conclusion, the proportion of eosinophils and levels of eosinophil cationic protein in sputum are particularly high at work in patients with occupational asthma, suggesting that the measurement of these factors can supplement other physiological outcomes in establishing the diagnosis of occupational asthma. (+info)
Alpha2-macroglobulin and eosinophil cationic protein in the allergic airway mucosa in seasonal allergic rhinitis.
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As previously demonstrated in seasonal allergic rhinitis, increased microvascular permeability and eosinophil activation are key features of allergic airway inflammation. In the present study, the hypothesis that exudation of alpha2-macroglobulin may cause the appearance of eosinophil cationic protein (ECP) in the airway lumen was explored. Nasal lavages were carried out using the nasal pool device before and during the pollen season both at baseline and after histamine challenge in 10 children with allergic rhinitis. Nasal lavage fluid levels of alpha2-macroglobulin and ECP were determined. All patients experienced nasal symptoms of allergic rhinitis during the pollen season (p<0.01-0.05). Baseline nasal lavage fluid levels of alpha2-macroglobulin and ECP were increased during the season (p<0.01-0.05) and were found to be well correlated (p<0.0001). Histamine produced concentration-dependent plasma exudation before and during the pollen season, but it was only during the pollen season that this caused an increase in the lavage fluid levels of ECP (p<0.05). These data suggest that exudation of plasma and increased tissue levels and output of eosinophil cationic protein characterize nasal mucosal inflammation in children with seasonal allergic rhinitis. The plasma exudation process in part may account for lumenal entry of eosinophil cationic protein molecules that have been released in mucosal tissue compartments. A combination of induced exudation and nasal lavage may improve the yield of important markers of inflammation in studies of nasal diseases. (+info)
Induced sputum in adolescents with severe stable asthma. Safety and the relationship of cell counts and eosinophil cationic protein to clinical severity.
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This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma. Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12-18 yrs of age, FEV1 65-110% of predicted, on 500-2,000 microg inhaled steroids daily). FEV1 was reversible by 13.3-2.3% pred. After sputum induction, FEV1 was still increased by 9.0+/-2.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4-59.5)% squamous cells, 47.3 (6.8-84.0)% macrophages, 39.0 (4.6-84.8)% neutrophils, 4.8 (1.0-12.4)% lymphocytes, 0.4 (0-10.8)% eosinophils and 3.6 (0-23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03). In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with beta2-agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma. (+info)
The effect of processing on inflammatory markers in induced sputum.
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The effects of the mucolytic agent, dithioerythritol (DTE), and the temperature at which sputum processing is conducted on cellular and biochemical markers in induced sputum was assessed. Samples from healthy and atopic asthmatic subjects were treated with either DTE or phosphate-buffered saline (PBS) at 22 or 37 degrees C and compared for cell counts and concentrations of histamine, tryptase, eosinophil cationic protein (ECP), free interleukin (IL)-8, immunoglobulin (Ig)A, IL-8/IgA complexes and secretory component (SC). In addition, the influence of DTE on in vitro mediator release from blood eosinophils, basophils and bronchoalveolar lavage (BAL) mast cells was studied. Processing with DTE improved cytospin quality and increased the cell yield and measurable ECP, tryptase, IgA and SC, but reduced levels of histamine in PBS-treated samples and had no effect on IL-8. Cell counts or mediator levels were similar when sputum was processed at 22 or 37 degrees C, even though DTE induced blood basophils and BAL mast cells to release histamine at 37 degrees C. In spiking experiments, recovery of added ECP, tryptase, total IL-8 and histamine from sputum was similar in DTE- and PBS-processed sputum, but reduced for free IL-8 in PBS-treated samples. In conclusion, dithioerythritol improves cell and mediator recovery without causing cell activation when sputum processing is conducted at room temperature. The extent of recovery depends on the mediator studied. (+info)