Sputum Of Asthmatic Patients Research Articles

Thrombin in the airways of asthmatic patients.

The mechanism of airway remodeling in asthmatic patients is poorly understood. Thrombin is a multifunctional protease that, in addition to its critical role in thrombotic processes, has also been described as inducing cellular and molecular events relevant to tissue remodeling. The present investigation was undertaken to evaluate the activity of thrombin in the sputum of asthmatic patients and its potential role in airway remodeling. The study population comprised 8 healthy subjects and 14 stable patients with bronchial asthma. The concentrations of thrombin, thrombin-antithrombin complex (TAT), and tissue factor were measured in the sputum of all subjects. The concentrations of thrombin (p = 0. 007), TAT (p = 0.01), and tissue factor (p = 0.02) in sputum were significantly higher in asthmatic patients than in healthy controls. The proliferative effects that sputum from asthmatic patients (p = 0. 01) and thrombin (p = 0.03) have on cultured human smooth muscle cells was inhibited significantly in the presence of recombinant hirudin, a specific thrombin inhibitor. Significant statistical correlation was observed between the degree of bronchial responsiveness and the sputum concentrations of thrombin (r = -0.8; p = 0.02) and TAT (r = -0.9; p = 0.01). The results of this study showed that increased thrombin generation occurs in the airway of patients with asthma and that it may play a role in the pathogenesis of airway remodeling. Further studies should be carried out to assess whether these findings are also observed in other airway diseases.

Increased levels of elastase and alpha1-antitrypsin in sputum of asthmatic patients.

Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels in sputum with reference to differential cell counts. We found that in induced sputum obtained from asthmatic and chronic bronchitis patients, the levels of both total and active elastase were significantly increased as compared with those of control subjects and healthy smokers and were significantly correlated with the percentage of neutrophils. In addition, in asthma and chronic bronchitis patients, the levels of active and total elastase were inversely correlated with the degree of airway obstruction as assessed from FEV1 values. This study shows that airway inflammation in asthma and chronic bronchitis is associated with high levels of active elastase, which may play a role in the pathogenesis of airway remodeling.

Clinical Implication of Protein Levels of IL-5 in Induced Sputum in Asthmatic Patients

To determine whether protein levels of interleukin-5 (IL-5) in induced sputum reflect the degree of eosinophilic inflammation, we evaluated the role of IL-5 on clinical characteristics in stable asthmatic patients. IL-5 level, differential eosinophil count, and level of eosinophil cationic protein (ECP) in induced sputum were all significantly higher for asthmatics than for normal controls. Both eosinophil counts and ECP levels in induced sputum were inversely correlated with the degree of airflow limitation (FEV1/FVC). In addition, patients with measurable IL-5 in sputum had significantly more eosinophils, higher levels of ECP in sputum, and lower FEV1 (percent predicted) than did patients with levels of IL-5 beneath the limit of detection. However, we found no significant difference in IL-5 levels between atopic and nonatopic asthmatics. IL-5 level in induced sputum is a good indicator of eosinophilic inflammation in atopic and nonatopic asthmatic patients.

Eosinophil Viability-enhancing Activity in Sputum from Patients with Bronchial Asthma: Contributions of Interleukin-5 and Granulocyte/Macrophage Colony-stimulating Factor

To investigate the mechanisms of eosinophil activation in the airways of patients with asthma, we attempted to detect eosinophil-activating cytokines in sputum extracts obtained from asthmatic patients during acute attacks or in remission by eosinophil survival assay. Purified guinea pig eosinophils were cultured in the presence or absence of sputum extracts, and the eosinophil viability was measured on Day 4. Eosinophil viability in the presence of sputum extracts derived from patients during moderate or severe attacks was significantly higher than that for sputum obtained from patients in remission or during mild attacks or from those with other respiratory diseases, including bronchiectasis and diffuse panbronchiolitis (p < 0.05). The total symptom score during the week prior to sputum collection correlated with the eosinophil viability (rs = 0.79, p < 0.01). Eosinophil viability-enhancing activity (EVEA) in the sputum of asthmatic patients with moderate or severe attacks was neutralized by anti-IL-5 antibody and by anti-GM-CSF antibody by 19.9 ± 13.7% and 76.9 ± 8.2% (mean ± SEM, n = 7), respectively. EVEA was completely neutralized by a combination of anti-IL-5 and anti-GM-CSF antibodies. There was a significant correlation between the concentration of eosinophil cationic protein (ECP) in sputum extracts and the eosinophil viability (rs = 0.54, p < 0.05). These findings suggest that IL-5 and GM-CSF are present in the sputum during asthma attacks and that these cytokines are at least partially responsible for eosinophil activation in asthma.

Eosinophil viability-enhancing activity in sputum from patients with bronchial asthma, Contributions of interleukin-5 and granulocyte/macrophage colony-stimulating factor.

To investigate the mechanisms of eosinophil activation in the airways of patients with asthma, we attempted to detect eosinophil-activating cytokines in sputum extracts obtained from asthmatic patients during acute attacks or in remission by eosinophil survival assay. Purified guinea pig eosinophils were cultured in the presence or absence of sputum extracts, and the eosinophil viability was measured on Day 4. Eosinophil viability in the presence of sputum extracts derived from patients during moderate or severe attacks was significantly higher than that for sputum obtained from patients in remission or during mild attacks or from those with other respiratory diseases, including bronchiectasis and diffuse panbronchiolitis (p < 0.05). The total symptom score during the week prior to sputum collection correlated with the eosinophil viability (rs = 0.79, p < 0.01). Eosinophil viability-enhancing activity (EVEA) in the sputum of asthmatic patients with moderate or severe attacks was neutralized by anti-IL-5 antibody and by anti-GM-CSF antibody by 19.9 +/- 13.7% and 76.9 +/- 8.2% (mean +/- SEM, n = 7), respectively. EVEA was completely neutralized by a combination of anti-IL-5 and anti-GM-CSF antibodies. There was a significant correlation between the concentration of eosinophil cationic protein (ECP) in sputum extracts and the eosinophil viability (rs = 0.54, p < 0.05). These findings suggest that IL-5 and GM-CSF are present in the sputum during asthma attacks and that these cytokines are at least partially responsible for eosinophil activation in asthma.

Sputum and blood eosinophils during corticosteroid treatment of acute exacerbations of asthma

Eleven patients with chronic bronchial asthma were studied during a noninfectious exacerbation. Each patient received 80 mg of prednisone daily for three days. Spirometric values, total blood eosinophil counts, and 24-hour quantitation of sputum eosinophils were studied. Three patients had total blood eosinophil counts of less than 250 at the time of presentation. Statistical comparisons with findings on Day 0 showed significant improvements for the one-second forced expiratory volume, total blood eosinophil count, and sputum eosinophil number. On Day 7, the one-second forced expiratory volume maintained a statistically significant difference from that on Day 0, but the total blood eosinophil count did not. Analysis of correlation coefficients showed significant relation between the total blood eosinophil count and one-second forced expiratory volume, the sputum eosinophil count and one-second forced expiratory volume, and the sputum eosinophil and total blood eosinophil counts. The conclusions are (1) blood eosinophilia is not an invariable feature of acute exacerbations of asthma; (2) numbers of blood and sputum eosinophils reflect the response of an acute exacerbation of asthma to corticosteroids; (3) sputum eosinophils may be more meaningful for monitoring the stable postcorticosteroid state; (4) there is no support for the belief that eosinophils disappear from the sputum of asthmatic patients with clinically effective doses of corticosteroids.

Allergy and immunology: an annotated bibliography of recent literature. Allergy and Immunology Committee, American College of Physicians.

Allergy and immunology: an annotated bibliography of recent literature. Allergy and Immunology Committee, American College of Physicians.

気管支喘息知見補遺

In order to make clear how Curschmann's spiral, especially its central fibre is produced in the respiratory tract, I have histologically and histochemically investigated not only the sputum of asthmatic patients, but also the trachea, the bronchus, their mucous, serous and mixed glands and their ducts in the autopsies of the patients died during asthmatic attacks.The materials of the lungs were carefully fixed in 10% formalin solution, which was kept warm at 38°C. They were partly cut by means of celloidin-method and partly frozen method. For general observation of the lungs haematoxylin-eosin staining method, for that of mucus cresylechtviolett staining method, and for that of nuclear component nuclear staining method (Feuigen) was used.The results were as follows:1. According to my investigation, Curschmann's spiral is chiefly composed of mucus. Although their central fibres are chiefly composed of far thicker mucus than the other parts of the spiral, they contain cellular components, specialy nuclear components, derived from mucous cells, leucocytes, eosinophil cells and plasma cells, as well.2. The fine central fibres are already produced in the mucous cells of mucous and mixed glands as well in tbeir ducts.3. Some of thick central fibres in the lumen of respiratory tract is composed of the mixture of thick mucus and cellular components caused by the destruction and fusion of the above cells in that tract.4. As soon as the fibres of various size enter into the lumen of the respiratory tract, they gather together and are twisted, because of the production of a whirl-pool of air in the lumen of the wall during asthmatic attacks. Thus, the thick central fibres are produced. However, I was not able to find anywhere that the central fibres are made of the mucus from the goblet cells. Therefore, whether or not these cells also takes part in production of central fibres, requires further minute investigalon.