[Clinical features of bronchial asthma with mucus hypersecretion].
Yoshiro TanizakiHikaru KitaniMorihiro OkazakiTakashi MifuneFumihiro MitsunobuRyo SodaShinya TadaKiyoshi TakahashiIkuro Kimura
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Fifty patients with bronchial asthma were divided into four groups according to the amount of expectoration per day: 0-24, 25-49, 50-99 and 100+ ml/day. Clinical features of patients with mucus hypersecretion (more than 50 ml/day of expectoration) were evaluated by age, severity of disease, cellular composition of bronchoalveolar lavage (BAL) fluid, and ventilatory function. 1. The proportion of patients with steroid-dependent intractable asthma (SDIA) in each group increased with increase in mucus hypersecretion. 2. Many of the patients with mucus hypersecretion (more than 50 ml/day) were over the age of 40. 3. The proportion of BAL eosinophils was significantly higher in patients with hypersecretion (more than 50 ml/day) than in those with expectoration of less than 49 ml/day. There was a significant correlation between the proportion of BAL eosinophils and the amount of expectoration per day (r = 0.48, p < 0.05). Proportions of lymphocytes and neutrophils in the BAL fluid were not related to the amount of expectoration per day. 4. There was no significant correlation between the amount of expectoration per day and ventilatory function in patients with asthma in this study.Cite
A relationship of cellular composition in the airways and the release of chemical mediators from the cells to bronchial hyperresponsiveness was examined in two age-matched asthma groups: 15 atopic and 15 nonatopic patients. 1. A significant correlation between the proportion of eosinophils in bronchoalveolar lavage (BAL) fluid and bronchial reactivity (BR) was found in patients with atopic and nonatopic asthma. The proportion of the cells (combined eosinophils and neutrophils) in BAL fluid was closely correlated with BR in patients with atopic asthma, but not in those with nonatopic asthma. There was no correlation between the proportion of BAL neutrophils and BR in the two asthma groups. 2. There was a significant correlation between histamine release from BAL cells and BR in patients with atopic asthma. In contrast, LTC4 release from BAL cells was significantly corrected with BR in patients with nonatopic asthma. The results suggest that the humoral and cellular components in the airways, that participate in bronchial hyperresponsiveness, are different between patients with atopic and nonatopic asthma.
Bronchial hyperresponsiveness
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Respiratory center
Center (category theory)
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Leukocyte-endothelial cell interaction is essential for leukocyte infiltration into inflammatory sites. Initiation of adhesion is through the up-regulated expression of adhesion molecules in the endothelium or epithelium and the activation of adhesion molecules on leukocytes. To our knowledge, there have been few reports concerning soluble intercellular adhesion molecule-1 (s1CAM-1) in patients with atopic bronchial asthma after allergen challenge. If the levels of s1CAM-1 vary between bronchial asthma patients and normal controls, this variance would be useful to assess the state of this disease. Therefore, we measured the levels of s1CAM-1 in sera from 17 patients with atopic bronchial asthma and normal control subjects. Levels of s1CAM-1 in sera from bronchial asthma patients in prechallenge conditions were higher than in normal control subjects. Levels of s1CAM-1 in sera from bronchial asthma patients 8 hr after challenge were higher than those in sera obtained during prechallenge periods. s1CAM-1 levels in bronchoalveolar lavage (BAL) fluids from bronchial asthma patients 8 hr after challenge were higher than at 30 min after challenge. These results suggest that higher levels of s1CAM-1 in sera and BAL fluids reflect the up-regulation of ICAM-1 expression in allergic bronchial asthma and these high levels may contribute to the pathogenesis of atopic bronchial asthma.
Pathogenesis
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We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 <80% predicted. BAL fluid was obtained from all subjects. The numbers of different cell types and the levels of 48 cytokines were measured in these fluids. Compared to healthy control subjects, patients with asthma had significantly more percentages of eosinophils and neutrophils, IL-1RA, IL-1α, IL-1β, IL-2Rα, IL-5, IL-6, IL-7, IL-8, G-CSF, GROα (CXCL1), MIP-1β (CCL4), MIG (CXCL9), RANTES (CCL5) and TRAIL in their BAL fluids. The only inflammatory markers that distinguished controlled asthma from uncontrolled asthma were neutrophil percentage and IL-8 levels, and both were inversely correlated with FEV1. We examined whether grouping asthma subjects on the basis of BAL eosinophil % or neutrophil % could identify specific cytokine profiles. The only differences between neutrophil-normal asthma (neutrophil≤2.4%) and neutrophil-high asthma (neutrophils%>2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1.
Endotype
Interleukin 8
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Methacholine
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Asthma is a complex disease. The heterogeneity of airway inflammation during asthma indicates there are different mechanisms involved. In order to further study the mechanisms of asthma, different mouse models were established to mimic corresponding subtypes of asthma in clinic. Eosinophilic asthma was established by intraperitoneal injections of ovalbumin (OVA) on day 0 and day 7, followed by inhalation of aerosolized OVA on days 14-17. Neutrophilic asthma was established by transtracheal administration of a high dose of lipopolysaccharide (LPS; 10 µg) on days 15 and 17 in combination with OVA sensitization and challenge as described previously. Mix-granulocytic asthma was established by transtracheal administration of a low dose of LPS (1 µg) on day 15, in combination with OVA sensitization and challenge as described previously. Compared with healthy controls, increased numbers of eosinophils, elevated levels of T helper (Th)2 cytokines in bronchoalveolar lavage fluid (BALF), and moderated inflammation of lung tissues was observed in eosinophilic asthma. Increased numbers of neutrophils, elevated levels of Th1 and Th17 cytokines in BALF and severe inflammation of lung tissues was observed in neutrophilic asthma. Increased numbers of both eosinophils and neutrophils, elevated levels of Th1, Th2 and Th17 cytokines in BALF and severe inflammation of lung tissues was observed in mix-granulocytic asthma. Airway hyperresponsiveness, increased bronchial mucus secretion, and elevated serum levels of immunoglobin (Ig)E and OVA-IgE were detected in all three asthma models. Dexamethasone reduced the pathogenic symptoms of the mice in eosinophilic asthma, however had no effect on neutrophilic asthma or mix-granulocytic asthma. Each model of asthma established in the present study represents corresponding subtypes of asthma in clinic.
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Chronic Obstructive Pulmonary Disease (COPD) is a public health problem worldwide.It is a polygenic disease and a classical example of gene-environment interaction.Of the many inhalational exposures that may be encountered over a lifetime, only tobacco smoke and occupational dusts and chemicals (vapors, irritants, and fumes) are known to cause COPD on their own.Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) may be impaired in patients with COPD.Aim of the study: to assess respiratory muscle function in male COPD patients by measuring MIP and MEP values and to identify possible correlation between MIP and MEP and the anthropometric parameters as well as degree of airflow obstruction among COPD patients. Subjects and methods:A case-control study was carried out on 50 COPD male patients and 50 of age and sex matched healthy subjects as a control group.All participants were subjected to assessment of respiratory muscle (RM) strength by MIP and MEP, pulmonary function tests {flow/volume spirometry, and MVV}, as well as the functional exercise capacity (6MWT) and the anthropometric measurements.Results: the values of MIP and MEP in COPD cases were lower than those of the control group with a statistically significant difference.In COPD cases the MIP and MEP were positively correlated with VC%, FEV1\FVC, FEV1%, FVC%, PEF%, MVV%, and 6MWD (p<0.00).Furthermore, COPD patients were subdivided according to the presence of respiratory muscle (RM) affection into two subgroups: Group A (patients with RM affection) and Group B (patients without RM affection).There was a significant difference between the two subgroups concerning smoking index , disease duration, VC% , FVC% ,FEV1\FVC, FEV1%, PEF%, MVV%, and 6MWD (P< 0.05). Conclusion:RM is affected in patients with COPD.Measurement of MIP and MEP indicates the state of RM which is related to smoking index, disease duration, and spirometric-indices (VC%, FVC%, FEV1\FVC, FEV1%, PEF%, and MVV %).Recommendation: Health care workers involved in the diagnosis and management of COPD patients especially those with severe airflow obstruction should consider the possibility of RM deterioration and should have an access to RM function assessment.
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