Overexpression of CD-11b and CXCR1 on circulating neutrophils: its possible role in COPD.

BACKGROUND: It has been shown that the beta2-integrin molecule is up-regulated in circulating neutrophils in COPD subjects. However, little has been reported about the expression of the cell surface molecules in such patients and their relationship with pulmonary function. The aim of the present study was to investigate the surface expression of molecules in circulating neutrophils and to clarify their possible role in the airflow limitation of COPD. METHODS: The surface expression of Mac-1 cells (ie, CD-11b and CD-18 cells) and CXC chemokine receptor (CXCR) 1 and CXCR2 of circulating neutrophils obtained from COPD patients and healthy subjects (HSs) was measured by flow cytometry analysis. The serum levels of interleukin (IL)-8 were measured by enzyme-linked immunosorbent assay. RESULTS: Both CD-11b and CXCR1 expression were significantly higher in COPD patients than in HSs (mean [+/- SE] CD-11b concentration: HSs, 9.7 +/- 1.0; COPD patients, 14.2 +/- 1.8 [p < 0.05]; mean CXCR1 concentration: HSs, 9.6 +/- 0.5; COPD patients, 11.9 +/- 0.4 [p < 0.01]). Although aging was positively correlated with the expression of CXCR1 (r = 0.440; p < 0.01), none of the other background factors, including smoking and body mass index, showed a correlation with the expression of the molecules. Although serum IL-8 levels were higher in patients with COPD than in HSs, no significant correlation between serum IL-8 levels and the expression of any molecule was seen. The expression of CD-11b (r = -0.317) and CXCR1 (r = -0.383) showed a significant negative correlation with the severity of airflow limitation (both p < 0.05). CONCLUSIONS: The overexpression of CD-11b and CXCR1 in circulating neutrophils may be associated with the development of airflow limitation in COPD patients.

The influence of free 3-nitrotyrosine and saliva on the quantitative analysis of protein-bound 3-nitrotyrosine in sputum.

BACKGROUND: We have recently developed a new technique for quantitatively measuring protein-bound 3-nitrotyrosine (3-NT), a footprint of nitrosative stress, utilizing high-performance liquid chromatography with an electrochemical detection (HPLC-ECD) system. Using this system, we showed that 3-NT formation was upregulated in the sputum of both COPD and asthmatic patients. However, in order to improve the accuracy of the measurement system, We have to resolve some problems which were the influence of free amino acid form of 3-NT and of salivary contamination. OBJECTIVES: We initially investigated the amount of the free amino acid form of 3-NT in induced sputum and compared with that of protein-bound 3-NT. Next, we evaluated the concentration of protein-bound 3-NT in saliva and compared with that in induced sputum by means of HPLC-ECD. METHODS: Five male COPD patients were enrolled. Induced sputum and saliva were obtained from the patients. The free amino acid form of 3-NT in sputum and saliva was measured by HPLC-ECD, and the protein-bound 3-NT and tyrosine in sputum and saliva were enzymatically hydrolyzed by Streptomyces griseus Pronase and measured for the protein hydrolysate by HPLC-ECD. RESULTS: The mean value of the amount of protein-bound 3-NT was 65.0 fmol (31.2 to 106.4 fmol). On the other hand, the amount of the free amino acid form of 3-NT was under the detection limit (<10 fmol). The levels of both 3-NT (sputum: 0.55 +/- 0.15 pmol/ml, saliva: 0.02 +/- 0.01 pmol/ml, p < 0.01) and tyrosine (sputum: 0.81 +/- 0.43 micromol/ml, saliva: 0.07 +/- 0.04 micromol/ml, p < 0.01) in saliva were significantly lower than in sputum. The percentage of 3-NT in saliva to that in sputum was about 3.1%, and that of tyrosine was about 9.0%. CONCLUSION: The free amino acid form of 3-NT does not affect the measurement of protein-bound 3-NT. Furthermore, the influence of salivary contamination on the measurement of protein-bound 3-NT in induced sputum by means of HPLC-ECD was very small and could be negligible.

Two cases of asthma in handicapped elderly persons in which assisted inhalation therapy was effective.

BACKGROUND: Chronic airway inflammation is a basic pathology of bronchial asthma and it is important to control the inflammation by anti-inflammatory therapy mainly with steroids. However, in asthma in the elderly, there are cases where physicians hesitate to introduce the inhaled corticosteroid (ICS) therapy based on the diagnosis that the use of inhalants is difficult due to the existence of a functional lesion accompanying asthma. METHODS & RESULTS: In cases where self-administrated inhalation therapy is difficult to execute due to the accompaniment of a functional lesion and in cases where sufficient curative effects of steroids are not produced in self-inhalation, administration of assisted inhalation resulted in improvement of clinical symptoms and pulmonary function and was proven effective. CONCLUSIONS: Assisted inhalation therapy is expected to be useful in general and also in terms of expanding the application of ICS in the asthma in the elderly.

Airway cytokine expression measured by means of protein array in exhaled breath condensate: correlation with physiologic properties in asthmatic patients.

BACKGROUND: Simultaneous monitoring of airway inflammation and physiology might be useful for asthma management. OBJECTIVE: We examined the upregulated molecules in asthmatic airways. Furthermore, we investigated the relationship between these molecules and the airway physiologic properties of asthma. METHODS: Ten nonsmoking healthy subjects and 16 steroid-naive asthmatic patients were enrolled. Exhaled breath condensate (EBC) sampling, spirometry, and methacholine inhalation challenge were performed on one occasion in this cross-sectional study. Peak expiratory flow was also measured for 4 weeks. Airway cytokine-chemokine-growth factor production was analyzed with a protein array. RESULTS: The expressions of IL-4, IL-8, IL-17, TNF-alpha, RANTES, IFN-gamma-inducible protein 10, TGF-beta, and macrophage inflammatory protein 1alpha and 1beta were significantly upregulated in asthmatic airways compared with those of nonsmoking healthy subjects. Among the upregulated molecules, RANTES expression was significantly correlated with the parameters that represent airway caliber, FEV(1) and respiratory resistance values. In addition, the levels of both TNF-alpha and TGF-beta were significantly correlated with the methacholine threshold and peak expiratory flow variability for the week. CONCLUSION: Inflammatory molecule analysis with EBC appeared to be useful for monitoring the asthmatic airway condition. CLINICAL IMPLICATIONS: Measurements of cytokine levels in EBC might be a promising approach to assess the efficacy of pharmacologic interventions and to investigate the pathophysiology of asthma.

[A case of hypersensitivity pneumonitis caused by Gyrodontium versicolor].

A 36-year-old woman was admitted to our hospital because of fever, dry cough, dyspnea on exertion and body weight loss in August 2000. Chest radiography and CT scanning showed diffuse ground glass opacity and small centrilobular nodules in the middle and lower lung fields of both lungs. Serum antibody against Trichosporon cutaneum was positive; and summer-type hypersensitivity pneumonitis was therefore initially diagnosed. Treatment with methylprednisolone and prednisolone decreased the symptoms, but the dyspnea reappeared when the patient was at home. Inspection of her house revealed the presence of fungi under the floor. After these were removed, her symptoms disappeared completely. The lymphocytic stimulation test of the peripheral blood was positive for the fungi, and it was therefore suggested that they were the cause of her hypersensitivity pneumonitis. The fungi were identified as Gyrodontium versicolor. This is the first report of hypersensitivity pneumonitis caused by Gyrodontium versicolor.