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Cellular profiles in asthmatic airways: a comparison of induced sputum, bronchial washings, and bronchoalveolar lavage fluid.

BACKGROUND: Analysis of bronchoalveolar lavage fluid has improved our understanding of the pathogenesis of asthma. Safety issues and access to expert resources limit this techniques as a research tool. Induced sputum is a non-invasive method of collecting airway fluid which is applicable to subjects with a range of severity of airflow obstruction. The method of sputum collection and processing differs between groups. A study was undertaken to compare induced sputum with bronchoscopically collected fluid. METHODS: Sixteen patients with mild stable asthma underwent both sputum induction and bronchoscopic examination with bronchial washings and bronchoalveolar lavage (BAL) in random order, with each procedure being separated by an interval of 12 days. Airway fluid was processed and stained for differential cell counting. RESULTS: Induced sputum was relatively rich in neutrophils and eosinophils compared with bronchial washings and BAL fluid (mean (SE) 1.3 (0.4)%, 5.0 (2.7)%, and 36.4 (3.7)% neutrophils and 0.6 (0.1)%, 1.6 (0.6)%, and 3.3 (1.1)% eosinophils in BAL fluid, bronchial washings, and induced sputum, respectively). The proportions of cells obtained at sputum induction correlated with those in bronchial washings but not BAL fluid (r = 0.6 and 0.7 for neutrophils and eosinophils, respectively, p < 0.05). By contrast, induced sputum had a lower proportion of lymphocytes and macrophages than bronchial washings or BAL fluid, without any correlation. CONCLUSION: Induced sputum is rich in neutrophils and eosinophils and poor in lymphocytes, suggesting an origin in the larger airways. Induced sputum adequately reflects the findings in fluid collected by direct bronchoscopy.

Adult↗

Endothelin-1 levels in induced sputum samples from asthmatic and normal subjects.

BACKGROUND: Endothelin-1 (ET-1) is a potent bronchoconstrictor which may have a role in the pathogenesis of asthma. The levels of ET-1 in saliva, induced sputum, and plasma from asthmatic and non-asthmatic subjects were compared. METHODS: Sputum induction was performed on 28 asthmatic subjects and nine normal volunteers. ET-1 levels were measured in plasma, saliva, and sputum samples and reversed phase high performance liquid chromatography (RP-HPLC) was performed on saliva and sputum samples. RESULTS: ET-1 was present in the following order of concentration in both normal and asthmatic subjects: saliva > sputum > plasma (saliva, median 30.1 and 23.9 pg/ ml, respectively; sputum, median 15.5 and 11.2 pg/ml; plasma, median 3.1 and 3.6 pg/ ml). There were no differences between asthmatic and normal subjects in the levels of ET-1 in each fluid. The levels of ET-1 in asthmatic subjects were not influenced by whether or not they were taking inhaled steroids. RP-HPLC of sputum and saliva confirmed the presence of ET-1 in these fluids. CONCLUSIONS: Levels of ET-1 can be measured in saliva and sputum obtained by sputum induction in asthmatic and healthy subjects and, although no difference was found in basal levels of ET-1 in sputum, saliva and plasma between normal subjects and asthmatics without bronchoconstriction, it is apparent that ET-1 is produced or released locally within the respiratory tract in concentrations higher than those in plasma.

Adult↗

A comparison of induced and expectorated sputum for the microbiological diagnosis of community acquired pneumonia.

BACKGROUND: Sputum induction has proved useful in the diagnosis of Pneumocystis carinii pneumonia and mycobacterial infections but there are scant data on its use in the diagnosis of community-acquired pneumonia (CAP). OBJECTIVE: To better define the usage of sputum induction by hypertonic saline in the setting of CAP. METHODS: A retrospective review of records of patients admitted to a community teaching hospital in the year 1995 with a diagnosis of CAP. RESULTS: Of 492 patients admitted with CAP, 71 (14%) had attempted sputum induction. A group of 66 patients with CAP and attempted sputum collection by spontaneous expectoration was compared with this group. Sputum induction failed to yield a sample in 22 patients (31%). Forty-five of 49 patients (92%) with induced sputum had received prior antibiotics as compared to 23 of 34 patients (68%) with expectorated samples (p < 0.05), due to sputum induction often being attempted later in the hospital course. The diagnostic yield of sputum induction was 14 of 71 (20%) compared to 16 out of 66 (24%) for attempted spontaneously expectorated samples. Antibiotic therapy was changed for 5 of 34 patients (15%) who spontaneously expectorated samples and for 9 of 49 patients (18%) with successful induction. CONCLUSIONS: Sputum induction is effective in obtaining sputum in some patients with CAP who fail to expectorate a sample. Attempting induction early, preferably before starting antibiotics, may increase its diagnostic yield.

Administration, Inhalation↗

Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage.

To determine the relationship between inflammatory cells in sputum, bronchoalveolar lavage (BAL), and bronchial mucosa, we counted the number of leukocytes in sputum, BAL, and bronchial biopsies obtained from subjects with asthma and with chronic bronchitis in stable condition or during exacerbations. Sputum was induced by inhalation of hypertonic saline in the asthma group. Spontaneous sputum was collected in the chronic bronchitis groups. Differential counts of leukocytes were performed on cytospin preparations of sputum and BAL. Eosinophils, macrophages, neutrophils, and lymphocytes were quantified in the submucosa of the bronchial biopsies. In asthma and in stable chronic bronchitis, the percentages of neutrophils were significantly higher in sputum than in BAL, whereas the opposite was true of the percentages of macrophages and lymphocytes. The lymphocyte was the predominant cell infiltrating the bronchial submucosa in all groups. BAL eosinophils correlated with submucosal and sputum eosinophils in the asthma and exacerbated chronic bronchitis groups. A similar trend was observed between submucosal and sputum eosinophils. In conclusion, the relative proportion of inflammatory cells was different in sputum, BAL, and bronchial mucosa. However, there was a fairly good agreement between the number of eosinophils counted with the three techniques in asthmatics and in exacerbated chronic bronchitics, suggesting that sputum cell analysis may be used for a noninvasive assessment of airway eosinophilia.

Adult↗

Cystic fibrosis sputum: a barrier to the transport of nanospheres.

Cystic fibrosis (CF) is characterized by the presence of a viscoelastic mucus layer in the upper airways and bronchi. The underlying problem is a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator protein. Clinical studies of gene transfer for CF are ongoing. For gene delivery to the airways of CF patients to be effective, the mucus covering the target cells must be overcome. We therefore examined the extent to which CF sputum presents a physical barrier to the transport of nanospheres of a size comparable to that of lipoplexes and other transfection systems currently being clinically evaluated for CF gene therapy. We observed that an extremely low percentage of nanospheres (< 0.3%) moved through a 220-microm-thick CF sputum layer after 150 min. The largest nanospheres studied (560 nm) were almost completely blocked by the sputum, whereas the smaller nanospheres (124 nm) were retarded only by a factor of 1.3 as compared with buffer. Surprisingly, the nanospheres diffused significantly more easily through the more viscoelastic sputum samples. We hypothesize that the structure of the network in sputum becomes more macroporous when the sputum becomes more viscoelastic. Sputum from a patient with chronic obstructive pulmonary disease retarded the transport of nanospheres to the same extent as did CF sputum. When directly mixed with CF sputum, recombinant human deoxyribonuclease I moderately facilitated the transport of nanospheres through CF sputum.

Cystic Fibrosis↗

Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum.

We studied sputum tobramycin concentrations after intravenous administration in 10 cystic fibrosis patients. Tobramycin concentrations were determined by a bioassay and a radioenzymatic assay (REA). The bacterial density of Pseudomonas aeruginosa in sputum was examined serially during therapy. Bioactivity of tobramycin in the sputum was low and increased little during treatment. In contrast, tobramycin content (as assayed by REA) showed a progressive accumulation of the drug to high concentrations: a mean of 82 micrograms/g sputum after 3 wk of therapy in 4 patients. Pseudomonas aeruginosa was eradicated from the sputum in 3 of 4 patients receiving antibiotic therapy for 3 wk. Eradication correlated with tobramycin sputum concentrations measured by REA, which were 20-fold greater than the apparent tobramycin inhibitory concentration. A bactericidal effect of aminoglycosides in the presence of sputum in vitro could only be reliably produced with concentrations 25-fold the MIC. We conclude that tobramycin penetrates cystic fibrosis (CF) sputum and accumulates over time. Although CF sputum antagonized the bioactivity of aminoglycosides, 3 wk of intravenous therapy combined with an antipseudomonal beta-lactam antibiotic may be effective in eradication of P. aeruginosa from sputum of certain CF patients.

Adolescent↗

Exhaled nitric oxide and sputum eosinophil markers of inflammation in asthmatic children.

Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.

Adolescent↗

Sputum and pulmonary function in asthma.

STUDY OBJECTIVE: To assess the relevance of sputum production to pulmonary function, in particular, persistent obstruction in patients with a primary clinical diagnosis of asthma. DESIGN: Cross-sectional study of all patients currently followed up in secondary care in a defined locality. SETTING: National Health Service and private clinics in north-east England. PATIENTS: All attenders, aged 18 years or older, with asthma, confirmed by reversibility of peak expiratory flow (PEF) by > or =15% and to > or =200 L/min. INTERVENTIONS: Pro forma history. Pulmonary function at attendance. Assessment of best function according to protocol. Measurement of actual FEV1, FVC, and PEF at attendance. MEASUREMENTS AND RESULTS: We studied 772 subjects; 387 (50%) were male; mean age was 55 years; atopic, 51%; current smokers, 11.5%; ex-smokers, 36%; and never smokers, 52.5%. Best pulmonary function was lower in chronic sputum producers (PEF, 83.2 vs 95.8; FVC, 67.9 vs 81.7% predicted). Chronic sputum production and its negative relationship with best function was strongly associated with smoking. There was little relationship between chronic sputum and persistent obstruction in nonsmokers. There were no univariate associations between sputum during attacks, or its color, and pulmonary function, but after allowing for demographic factors, including smoking, green sputum was associated with persistent obstruction. There was little relationship between sputum and actual/best function at attendance. CONCLUSIONS: Chronic sputum production is associated with persistent obstruction principally in those who have smoked, suggesting that the association reflects smoking rather than asthma. There is no interaction with atopy. After allowance for cigarette smoking, there is an association between green sputum production during exacerbations and persistent obstruction. Green sputum during relapse in asthma may indicate inflammation that is relevant to prognosis.

Adult↗

The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis.

STUDY OBJECTIVES: Identification of acid-fast bacilli (AFB) in the sputum smear at the completion of tuberculosis therapy is in some settings considered evidence of treatment failure. However, some patients with pulmonary tuberculosis (TB) will have positive smear results with negative sputum culture results at the end of therapy. The objectives of this study were to estimate the prevalence of persisting positive sputum smear results in patients with TB and to identify characteristics that distinguish patients with persistently positive sputum smear results who also had negative sputum culture results from patients identified as treatment failures. DESIGN: A population-based, historical cohort study with nested case control study. SETTING: British Columbia Division of Tuberculosis Control central case registry. PATIENTS: All 428 patients with culture-proven pulmonary TB in British Columbia over 7 years with sputum that was positive for AFB. METHODS: Review of laboratory data of all 428 patients, as well as clinical data of a subset of 30 patients with persistently positive smear results beyond 20 weeks. RESULTS: Sputum smears were positive for AFB in 205 patients (48%) at 4 weeks, in 30 patients (7%) at 20 weeks, and in 12 patients (3%) at 36 weeks. Of the patients with smear results that were persistently positive at 20 weeks, 23 (77%) had negative sputum culture results and 7 (23%) had positive sputum culture results (ie, they were treatment failures). Patients identified as treatment failures had more localized disease as shown on chest radiographs, had less radiographic improvement at follow-up, had a higher prevalence of drug resistance, and were less compliant with medications than patients with persistently positive smear results and negative culture results. No subject with a negative culture result relapsed over the 6- to 48-month observation period. CONCLUSION: Sputum that is persistently positive for AFB in patients in developed countries is more likely to be associated with negative culture results than with treatment failure.

Adult↗

Effect of physical and chemical methods of homogenization on inflammatory mediators in sputum of asthma patients.

BACKGROUND: Dithiothreitol (DTT), which is used for sputum homogenization, may split S-S bonds of the bronchial mucins as well as other proteins and, thus, may have a detrimental effect on inflammatory mediators that are present in sputum. OBJECTIVE: To evaluate the effects of physical sputum homogenization, using ultrasonic and chemical (ie, DTT) means, on the concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), and myeloperoxidase (MPO) in the sputum of patients with asthma. METHODS: The collection of sputum samples from nine patients with asthma was induced by their inhaling a sterile 3% saline solution for 10 min from an ultrasonic nebulizer. One half of the sputum sample was homogenized by ultrasound, and the other half was liquefied by DTT. The supernatant of the ultrasonically homogenized specimen was divided into the following three portions: (1) immediately frozen; (2) stored for 15 min at 37 degrees C; and (3) additionally treated with DTT. The supernatant of the sputum sample that was liquefied by DTT was divided into the following two portions: (1) immediately frozen; and (2) additionally subjected to ultrasound. The concentrations of ECP, EPO, EPX, and MPO in the sputum samples were measured using immunoassays. RESULTS: Statistically significant differences were found between the ultrasonically homogenized specimens that had been either processed immediately or stored at 37 degrees C and those treated by DTT, but only for concentrations of EPO and MPO (p < 0.005). No effect of temperature on the mediators in the ultrasonically homogenized specimens could be detected. Ultrasonic homogenization had no influence on the mediators in the samples liquefied by DTT. However, the addition of DTT to the cell-free supernatant of the ultrasonically homogenized sputum samples caused a significant fall in measured EPO and MPO concentrations. CONCLUSIONS: The sputum processing by DTT caused a statistically significant fall in EPO and MPO concentrations but did not significantly influence the measured concentrations of ECP and EPX.

Adult↗

Concentration of CCL11, CXCL8 and TNF-alpha in sputum and plasma of patients undergoing asthma or chronic obstructive pulmonary disease exacerbation.

Asthma and chronic obstructive pulmonary disease (COPD) are common respiratory illnesses characterized by chronic inflammation of the airways. The characterization of induced or spontaneously produced sputum is a useful technique to assess airway inflammation. In the present study, we compared the concentrations of CCL2, CCL11, CXCL8, and tumor necrosis factor-alpha (TNF-alpha) in plasma and induced sputum of patients with severe asthma or COPD and correlated the levels of these mediators with inflammatory cells in sputum. Asthmatic patients had elevated levels of eosinophils (40.1 +/- 6.24%) in sputum whereas neutrophils (63.3 +/- 4.66%) predominated in COPD patients. The levels of the chemokine CCL11 were markedly increased in sputum (708.7 +/- 330.7 pg/ml) and plasma (716.6 +/- 162.2 pg/ml) of asthmatic patients and correlated with the percentage of eosinophils in induced sputum. The concentrations of CXCL8 (817.0 +/- 105.2 pg/ml) and TNF-alpha (308.8 +/- 96.1 pg/ml) were higher in sputum of COPD patients and correlated with the percentage of neutrophils in induced sputum. There was also an increase in the concentrations of CXCL8 (43.2 +/- 6.8 pg/ml) in sputum of asthmatic patients. These results validate that sputum is a suitable method to assess chemokines and cytokines associated with asthma and COPD. Moreover, the mechanisms involved in the synthesis of CCL11 and CXCL8/TNF-alpha would be helpful to better understand the inflammatory profile associated with asthma and COPD, respectively.

Adult↗

Sputum induction as a method of analyzing pulmonary cells: reproducibility and acceptability.

Sputum induction has been proposed as a noninvasive method of sampling airway cells for assessing airway inflammation in asthma. Although useful in the research setting, the applicability of this technique to a respiratory clinic, where it might prove useful for clinical management of anti-inflammatory therapy, has not been assessed. We therefore studied the effect of sputum induction in terms of patient acceptability, effect upon airway caliber, and reproducibility of the total cell and differential cell count at 2 weeks in 20 asthmatic subjects first attending an asthma clinic. We compared such patients with normal controls. Thirty-seven subjects underwent sputum induction on two occasions (20 asthmatics and 17 normal subjects) separated by a 2-week interval, using a standardized protocol. Acceptability was assessed by questionnaire. Airway caliber was measured by serial spirometry, using albuterol premedication for asthmatic subjects. Sputum was induced by inhalation of 3.5% saline over 12 min. Total cell and differential counts on induced sputum were assessed and correlated with bronchial hyperresponsiveness, as well as reproducibility of the technique in the clinical setting. All subjects found the process acceptable, although mild side effects occurred in more than 90% of subjects. No differences in acceptability were found between asthmatic and normal subjects. Sputum induction was associated with a significant decrease in forced expiratory volume in 1 sec (FEV1) in normal subjects (from 4.1 +/- 0.17 to 4.02 +/- 0.19 L [p < 0.01] on visit 1 and on visit 2 from 4.01 +/- 0.15 to 3.90 +/- 0.16 L [p < 0.01]), but not in asthmatic subjects after albuterol premedication. Total pulmonary cell yield on the first and second sputum induction days was 1.97 +/- 0.06 x 10(6) cells/mL of sputum and 2.01 +/- 0.05 x 10(6) cells/mL of sputum, respectively, giving a reliability coefficient of 0.77. Less agreement was seen between individual cell differential counts within subjects, but most fell within the expected range on Bland-Altman plots. Sputum induction appears to be safe and acceptable in both normal and asthmatic subjects. A small decrease in FEV1 occurs in normal subjects, which is prevented by albuterol premedication in asthmatics. Reproducibility at 2 weeks yielded similar total numbers of pulmonary cells, but in a clinic population some variability was seen in the number of inflammatory cells, probably because of the small numbers of these cells. This technique may be less valuable in a clinical than a research setting.

Administration, Inhalation↗

Viscoelastic properties of bronchorrhoea sputum in bronchial asthmatics.

Dynamic viscoelastic properties of 13 bronchorrhoea sputum samples from asthmatics with bronchorrhoea, defined as the production of watery sputum of 100 ml or more per day during asthmatic attacks, were examined and then compared with 7 saliva and 12 mucoid sputum samples obtained from patients during remission. Dynamic viscosity (eta') and elasticity (G') of bronchorrhoea sputum increased rapidly with time up to 2 hours after collection and slowly thereafter, whereas eta' and G' of saliva and mucoid sputum remained unchanged up to 6 hours after collection. Then, eta' and G' of saliva, bronchorrhoea and mucoid sputum samples were measured between 2 to 4 hours after expectoration. Bronchorrhoea sputum samples showed significantly larger values at frequencies of both 0.1 and 1.0 rad/sec than did saliva samples and also significantly smaller values than did mucoid sputum samples. Thus, bronchorrhoea sputum differed in dynamic viscoelastic properties from saliva, indicating that it does not result from hypersalivation. Based on data of viscoelastic changes with time, it can be assumed that the viscoelasticity of bronchorrhoea sputum in the airways is considerably less than the optimal range reported previously for mucociliary velocity, suggesting the possibility of impaired mucociliary transport.

Adult↗

[Sensitivity of sputum eosinophil cationic protein level for monitoring asthmatic patients with normal peak expiratory flow].

Previous studies have shown that eosinophils and eosinophil cationic protein (ECP) levels in the sputum of patients with asthma closely reflect inflammatory activity of the bronchial mucosa. We examined whether the ECP level or eosinophil count in induced sputum provides information useful in determining whether to taper the dose of medications or to terminate treatment especially with inhaled corticosteroids in patients with well controlled asthma. We studied 15 adults with asthma who consistently maintained a peak expiratory flow (PEF) value within 80% or more of their predicted value (green zone) for at least 4 weeks with no asthmatic symptoms. All patients underwent at least two hypretonic saline inhalation tests. Forty sputum samples were obtained for evaluation of cell count and ECP level. Before the tests, patients were requested to record asthmatic symptoms, medications received, and morning and evening PEF values in a diary for more than 3 months. The relations among clinical and laboratory variables, including symptoms scores, medication scores, asthma scores (= symptom scores + medication scores). PEF values, forced expiratory volume (FEV1.0) during the test, and sputum eosinophil count or sputum ECP, were analyzed. The sputum ECP level correlated significantly with the percentage of eosinophils in the sputum (rs = 0.783). There were also significant correlations between the sputum ECP level and the mean weekly symptom scores (rs = 0.500-0.510), medication scores (rs = 0.510-0.540), and asthma scores (rs = 0.509-0.548). However, there were no significant correlations among sputum ECP level, mean morning PEF or evening PEF, daily variation in PEF, and FEV1.0. We conclude that the sputum ECP level is a sensitive laboratory variable useful in monitoring the presence of eosinophilic inflammation in the bronchial mucosa of patients with bronchial asthma, especially those who have mild or no symptoms with normal PEF.

Adult↗

[Correlations between chymase activity, levels of tryptase, and eotaxin in the sputum of patients with chronic obstructive pulmonary disease and their clinical implications].

OBJECTIVE: To investigate the correlations between chymase activity, levels of tryptase, interleukin-8 (IL-8), eotaxin, neutrophil and eosinophil numbers in the sputum of elderly patients with chronic obstructive pulmonary disease (COPD) and their clinical implications. METHODS: A total of 73 elderly patients with COPD (21 severe, 21 moderate and 31 mild) were recruited into the study. IL-8 and eotaxin levels were detected with Sandwich enzyme-linked immunosorbent assay (ELISA) procedures and tryptase levels were measured with antibody against tryptase with Uni CAP system. Chymase activity was determined spectrophotometrically (410 nm) by the rate of hydrolysis of 0.7 mmol/L N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (SAAPP) in NaCl 1.5 mol/L and Tris 0.3 mol/L The specific activity of chymase was expressed as mU/ml. Actions of protease inhibitors on chymase activities were also examined with enzyme assay. RESULTS: (1) At acute attack stage, the sputum levels of tryptase of patients with severe, moderate and mild COPD were 284.0, 215.0 and 59.5 ng/L, respectively. The sputum levels of tryptase in the severe and moderate patients were greater than that in mild patients (P <0.01). The tryptase levels in the sputum of all patients were significantly decreased following treatment( 151.0, 92.0, 3.3 ng/L respectively; P <0. 01). At acute attack stage, the sputum levels of IL-8 and eotaxin were 1 299. 8,454. 9,78.7 ng/L; 22.7, 15.1, 7.4 ng/L, respectively. Severe and moderate-patients were greater than that of patients at mild stages. At convalescent stage,the sputum levels of IL-8 and eotaxin were 1 037. 5,326.6, 67.9 ng/L; 7.9, 6.3, 6.8 ng/L, respectively. The IL-8 and eotaxin levels in the sputum of severe and moderate patients were significantly decreased following treatment (P < 0.01). (2) The specific chymase activities of severe and moderate patients were higher than mild patients. Native protease inhibitors alpha1-antitrypsin (alpha1-AT) and soy bean trypsin inhibitor (SBTI) inhibited 83% and 89% enzymatic chymase activity, respectively. (3) The numbers of neutrophils and eosinophils in sputum were increased in patients with COPD at the acute stage compared with the mild convalescent stage. At all remission stages, the elevated numbers of cells were significantly reduced. (4) At acute attack stage of patients with COPD, there were correlations between the sputum levels of tryptase, IL-8, eotaxin, neutrophils and eosinophils; and there were correlations between the sputum levels of tryptase, chymase and neutrophils. CONCLUSION: COPD is not merely a neutrophil associated disease, but mast cells, eosinophils and their released mediators also actively contribute to the pathogenesis of the disease.

Aged↗

[Change and clinical implication of urotensin II in plasma and induced sputum of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the roles of urotensin II (U-II) in chronic obstructive pulmonary disease (COPD). METHODS: Plasma and induced sputum were obtained from thirty four patients with stable COPD and ten healthy volunteers. The levels of U-II in plasma and induced sputum were measured by RIA kit. Lung function was performed routinely. Induced sputum cells were counted with hemacytometer and differentiated with Wright-Giemsa stain. RESULTS: The levels of U-II in induced sputum were 82 and 65 folds higher than those of plasma U-II in COPD patients and healthy controls (P<0.01). The levels of U-II in plasma were unrelated to those of induced sputum (r = 0.168, P>0.05). No difference was noted between COPD and healthy controls in the plasma U-II levels [1.46(1.15, 1.73) vs 1.61(1.31, 2.17) microg/L, medians with interquartile ranges, P>0.05]. Sputum U-II levels from COPD patients were 15% higher than those of healthy controls [119.87(105.03, 132.60) vs 104.44 (56.33, 122.24) microg/L, medians with interquartile ranges, P<0.05]. Induced sputum U-II levels of COPD patients had a trend of increase as lung function deteriorated and smoking index increases. Raised sputum total cell and neutrophil counts correlated strongly with the levels of U-II in induced sputum (r = 0.454, r = 0.431, both P<0.01). The levels of U-II in induced sputum correlated negatively with FEV(1)% predicted and p(O(2)) (r = -0.417, r = -0.518, both P<0.05). CONCLUSION: U-II may act locally, or, via paracrine or autocrine way, play a role in the mechanism of the airway inflammation and airway remodeling in COPD.

Aged↗

[Clinical and pathophysiological significance of neutrophil elastase in sputum and the effect of erythromycin in chronic respiratory diseases].

The concentration and activity of neutrophil elastase (NE) in sputa were measured in 24 patients with chronic respiratory diseases such as diffuse pan-bronchiolitis, bronchiectasis and and chronic bronchitis. The results were compared to the clinico-pathophysiological parameters such as clinical impairment score, concentration of albumin and ciliary transport velocity of the sputum. Furthermore, the relationship between the post-therapeutic change of NE in sputum and clinical effect of erythromycin (EM) was investigated in the same cases. Physico-chemical properties of the sputum, including rheological characteristics, mucus transport velocity, phospholipid composition, concentration of albumin and fucose were also analyzed before and after EM therapy. There was a significant positive correlation between NE in sputum and the clinical impairment score, which suggested that the concentration and activity of NE in sputum reflected the clinical severity in such diseases. The concentration and activity of NE also had significant positive and negative correlation to the concentration of albumin and ciliary transport velocity, respectively. Therefore, it was considered that NE in airway could bring the leakage of albumin from serum and interfere with mucociliary transport. The patients were divided into responders (n = 12) and non-responders (n = 12) after EM therapy based on the change of the clinical impairment score. The clinical effect of EM in chronic respiratory diseases was not associated with its bacteriostatic action, but with the quantitative and qualitative suppression of sputum NE. The decrease of the adhesive properties of the sputum, which was observed in responders after administration of EM, was considered to depend on the reduction of the concentration of albumin in sputum. Concerning the phospholipid composition of sputum, sphingomyelin and phosphatidyl-ethanolamine, which had been suggested to be components of serum and cellular membrane, had a tendency to decrease in responders. The proportion of phosphatidylcholine increased in responders. The improvement of ciliary transport velocity of the sputum, which was noted in responders, was probably due to the results mentioned above. In non-responders, these findings were not observed after EM therapy. EM had no influence on the production, release and activity of NE as a result of in vitro experiments using human peripheral neutrophils. Neutrophil chemotaxis was however suppressed after incubation with EM. These results suggest that the mechanisms of the effect of EM is not direct action on NE but through suppression of neutrophil chemotaxis.

Adult↗

The quality and diagnostic outcome of postbronchoscopic sputum.

In patients with a malignant lung process (146 patients with primary lung cancer and 21 patients with a metastatic lung malignancy), the quality and the percentage of true-positive diagnoses of sputum produced directly after bronchoscopy were evaluated. The quality of prebronchoscopic and postbronchoscopic sputum samples differed significantly, the former being of better quality for cytologic diagnosis. When calculated for the whole group, the quality of postbronchoscopy sputum was not related to any specific anamnestic or clinical patient data. Overall, there was no statistically significant difference between the percentages of true-positive diagnoses in prebronchoscopic and postbronchoscopic sputum specimens. However, the percentage of true-positive diagnoses was significantly higher in postbronchoscopic sputum in comparison with the results of sputum cytology prior to bronchoscopy when the results were calculated separately for patients with low forced expiratory volume values (less than 50% of the vital capacity) or for patients without a history of previous sputum production. In patients who produced bloody sputum, the percentage of true-positive diagnoses in prebronchoscopic sputum was significantly higher than in postbronchoscopic sputum.

Bronchoscopy↗