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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies using the CA 19-9 antibody have demonstrated that serum mucin levels in patients with cystic fibrosis (CF) are elevated and that the degree of elevation relates to the age of the patient and possibly to his or her clinical status. However, CA 19-9 only recognizes the mucin-associated blood group sialyl Le(a+) antigen, so mucin levels cannot be measured in patients without Lewis antigens. The present study used the 17B1 monoclonal antibody to measure serum mucin levels in normal subjects, and in patients with CF, patients with chronic obstructive pulmonary disease (COPD), and patients with lung transplants. Serum mucin levels were 25 ng/ml (+/- 1 SEM, n = 8) in normal subjects, 13,853 ng/ml (+/- 1,281, n = 25) in patients with CF, and 25.5 ng/ml (+/- 1.9, n = 17) in patients with COPD. Patients with CF who were sialyl Le(a-b-) also had elevated serum mucin levels (715 +/- 152, n = 2). Serum mucin levels of six lung transplant recipients with CF were elevated compared with those in normal subjects (4,621 +/- 765 ng/ml), but they were not different from serum mucin levels in six lung transplant recipients without CF (5,307 +/- 1.677 ng/ml). Preliminary characterization of the serum mucin antigen showed that: (1) in CF sera, the antigen is polydisperse and smaller than the antigen in normal sera; (2) the mucin antigen is distinct from ABO blood group antigens. Serum mucin levels may be a useful marker to follow a specific patient's response to therapy.
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PMID:Elevated levels of serum mucin-associated antigen in adult patients with cystic fibrosis. 834 2

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.
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PMID:Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis. 838 38

To evaluate the prognostic significance of the age at onset of chronic Pseudomonas aeruginosa colonization (OPCP) with respect to pulmonary disease progression in patients with cystic fibrosis (CF), a retrospective long-term analysis using annual chest radiographs was performed on 54 CF patients. Thirty-seven patients (68%) were chronically colonized before the age of 12 years (group 1), 17 patients (32%) thereafter (group 2). These two groups did not significantly differ in terms of mean duration of follow up (16.2 +/- 5.9 years), sex, CF genotypes, colonization with other respiratory pathogens, supportive medical treatment and death rate during the study period. Chest radiographs were evaluated according to the Chrispin-Norman score, increasing scores representing increasing severity of respiratory disease. In both groups, progression of score means was not accelerated of score means was not accelerated up to 6 years after OCPC (Scores at OCPC set 0; mean score +/- SEM 6 years prior to OCPC -5.6 +/- 2.0; 10 years after OCPC +3.6 +/- 0.7 points). Patients chronically colonized prior to age 12 years (group 1) scored significantly higher between age 2 and 11 years (maximum difference at age 8 years [mean +/- SEM]: 9.4 +/- 0.7 vs. 4.3 +/- 1.3 points; P = 0.002) as compared to group 2. After age 11 years, mean scores were similar in both groups, since in group 2 scores increased rapidly after age 8 years. We conclude that OCPC did not cause an immediate acceleration of CF lung disease judged by serial chest radiographs. Rapid progression in group 2 (OCPC after age 12 years) was independent of OCPC since it occurred earlier. These data indicate that OCPC may be a marker rather than the cause of respiratory disease progression.
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PMID:The age at onset of chronic Pseudomonas aeruginosa colonization in cystic fibrosis--prognostic significance. 852 15

Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.
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PMID:Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation. 879 58

Airway inflammation in children younger than 5 yr of age is difficult to assess, particularly in patients with cystic fibrosis (CF). Furthermore, determining responses to therapies is often subjective in infants, especially those with CF. To determine whether airway DNA levels could be used as an index of airway inflammation, we measured DNA levels in bronchoalveolar lavage fluid (BALF), using a Hoechst dye-binding assay. BALF DNA levels and neutrophils from 16 infants with CF were compared with levels obtained from seven older CF patients and nine control children who underwent bronchoalveolar lavage for evaluation of other pulmonary diseases. BALF DNA was increased in both infants (3.2 +/- 0.7 microg/ml) and older patients with CF (5.4 +/- 0.9 microg/ml) compared with the controls (0.7 +/- 0.2 microg/ml) (mean +/- SEM). BALF DNA levels were not significantly different between infants and older patients with CF. BALF neutrophil counts in CF patients were significantly higher than in controls. Furthermore, BALF DNA levels and total neutrophil counts in infants with CF correlated positively with one another. We conclude that: (1) DNA levels were easily quantifiable in BALF of young children; (2) DNA levels in BALF from CF patients were greater than in a group of children with other pulmonary diseases, and that in some infants with CF, BALF DNA levels were equivalent to those of much older patients with CF; (3) DNA levels in BALF correlate with BALF neutrophil number, an index of inflammation; and (4) some infants with CF have increased levels of DNA in BALF, which may justify a clinical trial of aerosolized rhDNase in this population.
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PMID:Increased DNA levels in bronchoalveolar lavage fluid obtained from infants with cystic fibrosis. 891 59

Sputum analysis is a useful technique for the study of airway inflammation. In asthma, dithiothreitol (DTT) is used to disperse cells from surrounding mucus; however, the applicability of these processing methods to cystic fibrosis (CF) sputum is unknown. In order to compare two methods for processing sputum of patients with CF, sputum was obtained from 11 subjects with CF (8 female, aged 9-21 years). The sample was split into 2 portions and sputum dispersal using DTT was compared with an enzyme mixture (E) of deoxyribonuclease, hyaluronidase, and galactosidase. Outcomes assessed were sample quality, cell viability (percent cells excluding trypan blue), total cell count (TCC), neutrophil count, and elastase immunoreactivity (percent cells positive). Sample quality (enzymes vs. DTT, 8.3 +/- 0.3 vs 7.6 +/- 0.4, mean +/- SEM) and cell viability (enzymes vs. DTT, 75.0% vs. 68.0%, median) were similar for both methods. Sputum total cell count (20.5 x 10(6)/ml vs. 12.0 x 10(6)/ml, median; P = 0.01) and neutrophil count (13.4 x 10(6)/ml vs. 5.5 > 10(6)/ml, median; P = 0.02) were significantly higher with E. Elastase immunoreactivity was lost after processing with E (19.0% vs. 39.5%, median; P = 0.04). When purified peripheral blood neutrophils were incubated with DTT and E, there was no reduction in neutrophil viability, suggesting that the reduced neutrophil number in CF sputum was not due to a toxic effect of DTT but rather incomplete dispersal. We conclude that published sputum processing methods for asthma using DTT give false results when applied to CF sputum, which should be processed using an enzyme mixture.
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PMID:Comparison of sputum processing techniques in cystic fibrosis. 901 74

Using digoxigenin-UTP-labelled human HAM-1 (92 bp) or SMUC41 (850 bp) cRNA probes, the expression and localization of MUC2 gene transcripts were determined by in situ hybridization in human nasal tissues obtained as biopsies from 12 patients with cystic fibrosis (CF): all had been part of a gene therapy trial in which CFTR cDNA-liposome complexes had been delivered by topical application to eight and liposome alone to four as a placebo control. For comparison, there were nasal tissues taken at surgical resection from four non-CF subjects and a further four biopsies taken from normal healthy volunteer controls. Both SMUC41 and HAM-1 probes provided a strong signal. MUC2 mRNA transcripts were present in serous and mucous acini of submucosal glands, ciliated and basal cells of the surface epithelium, and occasional mononuclear inflammatory cells. The percentages (mean +/- SEM) of serous and mucous acini showing positivity for MUC2 gene expression in the four samples surgically resected from non-CF subjects were 25.4 +/- 5.6 and 26.7 +/- 3.3 per cent, respectively. Compared with the non-CF subjects, the mean percentage of acini showing MUC2 gene expression in the four placebo-treated CF subjects was significantly higher for serous (80.5 +/- 12.7 per cent; P < 0.05, t-test), but not for mucous acini (53.1 +/- 16.8 per cent; P = 0.38). In CF and non-CF groups, where present, MUC2 positivity was strongly expressed and constituted approximately 84 per cent of the cell area in serous acini, whereas it was less obvious and was confined to the perinuclear area of cells in mucous acini. A significantly greater proportion of the surface epithelium was positive for MUC2 mRNA transcripts in the CF subjects (89.0, +/- 1.4 per cent) than in the surgically resected tissues of the four non-CF subjects (19.4, +/- 4.0 per cent) (P = 0.02). In the eight CFTR-cDNA-treated subjects, there was an overall trend to reduction, but no statistically significant alteration of MUC2 gene expression. It is concluded that the MUC2 gene is expressed at three- to four-fold higher levels in CF nasal mucosa than in non-CF nasal tissue and that it is expressed in a variety of cells additional to submucosal mucus-secreting glands.
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PMID:Localization and up-regulation of mucin (MUC2) gene expression in human nasal biopsies of patients with cystic fibrosis. 915 17

Cystic fibrosis (CF) is associated with impaired ion transport across epithelial membranes and an increased transepithelial potential difference (PD) that can be measured in airway epithelium. The aim of this study was to investigate the diagnostic value of nasal PD in CF, and to test a modified approach to the measurement of this PD. The reproducibility and diagnostic sensitivity and specificity of nasal PD measurements were tested with the perfusion technique and with a simplified modification of the technique done with a novel, solid-state exploring electrode. With the perfusion method, basal PD values were different in CF patients (mean +/- SEM: -51.6 +/- 0.9 mV, n = 104) than in normal (-15.5 +/- 0.9 mV, n = 58, p < 0.01) subjects. CF patients with acute rhinitis or other nasal pathology had mean PD values that were intermediate between those of the patients and normal and disease-control groups (-28.3 +/- 1.2 mV, n = 40, p < 0.01, different from normal). The diagnostic sensitivity of the perfusion method for CF was 91.3%, and the specificity was 96.4%. PD measurements with the modified technique correlated highly with the results achieved with the perfusion method (r = 0.94, n +/- 158). The measurement of nasal PD effectively distinguishes CF from control subjects. Care must be taken in the interpretation of measurements made on acutely inflamed epithelium. The modified method was simpler than the conventional perfusion technique, and equally effective.
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PMID:Conventional and modified nasal potential-difference measurement in cystic fibrosis. 919 94

Many cystic fibrosis patients with Pseudomonas lung infections receive intravenous (IV) antibiotics and chest physiotherapy (CPT) at home. Previous studies have suggested that home care, in the setting of a clinical study, is as efficacious as hospital care. This report compares the outcomes of home care with minimal supervision to outcomes of hospital care. We compared two groups of similar age and severity of lung impairment. Patients met strict definitions for home or hospital treatment (27 home care courses/33 hospital care courses). Five patients completed six courses of both home care and hospital treatment. Treatment in both groups included intravenous antibiotics and CPT. Primary outcome measures included changes in pulmonary function between the start of treatment and after 2 weeks of therapy, duration of treatment, and intervals between antibiotic courses. In hospitalized patients, forced vital capacity (FVC) increased by 17.4 +/- 3.1% (mean +/- SEM), and forced expiratory volume in one second (FEV1) increased by 23.3 +/- 4.1%, both significant at P < 0.001. The FVC and FEV1 of patients treated at home increased by 10.2 +/- 2.0% and 13.7 +/- 2.6% respectively, neither of which was a significant improvement. Similar results were found in the five patients completing both home and hospital courses. The average duration of treatment was twice as long and time between IV antibiotic courses only two-thirds as long for those treated at home compared with the hospitalized patients. Previous reports have claimed that home care in the setting of a prospective study is as efficacious as hospital care. Our experience indicates that routine home care with minimal supervision of patients is less effective than hospital care. Furthermore, home care as delivered to patients in this report increased the overall cost of care by as much as 30% because of longer and more frequent courses of antibiotic therapy.
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PMID:Effectiveness of home versus hospital care in the routine treatment of cystic fibrosis. 926 52

Increased serum levels of mucin-associated antigen have been previously demonstrated in patients with cystic fibrosis (CF) and interstitial pneumonia, and in lung-transplant recipients. The present study assessed the serum airway mucin levels in patients with acute respiratory distress syndrome (ARDS). An enzyme-linked immunosorbent assay (ELISA) method with a human-airway-mucin-specific monoclonal antibody (17Q2) was used to measure serum mucin levels in normal subjects, chronic smokers, patients with chronic bronchitis and other pulmonary diseases, patients with acute cardiogenic lung edema, and patients with ARDS. The serum mucin levels measured 9.9 +/- 0.8 ng/ml (mean +/- SEM, n = 59) in normal subjects, 12.7 +/- 1.6 ng/ml (n = 29) in chronic smokers, 21.8 +/- 1.9 ng/ml (n = 28) in patients with chronic bronchitis and other pulmonary diseases, 9.0 +/- 3.1 ng/ml (n = 5) in patients with acute cardiogenic lung edema. The serum mucin level was 53.8 +/- 6.6 ng/ml (n = 13) in patients with ARDS (p < 0.05, as compared with the four other groups). Serial measurements of serum mucin levels were obtained in patients with ARDS. Statistical analysis showed an inverse correlation of serial measurements of serum mucin with static respiratory-system compliance (p = 0.021), an inverse correlation of sequential serum mucin levels and log(Pa(O2)/Fl(O2)) (p = 0.016), and a positive correlation of sequential serum mucin levels and lung injury score (LIS) (p = 0.019). Gel-filtration analysis showed that mucin-associated antigens in ARDS sera were polydispersed and smaller than the antigens in normal sera. This study indicates that an increasing amount of degraded mucin occurs in patients with ARDS.
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PMID:Elevated serum levels of mucin-associated antigen in patients with acute respiratory distress syndrome. 937 60


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