lactoferrin and Bronchitis

Oral immunotherapy with inactivated non-typeable Haemophilus influenzae (NTHi) prevents exacerbations of chronic obstructive pulmonary disease, but the mechanism is unclear. The aim of this study was to determine the mechanism of protection. This was a placebo versus active prospective study over 3 months in 64 smokers. The active treatment was three courses of oral NTHi given at monthly intervals, followed by measurement of bacteriological and immunological parameters. The results can be summarized: (i) NTHi-specific T cells increased in the placebo treatment group over time (P<0.05); (ii) the T cell response in the oral NTHi group started earlier than that in the placebo group (P<0.05); and (iii) serum NTHi-specific immunoglobulin (Ig)G had significantly greater variation in the placebo group (P<0.0001). The increase in antibody in placebos over time correlated with exposure to live H. influenzae (P<0.05) determined from culture of gargles; (iv) reduction in saliva lysozyme over time (P<0.05) was detected only in the oral NTHi treatment group. These data are consistent with T cell priming of gut lymphoid tissue by aspiration of bronchus content into the gut, with oral immunotherapy augmenting this process leading to enhanced bronchus protection. The evidence for protection was a stable IgG antibody level through the study in the oral NTHi treatment group, contrasting with an increase in antibody correlating with exposure of the airways to H. influenzae in the placebo group. Saliva lysozyme was a useful biomarker of mucosal inflammation, falling after oral NTHi consistent with a reduction in the level of intralumenal inflammation.

Topics: Administration, Oral; Adolescent; Adult; Antibodies, Bacterial; Bronchitis; Carrier Proteins; Disease Progression; Female; Haemophilus influenzae; Haemophilus Vaccines; Humans; Immunity, Mucosal; Immunoglobulin G; Interferon-gamma; Lactoferrin; Male; Middle Aged; Muramidase; Nitric Oxide; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Saliva; Smoking; Sputum; T-Lymphocytes; Vaccines, Inactivated; Young Adult

Airway inflammation during infection is associated with increased transudation of serum proteins and increased production of protein by the airway epithelium. We therefore, assessed whether Haemophilus influenzae infections in patients with chronic bronchitis are associated with increased levels of transferrin and lactoferrin in the sputum compared to uninfected patients. Sputum sol phase and serum samples from 14 infected and 13 uninfected patients with chronic bronchitis and from 12 bronchial asthma patients were included in the study. The median Q-values (the concentration in sputum sol phase/the concentration in serum) x 10(3) of transferrin appeared increased in chronic bronchitis patients with an H. influenzae infection (26.0, n=13) compared to uninfected controls (9.5, n=11) and bronchial asthma patients (4.5, n=6). The ratio of the Q(transferrin)/Q(albumin) was >1 in infected chronic bronchitis patients, indicating local production of transferrin. Growth of H. influenzae was stimulated more in sputum from infected and uninfected patients with chronic bronchitis than in sputum from patients with bronchial asthma. The concentrations of lactoferrin were not significantly different in infected (n=14) and uninfected (n=13) chronic bronchitis patients and bronchial asthma patients (n=12) (median 137.4, 84.6, 87.1 mg x L(-1), respectively). We conclude that in patients with chronic bronchitis with Haemophilus influenzae infections, the levels of transferrin are increased and the levels of lactoferrin are not associated with infections.

Topics: Adult; Aged; Aged, 80 and over; Bronchitis; Chronic Disease; Exudates and Transudates; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Lactoferrin; Male; Middle Aged; Sensitivity and Specificity; Sputum; Transferrin

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Inhalation; Adult; Aerosols; Airway Obstruction; Albumins; Beclomethasone; Blood Gas Analysis; Bronchitis; Bronchoalveolar Lavage Fluid; Bronchoscopy; Chronic Disease; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Inflammation; Lactoferrin; Male; Middle Aged; Muramidase; Smoking; Transferrin; Vital Capacity

Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection.

Topics: Adolescent; Adult; Biomarkers; Bronchitis; Bronchoalveolar Lavage Fluid; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Cystic Fibrosis; Female; Humans; Immunity, Innate; Infant; Lactoferrin; Leukocyte Count; Leukocyte Elastase; Male; Muramidase; Respiratory Tract Infections; Secretory Leukocyte Peptidase Inhibitor; Young Adult

Since the ability of bacteria to compete with lactoferrin for iron contributes to the pathogenesis of mucosal infections, the presence of lactoferrin receptor activity in non-encapsulated Haemophilus influenzae was investigated. The growth of 18 H. influenzae isolates from the sputum samples of chronic bronchitis patients and of six of seven H. influenzae throat isolates from healthy adults was stimulated by iron saturated human lactoferrin. Apo-lactoferrin did not stimulate the growth of H. influenzae. Human lactoferrin binding to iron limited bacteria was detected for 16 H. influenzae strains from chronic bronchitis patients and for five of seven isolates from healthy adults. We conclude that the majority of H. influenzae isolates tested bind human lactoferrin and that the iron from lactoferrin is used for growth.

Topics: Adult; Bronchitis; Haemophilus Infections; Haemophilus influenzae; Humans; In Vitro Techniques; Iron; Lactoferrin; Receptors, Cell Surface

The aggregation of non-serotypable Haemophilus influenzae (NTHI) by whole saliva from patients with chronic obstructive lung disease (COLD) was investigated. Significant differences were observed between salivary aggregating activity of a control and COLD population (P < 0.001). Saliva from patients less prone to acute exacerbations had a greater capacity to aggregate bacteria compared with saliva from patients with a predilection to infection. The mechanism of saliva-mediated aggregation of NTHI was investigated and shown to be related to lysozyme content. Lysozyme activity in saliva was measured by the turbidimetric technique and results showed that patients with chronic bronchitis had increased levels of salivary lysozyme, with a subpopulation within the non-infection-prone group having greater amounts. A significant difference was observed in salivary lysozyme between controls and non-infection-prone (P < 0.005) and infection-prone (P < 0.05) patients, respectively: the non-infection-prone patients having significantly (P < 0.005) more than the infection-prone patients. There was significant correlation (r = 0.742, P < 0.001) between salivary aggregation of NTHI and lysozyme activity. Chromatographically purified human lysozyme had a similar aggregation profile to that of saliva. There was no difference in serum and saliva lactoferrin concentrations between groups, but there was a significant increase (P < 0.05) in serum lysozyme concentration in the non-infection-prone group. This study suggests that the level of salivary lysozyme derived from macrophages may play an important role in determining resistance or susceptibility to acute bronchitis.

Topics: Acute Disease; Adult; Aged; Bronchitis; Chronic Disease; Communicable Diseases; Female; Haemophilus influenzae; Humans; Inflammation; Lactoferrin; Lung Diseases, Obstructive; Macrophages; Male; Middle Aged; Monocytes; Muramidase; Neutrophils; Saliva; Salivation

Topics: Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Humans; Lactoferrin; Muramidase

Lactoferrin and lysozyme are proteins found in high concentrations on mucosal surfaces, and they have activities potentially important for the modulation of inflammation. To investigate whether these proteins might contribute to the modulation of the intraluminal airway inflammation associated with chronic bronchitis, lactoferrin and lysozyme were measured in bronchoalveolar lavage (BAL) fluid from 22 subjects with chronic bronchitis and, for comparison, with 10 symptom-free smokers and 16 normal subjects. As a further control, transferrin, a protein structurally homologous to lactoferrin but not known to arise in airway epithelial cells, was also measured. BAL was performed by sequentially instilling and retrieving five 20 ml aliquots of normal saline solution into each of three sites. Analyzing the first aliquots separately from the later four provided fluid that was enriched for airway contents. The concentration of lactoferrin (11.83 +/- 2.86 micrograms/ml vs 0.68 +/- 0.18 micrograms/ml, p less than 0.00001), and lysozyme (6.75 +/- 1.51 micrograms/ml vs 0.52 +/- 0.09 microgram/ml, p less than 0.00001), but not transferrin (3.22 +/- 0.38 microgram/ml vs 2.68 +/- 0.24 micrograms/ml, p = 0.55) was higher in the bronchial sample lavage fluid, suggesting an airway origin for lactoferrin and lysozyme. In subjects with chronic bronchitis, bronchial sample lactoferrin (23.1 +/- 0.5 micrograms/ml) and lysozyme (12.6 +/- 3.5 micrograms/ml) were elevated compared with the normal subjects' lactoferrin (1.9 +/- 0.5 micrograms/ml, p less than 0.0001) and lysozyme (0.77 +/- 0.22 microgram/ml, p less than 0.0001) and the symptom-free smokers' lactoferrin (4.1 +/- 0.8 micrograms/ml, p = 0.005) and lysozyme (4.9 +/- 1.3 micrograms/ml, p = 0.02). Transferrin concentrations did not demonstrate the same relationships. Finally, when the content of bronchial sample lactoferrin and lysozyme were compared with the content of bronchial sample neutrophils, poor correlations were found, which may imply an airway epithelial origin for the two proteins. Thus lactoferrin and lysozyme appear to arise in the lower respiratory tract within the airways and their levels are elevated in association with chronic bronchitis. This suggests that lactoferrin and lysozyme may contribute to the modulation of airway inflammation in chronic bronchitis.

Topics: Bronchi; Bronchitis; Bronchoalveolar Lavage Fluid; Chronic Disease; Epithelium; Humans; Lactoferrin; Lactoglobulins; Muramidase; Neutrophils; Pulmonary Alveoli; Respiratory Function Tests; Respiratory System; Smoking; Transferrin

Topics: Bronchitis; Chronic Disease; Humans; Lactoferrin; Lactoglobulins; Muramidase; Sputum

A study was made of the humoral (IgA, G, M, lysozyme and lactoferrin) and cellular links (phagocytic activity of alveolar macrophages) of pulmonary local defence as well as sputum adhesion in 177 patients with chronic nonspecific pulmonary diseases (80 patients with chronic obstructive bronchitis, 54 patients with pyo-obstructive bronchitis, 23 patients with chronic purulent bronchitis and 20 patients with chronic nonobstructive bronchitis). A rise of the level of lysozyme and lactoferrin in the bronchial content and sputum as compared to the initial level was accompanied by a decrease in the sputum adhesion and promoted the elimination of exacerbation. In the absence of a rise or reduction of the concentration of lysozyme and lactoferrin over time more prolonged exacerbations and a tendency to purulent complications were noted. A stable drop or absence of IgA in bronchial wash off were observed in patients with IgA selective deficiency, and lung lesions were characterized by inclination to frequent recurrences, lingering exacerbations, concomitant diseases of the accessory sinuses and GI tract disorders. Indices of the phagocytic activity of alveolar macrophages in patients with chronic purulent bronchitis, particularly against a background of chronic alcoholic intoxication, were significantly lower as compared to patients with catarrhal bronchitis.

Topics: Bronchiectasis; Bronchitis; Chronic Disease; Dysgammaglobulinemia; Humans; IgA Deficiency; Immunoglobulins; Lactoferrin; Lung; Macrophages; Muramidase; Phagocytosis; Pneumonia; Pulmonary Alveoli; Recurrence; Sputum

Bronchial secretions obtained during bronchoscopic examination of 60 children suffering from respiratory tract infections were studied for the concentration of immunoglobulins, anti-proteolytic factors, lactoferrin, and lysozyme. Eleven children having bronchial asthma without a history of chronic or recurrent infections of the respiratory tract were designated as a control. The results were analysed in relation to clinical diagnosis (chronic bronchitis, bronchitis, bronchiectasis) or to the local status of bronchial mucosa at the time of bronchoscopy (no inflammation, inflammation, inflammation with documented bacterial infection). The statistical analysis of the results revealed a decrease of lactoferrin and locally produced IgA in the group of children suffering from bronchitis and chronic bronchitis. Samples infected with Haemophilus species had significantly higher concentration of lactoferrin than any other group. Similarly, albumin in this group was higher than in the other group except that other bacteria were present. Samples infected with Haemophilus also had increased concentrations of S-IgA, IgG, and anti-proteolytic factors when compared with the group without local inflammation.

Topics: Bacterial Infections; Bronchi; Bronchitis; Child; Child, Preschool; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Lactoferrin; Mucus; Muramidase; Respiratory Tract Infections; Serum Albumin

Topics: Acute Disease; Bronchi; Bronchiectasis; Bronchitis; Child; Child, Preschool; Chronic Disease; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Lactoferrin; Muramidase; Pneumonia, Staphylococcal

Bronchial secretions from 207 children suffering from various pulmonary diseases and from 15 healthy controls were tested concentration of IgA, IgG, lactoferrin and lysozyme. The results obtained suggest that in many cases of chronic lung diseases in children the levels of lactoferrin and immunoglobulins, especially secretory IgA, are very low. In severe infections (cystic fibrosis, bronchiectases) significant increase of IgG concentration was observed.

Topics: Adolescent; Bronchi; Bronchiectasis; Bronchitis; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Lactoglobulins; Muramidase; Recurrence; Respiratory Tract Diseases; Respiratory Tract Infections

The concentration of immunoglobulins, lactoferrin and lysozyme we compared in bronchial secretions obtained from children with various chronic lung diseases. The IgG, lactoferrin and lysozyme, but not secretory IgA, concentrations were shown to be increased during chronic inflammatory response.

Topics: Adolescent; Bronchi; Bronchiectasis; Bronchitis; Bronchography; Bronchoscopy; Child; Child, Preschool; Chronic Disease; Cystic Fibrosis; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Lactoglobulins; Muramidase; Respiratory Tract Diseases

The concentrations of nine plasma proteins were determined by quantitative immunoelectrophoresis in sputum specimens from 29 patients with cystic fibrosis (CF) and from 24 patients with severe asthma and chronic bronchitis. The results suggested that the population of CF patients could be divided into two groups in spite of an absence of difference in clinical status between the groups. Average concentrations of seven plasma proteins in sputum of group I CF patients were identical with those in sputum of patients with bronchitis, but the average concentrations of six of these proteins in sputum from group II CF patients were higher than those in specimens from the bronchitic patients and were similar to corresponding concentrations in sputum from patients with asthma, all of whom were examined while in status asthmaticus. The average concentrations of 14 secretory proteins were the same in all sputum specimens whether or not they were produced by patients with cystic fibrosis, asthma or bronchitis. It was concluded that the concentrations in the bronchopulmonary secretions of proteins associated with host defence were not diminished in patients with cystic fibrosis, and failure to produce adequate concentrations of proteins with antimicrobial activity was unlikely to be responsible for the above average susceptibility to chest infection in cystic fibrosis. It is suggested that there exists a group of CF patients in whom a pulmonary allergic reaction generates an inflammatory response as severe as that characterizing status asthmaticus and that this response could be detrimental.

Topics: Adult; Aged; Albumins; Asthma; Beta-Globulins; Blood Proteins; Bronchitis; Child; Child, Preschool; Cystic Fibrosis; Female; Glycoproteins; Haptoglobins; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Male; Middle Aged; Muramidase; Sputum; Transferrin