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Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques versus Acapella.

BACKGROUND: The efficacy of a new airway clearance device (Acapella) has not been previously investigated. Active cycle of breathing techniques (ACBT) is the standard airway clearance technique used in patients with bronchiectasis. OBJECTIVE: The objective of this study was to compare the efficacy of ACBT with Acapella as methods of airway clearance in adults with stable, productive bronchiectasis. METHODS: Twenty patients (7 males), age 58 +/- 11 years (mean +/- SD), FEV1 64 +/- 22% predicted with stable (change of not greater than FEV1 10% predicted during 3 months prior to study), productive (history of expectoration of half an egg cup sputum/day) bronchiectasis attended the respiratory clinic on 3 days. Day 1: 40-min training session on ACBT and Acapella. Days 2 and 3: 30-min treatment session of either ACBT or Acapella. Treatment order was determined by a concealed randomization procedure. The following outcomes were measured before and after treatment spirometry, SpO2 and breathlessness by an independent assessor who was blinded to treatment order. Weight of sputum (during treatment plus 30 min after treatment), number of coughs and patient preference were also recorded. RESULTS: No significant differences were found at baseline indicating that patients were stable. No significant differences were found between weight of sputum expectorated with ACBT treatment and weight of sputum expectorated with Acapella treatment--mean difference 0.54 g (95% CI -0.39 to 1.46). A greater proportion of patients preferred Acapella (14/20). CONCLUSION: Acapella is as effective a method of airway clearance as ACBT and may offer a user-friendly alternative to ACBT for patients with bronchiectasis.

Airway Obstruction↗

Elevated levels of expired breath hydrogen peroxide in bronchiectasis.

Airway inflammation is important in the development and progression of many lung diseases, including bronchiectasis. Activation of inflammatory cells such as neutrophils, eosinophils, and macrophages induces a respiratory burst resulting in the production of reactive oxygen species such as hydrogen peroxide (H2O2). We have measured exhaled H2O2 in patients with documented bronchiectasis and investigated whether the concentration of H2O2 is related to the disease severity, as defined by lung function. We also investigated whether the concentrations of expired H2O2 were different in bronchiectatic patients who received inhaled corticosteroids compared with steroid-naïve patients. In 37 patients with bronchiectasis (mean age, 45 +/- 2.5 yr; FEV1, 59 +/- 3% pred), mean H2O2 concentration in exhaled breath condensate was significantly elevated as compared with the values in 25 age-matched (mean age, 42 +/- 2 yr) normal subjects (0.87 +/- 0.01 versus 0.26 +/- 0.04 microM, p < 0.001). There was a significant negative correlation between H2O2 and FEV1 (r = -0.76, p < 0.0001). Patients treated with inhaled corticosteroids had values of H2O2 similar to those of steroid-naïve patients (0.8 +/- 0.1 versus 0.9 +/- 0.1, p > 0.05). We conclude that H2O2 is elevated in exhaled air condensate of patients with bronchiectasis and is correlated with disease severity. Measurement of H2O2 may be used as a simple noninvasive method to monitor airway inflammation and oxidative stress.

Administration, Inhalation↗

Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis.

Mycobacterium avium complex (MAC) isolates among patients with chronic lung disease were studied for their heterogeneity using genetic identification methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of 7.3 cultures per patient were collected from 17 patients with nodular bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of 7.7 cultures per patient were collected from nine patients with upper lobe cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of 17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or more genotypes. In contrast a mean of 1.2 genotypes were identified in the patients with cavitary disease, with only 1 of 9 (11%) having two or more genotypes. Mycobacterium intracellulare was the most frequently recovered genotype in both groups and most isolates were rough or nontypable by seroagglutination. Some genotypes from the same patient considered different by current PFGE criteria had the same serotype and shared 11 to 20 common PFGE bands, suggesting they were related. These data demonstrate that patients with nodular bronchiectasis have multiple and/or repeated infections due to MAC whereas patients with upper lobe cavitary disease are usually infected with only a single strain.

Adult↗

Neutrophil-mediated degradation of lung proteoglycans: stimulation by tumor necrosis factor-alpha in sputum of patients with bronchiectasis.

Neutrophil-mediated degradation of bronchial matrix has been proposed as a pathogenetic factor in bronchiectasis. We hypothesize that neutrophils, found in abundance in the bronchial lumens of patients with bronchiectasis, are capable of degrading lung matrix proteoglycans and that proinflammatory mediators in bronchial secretions of these patients can enhance the degradative action of neutrophils. We used rat bronchoalveolar proteoglycans entrapped in polyacrylamide gel beads as a substrate for test incubations with neutrophils from healthy volunteers and sputum sol from patients with idiopathic bronchiectasis. Coincubations with specimens of sputum sol and neutrophils showed proteoglycan degradation indices (PDIs) in excess of the sum of indices due to incubation with either heat-inactivated sputum sol or heat-inactivated neutrophils, suggesting sputum stimulation of the neutrophil response. Mediation of this stimulation by tumor necrosis factor (TNF)-alpha was suggested because (1) indices for the coincubations correlated with sputum levels of TNF-alpha and (2) an anti-TNF-alpha antibody completely attenuated the sputum-stimulated effect. Furthermore, recombinant human TNF-alpha required accompanying sputum sol to exert an enhancing effect on neutrophil-mediated proteoglycan degradation. Because neutrophil-mediated proteoglycan degradation in the coincubations was inhibited largely (90%) by Eglin C and much less so (8% to 20%) by ethylenediamine tetraacetic acid, we conclude that serine proteases secreted by neutrophils were mainly responsible for degradation of proteoglycans in the model matrix and that the secretion was stimulated by TNF-alpha in the presence of cofactors in the bronchial secretions of patients with bronchiectasis.

Animals↗

Bronchial inflammation and colonization in patients with clinically stable bronchiectasis.

To evaluate the bronchial inflammatory response and its relationship to bacterial colonization in bronchiectasis, we performed a bronchoalveolar lavage (BAL) in 49 patients in stable clinical condition and in nine control subjects. BAL was processed for differential cell count, quantitative bacteriologic cultures, and measurement of inflammatory mediators. An increase was observed in the percentage of neutrophils (37 [0 to 98]) (median[range]) versus 1[0 to 4]%, p = 0.01), in the concentration of elastase (90.5 [8 to 2,930] versus 34 [9 to 44], p = 0.03), myeloperoxidase (9.1 [0 to 376] versus 0.3 [0.1 to 1.4], p = 0.01), and in the levels of TNF-alpha (4 [0 to 186] versus 0 [0 to 7], p = 0.03), IL-8 (195 [0 to 5,520] versus 3 [0 to 31], p = 0.001), and IL-6 (6 [0 to 115] versus 0 [0 to 3], p = 0.001) in patients with bronchiectasis compared with control subjects. Noncolonized patients showed a more intense bronchial inflammatory reaction than did control subjects. This inflammatory reaction was exaggerated in patients colonized by microorganisms with potential pathogenicity (MPP), with a clear relationship with the bronchial bacterial load. Patients with bronchiectasis showed a slight systemic inflammatory response, with poor correlations between systemic and bronchial inflammatory mediators, suggesting that the inflammatory process was mostly compartmentalized. We conclude that patients with bronchiectasis in a stable clinical condition present an active neutrophilic inflammation in the airways that is exaggerated by the presence of MPP, and the higher the bacterial load the more intense the inflammation.

Bacterial Infections↗

The bacteriology of bronchiectasis in Hong Kong investigated by protected catheter brush and bronchoalveolar lavage.

Bacteria often colonize the lower respiratory tract of patients with bronchiectasis. Although the role of these bacteria in the pathogenesis of the disease is uncertain, their accurate identification is important for epidemiologic and treatment purposes. Therefore, the aims of this study were: (1) to identify these bacteria in patients with bronchiectasis without cystic fibrosis using the protected catheter brush (PCB) in order to avoid oropharyngeal contamination, and (2) to compare the results of bronchoalveolar lavage (BAL) with PCB. Quantitative culture was performed on PCB and BAL specimens obtained from the most severely affected lobes of 23 patients with bronchiectasis. Results of PCB showed no significant growth (less than 10(3) colony-forming units [cfu]/ml) in nine patients and 17 significant isolates (greater than 10(3) cfu/ml) in the rest: H. influenzae, 5; P. aeruginosa, 4; K. ozaenae, 2; S. aureus, 2; P. fluorescens, 1; S. pneumoniae, 1; Veillonella, 1; and coag.-ve Staph., 1. For BAL, the results were the same (20 isolates) regardless of whether 10(4) or 10(5) cfu/ml was chosen as the cutoff point. More organisms were cultured from BAL specimens, and these included all but one of the organisms cultured from PCB. We conclude that the bacteriology of bronchiectasis in Hong Kong is different from that reported in sputum studies in the West (mainly H. influenzae, S. pneumoniae, and S. aureus), and with 10(4) cfu/ml as the cutoff point, BAL gives comparable results to PCB.

Adult↗

In situ hybridization studies of adenoviral infections of the lung and their relationship to follicular bronchiectasis.

We have used a probe against the adenovirus genome to study cultured epithelial cells specifically infected with various types of adenovirus and Graham 293 cells, which contain few copy numbers of a fraction of the adenovirus genome. We have also examined lung tissue obtained from three cases of acute adenovirus pneumonia, two cases of adenovirus pneumonia that had passed through the acute phase, and nine cases of follicular bronchiectasis. Our purpose was to determine whether the probe was effective in detecting a wide variety of adenovirus types, to determine whether it could detect adenovirus in lung tissue that had been fixed and stored in paraffin blocks for several years, and to test the hypothesis that adenovirus was an important cause of follicular bronchiectasis. The results show that the probe was able to detect adenovirus from Genera B1, B2, C, D, and E with a sensitivity of 5 to 10 copies/cell. The probe also detected adenovirus in 14 of 14 slides from three cases of acute disease, but failed to obtain a positive result in the cases examined after an acute infection or in any of the cases of follicular bronchiectasis. We conclude that the in situ hybridization technique is useful in the investigation of active adenovirus infection of the lung. The failure to show that the virus persisted in the chronic respiratory disease that follows adenovirus infection, or that it was present in cases of follicular bronchiectasis could be due to either a true absence, or to its presence in a latent form that is below the level of sensitivity of this technique.

Adenoviridae Infections↗

Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases.

To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.

Adult↗

Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis.

An unusual case of endobronchial polyposis associated with extensive bronchiectasis in the context of cystic fibrosis (CF) has been described. A 15-yr-old female patient with CF underwent partial pneumonectomy for extensive bronchiectasis and frequent infective pulmonary exacerbations. Cylindrical bronchiectasis with associated purulent bronchitis and bronchiolitis, together with inflammatory polyposis, was noted in the resected lung. To the best of the authors' knowledge, this is the first report of multiple endobronchial polyposis and may represent a rare complication of bronchiectasis in a patient with cystic fibrosis. On-going infection and the cellular composition of the polyps are discussed in relation to their possible aetiological relevance and relationship to upper respiratory tract polyps.

Adolescent↗

The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis.

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67), "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) % predicted levels at >or=2 yrs after presentation, longitudinal behaviour was characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or "stability". Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/-25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV(1) levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.

Adult↗

Nontuberculous mycobacteria in bronchiectasis: Prevalence and patient characteristics.

The aim of the current study was to investigate the prevalence and clinical associations of nontuberculous mycobacteria (NTM) in a well-characterised cohort of patients with adult-onset bronchiectasis. The sputum of all patients attending a tertiary referral bronchiectasis clinic between April 2002 and August 2003 was examined for mycobacteria as part of an extensive diagnostic work-up. NTM-positive patients subsequently had further sputa examined. A modified bronchiectasis scoring system was applied to all high-resolution computed tomography (HRCT) scans from NTM-positive patients, and a matched cohort without NTM. Out of 98 patients attending the clinic, 10 had NTM in their sputum on first culture; of those, eight provided multiple positive cultures. Three patients were treated for NTM infection. A higher proportion of NTM-positive than -negative patients were subsequently diagnosed with cystic fibrosis (two out of nine versus two out of 75). On HRCT scoring, more patients in the NTM-positive group had peripheral mucus plugging than in the NTM-negative group. In the current prospective study of a large cohort of patients with bronchiectasis, 10% cultured positive for nontuberculous mycobacteria in a random clinic sputum sample. Few clinical parameters were helpful in discriminating between groups, except for a higher prevalence of previously undiagnosed cystic fibrosis and of peripheral mucus plugging on high-resolution computed tomography in the nontuberculous mycobacteria group.

Aged↗

Long-term nasal intermittent positive pressure ventilation (NIPPV) in sixteen consecutive patients with bronchiectasis: a retrospective study.

Life expectancy and quality of life are poor in patients with chronic respiratory failure due to bronchiectasis. The indication for nocturnal nasal intermittent positive pressure ventilation (NIPPV) remains controversial in chronic obstructive lung disease. The purpose of the present study was to determine whether some of the objectives of home mechanical ventilation, i.e. improvement in blood gas values and reduced length of hospitalization, were fulfilled by NIPPV and oxygen plus medical treatment in patients with chronic respiratory failure due to bronchiectasis. Sixteen consecutive patients (12 females and four males; mean age 57 +/- 11 yrs) with chronic respiratory failure due to bronchiectasis, treated at home with nocturnal NIPPV in addition to oxygen therapy, were retrospectively studied in terms of blood gas values and duration of hospitalization before and after NIPPV. Details of the therapy received by each patient were recorded. Nine patients agreed to complete a questionnaire to determine their perception of the benefits of the treatment. NIPPV was performed using a volumetric respirator and was applied with a customized nasal mask modelled with silicone paste. NIPPV was used for a mean of 26 months (range 0.5-60 months). Eleven patients were alive 12 months after use of NIPPV. No significant improvement in blood gas values was noted on room air during NIPPV, but arterial carbon dioxide tension (Pa,CO2) stabilized after the period of worsening observed before initiation of NIPPV. Duration of hospitalization, the year before and the year after NIPPV, was 19 (3-40) and 16 (8-37) days, respectively (NS). For the 11 patients who were alive 2 yrs after the start of NIPPV, duration of hospitalization the year before NIPPV and between 12 and 24 months after NIPPV were 17 (4-40) and 7 (2-27) days, respectively (p < 0.05). Nine patients who had received NIPPV for at least 12 months at the time of the study reported an improvement in their quality of life. The results suggest that home ventilatory support by nasal intermittent positive pressure ventilation offers an acceptable alternative to tracheotomy, with less discomfort, in the management of severe respiratory failure due to bronchiectasis, in order to allow the patient to return home. These results should be confirmed by controlled studies.

Adult↗

Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa.

Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive disease in bronchiectasis. It is not known, however, whether infection with P. aeruginosa is the result or the cause of severe disease. We compared spirometry in patients with bronchiectasis before and after infection with P. aeruginosa, with that of patients infected by other organisms. All patients (n=12) with chronic colonization by P. aeruginosa (PA group) were studied. These were compared with other patients with bronchiectasis with no isolations of P. aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA group. The PA group, however, also had lower values at the time of initial colonization with P. aeruginosa than the current values for the non-PA group. Change in FEV1 and FVC over time was faster in the PA group than in the non-PA group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa colonization was intermediate, not being statistically different from either value above. Our results confirm the association of chronic P. aeruginosa colonization with poor lung function, but conclude that patients with bronchiectasis who become colonized by P. aeruginosa have poorer lung function when first colonized than those colonized by other organisms. Decline in lung function is faster in those chronically colonized by P. aeruginosa than in those colonized by other organisms. It is not clear whether chronic P. aeruginosa colonization causes an accelerated decline in lung function or whether it is simply a marker of those whose lung function is already declining rapidly.

Aged↗

Effect of sputum bacteriology on the quality of life of patients with bronchiectasis.

Bronchiectatic patients have impaired health-related quality of life (QoL) and are prone to chronic lower respiratory tract infections. We have investigated whether impaired QoL is related to sputum bacteriology. Eighty seven patients with non-cystic fibrosis (non-CF) bronchiectasis, in a stable phase of their illness, completed three QoL measures, underwent a computed tomography (CT) scan and lung function tests, and provided a fresh sputum sample for microscopy and culture. The QoL of patients colonized by Pseudomonas aeruginosa (Pa group) was significantly worse than all other patients grouped together (non-Pa group), and specifically those infected by Haemophilus influenzae (Hi group) or who had no bacterial growth (NG group) (p<0.05), but not those infected by other bacterial species (O group). The Pa group had worse lung function, but no significant differences were found between the groups for forced expiratory volume in one second (FEV1) and peak expiratory flow rate. The Pa group had significantly worse bronchiectasis scores than the O, NG and non-Pa groups, but not the Hi group. There were no significant differences between the groups with respect to the number of infective exacerbations in the last year, but the Pa group had significantly more hospital admissions. Patients infected by P. aeruginosa for more than 3 yrs had significantly worse FEV1 (p<0.03) and bronchiectasis scores (p<0.05) than those infected with P. aeruginosa for less time, but not significantly worse QoL. We conclude that, overall, patients infected with P. aeruginosa have worse quality of life, and that P. aeruginosa is associated with a greater extent of disease and worse lung function. Although patients infected with H. influenzae had extensive bronchiectasis their quality of life was better than the P. aeruginosa infected group.

Adult↗

Potentiative effects of neutral proteinases in an inflamed lung: relationship of neutrophil procollagenase (proMMP-8) to plasmin, cathepsin G and tryptase in bronchiectasis in vivo.

We attempted to study the possible relationships between neutrophil-type procollagenase/pro-matrix metalloproteinase (MMP-8) and the serine proteinases plasmin, cathepsin G and tryptase in bronchiectasis. The presence of the plasmin/plasminogen system and plasmin-, cathepsin G- and tryptase-like activities were compared to the activity of endogenously activated MMP-8 in bronchoalveolar lavage (BAL) fluid in 38 bronchiectasis patients and in 14 healthy controls by means of immunohistochemistry, Western-blot and substrate-based functional assays. In contrast to cathepsin G- and tryptase-like activities, the plasmin/plasminogen activator system in BAL fluid was observed to have a relatively weak activation stage and no correlation with disease severity. Neither plasmin-like activities nor concentrations of plasminogen activators from the bronchiectatic patients differed significantly from the values of healthy controls. Immunolocation of plasminogen activator inhibitor-1 showed a marked, but not significant, increase in bronchiectatic lung as compared to controls. In contrast to cathepsin G- and tryptase-like activities, with their strong and significant correlation with endogenously activated collagenase (r=0.9; p=0.0001; and r=0.6; p=0.03, respectively), no correlations were observed between plasmin-like and endogenously activated collagenase (r=0.3; p=0.2) in bronchiectasis. These findings suggest that cathepsin G- and tryptase-like activities may act as potent pro-matrix metalloproteinase-8 activators in patients with bronchiectasis, whereas the plasminogen activator/plasmin cascade was shown to be down-regulated.

Adolescent↗

Determinants of chronic infection with Staphylococcus aureus in patients with bronchiectasis.

Staphylococcus aureus is an uncommon pathogen in bronchiectasis not caused by cystic fibrosis (CF). The object of this study was to identify characteristics that cause patients to be prone to infection with S. aureus. The study population consisted of patients with bronchiectasis attending the authors' unit, excluding those with a diagnosis of overt CF. All patients had a high resolution computer tomographic scan (HRCT) of the thorax which demonstrated bronchiectasis. Cases that were currently chronically infected with S. aureus (isolated consecutively on more than two occasions >3 months apart) were identified (n = 12) and compared with 74 control patients who had not been chronically infected with S. aureus. Patients were carefully evaluated to determine the aetiology of their disease. Odds ratios (OR) and 95% confidence intervals (CI) as measures of the association between disease characteristics and chronic infection with S. aureus were calculated. The results for patients chronically infected by S. aureus demonstrated significant associations with allergic bronchopulmonary aspergillosis (ABPA; OR = 8.8, 95% CI 1.8-41.9), atypical variants of CF (OR = 12.0, 95% CI 1.8-81.7) or equivocal sweat sodium values (OR = 4.0, 95% CI 1.0-15.3). The associations persisted when the analysis was based on cases (n = 28) in whom S. aureus had ever been isolated from sputum. In the latter analysis there was also a significant association with predominant upper zone disease on HRCT. These results suggest that patients with bronchiectasis in whom S. aureus is isolated from sputum should be carefully evaluated to exclude allergic bronchopulmonary aspergillosis or atypical cystic fibrosis.

Adult↗

Helicobacter pylori and upper gastrointestinal symptoms in bronchiectasis.

The recently reported increase in seroprevalence of Helicobacter pylori, the causative pathogen in peptic ulceration, in bronchiectasis is unexplained. Therefore, the association of antibodies directed against cytotoxin-associated gene A(CagA), whose expression indicates virulence of H. pylori, and upper gastrointestinal symptoms in patients with stable bronchiectasis and healthy volunteers evaluated. One hundred patients (mean +/- SD age 55.1+/-16.7 yrs) and 94 healthy asymptomatic subjects (54.6+/-7.6 yrs) underwent clinical and physiological assessment and serum levels of anti-H. pylori CagA were determined using standard clinical and enzyme-linked immunosorbent assay techniques. Samples were positive for anti-H. pylori CagA in 11.7% of controls and 24% of bronchiectatic subjects (p = 0.03). There was, however, no association between serum H. pylori CagA immunoglobulin G level and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), sputum volume, respiratory symptoms or upper respiratory gastrointestinal symptoms (p>0.05). Patients who suffered from acid regurgitation or upper abdominal distension had significantly lower FEV1 and FVC (as a percentage of the predicted value) compared to their counterparts. The results of anticytotoxin-associated gene A measurements in this study contrasted with the previous finding that anti-Helicobacter pylori immunoglobulin G correlated with sputum volume. These findings, therefore, suggest that Helicobacter pylori, should it have a pathogenic role in bronchiectasis, could act via noncytotoxin-associated gene A-mediated mechanisms, and, in this context, gastro-oesophageal reflux might be of importance in bronchiectasis.

Adult↗

Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease.

Collagenases in bronchoalveolar lavage fluid (BALF) of patients with bronchiectasis and healthy subjects were characterized using specific functional and immunologic assays. The BAL fluid contained interstitial collagenase and collagenolytic proteinases of bacterial origin. Collagenase activities, obtained after organomercurial activation, correlated with the severity of bronchiectasis. In severe cases, collagenase activities were 3.5 x 10(-7) IU/L/48 h or 4.8 x 10(-6) IU/g/48 h (p < 0.01), in moderate ones 1.74 x 10(-7) IU/L/48 h or 3.35 x 10(-6) IU/g/48 h (p < 0.05), and in mild cases 0.32 x 10(-7) IU/L/48 h or 0.7 x 10(-6) IU/g/48 h (p < 0.05). The corresponding activities in healthy control subjects were 0.08 x 10(-7) IU/L/48 h or 0.13 x 10(-6) IU/g/48 h. The cellular origin of interstitial collagenase was assessed with doxycycline inhibition test utilizing the differential sensitivity of fibroblast-type collagenase/MMP-1 (IC50 = 280 microM) and neutrophil-type collagenase/MMP-8 (IC50 = 26 microM) to the anticollagenolytic, nonantimicrobial doxycycline action. Interstitial collagenase, contained in BALF, was totally inhibited by 100 microM of doxycycline. It can therefore be concluded that most of mammalian collagenase presented in inflamed fluid of bronchiectasis originated from neutrophils. The molecular forms of neutrophil-type collagenase/MMP-8 were confirmed and analyzed by Western-blot, which showed evidence of the proteolytic conversion of the latent 85-kD MMP-8 proenzyme species into active 65-kD molecular weight species. These findings strongly suggest involvement of proteolytic activation pathway of proMMP-8, especially in severe and moderate forms of bronchiectasis. Furthermore, collagenolytic proteases of bacterial origins may also participate in tissue destruction of the lung.

Adolescent↗