Measuring energy expenditure in cardiac patients using the Body Media Armband versus indirect calorimetry. A validation study.

AIM: The purpose of this study was to compare differences in energy expenditure using the newly developed SenseWear Armband body monitor to indirect calorimetry in cardiac rehabilitation patients. METHODS: Twenty-four (62+/-8.1 years) patients completed steady state exercise for 8 minutes on 4 modes of exercise (arm ergometry, treadmill walking, recumbent stepping and rowing ergometry). Total cumulative kilojoules were recorded simultaneously by indirect calorimetry and the SenseWear Armband. Statistical analyses assessed the degree of agreement between the 2 measurement methods and 3 different versions of the SenseWear software. RESULTS: The correlations between indirect calorimetry and version 2.2 of the SenseWear armband for arm and rowing ergometry, the treadmill and recumbent stepper were r=0.90, r=0.67, r=0 .80 and r=0.74, respectively. There were no between method differences during arm ergometry (p<1.000) and the recumbent stepper (p<0.102). Bland and Altman plots revealed the greatest spread of scores for the rower and the treadmill. Between method differences were minimal when using the preliminary cardiac software. The correlations for arm and rowing ergometry, the treadmill and recumbent stepper were r=0.90, r=0.84, r=0.78 and r=0.82, respectively. CONCLUSIONS: The accuracy of the BodyMedia SenseWear Armband appears to be exercise modality dependent in those with heart disease when using software developed for the general population. Therefore, the information should be interpreted cautiously, particularly during treadmill walking and rowing. Initial experiments with cardiac-focused software are promising, but preliminary.

Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) presents to general practitioners with symptoms pertinent to a variety of specialists because of the involvement of ciliated epithelium in the upper/lower respiratory tract, ears, eyes and genital tract. There is no easy, reliable screening test for PCD, and thus, the majority of patients remain undiagnosed. Nitric oxide (NO) is measurable in nasal air of normal subjects and found to be low in cystic fibrosis (CF) and very low in PCD. Recently, it was suggested to play an important role in regulating ciliary motility. The aim of this study was to evaluate whether measurements of nasal NO could be used to screen for PCD. Nasal NO was measured from the nasal cavity by a chemiluminescence analyser in subjects with PCD, healthy controls, CF, idiopathic bronchiectasis, Young's syndrome and lone sinusitis. Nasal NO was significantly lower in PCD (64.0+/-36.6) compared with normal controls (759+/-145.8), idiopathic bronchiectasis (734+/-163.7), CF (447.5+/-162.6), lone sinusitis (1487+/-734) and Young's syndrome (644+/-129.9). Nasal NO was also significantly lower in PCD than CF patients. Measurement of nasal nitric oxide may therefore be used clinically in various specialities to screen suspected patients for primary ciliary dyskinesia.

Comparison of exhaled and nasal nitric oxide and exhaled carbon monoxide levels in bronchiectatic patients with and without primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is associated with chronic airway inflammation resulting in bronchiectasis. METHODS: The levels of exhaled nitric oxide (eNO), carbon monoxide (eCO) and nasal NO (nNO) from bronchiectatic patients with PCD (n=14) were compared with those from patients with non-PCD bronchiectasis without (n=31) and with cystic fibrosis (CF) (n=20) and from normal subjects (n=37) to assess the clinical usefulness of these measurements in discriminating between PCD and other causes of bronchiectasis. RESULTS: Exhaled NO levels were lower in patients with PCD than in patients with non-PCD non-CF bronchiectasis or healthy subjects (median (range) 2.1 (1.3-3.5) ppb v 8.7 (4.5-26.0) ppb, p<0.001; 6.7 (2.6-11.9) ppb, p<0.001, respectively) but not lower than bronchiectatic patients with CF (3.0 (1.5-7.5) ppb, p>0.05). Nasal levels of nNO were significantly lower in PCD patients than in any other subjects (PCD: 54.5 (5.0-269) ppb, non-PCD bronchiectasis without CF: 680 (310-1000) ppb, non-PCD bronchiectasis with CF: 343 (30-997) ppb, control: 663 (322-1343) ppb). In contrast, eCO levels were higher in all patient groups than in control subjects (PCD: 4.5 (3.0-24.0) ppm, p<0.01, other bronchiectasis without CF: 5.0 (3.0-15.0) ppm, p<0.001; CF: 5.3 (2.0-23.0) ppm, p<0.001 v 3.0 (0.5-5.0) ppm). Low values in both eNO and nNO readings (<2.4 ppb and <187 ppb, respectively) identified PCD patients from other bronchiectatic patients with a specificity of 98% and a positive predictive value of 92%. CONCLUSION: The simultaneous measurement of eNO and nNO is a useful screening tool for PCD.

A comparison of serial computed tomography and functional change in bronchiectasis.

In bronchiectasis the morphological determinants of (marginal) fluctuations in pulmonary function tests are uncertain. The aim of the present study was to evaluate serial computed tomography (CT) changes in relation to pulmonary function trends in patients with bronchiectasis. The relationships between pulmonary function indices and CT scans in 48 adult patients with bronchiectasis were evaluated at baseline and at follow-up, at a median interval of 28 months (range 6-74 months). Two independent observers semiquantitatively scored CT features of bronchial and small airways disease. At initial assessment, the severity of airflow obstruction was linked primarily to the extent of mosaic attenuation. However, serial changes in pulmonary function indices were only associated with serial changes in mucous plugging scores. Alterations in mucous plugging on serial CT were associated with changes in the severity of bronchiectasis and bronchial wall thickness. Greater severity of all three morphological abnormalities at baseline CT were predictive of significant declines in forced expiratory volume in one second, with severe bronchial wall thickness being the most adverse prognostic determinant. Variations in mucous plugging on computed tomography correlate with minor fluctuations in pulmonary function tests in bronchiectasis. However, the severity of bronchial wall thickness is the primary determinant of subsequent major functional decline.

Relationship between psychological well-being and lung health status in patients with bronchiectasis.

Patients with bronchiectasis often complain of abnormal tiredness, difficulty in concentrating or low spirits. This study was carried out to examine levels of anxiety and depression in bronchiectasis and their relationship with other measures of lung health. One hundred and eleven patients with bronchiectasis determined by high-resolution computed tomography (CT) scan were studied using a range of physiological and psychological outcome measures. Patients completed anxiety and depression, health status (quality of life), fatigue and dypnoea questionnaires. Lung function was measured and exercise capacity was assessed using a shuttle walk test. Anxiety and depression scores formed a continuum. Moderate-severe anxiety was more frequent than equivalent levels of depression (17 vs 9% of patients). Anxiety and depression scores were associated with perceived health status (r=0.33 and 0.55). Neither anxiety nor depression was associated with the extent of bronchiectasis on CT scan. Depression was correlated with breathlessness and exercise performance (r=0.33 and 0.40), but anxiety was not. The correlation between depression and exercise performance was not simply due to the influence of somatic items in the depression questionnaire. We conclude that anxiety and depression are quite common in bronchiectasis in that 34% of patients had elevated scores for anxiety depression or both. The non-somatic components of depression were linked to dyspnoea and exercise performance, but anxiety was only related to perceived health. Therefore, treatment aimed at reducing symptoms and improving exercise capacity will not reduce levels of anxiety which need alternative therapy.

The role of nebulized antibiotics in treating serious respiratory infections.

The administration of a nebulized antibiotic in serious respiratory tract infections ensures high antibiotic concentrations at the site of infection, minimising systemic concentrations and their resultant risk of toxicity. Nebulized antibiotics have been used for the treatment of chronic infection with Pseudomonas aeruginosa, particularly in cystic fibrosis, but with variable clinical efficacy. Antibiotic delivery by nebulization is greatly influenced by the product formulation and the nebulizer. Use of intravenous formulations via a nebulizer can lead to exposure to potentially irritant or toxic additives and inappropriate pH or osmolality ranges, whilst the choice of nebulizer can greatly influence the drug deposition in the airway. Tobramycin Nebulizer Solution (TNS) is the first specific formulation for nebulization in cystic fibrosis using a designated nebulizer. The potential extrapolation of nebulized antibiotic therapy to other serious respiratory infections, in particular bronchiectasis and ventilator-associated pneumonia, is explored in this review.

Incremental spinal anaesthesia for elective Caesarean section in a patient with Eisenmenger's syndrome.

We describe a new approach to anaesthesia for elective Caesarean section in a woman with Eisenmenger's syndrome. Incremental regional anaesthesia was performed using a microspinal catheter and haemodynamic monitoring included transthoracic bioimpedance cardiography. This approach allowed the disadvantages of general anaesthesia and invasive cardiac output monitoring to be avoided.

Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epithelium in vitro.

Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin. Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL. Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.

The effect of erythromycin on mucociliary transportability and rheology of cystic fibrosis and bronchiectasis sputum.

BACKGROUND: Erythromycin has been shown to diminish sputum production in hypersecretory states by a mechanism that is still unclear. OBJECTIVES AND METHODS: We have investigated the effect of erythromycin on the ciliary transportability of cystic fibrosis and non-cystic fibrosis bronchiectasis sputum in vitro using the mucus-depleted bovine trachea. RESULTS: Additional erythromycin in concentrations up to 20 microg/g did not significantly alter the ciliary transportability of sputum from 6 cystic fibrosis and 6 bronchiectasis patients. Sputum viscoelasticity measured with parallel-plate rheology was also little changed. These erythromycin concentrations also had little effect on the beating frequency of bovine tracheal cilia. CONCLUSIONS: These results suggest that the presence of erythromycin in sputum neither alters the physical properties of the gel nor the activity of cilia. The clinical effects of erythromycin on pulmonary hypersecretory states therefore have another explanation.

CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.

The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.

Efficacy and respiratory effects of low-dose spinal morphine for postoperative analgesia following knee arthroplasty.

A randomized, double-blind study of 38 patients undergoing total knee replacement was undertaken to compare the efficacy and respiratory effects of low-dose spinal morphine and patient-controlled i.v. morphine against patient-controlled i.v. morphine alone. Patients received either morphine 0.3 mg or saline 0.3 ml with 0.5% heavy spinal bupivacaine 2-2.5 ml. Respiratory effects were measured continuously for 14 h postoperatively with an Edentec 3711 respiratory monitor. There was an improvement in pain relief in the intrathecal morphine group, with significantly lower median VAS pain scores on movement at 4 h (0 (median 0-1.5) vs 5 (1.25-7.75) P < 0.01), 12 h (2 (1-5) vs 6 (3-8) P < 0.01) and 24 h (3 (1-5) vs 5 (3-7) P < 0.05) postoperatively, despite using significantly less patient-controlled morphine (20 mg (10.25-26.25) vs 38.5 mg (27-51) P < 0.01) in the first 24 h. There was a small but statistically significant reduction in the median oxygen saturation (SpO2) in the intrathecal morphine group 97 (95-99)% compared with the placebo group 99 (97-99)% (P < 0.05). Although marked disturbances in respiratory pattern were observed in both groups, none of the patients in the study had severe hypoxaemia (SpO2 < 85% > 6 min h-1) and there was no significant difference in the incidence of mild (SpO2 < 94% > 12 min h-1) or moderate (SpO2 < 90% > 12 min h-1) hypoxaemia or in the incidence of episodes of apnoea or hypopnoea in the two groups.

Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function tests.

BACKGROUND: An obstructive defect is usual in bronchiectasis, but the pathophysiological basis of airflow obstruction remains uncertain. High resolution computed tomographic (CT) scanning now allows quantitation of static morphological abnormalities, as well as dynamic changes shown on expiratory CT scans. The aim of this study was to determine which static and dynamic structural abnormalities on the CT scan are associated with airflow obstruction in bronchiectasis. METHODS: The inspiratory and expiratory features on the CT scan of 100 patients with bronchiectasis undergoing concurrent lung function tests were scored semi-quantitatively by three observers. RESULTS: On univariate analysis the extent and severity of bronchiectasis, the severity of bronchial wall thickening, and the extent of decreased attenuation on the expiratory CT scan correlated strongly with the severity of airflow obstruction; the closest relationship was seen between decreased forced expiratory volume in one second (FEV(1)) and the extent of decreased attenuation on the expiratory CT scan (R(s) = -0.55, p<0. 00005). On multivariate analysis bronchial wall thickness and decreased attenuation were consistently the strongest independent determinants of airflow obstruction. The extent of decreased attenuation was positively associated with the severity of bronchial wall thickness, but was not independently linked to gas transfer levels. Endobronchial secretions seen on CT scanning had no functional significance; the severity of bronchial dilatation was negatively associated with airflow obstruction after adjustment for other morphological features. CONCLUSIONS: These findings indicate that airflow obstruction in bronchiectasis is primarily linked to evidence of intrinsic disease of small and medium airways on CT scanning and not to bronchiectatic abnormalities in large airways, emphysema, or retained endobronchial secretions.

Pseudomonas aeruginosa pyocyanin and 1-hydroxyphenazine inhibit fungal growth.

AIM: To examine strains of Pseudomonas aeruginosa for specific antifungal factors. METHODS: Two clinical strains of P aeruginosa with strong in vitro inhibition (by cross streak assay) of Candida albicans and Aspergillus fumigatus were examined. Both strains were isolated from sputum--one from a patient with cystic fibrosis and one from a patient with bronchiectasis. Bacterial extracts were fractionated by high performance liquid chromatography and examined by ultraviolet absorbance and mass spectroscopy. Antifungal activity against C albicans and A fumigatus was determined in a well plate assay. RESULTS: Pyocyanin was the major antifungal agent of P aeruginosa; 1-hydroxy-phenazine also possessed activity. Pyocyanin MICs for C albicans and A fumigatus were > 64 micrograms/ml. These phenazines were active against nine other yeast species pathogenic for man. Preliminary experiments also suggested possible inhibition of yeast mycelial transformation in C albicans by pyocyanin. CONCLUSIONS: There may be a role for pyocyanin and 1-hydroxyphenazine in the prevention of pulmonary candidiasis in patients colonised by P aeruginosa.

Effect of fluticasone propionate and salmeterol on Pseudomonas aeruginosa infection of the respiratory mucosa in vitro.

The purpose of this study was to investigate the effect of the corticosteroid, fluticasone propionate (FP), on Pseudomonas aeruginosa infection of the respiratory mucosa of an organ culture model in vitro. Organ cultures infected with P. aeruginosa had significantly (p< or =0.05) elevated levels of mucosal damage and significantly (p< or =0.05) less ciliated cells compared to controls. Preincubation of tissue with FP (10(-6) or 10(-5) but not 10(-7) M) prior to P. aeruginosa infection significantly (p< or =0.05) reduced the bacterially induced mucosal damage in a concentration-dependent manner. FP (10(-5) M) also significantly (p< or =0.05) prevented loss of ciliated cells. FP did not alter the density of bacteria adherent to the different mucosal features of the organ cultures, but did reduce total bacterial numbers due to the reduced amount of damaged tissue, which is a preferred site of P. aeruginosa adherence. It has previously been shown that the long-acting beta2-agonist salmeterol (4 x 10(-7)M) also reduces the mucosal damage caused by P. aeruginosa infection, probably via elevation of intracellular cyclic adenosine monophosphate concentrations. Preincubation of tissue with both 10(-7)M FP and 10(-7)M salmeterol, concentrations at which they did not by themselves influence the effect of P. aeruginosa infection, significantly (p< or =0.05) reduced P. aeruginosa-induced loss of cilia. However, there was no additional benefit from adding 4 x 10(-7)M salmeterol to 10(-6)M FP. In conclusion fluticasone propionate reduced mucosal damage caused by P. aeruginosa infection in vitro and preserved ciliated cells. There was a synergistic action with salmeterol in the preservation of ciliated cells.

Exposure of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils to the Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine is associated with impaired calcium efflux and potentiation of primary granule enzyme release.

The effects of pathologically relevant concentrations (0.38 to 12.5 microM) of the proinflammatory, Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine (1-hp) on Ca2+ metabolism and intracellular cyclic AMP (cAMP) in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 1 microM)-activated human neutrophils, as well as on the release of myeloperoxidase (MPO) and elastase from these cells, have been investigated in vitro. Ca2+ fluxes were measured by the combination of a fura-2/AM-based spectrofluorimetric method and radiometric procedures, which together enable distinction between net efflux and influx of the cation, while radioimmunoassay and colorimetric methods were used to measure cAMP and granule enzymes, respectively. Coincubation of neutrophils with 1-hp did not affect intracellular cAMP levels or the FMLP-activated release of Ca2+ from intracellular stores but did retard the subsequent decline in the chemoattractant-induced increase in the concentration of cytosolic free Ca2+. These effects of 1-hp on the clearance of Ca2+ from the cytosol of activated neutrophils were associated with decreased efflux of the cation from the cells and increased release of MPO and elastase, while the delayed store-operated influx of the cation into the cells was unaffected by the pigment. The plasma membrane Ca2+-ATPase rather than a Na+-Ca2+ exchanger appeared to be the primary target of 1-hp. These observations suggest that the proinflammatory interactions of 1-hp with activated human neutrophils are a consequence of interference with the efflux of cytosolic Ca2+ from these cells.

The effects of ketolides on bioactive phospholipid-induced injury to human respiratory epithelium in vitro.

The potential of the novel ketolide antimicrobial agents, HMR 3004 and HMR 3647, to antagonize the injurious effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the ciliary beat frequency and structural integrity of human ciliated respiratory epithelium in vitro was investigated, in the presence or absence of polymorphonuclear leukocytes (PMNL). The ciliary beat frequency of human nasal respiratory epithelium, obtained by nasal brushing of healthy volunteers, was measured using a photo-transistor technique, while superoxide generation by activated human PMNL and membrane-stabilizing activity were measured by lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL, at concentrations of 2.5 microg x mL(-1), caused significant (p<0.005) ciliary slowing and epithelial damage, while treatment of the epithelial strips with the ketolides, in particular HMR 3004, caused dose-related attenuation of these direct adverse effects of the PL on ciliated epithelium, apparently by a membrane-stabilizing mechanism. When epithelial strips were exposed to the combination of PMNL (1 x 10(6) cells x mL(-1)) and PAF (1 microg x mL(-1)), significant ciliary dysfunction and epithelial damage were also observed, which were mediated predominantly by neutrophil-derived oxidants. These injurious effects of PAF were antagonized by preincubation of the epithelial strips or the PMNL with HMR 3004 (10 microg x mL(-1)). The ketolide antimicrobial agents, in particular HMR 3004, antagonize the direct and polymorphonuclear leukocyte-mediated injurious effects of phospholipids on human ciliated epithelium and may have beneficial effects in inflammatory disorders of the airways, such as asthma, chronic bronchitis, diffuse panbronchiolitis and bronchiectasis.

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.

Effect of inhibition of nitric oxide synthase on Pseudomonas aeruginosa infection of respiratory mucosa in vitro.

We studied the effect of the nitric oxide synthase (NOS) inhibitor asymmetric dimethyl arginine (ADMA) and the inactive enantiomer N G-methyl-D-arginine (D-NMMA) on Pseudomonas aeruginosa infection of the respiratory mucosa in nasal turbinate organ cultures. We also investigated the effect of P. aeruginosa culture filtrate on the expression of inducible NOS (iNOS) messenger RNA (mRNA) by an epithelial cell line (A549). Organ cultures were preincubated with ADMA (0.1 to 4 x 10(-4) M) or D-NMMA (2 x 10(-4) M) for 30 min prior to bacterial infection. Infected organ cultures (8 h) had significantly (P <= 0.05) greater epithelial damage and fewer ciliated and unciliated cells than did control cultures. There was an increased level of nitrite in the medium feeding infected organ cultures as compared with control cultures. ADMA significantly (P <= 0.05) reduced both bacterially induced epithelial damage and loss of ciliated cells in a concentration-dependent manner. D-NMMA did not influence the effect of P. aeruginosa infection of the mucosa. ADMA, but not D-NMMA, significantly (P <= 0.04) reduced total bacterial numbers adherent to the respiratory mucosa. P. aeruginosa culture filtrates (24 h and 36 h) significantly (P = 0.02) increased iNOS with respect to glyceraldehyde-3-phosphate dehydrogenase mRNA expression. These results show that P. aeruginosa stimulates iNOS expression by a cell line and NO production by an organ culture. ADMA reduces mucosal damage and loss of ciliated cells, which suggests that NO may be a mediator of epithelial damage caused by P. aeruginosa.

Systemic markers of inflammation in stable bronchiectasis.

Patients with bronchiectasis have an active local and systemic inflammatory response during infective exacerbations. Systemic markers of inflammation were investigated during a stable phase of their illness, because continued inflammation could affect their general health and be involved in disease progression. The relationship between levels of various systemic markers of inflammation and extent of disease on computed tomographic scan, lung function, sputum bacteriology and health related quality of life (HRQoL) was investigated in 87 noncystic fibrosis bronchiectasis patients. Several markers were elevated and correlated with the extent of disease and poor lung function. The total white cell count, neutrophil count and erythrocyte sedimentation rate correlated with both disease measures. Sputum bacteriology did not correlate with inflammation markers and patients with positive and negative cultures were similar. C-reactive protein and total white cell count correlated with some components of a disease-specific HRQoL questionnaire. In conclusion, patients with bronchiectasis in a stable phase have raised systemic markers of inflammation. Some markers, particularly the neutrophil count, correlate with disease severity. This result is in keeping with the hypothesis that the level of inflammation determines disease progression and health status.

Mucus transportability: the bovine trachea and frog palate models compared.

For nearly 30 yrs, the mucus-depleted frog palate has been used to measure the ciliary transportability of respiratory and other mucus gels, but the data obtained from this amphibian digestive system may not be applicable to human airway mucociliary clearance. This study compared this model with the mucus-depleted bovine trachea, a mammalian respiratory system. Assessments were made of the reproducibility of each model, and of the behaviour of sputum subjected to changes to its salinity or hydration. The bovine tracheal model was more reproducible than the frog palate. On the trachea but not the frog palate, sputum was transported more slowly than mucus from healthy animals. Increasing the salinity of sputum caused it to be transported 129% more quickly by the trachea (p=.001), but made no significant change to its transportability by the frog palate. Removal of water by evaporation led to an 83% increase in its bovine tracheal transportability but a 60% fall in its frog palate transportability (p<0.001). Therefore, the models make opposite predictions for the clinical value of altering mucus osmolality. The applicability of the frog palate model in the study of airway mucociliary clearance should be seriously questioned.