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Biomedical subjects

B K Rubin

Publications and source records attributed to B K Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1999

Physiotherapy and bronchial mucus transport.

Cough and expectoration of mucus are the best-known symptoms in patients with pulmonary disease. The most applied intervention for these symptoms is the use of chest physiotherapy to increase bronchial mucus transport and reduce retention of mucus in the airways. Chest physiotherapy interventions can be evaluated using different outcome variables, such as bronchial mucus transport measurement, measurement of the amount of expectorated mucus, pulmonary function, medication use, frequency of exacerbation and quality of life. Measurement of the transport rate of mucus in the airways using a radioactive tracer appears to be an appropriate outcome variable for short-term studies. Evaluation of chest physiotherapy only with pulmonary function tests appears to be inadequate in short-term studies. The popularity of using pulmonary function tests is probably based more on the availability of the instruments than on a theoretical basis related to the question of chest physiotherapy improving mucus transport. Quality of life and progression of the disease are not often used as outcome variables, but it may be worthwhile to use these in the future.

Bronchi↗
PubMed1999

Perfluorooctyl bromide (perflubron) stimulates mucin secretion in the ferret trachea.

OBJECTIVES: Partial liquid ventilation with perfluorooctyl bromide (perflubron) has been shown to be safe and effective in animal models with respiratory failure. However, airway mucus accumulation has been reported to be a problem in human trials. We hypothesized that this might be because perflubron directly affects mucociliary clearance or stimulates mucus secretion. METHODS AND RESULTS: We first measured the mucociliary transportability of secretions on the mucus-depleted frog palate exposed to perflubron and demonstrated that the ciliated epithelium remained intact with preservation of mucociliary transport. We then measured mucin and lysozyme secretion from isolated ferret tracheal segments to evaluate the secretagogue potential of perflubron. There was an 86% increase in mucin secretion with perflubron incubation at 40 min (n = 19; p < 0.01) and a 52% increase after 4 h of exposure followed by evaporation of perflubron (n = 19; p < 0.01). There was no significant difference in lysozyme secretion at any time between perflubron-exposed or buffer-exposed tissue (n = 4). The secretagogue effect was completely blocked by nordihydroguaiaretic acid, an inhibitor of arachidonic acid (AA) metabolism. CONCLUSION: These data suggest that although perflubron does not seem to be harmful to the airway, it induces mucus secretion in a noninflamed airway, and that this can be modulated by inhibitors of AA metabolism.

Animals↗
PubMed1999

An in vitro comparison of the mucoactive properties of guaifenesin, iodinated glycerol, surfactant, and albuterol.

STUDY OBJECTIVE: The mechanism of action of potential mucoactive agents could relate to effects on the mucociliary apparatus or to direct effects on the secretions. The purpose of this study was to determine the in vitro effects of several agents on the properties of mucus simulants and sputum collected from 30 adults with stable chronic bronchitis. DESIGN: Sputum or simulants were analyzed untreated and after the addition of the test agent at 1:5 volume to volume ratio for a contact period of 60 s. The concentrations of the agents were as follows: guaifenesin, 20 mg/mL; iodinated glycerol, 3 mg/mL; surfactant (Exosurf; Glaxo Wellcome; Research Triangle Park, NC) containing 13.5 mg of phospholipid per milliliter; albuterol, 5 mg/mL; and amphibian Ringer's solution (ARS) as a control. Dynamic viscoelasticity and surface mechanical impedance were measured in a magnetic microrheometer. Cohesiveness was measured using a filancemeter. The wettability of a hydrophilic surface was measured using an image processing system. The mucociliary transportability of sputum was timed on the frog palate, and cough transportability (CTR) was measured in a cough machine. RESULTS: When compared to sputum that had no test agent or ARS added, all agents reduced sputum elasticity G', with surfactant, albuterol, and guaifenesin significant at p < 0.001. As well, guaifenesin (p = 0.006), albuterol (p = 0.003), and surfactant (p = 0.02) decreased surface mechanical impedance (frictional adhesiveness) compared to untreated sputum. However, there were no significant changes in wettability, hydration, cohesiveness, or CTR with any agent, and there were no significant changes in the properties of sputum or simulants treated with test agents when compared to those treated with ARS. Guaifenesin irreversibly disrupted mucociliary transport when applied directly to the frog palate. CONCLUSIONS: These agents appear to have a minimal direct action on sputum in vitro, suggesting that at the concentrations studied, these agents do not have a significant beneficial effect on either the mucociliary transportability or CTR of chronic bronchitis sputum. However, there could be an effect of some of these agents after oral administration, especially if there is a secondary effect of the agent on an effector cell.

Adult↗
PubMed1999

Mucus-controlling agents: past and present.

Airway mucus is the secretory product of the mucous cells. The mucus is a variable mixture of water, mucous glycoproteins, low molecular weight ions, proteins, and lipids, the physical properties of which are important for airway defense. The factors that contribute to the physical properties of mucus are complex, and there are several pharmacologic strategies that potentially can serve to improve the clearability of airway mucus. In vitro results suggest potential benefit from the additive effects of selected combinations of mucoactive medications. Further studies are required to confirm these findings, to perform direct assessments of mucus clearability, and to extend the observations to patients with various types of pulmonary diseases for which mucoactive treatments are required.

Drug Combinations↗
PubMed1998

Nitric oxide metabolites in cystic fibrosis lung disease.

Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and nitrite, were determined in the saliva and sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis patients during a pulmonary exacerbation, and in saliva and endotracheal secretions of normal controls. Median saliva concentrations of NO metabolites (nitrate plus nitrite) were 704 mumol/l (95% confidence interval (CI) 419 to 1477) in stable cystic fibrosis patients, 629 mumol/l (95% CI 382 to 1392) in cystic fibrosis patients presenting with pulmonary exacerbation, and 313 mumol/l (95% CI 312 to 454) in controls. Median sputum NO metabolite concentration in stable cystic fibrosis was 346 mumol/l (95% CI 311 to 504). This was not significantly different from cystic fibrosis patients presenting with pulmonary exacerbation (median 184 mumol/l, 95% CI 249 to 572), but significantly higher than in endotracheal secretions of controls (median 144 mumol/l, 95% CI 96 to 260). Sputum NO metabolite concentration in cystic fibrosis pulmonary exacerbation significantly increased during antibiotic treatment. A positive correlation was observed between sputum NO metabolites and lung function in stable cystic fibrosis, suggesting less airway NO formation in cystic fibrosis patients with more severe lung disease. These data indicate that decreased exhaled NO concentrations in cystic fibrosis patients may be due to retention and metabolism of NO within the airway secretions. However, sputum NO metabolites are not a useful marker of airway inflammation in cystic fibrosis lung disease.

Adolescent↗
PubMed1997

Effects of aerosolized surfactant in patients with stable chronic bronchitis: a prospective randomized controlled trial.

CONTEXT: Chronic bronchitis, estimated to affect more than 13 million adults in the United States, is characterized in part by retention of airway secretions, but no approved or effective therapy for airway mucus retention in patients with chronic bronchitis has been established. Surfactant reduces sputum adhesiveness, which contributes to difficulty in clearing secretions, but surfactant has not been tested in patients with chronic bronchitis. OBJECTIVE: To examine the effects of exogenous surfactant on sputum clearance and pulmonary function in patients with stable chronic bronchitis. DESIGN: A prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled comparison of the effects of 2 weeks of treatment with 3 doses of aerosolized surfactant (palmitoylphosphadidylcholine [DPPC]) or saline (placebo). SETTING: Four US teaching hospitals. PARTICIPANTS: A total of 87 adult patients with the diagnosis of stable chronic bronchitis. MAIN OUTCOME MEASURES: Pulmonary function, respiratory symptoms, and sputum properties before treatment (day 0), after 2 weeks of treatment (day 14), and 7 days after stopping treatment (day 21). RESULTS: A total of 66 patients were randomized to surfactant treatment and 21 to saline treatment. Patient demographic characteristics between groups were similar at baseline. In patients who received a DPPC dose of 607.5 mg/d for 2 weeks, prebronchodilator forced expiratory volume in 1 second (FEV1) increased from 1.22 L (SEM, 0.08 L) at day 0 to 1.33 L (SEM, 0.09 L) at day 21 (P=.05), an improvement of 11.4%; postbronchodilator FEV1 improved 10.4% by days 14 and 21 (P=.02); and the ratio of residual volume to total lung capacity, a measure of thoracic gas trapping, decreased 6.2% by day 21 (P=.009). In the surfactant groups, there was a dose-dependent increase in the ability of sputum to be transported by cilia in vitro. CONCLUSION: Aerosolized surfactant improved pulmonary function and resulted in a dose-related improvement in sputum transport by cilia in patients with stable chronic bronchitis.

Administration, Intranasal↗
PubMed1997

Regulation of mucin secretion in the ferret trachea.

Mucin is the major component of mucus and can be used as a marker for mucus secretion. The purpose of this study was to develop an in vitro method to evaluate the regulation of mucin secretion. To do this, we used a sandwiched enzyme-linked lectin assay to measure mucin secretion from isolated ferret tracheal segments. This assay entailed coating microtiter plate wells with dolichos biflorus agglutinin and detecting the bound mucin that was secreted into a buffer solution by the tracheal segments. We used this method to evaluate the secretory response to four secretagogues: prostaglandin F2alpha (PGF2alpha), adenosine triphosphate (ATP), methacholine, and human neutrophil elastase (HNE). Each agent stimulated mucin secretion above baseline secretion (ATP (p = 0.022), PGF2alpha (p = 0.009), and HNE (p < 0.05)), and the relative potency of these secretagogues was PGF2alpha < or = ATP < MCh < HNE. We also demonstrated that there is an anatomic gradient for both constitutive and stimulated mucin secretion, with the distal tracheal segments secreting more mucin per gram of weight than the proximal segments. This fairly simple and reproducible technique can be used to evaluate the regulation of mucin secretion in the airway and to assess the efficacy of agents that might alter the secretory response.

Adenosine Triphosphate↗
PubMed1997

Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis.

Erythromycin inhibits mucus glycoconjugate secretion from airway cells in vitro and may increase mucus clearance in patients with asthma or diffuse panbronchiolitis. Because mucus hypersecretion is common in purulent rhinitis, we questioned whether clarithromycin would change the properties of nasal mucus from subjects without sinus disease and from patients with acute purulent rhinitis. Nasal secretions were collected before and after nasal methacholine challenge from 10 adults without nasal symptoms and without methacholine from 10 patients with purulent rhinitis. After 2 wk of oral clarithromycin (500 mg twice daily), secretions were again collected from both groups. Secretions were analyzed for viscoelasticity, cohesion, hydration, and ciliary and airflow (sneeze) transportability. Compared with secretions from healthy subjects, rhinitis secretions had decreased wettability (contact angle on Teflon 100 degrees versus 84.67 degrees; p = 0.001), increased cohesion (36.8 versus 24.3 mm; p = 0.003), decreased sneeze clearability (20.6 versus 32 mm; p = 0.04), and increased percent solids (4.61 versus 2.82%; p = 0.04). After clarithromycin, the rheology, hydration, cohesion, and transportability of the rhinitis secretions were similar to those of the postclarithromycin secretions from the healthy subjects. Secretion volume also decreased (500.1 versus 28.3 mg; p = 0.01), and mucociliary transportability increased by 30% (0.76 versus 0.99; p = 0.005). Although clarithromycin reduced mucus secretion in both rhinitis patients and normal subjects, it did not alter the secretory response to methacholine.

Acute Disease↗
PubMed1997

Promoting meconium clearance from the lungs of the neonatal piglet with asymmetric high frequency oscillation.

To investigate the role of high frequency oscillation (HFO) in promoting meconium clearance from the airway, we used a commercially available ventilator configured with maximal expiratory flow exceeding inspiratory flow (asymmetric HFO or AHFO). We hypothesized that AHFO would move meconium in an expiratory direction (toward the ventilator). We first tested our hypothesis in vitro and, later, in vivo using the neonatal piglet. In vitro experiments using a Plexiglas airway confirmed meconium movement in an expiratory direction when bias ratio was > or = 2. For in vivo experiments, each piglet received a 3 mL/kg intratracheal bolus of a 44 g/100 mL meconium mixture followed by 45 min of mechanical ventilation. Then, in part 1, the piglet was placed in a 15 degree head down tilt position and randomized to either AHFO [ratio of inspiratory time/expiratory time (I:E) of 70:30] or HFO (I:E ratio of 30:70). After 30 min of either AHFO or HFO, the piglet was crossed over to the alternate strategy for an additional 30 min. For part 2, we maintained the piglet on either AHFO or HFO continuously for 4 h. Results demonstrate that, although there was a tendency for larger volumes of meconium to be aspirated from the airway during AHFO in part 1 experiments, there was no difference found in part 2. We also found no significant differences in blood gases or hemodynamic measurements between AHFO and HFO during the prolonged observation period in part 2 of our study. We conclude that AHFO is of no benefit in the treatment of meconium aspiration syndrome.

Animals↗
PubMed1997

Ultrasonic nebulization of albuterol is no more effective than jet nebulization for the treatment of acute asthma in children.

STUDY OBJECTIVE: Nebulizer systems used to generate therapeutic aerosols vary in their ability to deliver medication to the airway. In a recent study in 17 adults with stable asthma, albuterol given using an ultrasonic nebulizer (UN) appeared to produce greater bronchodilatation than the same dose of albuterol given by a jet nebulizer (JN). The purpose of this study was to determine if the UN used in that study would produce a better bronchodilator response in children with acute asthma than the JN system that has been in use at Cardinal Glennon Children's Hospital. DESIGN: Randomized, prospective, unblinded study. SETTING: An urban university children's hospital emergency department. PARTICIPANTS: One hundred thirteen children, aged 7 to 16 years, who presented for treatment of acute moderately severe asthma completed this study. INTERVENTIONS: After randomization and exclusion of dropouts, 46 children received albuterol by UN and 67 were treated by JN. MEASUREMENTS: Pulmonary function tests (PFTs) by spirometry, pulse oximetry, and symptom score at baseline and at 15 and 30 min following a single prescribed treatment. RESULTS: PFT on entry to the study was the same in both groups (FEV1; p>0.97). The change in FEV1 after therapy (UN+0.22 L vs JN+0.37 L) was significant (p<0.05) and favored JN. There was no difference in the improvement in pulmonary function between JN and UN therapy in children with an initial FEV1/FVC > 75% predicted but when FEV1/FVC < 75%, the improvement in FEV1 again favored the JN (UN+0.2 vs JN+0.47; p<0.05). CONCLUSION: For the treatment of acute exacerbations of asthma in children, there is no greater bronchodilator response when albuterol is administered by a UN than by a JN.

Acute Disease↗
PubMed1996

Use of anticholinergic bronchodilation in children.

Ipratropium bromide is a quaternary ammonium anticholinergic bronchodilator with minimal systemic absorption across the blood-airway barrier. Ipratropium bromide has become primary therapy for the treatment of adults with chronic bronchitis, but its use in children has been limited. Ipratropium bromide can be safely used in the management of acute bronchiolitis, recognizing that most infants do not appear to respond to any bronchodilator medication. When used with a beta-agonist bronchodilator for the therapy of acute childhood asthma, ipratropium bromide appears to provide bronchodilation beyond that achieved by either agent used alone. There are insufficient published data to determine the appropriate use if ipratropium bromide in infants with bronchopulmonary dysplasia, although many of those symptomatic after the age of 6 months seem to benefit from either ipratropium bromide or beta-agonists. As ipratropium bromide has no intrinsic anti-inflammatory properties, its role in the chronic therapy of asthma and related disorders is still unclear.

Asthma↗
PubMed1996

Therapeutic aerosols and airway secretions.

Despite common misconceptions, airway mucus is not an impermeable barrier that entraps and clears all inhaled material. To be therapeutically effective, an aerosol medication must efficiently deposit in the airway and then diffuse or translocate across the mucous barrier while retaining bioactivity. Characteristics of aerosols that affect their ability to penetrate the mucous barrier include particle charge, solubility, and size. Aerosol medications can also change the biophysical properties of secretions and influence how rapidly mucus is cleared. Surfactant is probably responsible for the displacement of inhaled particles through the mucous layer (Schürch et al., 1990). As well, exogenous surfactant has been shown to increase tracheal mucociliary clearance in anesthetized dogs (de Sanctis et al., 1994) and to improve the mucociliary clearability of secretions from babies with neonatal respiratory distress syndrome (Rubin et al., 1992). Using measurements of sputum-substrate contact angle and interfacial tension, cystic fibrosis (CF) sputum had been shown to have an abnormally high adhesion tension, (Girod et al., 1992). We assessed the in vitro effects of synthetic surfactant (Exosurf, Burroughs-Wellcome, Research Triangle Park, NC) on the physical and transport properties of sputum from 15 patients with CF and 30 patients with stable chronic bronchitis (CB). The concentration of ExosurfTM used was 13.5 mg of DPPC/ml corresponding to the reconstituted concentration for aerosol administration. The sputum was divided so that aliquots each were treated with Exosurf and amphibian Ringer's solution layered on the sputum at a concentration of 1:5 v/v for 15 min at 24 degrees C. There was a reduction in spinnability (p < 0.0001) in CF sputum from baseline and a fall in adhesion tension (0.05 < p < 0.1) with Exosurf treatment. Potentially important increases in both mucociliary and cough clearability were noted without associated changes in sputum rheology. In bronchitis sputum, surfactant reduced adhesiveness (p < 0.01), but this was not associated with improved clearability. Adhesive forces are involved in ciliary coupling and cough transport. This raises the possibility of using surfactant as a mucokinetic agent in the therapy of chronic suppurative lung disease.

Aerosols↗
PubMed1996

Ring distraction technique for measuring surface tension of sputum: relationship to sputum clearability.

Poor sputum clearance has been related to sputum adhesion tension. In this study, we describe a modified du Noüy ring method for measuring the surface tension (gamma) of small samples of sputum and for comparinge the calculated work of adhesion (Wad) for sputum specimens with the measured mucociliary transportability (MCTR) and cough transportability (CTR). The gamma, as measured by this method, correlates with gamma measured by sputum contact angle on a low-surface-energy solid (R2 = 0.368, P = 0.03). There is a small but significant difference in measurements made by these two methods (P = 0.03). Wad calculated from the surface tension ring method is inversely correlated with CTR (R2 = 0.181, P = 0.004) but has no correlation with MCTR in this study. The miniaturized ring method gives accurate and reproducible measurements of the surface tension of small amounts of respiratory secretions. Because sputum behaves enough like a liquid that the assumptions made in using the Young equation to calculate Wad appear valid, we also showed that the Neumann equation can be used to determine the surface tension of sputum by its contact angle on tetrafluoroethylene (Teflon).

Bronchitis↗
PubMed1996

The surface and transport properties of meconium and reconstituted meconium solutions.

Passage of meconium in utero and subsequent pulmonary aspiration of meconium admixed with amniotic fluid is a major cause of neonatal respiratory distress. Airway clearance is the first defense of the lung, and clearance is dependent on the bulk physical (rheologic) as well as the surface properties of airway material. We therefore evaluated the surface adhesive properties and the transport properties of freshly passed meconium and of two dilutions of reconstituted, blended, meconium as used to mimic the effect of meconium passage into the amniotic fluid in animal models of meconium aspiration syndrome. Reconstituted and fresh meconium had similar physical and transport properties, including an extremely high interfacial (adhesion) tension and very poor transportability by either airflow or cilia. The similarities between the freshly passed and reconstituted meconium suggest that the latter is an adequate substitute for use in animal models of meconium aspiration syndrome. The high adhesiveness of meconium suggests a potential role for surfactant administration as an adhesive to improve airway clearance after meconium aspiration.

Adhesives↗