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Biomedical subjects

D Pavia

Publications and source records attributed to D Pavia.

At least 37 records · Page 2Linked to original sources

Effect of four-week treatment with oxitropium bromide on lung mucociliary clearance in patients with chronic bronchitis or asthma.

The effect of oxitropium bromide on lung mucociliary clearance, pulmonary function and viscoelastic properties of sputum was investigated in 10 asthmatics and 10 chronic bronchitics. A controlled, double-blind, crossover study was performed. Following a baseline (B) measurement the patients were, in a random order, allocated placebo (P) or oxitropium bromide (O; 0.1 mg/puff), administered from metered dose inhalers, which they used for 4 weeks at a dose of 2 puffs t.d.s. This test medication was used in conjunction with their normal medication. At the end of the treatment period the patients were assessed, the treatments were then crossed over and a final assessment made 4 weeks later. The administration of oxitropium bromide resulted in (1) small but statistically significant increases in pulmonary function (less than 10% vs. placebo); (2) increased penetrance of radioaerosol into the lungs (mean +/- SEM alveolar deposition: 35 +/- 3, 26 +/- 3 and 24 +/- 3% for the O, P and B runs respectively; p less than 0.025); (3) no significant change in particle clearance rate from the lungs despite their deeper penetration (mean +/- SEM area under the tracheobronchial clearance curves between 0 and 6 h: 317 +/- 26, 324 +/- 25 and 287 +/- 25%.h for the O, P and B runs respectively; p greater than 0.1); (4) no alteration in sputum production, and (5) no significant changes in apparent viscosity (mean +/- SEM: 640 +/- 162, 446 +/- 79 and 557 +/- 115 mPa.s for the O, P and B runs, respectively; p greater than 0.1) and elasticity (mean +/- SEM: 3,682 +/- 1,383, 1,779 +/- 353 and 2,061 +/- 366 mPa for the O, P and B runs, respectively; p greater than 0.1) of sputum. When the two groups, i.e. the chronic bronchitics and asthmatics, were studied separately, no significant differences in any parameter measured (other than radioaerosol penetrance which was significantly enhanced on oxitropium bromide in chronic bronchitics) were noted between the three assessments.

Aged↗

Subcutaneous adrenaline versus terbutaline in the treatment of acute severe asthma.

Subcutaneous adrenaline and terbutaline have been compared in a double blind study of 20 patients with acute severe asthma presenting to an accident and emergency department. Ten patients received adrenaline 0.5 mg (0.5 ml) and 10 terbutaline 0.5 mg (0.5 ml) subcutaneously. Further treatment with nebulised salbutamol (5 mg), hydrocortisone (200 mg), and aminophylline (0.9 mg/kg/hour) was started 15 minutes later. All patients reported a reduction in chest tightness within three minutes of receiving both adrenaline and terbutaline and reported no adverse effects. Mean baseline values of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) did not differ significantly between the adrenaline group (130 1 min-1 and 0.83 l) and the terbutaline group (111 1 min-1 and 0.63 l). After administration of adrenaline PEF had increased by 21% and FEV1 by 40% five minutes after the injection, and by 35% and 64% at 15 minutes. Terbutaline caused a 23% increase in PEF and a 37% increase in FEV1 at five minutes, and a 40% and 58% increase at 15 minutes. There was no significant difference in PEF, FEV1, heart rate, blood pressure, or pulsus paradoxus between the two groups at any time. Continuous electrocardiographic recording showed no abnormalities in either group. Thus in this study subcutaneous adrenaline (0.5 mg) and terbutaline (0.5 mg) produced effective rapid bronchodilatation without serious side effects.

Acute Disease↗

Efficacy of "mucoregulatory" agents in Young's syndrome.

Eight patients with Young's syndrome were treated with four "mucoregulatory" agents for eight weeks in a randomised, open crossover study. There was no improvement in tracheobronchial clearance, pulmonary function, or sperm count.

Adult↗

Impaired mucus clearance in patients with chronic bronchial sepsis, sinusitis and dextrocardia.

Published reports have indicated that patients with Kartagener's syndrome (dextrocardia, sinusitis and bronchiectasis) have no significant lung mucociliary clearance. With a radioaerosol technique we measured over a 6-hour observation period the tracheobronchial clearance of 8 patients with dextrocardia, chronic bronchial sepsis and chronic sinusitis (DC). The tracheobronchial clearance of these patients was significantly reduced (p less than 0.02) compared with that of 29 healthy subjects of similar age. However, even when allowance was made for productive coughing during the observation period, the reduced clearance was much better than anticipated from published reports in patients with Kartagener's syndrome, which confined their observations to a 2-hour period. The tracheobronchial clearance of the DC patients, adjusted for productive coughing, was as bad as that found in an older group of patients with chronic obstructive airways disease who refrained from expectorating during the equivalent test period. Our study implies one or more of the following possibilities: (a) a spectrum of mucociliary impairment in patients with DC; (b) an effective cough clearance deeper in the lung than hitherto believed, and (c) two-phase flow of mucus cephalad as an effective clearance mechanism in patients with DC.

Bronchi↗

Variability and reproducibility in the measurement of tracheobronchial clearance in healthy subjects and patients with different obstructive lung diseases.

The purpose of this study was to establish the inter- and intra-subject/patient variability of tracheobronchial clearance, measured for 6 h, using a radioaerosol technique. Inter-subject variability was evaluated in five groups: 33 healthy non-smokers (NS); 19 asymptomatic smokers (S); 40 asthmatics (A); 27 chronic bronchitics (CB) and 12 bronchiectatics (B). Intra-subject variability was evaluated in 16 A and 27 CB who were studied twice. The inter-subject/patient coefficient of variation (CoV) of tracheobronchial clearance was 13% for NS and 28-39% for the remaining four groups. The intra-patient CoV was about half of the inter-patient CoV. Inter-subject CoV (for A and CB) appeared to be independent of initial tracheobronchial deposition of radioaerosol and frequency of cough. We were also able to estimate the approximate number of patients required for a crossover study in order to avoid statistical, type II errors when investigating the effect of a drug or of a therapeutic intervention on tracheobronchial clearance.

Adult↗

Respiratory epithelial permeability is unrelated to bronchial reactivity and small airway function in young smokers and nonsmokers.

We studied eight young smokers and ten nonsmokers, to determine whether respiratory epithelial permeability to radiolabelled diethylenetriamine penta-acetate (99mTcDTPA) was related to small airway function or bronchial reactivity. Permeability was measured in inner (containing central airways) and outer lung zones by gamma camera. Lung-to-blood half-time (LB-T1/2) was corrected for blood background. Histamine was inhaled tidally (2 min inhalations) using doubling concentrations from 2 to 64 mg.ml-1. Results of small airway function tests, and of bronchial reactivity (expressed as the threshold concentration (reducing forced expiratory volume in one second (FEV1) by 2 SD), and as the percentage reduction in FEV1 after histamine 16 mg.ml-1) were similar in smokers and nonsmokers. LB-T1/2 was shorter in smokers than in nonsmokers in both inner (median (range) 21 (5.5-33) vs 63.5 (41-115) min; p less than 0.004) and outer (20.5 (5.5-30) vs 58.5 (39-105) min; p less than 0.004) zones. Neither inner nor outer zone LB-T1/2 was related to small airway function or bronchial reactivity. Bronchial reactivity and small airway tests may be abnormal in middle-aged smokers, but neither is related to the increased respiratory epithelial permeability of young smokers, in whom it appears too sensitive an index of airway integrity.

Adult↗

Effect of terbutaline administered from metered dose inhaler (2 mg) and subcutaneously (0.25 mg) on tracheobronchial clearance in mild asthma.

Tracheobronchial mucus clearance was measured in nine mild asthmatics, using an objective radioaerosol technique, on 3 separate days at intervals of 1 week. Immediately after radioaerosol inhalation, drug or placebo was administered via subcutaneous injection (SC) plus metered dose inhaler (MDI)--2 puffs. Three randomized treatments were used: saline placebo SC plus 2 mg terbutaline by MDI (1 mg per puff); 0.25 mg terbutaline SC plus placebo (propellants and surfactant only) by MDI; and double placebo. Changes in lung mucociliary clearance showed an inverse relationship to baseline clearance of both proximal and distal ciliated airways following inhaled terbutaline, whereas terbutaline SC related inversely only to baseline clearance of the distal ciliated airways. This may reflect the surface concentrations of drug, established by each route.

Administration, Inhalation↗

Impaired tracheobronchial clearance in bronchiectasis.

Tracheobronchial clearance was measured by a radioaerosol technique in 12 patients with bronchiectasis, seven patients with chronic obstructive lung disease expectorating mucoid sputum daily (group X), eight patients with chronic obstructive lung disease but negligible sputum expectoration (group Y), and 10 healthy subjects. The patients with bronchiectasis all expectorated purulent sputum daily (mean wet weight 47 g/day), had reduced forced expiratory volume in one second (FEV1) (mean 47.5% predicted), and were unable to avoid coughing during the six hour observation period. None of the patients with bronchiectasis or the healthy subjects were current smokers. There were five current smokers in group X and six in group Y. The mean FEV1 in group X was 41% predicted and in group Y 52% predicted, both values similar to that of the patients with bronchiectasis. Tracheobronchial clearance in the first six hours after inhalation of radioaerosol was significantly (p less than 0.01) slower in patients with bronchiectasis than in matched healthy subjects despite more proximal deposition of radioaerosol (p = 0.01) and more coughing (p less than 0.01) in the former. Tracheobronchial clearance in patients with bronchiectasis was impaired to a similar degree to that in patients with chronic obstructive lung disease but no bronchiectasis.

Aged↗

Response and acclimatisation of symptomless smokers on changing to a low tar, low nicotine cigarette.

Ten symptomless smokers were switched from their usual cigarette to a low tar, low nicotine test cigarette for two weeks to investigate their immediate response and subsequent acclimatisation to the test cigarette. The tar (T) and nicotine (N) yields of the test cigarettes were T = 3.8 mg, N = 0.6 mg; the median yields of the usual cigarettes were T = 16.4 mg, N = 1.4 mg. The subjects were monitored over a six week period comprising a control period (usual cigarette), a test period (test cigarette), and a return period (usual cigarette), each lasting two weeks. The inhaled smoke volume (smoke from the burning tip of the cigarette which is subsequently inhaled) was measured with a non-invasive radiotracer technique. Puffing indices were recorded using an electronic smoking analyser and flowhead cigarette holder. Measurements were made at the beginning of the control period, at the beginning and end of the test period, and at the end of the return period. Subjects kept records of their cigarette consumption during each of the three periods. Apart from a small change in puff duration, cigarettes were smoked in the same way during the control and return periods. Mean and total puff volumes increased with the low tar, low nicotine cigarette but did not change from the beginning to the end of the test period. There was no significant change between the control, test, and return periods for mean inhaled smoke volume, total inhaled smoke volume, or cigarette consumption. It is concluded that when smokers are switched to a low tar, low nicotine cigarette the puff volume increases but there is no change in the inhaled smoke volume or daily consumption.

Adult↗

Mediators and mucociliary clearance in asthma.

Lung mucociliary clearance is significantly reduced in asthmatic patients compared to healthy controls even during clinical remission. Further retardation in mucous clearance occurs during sleep per se and this may be a contributing factor to nocturnal asthma. Chemical mediators of anaphylaxis appear to have various and, sometimes opposing effects on the two essential components for mucociliary clearance, namely cilia and mucus. Some mediators such as leukotrienes C4 and D4 are potent secretagogues and histamine increases the water flux into the lumen of the airways from the mucosa. Slow-reacting substance of anaphylaxis (SRS-A) reduces mucus transport whereas histamine enhances it. Ciliostimulation has been reported following allergen challenge and this contrasts with the cilioinhibitory effect of asthmatics' sputa. It appears however, that the net effect of the various chemicals of anaphylaxis is one of impairment of mucus clearance. Some pharmacological agents, used for the relief of bronchospasm and control of asthma, also stimulate mucociliary transport, a desirable additional effect.

Animals↗

General review of tracheobronchial clearance.

The human tracheobronchial tree possesses several mechanisms for keeping itself clean and sterile. Mucociliary clearance results from the beating action of cilia lining the conducting airways and propelling the overlying mucus cephalad. Locally produced biological debris and inhaled, insoluble material are swept with the mucus and removed from healthy lungs within one day. Cough augments the often impaired mucociliary clearance of patients with excessive secretions. Cough is limited in is efficacy to the proximal airways. Energy transfer from airflow to mucus transport in airways lined with excessive secretions has been put forward as a third mechanism (two-phase gas-liquid flow) for the removal of lung secretions. Other mechanisms that have been proposed for clearance of lung secretions are: 'milking', 'squeezing' and peristalsis.

Biomechanical Phenomena↗

Mucus clearance from peripheral airways.

Mucociliary clearance data obtained with 5 microns radioaerosol particles have been analyzed for asymptomatic young cigarette smokes and non-smokers. The rate and the amount of peripheral zone clearance were both considered in relationship to the overall depth of radioaerosol lung penetration. In the smokers, but not in the non-smokers, the forms of relationship found appeared compatible with prediction based on simple mathematical modelling of aerosol deposition sites within the lung. We suggest that the results found in the non-smokers are attributable to poor mucociliary defence (which is rarely required) of their more distal peripheral airways--due presumably to low levels of cross-linked glycoprotein mucus in these airways--whilst those in the smokers functionally reflect the presence of an increased supply of mucus appropriate for mucociliary transport.

Adult↗

Inhaled smoke volume and puff indices with cigarettes of different tar and nicotine levels.

Ten asymptomatic smokers each smoked a low, low-to-middle and a middle tar cigarette with approximately the same tar-to-nicotine ratio, in a randomised order. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded using an electronic smoking analyser and flowhead/cigarette holder. Throughout the study neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette changed significantly; however, the mean and total puff volumes were largest with the low tar cigarette and decreased with the higher tar brands. Puff volume was related to puff work (rs = 0.83, P less than 0.001) but was not related to puff resistance (rs = 0.10, P greater than 0.1). It is concluded that when switched between brands with the same tar-to-nicotine ratio, smokers increase their puff volumes with a lower tar cigarette but do not change the volume of smoke inhaled. Puff work and puff resistance were significantly correlated (rs = 0.45, P less than 0.02).

Adolescent↗

The separate effects of tar and nicotine on the cigarette smoking manoeuvre.

The separate effects of tar and nicotine on the cigarette smoking manoeuvre were investigated. Each of ten asymptomatic habitual smokers smoked three different commercially available cigarettes in a randomised order. The brands were chosen such that two had the same tar yield (10 mg) and two had the same nicotine yield (1.4 mg). The volume of smoke inhaled into the lungs was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded using an electronic smoking analyser and flowhead/cigarette holder. There was no difference in the total volume of smoke puffed from each of the cigarette brands. With cigarettes of the same tar level, the total inhaled smoke volume was lower with the higher nicotine cigarette (P less than 0.05): by contrast, with cigarettes of the same nicotine level, the total inhaled smoke volume was lower with the lower tar cigarette (P less than 0.02). Tar and nicotine appear to exercise independent control over the volume of smoke inhaled.

Adult↗

Cough and mucociliary clearance.

Cough is a host defence mechanism of the lungs. Theoretical considerations indicate that the efficacy of cough in clearing secretions is limited to the first few airway generations of the human lung. Studies utilizing radioaerosols as markers of mucus support the theoretical predictions and show that cough is effective in the proximal airways only in the presence of excess secretions. Limited studies on the efficacy of cough on regional clearance of secretions have been equivocal regarding its effect in the "peripheral" regions of the lungs. Persistent coughing can result in temporary slowing or even cessation of lung mucociliary clearance at the flow-limiting segments of the lung. The forced expiration technique, which is not accompanied by the compressive phase associated with cough, is more effective than coughing in clearing excess secretions from the lungs.

Aerosols↗

Sensory mechanisms in the upper respiratory tract affect the inhalation of cigarette smoke in man.

Cigarette puffing parameters (puff volume, puff duration, number of puffs, total smoking time) and inhaled smoke volume (by a radiotracer technique) have been measured in a group of 11 asymptomatic smokers, once after topical anaesthesia of the upper airways and once without anaesthesia. Topical anaesthesia significantly reduced the mean inhaled smoke volume per puff for the group from 41.1 ml to 30.6 ml (P less than 0.05) and the total inhaled smoke volume from 575 ml to 528 ml (P = 0.05), but cigarette puffing parameters were unchanged. It is concluded that stimulation of upper airway sensory receptors, probably sensitive to nicotine, may be an important mechanism in determining the amount of cigarette smoke inhaled by smokers.

Adult↗

Inhaled smoke volume, puffing indices and carbon monoxide uptake in asymptomatic cigarette smokers.

Nine asymptomatic smokers each smoked one cigarette of their usual brand on four separate occasions. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded by using an electronic smoking analyser and flowhead/cigarette holder. The expired air carbon monoxide concentration was measured immediately before and within 5 min of finishing smoking. The inhaled smoke percentage (total inhaled smoke volume/total puff volume) averaged 46% to 85% in different subjects. Neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette was significantly correlated with any of the puffing indices. Smokers took significantly smaller and shorter puffs, left longer between puffs and inhaled less smoke as the cigarette was smoked (P less than 0.01), although the proportion of the puff which was subsequently inhaled did not change significantly. There was no significant intra-subject difference in any index from one visit to another.

Adolescent↗