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B R Wiggs

Publications and source records attributed to B R Wiggs.

54 records · Page 3Linked to original sources
PubMed1990

A model of the mechanics of airway narrowing.

To examine the interaction between airway smooth muscle shortening and airway wall thickening on changes in pulmonary resistance, we have developed a model of the tracheobronchial tree that allows simulation of the mechanisms involved in airway narrowing. The model is based on the symmetrical dichotomous branching tracheobronchial tree as described by Weibel and uses fluid dynamic equations proposed by Pedley et al. to calculate inspiratory resistance during quiet tidal breathing. To allow for changes in lung volume, we used the airway pressure-area curves developed by Lambert et al. The model is easily implemented with a spreadsheet and personal computer that allows calculation of total and regional pulmonary resistance. At each airway generation in the model, provision is made for airway wall thickness, the maximal airway smooth muscle shortening achievable, and an S-shaped dose-response relationship to describe smooth muscle shortening. To test the validity of the model, we compared pressure-flow curves generated with the model with measurements of pulmonary resistance while normal subjects breathed air and 20% O2-80% He at a variety of lung volumes. By simulating progressive airway smooth muscle shortening, realistic pulmonary resistance vs. dose-response curves were produced. We conclude that this model provides realistic estimates of pulmonary resistance and shows potential for examining the various mechanisms that could produce excessive airway narrowing in disease.

Adolescent↗
PubMed1990

Small airway dimensions in smokers with obstruction to airflow.

The obstruction to airflow that develops in some cigarette smokers is thought to be related to inflammation of small airways. However, the mechanism by which inflammation leads to obstruction has not been elucidated. We performed morphometry to determine if the airways of patients with obstruction were thicker than normal. Sixty smokers were selected from those undergoing resectional lung surgery. They were grouped according to their FEV1/FVC ratio (FEV1% control = 77%, FEV1 obstructed = 55%) and matched for age, sex, and height. Wall area (mm2), perimeter (mm), and diameter (mm) were measured by a modification of the technique of James and coworkers (7). The relaxed luminal diameter (mm) and wall thickness (mm) were calculated from these values. A pathology score for inflammation and fibrosis was assigned to each patient, and the percentage of the wall made up of muscle, epithelium, and connective tissue was determined by point counting. Two hundred airways, 90% of which were membranous bronchioles, were measured in each group. The mean-measured luminal diameter in the controls was 0.81 mm and in the obstructed patients 0.70 mm (p less than or equal to 0.05). The regression lines relating wall thickness to calculated luminal diameter showed that the airways of the obstructed patients were thicker throughout the size range measured (p less than or equal to 0.005). The muscle, epithelium, and connective tissue were all increased in the obstructed patients (p less than or equal to 0.001). In addition, the wall thickness correlated with the pathology score (r = 0.6074, p less than or equal to 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Proportions and sizes of muscle fiber types in the hamster diaphragm.

This study demonstrated that there was interanimal and interregional variability of proportions and sizes of the muscle fiber types in the hamster diaphragm. Muscle fiber type proportions and sizes were determined for each side (right, left), surface (abdominal, thoracic), and region (sternal, anterior costal, posterior costal, crural) in six hamsters. There was marked regional and surface-to-surface variability and some interanimal variability in proportions and sizes of fiber type within the hamster diaphragm. The sternal and costal regions were relatively homogeneous. However, there were differences in both proportions and sizes of fiber types between the thoracic surface of the crural region and the abdominal surface of the crural region. These two surfaces of the crural region differed from the rest of the diaphragm. For muscle fiber type proportions, type 2a fibers demonstrated the most interanimal variability. Muscle fiber size varied little between animals.

Animals↗
PubMed1989

Regional pulmonary transit times in humans.

We measured the frequency distribution of erythrocyte (RBC) transit times in resected lobes of lungs in eight human subjects undergoing thoracotomy for peripheral lung tumors. RBC transit times were measured by the injection of radiolabeled blood flow and volume markers, which were counted in samples from the resected lung. In five of these subjects, the measurements from the resected lung were compared with preoperative measurements of the transit times of radiolabeled RBCs with a gamma camera-computer system. Time-activity curves from the cardiac chambers and the lung or its regions were obtained from which transit times were calculated by the centroid and deconvolution techniques. The reproducibility of transit times measured by this technique was assessed in another eight normal subjects, after sequential bolus injections of radiolabeled cells. The mean transit time of the upper lung region was longer (5.1 +/- 0.5 s) than that of the lower (4.1 +/- 0.6 s, P less than 0.05) in the preoperative study. Similarly, the mean transit time of the upper lung slice was longer (5.5 +/- 0.3 s) than that of the lower slice (3.8 +/- 0.3 s, P less than 0.05) in the resected lung specimens. We conclude that there was good agreement between these techniques and that there are long transit times in the upper regions of human lungs.

Blood Circulation Time↗
PubMed1989

The changes in airways structure associated with reduced forced expiratory volume in one second.

We compared the structure of the membranous and respiratory bronchioles of resected lungs from 111 patients with a normal predicted forced expiratory volume in one second (FEV1) to the structure of these airways from 45 patients with an FEV1 reduced below the 95% confidence limits for height and age. Membranous and respiratory bronchioles of less than 2 mm in internal diameter were counted and their diameter and wall thickness were measured. The data show that there were more membranous bronchioles of internal diameter less than 0.4 mm in patients with reduced FEV1. The wall thickness of respiratory bronchioles was increased in the obstructed group and there was also an increase in the ratio of wall thickness to lumen diameter in these airways. The walls of membranous bronchioles were not increased in thickness but there was an increase in the ratio of wall thickness to lumen diameter. Although the data is consistent with the hypothesis that airways obstruction in patients with chronic obstructive pulmonary disease is due to thickening of the airway wall and narrowing of the airway lumen, we cannot rule out distortion of the membranous bronchioles by loss of elastic recoil.

Aging↗
PubMed1988

Comparison of inflammatory cells in bronchoalveolar fluid with those in the lumen and tissue peripheral airways and alveolar airspace.

This study compares the inflammatory cell types in the alveolar airspace, peripheral airways, and bronchoalveolar lavage fluid of 65 human lung specimens removed surgically. The data show that the cellular population in the airway tissue is composed of approximately 2-4% neutrophils, and 96-98% mononuclear inflammatory cells. This contrasts with the airway lumen, which contains approximately 5-14% neutrophils, while the alveolar airspace contains 3%, and the lavage fluid contains 4% neutrophils. There is a significant correlation between the percentage of PMN in the walls of the membranous and respiratory bronchioles, as well as between the walls and lumens of respiratory and membranous bronchioles. We conclude that: 1. The lumen of the membranous bronchioles contains a greater percentage of PMN than the lumen of the respiratory bronchiole or of the alveoli. 2. Neutrophils are present in the alveolar airspace. 3. The percentages of PMN present in the lumen of the respiratory bronchiole, alveoli, and lavage fluid are similar. 4. The correlation between percentage of PMN in airway wall and lumen suggests a cellular equilibrium between the 2 sites. 5. In this groups of lungs, there is an apparent stereotypic inflammatory response in that the percentages of PMN in the different anatomical sites are relatively similar from case to case. Various workers have suggested that analysis of the cell types present in bronchopulmonary lavage can be used as a therapeutic index, or as a diagnostic test. Our data suggest that lavage does indeed sample the lower airways and alveolar spaces, and that such usage may well be justified.

Animals↗
PubMed1988

Pulmonary vascular structure and function in chronic obstructive pulmonary disease.

Cardiac catheterization data from eight patients with severe chronic obstructive lung disease and pulmonary hypertension at rest (greater than 25 mm Hg) were compared with those obtained from 14 patients with mild to moderate disease whose pulmonary artery pressure was within the normal range at rest (mean 15 (SEM 1) mm Hg), but increased with exercise (30 (2) mm Hg). We obtained lung sections from necropsy material from the group with severe disease, and from surgical specimens in the group with mild to moderate disease, and compared the structure of the vasculature in these groups with that obtained from surgical specimens in a non-smoking control group of seven patients. Oxygen administration either at rest or during exercise did not greatly affect the pulmonary arterial pressures. When cardiac index was plotted against pulmonary artery pressure at rest and during exercise and extrapolated to the axis there was no evidence for a critical closing pressure in either group. The vessels in the groups with mild to moderate and severe chronic obstructive lung disease showed intimal thickening (each 19% (SD 0.5%)) by comparison with the non-smoking group (16% (0.5%]. The group with severe disease, in addition, had medial hypertrophy (27% (0.5%) versus 24% (SD 1%) in the non-smoking group). These data are consistent with the idea that the diseased vessels are distorted and rigid. The lack of effect of breathing oxygen on the vascular response at rest and during exercise suggests that hypoxic vasoconstriction has a minimal role in the pulmonary hypertension of chronic obstructive lung disease. The data suggest that the intimal changes could narrow the vessel calibre in those patients with mild to moderate disease, and that the thickened media present in the vessels from patients with severe disease may act in concert with the enlarged intima to produce more severe vascular obstruction.

Blood Pressure↗
PubMed1988

Assessment of tight junctions between pulmonary epithelial and endothelial cells.

This study is intended to determine whether qualitative assessment of tight junction integrity from freeze-fracture data is reliable. We used lung parenchyma from a control mongrel dog's cardiac lung lobe, from a mongrel dog subjected to vascular high-pressure pulmonary edema (HPPE), and from a dog subjected to oleic acid-induced low-pressure pulmonary edema (LPPE) (6). Quantitative assessment was done on 115 freeze-fracture micrographs of epithelial tight junctions and on another 158 freeze-fracture micrographs of endothelial junctions from the 3 dogs. Quantitative assessment showed differences between the dogs in junction depth, fibril numbers, density, and complexity. for qualitative assessment, these same 273 micrographs were assessed in a single-blind fashion by having six investigators sort first the epithelial and then the endothelial junctions into normal or damaged categories. Qualitative assessment did not agree with quantitative data, suggesting that it is unreliable.

Animals↗
PubMed1987

Structure of central airways in current smokers and ex-smokers with and without mucus hypersecretion: relationship to lung function.

Forty-five patients who underwent thoracotomy and lung resection for tumour were studied to compare the structure of the central airways in current smokers and ex-smokers. The patients were divided into four groups: current smokers with mucus hypersecretion (n = 15), current smokers without mucus hypersecretion (n = 14), ex-smokers with mucus hypersecretion (n = 5), and ex-smokers without mucus hypersecretion (n = 11). Quantitative histological studies of the airway wall showed no difference in gland size, smooth muscle, connective tissue, or Reid index between the groups. The central airways of patients with mucus hypersecretion showed increased mucosal inflammation. The five ex-smokers in whom mucus hypersecretion persisted after they had stopped smoking had both central and peripheral airways affected by the inflammatory response, and these patients also had an abnormal result in the nitrogen washout test.

Humans↗
PubMed1987

Effect of cold and warm dry air hyperventilation on canine airway blood flow.

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.

Animals↗
PubMed1987

Regional differences in neutrophil margination in dog lungs.

We investigated the relationship between polymorphonuclear leukocyte (PMN) retention and erythrocyte (RBC) velocity in the lungs of mongrel dogs. Regional velocity was estimated by measuring regional RBC transit times and was correlated with the retention of PMN found in the same lung sample 10 min after the injection of a bolus of labeled cells. Data from the whole lung showed that the total number of cells marginated in the pulmonary vasculature was 2.4 times as great as the number present in the circulation and that this pool turned over at a rate of 1%/s. The regional data showed increased retention, indicating slower PMN turnover in the upper lung regions, which have longer transit times and therefore slower blood velocities than the RBC is attributed to a greater discrepancy between PMN and RBC is attributed to a greater discrepancy between PMN and capillary size and the fact that PMN are less deformable than RBC. The large number of capillary segments present in the lung allows neutrophils to move more slowly while RBC stream around them. We conclude that there are approximately 2.5 times as many PMNs marginated in the lung as there are in the total circulating blood volume of the dog and that the pulmonary marginated pool turns over at approximately 1%/s with slower turnover in the upper compared with the lower regions of the lung.

Animals↗
PubMed1986

Comparison of the cell content of lung lavage fluid with the presence of emphysema and peripheral airways inflammation in resected lungs.

This study was designed to investigate the relationship between the cellular components of lung lavage fluid and the presence of airways disease and emphysema in resected lung specimens, primarily from current and ex-smokers. Since standard bronchopulmonary lavage cannot be performed on these specimens, an intrapulmonary lavage technique was developed and compared to the results of bronchoalveolar lavage performed prior to surgery on the lung or lobe opposite to the one resected. The specimen lavage produced inflammatory cell differential counts similar to those obtained by bronchopulmonary lavage, and studies on postmortem lungs showed that the fluid washed alveoli, respiratory and membranous bronchioles, and small cartilaginous bronchi. The results show that the variation in peripheral airways inflammation and extent of lung destruction by emphysema did not correlate with the variation in cell content observed in the lavage fluid. Similarly, the differential counts performed in the lavage fluid did not correlate with the smoking habits of the patient. We conclude that the changes in cell content of the lavage fluid do not reflect the extent or severity of the inflammatory disease and lung destruction present in the lungs of this group of patients.

Body Fluids↗
PubMed1986

Nonspecific airway reactivity in cigarette smokers. Relationship to airway pathology and baseline lung function.

To examine the relationship of cigarette smoking, starting airway caliber, and airway pathology to nonspecific airway reactivity, we performed inhalation dose-response curves in 40 patients prior to lung surgery. Airway reactivity was assessed by the provocative concentration of methacholine (n = 30) or histamine (n = 10) resulting in a 20% fall in FEV1 (PC20). All patients had measurements of maximal expiratory flow, diffusing capacity, and lung volumes preoperatively. After resection, the specimens were graded for small and large airways pathology and emphysema. The patients were divided into 4 groups: PC20 less than or equal to 1 mg/ml (n = 6), PC20 1 mg/ml to less than or equal to 4 mg/ml (n = 11), PC20 4 mg/ml to less than or equal to 16 mg/ml (n = 14), and PC20 greater than 16 mg/ml (n = 9). Subjects with PC20 less than or equal to 1 mg/ml had reduced measurements of maximal expiratory flow (FEV1, FEV1/FVC, Vmax50, and Vmax25). There were no differences in measurements of cartilaginous airway disease among the 4 reactivity groups. We found significant independent correlations of cigarette consumption, membranous bronchiole inflammation, and maximal expiratory flow rates (FEV1 and Vmax50) to PC20. The data suggest that cigarette smoking, starting airway caliber, and airway inflammation are associated with nonspecific airway reactivity and that each exerts an effect on airway reactivity that is not dependent on the contribution of the other 2 factors.

Aged↗
PubMed1985

Reassessment of inflammation of airways in chronic bronchitis.

The term chronic bronchitis has been criticised because it is associated with hypersecretion of mucus rather than bronchial inflammation. This study was designed to establish the presence or absence of clinical chronic bronchitis and measure pulmonary function in 45 patients about to undergo resection of the lung. The condition in the cartilaginous and small airways and the severity of the emphysema were then measured in the resected specimen. The results from 20 patients who had clinical chronic bronchitis were compared with those in 25 patients who did not. The data show that patients with chronic bronchitis had greater inflammation (a) on mucosal surfaces (p less than 0.05) of all bronchi larger than 2 mm luminal diameter and (b) around glands (p less than 0.005) and gland ducts (p less than 0.05) in bronchi larger than 4 mm diameter. A variable degree of inflammation was present in the submucosa of smaller bronchi. The groups had equivalent proportions of mucous glands and Reid's indices in central airways, and no differences were noted in measurements of pulmonary function, condition of small airways, or emphysema. These data show that the term chronic bronchitis is justified by inflammation of cartilaginous airways and suggest that this abnormality may be the cause of the chronic productive cough.

Bronchi↗
PubMed1985

Role of tracheal and bronchial circulation in respiratory heat exchange.

Due to their anatomic configuration, the vessels supplying the central airways may be ideally suited for regulation of respiratory heat loss. We have measured blood flow to the trachea, bronchi, and lung parenchyma in 10 anesthetized supine open-chest dogs. They were hyperventilated (frequency, 40; tidal volume 30-35 ml/kg) for 30 min or 1) warm humidified air, 2) cold (-20 degrees C dry air, and 3) warm humidified air. End-tidal CO2 was kept constant by adding CO2 to the inspired ventilator line. Five minutes before the end of each period of hyperventilation, measurements of vascular pressures (pulmonary arterial, left atrial, and systemic), cardiac output (CO), arterial blood gases, and inspired, expired, and tracheal gas temperatures were made. Then, using a modification of the reference flow technique, 113Sn-, 153Gd-, and 103Ru-labeled microspheres were injected into the left atrium to make separate measurements of airway blood flow at each intervention. After the last measurements had been made, the dogs were killed and the lungs, including the trachea, were excised. Blood flow to the trachea, bronchi, and lung parenchyma was calculated. Results showed that there was no change in parenchymal blood flow, but there was an increase in tracheal and bronchial blood flow in all dogs (P less than 0.01) from 4.48 +/- 0.69 ml/min (0.22 +/- 0.01% CO) during warm air hyperventilation to 7.06 +/- 0.97 ml/min (0.37 +/- 0.05% CO) during cold air hyperventilation.

Animals↗
PubMed1984

The structure of tight junctions in the tracheal epithelium may not correlate with permeability.

To test the hypothesis that cigarette smoke produces changes in the morphology of tight junctions guinea pigs were exposed to cigarette smoke or air in a previously standardized fashion (Simani et al. 1974). Permeability is greatest one half hour following exposure to cigarette smoke (Hulbert et al. 1981). The animals were sacrificed at that time. The tracheal epithelium was studied using both thin-section and freeze-fracture techniques. A quantitative analysis of the organization and integrity of junctional complexes was performed for each animal. Organization was assessed by measuring and comparing areas delimited by PF fibers and EF furrows. PF fiber integrity was assessed by measuring uninterrupted lengths of fibers and furrows from freeze-fracture replicas. This assessment did not demonstrate a change in tight-junction morphology following exposure to cigarette smoke.

Animals↗
PubMed1984

Effect of pulmonary blood flow on leukocyte uptake and release by dog lung.

The effect of pulmonary blood flow on leukocyte uptake and release by the lung was examined in 10 anesthetized spontaneously breathing dogs. Pulmonary arterial and pulmonary venous blood was sampled with catheters placed into the right ventricle and aorta, respectively. Pulmonary blood flow was lowered by inflating a balloon catheter located in the inferior vena cava. In five experiments simultaneous blood samples were drawn from the right ventricle and aorta at 10-s intervals during a control period, a 2- to 3-min period of low flow, and a recovery period. In five additional experiments, less frequent samples were taken over periods of 15-60 min. Total leukocyte concentrations and differential counts were determined for each blood sample. The study shows that large numbers of leukocytes become sequestered within the lung when pulmonary blood flow is low and that an equivalent number of cells are released from the lung after deflation of the balloon catheter. Both the polymorphonuclear leukocytes and the lymphocytes were taken up by the lung when pulmonary blood flow was reduced. We conclude that pulmonary blood flow has a marked effect on the uptake and release of leukocytes by the dog lung.

Animals↗