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Biomedical subjects

H O Coxson

Publications and source records attributed to H O Coxson.

At least 19 recordsLinked to original sources
PubMed2006

Bronchiolitis obliterans following lung transplantation: early detection using computed tomographic scanning.

BACKGROUND: Computed tomographic (CT) scanning may enable earlier diagnosis of chronic lung allograft dysfunction than forced expiratory volume in 1 second (FEV1). A study was undertaken to determine intra-observer and inter-observer agreement of composite and air trapping CT scores, to examine the association of FEV1 with the composite and air trapping CT score, and to relate the baseline composite CT score to changes in FEV1 and changes in the composite CT score over 1 year. METHODS: Lung function and baseline CT scans following transplantation and at subsequent annual follow ups were analysed in 38 lung transplant recipients. Scans were randomly scored by two observers for bronchiectasis, mucus plugging, airway wall thickening, consolidation, mosaic pattern, and air trapping, and re-scored after 1 month. CT scores were expressed on a scale of 0-100 and correlated with FEV1 as a percentage of the post-transplant baseline value. RESULTS: The mean (SD) interval between baseline and follow up CT scans was 11.2 (4.7) months. Inter-observer and intra-observer agreement was good for both the composite and air trapping CT scores. There was a significant association between FEV1 and the composite CT score, with each unit of worsening in the baseline composite CT score predicting a 1.55% and 1.37% worsening in FEV1 over the following year (p<0.0001) and a 1.25 and 1.12 unit worsening in the composite CT score (p<0.0001) for observers 1 and 2, respectively. CONCLUSION: These findings indicate a potential role for a composite CT scoring system in the early detection of bronchiolitis obliterans.

Adolescent↗
PubMed2006

Computed tomographic estimation of lung dimensions throughout the growth period.

The aim of the current study was to use computed tomography (CT) to estimate airway wall and lumen, and arterial and parenchyma dimensions in children throughout the growth period, and to provide normative data to study alterations caused by pulmonary disease. Clinical CT scans reported as normal that were performed in children for nonpulmonary and noncardiac reasons were analysed for lung weight, gas volume, lung expansion, lung surface/volume ratio, airway wall area, airway lumen area, airway lumen perimeter, arterial area and airway surface length/area ratio. The age range of the 50 subjects was 0-17.2 yrs. The data showed only little increase in lung expansion throughout childhood (n = 32). There was substantial variability in lung expansion between subjects. Airway wall and lumen and arterial area were exponentially associated with subjects' height (n = 50). Airway surface length/area ratio was linearly associated to alveolar surface/volume ratio. The data from the current study provide normative computed tomography estimates of airway wall and lumen, and arterial and parenchyma dimensions throughout the growth period that may be useful for the study of alterations in disease.

Adolescent↗
PubMed2005

Computed tomographic imaging of the airways: relationship to structure and function.

Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.

Airway Obstruction↗
PubMed2003

Selection of patients for lung volume reduction surgery using a power law analysis of the computed tomographic scan.

BACKGROUND: A study was undertaken to test the hypothesis that patients respond better to lung volume reduction surgery (LVRS) if their emphysema is confluent and predominantly located in the upper lobes. METHODS: A density mask analysis was used to identify voxels inflated beyond 10.2 ml gas/g tissue (-910 HU) on preoperative and postoperative CT scans from patients receiving LVRS. These hyperinflated regions were considered to represent emphysematous lesions. A power law analysis was used to determine the relationship between the number (K) and size (A) of the emphysematous lesions in the whole lung and two anatomical regions using the power law equation Y=KA(-D). RESULTS: The analysis showed a positive correlation between the change in the power law exponent (D) and the change in exercise (Watts) after surgery (r=0.47, p=0.03). There was also a negative correlation between the power law exponent D in the upper region of the lung preoperatively and the change in exercise following surgery (r=-0.60, p<0.05). CONCLUSIONS: These results confirm that patients with large upper lobe lesions respond better to LVRS than patients with small uniformly distributed disease. Power law analysis of lung CT scans provides a quantitative method for determining the extent and location of emphysema within the lungs of patients with COPD.

Exercise Tolerance↗
PubMed2003

Estimation of lung growth using computed tomography.

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days-17.6 yrs. CT-measured lung weight was correlated with predicted post mortem values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL x g(-1) at 15 days, decreased to 0.79 mL x g(-1) by 2 yrs and then increased steadily to 5.07 mL x g(-1) at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.

Adolescent↗
PubMed2001

Core to rind distribution of severe emphysema predicts outcome of lung volume reduction surgery.

Computed tomography (CT) has shown that emphysema is more extensive in the inner (core) region than in the outer (rind) region of the lung. It has been suggested that the concentration of emphysematous lesions in the outer rind leads to a better outcome following lung volume reduction surgery (LVRS) because these regions tend to be more surgically accessible. The present study used a recently described, computer-based CT scan analysis to quantify severe emphysema (lung inflation > 10.2 ml gas/g tissue), mild/moderate emphysema (lung inflation = 10.2 to 6.0 ml gas/g tissue), and normal lung tissue (lung inflation < 6.0 ml gas/g tissue) present in the core and rind of the lung in 21 LVRS patients. The results show that the quantification of severe emphysema independently predicts change in maximal exercise response and FEV(1). We conclude that a greater extent of severe emphysema in the rind of the upper lung predicts greater benefit from LVRS because it identifies the lesions most accessible to removal by LVRS.

Female↗
PubMed2001

Amplification of inflammation in emphysema and its association with latent adenoviral infection.

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Adenoviridae Infections↗
PubMed2001

Pulmonary embolism: comparison of gadolinium-enhanced MR angiography with contrast-enhanced spiral CT in a porcine model.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare gadolinium-enhanced magnetic resonance (MR) angiography with contrast material-enhanced computed tomography (CT) for the detection of small (4-5-mm) pulmonary emboli (PE), with a methacrylate cast of the porcine pulmonary vasculature used as the diagnostic standard. MATERIALS AND METHODS: In 15 anesthetized juvenile pigs, colored methacrylate beads (5.2 and 3.8 mm diameter-the size of segmental and subsegmental emboli in humans) were injected via the left external jugular vein. After embolization, MR angiographic and CT images were obtained. The pigs were killed, and the pulmonary arterial tree was cast in clear methacrylate, allowing direct visualization of emboli. Three readers reviewed CT and MR angiographic images independently and in random order. RESULTS: Forty-nine separate embolic sites were included in the statistical analysis. The mean sensitivity (and 95% confidence intervals) for CT and MR angiography, respectively, were 76% (68%-82%) and 82% (75%-88%) (P > .05); the mean positive predictive values, 92% (85%-96%) and 94% (88%-97%) (P > .05). In this porcine model, PE were usually seen as parenchymal perfusion defects (98%) with MR angiography and as occlusive emboli (100%) with CT. CONCLUSION: MR angiography is as sensitive as CT for the detection of small PE in a porcine model.

Animals↗
PubMed2000

Preoperative severity of emphysema predictive of improvement after lung volume reduction surgery: use of CT morphometry.

STUDY OBJECTIVE: To determine how the volume and severity of emphysema measured by CT morphometry (CTM) before and after lung volume reduction surgery (LVRS) relates to the functional status of patients after LVRS. DESIGN: A histologically validated CT algorithm was used to quantify the volume and severity of emphysema in 35 patients before and after LVRS: total lung volume (TLV), normal lung volume (< 6.0 mL gas per gram of tissue), volume of mild/moderate emphysema (ME; 6.0 to 10.2 mL gas per gram of tissue), volume of severe emphysema (> 10.2 mL gas per gram of tissue), surface area/volume (SA/V; meters squared per milliliter), and surface area (SA; meters squared). Outcome parameters included maximal cardiopulmonary exercise (CPX) performance in 21 patients and routine pulmonary function in all patients. We hypothesized that baseline CTM parameters predict response to LVRS and that the change in these parameters may offer insight into mechanisms of improvement. PATIENTS AND INTERVENTION: Thirty-five patients with severe emphysema who had successful LVRS. RESULTS: The significant decrease in TLV following LVRS was entirely accounted for by a decrease in severe emphysema. The SA/V and the SA both increased significantly following LVRS. The change in maximal CPX in watts following surgery correlated significantly with baseline values of severe emphysema (r = 0.60), which was collinear with TLV, and SA/V. The change in diffusing capacity of the lung for carbon monoxide revealed a significant positive linear relationship with preoperative severe emphysema (r = 0.37) and a negative relationship with ME (r = -0.37). Change in watts revealed a strong relationship with changes in severe emphysema (r = -0.75) and weaker but significant relationships with change in TLV, ME, SA/V, and SA. Other measures of pulmonary function revealed significant albeit less dominant relationships with baseline CTM and change in these indexes. CONCLUSION: Using CTM, we have identified a close relationship between baseline severe emphysema, or change in severe emphysema, and the improvement in CPX after LVRS. These observations support a potential role of CTM in future clinical trials for predicting responders to LVRS and identifying mechanisms of improvement.

Algorithms↗
PubMed1999

A quantification of the lung surface area in emphysema using computed tomography.

Quantitative analysis of computed tomography (CT) has been combined with a stereologically based histologic analysis of lung structure to assess regional lung inflation and the structural features of the lung parenchyma. In this study, CT measurements of lung inflation were compared with histologic estimates of surface area in order to develop prediction equations that allow lung surface to volume ratio and surface area to be predicted from an analysis of the CT scan. The results show that mild emphysema is associated with an increase in lung volume and a reduction in surface to volume ratio, whereas surface area and tissue weight were only decreased in severe disease. The CT predicted surface to volume ratio correlated with histology, and both predicted and measured surface areas correlated with the diffusing capacity. We conclude that this CT analysis can be used to monitor the progression of emphysematous lung destruction in individual patients, and to assess the impact of both surgical and medical treatments for emphysema.

Aged↗
PubMed1997

Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.

We used computed tomography (CT) and histologic analysis to quantify lung structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF and control patients and lung volumes were estimated from measurements of voxel size, and X-ray attenuation values of each voxel. Quantitative estimates of lung structure were obtained from biopsies obtained from diseased and normal CT regions using stereologic methods. CT density was used to calculate the proportion of tissue and air, and this value was used to correct the biopsy specimens to the level of inflation during the CT scan. The data show that IPF is associated with a reduction in airspace volume with no change in tissue volume or weight compared with control lungs. Lung surface area decreased two-thirds (p < 0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate of fluid and cells was present in the airspace of the diseased lung regions and the number of inflammatory cells, collagen, and proteoglycans was increased per 100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content causing a loss of airspace and surface area without increasing the total lung tissue.

Aged↗
PubMed1996

Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease.

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment.

Adult↗
PubMed1995

Measurement of lung expansion with computed tomography and comparison with quantitative histology.

The total and regional lung volumes were estimated from computed tomography (CT), and the pleural pressure gradient was determined by using the milliliters of gas per gram of tissue estimated from the X-ray attenuation values and the pressure-volume curve of the lung. The data show that CT accurately estimated the volume of the resected lobe but overestimated its weight by 24 +/- 19%. The volume of gas per gram of tissue was less in the gravity-dependent regions due to a pleural pressure gradient of 0.24 +/- 0.08 cmH2O/cm of descent in the thorax. The proportion of tissue to air obtained with CT was similar to that obtained by quantitative histology. We conclude that the CT scan can be used to estimate total and regional lung volumes and that measurements of the proportions of tissue and air within the thorax by CT can be used in conjunction with quantitative histology to evaluate lung structure.

Biopsy↗
PubMed1994

Lung structure and function in cigarette smokers.

BACKGROUND: Cigarette smoking produces an inflammatory response in the airways of everyone but only 15-20% of smokers develop airways obstruction. The present study concerns the relative importance of peripheral airways inflammation and the emphysematous destruction of the parenchymal support of the airways in the pathogenesis of this obstruction. METHODS: A total of 407 patients with a diagnosis of lung tumour performed pulmonary function tests a day or two before a lung or lobar resection. The specimens were fixed in inflation and analysed at the gross and microscopic level to determine the extent and severity of the emphysematous process, the number of alveoli supporting the outer walls of the airways, and the average distance between alveolar walls. The severity of the inflammatory process in the respiratory and nonrespiratory bronchioles was also assessed using a previously established grading system. RESULTS: The lung function test showed that a decline in FEV1 was associated with an increase in residual volume and a decrease in the diffusing capacity for carbon monoxide and a reduction in the lung maximum elastic recoil pressure. The prevalence of grossly visible emphysema increased as FEV1 declined, but the extent and severity of these lesions and the number of alveoli supporting the outer walls of the peripheral airways was similar at all levels of FEV1. The system used to grade inflammatory response in the peripheral airways failed to identify a specific defect responsible for the physiological abnormalities. CONCLUSION: The reduction in FEV1 associated with chronic cigarette smoking can be partially explained by loss of lung elastic recoil pressure which reduces the force driving air out of the lung. This loss of elastic recoil pressure is attributed to microscopic enlargement of the air spaces rather than to grossly visible emphysema. The exact nature of the lesions responsible for the peripheral airways obstruction remains to be identified.

Aged↗
PubMed1994

Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries.

Pulmonary capillary transit times were examined in patients who required lung resection by use of 99mTc-labeled macroaggregates (99Tc-MAA) and chromium-labeled erythrocytes (51Cr-RBC) to measure regional blood flow and volume in the resected lung. Cell flow (cells.ml-1.s-1) to each resected lung sample was determined by multiplying the number of polymorphonuclear leukocytes (PMN) per milliliter of circulating blood by the blood flow to that sample. Capillary blood volume was obtained by multiplying the morphometrically determined fraction of pulmonary blood in capillaries by the total 51Cr-RBC volume in each sample. Cell concentrations (cells/ml) in capillary blood were calculated morphometrically, and capillary transit times were obtained by dividing cell concentration by cell flow. The results show that PMN transit times were 60-100 times longer than the RBC transit times, with a 22% overlap between their distributions. We conclude that PMN are concentrated with respect to RBC in pulmonary capillary blood because of differences in their transit times and that these long transit times provide an opportunity for PMN-endothelial interactions.

Blood Flow Velocity↗
PubMed1994

Quantitation of neutrophil migration in acute bacterial pneumonia in rabbits.

The circulating neutrophils must slow down, adhere to the vessel walls, and migrate out of the microvasculature into the tissue and air spaces to defend the lung against microorganisms. The present study was designed to provide quantitative information about each of these steps. Streptococcus pneumoniae was instilled into the left lower lobe of New Zealand White rabbits to induce a pneumonia, and this lobe was compared with the same region of the opposite lung. The distribution of blood flow was determined by using radiolabeled macroaggregated albumin, and the patterns of perfusion within the capillary bed were quantitated using Monastral blue. The number of neutrophils delivered to the pneumonic site was determined by multiplying the circulating neutrophil count and blood flow. The results show that retention of 51Cr-labeled neutrophils was increased in the pneumonic region 2, 4, and 8 h after instillation of the organisms. The number of intracapillary neutrophils was increased in the pneumonic regions at all time points and in the control regions at 1 and 4 h. Neutrophil migration occurred in the pneumonic site, but only 1-2% of the total neutrophils delivered to the region migrated out of the pulmonary vessels into the air space. We conclude that the circulating neutrophils undergo a generalized response that increases their margination throughout the lung, that increased margination in the pneumonic site changes the distribution of capillary flow, and that the majority of neutrophils delivered to a pneumonic site are returned to the circulation without migrating into the air space.

Acute Disease↗
PubMed1993

Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung.

Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation.

Animals↗