The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

We have examined the effect of airway wall thickening, loss of lung recoil, and airway smooth muscle shortening on the increase in airway resistance using a model of the human tracheobronchial tree. The values for airway wall thickening were determined morphometrically on the postmortem or surgically resected lungs of normal subjects, patients with moderate chronic obstructive pulmonary disease, and patients with severe asthma. Loss of recoil was simulated by deflating airways along their pressure-area curves by 1 to 3 cm H2O. Values of smooth muscle shortening between 20 and 40% were used in the model to generate sigmoidal-shaped "dose-response" curves. The analysis shows that moderate amounts of airway wall thickening, which have little effect on baseline resistance, can profoundly affect the airway narrowing caused by smooth muscle shortening--especially if the wall thickening is localized in peripheral airways. The combination of a loss of recoil and airway wall thickening are more than additive in their effect on simulated airway responsiveness. We conclude that airway wall thickening and a loss of lung recoil can partially explain the airway hyperresponsiveness observed in patients with chronic obstructive lung disease and asthma.

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)

Lung tissue from 20 patients undergoing resection for a peripheral carcinoma was studied using monoclonal antibodies to identify inflammatory cell types in the peripheral airways and to determine the location of the bronchial-associated lymphoid tissue (BALT). The patients were grouped according to their percent predicted FEV1 (%FEV1) into obstructed (%FEV1 less than 80%) and control (%FEV1 greater than 80%). The resected lungs were filled with dilute cryoembedding media (Tissue-Tek R), frozen over liquid nitrogen, sliced into 2-cm sagittal slices using a band saw, and sampled using a cork bore. Ten serial histologic sections cut from these samples were stained with monoclonal antibodies for specific inflammatory cell types, which were counted and expressed per square millimeter of airway wall area. The results showed that the patients with airway obstruction had more B-lymphocytes in the airway adventitia than did the control subjects (p less than 0.001) and that the number of submucosal polymorphonuclear leukocytes is related to the amount smoked (p less than 0.02). They also show the BALT has a different distribution in human than in rodent lungs in that the lymphoid collections are found in the outer walls of the airway rather than in the submucosa.