Mucous Gland Hyperplasia Research Articles

Goblet cells in the peripheral airways in chronic bronchitis.

It was not possible to demonstrate an increase in the proportion of goblet cells in the bronchioles of patients with chronic bronchitis and no emphysema, whereas other lesions, such as mucous gland hyperplasia, airway narrowing, and airway mucus were easily demonstrated in similar cases. Thus, it seems that goblet cell metaplasia is not an important factor in patients who have chronic bronchitis but little evidence of chronic airflow obstruction. Goblet cell metaplasia is an obvious feature of patients with chronic bronchitis and emphysema, especially in those with symptomatic or fatal chronic airflow obstruction, and it may be responsible for producing obstruction in the peripheral airways of these subjects. The role of goblet cell metaplasia in smokers with little airflow obstruction is uncertain from the data presented. No difference was noted in the proportion of goblet cells between bronchitic patients and nonbronchitic smokers who did not have clinical airflow obstruction.

The Distinction Between Lung Maturation and Limited Injury in Human Airways: Functional and Morphometric Studies in Postmortem Examination of Lungs

M orphologic alterations occur in the maturing and aging lung. These morphologic alterations are reflected in functional changes which, in the case of the aging lung, are qualitatively similar to those observed in advanced chronic obstructive pulmonary disease (COPD). Any study which attempts to evaluate the morphologic and functional changes of COPD must differentiate that part contributed by disease from that contributed by normal maturation and aging. In this report we attempt to characterize some of the functional and morphologic alterations in the airways of human nondiseased lungs over a wide age range as a basis for understanding additional changes which may be produced by disease, particularly those in early COPD. Studies of mechanics and morphometry were performed in postmortem examination of human lungs. Left lungs are obtained from male victims of sudden nonhospital death on whom autopsies were performed in the coroner’s office. Usual causes of death include traffic accidents, myocardial infarction and exsanguinating gunshot wounds. Stringent criteria are used in selecting the lungs. Lungs heavier than 450 gm are not accepted because they usually have microscopic evidence of edema. Similarly, lungs with hemorrhage, large pleural rents or excessive bronchial secretions are not used. Mechanics are studied immediately after obtaining the lung, and in all cases are completed within 24 hours of the person’s death. The lung is suspended by a bronchial cannula in a glass plethysmograph. Measurements of lung mechanics include static elastic recoil pressures, total pulmonary resistance by the method of Mead and Whittenberger,’ dynamic compliance and flow volume plots from passive and forced deflations. Barium sulfate is then insufflated into the bronchial tree and the mean diameter of all segmental bronchi is determined from the bronchogram. This value is considered a relative measure of the size of the central airways. The lung is inflated and fixed in formalin at 25-cm water pressure. Lung slices are carefully examined, and the amount of emphysema, if present, is determined by point count. Random histologic sections are obtained from which the number and mean diameter of all membranous bronchioles of less than 2 mm in diameter are determined. Mucous plugging in the peripheral airways is evaluated by quantitatively determining the proportion of bronchiolar lumen occupied by mucus on histologic section. Approximately 50 bronchioles are evaluated in each lung. The proportion of bronchial mucous gland is quantitatively determined from sections of lobar bronchi. The results reported are from the first 26 lungs studied. The age of the donors ranges from 10-82 years. Mild emphysema, less than 10 percent by gross point count, is present in five lungs. The population studied can be considered a reasonable cross section of an urban population, consisting of persons with normal and mildly diseased lungs. The relationship between the flow resistive properties of the lungs and measurements of airway caliber at different levels of the bronchial tree can be summarized as follows: A statistically significant (p <0.05) but weak correlation (R 0.39) is found between mean segment diameter and the reciprocal of pulmonary resistance, conductance. In contrast, a very close correlation (R 0.90) is found between mean bronchiole diameter and pulmonary conductance. This suggests that mean bronchiole diameter is the main determinant of variations in pulmonary conductance in normal and mildly diseased human lungs. The determination of pulmonary conductance, or resistance, is more sensitive than either maximal expiratory flow rates or dynamic compliance in detecting bronchiolar narrowing. Bronchial mucous gland hyperplasia is one of the pathologic abnormalities described in chronic bronchitis. When mucous glands occupy 15 percent or more of the bronchial wall, they are considered hyperplastic. The percentage of mucous glands in the bronchial wall exceeded this value in 6 of the 26 lungs studied (range 16.1 to 24.1 percent). Functional parameters are not significantly different in this group as compared to the other lungs studied. Emphysema or bronchiolar narrowing is not present in these six lungs, and the amount of mucus in the lumens of the peripheral airways is not increased. No age-related changes are seen in the percentage of bronchial mucous glands in this study. The bronchial mucous gland hyperplasia is not related to any functional abnormalities in this study and is not associated with other pathologic changes commonly found with COPD. The size of the central airways, as reflected by the mean segmental bronchial diameter does not change significantly beyond the age of 20 years (Fig 1). In contrast, highly significant age-related changes occur in the mean diameter of the membranous bronchioles (Fig 2). Maximal bronchiole diameter is not reached until well into the third decade of life, with a variable decrease thereafter. Matsuba and Thurlbeck,2 using nearly iden-

Bronchial cartilage in chronic obstructive lung disease.

We have assessed the amount of cartilage in bronchi in 19 patients with various degrees of anatomical emphysema, mucous gland hyperplasia, and clinical chronic bronchitis. Diminished cartilage was best related to emphysema and was most marked in the lower lobes and in segmental and first and second order subsegmental bronchi. Available evidence suggests that this cartilage loss is an associated finding in emphysema rather than the factor that produces expiratory flow limitation encountered in patients with emphysema.

Parenchymal, bronchiolar, and bronchial measurements in centrilobular emphysema. Relation to weight of right ventricle.

Measurements of lung parenchyma, membranous bronchioles, and bronchial mucous gland hyperplasia were made on lungs from eight cases of pure centrilobular emphysema (CLE) and on five normal lungs. The lungs were fixed in formalin and inflated under partial vacuum at a standard transpulmonary pressure of +30 cm. H₂O. The results obtained from the upper halves and the lower halves of the lungs were compared. The circulatory effects of the disease were measured by weighing the heart ventricles, by studying the small pulmonary arteries in microscopical sections, and by post-mortem arteriography. Whereas the parenchymal and internal surface areas destroyed by the emphysematous spaces were relatively moderate and localized, right ventricular hypertrophy was noted in most of the cases. In these cases bronchiolar stenoses were found scattered throughout the whole lung and there was a reduction in the number of these bronchioles, mainly in the upper halves of the lungs. In CLE ventilatory disturbances were caused not only by the centriacinar dilated spaces delaying gas diffusion, but also by scattered bronchiolar stenoses situated at the termination of the conducting air passages. The stenoses seemed the more important cause. It was shown statistically that chronic arterial pulmonary hypertension and right ventricular hypertrophy were mainly the result of functional disturbances, especially hypoxia and abnormalities of VA/Q produced by the two structural changes situated at the end of the small airways.

Chronic obstructive bronchopulmonary disease: II. Oxygen transport in two clinical types

Two contrasting types of patients with chronic airway obstruction were distinguished by purely clinical criteria: the emphysematous type (herein referred to as PP patients) and the bronchial type (BB patients). In the autopsy cases there was somewhat more extensive emphysematous destruction of the lungs and much less evidence of active bronchial mucous gland hyperplasia in the former type than in the latter. These two types of patients were studied physiologically and were found to have equivalent degrees of ventilatory impairment. However, PP patients had larger lungs, more uniform distribution of inert gas (helium) and hyperventilated both at rest and during exercise. BB patients had higher carbon dioxide tensions and much lower arterial oxygen saturations than did PP patients. The severe hypoxemia in BB patients was not caused by alveolar hypoventilation per se nor could it be satisfactorily explained by calculations of gas and blood flow distribution in the lungs. The most consistent measured difference relevant to pulmonary oxygen transport in the two types was in pulmonary blood flow: PP patients had subnormal and BB patients normal cardiac outputs both at rest and during exercise. The higher ratio of total ventilation to total blood flow in PP patients probably accounted for the nearly normal arterial oxygenation. The hypoxemia in BB patients is considered to be a form of diffusion impairment resulting from too rapid flow of red blood cells through hypoventilated alveoli. The most consistent measured difference relevant to tissue oxygenation in the two types was in the systemic oxygen transport (product of total blood flow and arterial blood oxygen content). Because of their low cardiac outputs, PP patients, although their arterial blood had a higher oxygen pressure, delivered less oxygen to their tissues than BB patients, who maintained a normal cardiac output despite a greater degree of pulmonary hypertension. These findings may account for the cachexia of the former and the cor pulmonale of the latter patients.