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Inflammatory cells are believed to play an important role in the pathogenesis of emphysema; however, a relationship between presence of cells in the lung parenchyma and its destruction has never been shown. The aim of this study was to quantitate alveolar septal cellularity in smokers' lungs and to investigate its relationship with parenchymal destruction and lung function. The lungs of 23 smokers (SS) undergoing thoracotomy for localized pulmonary lesions were compared with those of eight nonsmokers (NS) and five smokers (AS) who died suddenly of nonrespiratory causes. Pulmonary function tests were performed within 1 wk of surgery in SS. For each subject, we quantitated alveolar wall cells (CELLS), an index of alveolar wall destruction (DI), and the mean linear intercept (Lm). As no significant differences were found between S and AS with regard to these indices, we combined them (Group S) for comparison with NS. Although Lm was not significantly different between S and NS, (0.331 +/- 0.072 versus 0.288 +/- 0.038), CELLS and DI were higher in S than in NS (48 +/- 8 versus 25 +/- 2 cells/mm, p less than 0.001; 47 +/- 20 versus 17 +/- 5, p less than 0.001, respectively). Further, CELLS and DI were significantly correlated (r = 0.799, p less than 0.001). The number of polymorphonuclear cells (PMN) in S can exceed that in NS by as much as 5-fold; however, PMN were inversely correlated with parenchymal destruction (DI) (r = 0.598, p less than 0.01). Thus, smokers' lungs have alveolar septal hypercellularity, possibly inflammatory, and closely related to destruction involving cells other than the PMN.

Destruction of alveolar walls is considered by most observers to be the most important part in the definition of emphysema, yet it has never been precisely defined and quantitated. We therefore attempted to devise a reliable microscopic technique to quantitate alveolar destruction that would be both sensitive to disease and easy to perform. Using a point-count system, we obtained an index of parenchymal destruction that represents the percentage of destroyed space as a fraction of the total alveolar and duct space. We have called this measurement the destructive index (DI). In the lungs of 8 nonsmokers and 23 smokers, we quantitated the DI and compared it with the mean linear intercept (Lm) and with pulmonary function in smokers. Although Lm was not significantly different in the 2 groups, significant differences between the DI of smokers and nonsmokers (p less than 0.005) were found. In addition, the DI correlated with FEV1(-0.43, p less than 0.05), MMEF (r = -0.44, p less than 0.05), and recoil pressure at 90% TLC (r = -0.61, p less than 0.05) in smokers. These findings suggest that the destructive component of emphysema can be easily quantitated microscopically, occurs in smokers before dimensional changes are evident (i.e., increased Lm), and influences lung function. Therefore, the quantitation of this destruction (DI) could add greatly to the microscopic definition of emphysema, complementing the information given by the dimensional component of emphysema (Lm).

Elastic fibers are fairly uniform in the size around all alveolar orifices and taper and branch continuously in the alveolar wall to form a spiderweb-like structure. Unusually large gaps of the elastic fiber network in the alveolar wall frequently show coiled ends or tissue debris at the margin. The latex-filled capillaries interweave and intersect with the elastic fibers and in many of these places appear to angulate or narrow acutely; these angulations may alter with lung inflation, affecting pulmonary vascular resistance. Disruption of fine elastic fibers in the alveolar wall could be related to the development of pulmonary emphysema.

We studied post-mortem 9 nonsmokers' lungs and 9 smokers' lungs as well as 14 surgical smokers' lungs to examine the possible relationship of the number of alveolar attachments with airways inflammation and with lung function. Alveolar attachments are the alveolar walls radially attached to the small airways, and any discontinuity or rupture of these alveolar walls was considered abnormal. Normal and abnormal attachments were counted in nonsmokers and smokers and expressed as number of attachments, distance between attachments, and percentage of abnormal attachments. Although internal small airways diameter and mean linear intercept were not significantly different between smokers of either group and nonsmokers, significant differences in number of attachments (p less than 0.001), distance between attachments (p less than 0.01), and percentage of abnormal attachments (p less than 0.01) were found. The 3 indexes of alveolar attachments correlated significantly with the score for airways inflammation and with the elastic recoil pressure in smokers. No significant correlation with any other lung function test was found. We conclude that smokers have fewer alveolar attachments than do nonsmokers, and that the loss of alveolar attachments represents an early stage in the destruction of lung parenchyma, and is probably linked to inflammation of the small airways. Because of the strategic situation of this lesion, it could be responsible in part for the loss of elastic recoil seen in the initial stages of chronic obstructive pulmonary disease.

We studied 12 smokers' lungs with scanning electron microscopy in order to analyze the distribution and size of alveolar fenestrae and their relationship to the average distance between alveolar walls (Lm) and lung function. Alveolar fenestrae in areas near terminal airways (respiratory bronchioles and alveolar ducts) were consistently larger than fenestrae far from airways (alveoli). Fenestrae in near areas increased in size as Lm increased (r = 0.845, p less than 0.001), whereas no correlation between Lm and fenestrae size in far areas was found (r = 0.281, NS). The overall area of fenestrae (near and far) correlated significantly with FEV1 (r = -0.745, p less than 0.01), MMEF (r = -0.752, p less than 0.01), and PL90 (r = -0.804, p less than 0.05). However, when subdivided into near and far, only fenestrae near the small airways showed a significant correlation with function. These findings suggest that in smokers with mild to moderate emphysema, destruction affects preferentially the areas around the terminal airways (near areas), and these changes, although small, might play an important role in the lung function.

Scanning and transmission electron microscopy were used to study the epithelial surface development in fetal rabbit lungs. At 20 to 22 days of gestation, microvilli of the epithelial cells were scarce on the luminal surface but were concentrated along the cellular borders which had well-formed apical tight junctions and desmosomes. The epithelial intercellular spaces were frequently wide, and the basement membrane was thin and discontinuous, suggesting that transport or exchange of metabolites across the epithelium occurred easily. Attenuation of cytoplasm started at 26 days of gestation, and the cytoplasmic processes overlapped each other in various ways, so that both autonomous expansion and passive forces may be involved in attenuation of the pulmonary epithelial cells. The lining cells of the alveolus-like structures during late gestation and in the newborn rabbit showed pits with 0.1 to 0.5 mu diameters which probably reflected active production and release of osmiophilic bodies in the type 2 cells and increased micropinocytosis in the type 1 cell. No "gaps" between the epithelial cells were found to account for the resorption of lung liquid.