To assess the role of chest radiography in the differential diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP), records of 34 patients with biopsy-proved BOOP (16 patients) or UIP (18 patients) were reviewed. Chest radiographs taken before biopsy were available in 26 patients, clinical information in 33, and pulmonary function data in 22. These data were reviewed independently, without knowledge of the pathologic diagnosis. The clinical symptoms of BOOP were similar to those of UIP, although the duration of symptoms was longer in UIP (P less than .05), and the prevalence of systemic symptoms was higher in BOOP (P less than .025). The physical findings were similar except that finger clubbing was more common in patients with UIP than in those with BOOP (P less than .01). There was no significant difference in lung volumes, flows, or diffusing capacity between BOOP and UIP. The chest radiograph showed distinguishing features between UIP and BOOP in 23 of 26 patients. The most characteristic radiologic finding in BOOP was the presence of patchy areas of air-space consolidation (eight of 11 patients).

To assess the pulmonary structural and functional effects of smoking cessation, we exposed groups of guinea pigs to cigarette smoke for 4 and 8 mo and included a group of animals in which smoke exposure was stopped at 4 mo (ex-smokers). We found that, compared with control nonsmokers, the smokers at both 4 and 8 mo showed airflow obstruction with alterations in lung volume and morphological evidence of emphysema with increased alveolar air space size and decreased alveolar surface area-to-volume ratio. There was an alteration in the pulmonary vascular structure, with increased numbers of muscularized arterioles, in the smokers at both time periods, and this was associated with significantly increased pulmonary arterial pressure at 8 mo. Cessation of smoke exposure appeared to halt, but not reverse, these structural changes. The smokers at 8 mo showed clear evidence for a "healthy smoker" effect, underscoring the necessity for longitudinal studies even when using an animal model. We conclude that cessation of exposure to cigarette smoke is associated with an apparent halt, but not a reversal, of emphysematous lung enlargement and pulmonary arteriolar muscularization. However, the magnitude of improvement in pulmonary function is not as great as the apparent structural differences would imply, and there is no clear effect on the pulmonary arterial pressure.

To ascertain whether endothelin may play a role in cigarette smoke-induced cell proliferation in the airways and arterial vasculature of the lung, we exposed groups of seven Sprague-Dawley rats to either room air (control) plus saline infusion, an intravenous infusion of the selective endothelin A antagonist BQ-610 (control BQ-610), the smoke of 10 cigarettes (smoke only), or the smoke of 10 cigarettes after intravenous BQ-610 infusion (smoke + BQ-610). Cell proliferation was quantified by determining the percentage of cell nuclei labeled by 5-bromo-2'-deoxyuridine. We separately evaluated the cells in the epithelium and wall components of the bronchioles, and endothelium and wall components of the peribronchiolar and perialveolar ductular arteries. We found that cigarette smoke produced significant cell proliferation in the airway epithelium and wall, in the peribronchiolar arterial endothelial compartment, and in both the endothelial and wall compartments of the perialveolar ductular arteries. Pretreatment with BQ-610 reduced the peribronchiolar arterial endothelial and the perialveolar ductular arterial wall proliferation to control lev- els and reduced but did not totally abrogate the smoke-in- duced proliferation of the airway epithelial, airway wall, and perialveolar ductular arterial endothelial compartments. We conclude that cigarette smoke-induced cell proliferation of the airways and pulmonary arterial vessels is at least partially mediated through stimulation of the endothelin-A receptors.

Nonspecific bronchial hyperresponsiveness (NSBH) occurs in asthmatics and in smokers who have airway obstruction. NSBH may be caused by different mechanisms in these conditions. We hypothesized that NSBH in smokers was a consequence of the structural changes that occur in chronic obstructive pulmonary disease (COPD) and lead to airway obstruction. We measured nonspecific bronchial responsiveness, assessed by PC20, in 77 smokers who had mild to moderate airflow obstruction prior to lung resection for a pulmonary nodule. We related airway responsiveness to baseline airway function (FEV1 % predicted), to functional (PLmax, PL90, and P-V curve shape) and morphometric (alveolar attachments) markers of lung elasticity as well as to thickening in small airways. Airway wall thickness, internal and external to the outer border of smooth muscle was quantified by plotting the square root of airway wall area versus a marker of airway size, airway internal perimeter (Pi). PC20 was significantly related to FEV1% predicted and PLmax. and when these functional parameters were controlled for, PC20 was also inversely related to airway wall thickness. There was also a trend for the most responsive patients to have fewer alveolar attachments per millimeter on the external perimeter of the airway walls. These data suggest that exaggerated nonspecific airway narrowing in COPD is secondary to structural changes caused by the disease.

A longitudinal analysis of pulmonary function in rats during a 12 month cigarette smoke exposure. J.L. Wright, J-P. Sun, S. Vedal. ERS Journals Ltd 1997. ABSTRACT: We wanted to examine the longitudinal effects of chronic cigarette smoke exposure, and to determine whether the chronic alterations in pulmonary function induced by long-term cigarette smoke exposure in an animal model could be predicted by initial or early alterations in function.A group of Sprague Dawley rats was exposed to the smoke of 7 cigarettes·day -1 for 5 days·week -1 during a total period of 12 months. Lung volume, flow-volume curves and pressure-volume curves were recorded at baseline, and after 2, 4, 8 and 12 months of smoke exposure. A control group of rats was subjected to the same regimen of testing, but was not exposed to smoke.Thirteen rats completed the study in the smoke-exposed group and seven rats in the control group. We found that chronic exposure to cigarette smoke produced early abnormalities in pulmonary function, with the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio showing an acceleration of ageing effect, particularly between 4 and 8 months of exposure. In this model, although the two groups had significantly different airflow after 12 months, the initial values in each group were remarkably similar, and we could not identify any pulmonary function test which had predictive value.We conclude that longitudinal studies of cigarette smoke exposure in this rat model allow better characterization of the nature and time course of the effects of smoking on the lung. Eur Respir J 1997; 10: 1115-1119. In our laboratory, we have previously developed a guinea-pig model of cigarette smoke-induced alterations in pulmonary function [1,2]. Although this model has proved successful in that we have been able to show clear evidence of airflow obstruction and emphysematous lung destruction in smoke-exposed animals, it has also illustrated the problems inherent in such kinds of cross-sectional studies. In the guinea-pig, there was significant interanimal variation in pulmonary function, even when accounting for animal age and weight [3]. Furthermore, we found that our cross-sectional studies were biased by a "healthy smoker" effect, whereby the animals that were most affected by cigarette smoke tended to die before the end of the experiment; the final results were, thus, derived from the animals with the least disease [2,4]. Finally, the use of a single pulmonary function end-point does not allow for analysis of the temporal profile of the development of abnormalities, or for analysis of results that might predict response to cigarette smoke.It was for these reasons that, in the present study, a longitudinal study design was chosen, whereby each animal was used as its own control and function tests were performed at multiple time-points, thus making it possible to track each animal's function by calculating a percentage change from control values. This type of longitudinal analysis also had the advantage that...