The interpretation of spirometric measurements in epidemiologic surveys

Spirometry is a fundamental tool in pulmonary epidemiology. Published standards provide specific information on instrumentation, techniques of testing, calculation of results, and physiologic mechanisms. They do not provide guidelines on how to interpret the test results once obtained, e.g., on such questions as which predicted values to use, what value is abnormal, how many people in the general population are likely to be abnormal? It is with these questions that this paper is concerned. Standard normal values in wide use are not ideal but should be utilized for all subgroups of the population investigated, as well as for the comparison population. Conventional definitions of abnormality lack statistical rationale and result in many false-positive and some false-negative results. This is especially true for fixed ratios such as forced expiratory volume (?1 sec)/forced vital capacity <0.70. A statistical definition of abnormality would place 95% of the normal population above the lower limit (lower 95% confidence limit). Such a definition may be more applicable to overt than to early disease. The spirometric values of well-defined diseased groups must be characterized before it is possible to state that abnormality (a value below the lower limit of normal) means disease. The distribution of values (including the mean and standard deviation) should be used to assess epidemiologic risk factors. Prevalence rates separate abnormal from normal subjects. Such data may be used to identify those requiring preventive intervention, medical care, or compensation. Pathogenic mechanisms can be more easily isolated when abnormal subjects are separated from the majority of normal. Frequencies of spirometric abnormality in standard or normal populations serve as a reference to compare rates of similar abnormality in a population under investigation.     

Thymidine incorporation by lung fibroblasts as a sensitive assay for biological activity of asbestos

Three groups of Syrian golden hamsters were exposed to NO₂ for 6, 24, or 48 hr to determine acute effects on intercellular junctional morphology in distal airways and alveolar epithelium. A fourth group, exposed for 48 hr, was allowed to recover for 2 days prior to sacrifice. Light and transmission electron microscopy of bronchiolar epithelium show ciliary loss and surface membrane damage, loss of ciliated cells, and epithelial flattening at 24 and 48 hr. Moderate to marked epithelial hyperplasia and nonciliated cell hypertrophy are noted after 48 hr. Some restoration of normal histoarchitecture is noted in bronchioles of animals allowed a 48-hr recovery period. Freeze fracture platinum-carbon replicas of bronchiolar epithelium show the gradual evolution of a severe disruption of tight junctional networks after 6, 24, and 48 hr of exposure. Following 2 days of “recovery,” bronchiolar tight junctions from animals exposed for 48 hr remain fragmented. The wide distribution of the junctional material present suggests a regenerative process. Freeze fracture replicas of bronchial epithelium show similar fragmentation of tight junctions following 6-hr exposures. After longer intervals, however, there is a return to more normal appearances. Duration of NO₂ exposure has no systematic effect on the integrity of tight junctions in alveolar epithelium. The findings suggest that disruption of tight junctions may be an important specific determinant of increased bronchiolar epithelial permeability following brief exposures to nitrogen dioxide.     

Protective effects of zinc sulfate and L-lysine on acute ethanol toxicity in mice

Survival rates were determined in three groups of male CF-1 mice, treated ip with single and multiple doses of zinc sulfate and/or l-lysine, each alone and in combination, followed by administration of an acute toxic dose of ethanol 1 hr post-treatment. Significant protective effects were observed in all pretreated groups. Zinc and lysine (combined)-treated groups showed a maximal protective effect. Blood ethanol determinations were also made in mice similarly pretreated with zinc sulfate (5 μg/kg) and/or l-lysine (2.5 g/kg) ip and subjected to 4.55 g/kg ethanol ip 1 hr post-treatment. Blood ethanol values were significantly lower in the lysine-treated group (P < 0.05) at 0.5 hr and the zinc-lysine group (P < 0.001) at 1 hr. The zinc-treated group showed a steeper ethanol disappearance curve beyond 2 hr. Histological evaluations of livers from treated and ethanol control animals showed no pathological changes in any group.