Alcohol is one of the drugs of abuse and, when taken in excess, is clearly capable of producing irreversible damage to several organs, including the liver, brain, and myocardium. Yet it has certain felicitous effects, as a result of which it is used by the majority of the population of this country. Since excessive use has such significant effects, it has long been suspected that moderate consumption also may cause less obvious injury to these or other organs. One organ system which has been considered at risk is the respiratory tract. The susceptibility to tuberculosis and other pulmonary infections is increased, and lung abscesses due to aspiration also are more common.
It also has been reported that chronic lung disease may be associated with alcohol consumption. Sometimes this is identified more exactly as “obstructive lung disease” and even as “emphysema.” Recent papers, however, have called attention to the fact that drinkers have a higher prevalence of smoking than nondrinkers and that when pulmonary function data are adjusted for the smoking effects, the apparent role of alcohol disappears. Indeed, some aspects of pulmonary ventilation have been closer to predicted values in the drinking smoker population than in nondrinking smokers.
All epidemiologic reports dealing with these topics have consisted of clinical observations and pulmonary function tests. Some years ago the authors collected a series of inflation-fixed lungs which were studied by morphometric techniques. Background information as to smoking, occupation, and drinking also was obtained. This article will present data as to associations among age, smoking, and drinking, and the extent of emphysema, pulmonary pigmentation, and airway lesions.
Materials and Methods
During a four-year period, pathology residents at this Veterans Administration hospital were requested to save one lung from each autopsy performed so that it could be fixed in inflation for subsequent detailed morphometric study. Fixation was accomplished by one of two techniques, formalin fume fixation and air-drying or intrabronchial liquid formalin pressure fixation. Following fixation, each lung was examined by multiple parallel slices in the frontal plane extending from apex to base and from the medial to lateral pleural surfaces. At least one slice from each lung was preserved permanently, the liquid-fixed ones being sealed in transparent plastic bags containing enough formalin so that they remained inflated.
Groups of lungs were periodically examined for the purpose of classification. This was done solely on the gross appearance of the cut surface of the lung and without knowledge of other autopsy findings or clinical diagnoses. Lungs were classified as normal, centrilobular emphysema (CLE), or “other;” the last includes other forms of emphysema, fibrosis, neoplasia, and many other lesions. Lungs with acute terminal lesions, such as infections, could usually be identified as having been structurally normal or emphysematous prior to the final illness and were so classified. When this was not possible, they were classified as “other.”
Since classifications of the emphysemas are not uniform, it is necessary to present the concept followed in this laboratory. The authors use only five classes of emphysema: centrilobular (CLE), panlobular, localized, paradcatricial, and focal or coal-workers pneumoconiosis. “ In our experience, types of emphysema such as “primary” “essential,” “idiopathic,” and “atrophic”* regularly show areas with characteristics of CLE, especially in the least involved areas» which usually are lower lobes. Since chronic obstructive lung disease is clinically progressive and there is a continuous morphologic spectrum from slight involvement by CLE in cases with no clinical symptoms to severe lethal disease, it seems most logical to label all cases which show the CLE pattern in any portion of the lung tissue as cases of CLE. The other class terms are reserved for lungs showing only those particular morphologies. Tbese concepts and the reasoning which led to them have been presented in detail and illustrated previously. Tbe result is that about 85 percent of all lungs with emphysema seen in this laboratory are classified as CLE. The other 15 percent are about equally divided among the other four types.
All lungs classified as having CLE were subjected to mor-phometric determination of its extent using the well established procedure of “point-counting.In lungs which were structurally normal, the same procedure was used to measure extent of tissue pigmentation. For the point counts, complete slices of lungs were used, extending from apex to diaphragm and from medial to lateral pleural surface in the frontal plane, including the hilum. The point-count grid had points evenly distributed at 10 mm, and total points on a single lung slice ranged from 200 to 400, depending on the size of the lung. The proportion of these points falling on CLE lesions visible to the naked eye was used as the measure of the extent of emphysema.
Large and small airway lesions also were examined. For large airways, photomicrographic montages were prepared including the entire bronchial wall in cross section at a magnification of 40x. Mucous gland area as a proportion of the entire wall including cartilage was then determined by point-counting. Small airways were defined as structures no greater than 2 mm in smallest diameter; containing no cartilage in the wall, and lined entirely by columnar or cuboidal epithelium. Respiratory bronchioles were excluded. Data for small airways were reported as the proportion of all those seen that had 20 percent or more of goblet cells in the epithelium.
Finally, the clinical records of the patients were reviewed for information as to smoking history and alcohol use. This review was accomplished at a different time from the morphologic studies and without knowledge of their results. With respect to smoking, a clear recorded statement by a patient that he had never been a smoker was accepted as true. If a patient was a current smoker or had ever been a regular smoker, he was classified as a smoker. No attempt was made, for this study, to quantify intensity of smoking or to separate cigarette users from pipe or cigar smokers.
Tferminology regarding alcohol consumption varied considerably among clinical records and required interpretation by the chart reviewer. Again, a dear statement that the patient had never used alcohol was accepted as true. Known chronic alcoholic patients were classified as heavy drinkers. A statement that a patient consumed daily at least two mixed drinks or more than two bottles of beer or glasses of wine was interpreted as heavy drinking. In the absence of daily use, the regular weekend consumption of more than a six-pack of beei; at least one bottle of wine or at least one pint of spirits also was recorded as heavy drinking. All other drinking patterns, occasional, social, or regular consumption of less than the amounts listed above were recorded as slight-to-moderate alcohol use.
Tbe data were analyzed using programs in the SAS statistical package. Prevalences were calculated, and two-way tables were tested usingx tests for independence of pairs of variables. A logistic regression model was used to relate the measured variables (emphysema, mucous glands, goblet cells, and pigment) to the background factors: age, smoking, and alcohol use. For the logistic analysis, emphysema and goblet cell metaplasia were divided into four grades: 0 to 24 percent, 25 to 49 percent, 50 to 74 percent, and 75 to 100 percent Mucous gland volume percent and pigmentation were divided into four groups: 0 to 9 percent, 10 to 19 percent, 20 to 29 percent, and 30 to 39 percent.