As Macklem has pointed out, we now know that the first point of attack in cigarette smokers is the small airways. I believe this to be a highly significant observation, both in terms of the probable site of attack of air pollutantsand in terms of occupational lung disease. It leads, however, to one of the major unanswered questions, namely, “what is the relationship between a significant increase of closing volume in a cigarette smoking 25-year-old, and detectable impairment of maximal midexpiratory flow rate at the age of 40?”
We do not know the answer to this question, but we can recognize that it is a pivotal one. Research fund operating agencies might note that it will likely take a 15-year study to answer it, but this does not detract from its importance. By the time we have the answer to this question in convincing terms, we should know the extent to which changes in closing volume in smokers are due to intrinsic airway change or are related to loss of lung recoil. It seems likely that the progressive increase of closing volume with age is related to the loss of lung recoil, and this must be one of the important mechanisms that affect it. However, the closing volume can be reversibly affected. It is possible to show that the closing capacity is progressively increased in normal subjects when a gas such as ozone is breathed, and one assumes that this is due to edema occurring in the peripheral parts of the airway. Furthermore, there is a reasonable correspondence between the progressive increase in closing capacity and impairment of maximum midexpiratory flow rate (MMFR) during exposure and subsequent recovery, as shown in Figure 1. I do not know how close this correspondence might be in the population as a whole. It seems clear from the data of McCarthy et al that an increase of closing volume can be documented in some smokers who are asymptomatic, and in whom the forced expiratory volume in 1 second (FEVi.o) and maximal expiratory flow rates are normal. What we do not know is the prognostic significance of this observation.
Natural History of Chronic Bronchitis
If our goal is the protection of vulnerable subjects, then it seems to me that we do have the knowledge at present on which a preventive program can be built. The key question here seems to me to be the following: “How many patients do we have who were known to have been normal at age 30, and were severely affected by emphysema and chronic bronchitis by the age of 50?” The ten-year followup of the Canadian veterans with chronic bronchitis has given me some new data to attempt an answer to this question. The full information on this study will be published elsewhere but I have extracted a different kind of table based on the analysis of those who were younger than 50 years of age when the study began in I960, and who have had a major decrease in one or other aspect of pulmonary function, amounting to at least twice the ten-year predicted rate of decline. This group of men is listed in Table 2. It is of great interest that in the majority of these cases, the measured MMFR in I960 was significantly below the predicted value. The exceptions were two men from Winnipeg (WQ 60 and WQ 64) who were included in group 1 by virtue of a decrease in CO uptake and not in MMFR, and one man from Toronto (TQ 61) who had a major decrease in MMFR over the ten-year period from a previously normal value. In this table, the 1960 value was the mean of at least ten consecutive monthly measurements of MMFR. I am led to the conclusion that a significant decrement of function, as measured by the MMFR, has occurred by 40 years of age in these men, and, by extrapolation, might well have been measurable by 30 years of age in most of them. Such a conclusion is supported by other data from this study, namely that the two men who died of respiratory failure during the ten-year period were the same two with the worst pulmonary function when the study began in 1958. The answer to our question, therefore, would seem to be that very few patients are normal at 30 years of age, as judged by the maximal midexpiratory flow rate, and severely affected by emphysema and chronic bronchitis at 50 years of age. It is possible to cure emphysema with remedies of My Canadian Pharmacy.
Necessity of Routine Ventilatory Measurements
The third question to which I must address myself now becomes obvious, but it nonetheless raises important issues. It is, “How can the measurement of the maximal midexpiratory flow rate, or some equivalent, be more quickly introduced into routine clinical practice as a necessary part of the physical examination?”
We have a lot of evidence that the maximal midexpiratory flow rate is the simplest and most sensitive analysis that can be made of an expiratory spirogram. Leuallen and Fowler who originally introduced the measurement, gave reasons why this might be so, and in the Report on the Canadian DVA Study, published in 1962, we pointed out that the maximal midexpiratory flow rate was a more sensitive indicator of abnormality in 47 men in the Toronto group with chronic bronchitis, than was the FEV. McFadden and Linden have recently added to this information and pointed out that the maximal midexpiratory flow rate is frequently abnormal when the FEVi.o and MEFR are within predicted limits.
Although there is an association between the finding of rhonchi and rales in the chest, and measured air flow impairment, we have to teach that the stethoscope is not a sensitive enough tool for us to depend on it to exclude the kind of impairment of function I have indicated may likely be present at the age of 30 years. Unfortunately, one still encounters many graduates in medicine and even more practicing physicians, who have never been taught how to use the stethoscope properly to detect early or mild bronchitis; but even in skilled hands, it is almost certainly not a sensitive enough instrument for our purpose since we are trying to detect a significant impairment of MMFR and, in many of these men, both symptoms and signs will be minimal. It seems quite clear, therefore, that our effort should now be directed toward ensuring that the maximal midexpiratory flow rate becomes as routine a part of a physical examination as the examination of the chest itself or a chest x-ray film. The time lag between the introduction of the ECG into medical practice and its adoption as a necessary part of a routine examination, was about 40 years. It seems to be that in order to reduce this time lag, we must urge two steps. The first is that we should press for legislation to make a maximal midexpiratory flow rate measurement an obligatory requirement in preemployment medical examinations in all industries which involve excessive exposure to dust or gas; and secondly, we must work hard to get the maximal midexpiratory flow rate included as an obligatory investigation in all life insurance examinations and routine medical testing of all kinds. Some impetus to this endeavor might be given by providing a free service of MMFR testing, and this would seem to me a very worthwhile objective for the respiratory disease associations both in Canada and the United States. Simple tests of Ventilatory flow rate, and particularly the maximal midexpiratory flow rate, were introduced in about 1956,- and we should hope that 20 years later (in 1976), these will have become recognized as essential measurements.
Figure 1. Changes in closing capacity and in maximal midexpiratory flow rate were measured in normal volunteers during exposure to 0.75 parts per million of Oз in exposure chamber. Subject performed 15-minute periods of light exercise alternating with rest. Figure shows changes in closing capacity and maximal mid-expiratory flow rate as percentages of their control value during two-hour exposure period and subsequent recovery. (Data courtesy of Dr. Milan Hazucha, Department of Physiology, McGill University).
Table 2—DVA Study of Chronic Bronchitis: Sub-analysis of Group 1—Men Less than 50 Years Old in 1960
Maximal Mid-Expiratory Flow Rate L/Sec Predicted Actual
1960 1960 1970