How Flow Met Volume in Three-Dimensional Space

ROBERT E. HYATT

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The paper "Relationship Between Maximum Expiratory Flow and Degree of Lung Inflation" (Robert E. Hyatt, Donald P. Schilder, and Donald L. Fry. J. Appl. Physiol. 1958;13:331-336) described a simple way to relate maximal expiratory airflow to lung volume. It led directly to our understanding of the mechanical properties of the lung that determine maximal flow in health and in lung disease.

In 1956, while working as a research fellow studying fluid retention in a canine model of heart failure at the National Heart Institute at NIH, I contemplated going into the practice of academic cardiology. Dr. Robert Grant, a cardiologist, suggested I learn something about pulmonary function testing to supplement my cardiology practice. Practicing cardiologists in those days had very few techniques other than electrocardiogram and cardiac catheterization to utilize in their practice. As pulmonary research resided in the Heart Institute, he suggested I talk to Dr. Donald Fry, who had written about lung mechanics, but at the time was developing a method for measuring arterial blood flow with a catheter. So I went down the corridor of the seventh floor of the Clinical Center to where Don Fry worked. I found Fry to be receptive to my working in the area of pulmonary function. I also found him to be an outstanding cardiopulmonary physiologist and possibly the brightest individual I ever encountered. He gave me his recent papers on lung mechanics. Of special interest to me was a paper that he had published on lung mechanics in normal and emphysematous patients (Am. J. Med. 1954;16:80). I was particularly struck by the isovolume pressure-flow (IVPF) curves that he described in that article. As one breathes, lung volume changes and the airways continually change in size, making the analysis of resistance extremely difficult. By measuring pressure and flows at fixed lung volumes it was as if you held the lung at a constant volume and gradually increased the inspiratory and expiratory flow. The fact that the expiratory portions of these curves showed a limit to maximal flow struck me as very important, although initially I did not fully appreciate the significance of this fact. What followed was in a sense a fishing expedition that turned out to be very successful as we landed a "keeper."

I wanted to measure some of these IVPF curves, and Fry encouraged me to do so. This involved swallowing an esophageal balloon from which to estimate pleural pressure. To my dismay, Fry did not volunteer to swallow the device, so it was up to me to learn to swallow the balloon. I did not look forward to this, having a terrible gag reflex. But I had to somehow get that balloon in my esophagus. I retired to an empty laboratory, closed the doors, placed the balloon in some ice, placed an emesis basin nearby, covered the balloon with K-Y jelly, and started pushing it through my nose. After about an hour of gagging, swallowing water, and retching, I swallowed the darned thing. Now I was ready to measure IVPF curves on myself. We placed a spirometer with an attached potentiometer for measuring lung volume changes in series with a flow meter and a mouthpiece. We could thus record changes in transpulmonary pressure, lung volume, and respiratory flow simultaneously by tracing them on separate channels of a Sanborn recorder. I would breathe at increasing flow rates up to maximal flow. Every time the volume signal passed through the lung volume of interest I could measure the corresponding flow and transpulmonary pressure both during inspiration and expiration. By plotting flow against volume I could construct an IVPF curve at any lung volume of interest. To evaluate the effect of lung volume on these curves, I would draw additional lines on the paper at different volumes and repeat the process. Each IVPF curve also corresponded to a particular value of lung elastic recoil. Pretty soon the paper was filled with lines and the measurement process became increasingly tedious, thus limiting the number of IVPF curves you could measure. After making measurements of such curves on myself and several patients with emphysema, I was convinced that looking at lung mechanics in this way was very important. One could at a glance see the effect of changes in lung volume on flow resistance and maximal expiratory flow. But I also knew from personal experience that measurements requiring the swallowing of an esophageal balloon would never become routine!

I remember very clearly what happened next. I went in to talk with Don about the measurements and the discomfort associated with swallowing an esophageal balloon. As we sat in his office, I saw him gazing at an enlargement of Figure 13 from his 1954 paper that was pinned on the wall. This figure showed a three-dimensional plot of pressure, flow, and volume for a normal subject. He had noted in that paper that if you measured a great number of IVPF curves at different lung volumes, you could in theory create a 3D surface that would show the relations among pressure, flow, and volume during any breathing maneuver. Figure 13 was oriented in such a way as to emphasize the pressure-flow relationships. Suddenly, he excitedly pointed out that if we were to ignore the pressure axis and look at the flow and volume axes of this three-dimensional plot, we could measure maximal expiratory flow as a function of lung volume without having to measure transpulmonary pressure! This was because it takes relatively little effort to generate the pressures that produce maximal flow. Thus, the flow-volume curve of a maximal forced expiration would identify the maximal flow achievable at all lung volumes without needing an esophageal balloon! Furthermore, the flow maxima could be related to the underlying mechanical properties of the lung.

We were very excited by this possibility, and in two days devised a simpler technique for measuring IVPF curves that eliminated the need for the laborious Sanborn paper technique. This system also allowed us to measure flow-volume curves of maximal forced vital capacity efforts. The flow-volume and IVPF curves were recorded on an oscilloscope and photographed with an attached camera. To prove that we were indeed defining the pressure-flow maxima, we took the flow from IVPF curves measured at various lung volumes and plotted these on the subject's flow-volume curve at the corresponding lung volumes. The agreement was very close, proving that the flow-volume curve did indeed define maximum flow. Such data on normal subjects and patients with cardiac and obstructive lung disease were obtained over a relatively short period of time. We then spent hours writing this short paper. Not infrequently we would spend an hour on a single sentence. The message is that it is not easy writing a short, concise paper. But it was great fun and an exciting time. The paper was submitted and accepted with little changethe rest is history. This way of evaluating lung mechanics has been accepted worldwide.

I learned from this experience in Don Fry's laboratory the importance of persistence. If you keep asking questions and try to understand "why," good things often happen. This was true for my role leading to this paper. Needless to say, it is satisfying that in the following years there have been many publications utilizing this curve and its underlying mechanical determinants to great advantage in both pulmonary research and in the clinical evaluation of patients.

A word about why I chose this paper. It marked my introduction to Don Fry and pulmonary mechanics. It presented a new approach to analyzing and understanding the forced expiratory vital capacity maneuver, our most important pulmonary function test. It also caused me to abandon the idea of entering private practice and led to a personally rewarding career in academic medicine. And, of considerable importance, the flow-volume curve helped educate my children!

	Footnotes

Correspondence and requests for reprints should be addressed to Robert E. Hyatt, M.D., Pulmonary Function Laboratory, Mayo Clinic, 200 First Street, S.W., Rochester, MN 55905. E-mail: muldrow.patricia{at}mayo.edu