A Being Breathing Thoughtful Breaths*

E. J. MORAN CAMPBELL

Division of Respirology, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada

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I have chosen to write about a simple experiment I did in 1960 with three medical students (The ability of man to detect added elastic loads to breathing: E. J. M. Campbell, S. Freedman, P. S. Smith and M. E. Taylor; Clinical Science, Vol. 20, No. 2, April, 1961) fleshing out the circumstances that led up to it and what happened afterwards.

My father was a GP in James Herriot country, and when I went off to medical school he advised me, should I have the chance to spend a year studying some subject in depth, I should take it. Fortunately, my school was the Middlesex Hospital where the Professor of Physiology was Samson (Sammy) Wright, arguably the greatest teacher of physiology in the country. I caught his attention and together with three other students I took an extra year of physiology.

During my clinical training I kept in touch with Sammy and in 1951, the department being short-handed, he persuaded me to join as a lecturer. There was plenty of spare time for research but I preferred to do clinical work. However, Sammy was persuasive (dare I admit that I had to be persuaded to do research?) And so I found myself using the EMG to study the respiratory muscles, work which led to a Ph.D. I think that during these studies it occurred to me in a dim unfocused way that the proprioceptive control of these muscles deserved attention.

And then in 1955 on to Johns Hopkins and Dick Riley. Being the new boy I was "enrolled" as a subject in a number of experiments by Leon Farhi, Harry Martin, Dick Shepard, and Dick Riley himself. (Arthur Otis and Don Proctor were also around but I don't think I breathed for them.) In most of these experiments I was not required to think, but in all this breathing out of tubes, and through valves and taps, I could not help but notice that one was good at detecting obstructions such as kinks in the tubing, incompletely turned taps or sticky valves. In a vague way it occurred to me that this ability to detect such "loads" was worth studying quantitatively because of the possible light such findings might shed light on the proprioceptive control of breathing or even on dyspnea.

In late 1955 I was appointed Assistant Professor on the Medical Unit at the Middlesex. This was a modest affair consisting of the Professor, who was interested in obesity, a Senior Lecturer who was interested in endocrinology, and myself. Although not spelled out it was clear that my priorities were clinical and teaching, with research a distinct third. John Friend, my predecessor, had left behind a helium closed circuit for measuring lung volume (which Reuben Cherniack, Keith Westlake and I cannibalized and used to measure the O₂ cost of breathing). And that was the sum total of the equipment. I went to the prof with what I regarded as a modest list of equipment. He allowed me to have a Riley bubble bath constructed but said we could not afford anything else. I suggested we might apply for a grant but he demurred on the grounds that applying for outside funds was tantamount to admitting that he was not running the unit properly.

I was able to scrounge about two half days a week for research, but as we lived a hundred yards from the hospital I could supplement this by working odd hours.

For the next year or so I was engaged in other matters, but the problem of load detection, as I had come to call it, continued to irritate me. I decided to try and measure the ability to detect loads, not, I confess, because I had a hypothesis, but because I thought measurements might lead to a hypothesis. Furthermore, the equipment needed was simple. I could beg, borrow, or steal the essentials and make the rest.

I was spurred into action when approached by three students at the Middlesex led by Stan Freedman. They were taking the same honors year in physiology as I had taken 11 years earlier and wanted to "do some research." I told them what I could offer and they selected load detection. Then followed a few evening discussions in a local pub devoted to background and planning. On a pad of graph paper we drew P-V diagrams, designed circuits, and outlined protocols. These discussions led to something like the following clarification of my vague ideas:

Accepting a charge of teleology I reasoned that the sensory mechanisms subserving load detection were not there for that purpose alone; they must have a more fundamental role and the genesis of sensation is an epiphenomenon. Furthermore, intrathoracic receptors such as those subserving the Hering-Breuer reflex were unlikely participants because transpulmonary pressure is unaffected by an external load. And so I was led back to the respiratory muscles.

(In the spirit of these Essays I admit that this last paragraph flatters the clarity of my thinking at the time.)

We decided to try and measure the ability of normal subjects to detect added external elastic loads using rigid, empty drums (and Boyle's Law) to provide the loads. We began with a discarded 25-gallon drum from the dispensary, some tubing from an anesthesia machine, and one or two breathing taps borrowed from the physiology students' laboratory. In addition of course, we had to be able to measure pressure and this we did with a very simple, highly nonlinear rubber membrane manometer.

We put all this equipment together and tried it out. It proved easy to detect 25 gallons. Then followed a long search for drums and taps as we found how embarrassingly easy it was to detect even quite large drums. Eventually we had an assembly of drums which totaled 165 imperial gallons. To enable us to "narrow down" we also had some five gallon drums as "fine adjustment." This all amounted to 750 L or a "compliance" of 750 ml/cm H₂O.

There ensued a number of further sessions in which the circuit was refined and a protocol was hammered out. Eventually the equipment was so arranged that the experimenter was sitting in the middle of the set of drums with various taps in easy reach so he could manipulate the different volumes. The floor area of the laboratory was almost entirely occupied by these drums. When the experiment was in progress the operator looked like a one-man West Indian steel band or a tympanist in some bizarre orchestra. Esthetically the whole effect was rather pleasing because the drums varied in colour from a rich etruscan through various oranges, yellows, and greens to a nice deep royal blue.

After a few false starts we managed to follow a protocol that enabled us to complete a study in about 40 minutes. These studies had to be confined to the evenings when I had finished my clinical work and the students had finished their lectures. We completed a series of studies that took only about 8 hours in all. The analyses took much longer but the students could do them in their own time.

We found to our surprise that we could get reproducible results not only in an individual subject but also between subjects. They all detected 308 L (about 80 gallons) on about 50% of occasions. That is an elastic load, or elastance, of about 2.5 cm of water per liter.

When we began these studies we had expected the threshold of detection would require loads that caused a systematic reduction in tidal volume or a systematic increase in pressure. However, the changes in tidal volume and pressure were small compared with those occurring during ordinary breathing. Then the penny dropped: the loads were detected because they caused a change in the relationship between pressure and volume. To reduce this idea to simple dimensions we coined the term "length-tension appropriateness."

I reported the study to the Physiological Society and made the mistake of suggesting that the muscle spindles could be the peripheral neural mechanism subserving detection in that a load would increase misalignment between the extrafusal and intrafusal fibers. I was howled down by neurophysiologists who doubted the presence of spindles in the respiratory muscles (there are) and who doubted if the spindle is sentient (it is). Then I reported the study to the American Physiological Society in Chicago when, apart from some amusement provoked by a color slide of the equipment, it was met by resounding incomprehension that I can only attribute to the fact that the whole businessidea, methods, results, interpretationwas way outside the prevailing paradigms.

A year or so later, together with another group of Middlesex students, I studied the ability of normal subjects to detect added nonelastic (resistive) loads. We found a 50% level of detection of 0.6 cm H₂O/L/s. (Bennett et al., Clin Sci 1962; 23:155-162). The general implication was the same: a disturbance of length-tension appropriateness. (Most subsequent workers have used nonelastic in preference to elastic loads because the equipment is less unwieldy. There has been good agreement with a value of 0.6.)

I think I can honestly say that the relevance of these studies to dyspnea was only at the back of my mind. I was aiming to use sensation to elucidate mechanism rather than the other way around. However, when discussing the work I usually found myself hinting that length-tension inappropriateness may play an important role in the genesis of dyspnea.

I suspect these studies and the idea of length-tension appropriateness would have aroused little interest, but in 1961 Jack Howell and I were asked to take part in the Ciba Foundation Symposium on Pulmonary Structure and Function held in celebration of the centenary of the birth of J. S. Haldane. I decided to attempt a comprehensive account of possible proprioceptive mechanisms involved in breathing, incorporating these sensory studies and some ventilatory studies I had done with Jack Howell. (Incidentally I think Figure 6 in our contribution is still a good comprehensive depiction of these mechanisms.)

In the generous discussion period that is a feature of Ciba Symposia, Julius Comroe became quite excited about length- tension appropriateness and dyspnea and after the meeting the British Medical Journal published an annotation that gave a rather garbled account of our ideas. So Jack Howell and I wrote them the following letter (Brit Med J 1963;ii:868):

A respiratory physiologist offering a unitary explanation for breathlessness should arouse the same suspicions as a tattooed archbishop offering a free ticket to Heaven. But the euphoria is such that we are only a little sad that neither the writer of your annotation (August 10, p. 336) nor "other experts" have fully grasped the system of our delusion. They are right to seize on the word "inappropriate" which is certainly the key, but why try it on only the outer doors of the mystery?

At the risk of increasing confusion, the hypothesis can be explained as follows: dyspnea may be experienced (1) if the neurochemical demand for breathing is inappropriate to the apparent needs (as at attitude), (2) if the neuromuscular effort of breathing is inappropriate to the breathing that is achieved (as in asthma), or (3) if the neural effort is inappropriate to the muscular act that is achieved (as in muscular paralysis). On close examination, the messages in all these three states are not dissimilar. Moreover, in most clinical conditions there would be a mixture of two or three, so the sensation reaching consciousness may be compound or impure. [P.S. 2000: a perception rather than a sensation.]

Nearly 40 years later I still think the central idea of the letter is defensible butas the P.S. hintsboth we and others would have been advised to approach dyspnea more from the standpoint of a perception rather than a sensation.

I have several reasons for favoring this paper: the study was original; it cost little time and no money; it captured the enthusiasm and harnessed the originality of the students; it helped to promoted the use of psychophysics in the study of breathing; finally, the attention it received made me an "expert on dyspnea," and, of course, the status of "expert" tends to be self-perpetuating.

	Footnotes

Correspondence and requests for reprints should be addressed to E. J. Moran Campbell, M.D., F.R.C.P.C., F.R.S.C., Professor Emeritus, Division of Respirology, Department of Medicine, Faculty of Health Sciences, McMaster University, Rm. 3N516, 1200 Main Street, West Hamilton, ON, L8N 3Z5 Canada.