Airway Resistance

ARTHUR B. DUBOIS

John B. Pierce Laboratory and Yale School of Medicine, New Haven, Connecticut

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If the answer to an almost insoluble research problem arrives, you feel afterward the way you do when the cat falls asleep purring in your lap. And that is how I felt the day I first measured airway resistance, resulting in a paper entitled: A new method for measuring airway resistance in man using a body plethysmograph: Values in normal subjects and in patients with respiratory disease. A. B. DuBois, S. Y. Botelho, and J. H. Comroe, Jr. (J. Clin Invest. 1956;35:327-325). This method has been used in assessing asthma, bronchitis, and the effectiveness of bronchodilators.

My interest in mechanics of breathing began when I was five. A Cornell medical student who looked after us during the summer showed us how to use a straw to inflate the lungs of muskrats and woodchucks killed by our Chow dog "Chinky." The lungs collapse due to their elastic recoil at a rate limited by resistance to outflow.

Later, as a medical intern at The New York Hospital I was helping Drs. Carl Muschenheim and Walsh McDermott trying to find the right dose level of streptomycin for patients who had tuberculosis. Too much made patients dizzy and deaf; too little failed to cure them. As people with positive sputum were taken off the streets, tuberculosis decreased, but asthma, bronchitis, and pulmonary emphysema remained to be conquered. We had no way to measure lung function in such people and I knew we needed better scientific methods to tackle these diseases.

Then, as a medical officer at the U.S. Naval Academy, I had an opportunity to review and extend my physics courses cut short in college by an accelerated program. Could the physical principles governing airflow through tubes be applied in medical research? Could they define the width of the air passages of patients who had obstructive lung disease? However, I was not well enough equipped to pursue these questions. I needed more training.

After the Navy, I enrolled as a medical research fellow at the University of Rochester where Wallace Fenn, with the able assistance of Hermann Rahn and Arthur Otis, was conducting basic research in respiratory physiology. Their scientific approach toward pulmonary mechanics and gas exchange had begun during WW II in an effort to improve altitude tolerance of fighter pilots, and after the war these new quantitative methods were being introduced into medical research.

While in Rochester, I tried to measure alveolar pressure, first by inserting a ureteral catheter down the trachea of a dog until it stopped way out in the lungs, then by measuring intrapleural pressure versus airflow. Finally, I measured total resistance to breathing using a piston pump oscillating to and fro to drive air into and out of the lungs. But that resistance included tissue resistance of the lungs and chest wall. Airway resistance still eluded me.

After two exciting years in Rochester, I went to the Peter Bent Brigham Hospital as a senior assistant resident in medicine. The atmosphere was conducive to focusing basic science on the practice of internal medicine. It appeared to me that the best place to apply new methods in respiratory physiology to the study of pulmonary disease would be in the department of Julius H. Comroe, Jr., at the University of Pennsylvania. In July 1952, I started to work there on mechanical impedance of the human lungs and chest.

Comroe and Botelho already had an idea, based upon the compressibility of alveolar air, which eventually proved to be the key to measurement of airway resistance. Their experiments were brought to a halt by obstacles which neither they nor other investigators before them had been able to overcome. Undaunted, Comroe and Botelho built a two-chambered steel box with which they hoped to measure alveolar pressure during breathing. The subject sat in one chamber and breathed into the other one. By measuring the change in chest volume in the chamber where the subject sat, and the volume of the air he expired into the second chamber, they hoped to calculate the alveolar pressure that compressed or expanded air in the chest during the breathing.

For an alveolar pressure change of 1 cm H₂O during breathing, one could expect about 3 cc volume change. But these experiments were confounded by changes in temperature and humidity (about 34 cc volume change), and by differences between oxygen uptake and carbon dioxide output during the respiratory cycle (another 3 cc). These volume artifacts were much larger than the desired volume signal, and the body box sat in a corner gathering dust for the next two years while I was bouncing ripples of air into and out of the lungs.

Unknown to Comroe and Botelho, they were not the first to try to measure alveolar pressure changes by Boyle's law for compression of gases. In 1868, Paul Bert placed animals in bell jars, measuring their breathing with small spirometers connected to the bell jar, scratching lines on rotating smoked drums. In 1923, Carl Sonne tried similar experiments with human subjects in a chamber somewhat like Comroe's, but his efforts were overwhelmed by the same artifacts that were to defeat Comroe, Botelho, and their colleagues.

In December, 1953, the last research fellow to try to make the body box behave as it should gave up and left. Comroe moved it into room 825 in the Gates Pavilion of the Hospital of the University of Pennsylvania, and put me in with it just in case I wanted to try my hand.

Overcoming the artifacts did seem like an impenetrable problem; but I had been an amateur radio operator since age 15, had studied physics of airflow while at the Naval Academy, had used calculus to evaluate unsteady state pulmonary gas exchange in Rochester, and possessed the clinical skills needed to handle patients with airway disease. I had not only the incentive but also the background necessary to tackle this problem. In fact, it took me just two weeks to obtain the first accurate records of airway resistance. Here's how.

To measure the air pressure around the body of the subject, I connected a sensitive capacitance manometer attached to the body plethysmograph to the horizontal axis of a cathode ray oscillograph placed where I could watch it through the chamber's window. I sat inside the subject's portion of the chamber, closed the door, and sealed the chamber. I closed my mouth and simulated compression and expansion of the gas in my lungs, increasing or decreasing the pressure with my ribs and diaphragm. As I did so, the oscilloscope registered the change in pressure around my body.

Since the volume of air around my body was 600 liters, whereas in my lungs it was only 3 liters, the pressure change around my body was only 3/600 or 1/200 of the pressure change inside my lungs. If the alveolar pressure changed by 1 cm H₂O inside my lungs, the pressure in the air outside my body would change by only 0.005 cm H₂O. To measure this minute pressure change in the body plethysmograph, I used a very sensitive capacitance manometer recently invented by Dr. John Lilly in the Johnson Foundation for Medical Research. It was operated by radio frequency and was reputedly unstable, but I had been a ham radio operator and believed I could make it work.

My experiments were built around Boyle's Law. Since pressure changes are equal throughout a static fluid system, mouth pressure changes equaled alveolar pressure changes. Four days after I began using the body box, I assessed the thoracic gas volume by putting between my lips a tube leading to a gauge whose signal was recorded on the oscillograph's vertical axis. When I made positive and negative chest pressures against the static pressure tube in my mouth, the oscillograph showed a sloping line, reflecting changes in mouth pressure (and therefore alveolar pressure) versus changes in plethysmograph pressure. The line's slope depended on the thoracic gas volume. I now had a method of measuring alveolar pressure changes, under static conditions, during compression and decompression.

At the beginning of the second week, I replaced the mouth pressure tube with a Lilly pneumotachograph to measure airflow during dynamic breathing. Its gauge was connected to the vertical axis of the oscillograph, while the pressure gauge of the plethysmograph remained connected to the horizontal axis. Through my window in the body box, I could watch the slope of the line respond to the relationship between changes in plethysmograph pressure and airflow at the mouth.

I needed to cancel out the cooling and condensation of water vapor in expired air, and the respiratory fluctuations of oxygen and carbon dioxide exchange, to eliminate the pitfalls that had discouraged other researchers. With deep breathing, the plethysmograph pressure increased abruptly and went offscreen. But, with rapid shallow breathing (panting), the oscilloscope showed a nice S-shaped line (plethysmograph pressure versus airflow). I could change the slope of the S by clenching my teeth, increasing the resistance to airflow. I soon found that the same S-shaped line could be obtained during deeper breathing either by increasing the external dead space or by breathing back and forth from a hot water bottle half-full of warm water.

Thus, I had perfected a method for measuring the volume of gas in the chest, using Boyle's law for compression of gases, and could now measure alveolar pressure (as indicated by static mouth pressure) versus plethysmographic pressure. I had also devised a way to measure dynamic air flow versus plethysmographic pressure using rapid shallow breathing, a method that eliminated the problems caused by the effects of water vapor in expired air and the fluctuations of oxygen and CO₂ exchange. All that remained was to gauge alveolar pressure during airflow.

Airway resistance is expressed by a formula resembling Ohm's lawalveolar pressure divided by airflow. Comroe had simplified the teaching of this principle by saying that the alveolar pressure was to be measured during airflow. However, I first had to overcome this concept about airway resistance in order to actually measure it.

The solution was almost self-evident once one knew what it was. If I measured airflow during breathing and related it to plethysmograph pressure change, and if I then measured alveolar pressure with airflow stopped and related it to the plethysmograph pressure change, then the plethysmograph pressure change would be the common denominator to relate alveolar pressure to airfloweven though alveolar pressure had not been measured during airflow!

It's not often an investigator feels entitled to shout "Eureka!" but for me, this was one of those rare, heady moments.

Working with Comroe was the opportunity of a lifetime. I relished the chance to help advance the application of pulmonary physiology to medical practice, which was Comroe's long-term goal. But, airway resistance had intrigued me since medical school and my strongest personal reason for committing myself to this vexing problem was that it had seemed, at first, almost insurmountable. The satisfaction from solving such a problem makes you feel as if the cat had begun to purr.

View larger version (21K): [in this window] [in a new window]   Two drawings from lab notebook combined into a single illustration. Upper sketch drawn on Jan. 7, 1954, shows a person in the body plethysmograph generating changes of mouth pressure (which equals alveolar pressure) on the Y-axis and plethysmograph pressure on the X-axis of the cathode ray oscillograph. Lower circle drawn Jan. 14, 1954, shows airflow on the Y-axis and the plethysmograph pressure on the X-axis as the subject pants through a pneumotachograph (not shown). Division of the first slope (alveolar) by the second slope (airflow) cancels out plethysmograph pressure. The dividend is airway resistance.

	Footnotes

Acknowledgments: The author thanks Kristin White, Science Writer, for editorial assistance in the preparation of this manuscript.