Breath Taking. Michael J. Stephen

up very high in the chest cavity and lies just below the neck. I inserted the needle carefully.

      The issue with our patient from Maine was definitely one of impaired gas exchange—that I understood—but my resident’s term ARDS did not mean much to me at the time. The first known mentions of this mysterious lung disease in the medical literature were made in 1821 by the French physician René Laennec, who also invented the stethoscope. In his book A Treatise on the Diseases of the Chest, he described the death of a patient with lungs filled with water but without evidence of heart failure. Fluid in the lungs was certainly familiar to doctors at this time, but it was almost always preceded by the left side of the heart failing. The circulation in the chest begins as our veins empty blood into the right side of our heart, which pumps it to our lungs, where it travels to the left side of the heart to be pumped through the rest of the body. If the left chamber of the heart fails, as often happens with cardiac disease, the blood backs up into the lungs and fluid spills out into the alveoli. But Laennec noticed that in a certain subset of people, fluid was spilling into the lungs without heart failure, without high pressure. The capillaries of the lung were simply leaky, and patients were essentially drowning.

      Later in the twentieth century, more of these cases started being reported, often when a soldier was being resuscitated after sustaining an injury in battle. Soldiers would get revived with blood and recover from their wounds, but strangely, afterward, their lungs failed, filling with fluid and later hardening up like a stone. Names like “DaNang lung” and “post-traumatic lung” sprang up in the literature. The disease itself was largely a mystery. It was also a devastating illness, with the mortality rate approaching 80 percent.

Part of the mystery was solved in 1967 in a paper by Dr. David Ashbaugh, of Ohio State University, and colleagues at universities in Denver and Michigan. Together they gathered information on a series of similar cases and coined the new term: acute respiratory distress syndrome, or ARDS. Their paper, published in the journal Lancet, describes the injuries and lung pathology of twelve patients who had a pattern of respiratory failure caused by too much fluid in the lungs.33 The injuries the patients sustained before respiratory failure were disparate—some had trauma, others pneumonia, still others an inflamed pancreas. But their respiratory failure was similar—the extra fluid in their lungs, from leaking capillaries, would lead to dysfunctional inflammation and scarring, eventually turning their lungs rock-hard. As a result, all of these ARDS-afflicted lungs had trouble getting oxygen in and carbon dioxide out.

      Dr. Ashbaugh’s paper was a landmark study in that it put a name and a face to a mysterious condition, the first and often the most important step in successfully treating a disease. (One can’t study a disease that has not been properly and accurately described.) And, quite extraordinarily, much of what is described in the paper is still relevant today. Unfortunately, the continued significance of this paper is also a sign of failure. According to the paper, ARDS is a disease in which some dramatic insult to the body occurs, which then causes lung inflammation and capillary leakage with no evidence of heart disease. The findings have not changed because the syndrome is stuck at the stage of description. There was no cure in 1967, and there is still no cure today.

      So far, the efforts of physicians to slow or reverse the inflammation and leaky capillaries characteristic of ARDS have been futile. The journals are littered with descriptions of attempts involving different medicines—from steroids to inhaled nitric oxide to inhaled prostacyclin­—­that have come up short. Frequently, these treatments offered hope in mouse models, but every human drug trial has failed.

Even if no single medicine has been shown to improve outcomes, the mortality rate has dropped significantly, from the 80 percent in the 1960s to 40 percent today.34 This improvement reflects a persistent focus on appropriate ventilator settings, nutrition, and physical therapy. There is much one can do in medicine without using drugs, and the dramatic decline in ARDS mortality speaks to this. People like John B. West, investigating how the lung moves air and blood, have been a big part of this progress. Still, with 10 percent of all medical intensive care unit admissions resulting from ARDS, it remains a formidable problem.

      After we successfully put the central IV line into Mr. Joseph’s neck, Kevin and I took a closer look at his ventilator. It had initially been quiet, but now its high-pressure alarms were starting to trigger loud pinging noises, indicating a failure to push air into the patient’s very stiff lungs.

      We called the respiratory therapist, and he and my resident came up with a plan to lower the driving pressure of air from the ventilator while giving the air a longer time to get in, easing the flow into Mr. Joseph’s rigid lungs. We also had the nurse give him a paralyzing level of sedation, calming any involuntary fighting he was doing with his own respiratory muscles.

      The modifications seemed to work, and the ventilator alarms went quiet. But this only told us that the machine was happy. The resident instructed me to check the level of gases (oxygen and carbon dioxide) in the patient’s blood to see if his body was happy. A few minutes later the results were relayed from the lab. Our patient’s oxygen level was just above 60 mmHg, and his carbon dioxide was around 48, corresponding to a pH of 7.30. These numbers were not great, but good enough to get him through what remained of the night.

      For the rest of that month, I saw Mr. Joseph every morning at six o’clock, my first patient of the day. I would analyze how he was doing with oxygenation and ventilation, looking for any improvements. In the evening, at home, I would thumb through John B. West’s book. By the end of the month, I began to understand some of the nuances of how gas exchange works, how different parts of the lung receive very different amounts of oxygen and blood flow. Specifically, the lower lobes generally get both a lot more inhaled air and more blood flow. Some of this is likely due to the effect of gravity.

With this knowledge of variable blood flow and air flow within the lungs, researchers eventually came up with the idea to minimize airflow in stiff lungs like Mr. Joseph’s. The reasoning behind this idea is that, since blood flow and circulation are almost certainly compromised given the level of inflammation in the lungs, there is no need for a normal amount of air in each breath. Before this protocol was established, physicians had been blowing too much air into diseased lungs, creating too much stretch, and that extra stress was creating more inflammation. John B. West helped us appreciate that air flow and blood flow can be variable, and attempts should be made to match them. The breakthrough 2000 New England Journal of Medicine study showed that deaths were significantly fewer in ARDS patients who received less air when on the ventilator.35 Practice in medical intensive care units all over the world changed overnight. No study before this, and no study since, has had such a dramatic impact on what we do in the medical intensive care unit.

      Mr. Joseph was admitted to the hospital in January 2002, so this article was fresh in everybody’s mind, and throughout the month we kept the air flow in Mr. Joseph’s lungs to the absolute minimum possible while still maintaining ventilation. To compensate for a very low amount of air with each intake, we turned up his respiratory rate from the normal twelve breaths per minute to thirty, even thirty-four at times. Normally, a respiratory rate of thirty-four breaths per minute is not sustainable, but with a machine it is. We considered proning, or flipping Mr. Joseph onto his stomach, while he was on the ventilator, to further decrease stress on his lungs by reducing the effect of gravity, thus giving them a rest and a chance to heal. The front of the lungs is where alveoli are often less affected in diseases like ARDS. (Most recently, proning is commonly being used for patients with COVID-19 as the inflammation from pneumonia almost always begins in the lower part of the lungs.)

      Throughout the month, Dr. West taught me about theory, while Mr. Joseph taught me about the real world. Slowly but surely he made progress, his stiff ARDS lungs loosening up enough that he could breathe on his own during the day, while using the ventilator at night. He eventually went to a rehabilitation facility, and from there, presumably, home to the wilds of Maine. As happens so often in the practice of medicine, all we did was keep him alive until he was able to heal himself.

      Today, even though specific drug treatments for ARDS are nonexistent, other therapies have shown progress. Foremost among these is extracorporeal membrane oxygenation (ECMO), where blood is taken out of the body, run through a machine that removes carbon dioxide and adds oxygen,