From Laënnec’s Stethoscope to the Magic of Imaging, Big Data and Artificial Intelligence: A Timeline of Precision Medicine for Patients with Chronic Obstructive Pulmonary Disease

In February 1675, Isaac Newton wrote a letter to his friend Robert Hooke in which he commented, “If I have seen further it is because I am standing on the shoulder of giants.” This statement is as valid today as it was then; in the field of chronic obstructive pulmonary disease (COPD), the work of many “giants” of vision and perseverance has allowed us to stand on their shoulders. In this editorial, I summarize the work of some of those giants (Figure 1), whose ideas and work have complemented the deductive skills of good doctors to help us deliver precision-based COPD care.

Figure 1.

Timeline of some of the most important scientists who formulated the ideas that helped develop the tools we now use for precision diagnosis in patients with chronic obstructive pulmonary disease. The distances between dates on the time axis are not proportional.

René Laënnec, Inventor of the Stethoscope and Father of Precision Medicine in COPD

Slightly over 200 years ago, the French physician René Théophile Hyacinthe Laënnec, aided by the use of his invention, the wooden stethoscope, described the auscultatory findings of diseases of the lungs and heart, findings that were then confirmed by autopsies (1). The idea of the wood stethoscope was sparked by seeing two children sending signals to each other using a long piece of solid wood and a pin. With an ear to one end, each child received an amplified sound of the pin scratching the opposite end of the wood. In his subsequent book A Treatise of Diseases of the Chest and on Mediate Auscultation (2), Laënnec first described the auscultatory finding of “mucous rhonchus” in patients with chronic catarrh (chronic bronchitis), differentiating them from those of “cavernous disease” (tuberculosis). With his keen sense of observation, he first separated “emphysema” from the frequently diagnosed “asthma,” with which it was confused. In his description of the examination of a patient with emphysema, he stated, “The respiratory sound is inaudible over the greater part of the chest, and is very feeble in the points where it is audible: at the same time, a very clear sound is produced by percussion.” Laënnec not only provided physicians with the symbol of the profession, the stethoscope, but he clearly is also the father of precision medicine in COPD, as he first studied the disease that is at the center of this issue of the Journal.

Hutchinson’s Spirometer: Vital Capacity and Breathing Reserve

In 1846, John Hutchinson, in England, first reported the invention of a device capable of measuring the volumes of the respiratory system in normal subjects and patients (3). As a true scientist, he reported a strong relationship between a low volume of air exhaled after taking a full inspiration and risk of death. This volume he “precisely” termed vital capacity, which even today remains an excellent predictor of survival. It took a century to expand the use of the spirometer in patients with COPD when Robert Tiffeneau in 1947 related the volume forcefully expired in 1 second over the vital capacity as a useful test in the detection of obstructive lung diseases (4). Forced spirometry remains the tool for a precise diagnosis of COPD, to define prognosis and response to therapy.

Roentgen and the X-Ray: Seeing across Tissues

In 1895, in Germany, Wilhelm Roentgen, a mechanical engineer, first saw the bones of his hand on a plate photograph taken using an electron beam tube (5), a discovery that earned him the Nobel Prize in 1901. X-ray imaging caught on rapidly all over the world, first helping diagnose bone lesions but rapidly expanding to study chest lesions, primarily those of tuberculosis. Today, chest X-rays remain a routine tool for physicians caring for patients with respiratory symptoms. In COPD, the classical findings of hyperinflation, decreased vascular markings, small cardiac (teardrop) silhouette, and increased retrosternal space help support the diagnosis of advanced emphysema. Importantly, the chest Roentgenogram can differentiate other diseases that may present with symptoms resembling those of COPD, among them heart failure, bronchiectasis, pneumothorax, pneumonia, and lung tumors.

The Bronchoscope: A Voyage to the Lungs

In a review of the history of bronchoscopy, Panchabhai and Mehta (6) confirmed that the father of bronchoscopy is the German otolaryngologist Gustav Killian, who in 1897 examined the trachea and airways of volunteers and went on to extract objects from patients who had aspirated foreign bodies. Killian coined the term “direkte Bronchoskopie,” a term we continue to use today. After multiple modifications pioneered by, among others, Chevalier Jackson in Philadelphia, rigid bronchoscopy became the standard for direct evaluation of the airways. In 1962, the Japanese thoracic surgeon Shigeto Ikeda helped develop the first flexible fiber-optic bronchoscope (FOB). The widespread use of increasingly sophisticated instruments has revolutionized the field of diagnosis, therapy, and research of lung diseases, including COPD. The FOB is useful in obtaining direct lung samples for research purposes and in evaluating response to lung transplantation. The FOB is essential in performing lung volume reduction by deployment of unidirectional valves and coils in patients with emphysema and to ablate excessive mucous production in patients with symptomatic chronic bronchitis.

Stressing the Medical History: The Cornerstone of Precision Medicine

Although the anamnesis has been known since the teachings of Hippocrates, it was Sir William Osler who, in the latter part of the 19th century, transferred the teaching of medicine from the didactic environment of formal lectures to the medical wards and the bedside. His revolutionary method of establishing formal residency over several years, with intense exposure of trainees to direct patient contact in the wards and clinic, remains the gold standard in the formation of medical doctors. In his famous remark “Listen to your patient, he is telling you the diagnosis” (7), he summarized the most important tool in the precise diagnosis of any malady. Furthermore, he pioneered the practice of bedside teaching, making rounds with a small group of students or residents and demonstrating the value of a “thorough history and physical examination.”

The Pulse Oximeter: Real-Time Recording of the Fuel of Life

In Japan, Takuo Aoyagi, a Japanese bioengineer, pioneered the work that in 1974 led to the invention of the pulse oximeter (8). This noninvasive device, which enables determination of the oxygen saturation of the blood (the fifth vital sign), is credited as being the greatest advance for monitoring acutely ill patients, as has been the case in the management of millions of patients during the current severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) (coronavirus disease [COVID-19]) pandemic. In the field of COPD, the measurement of oxygen saturation helps guide supplemental oxygen therapy as well as oxygen desaturation during the night in cases of overlapping sleep apnea and COPD. With recent technological advances, it is possible today to monitor several vital signs with one simple instrument, thereby helping caregivers develop “precise” therapies for individual patients.

Thoracic Ultrasonography: Movement in Action

The history of ultrasonography typifies the cumulative experience of observations leading to the progress of science (9). In the 1700 s, Lazzaro Spallanzani, an Italian physiologist and priest, completed a set of experiments to explain how bats are able to fly at night. Spallanzani hypothesized that bats relied on the bouncing of sound, not their vision, to navigate. Subsequent investigators expanded these principles to practical use, developing sonar for the detection of objects in the water and radar to detect aircraft. It was Karl Theodore Dussik, an Austrian neuropsychiatrist at the University of Vienna, who in 1947 first used ultrasonic beams to diagnose brain tumors and dilatation of the ventricles The application of ultrasonography to most organs of the body has made this technique the most widely applied noninvasive tool in the medical armamentarium. Although not specifically used for the diagnosis of COPD, it does help in the differential diagnosis of conditions that may resemble COPD exacerbations, namely, heart failure, pneumonia, pneumothorax, and pleural effusions.

Chest Computed Tomography: Pathologic Anatomy without Pain or Fear

In the middle 1900 s, Italian radiologist Alessandro Vallebona invented radiographic tomography to define a single slice of the body (10). However, this radiographic technique provided poor soft tissue details. In 1967, Sir Godfrey Hounsfield invented the first computed tomography (CT) scanner in England, using X-ray technology supported by computerized methodology, which made the analysis of the images possible (11). The 1972 introduction of the first commercial CT scanner led to an explosion of studies using this technology in medicine. Overall improvements in speed, slice count, and image quality revolutionized CT use while lowering patients’ exposure to radiation. Chest CT has contributed to the management of patients with COPD. Whereas until recently, the diagnosis of emphysema was made on the basis of direct observation of lung tissue, chest CT can now detect not only its presence but also its distribution, severity, and phenotype, while also defining airway morphology and thickness. Chest CT imaging is crucial in selecting patients with COPD likely to respond to lung volume reduction surgery and can also detect frequently present, but clinically unrecognized, comorbidities that affect patients with COPD (12).

Big Data, Artificial Intelligence, and Deep Learning: Our Challenge Today

The increasing ability of computers to analyze big data and for practitioners to apply artificial intelligence and deep learning to those data is revolutionizing many areas of our lives, including in medicine (13, 14). This is already a reality in chest diseases, in which the detection of nodules likely to be malignant as determined by intelligent algorithms is being implemented in clinical practice (15). How we can precisely help our patients with COPD with these tools is currently a challenge facing all of us (16).

Just as the visionary dreamers of yesterday made possible all of the advances we have taken for granted over the past two centuries, it is our duty to harness these incredible resources to benefit the millions of persons who now live with COPD and the many more who will develop the disease as the causative agents responsible for its genesis continue to persist.