A COPD Screening Shift Could Bring Better Therapies

DECEMBER 19, 2019
Kevin Kunzmann
COPD

Heart disease, cancer, accidents, and chronic obstructive pulmonary disease (COPD). Those are the “big 4” killers in the US. As recently as 2017, Americans had a 56% chance of dying from one of those causes as they did anything else.

Which of these is not like the other? Of course, heart disease is recently established as the greatest disease in the country. Cancer is still close behind. Accidents are very broadly defined as unintentional injury, and is not really something that can be clinically addressed.

COPD, identified as “chronic lower respiratory disease,” is odd. One of its greatest drivers—smoking—has decreased substantially in the US population since 2000, yet annual deaths from the disease have increased 89% since 1990.

And its burden grows exponentially with age—even for a chronic condition. In 2017, an 11-times greater rate of men aged 65 years and older died from heart disease than those aged 45-54. That makes sense: the risk develops early, the disease progresses, and the fatal event occurs in later time.

In the same year, the difference for COPD events was 34-fold.

Broadly speaking, COPD is one of the greatest causes of death in the US. With some troubling context added—this is a chronic disease without a cure, the US population is becoming the oldest it has ever been, and clinicians have linked cigarette-substitute vaping devices to lung health concerns—its shadow looms even larger.

Patients of some other common chronic ailments benefitted from new, disease-altering therapy this decade. Others benefitted from groundbreaking data. Since 2010, the greatest thing to come for patients with COPD has been the stripping of its misinterpretations.

Through a series of related-field discoveries, unsubstantial clinical trial results, and the introduction of a tailored imaging tool, physicians have developed a better understanding of the fourth-greatest killer in the US. The groundwork has been laid to finally combat the disease.


First step, wrong step

In 2012, George R. Washko, MD, MS, of Brigham and Women’s Hospital, helped mark the shifting interests in COPD screening and monitoring. It had been long held that that lung function measured through spirometry was sufficient for both diagnosing and defining disease severity in patients with COPD.

Spirometry metrics, including forced expiratory volume over 1 second (FEV1) and forced vital capacity (FVC), are common marks in other respiratory diseases including asthma. Seeing as COPD has been consistently defined by the obstruction of reversible expiratory airflow, and its severity by lung function impairment, the testing metric seemed most ideal.

But it was missing a critical patient population: smokers. Washko wrote the destruction of lungs through smoking is believed to manifest as emphysema, which is visually classified as a centrilobular, panlobular, and paraseptal disease.

“Initial roentgenologic studies of the lungs of smokers identified several cardiac signs for the presence of emphysema such as increased lucency of the lung fields, narrowing of the cardiac silhouette, and pruning of the peripheral vasculature,” Washko wrote. “Such findings are sensitive but lack the specificity required for large scale clinical and research applications.”

This is where interest comes in imaging technology. Spirometric measure has become a more obviously inadequate gauge for understanding COPD impact, Washko noted, while new technologies held more promise. “Techniques in chest imaging and quantitative image analysis have advanced to the point where they can provide novel in-vivo insight into disease and potentially examine divergent responses to therapy,” he wrote.

The COPD Foundation has reported that computed tomography (CT) scans, particularly high-resolution grade scans—have been proven to be excellent for the detection and determination of bronchiectasis severity, a condition similar to COPD that effects the lung’s bronchial tubes.

“Though similar in function to an X-ray, a CT scan can take a number of smaller pictures whereas an X-ray can only take larger photos,” the foundation noted. “Consequently, the CT scan is the most sensitive and accurate option in detecting and measuring emphysema.”

A notable issue in the field—and perhaps the key driver of COPD diagnosis difficulties in the field—is the process by which COPD is first suspected and eventually assessed for. In 2017, a panel of pulmonologists told MD Magazine® the primary care physician is often the first to see the early signs: fatigue, dyspnea, a cough. But their instinct may be diabetes, or even anemia.

In fact, James F. Donahue, MD, noted he’s more likely to receive a referred patient from a cardiologist than a primary care physician.

“Who would have thought about COPD?” he said. “I think it’s important to remember that we do have some drugs now, for better or worse. But, we need better screening.”

A potentially greater issue may be having a primary care physician suspect COPD, but dismiss it because of a lack of resources. Not all frontline physicians have access to spirometry testing—and even for those who do, not all spirometry criteria entails COPD characteristics. It’s fairly common, Byron Thomashow, MD, said on the same panel, for a patient with classic COPD symptoms to go undetected on a spirometry, then later be confirmed in a CT scan.

“The question really is, ultimately, is spirometry the best answer for this?” Thomashow said. “Or, is it only one piece of a puzzle that ultimately, for us to make a difference, we need to move on from?”

 


Screening for Care

Indeed, data is beginning to buck against the spirometry practice. A meta-analysis assessment from South Korea earlier this year showed 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification did not show any differences in future exacerbation risk compared previous classifications, aside for FEV1 criteria. They believed the spirometry-achieved metric may not contribute significantly to future COPD exacerbation risk—meaning disease classifications which give it less weight would be more accurate.

That said, there’s value in assessing for FEV1 in already-diagnosed patients with COPD. Al Rizzo, MD, chief medical officer of the American Lung Association (ALA), told MD Mag treatment guidelines for COPD focus on symptom management and reduced exacerbation risk. Understanding their exacerbation risk through spirometry can dictate valuable controller therapy decision-making.

“Controlling the drugs, controlling the airway outflow obstruction, and then controlling the exacerbations is key to managing COPD,” Rizzo said.

The current and future use of CT scans in COPD may dictate the eventual move from controller therapy to tailored, targeted drugs that can alter the disease in severe patients—as has been the benefit of respiratory conditions including asthma in this last decade.

Sandeep Bodduluri, PhD, of the University of Alabama at Birmingham, and colleagues reported last year that CT has enabled the identification of multiple COPD progression biomarkers, including assessment of functional small airways disease and mechanically affected lung.

“Obtaining expiratory CT scans in conjunction with novel tools of image registration and parametric response mapping can add considerable anatomic and functional information in selected patients at risk for, or with, COPD,” they wrote.

What’s needed next is research catered toward understanding how such metrics can help assess pharmacotherapy response.


Tipping the Scales

Disease threats on a whole population fluctuate and flatten over time. Opioid use disorder overdose deaths have increased by almost 450% since 1990, and has reached epidemic status today. But in the same time period, deaths from previous epidemics such as HIV have dropped significantly.

On a constantly-shifting scale of new diseases spreading quickly and new therapies controlling their burden, COPD has been very steady. It is a constant, chronic, and deadly condition that has neither a cure nor cause for great public concern.

But the development of screening methods could lead to greater disease understanding. From there: therapies that could tip the scale for good. Part of an improved screening strategy is motivating patients—and what motivates them better than a chance at feeling better?

“What drives patients in to see the doctors is a therapy,” Donahue said. “People get sedentary for all of the reasons that we’ve heard. They assume that the shortness of breath is related to hitting middle age, getting old, and being obese. But now, because there are effective therapies, not great but they’re effective, it’s driving people in. I think that this will move people along.”

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