Scientists hope this simple test may lead to early diagnosis of the deadly disease that takes the lives of 158,000 Americans a year.
 

 Lung cancer can be a silent killer, often showing no symptoms until it's too late. But University of Louisville scientists have discovered a simple test that may someday help diagnose the deadly disease earlier — by analyzing exhaled breath.

The researchers made their findings while examining patients with suspicious lung lesions and testing their breath using a specially designed microchip. The probability of cancer was 95% for patients with elevated levels of three or four specific compounds.

"Patients are very enthusiastic about it. The concept of having a painless method to tell if you've got cancer is really appealing," said Dr. Michael Bousamra, who presented early data at the recent annual meeting of The Society of Thoracic Surgeons in Florida.

Bousamra and his colleague, Xiaoan Fu, said such a test could be publicly available in five years or less. They envision that it would first be used to help determine which patients should undergo potentially dangerous biopsies, and eventually may become a lung cancer screening tool.

Nancy Alvey of Louisville, Ky., a lung-cancer survivor and activist who was diagnosed in 2005, said she keeps up on local research, and considers these findings "fabulous."

"With lung cancer, it's been kind of stagnant as far as research is concerned, and now this gives another avenue," said Alvey, a 61-year-old grandmother of seven who quit smoking shortly after her diagnosis. "I think they're on the right path, and it makes me happy it's happening here, because there's a lot of lung cancer in Kentucky."

In fact, lung cancer strikes and kills Kentuckians at the nation's highest rates, with more than 3,500 deaths a year. Smoking is the leading cause of lung cancer, and Kentucky also has the nation's highest adult smoking rate at 28%.

Indiana has the sixth-highest smoking rate, 24%, and lung cancer kills 4,100 Hoosiers each year.

Nationally, lung cancer takes the lives of 158,000 Americans a year, making it the deadliest form of cancer. That's largely because it's so difficult to treat when found late.

Dr. Norman Edelman, a Long Island pulmonologist who is senior medical adviser for the American Lung Association, said he's encouraged by the University of Louisville study and a growing body of research looking at exhaled breath. In combination with low-dose CT scans for smokers — which are becoming more common — breath testing promises to help doctors find cancers when patients can still be saved.

"We're delighted to see this type of research going on. It's important," said Edelman. "The survival rate depends critically on early detection."

An easier test
National Cancer Institute statistics show that the 5-year survival rate among lung-cancer patients whose cancer has spread to other organs is less than 4%, compared with 54% for those with cancer confined to the lung. Overall, only 16.6% of lung cancer patients survive at least five years.

In their research, the University of Louisville team tested 150 patients with suspected or diagnosed lung cancer and 85 healthy "control" patients.

Study subjects blew into a bag, filling it like a balloon with a liter of air. The air was then pulled by a vacuum across a specially coated silicone microchip smaller than a quarter, developed by Fu, an assistant professor of chemical engineering at the university.

The chip captures specific compounds in the breath, which are then analyzed with a mass spectrometer, an instrument that measures the mass of a given molecule. Researchers matched their findings with pathology and clinical results from each patient.

Two of the four compounds they found in lung-cancer patients were previously known to be associated with the disease, but Fu discovered that the two others were also linked to lung cancer.

Bousamra, an assistant professor of cardiovascular and thoracic surgery, said patients with a mass and elevated levels of all four compounds "always had cancer." Having three or four elevated compounds was predictive of lung cancer in 95% of patients with a mass, and having two elevated compounds was predictive of lung cancer in two-thirds of patients.

Researchers tested exhaled breath for specific volatile organic compounds by using a silicone microprocessor and a mass spectrometer.(Photo: University of Louisville via The (Louisville, Ky.) Courier-Journal)

Conversely, the absence of elevated levels predicted a benign, or non-cancerous, mass in 80% of patients. And high levels of the compounds among those with lung cancer returned to normal after doctors removed the mass.

Currently, patients with suspicious findings on CT scans must often undergo surgical biopsies to check for cancer, which can cause complications such as a collapsed lung, bleeding into the lung or pneumonia.

"Instead of sending patients for invasive biopsy procedures when a suspicious lung mass is identified, our study suggests that exhaled breath could identify which patients may be directed for an immediate" surgical treatment, Bousamra said.

Bousamra said the team would now like to look into using the method as a screening tool.

"We'd love to do a study where patients come in for screening and we go head-to-head with PET scan" screenings, he said, noting that PET scans can cost more than $2,000, while he estimates breath analysis may wind up costing $50 or less.

Growing body of research
Researchers elsewhere have also been studying the use of exhaled breath in detecting lung cancer.

An October review of research in the Journal of Thoracic Disease, for instance, said many studies have analyzed the patterns of compounds in exhaled breath, and others have shown that "exhaled breath condensate" can reveal gene mutations and DNA abnormalities in patients with lung cancer.

Also in October, Cleveland Clinic researchers presented findings on exhaled breath analysis at the annual meeting of the American College of Chest Physicians. Their method involved using a chemical sensor.

The breath of the subjects — including some with lung cancer, some with benign nodules and some at risk for lung disease — was exposed to a sensor, called a colorimetric sensor array. The colors on the array change when exposed to certain chemicals, and if the breath contained markers for lung cancer, the array would show that in color changes.

Cleveland Clinic scientists said they were developing a breath-based test based on that research.

Such studies come in the wake of other efforts to detect early lung cancer. A large 2010 study found that CT imaging, which is much more sensitive than regular chest X-rays, can help reduce lung-cancer deaths by 20% among heavy smokers.

And late last year, the U.S. Preventive Services Task Force, an independent panel that advises the federal government, issued a recommendation urging annual lung cancer screening with low-dose CT in adults 55 to 80 years old with a 30 "pack-year" smoking history and who currently smoke or have quit in the past 15 years.

A pack year means someone has smoked an average of a pack a day for a year, so 30 pack years is a pack a day for 30 years, or two packs a day for 15.

Edelman said the recent research and emphasis on lung cancer promises to finally help doctors make real strides against the disease. But he said people should also keep in mind that a major key to progress involves quitting tobacco.

While lung cancer can be caused by radon or asbestos exposure or other factors, experts say about 85% of cases are linked to smoking.

"Half the people who are regular smokers will die of smoking-related disease," Edelman said. "The cure is very simple."