Janet Cothrell is no athletic coach. But listen outside the Pulmonary Function Lab on the sixth floor of the Seattle Cancer Care Alliance clinic, and you might hear one.
"Keep going, keep going, KEEP GOING, GOOD!" she shouts, loudly enough for her neighbors to suggest that her door remain closed.
Her patients emerge slightly winded, not from a jog on a treadmill but rather from completing breathing tests to reveal their lung fitness, an important step of their evaluation in preparation for a bone-marrow or stem-cell transplant.
"All allogeneic (non-self) transplant patients, and a subset of autologous (self) transplant patients, must have their lung function tested before treatment to establish a baseline," said Cothrell, one of two pulmonary function technologists in the laboratory. "Then we see them again after treatment and as part of their long-term follow-up to evaluate their lung capacity."
The Pulmonary Function Lab was an integral component of the Hutch transplant program for many years, but the facility serves an expanded role in the Alliance clinic. Alliance patients with cancers other than those of the blood also undergo chemotherapy and radiation treatment that can cause lung damage.
Drop-off in lung function
While lung function might seem an unlikely concern for those with leukemia, Dr. Joan Clark, the lab's medical director and an investigator in the Hutch Clinical Research Division, said a drop-off in lung function after transplantation is not uncommon and can affect recovery.
"Research at our institution has shown that even small lung abnormalities can be associated with a poorer outcome after transplantation," she said. "Monitoring patients before, during and after treatment helps us to look for signs of any diminished lung capacity. The good news is that most people usually recover this function after about a year."
This impairment of lung function can stem from the treatment itself as well as from complications common after transplant.
Transplant patients first must undergo high levels of full-body radiation and chemotherapy to destroy cancerous bone marrow before transfusion with healthy donor hematopoietic (blood and immune) stem cells. This harsh preconditioning regimen also inflicts damage on other cells that have a high turnover rate, which likely includes some lung tissue.
Infections such as pneumonia, primarily due to viruses, also can be a source of lung damage. Before donor stem cells have time to develop into a functioning immune system, patients are highly susceptible to infection by pathogens that are typically harmless to healthy individuals.
The most serious lung complications, Clark said, tend to occur in patients who develop graft-vs.-host disease, a potentially severe transplant complication in which donor stem cells react against tissue in the recipient. Symptoms can include inflammation of bodily linings, including the gastrointestinal tract.
"Some people develop severe obstructive lung disease after transplant," she said. "We observed this about 20 years ago here, as did doctors at other transplant centers. When we went back and looked at many of these patients, we established that this syndrome of airway disease, called bronchiolitis obliterans, occurs in people with graft-vs.-host disease. Our studies have shown that it's often underdiagnosed. We still don't know exactly why the syndrome develops."
For these and other studies, data collected on patients in the Pulmonary Function Laboratory play an important role in transplant research. Each patient undergoes tests to measure the total amount of air his or her lungs can hold.
To do this, patients sit in a windowed, telephone booth-like structure known as a body plethysmograph - what Cothrell refers to as "the box." Measurements are performed several times to ensure reproducible results.
Deep breaths
Cothrell or her colleague Tina Bielski coach a patient through the steps of each test, many of which include taking deep breaths and blowing out forcefully for as long as possible. The body plethysmograph contains a mouthpiece attached to equipment that measures air volume, and data is collected on a computer run by one of the technicians. Results of the tests are available immediately. Clark or Dr. David Madtes, both pulmonary specialists, evaluate the results and examine patients with abnormalities.
In addition to the lung-volume testing, Cothrell and Bielski measure the levels of oxygen in each patient's blood, an important indicator of the efficiency of oxygen uptake by the lungs. Blood samples are analyzed in an Alliance lab and results are usually available within an hour.
The coaching aspect of the technician's job is far more than just entertainment, Cothrell said.
"We really have to help patients blow out as long and hard as possible, which isn't easy. The manual that accompanies the body plethysmograph actually says that we should be embarrassed by all the noise we make. But after doing this job for a while, we can get resistant to embarrassment."
Given that she and Bielski, who each have worked in the laboratory (formerly at the Hutch) for more than 10 years, see a range of patients, they have learned to tailor their enthusiasm - and decibel level - to each individual.
"We deal with people of all ages, non-English speakers, autistic patients and people who are deaf," Cothrell said. "You've got to have sensitivity, although we find that most patients appreciate the noise. They really remember us."
