Screening for and Managing Pulmonary Dysfunction in Pediatric Cancer Survivors

Pulmonary dysfunction is a common side effect of some pediatric cancer treatments, such as chest radiotherapy. The long-term pulmonary damage stemming from pulmotoxic cancer therapies is believed to lead to 15-fold greater mortality in pediatric cancer survivors compared to the general population.

“We know that, compared to the general population, childhood cancer survivors have a five to six times greater risk of pulmonary disease compared to their siblings and most of that risk is from specific therapies,” says Cleveland Clinic pediatric oncologist Seth Rotz, MD.

The biggest driver of that risk in cancer survivors, he adds, is radiation to the chest, such as what is commonly given for patients treated for Hodgkin’s lymphoma. “Also, among bone marrow transplant patients those who have had chronic graft-versus-host disease are at risk of chronic lung diseases. Finally, there are a couple of chemotherapies known to cause problems with the lungs, including bleomycin, busulfan, and the nitrosoureas.”

Because early lung damage is often silent due to the large functional reserve of the lungs, early screening in pediatric patients undergoing these treatments is very important, explains Dr. Rotz. Spirometry is currently the method of choice for screening pediatric cancer survivors.

“Right now, the guidelines are to get one set of pulmonary function tests when patients enter long-term survivorship and then go from there,” he says. “But some data suggest that pulmonary changes are more progressive than we initially thought, so there are people who advocate for getting pulmonary function tests for a longer period.”

The utility of nitrogen multiple-breath washout in pulmonary function screening

According to Kimberly Medina, RRT, supervisor of the Pediatric Pulmonary Function Lab at Cleveland Clinic, spirometry is the baseline study that measures the volume of air a patient is able to take in and expel.” It can give the providers an idea of where the patient falls on the scale of normal lung volume. N2MBW, on the other hand, was initially indicated for patients who were not able to complete a traditional lung volume test.

“The N2MBW method is a little bit different — it is a continuous measurement that takes somewhere between 7 and 15 minutes,” she says. “The patient breathes in 100% oxygen while the machine analyzes the breath that they exhale, looking for the nitrogen concentration to be reduced from normal levels to almost 0, thus ‘washing out’ the nitrogen.” She continues, “This will give the doctors not only the volume measurements they’re looking for, that may not have been able to be obtained any other way, but it will also give them a picture into the effectiveness of the lungs.”

A study conducted recently by a group of experts from Europe assessed the ability of spirometry and N2MBW to detect pulmonary dysfunction in long-term survivors of childhood cancer. The study found that N2MBW identified more cases of pulmonary dysfunction, even in those patients who were treated with therapy that is not considered to be toxic to the lungs. The authors concluded that, along with spirometry, N2MBW could be a useful additional screening tool for early lung damage in this population of patients.

Ms. Medina largely agrees with these findings. “Some cancer therapies can cause changes that we may not see initially with the spirometry test, as spirometry will not immediately detect dysfunction that could be occurring at the parenchymal (tissue) level. The nitrogen washout test allows us, in theory, to be able to detect those deficiencies or dysfunctions a little bit earlier and to perhaps make decisions based on those results.”

Managing patients with pulmonary dysfunction

Although we don’t currently have drugs that protect the lungs from specific cancer therapies, certain steps can be taken to mitigate the pulmotoxic effects of cancer treatment, says Dr. Rotz.

“Let’s say we have a Hodgkin’s lymphoma patient and we’re using bleomycin — we’ll usually get a pulmonary function test every couple of cycles to make sure that we’re not injuring their lungs, and if we are, we will either reduce the dose or drop that drug,” he says. “Another situation in bone marrow transplant patients, in particular, is something called total body irradiation (TBI) which means that all the tissues of the body get radiation. Our radiation oncologists here will typically block the lungs and reduce the dose of radiation that the lungs get, to prevent long-term toxicity.”

As far as the management of patients once pulmonary dysfunction develops is concerned, Cleveland Clinic pediatric pulmonologist Nathan Kraynack, MD, says that it depends on the two types of dysfunction that may develop. The first type is irritation and inflammation of the lungs in response to “acute insults” from chemotherapy or radiation. In terms of symptoms, this type of dysfunction mimics asthma and can cause airway reactivity.

“The patient’s airways get narrowed, and we can give them a medication like an aerosol or an inhaler that will cause the airways to open up and the function will get better,” he says. “That’s certainly a lot easier to treat, but it’s also less common. We tend to see it more during the acute phase of chemotherapy or radiation therapy, rather than as a longer or later outcome.”

The late-onset dysfunction is more related to radiation and chemotherapy with certain drugs, he explains. “The primary problem that we end up with what we call restrictive lung disease, or interstitial lung disease, or pulmonary fibrosis,” he says. “The lungs can’t expand or contract as well or as easily, so people become short of breath. It can be hard to exercise or walk around, work out, climb stairs, etc. That’s frequently a fair bit harder to treat because we don’t have a lot of medications specifically for those problems that can become somewhat debilitating.” In this group of patients, Dr. Kraynack says, the treatment is symptomatic and may consist of supplemental oxygen and cardiovascular fitness training.

“One of the things that’s probably most important is the diagnosis of these latter conditions,” he adds. At Cleveland Clinic, pulmonary function testing and imaging (CT scan) are routinely used to help determine if patients have developed pulmonary dysfunction abnormalities or pulmonary dysfunction, as a result of their cancer treatment.