The respiratory system consists of the lungs and various structures that allow air to enter the lungs. Most air enters the body through the nose. As it passes through the nose and nasal cavity, it is warmed, moistened, and filtered.

The pharynx (throat) is the area where the passages from the nose and mouth come together. This area leads to the esophagus (a tube to the stomach) and the larynx (which contains the vocal cords). When you swallow, a flap of tissue called the epiglottis covers the larynx to prevent food from getting into the lungs.

The larynx leads to the trachea—the main passageway to the lungs. The lungs are two organs that surround the heart and fill up most of the space in the ribcage. The lungs are divided into sections called lobes. The left lung is slightly smaller and has fewer lobes than the right lung.

The trachea branches into two tubes called bronchi, which divide into smaller and smaller tubes called bronchioles. These tiny tubes end in air sacs called alveoli. The air you breathe carries oxygen that moves across the air sac walls into blood in capillaries in exchange for carbon dioxide. This carbon dioxide exits the body when you exhale. Figure 13-1 shows the respiratory system.

Figure 13-1. The respiratory system

Organ damage

A healthy adult’s lungs can hold up to 6 liters of air. During quiet breathing, only about half a liter of air is exchanged. Lung damage from treatment can reduce your lungs’ ability to expand and thus the amount of air they can hold (called restrictive lung disease). Lung growth and chest size can be affected in some survivors who were treated at a very young age. Treatment can also cause scarring in the lungs (called pulmonary fibrosis), which reduces the exchange of oxygen for carbon dioxide in the air sacs. Obstructive lung disease (narrowing of the airways) can also occur. A combination of these problems can develop after treatment for childhood cancer.

Lungs can be damaged by both radiation and chemotherapy. Certain types of chemotherapy drugs can intensify the damaging effects of radiation. Lung damage is common in survivors of transplants who develop chronic graft-versus-host disease. In addition, the parts of the body that house the lungs and help them expand and contract can be damaged by radiation. A study of more than 500 children and teens who were seen in a comprehensive follow-up clinic found that almost 13 percent of the survivors had some type of pulmonary late effect, although the vast majority of the problems were mild or moderate. ¹

Radiation

As shown in Figure 13-1 , the lungs are in the chest. If the chest is irradiated during childhood or adolescence, the growth of bones in the area (spine, ribs, and sternum), as well as growth of muscles in the chest wall, can be slowed or stopped. Survivors who had mantle radiation, for example, often have smaller chests than do those treated only with chemotherapy. This reduces the area in which the lungs can expand and contract. Survivors who received radiation to one side of the body (e.g., those treated for Wilms tumor) can develop curvature of the spine (scoliosis) that can also affect the space occupied by the lungs. The incidence of scoliosis has been greatly reduced because recent protocols include the entire backbone (vertebral body) in the field of radiation, which results in a symmetrical reduction of growth.

A small number of children and adolescents who received high-dose radiation to the lung area develop radiation pneumonitis during treatment. They may recover from the pneumonitis on their own, or they may require treatment with corticosteroids for a period of time. If the pneumonitis worsens, it can result in pulmonary fibrosis. Pulmonary fibrosis occurs when lung tissue becomes scarred and loses its elasticity. The amount of air the lungs can hold (lung volume) is then reduced and the amount of gases exchanged (oxygen and carbon dioxide) is lowered.

Fibrosis can develop months to years after treatment, and it can either stabilize or continue to progress. Symptoms depend on the amount of lung involved. Fibrosis usually occurs in those who had tumors in the chest or lungs (e.g., Hodgkin lymphoma, Ewing sarcoma, primitive neuroectodermal tumors, or lung metastases from cancers in other locations) and were treated with radiation. It can also occur in survivors who received total body radiation (TBI) as part of their preparation for stem cell transplantation.

The risk of developing pulmonary fibrosis or other pulmonary late effects is highest in survivors who received:

• A total dose of 1500 centigray (cGy) or higher of radiation to the lungs.

• A single dose of 600 cGy or higher to the lungs.

• TBI of 1200 cGy. ²

• TBI combined with any additional chest irradiation.

• Any radiation to the chest combined with bleomycin, busulfan, BCNU, CCNU, doxorubicin, or dactinomycin. ³

Survivors who were treated in the 1960s and 1970s with very high doses of radiation to the lungs (for example, mantle radiation for Hodgkin lymphoma) can have very severe and sometimes life-threatening fibrosis. Children or teens who get relatively low doses of radiation—less than 1500 centigray (cGy) given in fractions—may develop mild or moderate restrictive pulmonary disease, but it usually does not affect daily life activities. Most of these survivors can participate in sports and lead active lives.

In early bone marrow transplants (BMTs), children were sometimes given 1000–1200 cGy of radiation in a single dose. These survivors have an increased risk of moderate to severe fibrosis. Currently, fractionated (getting smaller doses more frequently) radiation is sometimes used prior to stem cell transplants or for tumors requiring radiation to lung areas. Lower doses of radiation given daily do not usually cause lung problems that affect the ability to lead an active life.

In one study it was noted that survivors of acute lymphoblastic leukemia (ALL), who were treated in the 70s and early 80s move a lower volume of air and have a decreased ability to exercise. Although not well understood, these late effects seem to be associated with lung infection during treatment, craniospinal radiation, and the chemotherapy drug cyclophosphamide. ⁴

Chemotherapy

Pulmonary fibrosis can also be caused by some chemotherapy drugs, such as bleomycin, busulfan, carmustine (BCNU), and lomustine (CCNU). Survivors treated with these drugs can develop problems during treatment or many years after treatment ends.

Survivors most at risk for pulmonary fibrosis are those who had doses of:

• 600 mg/m ² or higher of CCNU or BCNU. ⁵

• 500 mg or more of busulfan. ⁶

• 400 units/m ² or more of bleomycin. ⁷

Young age is also an additional risk factor for lung complications after receiving these chemotherapy drugs.

Lung toxicity may increase if cyclophosphamide or radiation was given at the same time as bleomycin. An additional concern for those who received bleomycin is a life-long risk for respiratory problems during and after receiving general anesthesia. ⁸ Oxygen and fluids should be monitored closely by your anesthesiologist, and you should not be given high concentrations of supplemental oxygen. Too much oxygen to someone who was previously treated with bleomycin can cause edema (fluid buildup) in the lungs. This complication can be avoided with planning and communication ahead of time.

Some parents report that their children developed asthma after treatment for childhood cancer. There is currently no research to support the theory that asthma is a late effect of treatment. There also has been an increasing incidence of asthma in the general population during the last 20 years. However, regardless of the cause, treatment is the same.

Signs and symptoms

Signs and symptoms of pneumonitis are as follows:

• Cough

• Fever

• Shortness of breath

• Rapid heartbeat

• Painful breathing

Symptoms of lung fibrosis include the following:

• Chronic cough (with or without fever)

• Shortness of breath

• Painful breathing

• Tiring easily during exercise

• Increasing difficulty with activities of daily life

Screening and detection

Part of comprehensive follow-up care should be a discussion about any risks to your lungs from treatment. If you are at risk, you should tell your healthcare provider how you breathe at rest and while exercising.

If you took bleomycin, BCNU, CCNU, or busulfan; had chest, spine, or flank irradiation; or have any symptoms of fibrosis, you should have the following tests performed:

• Pulmonary function tests (PFTs)

• Chest x-ray

• Evaluation of chest wall growth

• Evaluation for scoliosis (curvature of the spine)

• Evaluation of trunk length and size of chest cavity

Current guidelines generally recommend monitoring during therapy, at the and at completion of therapy. If you have symptoms, or if the tests show abnormalities, you will be monitored periodically.

Most follow-up clinics do PFTs before and after administration of bronchodilators (medications given through an inhaler). If the chest x-ray or PFTs suggest fibrosis, a referral to a pulmonologist is usually made for further evaluation. Some treatment protocols include specific schedules for monitoring.

If you received bleomycin, you should have PFTs done before having general anesthesia. Make sure you tell the anesthesiologist about your cancer history, bleomycin treatment, and results of your PFTs.

Medical management

Some children and teens with pulmonary fibrosis respond well to bronchodilating medicines. If you have pulmonary fibrosis, you should maintain as active a lifestyle as possible to maximize your lung function. You should also be seen periodically by a pulmonologist.

All survivors who had pulmonary radiation or potentially lung-toxic chemotherapy should get a yearly influenza vaccine. They should also receive pneumococcal vaccine once they are off therapy and their immune system is functional—about 6 months to 1 year out from most conventional therapy, and later for those who had a stem cell transplant. This vaccine will not prevent all types of pneumonia, because many types are due to organisms not covered by these vaccines. An ounce of prevention—avoiding close contact with people who have a respiratory infection—is wise.

Careful management of upper respiratory infections is necessary if you have pulmonary fibrosis. If there are increasing signs of pulmonary distress, such as breathing difficulties, increased sputum production, or increased shortness of breath, call your healthcare provider.

Survivors who had chemotherapy and/or radiation that can affect the lungs should have PFTs done and possibly see a pulmonary specialist prior to SCUBA diving.

You should not smoke cigarettes, marijuana, or anything else if you are a cancer survivor. This is especially important if you had any treatment that is potentially toxic to your lungs. Your medical management should include a frank discussion about the dangers of smoking. To protect your lungs, try to avoid fumes from chemicals, solvents, and paints and observe respiratory safety precautions in the workplace. For more information about keeping your lungs healthy after treatment for childhood cancer, visit www.survivorshipguidelines.org/pdf/PulmonaryHealth.pdf .