Chemotherapy drugs can cause unintended damage to healthy tissues throughout the body. A serious side effect is chemotherapy-induced pulmonary toxicity (CIPT). This condition can range in severity from mild inflammation to severe, life-threatening respiratory failure. Understanding which drugs are most frequently implicated and the specific types of injury they cause is important for early symptom recognition and complication management.
Mechanisms and Types of Chemotherapy-Induced Lung Injury
Chemotherapy-induced lung injury encompasses several distinct pathological processes. Toxicity can develop rapidly (within days of treatment) or insidiously (months to years later). The damage often results from the drug directly injuring lung cells or by triggering an immune-mediated inflammatory response.
One frequently observed pattern is pneumonitis, inflammation of the lung tissue, typically affecting the interstitium. If left untreated, severe pneumonitis can lead to permanent structural changes.
Pulmonary fibrosis is a chronic injury characterized by the development of stiff, scar tissue within the lungs. This scarring reduces elasticity, making it difficult to fully expand and exchange oxygen efficiently. Fibrosis can be a late consequence of pneumonitis or develop independently.
Organizing pneumonia (OP) involves inflammation and excessive connective tissue growth within the small airways and air sacs. Another pattern is pulmonary edema, the accumulation of fluid in the lungs, often resulting from damage to leaky capillary blood vessels.
Key Chemotherapy Agents Associated with Pulmonary Toxicity
The risk of lung damage varies significantly among different chemotherapeutic agents. Bleomycin is the most recognized culprit, known for its high association with pulmonary fibrosis and interstitial pneumonitis. The drug causes damage through the generation of reactive oxygen species, and its toxicity is dose-dependent and exacerbated by high concentrations of oxygen.
Among the alkylating agents, Carmustine (BCNU) and Busulfan are frequently implicated. Carmustine is strongly associated with interstitial lung disease and fibrosis, with risk increasing with the cumulative dose. Busulfan, primarily used before bone marrow transplantation, can cause interstitial pneumonitis that may progress to pulmonary fibrosis, sometimes presenting years after treatment.
The antimetabolite Methotrexate commonly causes a hypersensitivity pneumonitis, thought to be an immune-mediated reaction. This toxicity can present acutely or subacutely. Similarly, Gemcitabine has been linked to pulmonary toxicity, including interstitial pneumonitis and, in some cases, acute respiratory distress syndrome (ARDS).
The Taxanes, such as Paclitaxel and Docetaxel, are associated with pulmonary complications. Paclitaxel can cause acute reactions like bronchospasm, while both taxanes have been linked to interstitial pneumonitis and organizing pneumonia. Newer targeted therapies, such as Trastuzumab Deruxtecan (Enhertu), have also shown a significant association with interstitial lung disease.
Recognizing Symptoms and Identifying Patient Risk Factors
The symptoms of chemotherapy-induced lung injury are often nonspecific, making them challenging to distinguish from infection or heart failure. The most common complaints are a persistent dry cough and shortness of breath (dyspnea), particularly with exertion. Patients may also experience a low-grade fever and fatigue.
Symptom onset varies widely, appearing hours after an infusion or many months after therapy completion. A professional evaluation is necessary because lung toxicity can be mistaken for cancer recurrence or a respiratory infection. Early identification and prompt communication with the care team are important.
Several factors increase a patient’s susceptibility to developing CIPT:
- Pre-existing lung conditions, such as COPD or other interstitial lung diseases.
- Advanced age (typically over 40 years).
- The overall amount of drug received, known as the cumulative dose, especially for agents like Bleomycin and Carmustine.
- Combining chemotherapy with other lung-damaging treatments, such as radiation therapy to the chest.
- The use of high concentrations of supplemental oxygen during or shortly after treatment with certain drugs, like Bleomycin.
Clinical Monitoring and Management of Lung Injury
Clinical teams employ various methods to monitor for potential lung injury, though no single test is perfectly predictive. Monitoring often includes Pulmonary Function Tests (PFTs), which measure lung capacity and efficiency. A decline in the diffusing capacity of the lung for carbon monoxide (DLCO) can be an early indicator of damage. Chest X-rays and High-Resolution Computed Tomography (HRCT) scans visualize the lungs for signs of inflammation or scarring.
The diagnosis of CIPT is often one of exclusion, requiring doctors to rule out other causes like infection, heart failure, or cancer progression. In some cases, a bronchoalveolar lavage (BAL) may be performed to collect fluid and check for inflammation. A definitive diagnosis usually requires a lung biopsy, which is not always feasible.
The cornerstone of management is the immediate discontinuation of the offending drug. For patients with mild symptoms, removing the drug may allow lung tissue to recover. For more severe cases, treatment involves high-dose corticosterids (such as prednisone) to reduce inflammation. Early detection and prompt initiation of steroid treatment improve outcomes.