Pulmonary Complications of Cancer

Original Editor - Donald John Auson Top Contributors - Donald John Auson and Kim Jackson

Infectious Complications

Cancer patients are susceptible to infection, particularly those undergoing chemotherapy and radiation therapy. Aside from that, there are a variety of factors that predisposes the cancer patient to infection such as immune deficiencies, organ dysfunction, concurrent illness and past infections, nutritional status, psychological stress, surgery and diagnostic and invasive procedures.

Bacterial Infection

Bacterial infection in cancer patients present in the form of pneumonia. The severity of bacterial pneumonia depends on the underlying immunologic defect, the duration of the immunocompromised state, whether the infection is community acquired or hospital acquired and the pathogen involved.

Common bacterial pathogens:

• Streptococcus pneumoniae
• Haemophilus influenzae
• Pseudomonas aeruginosa
• Escherichia coli
• Klebsiella species
• Legionella pneumophila
• Mycoplasma pneumoniae
• Nocardia and Actinomyces species
• Moraxella catarrhalis

Viral Infection

Viruses that causes pneumonia in immunocompromised cancer patients include:

• Cytomegalovirus
• Varicella-zoster
• Herpes simplex
• Respiratory syncytial virus
• Adenovirus
• Influenza virus

Fungal Infection

Pneumocystis Jirovecii Pneumonia- one of the most common opportunistic fungal infection in immuno-compromised conditions such as haematological malignancy, congenital immunodeficiency, organ transplantation, immunosuppressive therapy, under medication and predominantly in Human Immunodeficiency Virus (HIV).

Other common fungal pathogens include:

• Aspergillus species
• Mucor species
• Candida species
• Cryptococcus neoformans
• Histoplasma capsulatum
• Coccidioides immitis
• Blastomyces dermatitides

Non-Infectious Complications

Cancer patients can suffer from pulmonary complications not caused by infections. these complications can be result of primary malignancy, metastasis or treatment.

Metastatic Disease

Metastatic disease pertains to the complication of cancer wherein the cancer cells have spread to either a distant site or an adjacent structure. Metastasis to the lungs can happen through hematogenous, lymphatic or direct invasion. The lungs are the second most common site of metastasis.

Pulmonary metastasis can occur as:

• Nodular
• Lymphangitic carcinomatosis- interstitial form of pulmonary metastasis and can occur unilaterally or bilaterally. it can present with persistent dry cough and dyspnea.

Symptoms include:

• Cough
• Dyspnea
• Pleural effusion
• Hemoptysis
• Fatigue
• Nausea
• Anorexia
• Weight loss

Pulmonary effusion is a common extrapulmonary manifestation of metastatic disease and can affect lung volumes.

Obstructive Lung Disease

Obstructive lung disease can be caused by several factors such as primary lung cancer, metastasis to the lungs or as an adverse reaction to medications or treatment. some of the mechanisms are:

• Acute bronchospastic reaction- secondary to administration of medications (gemcitabine)
• Airway tumor- can occlude airway and manifest as obstructive lung disease
• Pre-existing COPD- can be excacerbated and is also a risk factor for the development of radiation and chemotherapy pneumonitis

Restrictive Lung Disease

Restrictive lung disease can be a result of:

• Primary malignancy
• Malignant pleural effusion
• Kyphoscoliosis- can be a result of metastatic lesions to the thoracic spine or osteoporosis from treatment of the primary malignancy
• Neuromuscular disease complications- usually associated with Lambert-Eaton Myesthenic Syndrome, which is usually associated with small cell lung cancer ~60%.
• Phrenic nerve paralysis- can be a result of extrathoracic tumors (rare), primary lung tumor (more frequent), mediastinal tumor, surgery (lung or radical neck dissection), toxicity from chemotheraphy (5-fluorouracil or doxorubicin).
• Pulmonary fibrosis- from radiation and chemotherapy

Restrictive lung disease from the said conditions can produce symptoms such as dyspnea and can lead to respiratory failure.

Radiation Therapy Complications

See Radiation Side Effects and Syndromes for additional reading.

Radiation Pneumonitis

Radiation pneumonitis is seen in patients receiving external beam radiation in the chest for lung cancer or other tumors. It is dose-related; higher doses leads to more severe complications. Mild radiation pneumonitis can be self-limited and resolves with the use of corticosteroids. Severe radiation pneumonitis can result to fibrosis and restrictive lung disease leading. It also has a high mortality rate and low survival rate.

Risk Factors for the development of radiation pneumonitis include:

• Old age
• Gender (Female)
• Chemotherapy (Cisplatin, Paclitaxel)
• History of smoking
• Tumor location
• Low pulmonary function status

Chemotherapy Complications

Certain chemotherapeutic agents are known to induce lung damage and cause pulmonary complications. Some of these are:

• Bleomycin
• Mitomycin-C
• Actinomycin-D
• Busulfan
• Cyclophosphamide
• Methotrexate
• Cytosine Arabinoside (Ara-C)
• Gemcitabine
• Fludarabine
• Carmustine (BCNU)

Pulmonary Vascular Disease

Pulmonary embolism is also seen in cancer patients and occurs in two forms:

• Thromboembolism- due to hypercoagulabity of the blood
• Tumor emboli- due to microemboli involving small arteries, arterioles and capillaries

Increased risk of pulmonary thromboembolism with:

• Pancreatic cancer
• Lymphoma
• Malignant brain tumors
• Liver cancer
• Leukemia
• Colorectal cancer
• Other digestive system cancer
• Patients receiving cytotoxic chemotherapy
• Tamoxifen
• Central venous catheters
• History of thromboembolism
• Surgical procedures

Drug Toxicities

Certain drugs have been shown to increase the risk for the development of pulmonary complications such as respiratory failure. This include tyrosine kinase inhibitors, mTOR kinase inhibitors, monoclonal antibody, taxanes.  A study showed that exposure to one of more of these medications was a significant risk factor in the development of respiratory failure.

Diagnosis

Diagnostic Imaging usually used to diagnose and assess cancer patients of their pulmonary complications include:

• Chest Radiographic Imaging
• High- Resolution CT Scan
• PET Scan
• Diagnostic bronchoscopy

Rehabilitation Treatment

Patients with pulmonary complications can undergo pulmonary rehabilitation. Chest physiotherapy techniques can be done to alleviate symptoms and improve respiration. Some chest physiotherapy techniques that can be done are:

• Percussions
• Vibrations
• Postural drainage
• Mobilization of patient
• Deep breathing exercises
• Segmental breathing exercises
• Coughing exercises

Considerations

Precautions must be made especially when treating patients with attachments, such as drains, as well as those with recent surgery to the chest. Probable osteoporosis, bony metastasis and primary malignancy over the chest area must be ruled out before performing percussions. If percussion is contraindicated to the case of the patient, other techniques can be applied such as vibrations, postural drainage, deep breathing exercises, and coughing exercises.