Pneumonia

A significant number of infections in cancer patients are due to pneumonia. For example, 25% of documented infections in patients with nonlymphocytic leukemia are caused by pneumonia. Also, 50% of allogeneic HCT recipients develop pneumonia.

Etiology and Risk Factors

Some of the risk factors that predispose cancer patients to pneumonia are cellular and humoral immune deficiencies, neutropenia, impaired tracheobronchial clearance, use of antibiotics and steroids, and surgery.

Etiologic agents

The etiologic agents responsible for pneumonia in the cancer patient run the gamut of most bacterial, fungal, and viral organisms (Figure 4).

Noninfectious processes mimicking pneumonia

Numerous noninfectious processes can mimic pneumonia in cancer patients. They include congestive heart failure, aseptic emboli, metastatic disease, adult respiratory distress syndrome, diffuse alveolar hemorrhage, a peri-engraftment infiltrate, radiation injury, hypersensitivity disorders and reactions, and trauma.

Pinpointing the pathogen

Certain characteristics of each cancer patient may help predict the specific etiologic agent.

FIGURE 4Pneumonia in a neutropenic/ immunocompromised host.

FIGURE 5Timing of infectious syndromes after bone marrow transplantation.

Type of immunosuppression. One characteristic that is particularly useful is the type of immunosuppression that the patient is experiencing. This depends on the type of neoplastic disease (eg, lymphoma, leukemia) and, more importantly, the type of therapy (eg, chemotherapy, radiation therapy, allogeneic HCT). For example, certain gram-negative and gram-positive bacteria are more prevalent during neutropenia, whereas other bacteria (S pneumoniae, Haemophilus influenzae) are more common with a humoral immune deficiency, such as occurs after splenectomy.

Timing of pneumonia. Another important characteristic is the timing of the pneumonia; in other words, the phase of the immunosuppression can help predict the etiology. For example, an interstitial pneumonia occurring during the first 30 days after allogeneic HCT would not be expected to be due to CMV (Figure 5).

Other factors

Finally, other factors such as the duration of neutropenia, prior antimicrobial therapy, other agents (such as steroids and alemtuzumab) used, and the specific local microbiota help in prediction. For example, if an allogeneic HCT patient receiving steroids for graft-versus-host disease (GVHD) develops nodular infiltrates after weeks of treatment with broad-spectrum antibacterial antibiotics, an Aspergillus species would be highly suspected.

Signs and Symptoms

Although a productive cough is almost always present in a normal host with pneumonia, often neither a cough nor sputum is seen in an immunocompromised cancer patient with such an infection.

Fever, however, is almost invariably present in the cancer patient with pneumonia and, by itself, should prompt a workup for pneumonia.

Other possible symptoms include shortness of breath, pleuritic chest pain, and hemoptysis.

Diagnosis

Identification of the etiologic agent for pneumonia in immunocompromised host is often difficult. Also, pneumonia can progress rapidly, resulting in high morbidity and mortality. Therefore, aggressive workup and treatment are warranted by the managing clinician.

The diagnosis of pneumonia is most commonly made by a simple chest radiograph. However, there are occasions when a pulmonary infiltrate or small nodular lesion is seen only on a CT scan.

Etiologic diagnosis

An etiologic diagnosis is made by the following procedures: sputum (expectorated or induced) testing, bronchoscopy with bronchoalveolar lavage and transbronchial biopsy, transthoracic needle biopsy/aspiration, and thoracoscopic and open lung biopsy.

Sputum. An adequate sputum specimen is difficult to obtain from cancer patients, especially during neutropenia.

Bronchoscopy with bronchoalveolar lavage. Bronchoscopy with bronchoalveolar lavage is a much more sensitive technique than sputum analysis but may miss the organism when the pulmonary disease is peripheral or nodular.

Transthoracic needle biopsy/aspiration. Transthoracic needle biopsy/aspiration under CT guidance may be helpful if the lesion is distal but may be contraindicated in a severely thrombocytopenic patient. This procedure is indicated when there is a focal/nodular lesion in the periphery.

FIGURE 6Diagnostic approach to pneumonia.

Open lung biopsy. Open lung biopsy is the most definitive diagnostic procedure but also the most invasive. It is still not clear whether the information obtained by open biopsy improves overall survival. The less invasive thoracoscopic lung biopsy is becoming more popular than open lung biopsy.

Smears and cultures. Both fluid and tissue specimens should be sent for bacterial smears (including acid-fast bacilli and modified acid-fast bacilli) and cultures (including those for anaerobes, acid-fast bacilli, and Legionella organisms), fungal smears (potassium hydroxide) and cultures, direct fluorescent antibody test for viruses, cytology (for viral inclusions and silver stains for fungi and P jirovecii), histopathology, and Aspergillus PCR and Mucor PCR on bronchoalveolar lavage.

Diagnostic approach. The diagnostic approach to pneumonia is depicted in Figure 6 using risk stratification (low vs high risk). Patients with suspected pneumonia should undergo an aggressive etiologic workup along with broad-spectrum empiric antimicrobial treatment. Preemptive antifungal therapy should be based on risk. Treatment is then tailored accordingly.

Treatment

The therapeutic approach to pneumonia in the cancer patient should take into consideration the category of immunosuppression (neoplastic disease and immunosuppressive therapy), as well as the timing of onset and the pattern of the pneumonia.

Empiric antibiotic therapy

In neutropenic patients experiencing their first episode of fever and localized pulmonary infiltrates, one can justify initiating empiric therapy similar to that used for febrile, neutropenic patients (see previous discussion), because the majority of pneumonias in this setting are caused by gram-negative bacteria. However, in other situations—such as pneumonia that has a later onset, develops after empiric antibiotics have been initiated, is more aggressive or severe, occurs in a more severely compromised host (eg, a patient who has had allogeneic HCT), or is characterized by a diffuse or interstitial infiltrate—one should proceed to immediate bronchoscopy with bronchoalveolar lavage (and possibly transbronchial biopsy).

Additions to empiric therapy

If no diagnosis is forthcoming after bronchoscopy and bronchoalveolar lavage, additions to empiric therapy should be made.

Anaerobic, gram-positive, and Legionella coverage. Certainly, anaerobic coverage should be considered, as well as gram-positive coverage. Legionella coverage should be added, especially if warranted by the epidemiologic setting.

Antifungal and antituberculous therapy. Finally, antifungal therapy should be initiated if there is no response to antibacterial therapy and especially if there are nodular or cavitary lesions. In addition, if such lesions are present and/or the epidemiologic setting is compatible, antituberculous therapy should be added.

FIGURE 7Antimicrobial treatment approach.

Further diagnostic procedures. If bronchoscopy with bronchoalveolar lavage does not reveal an etiology and the pneumonia is progressing despite empiric therapy, consideration should be given to transthoracic needle biopsy/aspiration and open lung biopsy. As mentioned previously, if there is a peripheral, focal lesion, transthoracic needle biopsy/aspiration can be attempted.

The ultimate diagnostic procedure is open biopsy, but because its contribution to increased survival is unknown, the decision to proceed with this most invasive procedure must be undertaken carefully.

Specific antimicrobial therapy

A specific treatment approach is suggested in Figure 7 based on whether treatment is empiric or targeted.

Prevention

Methods to prevent pulmonary infections fall into the following categories: colonization prevention, antimicrobial prophylaxis (and preemptive treatment), vaccination, and immunomodulation.

The simplest method of colonization prevention is hand-washing.

Other colonization-prevention methods, such as protective environments, are discussed in the previous section.

With regard to pulmonary pathogens, HEPA-filtered rooms can eliminate Aspergillus spores from the immediate environment. Water supplies can be checked for Legionella contamination and/or adequate disinfection maintained (eg, chlorination, copper/silver ionization, temperature [60°C]).

Antimicrobial prophylaxis is discussed in the previous section.

The influenza and pneumococcal (killed) vaccines should be administered to cancer patients.

Immunomodulators, such as granulocyte colony-stimulating factor (G-CSF, filgrastim) and granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim), may help to reduce infection risk by decreasing the duration of neutropenia.