Pulmonary infections are the most common, and the most deadly, infections in patients with immune systems that have been altered by disease, disease treatment, or immune modulation.

“Most of our patients walk out of the hospital unless they develop pneumonia,” said Scott E. Evans, MD, FCCP, Professor and Chair ad interim of Pulmonary Medicine at the University of Texas MD Anderson Cancer Center. “Pneumonia not only threatens life but also threatens the use of life-saving cancer therapies.”

Dr. Evans discussed the latest approaches to pulmonary infections in cancer patients during Approach to the Management of Pulmonary Infections in Immunocompromised Patients on Wednesday. Pneumonia is the leading hazard for death during induction therapy for cancer and the leading cause of death following hematopoietic stem cell transplantation. About 10% of admissions to MD Anderson relate to pneumonia, he said, and about 32% of leukemia patients are either admitted with pneumonia (12%) or develop pneumonia within 28 days after admission (20%).

The risk of pulmonary infection is related to the depth and duration of neutropenia, whether caused by cancer or treatment. Cancer and its treatments cause both quantitative and qualitative defects in the immune system, increasing the risk for opportunistic infection by bacteria, viruses, fungi, mycobacteria, and multiple atypical organisms. Individuals with cancer may also have genetic polymorphisms leading to defects in innate immune pathogen surveillance.

“Identifying pathogens is extremely important,” Dr. Evans said. “Early bronchoscopy is associated with declines in both early and late mortality. And you can’t talk about pneumonia in 2021 without talking about COVID.”

Cancer patients with COVID-19 tend to have more severe outcomes, he said, and may have inadequate response to vaccination. Prompt treatment is essential.

HIV infection also predisposes patients to opportunistic pulmonary infections, said Kristina Crothers, MD, Professor of Pulmonary, Critical Care, and Sleep Medicine at the University of Washington. Differential diagnosis for fungal, viral, bacterial, and mycobacterial pulmonary infiltrates is largely driven by the patient’s history, CD4 cell count, and chest imaging patterns.

Not all individuals living with HIV know their status, Dr. Crothers noted. HIV infection increases the risk of pulmonary infection regardless of CD4 cell count as well as non-Hodgkin lymphoma and noninfectious complications such as COPD, ARDS, and lung cancer.

History includes the individual’s HIV risk status and potential exposures, habits, comorbidities, travel and residence locations, use of antiretroviral therapy, HIV prophylaxis, lab results, and signs of extrapulmonary disease. A higher CD4 cell count is associated with bacterial pneumonia, community-acquired pneumonia, and reactivation of latent tuberculosis (TB). As the CD4 count declines, the risk shifts to bacteremia, primary TB, and atypical TB.

“You need a definitive diagnosis to target therapy,” Dr. Crothers said. “And there may be multiple infectious processes in play in 10% to 20% of patients. If a patient has had an empiric diagnosis, do a bronchoscopy to obtain a definitive diagnosis if it was not initially performed. Evaluation and management should always be tailored to HIV.”

Evaluation and management should also be tailored in patients on immune modulators and biologics.

“Pulmonary infections are the most common infection in immune-altered populations,” said Kelly M. Pennington, MD, Assistant Professor of Medicine at Mayo Clinic. “Immune modulators and biologics alter the immune system. Our patients commonly have multiple defects, including T cell deficiencies, B cell deficiencies, antibody depletion, and cytokine/chemokine inhibition. The differential diagnosis is based in large part on the type and degree of immune suppression.”

The key challenge is balancing the patient’s continuing need for immune suppression with the risk of infection. If possible, immune suppression should be decreased or stopped entirely.

Immune reconstitution is likely to occur within 1 week to several months after stopping immune suppression, Dr. Pennington said, which may result in graft rejection for transplant recipients. Stopping TNF-alpha inhibition typically results in immune reconstitution, which can help combat infection.

“At least temporary discontinuation of the biologic is recommended in most cases,” she said, “and can likely be restarted about 12 months after the infection is cleared.”

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