Thoracic fungal infections have a complex and variable presentation, ranging from benign self-limited processes, which spontaneously resolve, to severe life-threatening infections associated with disabling morbidity and high mortality. Persistent fungal infections in normal individuals may either resolve without producing symptoms, or worsen leading to severe complications of hemoptysis, mediastinal fibrosis, empyema, and meningitis. Immune-compromised hosts demonstrate greater susceptibility to fungi than normal individuals and have more severe outcomes including vascular invasion, septicemia with fungal dissemination, organ infarction, and death. Adding to this complexity, the epidemiology of fungal disease is constantly changing as species emerge or relocate or increase in virulence. Early intervention can improve survival and in some cases obviate the necessity of surgery. It is critical therefore to recognize the clinical manifestations of thoracic fungal infection early in its clinical course. Fortunately, recent advances in knowledge concerning fungal biology including the functional genome, the structure of the cell wall and membrane, and the use of molecular and epidemiologic techniques have led to rapid identification of pathogens and the institution of effective, less toxic antifungal agents.¹

Fungi that are implicated in pulmonary pathology consist primarily of dimorphic organisms. They begin as airborne spores and later convert to yeast forms after entering the pulmonary system. The lung is a common portal of entry and represents the primary portal and site of infection in both immune-competent and immune-suppressed individuals. Opportunistic hospital-acquired infections generally arise in ICU patients with indwelling vascular or catheter instrumentation or following solid organ or hematopoietic stem cell transplantation.² Occasionally, infection may occur by nonpulmonary portals such as cutaneous inoculation, for example, sporotrichosis. Human-to-human transmission is extremely rare and primarily occurs in the organ transplant population.

Opportunistic fungal organisms may also persist in a chronic latent state, allowing possible future activation and infection if there is compromise of the immune system. As humans are often colonized with fungal organisms, the distinction between colonization and infection may be diagnostically challenging, and outcomes from fungal infection may vary depending on the degree and extent of fungal invasion based on a balance of factors between the host and organism.

The presence of endemic fungal infection in at-risk individuals may initially be suspected by a history of travel to niche areas of fungal prevalence (Fig. 103-1).³ However, with current global travel opportunities, latent fungal reactivation can occur following distant past travel which may require extensive individual interrogation as to possible fungal exposure from prevalent areas. It is also important to remain vigilant as fungal infections can resemble or coexist with malignant disease.

The epidemiology of thoracic fungal infections is constantly changing. The pace of this change has accelerated in recent decades, and four factors have been identified to account for this rapid change: an increasingly mobile world population, the aging population in Western countries, climatic environmental changes, and increased immune suppression for organ transplantation. The recognition and treatment of fungal infection is also dependent on microbiologic reclassification patterns. Actinomycosis and nocardia, for example, are no longer classified as fungal infections, since the source of infection recently has been identified as bacterial.⁴ Emerging and opportunistic infections undergo epidemiologic changes associated with climactic changes which alter current endemic fungal niches allowing for the emergence of new pathogens. In addition, alterations in immune pharmacologic management with new biologic immunosuppressant agents (e.g., TNF-alpha inhibitors), potent transplant rejection drugs, or chronic steroid use for chronic pulmonary conditions influence host predisposition for fungal infections.⁴

Thoracic fungal infections are categorized by host factors (immune competence and host defenses) or by invading organisms which are based on geography and virulence factors. Host defense categories include the following subpopulations: immune-competent or immune-deficient individuals with or without defective pulmonary defenses. Fungal invasion factors involve endemic versus opportunistic fungal organisms. Opportunistic fungi serve as common pathogens primarily for immune-suppressed individuals who also remain susceptible to endemic fungi. These individuals are additionally at risk of infection by saprophytic fungi (i.e., fungi that grow on dead organic matter) and emerging (mostly opportunistic) fungi.

Individuals presenting with clinical disease due to fungal infection are categorized by their immune status: immune-competent versus immune-suppressed. The latter group is comprised of transplant recipients, patients receiving biologic immunosuppressive agents, and patients with malignant and/or hematologic conditions or acute debilitating injuries which suppress the individual’s immune state. Most fungal infections that afflict immune-suppressed hospitalized patients occur in the ICU setting or in the immediate post-transplant recipient. Therefore, early determination of the patient’s immune status will help to establish the individual’s exposure risk for well-defined geographically prevalent areas of fungal infection (see Fig. 103-1).³

Radiography has an important role in diagnosing fungal disease since the radiographic abnormalities observed with fungal infection overlap with the radiographic signs of thoracic malignancy. For example, both entities may exhibit signs of patchy parenchymal infiltrates, pulmonary nodules, consolidation, cavitation, and pleural effusion. In addition, patients with endemic fungal disease may have unilateral or bilateral mediastinal adenopathy. The presence of a halo or a reversed halo sign on a lung CT, often seen in thoracic malignancy, is also a common sign of mucormycosis and may suggest fungal parenchymal disease (Fig. 103-2). Chest CT along with a heightened index of clinical suspicion has a prominent role in the diagnosis and separation of fungal infections. Marom and Kontoyiannis⁵ demonstrated a survival advantage when early CT was performed in immune-compromised patients with neutropenic fever.

A fungal infection may also be multicentric, having the appearance of a metastatic process. For example, a case of disseminated aspergillosis, shown in Figure 103-3, was initially mistaken for a metastatic cancer. An incidental pulmonary nodule arising in a patient who resides in or has recently traveled to a niche area of endemic fungal infection needs to be differentiated from a solitary pulmonary malignant nodule as shown in Figure 103-4.

Special consideration for rapid diagnosis of fungal infections is given to immune-suppressed individuals who are predisposed to opportunistic infection. Moreover, there are clear differences in disease severity and survival between groups of transplant recipients, for example, solid organ transplant recipients (SOT) versus hematologic stem cell transplant (HSCT) recipients, with the latter exhibiting greater susceptibility and mortality to fungal infections.⁶ Subgroup differences also may be found within these subpopulations.

Although surgical therapy for fungal lung disease is uncommon, given the development of effective antimicrobial agents, the thoracic surgeon may be called upon to perform diagnostic lung biopsies, and occasionally for the primary treatment of complications of fungal infections (see Table 103-1).⁷