Pulmonary Fungal Infections

Fungal infections continue to increase in incidence in many of our patient populations, including the ever-enlarging pool of immunocompromised individuals. Persons at risk include the traditional group of persons with human immunodeficiency virus (HIV) infection, individuals who have and are being treated for malignancy, or those who have received stem cell or solid organ transplantation. This pool also now includes those receiving prolonged immunosuppressive therapy with corticosteroids and newer agents, such as the tumor necrosis factor-α (TNF-α) inhibitors, given for an ever-widening array of diseases. Fungal infections (mycoses) are also a secondary effect of our technologies used to support the very ill in the intensive care unit (ICU), including our burn and trauma patients.

Opportunistic fungi that primarily infect the lungs chiefly include the Aspergillus species, but disease secondary to the rarer molds (e.g., the Zygomycetes, Fusarium, and Scedosporium) and yeasts (e.g., Trichosporon) appear to be increasing in incidence. As populations expand, infection and outbreaks in immune-competent hosts have also become more common (or better recognized). Urbanization of the US Southwest has produced increased cases of coccidioidomycosis. Recent outbreaks of histoplasmosis and cryptococcosis have also been described. Clinicians need to be able to recognize endemic fungal infections presenting outside of their endemic areas, in travelers and those who have relocated.

The pharmaceutical industry has risen to meet this challenge with the introduction of new antifungal agents, often with less toxicity and improved spectrums of activity. Unfortunately, no current antifungal, even amphotericin B, possesses a spectrum of activity that includes all the current and potential fungal pathogens.

Improvements in diagnostic technologies, including in radiographic imaging and new serological tests (e.g., the galactomannan antigen assay), have also come to the aid of the clinician. Unfortunately, the diagnosis of fungal infections still relies heavily on clinician suspicion in the proper setting, based on host risk factors, presentation, and exposures. Many of the mycoses have nonspecific presentations, and delays in diagnosis and treatment typically result in poorer outcomes. Awareness of risk factors and clinical presentations of the human mycoses may allow clinicians to develop an inclusive approach to their timely diagnosis.

This issue of Seminars in Respiratory and Critical Care Medicine is dedicated to review those fungi that cause pulmonary infections, in both immunocompromised and immunocompetent patients. Since the last issue of Seminars that focused on the pulmonary mycoses (2004) much has changed in our understanding of these diseases, their diagnosis, and their treatment. In that time period two additional echinocandins (micafungin, 2005; anidulafungin, 2006) and a second broad spectrum azole (posaconazole, 2006) have become available.

Updates on current understanding of the opportunistic fungal pathogens are provided in the first papers, beginning with reviews of aspergillosis by Drs. Thompson and Patterson, and of zygomycosis by Dr. Pyrgos and colleagues. These are followed by an update on the rare and emerging opportunistic fungal infections by Drs. Varkey and Perfect, and of Pneumocystis pneumonia by Dr. D'Avignon and colleagues. Drs. Jarvis and Harrison provide a state-of-the art review of cryptococcosis, a yeast that can infect both the immunosuppressed and the immune competent. This provides a transition to four excellent updates on the endemic mycoses: histoplasmosis by Dr. Hage and colleagues, coccidioidomycosis by Dr. Spinello and colleagues, blastomycosis by Dr. Bradsher, and paracoccidioidomycosis by Dr. Restrepo and colleagues. The final two papers of this issue update the reader on the current status of the newest groups of antifungals, the azoles and echinocandins. These are superbly reviewed by Drs. Zonios and Bennett, and Drs. Kauffman and Carver, respectively.

Fungal infections have pushed their way to the forefront of modern medicine over the past several decades. Their importance is unlikely to diminish sufficiently over the next few decades. Clinicians need to be aware of these potentially devastating infections and strive to build their skills in diagnosing and treating the human mycoses. I would like to thank all the authors who have contributed to this issue of Seminars in Respiratory and Critical Care Medicine dedicated to pulmonary fungal infections.