Chest
Volume 80, Issue 2, August 1981, Pages 220-225
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Review
Fungal Pneumonia (Part 4): Invasive Pulmonary Aspergillosis

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MYCOLOGY-EPIDEMIOLOGY

Aspergillus is a ubiquitous soil saprophyte, frequently isolated on settle plates on hospital wards where unfiltered outside air circulates through open windows.3 There is a significant decline in both settle plate Aspergillus counts and cases of nosocomial aspergillosis when mechanical ventilation air filtration systems are introduced in-hospital.4 This suggests that aspergillosis is acquired via airborne spore inhalation. In man aspergillosis most often is due to A fumigatus, A flavus, and A

PATHOGENESIS OF IPA

There have only been 15 documented cases of IPA in normal hosts.5, 6, 7 The vast majority of IPA cases occur in patients with hematologic malignancies,8, 9 especially during induction or maintenance chemotherapy for acute, nonlymphocytic leukemia. In addition, recipients of renal and cardiac transplants10, 11 are at increased risk for IPA, particularly during episodes of organ rejection, when immunosuppressive therapies are generally intensified. Occasionally, IPA has complicated such diseases

HISTOPATHOLOGY

The histopathology of human IPA has been elegantly delineated by Orr et al.13 On gross macroscopy, the typical early lesions are 1 to 3-cm nodules or target lesions composed of a central yellow-gray zone of tissue necrosis and a surrounding rim of hemorrhage, with a thrombosed artery at the edge of the lesion (Fig 2). These lesions arise via endobronchial hyphal proliferation followed by transbronchial invasion of subjacent pulmonary arterioles, with ischemic necrosis of small areas of the

EXTRAPULMONARY INVOLVEMENT IN IPA

In about 10 to 25 percent of patients with IPA, extrapulmonary dissemination is found at autopsy.8, 9 The organs most frequently involved are the gastrointestinal tract, brain, heart, liver, spleen, kidney, and thyroid.

CLINICAL FEATURES OF IPA

Physical findings in IPA are nonspecific, consisting generally of fever and pulmonary rales or rhonchi. Although extrapulmonary aspergillus dissemination occurs in only about 25 percent of patients with IPA, extrapulmonary Aspergillus dissemination may present dramatic clinical syndromes and should be carefully examined for clues to underlying IPA. Mucosal ulceration secondary to hyphal invasion may occur anywhere in the alimentary tract and present as major gastrointestinal hemorrhage.8 In the

DEFINITIVE DIAGNOSIS

Aspergillus has been recovered from sputum in <10 percent of patients with proved IPA, even when specifically sought in perspective studies of deep mycoses in leukemic patients.8, 9, 19 As noted previously, isolation of Aspergillus from surveillance nasal cultures of immunocompromised patients is significantly correlated with concurrent or subsequent IPA; negative nasal cultures, however, do not preclude the diagnosis of IPA.

To make the definitive diagnosis of IPA, parenchymal invasion of lung

SEROLOGIC STUDIES IN ASPERGILLOSIS

Since IPA (as well as disseminated aspergillosis) is a difficult diagnosis to establish without tissue biopsy, and empiric antifungal chemotherapy may be unwarranted because of potentially severe drug toxicities, much investigation into antibody sero-diagnosis of aspergillosis has been performed. The standard Aspergillus precipitin assay (by gel immunodiffusion), often positive in high titers in allergic bronchopulmonary aspergillosis and pulmonary aspergillomas, in IPA is generally

THERAPY FOR IPA

Parenteral antifungal therapy is the cornerstone of treatment of IPA. Unfortunately, there is a wide strain-to-strain variability in terms of in vitro sensitivity to amphotericin B; also, there is to date27 no standard accepted method for sensitivity testing of this fungus. In general, it appears that most A fumigatus strains have minimal fungistatic concentrations (MFCs) to amphotericin B within readily achievable serum levels of the drug (0.5 to 1.5 µg/ml); however, A flavus strains tend to

PROGNOSIS OF IPA

As in most deep mycoses in immunocompromised hosts, the outcome of IPA is directly correlated with early diagnosis and therapy, induction of remission of the underlying disease, and with reversal of chemotherapy-induced marrow suppression. Of note, the prognosis of IPA in patients with renal and cardiac transplantation appears more favorable than in patients with underlying leukemia. This may relate to the ability to adjust steroid-cytotoxic drug regimens more freely in organ transplantation

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Parts 1-3 of this series have appeared in the May, June and July, 1981 issues of Chest.

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