Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

doi:10.1016/j.ejrad.2005.01.001

European Journal of Radiology

Volume 55, Issue 3, September 2005, Pages 437-444

https://doi.org/10.1016/j.ejrad.2005.01.001 Get rights and content

Abstract

Purpose:

To assess early high-resolution computer tomographic (CT) signs of invasive pulmonary aspergillosis (IPA) in non-HIV immunosuppressed patients and their potential association with patient's outcome, including frequency and severity of pulmonary hemorrhage, taking also in consideration the impact of other known risk factors contributory to IPA.

Material and methods:

A retrospective review of serial CT scans was performed in 45 immunocompromised patients with a total of 46 episodes of invasive pulmonary aspergillosis. All patients underwent CT beginning with the day they showed clinical or laboratory signs of infection. Serial follow-up CT included more than two, up to 12 CT examinations. Patient's outcome was judged by clinical and radiological follow-up and classified as survival, death by IPA, or death unrelated to IPA. The influence of patient's age, underlying disease, hematopoietic stem cell transplantation, neutropenia, graft versus host disease, and antifungal therapy onset was also statistically considered.

Results:

Three main CT findings were identified: small nodules (<1 cm) 43% (20/46), large nodules 21% (10/46) and consolidations, either in patchy ± segmental 26% (12/46), or peribronchial distribution ± tree in bud 9% (4/46). In 11 patients (24%) we found a combination of two or more of these signs: 9 (19%) patients presented concurrent small nodules accompanied by reticulation, tree in bud or peribronchial infiltrates, while 2 (4%) patients showed large pulmonary nodules accompanied by large consolidations. An accompanying “halo” sign was observed in 38 patients (82%). Crescent sign followed by cavitation was encountered in 29 patients (63%). Two patients succumbed to massive pulmonary bleeding caused by IPA. Twenty-one patients (15/46) deceased in this series, 12 of them succumbed to IPA, 1 died from cerebral invasive aspergillosis, while in 9 patients the cause of death was not primarily IPA. Manifest pulmonary hemorrhage occurred in 19% (9/46) of IPA episodes.

Conclusion:

Initial CT findings of invasive pulmonary aspergillosis consist mainly of small nodules or patchy consolidations, showing in 82% of cases an early halo sign. Serious pulmonary hemorrhage was an infrequent clinical complication in our series, with an attributable mortality of 4.3%. IPA-related lethality was 26%, in our cohort. None of the early HRCT signs seemed to predict outcome.

Introduction

Invasive aspergillosis is a relatively common pulmonary complication of severely immunocompromised hosts such as patients with hematologic malignancies, especially acute and chronic myelogenous leukemia, patients who have undergone hematopoietic stem cell transplantation (HSCT), patients treated with immunosuppressive agents such as high-dose corticosteroids, as well as patients with AIDS [1]. A major predisposing factor in these patients is severe neutropenia (absolute neutrophil count of <500 cells/μL) [2], [3], [4]. Other risk factors affecting the course of IPA include host variables (age, underlying disease), immunosuppression associated with acute or chronic graft versus host disease (GvHD) and concomitant viral infection.

The major clinicopathological manifestations of invasive pulmonary aspergillosis include acute bronchopneumonia, angioinvasive aspergillosis, acute tracheobronchitis and chronic necrotizing aspergillosis [5]. Rare forms of IPA comprise bronchiolitis, bronchiolitis obliterans and miliar disease [6]. Although CT findings are suggestive for each type of aspergillosis, differentiation between these forms requires histologic examination.

Patients with invasive pulmonary aspergillosis have a poor prognosis with a mortality rate ranging between 30% and 80% [7], [8], [9]. Therefore, early recognition of this disease and differentiation from pulmonary complications caused by other pathogens is imperative to improve survival. Alternatively, empiric therapy with antifungals, antibiotics and sometimes additional antiviral therapy can be instituted in case that the etiology of infection remains unclear [10]. Broad-spectrum empiric antimicrobial therapy, however, has side effects, jeopardizing renal and liver function, and increasing therapy costs.

The outcome of IPA has been considered poor in immunocompromised patients, especially in allogeneic bone marrow recipients. This might be partly due to delayed diagnosis and subsequently to late onset of antifungal therapy.

In addition to the above-mentioned risk factors for IPA, early CT findings might also help in assessing risk and prognosis in patients with IPA.

Therefore, the aim of our study was to assess early CT findings of IPA and determine their eventual predictive value for clinical outcome, with emphasis on the frequency of manifest pulmonary hemorrhage and associated mortality. To this end, we also considered the potential role of other well-known risk factors for IPA.

Section snippets

Material and methods

Our patient's cohort included 45 consecutive patients with a total of 46 infectious episodes of invasive pulmonary aspergillosis, who were diagnosed at our department from February 2000 to June 2004. Another 50 immunocompromised patients with acute pulmonary infections, clinically and radiologically judged as IPA and investigated interspersed with the 45 patients in our series within the same time interval at our department, had to be excluded from this study, due to missing microbiological

Results

Three main CT findings were identified: small nodules (<1 cm) 43% (20/46) (Fig. 1), patchy or segmental consolidations 26% (12/46) (Fig. 2), large nodules (masses) 21% (10/46) (Fig. 3) and peribronchial infiltrates (Fig. 4), associated or not with tree in bud 9% (4/46). In 1 patient (2%) we found only very small nodules (miliary pattern), in bilateral distribution (Fig. 5).

In 11 (24%) patients we found a combination of 2 or more of these signs as follows: 9 patients presented with small nodules

Discussion

The pathologic and radiologic features of IPA during the course of infection have been extensively studied by different authors, who described the major patterns of manifestation, reaching from patchy infiltration, over-consolidation, up to well, or ill-defined nodules [14], [15], [16], [17]. Rare manifestations of IPA include tracheobronchitis, bronchiolitis, as well as BOOP, or miliary forms. Histological analysis enables differentiation of the several different forms of IPA, especially of

Conclusion

In summary, we did not find any of the above-mentioned early CT findings of pulmonary infection to be prognostic for the outcome in immunocompromised patients with IPA. The most salient fact is that the halo seems to predict survival by IPA, about as well, as the timing of therapy onset does. Other known risk factors exhibited far less extreme ORs.

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Initial CT manifestations of invasive pulmonary aspergillosis in 45 non-HIV immunocompromised patients: association with patient outcome?

Abstract

Purpose:

Material and methods:

Results:

Conclusion:

Introduction

Section snippets

Material and methods

Results

Discussion

Conclusion

Chest

Clin Radiol

Chest

Blood

The spectrum of pulmonary aspergillosis

J Thorac Imaging

Favourable outcome of invasive aspergillosis in patients with acute leukaemia

J Clin Oncol

Invasive pulmonary aspergillosis: prediction at thin-section CT in patients with neutropenia – a prospective study

Radiology

Aspergillosis: the spectrum of the disease in 98 patients

Medicine

Bronchiolitis associated with the finding of the fungus aspergillus: report of two cases

Conn Med

Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation

J Infect Dis

Progress in the diagnosis and management of aspergillosis in bone marrow transplantation: 13 years’ experience

Clin Infect Dis

Epidemiology and diagnosis of invasive pulmonary aspergillosis in bone marrow transplant patients: results of a 5-year retrospective study

Bone Marrow Transplant

Favourable outcome of invasive aspergillosis in patients with acute leukaemia

J Clin Oncol

Antifungal and surgical treatment of invasive aspergillosis: review of 2121 published cases

Rev Infect Dis

Invasive pulmonary aspergillosis in acute leukemia: the contribution of CT to early diagnosis and aggressive management

Chest