Diagnostic and therapeutic strategies in the management of nosocomial pulmonary aspergillosis, in patients with hematological malignancies

Invasive pulmonary aspergillosis (IPA) remains a life-threatening complication in immunocompromised hosts and especially in neutropenic patients. The authors report their experience (since 1988) in the diagnostic and therapeutic management of IPA (including 25 histologically proven cases) in 45 patients with hematological malignancies. All patients but 1 were neutropenic (PMN < 500/mm(3); median duration = 19 days), when IPA was diagnosed. Chest pain and hemoptysis were recorded in 73 % and 53 % of cases, respectively. Aspergillus antigenemia was positive at the time of IPA diagnosis in 15 out of 42 tested cases. A broncho-alveolar lavage (BAL) was positive in 23 out of 39 cases. Interestingly, Aspergillus antigen test on BAL fluid was positive in 19 out of 24 tested cases (including 10 out of 12 positive results among histologically proven IPA). Since October 1991, the systematic use of thoracic CT-scan in febrile neutropenic patients with chest X-ray infiltrates, has allowed us to see an early CT halo sign (highly suggestive of IPA in neutropenic patient) in 94 % of the cases. Since we have systematically used thoracic CT to search for signs of IPA, the average delay before IPA diagnosis has been dramatically reduced from 7 to 2 days. 18 patients underwent a pulmonary surgical resection of aspergillary site. In 10 cases, the resection was performed as an elective procedure (either as a curative procedure in 6 cases or a diagnostic procedure in the 4 remaining cases). In 8 patients, surgery was an emergency procedure to prevent a massive hemoptysis (in case of pulmonary vessel fungal erosion). Interestingly, in 14 of these 18 patients, the main criteria for IPA diagnosis before surgery were based on CT findings alone. In all surgical cases, the diagnosis of DPA was definitely established by pathological analysis. Overall, 71 % of patients were successfully treated with an antifungal therapy (itraconazole and/or amphotericin B or voriconazole) combined with surgery if necessary. Obtaining hematological response, early diagnosis (since the systematic use of thoracic CT in the diagnostic strategy), unilateral pulmonary involvement of TPA, and the highest level of fibrinogen value < 9 g/l during the 10 days after IPA diagnosis were all associated with improved survival in neutropenic patients with IPA. In conclusions, we think that the systematic use of thoracic CT in febrile neutropenic patients with IPA allows to reach an earlier diagnosis. Early treatment with antifungal agents, combined with pulmonary surgical resection if necessary, dramatically improve TPA prognosis in these patients.