Mycological Diagnosis of Invasive Pulmonary Aspergillosis Should Depend on Both the Underlying Condition and the Neutropenia Status of Patients with Hematologic Malignancies

Accurate identification of the causative organism in invasive pulmonary aspergillosis (IPA) is important for both epidemiological reasons and optimal management of patients (pts); therefore, it is now recommended. The most efficient strategy to isolate the fungus, however, is not well-established. The reported mycological yield of bronchoscopy, the most commonly used noninvasive approach, does not exceed 40–60%. In the context of IPA, we investigated whether a mycological diagnostic strategy could be optimized based on pt characteristics.

We used a database of 57 pts with IPA enrolled between May 2005 and February 2007 in a prospective multicenter study primarily designed to determine the performance of several microbiological tools in predicting the outcome of IPA. The study protocol was approved by the ethics committee of Saint-Louis Hospital, and all pts provided informed consent. Statistical methods: Predictive factors of positive microbiological results (cytology and/or culture) were analyzed by Fisher's exact test and multiple regression models. Whenever necessary, groups of pts were compared by Fisher's exact test. Analyses were carried out using R version 2.6.2 statistical software (the R Foundation for Statistical Computing, Vienna, Austria).

Pt and IPA characteristics according to the underlying condition.

The presence of Aspergillus in respiratory samples was significantly more frequent in non-acute leukemia (AL) pts (83%) than in AL pts (25%) (p=0.0003), and in pts with ANC > 100/mm³ (p=0.0002). In a logistic regression model, these 2 factors appeared independent, with an adjusted OR of 7.27 (95% CI 1.42 to 37.3) for non-AL pts and an adjusted OR of 7.20 (95% CI 1.38 to 37.7) for ANC > 100/mm³. A positive mycological yield was detected in 95% of the non-AL pts with ANC > 100/mm³ vs. 23% of the AL pts with ANC < 100/mm³ (p=0.0002). A positive mycological result was also more frequent among pts with lung CT scan signs of invasive airway disease than among other patients (p=0.026). Furthermore, the CT scan findings were strongly associated with the underlying condition and ANC counts of the pt. In particular, invasive airway signs were significantly more frequent among non-AL pts (p=0.049), whereas angioinvasive disease was significantly more frequent among both AL pts (p=0.01) and patients with ANC < 100/mm³ (p=0.0001). Steroid therapy (yes/no and > or < 1 mg/kg) and previous anti-mold therapy had no significant effect on the results. Notably, a concomitant pulmonary infection was identified with bronchoscopy more frequently among non-AL pts (p=0.0009).

We strongly recommend bronchoscopy for a specific diagnosis of aspergillosis among non-AL patients, particularly among allogeneic stem cell transplant recipients. Among AL pts with severe neutropenia, another diagnostic strategy should be considered.

No relevant conflicts of interest to declare.