Introduction
Pulmonary complications are a relevant clinical issue in patients with hematologic malignancies. However, the causative agent of lung infiltrates remains undetected in the majority of cases. Although conventional cultures and non-culture-based serological diagnostic assays may help identify the causative agent, bronchoscopy coupled with bronchoalveolar lavage (BAL) appears the most effective approach for lung infiltrates diagnosis. However, considering the high-risk of procedure-related complications in such “difficult patient population”, both hematologists and thoracic surgeons often consider bronchoscopy with extreme caution. Nevertheless, a proper diagnostic approach at lung infiltrates is particularly relevant in neutropenic patients and/or in patients with an unfavorable clinical response to broad-spectrum antibiotics, in which the cause of lung infiltrates are often filamentous fungi, such as Aspergillus spp. To date, there is not a general consensus on the diagnostic panel to perform in hematologic patients undergoing bronchoscopy for lung infiltrates.
Based on these considerations, we decided to carry out a multicenter prospective study on comprehensive diagnostic approach of lung infiltrates in patients with hematologic malignancies with the main objective of evaluate the efficacy and feasibility of BAL in identifying a causal agent of lung infiltrates in these patients. Secondary objectives are: 1) to correlate the results of BAL with radiological features of lung infiltrates, particularly for atypical infiltrates, which are not sufficient for a diagnosis of probable invasive fungal infection according the published diagnostic criteria; 2) to establish the best cut-off for galactomannan determination on BAL; 3) to establish the safety of performing a bronchoscopy in patients with hematologic malignancies.
This is a prospective, multicenter observational and non-interventionist study involving 19 hematology units (three of these pediatric) participating in SEIFEM cooperative group and undergoing a procedure of bronchoscopy with BAL according to the standards of good clinical practice. The study will be 6-9 months long and we will aspect to enroll about 150 patients. Patients are included in the study according to the following criteria: a) any hospitalized patient with hematologic malignancies with host criteria for invasive fungal infection and in any phase of disease with lung infiltrates occurrence without any microbiological documentation by conventional diagnostic methods (blood cultures, galactomannan, respiratory viruses) and/or not responding to broad-spectrum antibiotics. Criteria for no response to broad-spectrum antibiotics were defined as persistent (> 48 h) fever and/or persistent respiratory distress. Based on clinical judgmental, these patients could be candidate to perform a bronchoscopy with BAL using the following work-up diagnostic panel: microbiological exam, galactomannan, PCR for respiratory viruses, PCR for respiratory bacteria, PCR for Pneumocystiis jiroveci, PCR for Aspergillus spp.