Positive Bronchoalveolar Lavage Galactomannan Research Articles

A 2-year Review of the Diagnostic Performance of Serum and Bronchoalveolar Lavage Galactomannan Testing in Lung Transplant Recipients in a National Heart and Lung Transplant Centre.

The 2015 International Society for Heart and Lung Transplant (ISHLT) fungal guidelines recommend the use of bronchoalveolar lavage (BAL) galactomannan over serum galactomannan for the diagnosis of invasive aspergillosis (IA) in lung transplant (LTx) recipients, based on limited evidence. Galactomannan testing is costly. A single-center, retrospective cohort study reviewing all 814 serum and BAL galactomannan samples received from 184 LTx recipients in our center between 2021 and 2022 and assessing their diagnostic performance in the diagnosis of IA. Over the study period, 394 serum galactomannan samples were received from 144 patients and 420 BAL galactomannan samples from 143 patients. Using a cut-off of ≥ 1.0 for BAL galactomannan, the sensitivity and specificity were 65.9% and 98.4%, respectively. In total, 30 patients had positive BAL galactomannan. Antifungal therapy was commenced or continued in 29 of these patients either as targeted or pre-emptive treatment. Using a cut-off of ≥ 0.5 for serum galactomannan, the sensitivity and specificity were 9.7% and 99.7%, respectively. In total, four patients had a positive serum galactomannan. All four patients were either already on antifungal treatment for IA or were started before the serum galactomannan result was available, supported by laboratory, clinical, and radiological findings. A positive serum galactomannan was used to monitor treatment response in one patient. Serum galactomannan is not a valuable test in the diagnosis of IA in our LTx recipients, is costly, and does not remove the need for bronchoscopy and BAL galactomannan. This supports the ISHLT recommendation.

The Utility of Early Broncholaveolar Lavage in Prolonged Neutropenic Patients with Pulmonary Nodules

▪IntroductionManagement of patients with hematologic malignancies (HM) post induction chemotherapy or allogeneic hematopoietic cell transplant (Allo HSCT) is often complicated by neutropenic fever associated with nodular pulmonary infiltrates, and may result in acute respiratory failure and death. The presence of a halo sign in a neutropenic patient with nodular infiltrates is highly suggestive of invasive pulmonary aspergillosis (IPA).Fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is the preferred procedure for identifying the infectious aetiology of pulmonary infiltrates in post Allo-HSCT or post chemotherapy in HM patients with neutropenic fever. The diagnostic value of FOB with BAL in such patients is controversial, however, it has been suggested that the microbiologic yield from FOB and BAL is higher when bronchoscopy is performed within 24 hours of presentation, allowing subsequent BAL-guided therapeutic adjustment.With a view towards improving health care resource utilization, we re-evaluated this diagnostic strategy.MethodsWe conducted a prospective observational study of 100 participants with the following diagnoses: acute myeloid leukemia (AML), 76%; myelodysplastic syndrome (MDS), 9%; acute lymphoblastic leukemia (ALL), 6%; and acute promyelocytic leukemia (APL), 6%. One hundred sequential patients who underwent FOB after August 2016 and provided informed consent, were enrolled and followed for 30 days. Sixty six percent were admitted for induction chemotherapy; 17% for re-induction chemotherapy; 10% for conditioning pre- Allo- HSCT; 4% for consolidation chemotherapy; and 3% for other therapy.Data collected included patients' demographics, dates of onset of fever and of baseline chest CT scan, findings on CT scan, dates of initiation of empirical antibiotic and antifungal therapy, BAL results, and the impact on antimicrobial choices. Other outcomes included transfer to ICU and death.We assessed the utility of performing early FOB (within 48 hours of performing a low dose chest CT scan) vs Late FOB (after 48 hours from low dose chest CT scan) in post-chemotherapy HM and Allo-HSCT patients.ResultsOf the 100 enrolled participants, 61 and 39 underwent early and late FOB, respectively (Figure-1: Table of results) . A positive BAL Galactomannan was observed in 7 (11.5%) early FOB cases, compared to only 1 (2.6 %) in late FOB case (p=0.15), with a subsequent impact on the choice of antifungal in 6 cases (9.8 %) and 1 case (2.6 %), respectively (p=0.042).BAL culture was positive in 2 cases (3.3%) in the early FOB group, compared to only 1 case (2.6%) in the late FOB group (p=0.99). The choice of antibiotic was influenced by BAL results in 1 of the 2 early FOB cases.Eight (13.3%) and 7 (17.9%) of early and late FOB patients, respectively, were transferred to the ICU (p=0.57); and 6 (9.8%) of the early FOB and 3 (7.7 %) of late FOB patients died (p=0.99).ConclusionThe diagnostic yield of early FOB was greater than that of late FOB, as assessed by GM positivity, and more frequently permitted targeted antifungal therapy. There was no difference in the rate of antibiotic use between the two groups. [Display omitted] DisclosuresGupta:Incyte: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Schuh:Amgen: Consultancy, Honoraria. Yee:Astex: Research Funding; Oncoethix: Research Funding; Karyopharm: Research Funding; Novartis Canada: Honoraria; Celgene Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Diagnostic yield of a bronchoalveolar lavage fluid galactomannan assay in patients with negative serum galactomannan results suspected to have invasive pulmonary aspergillosis.

There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n=24) or BAL fungal culture results (n=8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193]). Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.

747. Diagnostic Performance of Bronchoalveolar Lavage Fluid Galactomannan Assay in Patients with Negative Serum Galactomannan Assay Suspected with Invasive Pulmonary Aspergillosis

BackgroundThere are limited data in real clinical practice on the diagnostic value of BAL (bronchoalveolar lavage) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results.MethodsThis study was performed at Asan Medical Center, a 2700 bed tertiary-care hospital in Seoul, South Korea between May 2008 and April 2019. All patients with suspected IPA whose serum GM assays revealed negative results and sequentially underwent BAL were enrolled in this study. Patients were classified as proven, probable, possible or not IPA by the revised 2019 EORTC/MSG definition.ResultsA total of 341 patients with suspected IPA including 4 proven IPA, 38 probable IPA, 107 possible IPA, and 192 not IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven or probable IPA who had initial negative serum GM results, 24 (57%) revealed positive BAL GM results (n=24) or BAL fungal culture (n=8). Among the remaining 18 (43%), 2 (5%) were diagnosed as proven IPA by the histopathologic exam from transbronchial lung biopsy, 6 (14%) as probable IPA by subsequent sputum fungal culture, and 10 (24%) as probable IPA by repeated serum GM assay after BAL. Of 192 patients with not IPA, 14 (7%) revealed positive BAL GM results (n=14) or BAL fungal culture (n=8). The diagnostic performance of various tests is shown in Table 1.Table 1. Diagnostic performance of various diagnostic tests in patients with suspected IPA who had negative serum GM results ConclusionSequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in about half of patients.Disclosures All Authors: No reported disclosures

A positive BAL galactomannan in non-haemato-oncology patients risks harmful overtreatment.

Introduction. Evidence for the clinical utility of bronchoalveolar lavage (BAL) galactomannan in the management of fungal disease outside of haemato-oncology patients is limited.Aim. To determine how the introduction of BAL galactomannan testing impacted on the diagnosis and management of invasive aspergillosis and other fungal diseases in non-haemato-oncology patients.Methodology. Retrospective review of all adult patients (age ≥16 years) without a diagnosis of haematological malignancy who had a positive BAL galactomannan from 1 November 2014 to 30 April 2018. Using electronic patient records we obtained demographic data, clinical details, laboratory investigations, relevant radiology and antimicrobial history for each case.Results. In total, 121 episodes with a galactomannan OD index of ≥0.500 were included in the study; 29 cases (24 %) were felt to reflect fungal disease. Antifungal therapy was commenced as a direct consequence of a positive BAL galactomannan result in 13 patients where the ultimate diagnosis was subsequently considered to be non-mycological: associated medication-related side-effects in this group included deranged liver function tests (n=3), rash (n=1) and fever (n=1), related to amphotericin B (n=1) and voriconazole (n=4).Conclusion. We show that vigilance is required when interpreting galactomannan results in non-haematology patients to avoid potentially harmful overtreatment.

Post-operative antifungal prophylaxis in lung transplant recipients: Unprecedented evidence

Introduction/objectives Despite recent advances in lung transplantation, Aspergillus infections are still a major concern in lung transplant (LT) recipients. The genus Aspergillus may manifest as colonization or infection forms. The latter being associated with significant mortality and morbidity. Colonization, defined as bronchoalveolar lavage or bronchial aspirate, or positive bronchoalveolar lavage galactomannan test, or at least two positive sputum cultures, or tracheal aspirate for Aspergillus spp. in asymptomatic patients with normal-appearing respiratory mucosa or absence of endobronchial lesions, usually precedes infectious forms and complicates transplantation course. While several antifungal prophylactic strategies have been used to limit this deadly disease that mess with this complex endeavor, evidence from retrospective or prospective studies is lacking. In a recent international survey, only 50% of lung transplants’ centers use antifungal prophylaxis, yet, substantial differences regarding the duration and the modality of antifungal prophylaxis exist among centers and, hence, increase the unmet need for clear recommendations. Since airways’ colonization usually precedes Aspergillus infections and LT recipients are most vulnerable, in particular, during the early post-operative period due to anastomotic ischemia, Aspergillus’ eradication seems to be a plausible solution to prevent or minimize Aspergillus colonization/infections post-transplantation. Consequently, all patients who underwent single or double lung transplantation in our center after 2014 received antifungal prophylaxis started on day 1 post-transplantation and carried on till healing of bronchial anastomosis. We report our 4-year experience with antifungal prophylaxis in LT recipients. Methods A retrospective analysis was conducted and compared LT recipients who systematically received inhaled amphotericin B deoxycholate (6 mg twice daily) and 200 mg twice daily oral voriconazole (2014–2017) to those who did not (2008–2013). Only non-cystic fibrosis LT recipients were included in the analysis given that cystic fibrosis patients usually harbor aspergillus species in their sino-nasal/respiratory tract, a fact that may underestimate such therapeutic strategy benefit and Aspergillus’ eradication may not be achieved. The data showed in this analysis was traced till hospital discharge. Results A total of 142 non-cystic fibrosis patients had undergone single/double lung transplantation. Between 2014 and 2017, 59 LT recipients received antifungal prophylaxis and Aspergillus spp. was found in 20 patients (incidence of 33%), while in the control group (n = 83) Aspergillus spp. was recovered from 42 patients (incidence of 50%). The difference between these 2 groups was statistically significant (P = 0.04) suggesting a potential beneficial effect of prompt post-operative antifungal prophylaxis in reducing Aspergillus colonization. Aspergillus fumigatus, A. niger, and A. flavus were most commonly found. Conclusions Immediate post-operative antifungal prophylaxis using amphotericin B deoxycholate and oral voriconazole significantly reduced nosocomial Aspergillus colonization in non-cystic fibrosis LT recipients. A finding that might decrease subsequent Aspergillus related complications and reduce unnecessary morbidity. However, prospective controlled randomized trials with long-term follow-up are eagerly awaited.

Detection of galactomannan in bronchoalveolar lavage of the intensive care unit patients at risk for invasive aspergillosis.

Background and Purpose:Invasive aspergillosis (IA) is one of the most common life-threatening fungal infections among the critically ill patients including intensive care unit (ICU) patients. Delayed diagnosis and therapy may lead to poor outcomes. Diagnosis may be facilitated by a test for molecular biomarkers, i.e. detection of galactomannan (GM) antigen based on enzyme immunoassay, which is of increasing interest in the clinical settings for the diagnosis of IA. In the present study, we assessed GM testing of bronchoalveolar lavage (BAL) fluid as a tool for early diagnosis of IA among ICU patients who were at risk for developing IA.Material and Methods:A prospective study was performed in ICU patients with underlying predisposing conditions for IA between August 2010 and September 2011. BAL samples for direct microscopic examination, culture, and GM detection were obtained once or twice weekly. GM in BAL levels was measured using the Platellia Aspergillus EIA test kit. According to modified European Organization for the Research and Treatment of Cancer/ Mycoses Study Group (EORTC/MSG) criteria, patients were classified as having probable or possible IA.Results:Out of 43 suspected patients to IA, 13 (30.2%) cases showed IA. According to the criteria presented by EORTC/MSG, they were categorized as: 4 cases (30.8%) of possible IA and 9 (69.2%) of probable IA. Out of 21 BAL samples from patients with IA, 11 (52.4%) had at least one positive BAL GM index. Using a cutoff index of 0.5, the sensitivity and specificity, positive and negative predictive values of GM detection in BAL fluid were 100%, 85.7%, 65.7% and 96%, respectively. The sensitivity and specificity was 73% and 92.7% at cutoff ≥1.0, respectively. In 6 of 13 IA cases, BAL culture or direct microscopic examination remained negative, whereas GM in BAL was positive. Conclusion:Our data have revealed that the sensitivity of GM detection in BAL was better than that of conventional tests. It seems that GM detection in BAL is beneficial to establish or exclude the early diagnosis of IA in ICU patients.

Utility of galactomannan antigen detection in bronchoalveolar lavage fluid in immunocompromised patients

Diagnosis of invasive pulmonary aspergillosis (IPA) is a challenging process in immunocompromised patients. Galactomannan (GM) antigen detection in bronchoalveolar lavage (BAL) fluid is a method to detect IPA with improved sensitivity over conventional studies. We sought to determine the diagnostic yield of BAL GM assay in a diverse population of immunocompromised patients. A retrospective review of 150 fiberoptic bronchoscopy (FOB) with BAL for newly diagnosed pulmonary infiltrate in immunocompromised patients was performed. Patient information, procedural details and laboratory studies were collected. BAL and serum samples were evaluated for GM using enzyme-linked immunoassay. Of 150 separate FOB with BAL, BAL GM was obtained in 143 samples. There were 31 positive BAL GM assays. In those 31 positive tests, 13 were confirmed as IPA, giving a positive predictive value of 41.9%. There was one false negative BAL GM. Of the 18 false positive BAL GM, 4 were receiving piperacillin-tazobactam and 11 were receiving an alternative beta-lactam antibiotic. BAL GM assay shows excellent sensitivity for diagnosing IPA. There was a significant number of false positive BAL GM assays and several of those patients were receiving beta-lactam antibiotics at the time of bronchoscopy.

INVASIVE ASPERGILLOSIS IN INTENSIVE CARE UNIT PATIENTS IN IRAN

We assessed the intensive care unit (ICU) patients for Invasive aspergillosis (IA) with culture and non-culture based diagnostic methods from Iran. Thirty-six ICU patients with underlying predisposing conditions for IA were enrolled in the study. Sixty eight Bronchoalveolar lavage (BAL) samples were collected by bronchoscope twice a weekly. BAL samples were analyzed by microscopic examination, fungal culture and galactomannan (GM) detection. The Platelia Aspergillus GM EIA was used to quantify GM indices. Samples with a BAL GM index > or = 1 were considered as positive for GM. Patients were classified as having probable or possible IA. Out of 36 suspected patients to IA, 36.1% of cases showed IA which were categorized as: 4 cases of possible IA and 9 of probable IA. 76.2% of BAL samples were positive for GM. From 13 patients with IA, 11 (84.6%) had at least one positive BAL GM index. Of these patients, 9 (81.8%) showed probable IA. The main underlying predisposing conditions were neutropenia (53.8%) and COPD (30.8%). Our study has indicated that COPD must be considered as one of the main predisposing condition for occurrence of aspergillosis in ICU patients. Our data have also revealed that GM detection in BAL samples play a significant role to IA diagnosis.

Comparison of Sensitivity of Low-Dose CT Scan and Serum Galactomannan in Patients with Hematologic Malignancies and Positive Bronchoalveolar Lavage for Invasive Pulmonary Aspergillosis

Abstract 1490▪▪This icon denotes a clinically relevant abstract Background:Invasive pulmonary aspergillosis (IPA) is associated with considerable morbidity and mortality in patients with acute leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Timely diagnosis of IPA is crucial, but difficult. Strategies for early detection of IPA include serum galactomannan (GM), bronchoalveolar lavage (BAL) GM and characteristic radiologic abnormalities on CT scan; however, the relative sensitivity of these diagnostic tests is unclear. We sought to determine the utility of serum GM and characteristic CT radiologic abnormalities in diagnosing IPA in patients with hematologic malignancies who had a positive BAL for Aspergillus. Methods:We performed a single center retrospective cohort study from 2010 to 2012 to determine the sensitivity serum GM (OD > 0.5) and low dose CT scan in patients with hematologic malignancies. All positive BAL GM samples and Aspergillus isolates from BAL fluid cultures from patients with acute leukemia and those undergoing HSCT were reviewed; all patients had abnormal chest CT scans consistent with pulmonary infection. IPA was classified as proven, probable or possible according to EORTC/MSG criteria. Recent low dose CT scans correlating to the date of the positive BAL GM or Aspergillus isolation were reviewed and graded: halo signs, cavities, crescents and nodules were deemed to be consistent with IPA, while other changes (e.g. ground-glass changes, consolidation) were considered non-specific. Results:A total of 49 BAL samples were included; of these, 31 were considered probable IPA and 18 possible IPA (on the basis of non-specific radiologic findings). Most patients had either no prior or 1–2 days of mold-active antifungal agents. There were 43 cases with positive BAL GM and 11 cases of positive Aspergillus BAL isolates; 5 patients had both. Of the positive BAL GM cases, 27 (63%) were associated with radiologic findings consistent with IPA. The remaining cases were associated with non-specific radiologic findings. Of the patients with Aspergillus isolates on BAL, 55% (6/11) had radiologic features consistent with IPA, while the remaining cases had non-specific radiologic findings.We next evaluated the sensitivity of serum GM. Of 34 patients with BAL GM positivity who had concomitant serum GM testing, 4 (12%) had positive serum GM. Of 8 patients with Aspergillus species isolated on BAL who had serum GM performed, only 1 (12.5%) had positive serum GM. In contrast, 5/8 patients (63%) with Aspergillus isolates on BAL had a positive BAL GM. The combined sensitivity of serum GM was 12% (5/42). Conclusions:Although the majority of patients with positive BAL for Aspergillus (+GM and/or isolates) had characteristic radiologic findings on CT scan, the absence of such findings did not exclude this diagnosis, as over one third had only non-specific radiologic findings. Serum GM had very low sensitivity in this population and should not be used in isolation to diagnose IPA. Disclosures:No relevant conflicts of interest to declare.

Aspergillus galactomannan antigen assay in bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis

A recently developed bronchoalveolar lavage (BAL) galactomannan (GM) assay shows promising results. We evaluated the diagnostic performance of this assay and analyzed risk factors for false-positive results. A prospective cohort study was performed in a tertiary hospital over a 9-month period. We reviewed all adult patients who underwent GM assays of BAL. Patients were categorized with proven, probable, or possible invasive pulmonary aspergillosis (IPA) according to revised EORTC/MSG definitions. Each patient with a false-positive BAL GM result was matched with three patients with true-negative BAL GM result, and the risk factors for false-positive BAL GM results were determined. Of 359 enrolled patients, 22 (6%) were diagnosed with IPA (1 proven, 17 probable, and 4 possible). Of the 22 patients with IPA, 17 (77%) had already received antifungal agents before the BAL GM assay was conducted. At an index cutoff value of ≥0.5, the BAL GM assay had a sensitivity of 64% (95% CI 41%-83%) and a specificity of 89% (95% CI 85%-92%). However, at an index cutoff value of ≥0.2, the BAL GM assay had a sensitivity of 86% (95% CI 65%-97%) and a specificity of 74% (95% CI 69%-79%). Of the 52 patients with positive BAL GM assay (≥0.5), 25 (7%) were false-positives. Univariate and multivariate analysis revealed that treatment with piperacillin-tazobactam or ampicillin-sulbactam was associated with false-positive BAL GM results. The BAL GM assay appears promising for the diagnosis of IPA. However, treatment with certain antibiotics may interfere with the results of the BAL GM assay.

Diagnosis of Invasive Aspergillosis in Lung Transplant Recipients by Detection of Galactomannan in the Bronchoalveolar Lavage Fluid

Galactomannan (GM) detection in serum samples has been used to diagnose invasive aspergillosis (IA). Limited sensitivity has been observed in lung transplant recipients, for whom bronchoalveolar lavage (BAL) testing has been advocated. Because airway colonization with Aspergillus species occurs frequently in these patients, false-positive GM results have been reported if the cutoff validated for sera is used (i.e., 0.5). Herein, we prospectively studied BAL fluid samples from 60 lung transplant patients to determine the optimal cutoff for BAL GM testing. Only one sample per patient was studied. BAL samples were vortexed and processed according to the manufacturer's instructions for serum samples. Sensitivity, specificity, and likelihood ratios were calculated in reference to proven or probable IA cases using receiver operating characteristic analysis. Eight patients had IA during the study (incidence 13.3%), including four patients with proven IA. Aspergillosis increased 5-fold the risk of death in lung transplant recipients. The positive predictive value of a positive BAL GM test at the 0.5 cutoff was low (24.2%). Raising the cutoff improved test specificity without compromising sensitivity. The best cutoff was defined at 1.5 (sensitivity 100% and specificity 90.4%). This study reinforces the importance of BAL GM testing in lung transplant recipients, particularly to exclude the diagnosis of IA. To minimize the frequency of false-positive results, a higher test cutoff should be applied to BAL samples, in comparison with serum samples.

A Novel Non-Invasive Method of Detecting Galactomannan in Suspected Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) is now the leading cause of infectious mortality in stem cell transplant recipients. Despite recent advances in molecular diagnostic techniques the diagnosis remains problematic. The mycological yield from bronchoalveolar lavage (BAL) is poor, especially if the patient has been exposed to antifungal drugs. Galactomannan (GM), a component of Aspergillus' cell wall is detectable in serum and BAL fluid in IPA, though its role in the latter has not been validated. Exhaled breath condensate (EBC) collection provides a non-invasive means of sampling the airway lining fluid. This method has been used in respiratory disease to detect markers of inflammation and oxidative stress. EBC is collected by breathing into a tube surrounded by a cooled insulated metal sleeve (RTube®, Respiratory Research, USA) and results in 1–2 millilitres of fluid. The application of EBC detection of volatile and non-volatile organic compounds has not been explored in this setting. We report on pilot data of the detection of GM in EBC from a subset of patients at high risk of infection forming part of a prospective study into the early diagnosis of IPA in allogeneic transplant recipients and patients with acute leukaemia. Patients were recruited prior to commencing treatment for their underlying haematological condition; the study period finished at neutrophil recovery (> 0.5 x 109/L) or discharge from hospital. EBC and serum were collected once and twice weekly respectively, throughout the study period. High resolution CT (HRCT) imaging of the chest was carried out after 72 hours of neutropenic fever unresponsive to broad-spectrum antibiotics. Where possible, BAL was carried out in the most affected lobe in patients with an abnormal HRCT chest. GM was measured in EBC, serum and, where applicable, BAL fluid using a commercially available kit (Platelia® Aspergillus, Bio-Rad, France). The likelihood of IPA was assigned using criteria published by European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) by 2 investigators blinded to clinical details (Ascioglu et al, CID 2002). Of 39 patients, 6 had proven/probable IPA, 9 possible and 24 had no evidence of IPA. Four of the 6 patients with proven/probable disease had GM-positive BAL fluid; 3 of these 4 had persistently negative GM in serum. In 1 of the 6, the EBC GM was positive 3 weeks earlier than the development of HRCT evidence of IPA and a positive BAL GM. In another, the EBC GM was positive early in the infection, whilst BAL GM remained negative. EBC and serum GM followed the same trend in all 6 patients, although the values for both EBC and serum remained below the currently recognised positive cut-off of 0.5 in 2 patients. In patients with possible or no evidence of IPA, GM was negative in all but 2 of 111 EBC samples. These results suggest that GM can be detected in EBC and follows the same trend as in serum. It may even predate GM detection in BAL fluid or abnormal HRCT signs, thereby obviating the need for more invasive investigations. Elevated EBC GM levels early in the course of neutropenia may represent infection and could be applied to the employment of pre-emptive treatment strategies.

Bronchoalveolar Lavage Galactomannan in Diagnosis of Invasive Pulmonary Aspergillosis among Solid-Organ Transplant Recipients

We review the experience at our institution with galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16), there were five cases of proven or probable IPA. All five patients had BAL GM of > or = 2.1 and survived following antifungal therapy. The sensitivity, specificity, and positive and negative predictive values for BAL GM testing at a cutoff of > or = 1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The sensitivity of BAL GM testing was better than that of conventional tests such as serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed IPA several days to 4 weeks before other methods for three patients. Twelve patients had BAL GM of > or = 0.5 but no evidence of IPA. Among these, lung transplant recipients accounted for 41.7% (5/12) of the false-positive results, reflecting frequent colonization of airways in this population. Excluding lung transplants, the specificity and positive predictive value for other solid-organ transplants increased to 92.9% and 62.5%, respectively (cutoff, > or = 1.0). In conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the institution of antifungal therapy among non-lung solid-organ transplant recipients and helped to rule out IPA.