Cases Of Invasive Pulmonary Aspergillosis Research Articles

Clinical analysis of 16 cases of invasive pulmonary aspergillosis in children

To investigate the diagnosis and treatment of invasive pulmonary aspergillosis (IPA) in children. The clinical data of 16 cases of proven or probable IPA who had been in our Hospital from January 2006 to June 2014 were retrospectively analyzed. Among the 16 patients, 11 were males and 5 were females. One child had proven IPA and 15 children had probable IPA. Host risk included long duration use of multiple broad-spectrum antibiotics in 16 cases, neutropenia in 9 cases, invasive mechanical ventilation in 3 cases, primary immunodeficiency disease in 2 cases, long-term use of glucocorticoids in 2 cases, measles in 2 cases, and congenital pulmonary hypoplasia in 1 case. Fever, cough and expectoration were present in all the children with IPA. At the time of diagnosis, the halo sign and subpleural wedge consolidation shadows were more common in neutropenia group (5/9, 7/9) than those in non-neutropenia group(0/7, 1/7)(P<0.05). The cavities and"air-crescent sign"were more common after 15 days to 1 month when the children had been treated with anti-aspergillosis drugs than that at the onset of diagnosis of IPA (P<0.05). The positive rate of serum galactomannan (GM) test was higher than that of sputum culture and serum G test (P<0.05). Thirteen children received voriconazole, in 7 of the children the treatment was effective. Neutropenia were the common host risk factors in children with IPA. Subpleural wedge consolidation shadows, the halo sign and the"air-crescent"sign were highly suggestive of the diagnosis of IPA in children. Subpleural wedge consolidation shadows and the halo sign were more common in neutropenia group than in non-neutropenia group in the early stage of the course. Serum GM test played an important role in the diagnosis of IPA in children. Voriconazole was effective in majority of the children with IPA.

Galactomannan Assay and Invasive Pulmonary Aspergillosis - Comparison of the Test Performance at an in-house and the Kit Cut-off.

Invasive Pulmonary Aspergillosis (IPA) is an important opportunistic infection with a high degree of mortality and morbidity. Galactomannan assay (GM assay) is found to be useful for diagnosis of IPA in patients with neutropenia. However the utility of this assay has not been evaluated in a mixed patient population with other co-morbid conditions. Though a kit cut-off of 0.5 has been recommended for the diagnosis of IPA, studies have reported a higher sensitivity with cut-offs more than 0.5. To establish an in-house cut-off and compare its utility with the kit cut-off to diagnose and categorize IPA as proven, probable and possible in patients with varied underlying risk factors. This observational study was done in St John's Medical College, Bangalore, Karnataka, India from January 2013-December 2014. GM assay was performed on 25 each of healthy controls and clinically diagnosed cases of IPA. The in-house cut-off was calculated by plotting the Receiver Operating Characteristic Curve (ROC). The in-house cut-off was calculated to be 0.52. Using this and the kit cut-off (0.5), the Sensitivity, Specificity, Positive Predictive Value (PPV) and the Negative Predictive Value (NPV) were found to be 75%, 79%, 76%, 82% and 79%, 71%, 77%, 82% respectively. Diabetes mellitus was found to be associated with more than 50% of the patients. The established in house cut-off using healthy controls and patients with clinical diagnosis of IPA was not significantly different from that of the kit cut-off. Using either of these cut-offs, we could re-categorize two of the possible IPA cases in the probable group. This study helped to understand the clinical utility of this assay even in a mixed patient population with multiple co-morbidities.

A 10-year study reveals clinical and laboratory evidence for the ‘semi-invasive’ properties of chronic pulmonary aspergillosis

In recent years, infections caused by Aspergillus sp. have become an emerging focus of clinical microbiology and infectious disease, as the number of patients infected with Aspergillus sp. has increased markedly. Although chronic pulmonary aspergillosis (CPA) is considered a ‘semi-invasive’ or ‘intermediate’ disease, little data are available for the direct comparison of CPA with invasive pulmonary aspergillosis (IPA) and pulmonary aspergilloma (PA) to quantify invasiveness. In this study, we compared the characteristics of CPA with those of IPA and PA among hospitalized patients over a 10-year period. A total of 29, 51 and 31 cases of CPA, IPA and PA, respectively, were included. An increasing trend in galactomannan antigen seropositivity rate from PA (24.1%) to CPA (35.7%) to IPA (54.9%) and an opposite trend for anti-Aspergillus antibody (PA (71.0%) to CPA (45.8%) to IPA (7.1%)) were observed. Eight percent of CPA patients were infected with more than one Aspergillus sp. The survival rate of the CPA group also fell between the survival rate of PA and IPA, confirming the intermediate severity of CPA. The survival rate of the CPA group became significantly higher than that of the IPA group from day 180 onwards until 2 years after admission (P<0.05). The survival rate of the CPA group remained lower than that of the PA group from day 30 onwards until 2 years after admission. Poor prognostic factors for CPA included older age (P=0.019), higher total leukocyte count (P=0.011) and higher neutrophil count (P=0.012) on admission. This study provided clinical and laboratory evidence for the semi-invasive properties of CPA.Emerging Microbes and Infections (2016) 5, e37; doi:10.1038/emi.2016.31; published online 20 April 2016

A Critical Reappraisal of Prolonged Neutropenia as a Risk Factor for Invasive Pulmonary Aspergillosis.

Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients.

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens.

Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment for hematologic malignancy. Upon further validation, early detection of probable IPA in leukemia treatment will provide opportunities for earlier interventions and interventional clinical trials.

The Effectiveness of Culture-Directed Preemptive Anti-Aspergillus Treatment in Lung Transplant Recipients at One Year After Transplant.

Invasive pulmonary aspergillosis (IPA) is a significant complication after lung transplantation. However, the risk factors for IPA in patients colonized with Aspergillus species, and the effectiveness of culture-directed preemptive treatment, are not well known. We studied 328 lung transplant recipients, from January 2006 to July 2009, with 1-year follow-up. Risk factors and effectiveness of culture-directed preemptive treatment were evaluated via a Cox-proportional hazard model. Seventy-one recipients (21.6%) developed invasive fungal infections, including 29 patients (8.8%) with IPA. Only 48.3% (14/29) of patients with IPA had pretransplantation or posttransplantation airway colonization with Aspergillus spp. In the Cox-proportional hazard model, treatment with rabbit antithymocyte globulin was significantly associated with posttransplant IPA in patients with Aspergillus colonization (hazards ratio, 4.25; 95% confidence interval, 1.09-16.6). Preemptive antifungal treatment for 3 months was significantly associated with a lower rate of IPA (0% [0/36] vs 18% [14/77]; P = 0.003, odds ratio, 0.8; 95% confidence interval, 0.7-0.9) but did not impact mortality. Our data suggest that almost half the cases of IPA occurred in patients without pretransplantation or posttransplantation airway colonization with Aspergillus spp. Among patients with Aspergillus colonization, use of rabbit antithymocyte globulin was associated with 4-fold risk of subsequent development of IPA. Invasive pulmonary aspergillosis was an independent risk factor for 1-year mortality. Use of preemptive antifungal treatment for 3 months may be associated with significant reduction of IPA without influencing mortality.

Combining standard clinical methods with PCR showed improved diagnosis of invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia

BackgroundWe assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case–control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia.MethodsIn this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with “proven” or “probable” invasive pulmonary aspergillosis (25.93 %) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 %). In 44.44 % of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 % of patients died during the study period. Postmortem histology was pursued in 53.85 % of fatalities.ResultsConcordant negative galactomannan and computed tomography supported by a polymerase chain reaction assay were shown to have the highest discriminatory power to exclude invasive pulmonary aspergillosis. Bronchoalveolar lavage was performed in 6 cases of invasive pulmonary aspergillosis and in 15 controls. Although bronchoalveolar lavage proved negative in 93 % of controls it did not detect IPA in 86 % of the cases. Remarkably post mortem histology convincingly supported the presence of Aspergillus hyphae in lung tissue from a single case which had consecutive positive polymerase chain reaction assay results but was misdiagnosed by both computed tomography and consistently negative galactomannan assay results. For the galactomannan enzyme-immunoassay the diagnostic odds ratio was 15.33 and for the polymerase chain reaction assay it was 28.67. According to Cohen’s kappa our in-house polymerase chain reaction method showed a fair agreement with the galactomannan immunoassay. Combined analysis of the results from the Aspergillus galactomannan enzyme immunoassay together with those generated by our polymerase chain reaction assay led to no misdiagnoses in the control group.ConclusionThe data from this pilot-study demonstrate that the consideration of standard clinical methods combined with biomarker testing improves the capacity to make early and more accurate diagnostic decisions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0995-8) contains supplementary material, which is available to authorized users.

Comparison of computed tomographic findings in pulmonary mucormycosis and invasive pulmonary aspergillosis

Because there are no available molecular markers for pulmonary mucormycosis (PM), which has low culture sensitivity, early diagnosis and treatment rely heavily on imaging modes such as computed tomography (CT). However, there are limited data comparing CT findings for PM with those for invasive pulmonary aspergillosis (IPA). Adult patients who met the modified criteria for proven and probable PM (over an 11-year period) and IPA (over a 6-year period, owing to the availability of the galactomannan assay) according to the modified European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions were retrospectively enrolled. IPA cases were selected at a 1 : 4 (PM/IPA) ratio. Thoracic CT scans were reviewed by two experienced radiologists blinded to the patients' demographics and clinical outcomes. A total of 24 patients with PM, including 20 (83%) with proven PM and four (17%) with probable PM, and 96 patients with IPA, including 12 (13%) with proven IPA and 84 (87%) with probable IPA, were eventually analysed. The reverse halo sign was more common in patients with PM (54%) than in those with IPA (6%, p < 0.001), whereas some airway-invasive features, such as clusters of centrilobular nodules, peribronchial consolidations, and bronchial wall thickening, were more common in patients with IPA (IPA 52% vs. PM 29%, p 0.04; IPA 49% vs. PM 21%, p 0.01; IPA 34% vs. PM 4%, p 0.003, respectively). The reverse halo sign was more common, and airway-invasive features were less common, in patients with PM than in those with IPA. These findings may help physicians to initiate Zygomycetes-active antifungal treatment earlier.

Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.

Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (<10 mm, clustered) were more frequent in tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA.

Prophylaxis of Invasive Pulmonary Aspergillosis with Nebulized Lipid Complex Amphotericin B Is Feasible, Well Tolerated and Safe in Children with Acute Leukemia. Results of a Phase II Open Trial

▪ BACKGROUNDAcute leukemia is the most frequent cancer in childhood. The use of dose-intensive chemotherapy regimens has significantly increased the overall survival of acute leukemia during the last years. As a result of more dose-intensive myelosuppressive and immunosuppressive therapies there is a higher risk of systemic fungal infections. Invasive pulmonary aspergillosis (IPA) represents a significant source of morbidity and mortality (>50%), and therefore measures that effectively prevent IPA are needed. Prophylaxis of IPA with anti-mold azoles is effective, but has adverse systemic effects and important drug interactions with some chemotherapeutic agents (i.e. vincristine). Currently there is no optimal prophylaxis for IPA in pediatric patients so new strategies are needed. Because IPA originates from the inhalation of conidia, a prophylactic approach is the topical administration of antifungals inside the lungs. Aerosolized lipid formulations of amphotericin B could prevent IPA and avoid systemic adverse events and drug interactions. There are no published studies reporting feasibility and safety of inhaled lipidic amphotericins in the pediatric population. PATIENTS AND METHODSThe safety, feasibility and tolerance of nebulized lipid complex amphotericin B (ABCL) was evaluated in a phase II open label single arm trial on the use in pediatric patients (3 to 18 year-old) with acute leukemia during intensive chemotherapy. Nebulized therapy was administered by a PARI eFlow®rapid nebulizer system twice weekly, at 50 mg the first week and then 25 mg during intensive chemotherapy until recovery of neutropenia (3 consecutive absolute neutrophil count (ANC) ≥1x109/L or one ANC ≥1.5x109/L). Treatment was resumed during neutropenic episodes following subsequent chemotherapy cycles. Serum galactomannan assay was performed twice weekly during neutropenia. High-resolution chest computed tomography was done when there was a clinical suspicion of IPA. Fluconazole was allowed but antifungal drugs with anti-mold activity were not permitted. The trial is registered at www.clinicaltrials.gov as NCT01615809. RESULTSThirty-two patients were included, 19 were male (59.4%), median age was of 5.5 years (range 3-16). Twenty-nine patients were diagnosed with acute lymphoblastic leukemia (ALL), 3 with acute myeloid leukemia. Among the patients with ALL, 24 had a de novo ALL and 5 a relapsed ALL. A total of 389 administrations of nebulized ABCL were performed, with a median per patient of 13 (range 1-19). All patients tolerated the drug and no patient had to discontinue it due to intolerance or an adverse event. No patient presented a severe adverse event in relation to ABCL. Five patients suffered from mild adverse events (cough, eye discomfort). Nine patients were withdrawn from the study, 2 were referred to another institution to undergo bone marrow transplantation and 7 due to systemic administration of an antifungal agent with anti-mold activity. Three of these patients developed a possible or probable IPA. There were no other cases of IPA. CONCLUSIONSProphylactic nebulizations with ABCL were well tolerated, safe and feasible in children aged 3-18 years diagnosed with acute leukemia. There is a need to perform further studies with a higher number of patients to evaluate the efficacy of this approach. DisclosuresRives:Teva Pharma: Other. Off Label Use: Nebulized Amphotericin-B lipid complex is not approved for prophylaxis of invasive fungal infection in pediatric patients with acute leukemia.

Bone Suppression Increases the Visibility of Invasive Pulmonary Aspergillosis in Chest Radiographs

ObjectiveChest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA.MethodsThe frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0–100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive.ResultsThe average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%.ConclusionThe detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity.

Approach to invasive pulmonary aspergillosis in critically ill patients

Apparently immunocompetent critically ill patients represent an increasing population at risk for invasive pulmonary aspergillosis (IPA). The current review gives an update on the epidemiology, diagnosis, and management of IPA in the ICU. Patients without apparent severe immunosuppression (e.g. chronic obstructive pulmonary disease, decompensated liver disease, etc.) represent the majority of ICU IPA cases. IPA diagnosis is problematic and the true incidence of IPA is difficult to be estimated because of the nonspecific clinical presentation. A user-friendly clinical diagnostic algorithm for IPA is valuable, particularly through a high negative predictive value. IPA carries a poor prognosis and has an important impact on hospital costs. Timely diagnosis and prompt administration of appropriate treatment may improve the outcomes. Intravenous voriconazole is the recommended primary IPA treatment, but liposomal amphotericin B also has clinical utility. Voriconazole presents bioavailability and toxicity issues, and drug level monitoring is advocated. Caspofungin or antifungal combinations are recommended as salvage therapy. A high level of suspicion in critically ill patients presenting with Aspergillus-positive respiratory tract cultures or nonresolving pulmonary infection may lead to earlier IPA diagnosis. Dosage individualization may decrease treatment discontinuation and improve clinical efficacy.

Clinical utility of Aspergillus galactomannan and PCR in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies

Interpretation of Aspergillus galactomannan (GM) and PCR results in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with haematological malignancies requires clarification. A total of 116 patients underwent BAL for investigation of new lung infiltrates: 40% were neutropenic, 68% and 36% were receiving mould-active antifungal agents and β-lactam antibiotics. The diagnosis of proven IPA (n=3), probable IPA (n=15), and possible invasive fungal disease (IFD, n=50) was made without inclusion of GM results. BAL GM (at cut-off of 0.8) had lower diagnostic sensitivity for IPA than PCR (61% versus 78%) but higher specificity (93% versus 79%). Both tests had excellent negative predictive values (85–90%), supporting their utility in excluding IPA. The use of BAL GM and PCR results increased the certainty of Aspergillus aetiology in 7 probable IPA cases where fungal hyphae were detected in respiratory samples by microscopy, and upgraded 24 patients from possible IFD to probable IPA. Use of BAL GM and PCR improves the diagnosis of IPA.

Clinical findings in 19 cases of invasive pulmonary aspergillosis with liver cirrhosis

Background: Aspergillus infection was mostly reported with high mortality rates and a bad prognosis in immunocompromised patients, but data were lacking on the clinical characteristics of aspergillus infection in liver cirrhosis. The aim of this study was to retrospectively assess the morbidity and mortality rate, clinical manifestation, risk factors, and medication of invasive pulmonary aspergillosis (IPA) in liver cirrhosis in The First Affiliated Hospital, College of Medicine, Zhejiang University.&#x0D; Methods: Patients with liver cirrhosis who had been diagnosed with proven or probable IPA by clinical and laboratory parameters from 1st December 2008 to 1st May2012 were retrospectively evaluated for predisposing factors for IPA and clinical outcome. The follow up ended on 30th July2012. IPA was defined according to European Organization for Research and Treatment of Cancer/Mysoses Study group criteria.&#x0D; Results: In total, 6,600 patients with liver cirrhosis were enrolled, and 19 out of these developed IPA. Seventeen out of 19 patients died. Imaging findings such as the halo sign and lower respiratory tract infection symptoms contributed to the early diagnosis of IPA. Possible risk factors for IPA included a high Child-Turcotte-Pugh (CTP) score, broad antibiotic usage and steroid exposure. The use of antifungal compounds may prolong a patient’s life.&#x0D; Conclusions: The mortality of liver cirrhosis with IPA is high. Liver cirrhosis should be considered a risk factor of IPA. Once patients with high CTP scores and steroid and broad spectrum antibiotics exposure present cough and fever, IPA should be taken into consideration and antifungal agents should be used as soon as possible.

Clinical findings in 19 cases of invasive pulmonary aspergillosis with liver cirrhosis

BackgroundAspergillus infection was mostly reported with high mortality rates and a bad prognosis in immunocompromised patients, but data were lacking on the clinical characteristics of aspergillus infection in liver cirrhosis. The aim of this study was to retrospectively assess the morbidity and mortality rate, clinical manifestation, risk factors, and medication of invasive pulmonary aspergillosis (IPA) in liver cirrhosis in The First Affiliated Hospital, College of Medicine, Zhejiang University.MethodsPatients with liver cirrhosis who had been diagnosed with proven or probable IPA by clinical and laboratory parameters from 1st December 2008 to 1st May2012 were retrospectively evaluated for predisposing factors for IPA and clinical outcome. The follow up ended on 30th July2012. IPA was defined according to European Organization for Research and Treatment of Cancer/Mysoses Study group criteria.ResultsIn total, 6,600 patients with liver cirrhosis were enrolled, and 19 out of these developed IPA. Seventeen out of 19 patients died. Imaging findings such as the halo sign and lower respiratory tract infection symptoms contributed to the early diagnosis of IPA. Possible risk factors for IPA included a high Child-Turcotte-Pugh (CTP) score, broad antibiotic usage and steroid exposure. The use of antifungal compounds may prolong a patient’s life.ConclusionsThe mortality of liver cirrhosis with IPA is high. Liver cirrhosis should be considered a risk factor of IPA. Once patients with high CTP scores and steroid and broad spectrum antibiotics exposure present cough and fever, IPA should be taken into consideration and antifungal agents should be used as soon as possible.

Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Invasive pulmonary aspergillosis (IPA) is difficult to diagnose in chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate whether detection of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) might be a useful means of making the diagnosis. Patients with COPD and new pulmonary infiltrates were enrolled. BALF was collected for culture and detection of GM. Venous blood was also sampled for GM detection. Biopsy samples were obtained whenever possible. Eleven cases of IPA were diagnosed (three proven and eight probable); 80 controls without IPA diagnosed were recruited. At a GM cut-off of 0.5, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing IPA were 90.9, 66.3, 27.0 and 98.1% in serum, and 90.9, 62.5, 25.0 and 98.0% in BALF, respectively. At a cut-off of 1.0, the specificity, PPV and NPV in BALF increased to 95.0, 71.4 and 98.7%; the sensitivity remained 90.9%. The sensitivity in serum was substantially lower than BALF (45.5% versus 90.9%). Receiver operating characteristic curve analysis identified an optimal BALF GM cut-off value of 1.25, with a sensitivity of 90.9% and a specificity of 96.3% for diagnosing IPA. At a relatively high cut-off value, BALF GM detection is a useful tool for the diagnosis of IPA in COPD. Besides piperacillin-tazobactam and amoxicillin-clavulanate, many other factors may also cause false-positive of GM detection in patients without IPA. Further work is needed to identify factors that might lead to false-positive or false-negative results.

Invasive pulmonary aspergillosis in non‐neutropenic patients with and without underlying disease: A single‐centre retrospective analysis of 52 subjects

Invasive pulmonary aspergillosis (IPA) remains a life-threatening infection in patients with prolonged neutropenia. Few data are available on IPA in non-neutropenic patients without underlying immunocompromising conditions. All non-neutropenic patients managed at the institution for a proven and probable IPA over the last 10 years were reviewed retrospectively, and the difference between non-neutropenic patients with and without underlying disease was investigated. Among 52 cases of IPA analysed here, 33 were histologically proven; 19 were probable. Forty-two (80.8%) patients had underlying diseases; 10 (19.2%) patients had no any underlying diseases. There is a significant difference in seasonal distribution among patients with underlying conditions (P = 0.026), but no seasonal difference was found in the other group (P = 0.622). The only significant difference in symptoms between the two groups was fever (P = 0.015). Radiological findings were non-specific in the two groups. Despite treatment, the overall crude mortality rate among 52 patients was 39%. The overall mortality rate in patients with underlying disease was 45%, while that in patients without underlying conditions was 11%. A Cox multivariate analysis showed that organ failure (hazard ratios: 8.739, 95% CI: 3.770-20.255; P = 0.000) was independently associated with overall mortality. Clinical features of IPA are not well known in non-neutropenic patients, especially in those without underlying conditions. In this study, organ failure was associated with a lower rate of survival of non-neutropenic patients with IPA.

Invasive pulmonary aspergillosis in the ICU: reply to Wichmann et al.

Dear Editor, We thank Dr. Wichmann and colleagues for their interesting remarks and discussion on our study [1] and we aim to further clarify their concerns. Although the diagnosis of invasive pulmonary aspergillosis (IPA) was made before or on the day of ICU admission in three of the five proven IPA patients, IPA diagnosis was made a median of 2 days after H1N1 diagnosis, as stated in the ‘‘Results’’ section of the paper. In none of the nine IPA patients (5 proven, 4 probable) was the diagnosis of IPA established before the diagnosis of H1N1. Moreover, respiratory symptoms, myalgia and fever were present before formal H1N1 diagnosis based on the respiratory sample taken at hospital or ICU admission, suggesting a delay in H1N1 diagnosis. We do acknowledge that the retrospective character of the study does not allow one to confirm a causal relationship and our findings have to be confirmed in larger prospective studies. On the other hand, the incidence of IPA in solid organ transplant patients is known to be about 0.5 % for kidney and up to 12 % for lung transplants [2–4]. The higher incidence (23 %) found in our study again may suggest that IPA is probably a true H1N1related superinfection on top of the existing risk for fungal infection associated with a solid organ transplant. We appreciate Wichmann et al.’s concern that some of the probable IPA cases were merely colonization. The clinical condition of critically ill patients, however, often does not allow invasive diagnostic procedures. However, even if only taking into account the five proven IPA cases, H1N1-related IPA incidence still was much higher than the 1.6–1.8 % reported so far in current literature [5, 6].

A Case of Acute Cerebral Aspergillosis Complicating Influenza A/H1N1pdm 2009

Invasive aspergillosis is a rare complication in patients with influenza infection. Several cases of invasive pulmonary aspergillosis accompanying influenza infections were reported during the influenza A/H1N1pdm 2009. We encountered a case of acute cerebral aspergillosis in a patient with influenza A/H1N1pdm 2009 infection. A 24-year-old man with uncontrolled diabetes was diagnosed with influenza A/H1N1pdm 2009 infection. Initial evaluation indicated methicillin-sensitive Staphylococcus aureus pneumonia and diabetic ketoacidosis along with influenza. During his hospital course, multiple new rim-enhancing mass lesions not evident in the initial evaluation developed in the fronto-parietal cortical and subcortical white matter and right cerebellum. Pathology and culture results confirmed the presence of Aspergillus fumigatus. Surgical drainage combined with a total of 18 weeks of antifungal therapy resulted in complete resolution of the infection. This case demonstrates that cerebral aspergillosis can present alongside influenza in patients with diabetes or those under intensive care. Clinical suspicion of invasive aspergillosis is required for a definite diagnosis and better prognosis in such cases.

Clinical analysis on 20 cases of invasive pulmonary aspergillosis

Objective To investigate high-risk factors, clinical features, imaging features, treatment and prognosis factors in the incidence of invasive pulmonary aspergillosis. Methods A retrospective analysis was carried out to 20 cases of clinical data in our hospital diagnosed as pulmonary aspergillosis infection from January 2008 to June 2012.Resuhs In the 20 cases of invasive pulmonary aspergillosis, there were 15 patients found with immunodeficiency, 5 cases of previously healthy. Clinical features： fever 14 cases （70%）, cough in 12 patients （60%）, sputum in 10 patients （50%）, shortness of breath, 8 cases （40%）, pleural effusion in 4 cases （20%）, 4 cases of chest pain （20%）, hemoptysis in 12 cases （60%）. Imaging features： 5 cases of nodules, lumps shadow 3 cases, 2 cases of ground-glass infiltrates, 4 cases of empty and crescent sign 3 cases, large tracts of real change 3 cases. 18 patients with the antifungal drug voriconazole, 2 cases of surgical treatment. Prognosis： cured 10 cases, 5 cases effective, 2 cases giving up, and 3 patients died. Conclusion The clinical features and imaging features of invasive pulmonary aspergillosis are not specific, the diagnosis relies on etiology and pathological examination. Early diagnosis to patients with immunodeficiency by using voriconazole therapy can improve the cure rate, and provide a good prognosis for patients without high risk factors. Key words: Pulmonary aspergillosis; Voriconazole