Aspergillus Colonization Research Articles

YKL-40 Production Is Increased in the Lung during Aspergillus Colonization and BOS after Lung Transplantation

Purpose YKL-40 is a chitinase-like protein involved in the innate immune response to chitin containing organisms. Dysregulation of YKL-40 is seen with numerous human diseases characterized by inflammation and tissue remodeling including airway remodeling in asthma. In a small exploratory study, we found that YKL-40 transcription during Aspergillus colonization was associated with the future development of BOS. We sought to validate the relationship of YKL-40 with Aspergillus and BOS in a larger longitudinal study after lung transplantation. Methods and Materials We performed a retrospective study of adult lung transplant recipients from 2000-2008 with at least one available bronchoalveolar lavage fluid (BALF) specimen. YKL-40 protein concentrations were determined in BALF specimens using the MicroVue YKL-40 EIA Kit (Quidel) according to manufacturer instructions. Given that YKL-40 was repeatedly measured over time within a patient, we fit a random effects generalized linear model to investigate the effects of Aspergillus and other covariates on YKL-40 over time. Results We assayed 750 BALF samples from 204 lung transplant recipients. Aspergillus colonization was associated with a higher BALF concentration of YKL-40. YKL-40 concentrations were also significantly elevated after a diagnosis of BOS. YKL-40 concentrations were not significantly affected by acute rejection. Conclusions In a large longitudinal cohort of lung transplant recipients, YKL-40 production in the lung is increased during Aspergillus colonization and after BOS, validating transcriptional profiles in a smaller exploratory study. YKL-40 may play a role in a continuum of pathogenesis from Aspergillus colonization to BOS. Factors Influencing BALF YKL-40 Concentration Estimate Standard Error P value Intercept 144.81 14.69 Log months to BAL -14.23 2.81 Acute cellular rejection (A2 or greater) 12.23 8.54 0.15 BOS at time of sample collection 53.32 9.96 Aspergillus colonization 25.39 8.78 0.004

Preemptive treatment with voriconazole in lung transplant recipients

Invasive fungal infection (IFI) is associated with high mortality in lung transplant (LTx) recipients. Data for voriconazole use in preemptive treatment remain scant. A single-center, retrospective cohort study was conducted to investigate the efficacy and safety of voriconazole preemptive treatment for post-LTx colonization. We reviewed 62 adult LTx patients, who received their first course of voriconazole prophylaxis (i.e., as preemptive treatment) between July 2003 and June 2010. Outcomes were determined at 6 and 12 months after commencing therapy. Aspergillus fumigatus (75.8%) was the most common colonizing isolate. Median duration of voriconazole prophylaxis was 85 days. At 6 months, 1 LTx patient (1.6%) had IFI, 47 (75.8%) cleared their colonizing isolate, 3 (4.8%) had persistent colonization, 7 (11.3%) had recurrent colonization, 1 (1.6%) had new colonization, 2 (3.2%) had aspergilloma, and 1 (1.6%) was clinically unstable with no culture results. Sixteen (25.8%) had died by 12 months. Ten (16.1%) had likely drug-related hepatotoxicity. LTx patients with diabetes mellitus within 30 days before commencing prophylaxis were at higher risk of recurrent Aspergillus colonization at 6 months (P = 0.030). Chronic rejection within 30 days before prophylaxis was associated with 12-month mortality (P = 0.007). Voriconazole preemptive treatment resulted in low incidence of IFI and IFI-related mortality.

Aspergillus colonization in hydatid cyst: Addition of a case

Aspergillus is a common saprophytic fungus that causes invasive or non-invasive disease in humans. It commonly colonizes pre-existing lung cavities. It has been earlier reported to coexist in previously operated or ruptured hydatid cysts. However there have been only few case reports of its occurrence in previously unoperated cysts in immunocompetent hosts. The present case adds to this category.

Endobronchial Aspergilloma (EBA) - An Enigma in Itself

Abstract SESSION TYPE: Infectious Disease Case Report Posters IIPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PMINTRODUCTION: Endobronchial aspergilloma is a rare disease entity with pulmonary involvement of aspergillus. Definition of this entity is not well described in the literature and is not usually classified with other pulmonary aspergillosis. This is an unusual form of a fungus ball, found inside of the bronchus with or without a parenchymal lesion and/or cavity. Few cases of endobronchial aspergillosis associated with tumors have been reported in the literature.CASE PRESENTATION: A 49 year old, non smoker male with prior history of rectal cancer treated with surgery and chemo-radiation 6 years back and in remission presented with three weeks of dry cough and occasional hemoptysis. Patient was still symptomatic after a course of antibiotics. Chest X ray demonstrated left upper lobe (LUL) infiltrate and Computed Tomography (CT) of chest demonstrated LUL mass with adjoining atelectasis. Bronchoscopy revealed a pearly white lesion in LUL bronchus which was biopsied and pathology was consistent with necrotic tissue with surrounding Aspergillus species without local tissue invasion. CT guided biopsy of LUL mass showed Metastatic Adenocarcinoma positive for rectal tumor markers. Positron Emission Tomography revealed no other metabolically active lesion except the LUL mass. Our patient was treated with itraconazole for 3 months along with chemotherapy with significant improvement in clinical and radiographical findings.DISCUSSION: EBA is a rare disease entity with involvement of Pulmonary bronchus with Aspergillus species. It is hard to differentiate true EBA with colonization of Aspergillus with underlying cancer. 50 % of the patients are immunocompromised. Clinically patient exhibit symptoms of cough, fever, wheezing or hemoptysis. Radiographically, CT chest shows endobronchial lesion with lobar or segmental atelectasis. Bronchoscopy with endobronchial biopsy is diagnostic of EBA. Bronchoscopic findings vary from yellowish-white necrotic material-plaques to whitish nodules. Optimal treatment of EBA has not yet been established. Duration of therapy vary between 1 and 48 months in different case series based on disease severity. Treatment options include Amphotericin B, Voriconazole, Itraconazole or Capsofungin. Invasive procedures including debridement, surgical resection, stent placement and Nd-YAG laser has limited role in literature.CONCLUSIONS: EBA is a rare pulmonary manifestation of Aspergillus species. Treatment of EBA is a challenge since there is limited literature on the ideal duration and type of treatment.1) Endobronchial Aspergilloma: Report of 10 Cases and Literature Review- Yonsei Med J. 2011 September 1; 52(5)2) Endobronchial Aspergilloma in a 30-year-old Man- Journal of Bronchology: July 2007 - Volume 14 - Issue 33) Endobronchial Fungal Disease: An Under-Recognized Entity- Respiration 2007DISCLOSURE: The following authors have nothing to disclose: Aman Sethi, Nitesh Jain, Hasnain Bawaadam, Puja Sethi, Nisha Jain, Fazila Barodawala, Sivashankar SivaramanNo Product/Research Disclosure InformationChicago Medical School/Rosalind Franklin University of Health a Science, North Chicago, IL.

RETRACTED: Effect of Aspergillus Fumigatus sensitization and colonization on lung function and airways inflammation in asthma

RETRACTED: Effect of Aspergillus Fumigatus sensitization and colonization on lung function and airways inflammation in asthma

WS9.7 Modulatory effects of Aspergillus colonization and ABPA on blood and sputum eosinophils and neutrophils in CF

WS9.7 Modulatory effects of Aspergillus colonization and ABPA on blood and sputum eosinophils and neutrophils in CF

A Clinical Algorithm to Diagnose Invasive Pulmonary Aspergillosis in Critically Ill Patients

The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.

Evaluation of infections in the lung transplant patient

Infections in lung transplant recipients (LTRs) are a serious complication that is associated with high mortality. Early and accurate diagnosis is critical in the management of these infections in order to achieve improved outcomes. This review focuses on studies published in the last 2 years related to the evaluation and management of infections following lung transplantation. Valganciclovir is well tolerated and effective for long-term cytomegalovirus prophylaxis. Recently published guidelines recommend that foscarnet be added to ganciclovir for patients with life-threatening or sight-threatening disease while waiting for genotypic assay results because of ganciclovir-resistant strains. Mycobacterium abscessus has emerged as a significant pathogen in LTRs and should be eradicated in potential recipients before transplantation is performed. Preoperative Aspergillus colonization appears to not increase the risk of death after transplant. Azithromycin is protective against the development of bronchiolitis obliterans syndrome (BOS) and reduces mortality in LTRs. Eradication of Staphylococcus aureus in patients colonized prior to surgery can decrease postoperative surgical site infections from it by 80%. RNA interference therapy improves the symptoms of BOS in LTRs but does not have a direct antiviral effect. Although life-saving for most recipients, lung transplantation can be complicated by serious postoperative infections. Additional prospective studies are needed to better elucidate the role of molecular testing in the diagnosis of infections, to determine whether eradication of S. aureus colonization improves outcomes in LTRs, and to further evaluate the role of RNA interference therapy for infections in LTRs.

The Performance of Real-Time PCR, Galactomannan, and Fungal Culture in the Diagnosis of Invasive Aspergillosis in Ventilated Patients with Chronic Obstructive Pulmonary Disease (COPD)

Emerging reports have associated chronic pulmonary obstructive disease (COPD) with invasive aspergillosis (IA), particularly in patients treated with mechanical ventilation and/or corticosteroids. This is a multicentre study in which COPD patients demonstrating a new lung infiltrate while being mechanically ventilated were prospectively evaluated for the presence of IA. From the 47 patients studied, Aspergillus fumigatus was recovered in culture in two patients (4.2%). While serum galactomannan (GM) was negative for 94% of patients, GM levels in respiratory samples were >0.5, >1.0 and >1.5 for 74.5, 40.5, and 21.3% of patients, respectively. PCR was positive for 10 patients in the study but did not differentiate Aspergillus colonization from infection. The combination of PCR and GM in respiratory samples may be an interesting alternative to diagnose IA in COPD patients.

Fungal Colonization Within A Tissue Expander

Fungal contamination derived from prosthetic substances is not common, although because of the following reasons the number of cases has increased in the recent years: increased life expectancy, and therefore a greater number of surgical candidates; higher rates of underlying diseases, which are accompanied by immunosuppressive disorders that can cause a higher susceptibility for such infections. Most reports of infection in breast prosthesis and tissue expanders are bacterial infections, and fungi cases are still rare. Hereby, we report a case of Aspergillus colonization in a tissue expander of a patient with an old burn scar. This fungal growth inside saline-filled tissue expander was asymptomatic and not troublesome. It also caused no changes in the patient's treatment course.

Two cases of endobronchial carcinoid masked by superimposed aspergillosis: a review of the literature of primary lung cancers associated with Aspergillus

We describe 2 cases of endobronchial pulmonary carcinoid tumor with superimposed Aspergillus colonization. The Aspergillus hyphae were associated with fibrin, ulcer debris, and granulomatous inflammation in part masking the carcinoid tumor. Presence of necrotic debris made diagnosis on biopsy difficult, and atypical carcinoid could not be ruled out. The association of carcinoid tumor with aspergillosis is rare and has been reported in 4 other cases thus far. A review of the literature reveals at least 35 cases of lung carcinoma with coexisting Aspergillus upon presentation. Most of these carcinomas are either cavitary squamous cell or adenocarcinomas harboring an aspergilloma. The other carcinomas are associated with bronchial obstruction as in carcinoids or are a minor component of a preexisting cavity raising the possibility of "scar carcinoma." As in aspergillomas not associated with carcinoma, upper lobe involvement predominates. Diagnosis can be challenging with delayed discovery of underlying neoplasm leading to suboptimal treatment.

116 Effect of nebulised antibiotics on Aspergillus colonisation and complications

Nebulised antibiotics are associated with increased Aspergillus colonisation. It is not known whether this effect leads to increased Aspergillus antibodies or more frequent use of anti-fungal medication. Recent in-vitro data also suggests that colomycin may have fungicidal properties. We reviewed 129 adult patients classified as chronically colonised with Pseudomonas. Patients were receiving either long-term nebulised colomycin, nebulised tobramycin, or no antibiotic (Table 1). Patients not receiving nebulised antibiotics had lower Aspergillus positivity in sputum (p = 0.003) and lower specific Aspergillus IgE levels (p = 0.001). There was a trend to lower total IgE and use of anti-fungal medication. No significant differences were seen between the colomycin and tobramycin groups aside from the colomycin group received less anti-fungal medication (p = 0.03).

117 Results of an on-line survey of cystic fibrosis microbiology practices in UK laboratories

Nebulised antibiotics are associated with increased Aspergillus colonisation. It is not known whether this effect leads to increased Aspergillus antibodies or more frequent use of anti-fungal medication. Recent in-vitro data also suggests that colomycin may have fungicidal properties. We reviewed 129 adult patients classified as chronically colonised with Pseudomonas. Patients were receiving either long-term nebulised colomycin, nebulised tobramycin, or no antibiotic (Table 1). Patients not receiving nebulised antibiotics had lower Aspergillus positivity in sputum (p = 0.003) and lower specific Aspergillus IgE levels (p = 0.001). There was a trend to lower total IgE and use of anti-fungal medication. No significant differences were seen between the colomycin and tobramycin groups aside from the colomycin group received less anti-fungal medication (p = 0.03).

Comparison of an Aspergillus Real-time Polymerase Chain Reaction Assay With Galactomannan Testing of Bronchoalvelolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis in Lung Transplant Recipients

Early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) improves outcome. We compared the performance of publicly available pan-Aspergillus, Aspergillus fumigatus-, and Aspergillus terreus-specific real-time polymerase chain reaction (PCR) assays with the Platelia galactomannan (GM) assay in 150 bronchoalveolar lavage (BAL) samples from lung transplant recipients (16 proven/probable IPA, 26 Aspergillus colonization, 11 non-Aspergillus mold colonization, and 97 negative controls). The sensitivity and specificity of pan-Aspergillus PCR (optimal quantification cycle [Cq], ≤35.0 by receiver operating characteristic analysis) and GM (≥.5) for diagnosing IPA were 100% (95% confidence interval, 79%-100%) and 88% (79%-92%), and 93% (68%-100%) and 89% (82%-93%), respectively. The sensitivity and specificity of A. fumigatus-specific PCR were 85% (55%-89%) and 96% (91%-98%), respectively. A. terreus-specific PCR was positive for the 1 patient with IPA due to this species; specificity was 99% (148 of 149 samples). Aspergillus PCR identified 1 patient with IPA not diagnosed by GM. For BAL samples associated with Aspergillus colonization, the specificity of GM (92%) was higher than that of pan-Aspergillus PCR (50%; P = .003). Among negative control samples, the specificity of pan-Aspergillus PCR (97%) was higher than that of BAL GM (88%; P = .03). Positive results for both BAL PCR and GM testing improved the specificity to 97% with minimal detriment to sensitivity (93%). A recently developed pan-Aspergillus PCR assay and GM testing of BAL fluid may facilitate the diagnosis of IPA after lung transplantation. A. fumigatus- and A. terreus-specific real-time PCR assays may be useful in rapidly identifying the most common cause of IPA and a species that is intrinsically resistant to amphotericin B, respectively.

Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population

To determine if sputum colonization with Aspergillus species in patients with cystic fibrosis (PWCF) correlates with radiological abnormalities and/or a reduction in pulmonary function (FEV1). We prospectively evaluated 32 PWCF utilizing high resolution computed tomography (HRCT) of the thorax and pulmonary function testing (PFT). The cohort was assessed as two groups: Aspergillus positive (n=16) and Aspergillus negative (n=16) based on sputum culture for Aspergillus species. A modified Bhalla scoring system was applied to each HRCT scan by two blinded radiologists. Aspergillus positive patients had more severe and significant bronchiectasis compared to those Aspergillus negative (p<0.05). This was most marked in the right upper and lower lobes (RUL, RLL). Total Bhalla score was clinically significant in both groups and approached statistical significance between groups (p=0.063). No difference in pulmonary function between the groups was detected. PWCF colonized by Aspergillus species have greater radiological abnormalities undetectable by PFTs. Early radiological evaluation of Aspergillus colonized PWCF is therefore warranted.

Aspergillus colonization of an echinococcal cyst cavity: case report

Although lungs are common sites for the occurrence of saprophytic or invasive mycosis as well as hydatid cyst, aspergilloma within a hydatid cyst is a rare occurrence. A 36-year-old immunocompetent male presented with hemoptysis episodes of about 1 year duration. Chest X-ray revealed a smooth countered mass lesion located in the upper part of lower lobe of left lung. Surgical enucleation of the cyst wall was performed. Microscopic examination showed that the laminated membranes of hydatid cyst were invaded by septated fungal hyphea oriented with acute angles consistent with aspergillus. Herein, we report such a unique coexistence of hydatid cyst and aspergilloma, and emphasize possible complications depending on the immunostatus of the patient, if the aspergillus colonization is unnoticed in resected cystectomy material.

Management of voriconazole hepatotoxicity in a lung transplant patient

Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46-year-old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known dose-dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively.

Control of Early Aspergillus Mortality After Lung Transplantation: Outcome and Risk Factors

Historic treatment strategies in our institute had resulted in 10% Aspergillus mortality within the first posttransplant year. Despite nebulized amphotericin B (nAmB) prophylaxis, a significant incidence of Aspergillus infection, usually with poor outcome, is still reported. The aim of this single-center retrospective study was to evaluate the outcomes of patients receiving either standard nAmB or additional systemic caspofungin prophylaxis for selected high-risk patients. We also tried to define independent risk factors for either fungal infection or death. We followed 76 consecutive lung transplant patients performed at our center between 2002 and 2010 from the day of transplantation. The median follow-up duration was 953 days (2.6 years; range, 16–2,751 days). The endpoints were postoperative Aspergillus colonization or disease or death due to any cause. All patients received either nAmB deoxycholate (nAmBd, 15 patients) or nAmB lipid complex (nAmBLC, 61 patients). In addition, 33 patients also received short-term caspofungin prophylaxis. The overall cumulative mortality during the entire follow up was 14.5%. No clinically confirmed invasive Aspergillus infections (IPA) occurred during the first 2 postoperative years; however, there was 1 possible and 1 probable IPA. One patient died of bronchiolitis obliterans and IPA at 2 years 3 months. Twelve patients showed transient Aspergillus colonization. The antifungal prophylactic regimens were well tolerated. The risk factors for death were age >55 years and postoperative Aspergillus detection ( P = .011 and P = .015, respectively). Preoperative Aspergillus colonization/disease was not a risk factor for death ( P = 1.000). The strongest predictor of death was age >55 years, due to the elder probably being more susceptible to the adverse effects of immunosuppressants. Postoperative detection of Aspergillus still seems to be an indicator of a poorer outcome. Preoperative Aspergillus colonization is not necessarily a threat with prompt institution of antifungal prophylaxis.

S19 Real time PCR in the identification and management of Aspergillus in CF

PurposeThe reported prevalence of Aspergillus fumigatus in CF sputum varies widely from 12 to 57%. While patients with ABPA are routinely treated with antifungals, it is not know whether colonised...

Aspergillus Colonization and Aflatoxin Contamination of Maize and Sesame Kernels in Two Agro-ecological Zones in Senegal

Aflatoxin contamination of major food crops is a serious problem in Senegal. Maize and sesame samples were collected during a survey in five districts located in two agro-ecological zones in Senegal to determine levels of aflatoxin contamination and the distribution and toxigenicity potential of members of Aspergillus section Flavi. Maize samples from the Guinea Savannah zone (SG) exhibited lower aflatoxin content and colony-forming units (cfu) than those collected from the Sudan Savannah (SS) zone. In maize, aflatoxin concentration and cfu of A.flavus varied with cultivars, shelling practices and storage methods. The maize variety 'Jaune de Bambey' had high aflatoxin levels in both agro-ecological zones. Aflatoxin content in machine-shelled maize (120 ng/g) was more than 10-fold higher than that in manually shelled (8 ng/g) or unshelled maize. Aflatoxin content (between 0.1 and 1.2 ng/g) and cfu values (between 13 and 42 000 cfu/g) of sesame were low, suggesting a low susceptibility to A. flavus. In both agro-ecological zones, and in all storage systems, aflatoxin contamination was lower in sesame than in maize. In this study, only three species of Aspergillus section Flavi (A. flavus, A. tamarii and the unnamed taxon S BG ) were observed with the frequency of toxigenic strains remaining below 50% in maize from the SG zone compared with 51% of isolates from samples collected in Sedhiou district in SS zone. The proportion of toxigenic strains isolated from sesame was variable. For both crops, L-strains were the most prevalent in the two agro-ecological zones. Some of the atoxigenic strains collected could be valuable microbial resources for the biological control of aflatoxin in Senegal.