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Allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) are diseases caused by Aspergillus infection, and CPA can develop from ABPA in some cases. We herein report a patient with CPA overlapping with ABPA. Serum cytokine levels were evaluated at 4 time points: the ABPA diagnosis, CPA diagnosis, 6 months after the start of voriconazole (VRCZ), and 12 months after re-administration of VRCZ. Interleukin (IL)-13 levels decreased upon glucocorticoid treatment, whereas IL-25 and IL-33 levels decreased rapidly with the initiation of antifungals. Early antifungal therapy may be important to control disease progression and prevent CPA overlap.

Objective: To evaluate the diagnostic performance of galactomannan (GM) detection in serum and bronchoalveolar lavage fluid (BALF) for invasive pulmonary aspergillosis (IPA) in non-neutropenic patients., Methods: A total of 291 non-neutropenic patients in the Second Xiangya Hospital of Central South University were included. According to the 2019 EORTC/MSG guidelines, all cases were divided into an IPA group (n = 24) and a non-IPA group (n = 267). Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficiency of GM detection in BALF and serum., Results: According to the receiver operating characteristic curves of BALF and serum GM, the areas under the curve were 0.961 and 0.699, respectively. The optimal BALF GM detection was found when the cutoff value was set to 0.87, whereas the sensitivity and specificity were 91.7% and 92.5%, respectively., Conclusions: BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Chronic pulmonary aspergillosis (CPA) is an emerging global disease with tuberculosis (TB) being the most important risk factor. Epidemiologic data on the seroprevalence of Aspergillus IgG and prevalence of CPA in different areas, especially in country with intermediate burden of TB, are lacking., Methods: We prospectively recruited healthy volunteers, TB close contacts, active TB patients and participants with old pulmonary TB in Taiwan during 2012-2019. We measured serum Aspergillus fumigatus and niger-specific IgG levels and assessed if the participants were having CPA., Results: A total of 1242 participants (including 200 healthy volunteers, 326 TB close contacts, 524 active TB patients and 192 old TB cases) were recruited. Using 27 mgA/L (milligrams of antigen-specific antibodies per liter) as cut-off level, the seropositive rate of A. fumigatus-specific IgG was 33.0% (66/200), 37.7% (123/326), 26.5% (139/524) and 43.2% (83/192) among the four groups, respectively. In multivariate logistic regression, pulmonary cavitation (OR 1.73; 95% CI 1.07-2.80), female sex (OR 1.49; 95% CI 1.14-1.95), old TB (OR 1.59; 1.05-2.42) were independent risk factors for Aspergillus IgG positivity. One (0.2%) active TB patient and four (2.1%) old TB patients developed CPA. Correlation between A. fumigatus and A. niger-specific IgG was high (Spearman correlation coefficient: 0.942)., Discussion: Geographic variation in Aspergillus IgG seroprevalence and CPA prevalence exists. A universal cut-off value for Aspergillus IgG may not exist. In areas and populations in which background Aspergillus IgG level is unknown, Aspergillus IgG may be better used as a test of exclusion for CPA using prespecified cut-off level., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown., Research Question: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap?, Study Design and Methods: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles., Results: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations., Interpretation: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: The treatment response in chronic pulmonary aspergillosis (CPA) is usually assessed based on the improvement in clinical and imaging findings. Herein, we evaluate serum Aspergillus fumigatus-specific IgG, serum galactomannan, weight change, and lung function for assessing treatment response in subjects with CPA., Methods: We categorized treatment response as favourable (improved or stable clinical response with radiologically improved or stable disease) or unfavourable (worsening of symptoms or radiological progression) after 6 months of treatment with antifungal azoles. We measured A. fumigatus-specific IgG, serum galactomannan, weight, and lung function at baseline, 3 months, and 6 months in those with favourable and unfavourable treatment response., Results: One hundred and twenty-six consecutive treatment-naïve subjects (53.2% (67/126) males; mean ± SD age, 42.3 ± 14.7 years) with CPA were included. One hundred and six and 20 were classified as having favourable and unfavourable response, respectively. After 6 months of treatment, the decline in serum A. fumigatus-specific IgG (n = 119) was similar in those with favourable or unfavourable response (mean ± SD, -26.3 ± 45.5 mgA/L vs. -3.4 ± 65.6 mgA/L; p 0.20). There was no significant change in the serum galactomannan (favourable vs. unfavourable: mean ± SD, -0.11 ± 2.8 vs. -0.62 ± 2; p 0.92) or FEV1 (favourable vs. unfavourable: mean ± SD, 24 ± 250 mL vs. -62 ± 154 mL; p 0.19) after 6 months of treatment. There was significant loss of weight (mean ± SD, -2.5 ± 4.5 kg) in subjects with unfavourable response., Conclusion: Serum A. fumigatus-specific IgG and serum galactomannan inconsistently decrease following treatment and may not be useful indicators for monitoring treatment response in CPA. Similarly, there is little change in pulmonary function following treatment. A gain in body weight is seen in those with favourable response., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA., Methods: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit., Results: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively., Conclusions: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis., Trial Registration: NCT03027089 . Registered 20 January 2017.

The Aspergillus -specific lateral-flow device (AspLFD) test is a newly developed point-of-care diagnostic method for invasive pulmonary aspergillosis. However, evidence of the diagnostic performance of the AspLFD for chronic pulmonary aspergillosis (CPA) is limited. Therefore, we conducted a retrospective study to investigate this in comparison with the galactomannan (GM) β-d-glucan (BDG) test. Fifty patients with chronic pulmonary aspergillosis and 65 patients with respiratory disease, as a control, were enrolled in this study. The majority of the CPA disease entities were chronic pulmonary aspergillosis (64.0%, n  = 32), followed by subacute invasive pulmonary aspergillosis (IPA) (20.0%, n  = 10) and simple pulmonary aspergilloma (SPA) (16.0%, n  = 8). The sensitivity and specificity of the AspLFD test in serum samples were 62.0% and 67.7%, respectively. The GM test (cutoff index, 1.54) showed a sensitivity of 22% and a specificity of 92.3%, while the sensitivity and specificity of the BDG test (cutoff, 19.3 pg/ml) were 48% and 90.8%, respectively. In bronchoalveolar lavage fluid samples, the AspLFD test showed a sensitivity of 66.7% and a specificity of 69.2%, while those of the GM test (cutoff index, 0.6) were 72.7% and 83.1%, respectively. The Aspergillus precipitating antibody test had 70% sensitivity. Unlike the Aspergillus precipitating antibody test, the AspLFD on serum samples showed similar sensitivity to non- fumigatus Aspergillus species. Patients with false-positive results for the AspLFD on serum samples were of a significantly higher age and had a higher prevalence of cavitary lesions in chest computed tomography than patients with negative results in the control group. Given the results in this study, the performance of the AspLFD using serum was acceptable as a point-of-care test for the diagnosis of CPA., (Copyright © 2019 American Society for Microbiology.)

Objectives: Pentraxin 3 (PTX3) contributes to resistance to Aspergillus infections. This study aimed to evaluate the presence of PTX3 in bronchoalveolar lavage fluid (BALF) and plasma in non-neutropenic patients with pulmonary aspergillosis., Methods: BALF (n = 211) and plasma samples (n = 307) were collected from patients initially suspected of having pulmonary aspergillosis. Among these, 112 cases (51 BALF samples and 89 plasma samples) were proven to be pulmonary aspergillosis. These cases were classified as invasive pulmonary aspergillosis (IPA), subacute invasive aspergillosis (SAIA) and chronic pulmonary aspergillosis (CPA). The remaining cases were non-aspergillosis controls and were diagnosed with community-acquired pneumonia (CAP), lung cancer and pulmonary cryptococcosis. Plasma samples from healthy controls (n = 30) were also collected., Results: The median (interquartile range, IQR) BALF PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases: 6.97 (2.91-13.51) ng/mL versus 1.26 (0.76-1.76) ng/mL. When the PTX3 threshold was set at 1.9 ng/mL, sensitivity and specificity of BALF PTX3 for aspergillosis were 86.3% (95%CI 83.8-88.4%) and 82.5% (95%CI 79.7-85.0%), respectively. The median (IQR) plasma PTX3 for aspergillosis cases was significantly higher than for non-aspergillosis cases and healthy controls: 7.10 (3.36-9.53) ng/mL versus 1.57 (0.86-2.35) ng/mL versus 1.10 (0.49-1.51) ng/mL. With a PTX3 threshold of 2.3 ng/mL, sensitivity and specificity were 79.8% (95%CI 70.1-81.2%) and 72.1% (95%CI 69.5-74.5%) respectively., Conclusions: BALF and plasma PTX3 may be biomarkers for differentiating aspergillosis from other conditions such as CAP, lung cancer, and pulmonary cryptococcosis in non-neutropenic patients., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Chronic pulmonary aspergillosis (CPA) complicates underlying lung disease, including treated tuberculosis. Measurement of Aspergillus-specific immunoglobulin G (IgG) is a key diagnostic step. Cutoffs have been proposed based on receiver operating characteristic (ROC) curve analyses comparing CPA cases to healthy controls, but performance in at-risk populations with underlying lung disease is unclear. We evaluated optimal cutoffs for the Siemens Immulite Aspergillus-specific IgG assay for CPA diagnosis in relation to large groups of healthy and diseased controls with treated pulmonary tuberculosis. Sera from 241 patients with CPA attending the UK National Aspergillosis Centre, 299 Ugandan blood donors (healthy controls), and 398 Ugandans with treated pulmonary tuberculosis (diseased controls) were tested. Radiological screening removed potential CPA cases from diseased controls (234 screened diseased controls). ROC curve analyses were performed and optimal cutoffs identified by Youden J statistic. CPA versus control ROC area under curve (AUC) results were: healthy controls 0.984 (95% confidence interval 0.972-0.997), diseased controls 0.972 (0.959-0.985), screened diseased controls 0.979 (0.967-0.992). Optimal cutoffs were: healthy controls 15 mg/l (94.6% sensitivity, 98% specificity), unscreened diseased controls 15 mg/l (94.6% sensitivity, 94.5% specificity), screened diseased controls 25 mg/l (92.9% sensitivity, 98.7% specificity). Results were similar in healthy and diseased controls. We advocate a cutoff of 20 mg/l as this is the midpoint of the range of optimal cutoffs. Cutoffs calculated in relation to healthy controls for other assays are likely to remain valid for use in a treated tuberculosis population., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) are presumed to represent 2 distinct manifestations of Aspergillus species in the lung., Objective: To investigate any possible overlap of the immunological tests used for diagnosing ABPA in proven cases of CPA., Methods: In consecutive subjects with CPA, we calculated the proportion of subjects who tested positive for all the immunological investigations used to diagnose ABPA (Aspergillus fumigatus specific IgE >0.35 kUA/L, total IgE ≥500 IU/mL, and eosinophil count ≥500 cells/μL) or obligatory criteria (A. fumigatus specific IgE >0.35 kUA/L and total IgE ≥500 IU/mL)., Results: A total of 269 subjects (53.5% males) of CPA with the mean (standard deviation [SD]) age of 44.3 (14.7) years were enrolled. The most common underlying disease was previously treated pulmonary tuberculosis (n = 230, 85.5%). Ninety-three (34.6%) subjects had total IgE ≥500 IU/mL, whereas A. fumigatus specific IgE >0.35 kUA/L was seen in 112 (41.6%) subjects. Thirteen (4.8%) subjects met all the immunological criteria for ABPA, whereas 59 (21.9%) subjects met the obligatory criteria. Subjects meeting the obligatory criteria had significantly higher eosinophil count (P ≤ .0001), greater immediate cutaneous reactivity to Aspergillus antigen (CPA-others vs obligatory criteria, 9.8 ± 13.9 vs 13.9 ± 14.9 mm, P value = .048), higher A. fumigatus specific IgG (99.3 ± 61.9 vs 122 ± 66.6 mgA/L, P = .015), and greater number of fungal balls (0.9 ± 0.7 [range, 0-3] vs 1.1 ± 0.9 [range, 0-4], P = .026) compared with those without., Conclusions: Approximately 5% of subjects with CPA fulfilled all the immunological criteria used for diagnosing ABPA, whereas 22% met the obligatory criteria for ABPA. Whether these patients would require a different management protocol requires further investigation., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The early diagnosis of chronic pulmonary aspergillosis (CPA) remains challenging. Currently, a new quantitative IgM antibody assay that enveloped purified galactomannan extracted from Aspergillus fumigatus as antigen was commercially available in China, but its diagnostic value remains to be established., Methods: To evaluate the role of this commercial IgM assay for diagnosis of CPA, a multi-center prospective study was performed in 12 hospitals in Zhejiang Province, from January 1 to December 31, 2016. Adult inpatients without severe immunocompromised condition and those with persistent clinical symptoms/radiological findings ≥3 months or a consistent appearance in chest CT that was suggestive of CPA were included. The clinical data were compiled using a structured questionnaire., Results: A total of 87 cases were enrolled, including 43 CPA. The sensitivity ranged from 16.3% to 46.5%, and the specificity from 77.3% to 95.5% when cutoffs were from 50 to 80 arbitrary unit (AU)/mL. The receiver operating characteristic analysis revealed an area under the curve of 0.627. When a cutoff of 38.12 AU/mL was applied, the sensitivity and specificity were 69.8% and 56.8%, respectively, which represents the best performance., Conclusions: To our knowledge, this study was the first to evaluate this commercial A. fumigatus-specific IgM antibody assay in CPA patients in China and indicates that this IgM assay has a limited value and should not be a prior recommendation for CPA diagnosis., (© 2018 John Wiley & Sons Ltd.)

Background: The number of patients with pulmonary nontuberculous mycobacterial disease complicated by chronic pulmonary aspergillosis (CPA) has been increasing. Additionally, CPA is reportedly associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). In the present study, we aimed to identify risk factors for developing CPA and stratify the risk for CPA development in patients with MAC-LD., Methods: We retrospectively examined 361 patients newly diagnosed with MAC-LD. Risk factors for CPA development were examined using multivariate Cox proportional hazards regression analyses. A risk stratification system was established using the risk factors and receiver operating characteristic curve analyses., Results: CPA developed in 20 (5.5%) of the 361 patients. Independent risk factors for CPA development included the presence of pulmonary emphysema, baseline steroid use, a serum albumin level <3.5 g/dL, and the presence of MAC-LD cavities. A 4-point scoring system was established to stratify patients into low-risk (0-1 point) and high-risk (2-4 points) groups. The 5-year incidence rates of CPA were 2.2% and 31% in the low- and high-risk groups, respectively (P < 0.001)., Conclusions: We identified independent predictors of CPA development and established a simple risk stratification system for identifying patients with MAC-LD who were at a high risk of developing CPA., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Aspergillus fumigatus is frequently encountered in sputum samples of patients with cystic fibrosis (CF), which traditionally has been interpreted as saprophytic airway colonization. However, this mere bystander role has been challenged by recent data. There is now evidence that Aspergillus fumigatus accelerates the decline of pulmonary function. (1→3)-β-D-glucan (BDG) and galactomannan (GM) are highly sensitive fungal biomarkers that are used to diagnose invasive fungal disease. However, their diagnostic value in CF patients is largely unknown., Methods: We conducted a retrospective cohort study on 104 CF patients to determine whether serum BDG and GM levels correlate with parameters such as Aspergillus-positive sputum cultures and lung function., Results: Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were significantly higher than in those without persistent Aspergillus detection (89 versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively). 27 and 7 patients had elevated BDG (≥ 60 pg/ml) or GM levels (> 0.5 ODI), respectivly. BDG and GM levels showed a significant correlation (p = 0.004). Patients with increased serum concentrations of BDG were more frequently Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower forced expiratory volume in one second (FEV1) than patients with a normal BDG (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or the growth of A. fumigatus, proved to be an independent predictor for the FEV1., Conclusions: CF patients with persistent Aspergillus detection have elevated BDG and GM levels which ranged between healthy and invasively infected patients. Serum BDG may be superior to GM and fungal culture in predicting an impaired lung function in CF patients.

Objectives: Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS)., Design & Methods: Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations. The samples were prepared by solid phase extraction, and then subject to UPLC-MS/MS quantification., Results: The assay fulfilled the requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines for assay validation, with a lower limit of quantification of 10ng/mL for total itraconazole and hydroxyitraconazole, and 0.1 and 0.5ng/mL for free itraconazole and hydroxyitraconazole, respectively. Recovery rates of total itraconazole and hydroxyitraconazole from whole plasma ranged from 53.3% to 64.0%, and recovery rates of free itraconazole and hydroxyitraconazole from ultrafiltrated plasma ranged from 81.6% to 98.7%. Matrix effect varied between 79.1% and 109.4% for total itraconazole and hydroxyitraconazole, and between 81.3% and 99.7% for free itraconazole and hydroxyitraconazole. The assay was successfully applied to therapeutic drug monitoring of itraconazole in three patients with chronic progressive pulmonary aspergillosis or invasive pulmonary aspergillosis. Plasma free hydroxyitraconazole concentrations were 8.1-, 23.3-, and 51.1-fold higher than plasma free itraconazole concentrations in the three patients., Conclusions: A method for sensitive and selective quantification of plasma total and free itraconazole and hydroxyitraconazole concentrations was developed using UPLC-MS/MS. Free hydroxyitraconazole concentration may be most important in therapeutic drug monitoring of itraconazole., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Patients with coexisting chronic pulmonary aspergillosis and nontuberculous mycobacterial lung disease may undergo treatment with both the antifungal itraconazole and the antimycobacterial rifamycin. However, rifamycins interact with itraconazole. We examined the effects of a 150 mg dose of rifabutin on serum itraconazole levels and found significantly lower levels in 28 patients receiving itraconazole with rifabutin (median, 0.65 μg/ml) compared with 65 patients receiving itraconazole alone (median 3.45 μg/ml, P < 0.001). One-third of patients receiving itraconazole and rifabutin reached the therapeutic range of serum itraconazole concentration. Therapeutic drug monitoring is strongly recommended during concomitant use of rifabutin and itraconazole., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly., (Copyright © 2017 American Society for Microbiology.)

Introduction: A steroid-immunosuppressed rat model of invasive pulmonary aspergillosis was use to examine the usefulness of galactomannan enzyme immunoassay (GM) and quantitative real time PCR (RT-PCR) in evaluating the association between response and exposure after a high dose of prophylactic posaconazole., Methods: Two different strains of Aspergillus fumigatus with different in vitro posaconazole susceptibility were used., Results: Serum concentrations demonstrated similar posaconazole exposure for all treated animals. However, response to posaconazole relied on the in vitro susceptibility of the infecting strain. After prophylaxis, galactomannan index and fungal burden only decreased in those animals infected with the most susceptible strain., Conclusion: This study demonstrated that both biomarkers may be useful tools for predicting efficacy of antifungal compounds in prophylaxis., (Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

The diagnosis of chronic pulmonary aspergillosis (CPA) depends on the radiologic image and the identification of specific antibodies. The present study aimed to evaluate accuracy parameters of enzyme-linked immunosorbent assay (ELISA) and of the determination of serum galactomannan level in the diagnosis of patients with CPA, comparing these results with the double agar gel immunodiffusion (DID) test. In addition, the prevalence of cross-reactivity and the serological progression after treatment were evaluated by comparing DID and ELISA. Six study groups were formed: G1: 22 patients with CPA, 17 of whom had Aspergillus fungus ball, one chronic cavitary pulmonary aspergillosis (CCPA) and four chronic fibrosing pulmonary aspergillosis (CFPA); G2: 28 patients with pulmonary tuberculosis (TB); G3: 23 patients with histoplasmosis (HST); G4: 50 patients with paracoccidioidomycosis (PCM); G5: 20 patients with cryptococcosis (CRC); and G6: 200 healthy controls. Serum antibodies were measured by DID and ELISA, with two antigen preparations--Aspergillus fumigatus (DID1, ELISA1) and a pool of A. fumigatus, A. flavus and A. niger antigens (DID2, ELISA2). The Platélia Aspergillus Enzyme Immunoassay (EIA) kit was used to measure galactomannan. The cut-off points of ELISA were determined for each antigen preparation and for the 95% and 99% confidence intervals. Despite the low sensitivity, DID was the technique of choice due to its specificity, positive and negative predictive values and positive likelihood ratio-especially with the antigen pool and due to the low frequency of cross-reactivity. ELISA1 and a 0.090 cut-off showed high sensitivity, specificity and negative predictive value, but a high frequency of cross-reactivity with CRC. The best degree of agreement was observed between ELISA1 and ELISA2. The detection of serum galactomannan showed high sensitivity, comparable to ELISA2. The immunodiffusion test showed an excellent relationship with the progression after treatment, which made it the reaction of choice for patient follow-up.

Background and Objective: There is limited data on size change during natural progression of pulmonary aspergilloma. We aimed at elucidating the clinical course and prognosis of aspergilloma according to its size change., Methods: A multicentre retrospective observational study was performed in 143 adult pulmonary aspergilloma patients with serial chest computed tomography images. The clinical course and risk of haemoptysis according to the size change of the cavity or mass of aspergillomas was evaluated., Results: Median follow-up duration was 5.1 years. The size of aspergillomas changed in 39.2% of study subjects. Decreased and increased volumes of aspergilloma were observed in 13.3% and 25.9%, respectively. Patients with decreased volume had significantly higher C-reactive protein, and more severe bronchiectasis and tuberculosis-destroyed lung. Clinically significant haemoptysis occurred in 50.3% of patients and was significantly associated with the cavity and mass volume of aspergilloma, but not the extent of volume change. A mean cavity diameter of more than 22 mm and a mass diameter of more than 18 mm increased the risk of clinically significant haemoptysis., Conclusions: A significant portion of pulmonary aspergilloma changed size in our population. The prevalence of clinically significant haemoptysis was associated with absolute size of cavity and mass of aspergilloma., (© 2014 Asian Pacific Society of Respirology.)

Several studies suggest mannose-binding lectin (MBL) deficiency is associated with various manifestations of aspergillosis. MBL serum levels and function are genetically determined, but levels rise during inflammation. We address the relative frequency of deficient genotypes, the relationship between serum level and genotype and both age and disease manifestations in patients with chronic pulmonary (CPA) and allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). DNA was extracted from blood samples, and MBL2 genotyping was performed using the INNO-LiPA MBL2 kit. Serum MBL concentrations were determined using ELISA. One hundred and eight patients were evaluated, 70 (65%) with CPA, 38 (35%) with allergic disease (ABPA, SAFS or undefined) and 13 (12%) had both CPA and ABPA. The mean MBL serum level was 1849 μg L(-1) and did not differ between groups. Forty subjects (37%) had exon 1 genotypes producing nonfunctional MBL (A/B, A/C, A/D and O/O), a frequency not different from published normal controls. A/A subjects with CPA had higher levels (2981 μg L(-1)) compared with allergic A/A subjects (2202 μg L(-1)) (pc0.012). No single haplotype, genotype or allele was significantly related to any aspergillosis phenotype. Worse breathlessness was associated with higher MBL levels among A/A subjects (P = 0.009) and conversely nonfunctional genotypes. Mean MBL values were higher in those with an Medical Research Council (MRC) breathlessness score of 5 compared with those with and MRC score of 1 (P = 0.023). A/A allergic subjects (n = 27) in this study were ≈ 11 years younger than allergic A/O subjects (n = 11, P = 0.02). Subjects with worse respiratory status or more severe CPA had higher MBL serum levels (P = 0.023; P = 0.034). Bronchiectasis was not associated with MBL levels in CPA or allergic aspergillosis. MBL genotype and serum level modulate progression of aspergillosis., (© 2012 Blackwell Publishing Ltd.)

A 31-year old female with anorexia nervosa was referred to the Department of General Surgical Science at Gunma University for a surgical resection of a pulmonary aspergilloma. The patient had received treatment for anorexia nervosa at the Department of Psychiatry of the Hospital of Gunma University Graduate School of Medicine. A chest radiograph showed an infiltrative shadow with apical pleural thickening in the left upper lung field. A contrast enhanced computed tomography showed an irregular mass shadow with cavity formation that involved spherical clusters in the left upper lobe. The patient was diagnosed with pulmonary aspergilloma by serological studies and radiological features. A pulmonary segmentectomy of the left apical segment (S1 + 2) through a lateral thoracotomy was successfully performed. She had an uneventful postoperative recovery, and the final histopathological examination confirmed the diagnosis of pulmonary aspergilloma. This is a rare case study of a young female patient with anorexia nervosa who developed pulmonary aspergilloma.

We present a case of intralobar pulmonary sequestration (IPS) and pulmonary aspergillosis (PA) in a 32-year-old Japanese man. Immunological examination indicated an initial diagnosis of PA and an antifungal agent was administered. Since an abnormal chest shadow persisted, another causative lung disease was suspected to exist. Further inspection revealed the presence of IPS and surgical resection was performed. The symptoms of IPS are usually secondary to pyogenic infection; nevertheless, Aspergillus is a possible causative microorganism.

Introduction: Invasive aspergillosis is a major cause of mortality in allogeneic bone marrow transplant recipients and patients treated for blood malignancies. The diagnostic tools, treatments and preventive strategies, essentially developed for neutropaenic patients, have not been assessed in populations whose immune systems are considered to be competent., State of the Art: Beside the standard picture of chronic Aspergillus infection, the incidence of invasive aspergillosis is increasing in non neutropaenic patients, such as those with chronic lung diseases or systemic disease treated with long-term immunosuppressive drugs and solid organ transplant recipients. This study reviews the specific features of invasive aspergillosis in non neutropaenic subjects (NNS) and discusses the value of the diagnostic tools and treatment in this population., Prospects: A better understanding of the pathophysiology and the epidemiological characteristics of invasive aspergillosis would provide a means of adapting the staging and classification of the disease for NNS., Conclusions: Invasive aspergillosis is under diagnosed in NNS who may already be colonised when they receive immunosuppressive treatment; this can lead to an adverse outcome in patients who are considered to be a moderate risk population., (Copyright © 2010. Published by Elsevier Masson SAS.)

Generally, the primary lesion of a mold infection is in the airway, an extravascular site. Therefore, the antifungal drug concentration at the actual tissue lesion of a mold infection is as important as in the blood compartment. Although our antifungal armamentarium has expanded recently, polyenes are still often needed in clinical practice because of their potent fungicidal activity and the rarity of resistance. Nevertheless, the distribution of amphotericin B (AmB) in infected lung tissue has not yet been evaluated. Using high-performance liquid chromatography analysis, we determined the concentrations of AmB in plasma and infected and uninfected tissues of resected lung simultaneously, in a patient with pulmonary aspergillosis treated with liposomal amphotericin B (L-AmB). The AmB concentration in the infected lesion of the lung was approximately 5.2 times higher than that in plasma and 3.7 times higher than in uninfected lung tissue. L-AmB accumulated in the infected lesion of the lung at a higher concentration. Although our data are from only one patient, they may be useful in helping to develop better strategies for the use of L-AmB against pulmonary fungal infections., (Copyright © 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Itraconazole is a widely prescribed triazole antifungal drug, often given for long periods. The authors report five cases of tremor related to itraconazole therapy, which occurred within 1-12 months of initiating treatment and resolved gradually following itraconazole withdrawal.

Background and Objective: The usefulness of two tests in the serodiagnosis of chronic pulmonary aspergillosis (CPA) was compared. The tests were the serum Aspergillus galactomannan antigen test (Platelia (R) Aspergillus) by enzyme-linked immunoassay (EIA) using old and new cut-off indexes, and the Aspergillus precipitating antibody test., Methods: Both Aspergillus-precipitating antibody and Platelia Aspergillus EIA positivity were measured in the sera of 28 patients at the time of diagnosis of CPA., Results: Serum Aspergillus precipitating antibody positivity was 89.3% (25/28) in CPA patients. Serum Platelia Aspergillus EIA positivity was 21.4% (6/28) using the old cut-off index (> or =1.5) and 50% (14/28) using the new cut-off index (> or =0.5)-still less than that for Aspergillus precipitating antibody. Three of the 28 CPA patients had positive reactions in the Platelia Aspergillus EIA using the old cut-off index but not in the Aspergillus precipitating antibody test. Positivity for (1,3) beta-d glucan was 15.4%, and that for culture on CHROMagar Candida was 17.9%. One patient with pulmonary actinomycosis had a false-positive reaction in the Platelia Aspergillus test with the new cut-off index., Conclusions: For the diagnosis of CPA, Aspergillus precipitating antibody testing is more sensitive than the Platelia Aspergillus EIA, even with the new cut-off index. False-positive reactions are observed with the Platelia Aspergillus EIA in patients with conditions such as pulmonary actinomycosis. Results should be interpreted with care when patients are positive for the Platelia Aspergillus EIA but negative for Aspergillus precipitating antibody.