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Influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) are increasingly recognised as important complications in patients requiring intensive care for severe viral pneumonia. The diagnosis can typically be made in 10-20% of patients with severe influenza or COVID-19, but only when appropriate diagnostic tools are used. Bronchoalveolar lavage sampling for culture, galactomannan testing, and PCR forms the cornerstone of diagnosis, whereas visual examination of the tracheobronchial tract during bronchoscopy is required to detect invasive Aspergillus tracheobronchitis. Azoles are the first-choice antifungal drugs, with liposomal amphotericin B as an alternative in settings where azole resistance is prevalent. Despite antifungal therapy, IAPA and CAPA are associated with poor outcomes, with fatality rates often exceeding 50%. In this Review, we discuss the mechanistic and clinical aspects of IAPA and CAPA. Moreover, we identify crucial knowledge gaps and formulate directions for future research., Competing Interests: Declaration of interests SF received travel grants for conference attendance from Pfizer and Gilead and a speakers' fee from The Healthbook Company. AC received speakers' fees from Gilead. CJC reports research grants from Merck and Cidara; consulting fees or participation on advisory boards for Shionogi, Scynexis, and Venatorx; and lecture honoraria from Gilead. J-PG received consultancy and speaker fees from Gilead, Mundipharma, and Pfizer. MH received grants and research funding from Astellas, Gilead, MSD, Pfizer, Euroimmun, F2G, Pulmocide, AiCuris, Partners, IMMY, Melinta, Mundipharma, Shionogi, and Scynexis. KL received consultancy fees from MRM Health and Mundipharma; speakers' fees from Pfizer and Gilead; a service fee paid to the institution from Thermo Fisher Scientific and TECOmedical; and fees for advisory board participation from MSD and Pfizer. BJAR received research grants from Gilead; consulting fees from F2G; payment for lectures from Gilead; support for attending meetings from Pfizer, Gilead, and F2G; and reports participation on a data safety monitoring and advisory board for Exevir. LV received support for a public doctoral defence from Pfizer; and travel support from Gilead and Pfizer for conference attendance. PEV received research grants from F2G and Gilead; and speakers' fees from Mundipharma, F2G, Gilead, and Pfizer. JW received an institutional research fund from Pfizer; investigator-initiated grants from Pfizer, Gilead, and MSD; speakers' and travel fees from Pfizer, Gilead, and MSD; declares participation in advisory boards of Pfizer and Gilead; and declares receipt of study drugs from MSD. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Timely detection of Aspergillus infection is crucial given the high mortality rate of pulmonary aspergillosis (PA). Here, the diagnostic performances for PA of mycological culture, Aspergillus real-time PCR, and metagenomic next-generation sequencing (mNGS) assay from bronchoalveolar lavage fluid, were evaluated. In total, 139 patients with suspected fungal pneumonia were enrolled between December 2021 and July 2023, collecting 139 bronchoalveolar lavage fluid samples for real-time PCR and culture, with 87 undergoing mNGS assay. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with 95% CIs of these assays for PA were as follows: 35.3% (14.2%-61.7%), 100.0% (94.0%-100.0%), 100.0% (54.1%-100.0%), 84.5% (79.3%-88.6%), and 0.676 (0.560-0.779), respectively, for culture; 82.4% (56.6%-96.2%), 98.3% (91.1%-100.0%), 93.3% (66.4%-99.0%), 95.2% (87.6%-98.2%), and 0.903 (0.815-0.959), respectively, for same diagnostic performance of real-time PCR and mNGS; and 94.1% (71.3%-99.9%), 96.7% (88.5%-99.6%), 88.9% (67.1%-96.9%), 98.3% (89.6%-99.7%), and 0.954 (0.880-0.989), respectively, for real-time PCR combining mNGS; real-time PCR, mNGS, and their combination significantly improved in area under the curve values over culture (P < 0.001), but real-time PCR testing and mNGS had no significant difference with each other and their combination. Overall, the performance of culture was limited by low sensitivity; both real-time PCR and mNGS assays as single diagnostic tests are promising compared with culture and combined tests., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosing chronic pulmonary aspergillosis (CPA) is still challenging, and infection with Aspergillus spp. must be detected early. The aim of this study was to evaluate, for the first time, the usefulness of a new loop-mediated isothermal amplification (LAMP) test kit in diagnosing CPA., Methods: This cross-sectional study was performed at the National Hospital Organization Kinki-Chuo Chest Medical Center. We prospectively enrolled patients with and without CPA. The primary outcomes of this study were the sensitivity and specificity of LAMP for the diagnosis of CPA., Results: In total, 34 patients with CPA and 21 without CPA (the control group) were enrolled between October 2019 and December 2021. Among the 34 patients with CPA, cultures were positive for CPA in 16 and negative for 18. The majority of fungi isolated in sputum were A. fumigatus in 15 specimens; Aspergillus flavus was isolated in 1) LAMP demonstrated 55.9% sensitivity (95% confidence interval [CI] 37.9-72.8) and 100.0% specificity (95% CI 77.2-100.0)., Conclusion: LAMP is an acceptable tool for diagnosing CPA, and its application in clinical practice necessitates more studies., Competing Interests: Declaration of competing interest No conflict of interest is declared., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The disease chronic pulmonary aspergillosis (CPA), which has 3 million cases globally, has a substantial impact on global health. The morbidity and mortality it cause are also rather severe. Patients with modest immune suppression or those with underlying structural and chronic lung illnesses are more likely to develop this condition. CPA pose a diagnostic and management challenge to clinicians. The condition causes patients to have persistent respiratory difficulties, which lowers their quality of life, and the therapy is lengthy and offers few choices. Particularly in a nation like India, where tuberculosis (TB) is prevalent and patients exhibit identical signs and symptoms, a strong index of suspicion is required. Treated pulmonary TB patients, presenting with symptoms or chest x-ray abnormalities, especially those with presence of cavity are also more prone to develop CPA. The constellation of symptoms together with presence of microbiological criteria and suggestive radiology can help to reach at the diagnosis. The field of mycology has made major developments, but there is still much to understand about this illness and to establish timely diagnoses and make the best use of the existing treatment choices. The burden of CPA in patients with treated TB is highlighted in this article along with the most recent research and clinical guidelines., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Aspergillus is one of the important pathogens that contribute to high mortality in patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). Although incidence rates of Aspergillus coinfection are high globally, a Japanese national survey reported a low incidence. This study aimed to describe the clinical characteristics of patients with COVID-19-associated pulmonary aspergillosis at our institute., Methods: We identified patients with microbiologically confirmed COVID-19 on mechanical ventilation in the ICU. Of these patients, we identified patients in whom Aspergillus was cultured from the respiratory specimen., Results: Of a total of 169 patients, seven had aspergillosis (4.1%), which included three patients, three patients, and one patient with possible, probable, and proven aspergillosis, respectively, according to the criteria of the European Confederation of Medical Mycology International Society. All patients received systemic steroid therapy. Two patients (one each with proven and probable aspergillosis) had tracheobronchitis diagnosed by bronchoscopy. All patients in whom Aspergillus was repeatedly isolated from samples died. The mortality rates for all cases and probable and proven cases were 57% (4/7) and 75% (3/4), respectively., Conclusions: The incidence rate of aspergillosis in patients with COVID-19 in the ICU was higher in our institute than that reported by a Japanese national survey (4.1% vs. 0.5%). Repeated detection of Aspergillus might suggest a true Aspergillus infection, such as chronic aspergillosis, rather than colonization. In patients with severe COVID-19 patients, it is important to always keep CAPA in mind., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Pulmonary aspergilloma is chronic and invasive, potentially leading to life-threatening massive hemoptysis. The role of surgery for treating pulmonary aspergilloma and its effect on long-term survival needs more study., Methods: We reviewed 166 patients with aspergillomas treated at Shanghai Pulmonary Hospital from 2004 to 2017. Surgery indications included destroyed lung parenchyma, recurrent hemoptysis, despite appropriate medical treatment, and isolated pulmonary nodules suspected to be aspergilloma. Pulmonary aspergillomas are classified as simple (in an isolated thin-walled cavity, ≤3 mm) or complex (a thick-walled cyst, >3 mm) based on computed tomographic scan findings., Results: Aspergilloma was complex in 100 patients (60.2%) and simple in 66 (39.8%). The median (interquartile range) size of complex aspergillomas (2.5 [0.3-8.0] cm) was larger than that (2.0 [0.2-6.0] cm) of simple types (P < .001). Hemoptysis occurred in 72 patients (72%) with complex disease and in 35 (53%) with simple disease (P = .014). Video-assisted thoracoscopic surgery was performed in 42 patients (63.6%) with simple aspergillomas, and 75 patients (75%) with of complex aspergillomas underwent thoracotomy. Prolonged air leakage (>7 days) was the most common (17 [10.2%]) postoperative complication. A bronchopleural fistula developed postoperatively in 1 patient (0.6%). One patient (0.6%) died of respiratory failure within 30 days postoperatively. Two patients (1.2%) experienced recurrence during follow-up. The overall 10-year survival rates were 87.7% for complex aspergillomas and 94.97% for simple aspergillomas (P = .478). Diabetes (12 [7.2%]; hazard ratio, 13.15; 95% CI, 1.12-154.46) was associated with a worse prognosis., Conclusions: The perioperative morbidity and mortality of pulmonary aspergillomas are acceptable. Overall survival rates of simple and complex types are comparable., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies., Objectives: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions., Data Sources: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021., Study Eligibility Criteria: ICU cohort studies and CAPA case series including ≥3 patients were included., Participants: Adult patients in ICUs with COVID-19., Interventions: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews., Methods: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis., Results: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival., Conclusions: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Chronic pulmonary aspergillosis (CPA) is an infection of the lung usually caused by Aspergillus fumigatus in patients with pre-existing pulmonary diseases. Its diagnosis hinges on demonstrating IgG antibodies against A. fumigatus. Herein, we evaluated the performance of a newly introduced point of care test (POCT) kit, the LDBio Aspergillus IgG/IgM lateral flow assay (LFA) in India with the standard ImmunoCAP kit for diagnosing CPA., Methods: A total of 60 serum samples (30 CPA cases and 30 controls) were evaluated by the Aspergillus immunochromatographic test (ICT) IgG/IgM LFA. Fluorescent-enzyme immunoassay was used to determine specific A. fumigatus-IgG concentrations (positive >27 mgA/L). Further, a systematic review and meta-analysis of studies (up to August 26, 2021) reporting the performance of LDBio ICT for the diagnosis of CPA was performed., Result: A sensitivity of 86.7%, specificity of 90%, negative predictive value of 87.1%, positive predictive value of 89.7%, negative likelihood ratio of 0.15, positive likelihood ratio of 8.67, and was observed for the LDBio IC. There was good agreement between LDBio ICT and ImmunoCAP (88.3%) with a Cohen's Kappa score of 0.77. Our systematic review identified four studies and the pooled sensitivity of 90%, specificity of 91%, area under the curve of 0.94 and diagnostic odds ratio of 57.2, for CPA diagnosis by LDBio ICT., Conclusion: Aspergillus LDBio ICT assay exhibits good sensitivity and can be used to screen CPA cases., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Objectives: The severe coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) and risk of fungal co-infection, pulmonary aspergillosis in particular. However, COVID-19 associated pulmonary aspergillosis (CAPA) cases remain limited due to the difficulty in diagnosis., Methods: We describe presumptive invasive aspergillosis in eight patients diagnosed with COVID-19 in a single center in Shenzhen, China. Data collected include underlying conditions, mycological findings, immunodetection results, therapies and outcomes., Results: Four of the eight patients had tested positive for Aspergillus by either culture or Next-generation sequencing analysis of sputum or bronchoalveolar lavage fluid (BALF), while the rest of patients had only positive results in antigen or antibody detection. Although all patients received antifungal therapies, six of these eight patients (66.7%) died., Conclusion: Due to the high mortality rate of CAPA, clinical care in patients with CAPA deserves more attention., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A 61-year-old man presented to the ED with fever, chills, cough, purulent sputum, and progressive shortness of breath for 7 days. The patient was an active smoker with at least 80 pack-year smoking history. He had no other medical or surgical history and was not on any medication at home., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). However, the clinical significance of the positivity of Aspergillus precipitating antibody (APAb), a serodiagnostic test for pulmonary aspergillosis (PA), at the time of MAC-LD diagnosis is unknown. The objective of this study was to investigate the effects of APAb test results on the clinical outcomes of patients with MAC-LD., Methods: We retrospectively analyzed patients who were newly diagnosed as having MAC-LD between 2007 and 2014 in our hospital and checked for APAb at the time of diagnosis., Results: We enrolled 131 patients in this study. Of these patients, 20 (15.3%) tested positive for APAb at the diagnosis of MAC-LD. The APAb-positive patients were more frequently male (70.0% vs. 37.8%, P = 0.013) and more frequently had pulmonary emphysema (60.0% vs. 13.5%, P < 0.001) and interstitial pneumonia (15.0% vs. 1.8%, P = 0.025) compared with the APAb-negative patients. During a median follow-up period of 4.0 years, PA developed in 12 of the APAb-positive patients (60.0%, CPA: 9 and allergic bronchopulmonary aspergillosis: 3) and 12 APAb-negative patients (10.8%, CPA: 12) (P < 0.001). The APAb-positive patients had a significantly higher rate of mortality than did the APAb-negative patients (P = 0.004). A multivariate analysis indicated that older age, lower albumin, fibrocavitary or fibrocavitary and nodular/bronchiectatic radiographic features, and APAb positivity were negative prognostic factors., Conclusions: APAb-positive patients with MAC-LD more frequently develop PA and may have an unfavorable prognosis., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published., Objectives: To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS., Sources: Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019., Content: In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug-drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials., Implications: The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.)

A 21-year-old patient presented with a short history of fatigue and dyspnea on a background of double-lung transplantation for cystic fibrosis and preexisting chronic superior vena cava obstruction. Computed tomography of the chest demonstrated a 3-cm mass occluding the right pulmonary veins, with associated right upper and lower lobe pulmonary parenchymal infiltrates. Two invasive procedures were performed, with similar complications in both procedures., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Notable progress has been made in the past years in the classification, diagnosis and treatment of pulmonary aspergillosis. New criteria were proposed by the Working Group of the International Society for Human and Animal Mycology (ISHAM) for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The latest classification of chronic pulmonary aspergillosis (CPA) suggested by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) has become widely accepted among clinicians. Subacute invasive pulmonary aspergillosis is now considered a type of CPA, yet it is still diagnosed and treated similarly to invasive pulmonary aspergillosis (IPA). Isavuconazole, an extended-spectrum triazole, has recently been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of IPA. The most recent Infectious Diseases Society of America (IDSA) guidelines strongly recommend reducing mold exposure to patients at high risk for pulmonary aspergillosis. The excessive relapse rate following discontinuation of therapy remains a common reality to all forms of this semi-continuous spectrum of diseases. This highlights the need to continuously reassess patients and individualize therapy accordingly. Thus far, the duration of therapy and the frequency of follow-up have to be well characterized., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A 60-year-old man was admitted to the hospital with productive cough and yellowish sputum, severe fatigue, and weight loss of 4 kg over the past month; furthermore, he reported a slowly progressive shortness of breath on exertion over the past 6 months. Before admission, he received ampicillin/sulbactam (750 mg) orally twice daily for 7 days without significant clinical improvement., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary non-tuberculous mycobacterial disease (PNTM) is a known risk factor for chronic pulmonary aspergillosis (CPA). However, few studies have focused on the prognosis of PNTM-associated CPA. In the present investigation, we aimed to elucidate the clinical course and prognostic factors of CPA in patients with PNTM., Methods: We retrospectively investigated the medical records of 62 patients with CPA and a history of PNTM who were admitted to Kinki-chuo Chest Medical Center between 2010 and 2015. Co-morbidities, causative microorganisms, radiological findings, and outcomes were evaluated., Results: The patients' median age was 69.5 years, and the median follow-up period was 4.2 years. The major underlying diseases, other than PNTM and CPA, were old pulmonary tuberculosis, chronic obstructive pulmonary disease, and interstitial pneumonia. The most common causative NTM species were Mycobacterium avium complex (MAC; 37 patients; 59.7%) and Mycobacterium kansasii (20 patients; 32.3%). Survival was 83% after 1 year and 61% after 5 years. Use of systemic corticosteroids (hazard ratio: 3.32, 95% confidence interval: 1.23-9.51; P=0.00177) and C-reactive protein levels ≥ 5.0 mg/dL (hazard ratio: 8.96, 95% confidence interval: 2.15-62.9; P=0.0014) at the time of CPA diagnosis were associated with increased over-all mortality., Conclusions: CPA frequently developed in patients with MAC and M. kansasii PNTM. The treatment course of PNTM was not associated with all-cause mortality. However, systemic corticosteroid use and high CRP levels were negative prognostic factors of CPA in patients with PNTM. Since the prognosis is poor, early diagnosis and treatment of CPA are important in patients with PNTM., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Rationale: Little is known about the role of Aspergillus precipitating antibody (APAb) in patients with Mycobacterium avium complex lung disease (MAC-LD)., Objectives: We investigated the clinical characteristics of patients with MAC-LD positive for APAb., Methods: We conducted a cross-sectional study targeting patients with MAC-LD. APAb was checked in all participants. Clinical variables included laboratory data, pulmonary function, high-resolution computed tomography findings, and health-related quality of life., Results: We analyzed 109 consecutive patients. Their median age was 68 years, and the median duration of MAC-LD was 4.8 years. Twenty (18.3%) patients tested positive for APAb. APAb-positive patients had significantly longer duration of MAC-LD (9.4 vs. 4.0 years, P = 0.017), more severe bronchiectasis evaluated by modified Reiff score (6.5 vs. 4, P = 0.0049), and lower forced expiratory volume in 1 s (%FEV 1 ) (75.1% vs. 86.2%, P = 0.013) than APAb-negative patients. Analysis of covariance adjusted for background factors and underlying pulmonary disease revealed that %FEV 1 was also significantly lower in patients with APAb (P = 0.045). Ten patients were newly diagnosed with chronic pulmonary aspergillosis (N = 5) or allergic bronchopulmonary aspergillosis (N = 5)., Conclusions: APAb is associated with lower pulmonary function, and observed especially in patients with longer duration of MAC-LD and severe bronchiectasis, even in the absence of cavitary lesions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Case Presentation: An African American man in his late 30s was referred to the pulmonary clinic for evaluation of a persistent cough of several weeks' duration. Cough was productive of mucopurulent sputum mixed with blood. He also noted generalized weakness and dyspnea with minimal exertion., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Aspergillus fumigatus is frequently recovered from respiratory secretions of cystic fibrosis (CF) patients. Azole resistance has been increasingly reported., Objectives: To assess the prevalence of azole resistance in A. fumigatus isolates from patients followed by two CF centers of northern Italy., Methods: 423 isolates (220 patients) were screened for azole resistance. Resistance was confirmed with the EUCAST method and cyp51A gene sequencing. Microsatellite genotyping was performed and results were compared with those of environmental resistant isolates., Results: No resistance was detected in one center, while 8.2% of the patients of the other center harbored resistant isolates. The TR 34 /L98H alteration in the cyp51A gene, present in seven cases, resulted associated with poor in-vitro activity of all tested azoles., Conclusions: The environmental origin of the resistance seems to be probable since azole resistance was found also in naïve patients and an identical microsatellite genotype in clinical and environmental isolates was observed., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables., Methods: Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated., Results: Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P < .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen's κ, -0.13 to -0.24)., Conclusions: Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Endobronchial aspergilloma is a rare and unusual presentation of lung aspergilloma; the natural history for such rare diseases is poorly understood. This report presents two cases of endobronchial aspergilloma complicated by primary and metastatic lung cancer, and summarizes previous reports that suggest that an endobronchial lung cancer lesion may promote the colonialization and growth of Aspergillus species in the bronchus. Therefore, if endobronchial aspergilloma is found, the complication of primary or metastatic endobronchial lung cancer should be carefully considered., (Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Chronic pulmonary aspergillosis (CPA) is a slowly progressing pulmonary syndrome caused by Aspergillus spp. Specific knowledge regarding the disease entity, diagnosis method, and management is needed. This review focuses on the recent advances in our understanding of CPA. A new clinical disease entity of chronic progressive pulmonary aspergillosis consisting of chronic necrotizing pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis is proposed. Although newer antifungals are not available, evidence describing the treatment of CPA is accumulating. Longer administration of azoles is required for a better prognosis, but there is a risk of inducing azole resistance. Therapeutic drug monitoring and patient education are required. Establishing a drug-susceptibility test that can be performed in the general laboratory and the referral center are also important. Although the number of publications regarding CPA is growing, there are still many unanswered questions. Additional evidence and translational research regarding diagnosis, management, and drug resistance are urgently needed to improve the outcome of CPA., (Copyright © 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

A 60-year-old asymptomatic woman was referred to our hospital because of an abnormal chest roentgenogram during a routine medical checkup. The patient had no history of memorable infectious diseases, except a liver abscess caused by Serratia marcescens at age 46 years. Her son was diagnosed with chronic granulomatous disease at the age of 1 year. She had never smoked cigarettes and drank only occasionally.

Both inherited and acquired immunodeficiency and chronic pulmonary disease predispose to the development of a variety of pulmonary syndromes in response to Aspergillus, a fungus that is ubiquitous in the environment. These syndromes include invasive aspergillosis, which is now recognized to occur in patients with critical illness without neutropenia and in those with mild degrees of immunosuppression, including from corticosteroid use in the setting of COPD. Chronic pulmonary aspergillosis includes simple aspergilloma, which is occasionally complicated by life-threatening hemoptysis, and progressive destructive cavitary disease requiring antifungal therapy. Allergic bronchopulmonary aspergillosis occurs almost exclusively in patients with asthma or cystic fibrosis. Recent advances in each of these syndromes include a greater understanding of the underlying pathophysiology and hosts at risk; improved diagnostic algorithms; and the availability of more effective and well-tolerated therapies. Improvement in outcomes for Aspergillus pulmonary syndromes requires that physicians recognize the varied and sometimes subtle presentations, be aware of populations at risk of illness, and institute potentially life-saving therapies early in the disease course.

A 64-year-old man presented with dyspnea, chest pain, cough, expectoration, and continuous low-grade fever. Chest radiography and computed tomography revealed a right-sided, thick-walled cavity with diseased lung parenchyma, and sputum microscopy confirmed fungal forms of aspergillus. He subsequently developed a left-sided pneumonia caused by aspiration of the right-sided abscess. Because lung resection was considered too invasive, we performed simplified cavernostomy using the Alexis Wound Protector (XXS) using local anesthesia. In addition to the excellent drainage outcomes, this procedure was both simple and efficient. Moreover, the procedure was associated with less pain and physical limitation for the patient., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Recommendations for the use of diagnostic testing in low respiratory infection in children older than 3 months were produced by the Groupe de Recherche sur les Avancées en Pneumo-Pédiatrie (GRAPP) under the auspices of the French Paediatric Pulmonology and Allergology Society (SP(2)A). The Haute Autorité de santé (HAS) methodology, based on formalized consensus, was used. A first panel of experts analyzed the English and French literature to provide a second panel of experts with recommendations to validate. Only the recommendations are presented here, but the full text is available on the SP(2)A website., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: A variety of complications occur in patients with pulmonary aspergilloma. The safety and feasibility of a thoracoscopic approach to therapeutic lung resection for pulmonary aspergilloma have not been well evaluated., Methods: The medical records of patients who underwent video-assisted thoracic surgery (VATS) or a thoracotomy for therapeutic resection of pulmonary aspergilloma between January 2005 and December 2012 were retrospectively reviewed for age, sex, indications for surgery, approach and procedures, postoperative pain, operative time, blood loss, hospital stay, cost, and complications., Results: A total of 310 patients underwent thoracotomy, 76 patients underwent attempted VATS lobectomy. Seventy-six patients from 310 patients for thoracotomy were selected and compared with the VATS group. Nine cases (11.8%) in the VATS group were converted to a thoracotomy for the following reasons: bleeding (n =2); dense fibrous adhesions (n =3); fused interlobar fissure (n =2); and hilar lymphadenopathy (n = 2). Lesions treated with pneumonectomy failed to be done using VATS. There was no difference in the blood loss and median operative time between the 2 groups, but the patients with VATS had shorter length of stay in the hospital (p = 0.035) and fewer complications (p = 0.032) than those with thoracotomy., Conclusions: Video-assisted thoracic surgery is an alternative to open procedures in the management of pulmonary aspergilloma. Simple aspergilloma and complex aspergilloma without infiltration of the hilum are good candidates for VATS resection. Aspergilloma lesions that require a pneumonectomy are still a major challenge for VATS., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Multiple causes for tree-in-bud (TIB) opacities have been reported. However, to our knowledge the relative frequencies of the causes have not been evaluated. The purpose of this study was to determine the relative frequency of causes of TIB opacities and identify patterns of disease associated with TIB opacities., Methods: Cases with TIB opacities in the radiology report in 2010 were identified by searching the Radiology Information System. Medical records and CT scan examinations were reviewed for the causes of TIB opacities. Patterns of disease associated with TIB opacities were evaluated., Results: Causes for TIB opacities were established in 166 of 406 (40.9%) cases. Respiratory infections (119 of 166, 72%) with mycobacteria (65 of 166, 39%), bacteria (44 of 166, 27%), viruses (four of 166, 3%), or multiple organisms (six of 166, 4%) were most common. Aspiration was the cause in 42 of 166 (25%). Alternating areas of normal lung with regions of small airways disease (TIB opacities, bronchiectasis) (random small airways pattern) was specific (0.92) for Mycobacterium avium complex infection. Nearly uniform distribution of bronchiectasis (widespread bronchiectasis pattern) was specific for "diseases predisposing to airway infection" (specificity 0.92), such as cystic fibrosis, primary ciliary dyskinesia, allergic bronchopulmonary aspergillosis, and immunodeficiency states. Consolidation and TIB opacities (bronchopneumonia pattern) were usually due to bacterial infection or aspiration. Dependent distribution (specificity 0.79) and esophageal abnormality (specificity 0.86) with TIB opacities were associated with aspiration. Chronicity of findings was associated with mycobacterial infection (P &lt; .0001, sensitivity 0.96). Acuteness of findings was associated with bacterial infection (P &lt; .001, specificity 0.87)., Conclusions: TIB opacities are most often a manifestation of infections or aspiration. Patterns of disease can provide clues to the most likely diagnosis.

Background: The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear., Methods: The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured., Results: In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve., Conclusion: The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Tuberculosis (TB) is a disease as old as mankind, whereas in India the first case of Human Immunodeficiency Virus (HIV) was reported in 1986. HIV and TB are so closely connected that their relationship is often described as a co-epidemic. Aspergilloma (Fungal Ball, Mycetoma) represents a saprophytic growth of aspergillus that colonizes in the preformed cavities commonly due to pulmonary tuberculosis (PTB). We report a case of HIV, active pulmonary tuberculosis and aspergilloma occurring in the same patient. Despite our best efforts, we could not lay our hands on any similar case in the medical literature.

There are only a few case reports in the literature on the coexistence of aspergillosis and echinococcosis. We report a case of a 45-year-old immunocompetent patient who presented with a history of intermittent fever and cough with haemoptysis. Chest x-ray and CECT showed a large cystic lesion in right lower lobe with multiple floating membranes. Histopathological examination of cyst wall revealed the laminated membrane of hydatid cyst along with infiltration of its wall with septate fungal hyphae with acute angle branching suggestive of aspergillosis.

Aspergillomas are fungal balls within lung cavities. The natural history is variable. Hemoptysis is a dangerous sequela. Medical therapy is ineffective because of the lack of a lesion blood supply. Randomized trials are lacking. Surgery should be the treatment of choice in cases of hemoptysis, and even in asymptomatic patients, if lung function is not severely compromised. Cavernostomy and cavernoplasty may be options for high-risk patients. Percutaneous therapy should be reserved for patients who are not fit for surgery. Bronchial artery embolization is appropriate for symptomatic patients not suitable for surgery. Embolization could be considered a preoperative and temporary strategy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 75-year-old woman with no history of pulmonary disease was admitted to the hospital complaining of fever and chills. Chest computed tomography and bronchoscopy suggested a broncholith-like calcified endobronchial lesion and postobstructive pneumopathy in the left lower bronchus. The mass obstructing the airway was removed using grasping forceps and it was diagnosed pathologically as endobronchial aspergillosis. Endobronchial aspergilloma presenting radiographically as a calcification without adjacent calcified lymph nodes is a rare condition, even though pulmonary fungal diseases including endobronchial actinomycosis can mimic broncholithiasis.

Background: The details of the clinical characteristics of patients with chronic pulmonary aspergillosis (CPA) have not been fully understood., Method: One hundred twenty-nine consecutive patients with isolation of Aspergillus species by culture from respiratory specimens who attended our hospital between October 2001 and September 2009 were enrolled. Patients diagnosed with chronic pulmonary aspergillosis (CPA) were retrospectively reviewed for clinical characteristics and prognosis, compared with patients with Aspergillus species colonization., Results: Forty-two (32.6%) were diagnosed with CPA, whereas 87 (67.4%) with colonization. Aspergillus fumigatus was significantly more frequently detected in the CPA group than in the colonization group. Regarding underlying diseases, CPA patients had a significantly higher prevalence of a history of pulmonary tuberculosis and diabetes mellitus than colonization patients. There were no significant differences between the CPA and colonization group in Aspergillus antigen titers. Positivity for Aspergillus precipitating antibody was 74.3% in CPA and 15.8% in colonization, respectively. Sensitivity and specificity of Aspergillus precipitating antibody for the determination of CPA was 74.4% and 84.1%, respectively.Patients with CPA had significantly shorter survival than patients with colonization (mortality rate 50.0% vs. 13.8%, observation periods: 28.7 ± 26.6 months) (p < 0.0001). Multivariable analysis revealed that BMI was an independent predictor of prognosis (Odds Ratio, 1.973; p = 0.0223)., Conclusions: CPA is a disease with a poor prognosis, which shows distinct clinical characteristics from colonization., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: A serum galactomannan (GM) assay has been approved for diagnosing invasive aspergillosis (IA). However, the role of the BAL-GM assay has not been well established. Therefore, we conducted a metaanalysis to determine the overall accuracy of BAL-GM in the diagnosis of IA., Methods: After a systematic review of English-language studies, the sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of BAL-GM for the diagnosis of IA were pooled using a bivariate metaanalysis. Hierarchic summary receiver operating characteristic curves were used to summarize overall test performance. Potential between-study heterogeneity was explored by subgroup analyses. We calculated posttest probability to evaluate clinical usefulness., Results: Twelve reports, including 13 studies, met our inclusion criteria. The summary estimates of the BAL-GM assay for proven or probable IA were as follows: SEN, 0.90 (95% CI, 0.79-0.96); SPE, 0.94 (95% CI, 0.90-0.96); PLR, 14.87 (95% CI, 8.89-24.90); and NLR, 0.10 (95% CI, 0.04-0.24). The four summary estimates of the BAL-GM assay for proven IA were 0.94 (95% CI, 0.86-0.98), 0.79 (95% CI, 0.68-0.86), 4.41 (95% CI, 2.87-6.77), and 0.07 (95% CI, 0.03-0.09), respectively. Significant heterogeneity was present., Conclusions: BAL-GM determination is a sensitive and specific test for the diagnosis of proven and probable IA. The measurement of BAL-GM is thus likely to be a useful tool for diagnosing IA. Further studies focused on the impact of treatment agents are needed.