Subacute Invasive Aspergillosis Research Articles

Sensitivity of Antigen, Serology, and Microbiology Assays for Diagnosis of the Subtypes of Chronic Pulmonary Aspergillosis at a Teaching Hospital in São Paulo, Brazil.

Chronic pulmonary aspergillosis (CPA) is divided into five subtypes. The diagnosis of CPA is complicated due to poor sensitivity of the laboratory tests. Diagnostic performance of different antigen, serological, and microbiological methods in subtypes of CPA is unknown. The purpose of this study was to evaluate the diagnostic performance in different subtypes of CPA. A total of 91 participants with CPA were included, and the study was performed at Hospital das Clínicas of University of São Paulo. Bronchoalveolar lavage galactomannan (73%, 11/15), serology by immunodiffusion test (81%, 61/75), and histology (78%, 39/50) had the best sensitivity. The counterimmunoelectrophoresis (CIE) titers had a significant statistical difference between the CPA subtypes (P < 0.001), in which the forms chronic fibrosing pulmonary aspergillosis (CFPA) and subacute invasive aspergillosis (SAIA) had higher titers: 1/64 (interquartile range [IQR]: 1/32-1/256) and 1/64 (1/32-1/128). C-reactive protein generally presented lower values (median 15 mg/L, IQR: 6-33), with higher values in SAIA and lower values for Aspergillus nodule. Overall, we found a low diagnostic sensitivity of current tests. Regarding the CPA subtypes, we did not find great differences in the performance of the tests, but it is observed that the inflammatory markers and CIE titers tend to be higher in forms of the more extensive lung parenchyma involvement, such as SAIA and CFPA.

A Case of Invasive Pulmonary Aspergillosis vs. Pulmonary Aspergilloma in Immunocompromised Patient With Preexisting Lung Cavity

Subacute invasive aspergillosis (SAIA) occurs in immunocompromised patients and/or patients with preexisting pulmonary pathology. An aspergilloma is a fungus ball that occurs in preexisting lung cavities and can be relatively asymptomatic without tissue invasion. In contrast to an aspergilloma, SAIA invades local tissue and parenchyma, resulting in tissue necrosis. We present a case of a 68-year-old immunocompromised female with a past medical history of hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), stage IIIA adenocarcinoma, and a preexisting pulmonary cavity with chronic invasive aspergillosis vs. pulmonary aspergilloma treated with oral (PO) voriconazole. This case demonstrates that invasive aspergillosis should be considered in the differential diagnosis of any pulmonary lung lesion showing tissue invasion and expansion in an immunocompromised patient.

Clinical Features, Diagnostic Test Performance, and Prognosis in Different Subtypes of Chronic Pulmonary Aspergillosis

ObjectiveThe aim of this study was to describe clinical features in different subtypes of chronic pulmonary aspergillosis (CPA)-simple aspergilloma (SA), chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN), and subacute invasive aspergillosis (SAIA), respectively, and identify long-term prognosis of CPA.MethodsWe reviewed patients diagnosed with different subtypes of CPA from 2002 to 2020 at Nanjing Jinling Hospital, China. We analyzed the clinical and survival information of five different subgroups. A Cox regression model was used to explore proper antifungal duration and long-term survival factors of CCPA and SAIA.ResultsA total of 147 patients with CPA were included, consisting of 11 SA, 48 CCPA, 5 CFPA, 12 AN, and 71 SAIA. The most common underlying pulmonary disease was pulmonary tuberculosis (n = 49, 33%), followed by bronchiectasis (n = 46, 31.3%) and chronic obstructive pulmonary disease (COPD) or emphysema (n = 45, 30.6%), while in SAIA and CFPA groups, the most common was COPD or emphysema (45.1 and 100%). Cough (85%), expectoration (70.7%), hemoptysis (54.4%), and fever (29.9%) were common symptoms, especially in CCPA, CFPA, and SAIA groups. The common imaging manifestations included cavitation (n = 94, 63.9%), fungal ball (n = 54, 36.7%), pleural thickening (n = 47, 32.0%), and bronchiectasis (n = 46, 31.3%). SAIA and CFPA groups had a lower value of hemoglobin (HB) and serum albumin (ALB) with higher C-reactive protein and erythrocyte sedimentation rate. The positive rate of sputum culture, serum galactomannan (GM), and bronchoalveolar lavage fluid GM was 32.7% (36/110), 18.4% (18/98), and 48.7% (19/39), respectively. There were 64.6% (31/48) patients with CCPA and 25.4% (18/71) patients with SAIA who received surgery and the 5-year cumulative survival rate was 92.1 and 66.6%, respectively. SAIA, old age, male, low body mass index (BMI), COPD or emphysema, multiple distribution, low serum ALB, and positive sputum culture were adverse prognosis factors for SAIA and CCPA group, and BMI ≤ 20.0 kg/m2 was independently associated with increased mortality (hazard ratio (HR) 5.311, 95% CI 1.405–20.068, p = 0.014). Multivariable Cox regression indicated that surgery (HR 0.093, 95% CI 0.011–0.814, p = 0.032) and antifungal duration >6 months (HR 0.204, 95% CI 0.060–0.696 p = 0.011) were related to improved survival.ConclusionThe clinical features and laboratory test performance are different among SA, CCPA, CFPA, AN, and SAIA. Low BMI was an independent risk factor for survival. Selective surgery and antifungal duration over 6 months were associated with improved survival.

Diagnostic cut-off value for Aspergillus fumigatus- and flavus-specific IgG with clinical relevance in chronic pulmonary Aspergillus infection: A pilot study in Taiwan.

The diagnostic cut-off value for chronic pulmonary Aspergillosis (CPA) by Aspergillus fumigatus-specific IgG has never been evaluated In Taiwan. The cut-off value for Aspergillus flavus-specific IgG has not been evaluated worldwide. Evaluate diagnostic cut-off value of Aspergillus IgG and its application characteristics. Blood from control groups and treatment-naïve patients with CPA infections was collected for Aspergillus-specific IgG measurements. Controls were patients who had chest radiographic abnormalities and signs of respiratory tract infection, but were negative for Aspergillus and resolved without anti-mould therapy. Confirmation and probability of CPA were defined according to radiological features and positivity for an Aspergillus or galactomannan index. Chest computer tomography patterns were recorded for the presence of aspergilloma or nodules, subacute invasive aspergillosis, chronic cavitary pulmonary aspergillosis and chronic fibrotic pulmonary aspergillosis. A total of 35 cases and 50 disease controls were included. The levels of A.fumigatus- and A.flavus-specific IgG correlated with CPA progression (P<.05) but not with the presence of Aspergillus species from clinical specimens (P>.05). The best cut-off value for A.fumigatus IgG was 21.7mg/L with area under curve (AUC) for receiver operating characteristic curve (ROC) 0.934 and had 85.7% sensitivity and 92.0% specificity. For A.flavus IgG, the best cut-off value was 22.1mgA/L and the AUC was 0.928 with 88.2% sensitivity and 94.1% specificity. The level of Aspergillus-specific IgG correlated with radiographic characteristics in patients with CPA and the best cut-off values compared to controls were 21.7mgA/L for A.fumigatus-specific IgG and 22.1mgA/L for A.flavus-specific IgG.

A CASE OF CHRONIC PULMONARY ASPERGILLOSIS IN A HEALTHY IMMUNOCOMPETENT PATIENT

SESSION TITLE: Chest Infections: Find the Fungus SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/21/2019 3:15 PM - 4:15 PM INTRODUCTION: Chronic pulmonary aspergillosis (CPA), and specifically its most common form – chronic cavitary pulmonary aspergillosis (CCPA) - is an uncommon pulmonary disease (1). It may be seen in either patients are who are immunocompromised or patients who are immunocompetent with underlying lung disease. We present a case of CCPA complicated by recurrent hemoptysis necessitating surgical resection in a healthy 19-year-old female without known underlying lung disease. CASE PRESENTATION: A 19 year-old female presented with one month of hemoptysis. She was healthy, without any known medical problems until age 17 when she was found to have a mycetoma and cavitary pneumonia. She underwent an extensive workup, including HIV and Quantiferon Gold testing, at that time which was negative and was treated with antibiotics. She was unable to complete a prolonged course of voriconazole due to financial constraints. Interval imaging demonstrated multiple cavitary lesions with air fluid levels and soft tissue density consistent with aspergilloma. She was asymptomatic between age 17 and 19, when she began to experience hemoptysis. The patient presented to our hospital with persistent hemoptysis. She underwent robotic video-assisted thorascopic surgery (VATS) with right lower lobectomy. The parenchyma was noted to contain numerous cystic cavities. Histological examination demonstrated free-floating aspergillus hyphae within a cyst wall. Although not definitive, the aspergilloma may have formed in an area of interlobar pulmonary sequestration or congenital cystic adenoid malformation. Five days following surgery, the patient had no further hemoptysis and was discharged home. DISCUSSION: CCPA is a common form of CPA, which also encompasses aspergillus nodules, simple aspergilloma, and subacute invasive aspergillosis (SAIA) or chronic necrotizing pulmonary aspergillosis. Left untreated, CCPA may progress to chronic fibrosing pulmonary aspergillosis (CFPA), which is characterized by extensive pulmonary fibrosis. It is exceedingly unusual for CCPA to develop in immunocompetent individuals without underlying pulmonary disease. Our patient is a young and healthy female who had no prior respiratory symptoms who presented at the age of 17 with an already formed aspergilloma. Oral antifungal therapy is considered standard of care for treatment of CCPA (1). Response is slow and requires a minimum of four months. Hemoptysis may necessitate surgical resection in those with adequate pulmonary function. CONCLUSIONS: CCPA may occur in imunnocompetent patients with no prior history of lung disease. The possibility of the presence of a previously unknown and asymptomatic congenital malformation may increase the risk for the development of CPA. Reference #1: Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J 2016;47:45-68. DISCLOSURES: No relevant relationships by Craig Fryman, source=Web Response No relevant relationships by Sameer Khanijo, source=Web Response No relevant relationships by Kelvin Wong, source=Web Response

SUBACUTE INVASIVE ASPERGILLOSIS: A DIAGNOSIS BASED ON EVERYTHING IT'S NOT

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Daily exposure to Aspergillus is common, but illness typically only develops in those with an altered immune system or underlying lung pathology. Whether a patient develops allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), or invasive pulmonary aspergillosis (IPA) is dependent on the host immune response and interaction with the fungus. CASE PRESENTATION: A 64 year old female with no significant medical history and 10 months of cough presented with three weeks of chest tightness and progressive dyspnea. Due to severe symptoms and diffuse expiratory wheezing she was admitted for treatment and observation. Given her exam, history of atopy and allergic rhinitis and subsequent pulmonary function tests demonstrating severe obstruction, she was diagnosed and treated for an asthma exacerbation. Her symptoms did not improve and she progressed to requiring supplemental oxygen at rest despite being on high dose steroids. A CT Chest was obtained and she revealed groundglass opacification isolated to the right upper lobe with associated mucus plugging. A wide differential was considered to include CEP/AEP, HP, atypical infections, MR, PAP or a vasculitis. Following an acute decompensation the patient was transferred to the ICU and intubated. A bronchoscopy was conducted showing mucus plugging of the left main bronchus. During her extensive evaluation IgE levels were within normal limits and Aspergillus galactomannan was negative, however respiratory cultures grew Aspergillus fumigatus. Based on the respiratory culture and clinical presentation, the patient was diagnosed with subacute invasive aspergillosis and started on voriconazole. The patient’s clinical symptoms and radiographic findings rapidly improved with antifungal treatment. Immunologic evaluation following diagnosis was unrevealing. DISCUSSION: Subacute invasive aspergillus is a rare, but increasingly recognized infectious presentation of an otherwise common mold. This case highlights the spectrum of disease seen with pulmonary aspergillosis. Although subacute invasive aspergillosis primarily occurs in the immunocompromised, our patient had no history of immunosuppression and subsequent evaluation showed no defects. Because aspergillus was not considered early in our evaluation, the patient progressed to hypoxia and ICU admission. CONCLUSIONS: Clinicians should not discard the possibility of pulmonary aspergillosis in the immunocompetent. Reference #1: Kanj A, et al. The spectrum of pulmonary aspergillosis. Respiratory Medicine 2018; 141: 121-131. Reference #2: Kosmidis C and Denning D. The clinical spectrum of pulmonary aspergillosis. Thorax 2015; 70: 270-277. Reference #3: Riscili BP and Wood KL. Noninvasive Pulmonary Aspergillus Infections. Clin Chest Medicine 2009; 30: 315-335. DISCLOSURES: No relevant relationships by Tara Brown, source=Web Response Consultant relationship with MedicalConsultant to CSA Medical Please note: $5001 - $20000 Added 03/11/2019 by Robert Browning, source=Web Response, value=Consulting fee Consultant relationship with Inovital Medical Please note: $1001 - $5000 Added 03/11/2019 by Robert Browning, source=Web Response, value=Consulting fee My spouse/partner as a Employee No relevant relationships by Nikhil Huprikar, source=Web Response

Chronic pulmonary aspergillosis in a tertiary care centre in Spain: A retrospective, observational study.

The aim of this study was to describe the characteristics of patients with chronic pulmonary aspergillosis (CPA) in a tertiary care centre in Spain. Retrospective cohort study of all patients diagnosed with CPA between January 2010 and December 2015. The patients were identified through the Microbiology Registry. Demographic, clinical, laboratory, radiological, microbiological and clinical data were recorded. Patients were followed up for 12months. Fifty-three patients were included; median age was 61.5years. Forty-seven had a lung condition, 25 suffered from COPD, 19 an active malignancy, 10 had previous pulmonary tuberculosis and 9 lung interstitial disease. Twenty-eight patients presented with chronic cavitary pulmonary form (CCPA) and 20 with subacute invasive aspergillosis (SAIA). Species identified were Afumigatus (34), Aniger (5), Aterreus (4) and Aflavus (3). All-cause 1-year mortality was 56%. Predictors of mortality were cancer history (OR, 9.5; 95% CI, 2.54-35.51; P<0.01) and SAIA (OR, 5.49; 95% CI, 1.49-19.82; P<0.01). Previous pulmonary tuberculosis, surgery for the treatment of CPA and CCPA were found to be associated with lower mortality (OR, 0.05; 95% CI, <0.01-0.47; P<0.01; OR, 0.16; 95% CI, 0.03-0.88; P=0.035 and OR 0.2, 95% CI, 0.01-0.67; P=0.01, respectively). This is the first study providing an overview of the features of CPA in patients from Spain. CCPA was the most frequent form of CPA and Afumigatus the most frequently isolated species. Patients with cancer history and SAIA had a worse prognosis.

Role of the Aspergillus-Specific IgG and IgM Test in the Diagnosis and Follow-Up of Chronic Pulmonary Aspergillosis

BackgroundChronic pulmonary aspergillosis (CPA) has a high rate of misdiagnosis and has been reported to have an increasing rate of morbidity and mortality. In this article, we assessed the serum Aspergillus-specific IgG and IgM test in the diagnosis of patients with CPA.MethodsA prospective study was conducted from January 2016 to July 2017 in Nanjing Jinling Hospital. Serum samples were collected from CPA patients (178 sera, 82 patients) and from non-aspergillosis patients (125 sera) with community-acquired pneumonia (CAP), active tuberculosis, bronchiectasis or lung tumors. Additionally, we included a control group of healthy patients(50 sera). Aspergillus-specific antibody detection was performed using a Dynamiker ELISA kit, and the results were compared with the value of galactomannan (GM) in bronchoalveolar lavage fluid (BALF).ResultsThe sensitivity and specificity of the Aspergillus-specific IgG antibody in the diagnosis of CPA were 84.1 and 89.6%, respectively. These values were slightly higher compared to those obtained for the sensitivity and specificity using the BALF GM test (79.1 and 84.2%, respectively). However, the sensitivity and specificity of Aspergillus-specific IgM antibody were only 43.9 and 87.2%, respectively. Moreover, the positive rate of IgG in patients with subacute invasive aspergillosis (SAIA) was 87%, compared to the positive rates of IgG in CPA patients sick for 3–6 months (80.0%), 6–9 months (81.8%) and ≥9 months (80.0%). Meanwhile, the positive rate of IgM in SAIA patients was 63%, compared to the positive rate of IgM in CPA patients sick for 3–6 months (46.7%), 6–9 months (0%) and ≥9 months (0%), respectively. Furthermore, serum IgG levels decreased gradually in the majority of CPA patients who showed positive response to antifungal therapy, and IgG levels increased in two CPA patients when their disease worsened.ConclusionA serum Aspergillus-specific IgG test is a valuable tool for the diagnosis of CPA and SAIA, while an Aspergillus-specific IgM test is only modestly specific for the diagnosis of SAIA. Overall, the variation trend of Aspergillus-specific IgG levels may reflect the therapeutic effectiveness in the long-term follow-up of CPA.

Clinical manifestations and outcomes of pulmonary aspergillosis: experience from Pakistan

IntroductionPulmonary aspergillosis has variable course of illness, severity and outcomes depending on underlying conditions. There is limited data available on the clinical manifestations and outcome of pulmonary aspergillosis from Pakistan.MethodsTo...

Primary aspergilloma and subacute invasive aspergillosis in two AIDS patients

Although uncommon, invasive aspergillosis in the setting of AIDS is important because of its peculiar clinical presentation and high lethality. This report examines two AIDS patients with a history of severe cellular immunosuppression and previous neutropenia, who developed subacute invasive aspergillosis. One female patient developed primary lung aspergilloma, with dissemination to the mediastinum, vertebrae, and spine, which was fatal despite antifungal treatment. The second patient, who had multiple cavitary brain lesions, and eye and lung involvement, recovered following voriconazole and itraconazole, and drugs for increasing neutrophil and CD4+ lymphocyte levels. These cases demonstrate the importance of Aspergillus infections following neutropenia in AIDS patients, and emphasize the need for early and effective antifungal therapy.

L’aspergillose en pratique pour le pneumologue

Aspergillus is involved in various lung illnesses related to type of exposition and immunity host response, local (tracheobronchial) and global. Allergic bronchopulmonary aspergillosis is due to a hypersensitivity response, diagnosis must be considered in presence of severe asthma with radiologic opacities, blood eosinophilia and elevated total serum IgE levels. Bronchial colonization is often accidentally discovered, but needs a monitoring. Pulmonary aspergilloma, often asymptomatic, grows in a preexisting cavity. Aspergillus bronchitis is a prolonged superficious endobronchial infection. Pseudomembranous necrotizing tracheobronchitis is a microinvasive bronchial infection, which prognosis is very bad. Acute invasive pulmonary aspergillosis affects quite always immunocompromised patients, but cases are not exceptional in patients with prior lung disease. Chronic necrotizing pulmonary aspergillosis may be divided in chronic cavitary and chronic fibrosing pulmonary aspergillosis, and subacute invasive aspergillosis according to the course of the disease, radiological outcome first. Management of diseases caused by Aspergillus is evolving with new diagnostic tools (PCR, Aspergillus antigenemia) and with new generation antifungal drugs.

Voriconazole for Aspergillosis

Subacute invasive aspergillosis (SIA) and chronic pulmonary aspergillosis (CPA) are most commonly seen in patients with AIDS, diabetes mellitus, or

Voriconazole Treatment for Subacute Invasive and Chronic Pulmonary Aspergillosis

Backround Voriconazole is a novel triazole antifungal with a broad spectrum including Aspergillus species. We conducted an open, noncomparative multicenter study to evaluate the efficacy and safety of voriconazole in subacute invasive and chronic pulmonary aspergillosis (CPA). Methods Patients without profound neutropenia and a proven or probable diagnosis of subacute invasive aspergillosis (IA) or CPA received voriconazole 200 mg twice daily for a period of 4-24 weeks as primary or salvage therapy. Dose escalation was allowed if efficacy was suboptimal, and toleration and safety were satisfactory. Response was assessed by clinical, radiological and mycological changes. A complete or partial response in subacute IA and improved or stable in CPA were assessed as favorable responses. Results Of 39 patients treated, 36 were assessable. The majority of patients had subacute IA (n = 21), proven in all 11 extra-pulmonary and in 23/25 (92%) of the pulmonary cases. Voriconazole was given as primary therapy in 22 (61%). All patients receiving salvage therapy (n = 14) had refractory IA, having failed itraconazole or amphotericin B (AmB) or both. Overall, a complete or partial response was seen in 9/21(43%) of subacute IA and improved or stable in 12/15 (80%) of those with CPA. Adverse events, mainly liver function test abnormalities, skin reactions, and visual disturbances were mild and transient, leading to early discontinuation of treatment in 5 cases. Conclusions In patients with subacute IA and CPA, voriconazole was efficacious as salvage or primary therapy.