scholarly journals A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians

2020 ◽  
Vol 6 (3) ◽  
pp. 106
Author(s):  
Paige M. K. Larkin ◽  
Ashrit Multani ◽  
Omer E. Beaird ◽  
Ayrton J. Dayo ◽  
Gregory A. Fishbein ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Molecular Mechanisms ◽  
Antifungal Susceptibility ◽  
Clinical Infectious Disease ◽  
High Morbidity ◽  
Fungal Culture ◽  
Metagenomic Sequencing ◽  
Pulmonary Aspergillosis ◽  
Aspergillus Infection ◽  
Chronic Pulmonary Aspergillosis

Chronic pulmonary aspergillosis (CPA) refers to a spectrum of Aspergillus-mediated disease that is associated with high morbidity and mortality, with its true prevalence vastly underestimated. The diagnosis of CPA includes characteristic radiographical findings in conjunction with persistent and systemic symptoms present for at least three months, and evidence of Aspergillus infection. Traditionally, Aspergillus infection has been confirmed through histopathology and microbiological studies, including fungal culture and serology, but these methodologies have limitations that are discussed in this review. The treatment of CPA requires an individualized approach and consideration of both medical and surgical options. Most Aspergillus species are considered susceptible to mold-active triazoles, echinocandins, and amphotericin B; however, antifungal resistance is emerging and well documented, demonstrating the need for novel therapies and antifungal susceptibility testing that correlates with clinical response. Here, we describe the clinical presentation, diagnosis, and treatment of CPA, with an emphasis on the strengths and pitfalls of diagnostic and treatment approaches, as well as future directions, including whole genome sequencing and metagenomic sequencing. The advancement of molecular technology enables rapid and precise species level identification, and the determination of molecular mechanisms of resistance, bridging the clinical infectious disease, anatomical pathology, microbiology, and molecular biology disciplines.

Diagnostic Aspects of Chronic Pulmonary Aspergillosis: Present and New Directions

2019 ◽  
Vol 13 (4) ◽  
pp. 292-300 ◽  
Author(s):  
Bayu A. P. Wilopo ◽  
Malcolm D. Richardson ◽  
David W. Denning
Keyword(s):  
Point Of Care ◽  
Fungal Culture ◽  
Pulmonary Aspergillosis ◽  
Pleural Thickening ◽  
Point Of Care Test ◽  
Recent Innovation ◽  
Inappropriate Treatment ◽  
Chronic Pulmonary Aspergillosis ◽  
Diagnostic Approaches ◽  
Similar Appearance

Abstract Purpose of Review Diagnosis of chronic pulmonary aspergillosis (CPA) is important since many diseases have a similar appearance, but require different treatment. This review presents the well-established diagnostic criteria and new laboratory diagnostic approaches that have been evaluated for the diagnosis of this condition. Recent Findings Respiratory fungal culture is insensitive for CPA diagnosis. There are many new tests available, especially new platforms to detect Aspergillus IgG. The most recent innovation is a lateral flow device, a point-of-care test that can be used in resource-constrained settings. Chest radiographs without cavitation or pleural thickening have a 100% negative predictive value for chronic cavitary pulmonary aspergillosis in the African setting. Summary Early diagnosis of CPA is important to avoid inappropriate treatment. It is our contention that these new diagnostics will transform the diagnosis of CPA and reduce the number of undiagnosed cases or cases with a late diagnosis.

scholarly journals A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL)

2021 ◽  
Author(s):  
Findra Setianingrum ◽  
Anna Rozaliyani ◽  
Robiatul Adawiyah ◽  
Ridhawati Syam ◽  
Mulyati Tugiran ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
De Novo ◽  
Significant Risk ◽  
Fungal Culture ◽  
Bottom Line ◽  
Pulmonary Aspergillosis ◽  
Prospective Longitudinal Study ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg ◽  
Prospective Longitudinal

AbstractObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary tuberculosis (TB). CPA may also be misdiagnosed as bacteriologically-negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia; a country with a high incidence of TB.MethodsIn this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0-8 weeks) and at the end (5-6 months) of TB therapy. CPA diagnosis was based on symptoms (>3 months), characteristic radiological features and positive Aspergillus serology, and categorized as proven, probable and possible.ResultsOf the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence of proven and probable CPA at baseline was 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (2 with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA.ConclusionCPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.Key messagesWhat is the key question?Do what extent is chronic pulmonary aspergillosis (CPA) both a) mistaken for TB and b) co-exists with TB during the course of 6 months therapyWhat is the bottom line?Features consistent with CPA were present in 6% of patients when starting TB therapy and 8% at the end of therapy, with some resolving and some developing CPA de novo during TB therapy. At the end of B therapy symptoms, cavitations with Aspergillus-specific IgG detectable were the key features of CPA.Why read on?Co-existence of TB and CPA is present in a substantial minority of patients starting and ending TB therapy, and needs addressing in terms of diagnosis, dual therapy and follow up.

scholarly journals A prospective longitudinal study of chronic pulmonary aspergillosis in pulmonary tuberculosis in Indonesia (APICAL)

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216464
Author(s):  
Findra Setianingrum ◽  
Anna Rozaliyani ◽  
Robiatul Adawiyah ◽  
Ridhawati Syam ◽  
Mulyati Tugiran ◽  
...  
Keyword(s):  
Significant Risk ◽  
Incidence Rates ◽  
Fungal Culture ◽  
Pulmonary Aspergillosis ◽  
Laboratory Findings ◽  
Prospective Longitudinal Study ◽  
Pulmonary Tb ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg ◽  
Prospective Longitudinal

ObjectivesChronic pulmonary aspergillosis (CPA) can complicate recovery from pulmonary TB. CPA may also be misdiagnosed as bacteriologically negative TB. This study aimed to determine the incidence of CPA in patients treated for TB in Indonesia, a country with a high incidence of TB.MethodsIn this prospective, longitudinal cohort study in patients treated for pulmonary TB, clinical, radiological and laboratory findings were analysed. Sputum was collected for fungal culture and TB PCR. Patients were assessed at baseline (0–8 weeks) and at the end (5–6 months) of TB therapy. CPA diagnosis was based on symptoms (≥3 months), characteristic radiological features and positive Aspergillus serology, and categorised as proven, probable and possible.ResultsOf the 216 patients recruited, 128 (59%) were followed up until end of TB therapy. At baseline, 91 (42%) had microbiological evidence for TB. Aspergillus-specific IgG was positive in 64 (30%) patients and went from negative to positive in 16 (13%) patients during TB therapy. The incidence rates of proven and probable CPA at baseline were 6% (n=12) and 2% (n=5) and end of TB therapy 8% (n=10) and 5% (n=7), respectively. Six patients (two with confirmed TB) developed an aspergilloma. Diabetes mellitus was a significant risk factor for CPA (p=0.040). Persistent cough (n=5, 50%; p=0.005) and fatigue (n=6, 60%; p=0.001) were the most common symptoms in CPA.ConclusionCPA should be considered a relatively frequent differential diagnosis in patients with possible or proven TB in Indonesia. Lack of awareness and limited access to Aspergillus-specific IgG tests and CT imaging are obstacles in establishing a CPA diagnosis.

scholarly journals Chronic Pulmonary Aspergillosis Following Nontuberculous Mycobacterial Infections: An Emerging Disease

2020 ◽  
Vol 6 (4) ◽  
pp. 346
Author(s):  
Pakpoom Phoompoung ◽  
Methee Chayakulkeeree
Keyword(s):  
Lung Disease ◽  
High Dose ◽  
Fungal Culture ◽  
Pulmonary Aspergillosis ◽  
High Dose Corticosteroid ◽  
Reactive Protein ◽  
Chronic Pulmonary Aspergillosis ◽  
Dose Corticosteroid ◽  
Ntm Lung Disease ◽  
Higher Sensitivity

Chronic pulmonary aspergillosis (CPA) following nontuberculous mycobacterial (NTM) lung disease is being increasingly recognized, especially in countries where tuberculosis is not endemic, with an incidence rate of 3.9–16.7%. NTM lung disease has been identified as a predictor of mortality in CPA patients. The major risk factors for NTM-associated CPA include fibrocavitary NTM lung disease, the presence of pulmonary emphysema, and high-dose corticosteroid use. The onset of CPA is 1.5–7 years following the diagnosis of NTM lung disease. The diagnosis can be made using standard criteria; however, serological diagnosis using Aspergillus precipitin has demonstrated a higher sensitivity and specificity when compared with fungal culture from respiratory specimens. Treatment is challenging since rifampicin and oral triazoles should not be used concomitantly. The prognosis is poor, and the factors associated with worse prognosis are corticosteroid use and high C-reactive protein level.

scholarly journals CPAnet Registry—An International Chronic Pulmonary Aspergillosis Registry

2020 ◽  
Vol 6 (3) ◽  
pp. 96
Author(s):  
Christian B. Laursen ◽  
Jesper Rømhild Davidsen ◽  
Lander Van Acker ◽  
Helmut J.F. Salzer ◽  
Danila Seidel ◽  
...  
Keyword(s):  
Clinical Data ◽  
Research Collaboration ◽  
Descriptive Analysis ◽  
Research Network ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Pulmonary Aspergillosis ◽  
Specific Patient ◽  
First Line Therapy ◽  
Chronic Pulmonary Aspergillosis

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study’s aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.

Unusual case of chronic cavitary pulmonary aspergillosis presenting as spontaneous pneumothorax in an immunocompromised man

2021 ◽  
Vol 14 (8) ◽  
pp. e241655
Author(s):  
Swasthi S Kumar ◽  
Animesh Ray ◽  
Naval Kishore Vikram ◽  
Surabhi Vyas
Keyword(s):  
Potassium Hydroxide ◽  
Unusual Case ◽  
Acute Onset ◽  
Middle Lobe ◽  
Fungal Culture ◽  
Pulmonary Aspergillosis ◽  
History Of ◽  
Chronic Pulmonary Aspergillosis ◽  
Right Middle Lobe ◽  
Pleural Involvement

Chronic cavitary pulmonary aspergillosis (CCPA) is a slow destructive type of chronic pulmonary aspergillosis, characterised by multiple pulmonary cavities that develop and expand over several months or years. Pleural involvement in the form of pneumothorax has been rarely reported in CCPA. We report such an unusual case of an immunocompromised male, with a history of chronic cough and fever, presenting with acute onset of shortness of breath. Chest imaging showed bilateral multiple cavitating nodules, ground glass opacities and dense right middle lobe consolidations and right-sided pneumothorax. Bronchoalveolar lavage (BAL) showed septate hyaline hyphae on KOH (potassium hydroxide) staining and fungal culture grew Aspergillus fumigatus. BAL and serum galactomanan were positive and serum IgG for A. fumigatus was 58 MgA/L (0–40MgA/L) confirming the cause of spontaneous secondary pneumothorax in our patient as CCPA.

scholarly journals Misdiagnosis of chronic pulmonary aspergillosis as pulmonary tuberculosis at a tertiary care center in Uganda: a case series

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Richard Kwizera ◽  
Andrew Katende ◽  
Felix Bongomin ◽  
Lydia Nakiyingi ◽  
Bruce J. Kirenga
Keyword(s):  
Pulmonary Tuberculosis ◽  
Treatment Outcomes ◽  
Diagnostic Criteria ◽  
Tertiary Care ◽  
Chest Imaging ◽  
Resource Limited Settings ◽  
Pulmonary Aspergillosis ◽  
Resource Limited ◽  
Chronic Pulmonary Aspergillosis ◽  
Hiv Negative

Abstract Background Diagnosis of chronic pulmonary aspergillosis (CPA) is based on a combination of clinical symptomatology, compatible chest imaging findings, evidence of Aspergillus infection and exclusion of alternative diagnosis, all occurring for more than 3 months. Recently, a rapid, highly sensitive and specific point-of-care lateral flow device (LFD) has been introduced for the detection of Aspergillus-specific immunoglobulin (Ig)G, especially in resource-limited settings where CPA is underdiagnosed and often misdiagnosed as smear-negative pulmonary tuberculosis (PTB). Therefore, in our setting, where tuberculosis (TB) is endemic, exclusion of PTB is an important first step to the diagnosis of CPA. We used the recently published CPA diagnostic criteria for resource-limited settings to identify patients with CPA in our center. Case presentation Three Ugandan women (45/human immunodeficiency virus (HIV) negative, 53/HIV infected and 18/HIV negative), with a longstanding history of cough, chest pain, weight loss and constitutional symptoms, were clinically and radiologically diagnosed with PTB and empirically treated with an anti-tuberculous regimen despite negative microbiological tests. Repeat sputum Mycobacteria GeneXpert assays were negative for all three patients. On further evaluation, all three patients met the CPA diagnostic criteria with demonstrable thick-walled cavities and fungal balls (aspergilomas) on chest imaging and positive Aspergillus-specific IgG/IgM antibody tests. After CPA diagnosis, anti-TB drugs were safely discontinued for all patients, and they were initiated on capsules of itraconazole 200 mg twice daily with good treatment outcomes. Conclusions The availability of simple clinical diagnostic criteria for CPA and a LFD have the potential to reduce misdiagnosis of CPA and in turn improve treatment outcomes in resource-limited settings.

scholarly journals Performance of LDBio Aspergillus WB and ICT Antibody Detection in Chronic Pulmonary Aspergillosis

2021 ◽  
Vol 7 (4) ◽  
pp. 311
Author(s):  
Anna Rozaliyani ◽  
Findra Setianingrum ◽  
Sresta Azahra ◽  
Asriyani Abdullah ◽  
Ayu Eka Fatril ◽  
...  
Keyword(s):  
Receiver Operating Curve ◽  
Antibody Detection ◽  
Pulmonary Aspergillosis ◽  
Comparative Performance ◽  
Tuberculosis Patients ◽  
Chronic Pulmonary Aspergillosis ◽  
Screening Assays ◽  
Roc Area ◽  
Flow Detection ◽  
Sensitivity Specificity

The detection of Aspergillus antibody has a key role in the diagnosis of chronic pulmonary aspergillosis. Western blot (WB) and immunochromatography (ICT) lateral flow detection of Aspergillus antibody can be used as confirmatory and screening assays but their comparative performance in TB patients is not known. This study investigated the performance of these assays among 88 post-tuberculosis patients with suspected CPA. Sensitivity, specificity, receiver operating curve (ROC), area under-curve (AUC) and the agreement between two assays were evaluated. Both WB and ICT showed good sensitivity (80% and 85%, respectively) for detection of Aspergillus antibodies. Substantial agreement (0.716) between these assays was also obtained. The highest AUC result (0.804) was achieved with the combination of WB and ICT. The global intensity of WB correlated with the severity of symptoms in CPA group (p = 0.001). The combination of WB and ICT may increase specificity in CPA diagnosis.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

Sign in / Sign up

Export Citation Format

Share Document