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 Evaluation of Aspergillus-Specific Lateral-Flow Device Test Using Serum and Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

2019 ◽  
Vol 57 (5) ◽  
Author(s):  
Takahiro Takazono ◽  
Yuya Ito ◽  
Masato Tashiro ◽  
Keitaro Nishimura ◽  
Tomomi Saijo ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Point Of Care ◽  
Invasive Pulmonary Aspergillosis ◽  
Antibody Test ◽  
Lavage Fluid ◽  
Serum Samples ◽  
Pulmonary Aspergillosis ◽  
Flow Device ◽  
Chronic Pulmonary Aspergillosis

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

scholarly journals Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation

2019 ◽  
Vol 53 (3) ◽  
pp. 1801184 ◽  
Author(s):  
Iain D. Page ◽  
Rosemary Byanyima ◽  
Sharath Hosmane ◽  
Nathan Onyachi ◽  
Cyprian Opira ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Chest Radiography ◽  
Chronic Cough ◽  
Reasonable Accuracy ◽  
Pulmonary Aspergillosis ◽  
Pulmonary Tb ◽  
Pleural Thickening ◽  
Radiological Features ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg

Chronic pulmonary aspergillosis (CPA) complicates treated pulmonary tuberculosis (TB), with high 5-year mortality. We measured CPA prevalence in this group.398 Ugandans with treated pulmonary TB underwent clinical assessment, chest radiography and Aspergillus-specific IgG measurement. 285 were resurveyed 2 years later, including computed tomography of the thorax in 73 with suspected CPA. CPA was diagnosed in patients without active TB who had raised Aspergillus-specific IgG, radiological features of CPA and chronic cough or haemoptysis.Author-defined CPA was present in 14 (4.9%, 95% CI 2.8–7.9%) resurvey patients. CPA was significantly more common in those with chest radiography cavitation (26% versus 0.8%; p<0.001), but possibly less frequent in HIV co-infected patients (3% versus 6.7%; p=0.177). The annual rate of new CPA development between surveys was 6.5% in those with chest radiography cavitation and 0.2% in those without (p<0.001). Absence of cavitation and pleural thickening on chest radiography had 100% negative predictive value for CPA. The combination of raised Aspergillus-specific IgG, chronic cough or haemoptysis and chest radiography cavitation had 85.7% sensitivity and 99.6% specificity for CPA diagnosis.CPA commonly complicates treated pulmonary TB with residual chest radiography cavitation. Chest radiography alone can exclude CPA. Addition of serology can diagnose CPA with reasonable accuracy.

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.

Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities

2021 ◽  
Vol 25 (7) ◽  
pp. 537-546
Author(s):  
J. B. Baluku ◽  
E. Nuwagira ◽  
F. Bongomin ◽  
D. W. Denning
Keyword(s):  
Low Income ◽  
Lung Diseases ◽  
High Sensitivity ◽  
Radiological Findings ◽  
Pulmonary Aspergillosis ◽  
Pulmonary Tb ◽  
Pleural Thickening ◽  
Chronic Pulmonary Aspergillosis ◽  
Specific Igg ◽  
Parenchymal Lung

BACKGROUND: Pulmonary TB (PTB) and chronic pulmonary aspergillosis (CPA) are both progressive and debilitating parenchymal lung diseases with overlapping risk factors, symptomatology and radiological findings that often result in misdiagnosis of either disease.METHODS: We undertook a narrative review approach to describe the clinical and radiological manifestations of CPA and PTB and highlight the salient features that differentiate these two closely related maladies.RESULTS: CPA is a frequent complication of treated PTB. In fact, 15–90% of CPA cases occur in patients with residual lung lesions following treatment for PTB. While CPA predominantly affects older patients with underlying lung diseases, both PTB and CPA present with clinically indistinguishable symptoms. Chest imaging findings of cavitation and fibrosis are common to both diseases. However, lymphadenopathy, miliary pattern and pleural effusion are predictive of active PTB, while aspergilloma, pleural thickening and paracavitary fibrosis are more common in CPA. Aspergillus-specific IgG serology has a central role in differentiating PTB (both active and healed) from CPA with a high sensitivity and specificity.CONCLUSION: Aspergillus-specific IgG serology is key in differentiating PTB and PTB relapse from CPA. It may be worthwhile developing clinical predictive scores that can be used in low-income settings to differentiate active TB, post-TB disease and TB+CPA co-infection.

scholarly journals Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa

2021 ◽  
Vol 8 ◽  
pp. 204993612110342
Author(s):  
Iriagbonse Iyabo Osaigbovo ◽  
Felix Bongomin
Keyword(s):  
Fungal Infections ◽  
Point Of Care ◽  
Invasive Fungal Infections ◽  
Antigen Test ◽  
Pulmonary Aspergillosis ◽  
Middle Income ◽  
Middle Income Countries ◽  
Disseminated Histoplasmosis ◽  
Chronic Pulmonary Aspergillosis ◽  
Point Of Care Tests

Invasive fungal infections (IFIs) such as cryptococcosis, disseminated histoplasmosis, and chronic pulmonary aspergillosis are significant causes of morbidity and mortality in Africa. Lack of laboratory infrastructure and laboratory personnel trained in diagnostic mycology hamper prompt detection and management of IFIs on the continent. Point-of-care tests (POCT) obviate the need for complex infrastructure, skilled technicians, and stable electricity and have had major impacts on the diagnosis of bacterial, viral, and parasitic infections in low- and middle-income countries. Over the last 10 years, POCTs for IFIs have become increasingly available and they have the potential to revolutionize the management of these infections if scaled up in Africa. At the beginning of 2021, the World Health Organization (WHO) Essential Diagnostic List (EDL) included a cryptococcal antigen test for the diagnosis of cryptococcosis, Histoplasma antigen test for the diagnosis of disseminated histoplasmosis, and Aspergillus-specific test for the diagnosis of chronic pulmonary aspergillosis. All of these are available in formats that may be used as POCTs and it is hoped that this will improve the diagnosis of these life-threatening IFIs, especially in low- and middle-income countries. This perspective review discusses commercially available POCTs and outlines strategies of a blueprint to achieve their roll-out in Africa. The strategies include raising awareness, conducting research that uncovers the exact burden of IFIs, increasing advocacy, integrating diagnosis of IFIs into existing public health programs, adoption of the WHO EDL at country levels, and improving logistics and supply chains.

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 Situation among Post Tuberculosis Patients in Vietnam: An Observational Study

2021 ◽  
Vol 7 (7) ◽  
pp. 532
Author(s):  
Ngoc Thi Bich Nguyen ◽  
Huy Le Ngoc ◽  
Nhung Viet Nguyen ◽  
Luong Van Dinh ◽  
Hung Van Nguyen ◽  
...  
Keyword(s):  
Diagnostic Tools ◽  
Chronic Obstructive ◽  
High Resolution Computed Tomography ◽  
Pulmonary Aspergillosis ◽  
Obstructive Pulmonary Disease ◽  
Female Ratio ◽  
High Burden ◽  
Pleural Thickening ◽  
Number Of Patients ◽  
Chronic Pulmonary Aspergillosis

This study provides a brief view of chronic pulmonary aspergillosis (CPA) in the post-tuberculosis treatment community in Vietnam, a high burden tuberculosis (TB) country. In three months in late 2019, 70 post-TB patients managed at Vietnam National Lung Hospital were enrolled. Of these, 38 (54.3%) had CPA. The male/female ratio was 3/1 (28 males and ten females). CPA patients had a mean age of 59 ± 2.3 years (95%CI 54.4–63.6). The mean Body mass index (BMI) was 19.0 ± 0.5 (18.0–20.0) and 16 of 38 (42.1%) patients had concurrent diseases, the most common of which were chronic obstructive pulmonary disease (COPD) and diabetes. Twenty-six patients (68.4%) developed hemoptysis, 21 (55.3%) breathlessness, and weight loss was seen in 30 (78.9%). Anaemia was seen in 15 (39.5%) and 27 of 38 (71.1%) patients had an elevated C-reactive protein (CRP). The most common radiological findings were multiple cavities (52.6%) and pleural thickening (42.7%), followed by aspergilloma (29.0%) and non-specific infiltrates. There were five of 38 patients (13.2%) with a cavity containing a fungal ball on the chest X-ray, but when the high resolution computed tomography (HRCT) was examined, the number of patients with fungal balls rose to 11 (28.9%). Overall, 34 of 38 (89.5%) cases had an elevated Aspergillus IgG with an optical density ≥ 1, and in 2 cases, it was 0.9–1.0 (5%), borderline positive. In nine patients (23.7%) Aspergillus fumigatus was cultured from sputum. CPA is an under-recognised problem in Vietnam and other high burden TB countries, requiring a different diagnostic approach and treatment and careful management. HRCT and Aspergillus IgG serum test are recommended as initial diagnostic tools for 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 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.

scholarly journals Fatal Case of Chronic Pulmonary Aspergillosis and Tuberculosis: A Case Report from an University Hospital in Colombia

2020 ◽  
Author(s):  
Carlos Andres Celis-Preciado ◽  
July Torres-González ◽  
Lina Arbelaez-Collazos ◽  
Camila Betancur-Palacio ◽  
Óscar David Lucero Pantoja
Keyword(s):  
Soft Tissues ◽  
Fatal Case ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Left Lung ◽  
Middle Lobe ◽  
University Hospital ◽  
Pulmonary Aspergillosis ◽  
Pleural Thickening ◽  
Chronic Respiratory Diseases ◽  
Chronic Pulmonary Aspergillosis

Abstract BackgroundThe term aspergillosis from a clinical point of view includes allergic bronchopulmonary aspergillosis, invasive forms of the airway, cutaneous and extrapulmonary aspergillosis and finally chronic non-invasive or semi-invasive pulmonary forms. All of them produced by different species of Aspergillus. In addition, the presentation of aspergillosis together with tuberculosis are rare in scientific literature. We report a case of Chronic pulmonary aspergillosis and tuberculosis in a 72-year-old man Case presentation The patient is a 72-year-old man who was admitted with a 2-year history of constitutional syndrome, dry cough and moderate exertion dyspnea. Chest X-ray showed a rounded mass in the upper lobe of the left lung surrounded by radiolucent areas that suggest cavitations. Computed tomography with chest contrast revealed "tree in bud" pattern in the upper right and middle lobe and lesions of a cystic appearance with the presence of multiple masses with a density of soft tissues. Bronchioalveolar lavage analyses demonstrate Aspergillus fumigatusConclusionsChronic cavity aspergillosis is an uncommon form characterized by cavitation, fibrosis and pleural thickening seen in immunocompetent or mildly immunocompromised patients with chronic respiratory diseases, especially TB.

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