Chronic Pulmonary Aspergillosis

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 46859

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National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
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Dear Colleagues,

Chronic pulmonary aspergillosis (CPA) is an increasingly recognised entity in patients without the classical risk factors for invasive fungal disease. It mainly complicates previously treated tuberculosis (TB) and COPD; due to the numbers of people with these conditions, the global burden of CPA is significant, particularly in low-resource settings. Despite the obvious global health implications, surprisingly little is known about the pathogenesis, diagnosis, and management of the disease. Some evidence of the presence of subtle immune defects or a genetic susceptibility to CPA has emerged. Diagnosis relies on a combination or radiological and microbiological features and clinician expertise; better validation of diagnostic tests is required. Finally, treating this disease is extremely challenging as long-term treatment is needed, there is only one class of oral agents, the azoles, and resistance develops promptly, especially in patients with extensive disease and aspergillomas. An individualised, host-targeted approach is most beneficial.        

I am pleased to invite you to submit a manuscript to a Special Issue of the Journal of Fungi dedicated to CPA. We welcome reviews and original research on host pathogenesis, mycological aspects, diagnostic challenges, and management issues in high- and low-resource settings.

Dr. Chris Kosmidis
Guest Editor

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Keywords

  • Chronic pulmonary aspergillosis
  • Aspergillus
  • Diagnosis
  • Pathogenesis
  • Treatment

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Published Papers (13 papers)

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Editorial

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2 pages, 168 KiB  
Editorial
Special Issue: Chronic Pulmonary Aspergillosis
by Chris Kosmidis
J. Fungi 2022, 8(7), 714; https://doi.org/10.3390/jof8070714 - 08 Jul 2022
Viewed by 1306
Abstract
I would like to thank all authors who contributed to this Journal of Fungi Special Issue on Chronic Pulmonary Aspergillosis (CPA) [...] Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)

Research

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11 pages, 1580 KiB  
Article
Mapping of Chronic Pulmonary Aspergillosis in Africa
by Ronald Olum, Iriagbonse Iyabo Osaigbovo, Joseph Baruch Baluku, Jannik Stemler, Richard Kwizera and Felix Bongomin
J. Fungi 2021, 7(10), 790; https://doi.org/10.3390/jof7100790 - 23 Sep 2021
Cited by 15 | Viewed by 2717
Abstract
Africa has a high burden of tuberculosis, which is the most important risk factor for chronic pulmonary aspergillosis (CPA). Our goal was to systematically evaluate the burden of CPA in Africa and map it by country. We conducted an extensive literature search for [...] Read more.
Africa has a high burden of tuberculosis, which is the most important risk factor for chronic pulmonary aspergillosis (CPA). Our goal was to systematically evaluate the burden of CPA in Africa and map it by country. We conducted an extensive literature search for publications on CPA in Africa using the online databases. We reviewed a total of 41 studies published between 1976 and 2021, including a total of 1247 CPA cases from 14 African countries. Most of the cases came from Morocco (n = 764, 62.3%), followed by South Africa (n = 122, 9.9%) and Senegal (n = 99, 8.1%). Seventeen (41.5%) studies were retrospective, 12 (29.3%) were case reports, 5 case series (12.2%), 5 prospective cohorts, and 2 cross-sectional studies. The majority of the cases (67.1%, n = 645) were diagnosed in men, with a median age of 41 years (interquartile range: 36–45). Active/previously treated pulmonary tuberculosis (n = 764, 61.3%), human immunodeficiency virus infection (n = 29, 2.3%), diabetes mellitus (n = 19, 1.5%), and chronic obstructive pulmonary disease (n = 10, 0.8%) were the common co-morbidities. Haemoptysis was the most frequent presenting symptom, reported in up to 717 (57%) cases. Smoking (n = 69, 5.5%), recurrent lung infections (n = 41, 3%) and bronchorrhea (n = 33, 3%) were noted. This study confirms that CPA is common in Africa, with pulmonary tuberculosis being the most important risk factor. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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10 pages, 1426 KiB  
Article
Chronic Pulmonary Aspergillosis Situation among Post Tuberculosis Patients in Vietnam: An Observational Study
by Ngoc Thi Bich Nguyen, Huy Le Ngoc, Nhung Viet Nguyen, Luong Van Dinh, Hung Van Nguyen, Huyen Thi Nguyen and David W. Denning
J. Fungi 2021, 7(7), 532; https://doi.org/10.3390/jof7070532 - 30 Jun 2021
Cited by 16 | Viewed by 2969
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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9 pages, 1302 KiB  
Article
Performance of LDBio Aspergillus WB and ICT Antibody Detection in Chronic Pulmonary Aspergillosis
by Anna Rozaliyani, Findra Setianingrum, Sresta Azahra, Asriyani Abdullah, Ayu Eka Fatril, Harmi Rosianawati, Erlina Burhan, Diah Handayani, Arief Riadi Arifin, Jamal Zaini, Mulyati Tugiran, Robiatul Adawiyah, Ridhawati Syam, Heri Wibowo, Retno Wahyuningsih, Chris Kosmidis and David W Denning
J. Fungi 2021, 7(4), 311; https://doi.org/10.3390/jof7040311 - 18 Apr 2021
Cited by 7 | Viewed by 3088
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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10 pages, 3971 KiB  
Article
Chronic Pulmonary Aspergillosis in Post Tuberculosis Patients in Indonesia and the Role of LDBio Aspergillus ICT as Part of the Diagnosis Scheme
by Anna Rozaliyani, Harmi Rosianawati, Diah Handayani, Heidy Agustin, Jamal Zaini, Ridhawati Syam, Robiatul Adawiyah, Mulyati Tugiran, Findra Setianingrum, Erlina Burhan, Chris Kosmidis and Retno Wahyuningsih
J. Fungi 2020, 6(4), 318; https://doi.org/10.3390/jof6040318 - 27 Nov 2020
Cited by 24 | Viewed by 3897
Abstract
Chronic pulmonary aspergillosis (CPA) is a common sequela of pulmonary tuberculosis (TB). The diagnosis of CPA is difficult and often misdiagnosed as smear-negative TB in endemic settings. Aspergillus IgG detection is the cornerstone of CPA diagnosis. There are a lack of studies on [...] Read more.
Chronic pulmonary aspergillosis (CPA) is a common sequela of pulmonary tuberculosis (TB). The diagnosis of CPA is difficult and often misdiagnosed as smear-negative TB in endemic settings. Aspergillus IgG detection is the cornerstone of CPA diagnosis. There are a lack of studies on the prevalence of CPA in GeneXpert/smear-negative TB patients in Indonesia, despite a high number of TB cases. This study aims to determine the CPA rate in HIV-negative, GeneXpert-negative patients presenting with symptoms following completion of TB therapy and to evaluate the performance of LDBio Aspergillus immunochromatographic technology (ICT) lateral flow assay in the diagnosis of CPA. CPA was diagnosed on the basis of symptoms for ≥3 months, characteristic chest imaging and positive Aspergillus culture. Twenty (22%) out of 90 patients met the criteria for CPA. The LDBio test was positive in 16 (80%) CPA patients and in 21 (30%) non-CPA patients (p < 0.001) with 80% sensitivity and 70% specificity. Logistic regression revealed a positive LDBio Aspergillus ICT result, smoking history and diabetes to be important predictors of CPA diagnosis. Although CPA is an unrecognised disease in Indonesia, this study suggests that more than one in five GeneXpert negative patients with persistent symptoms following completion of TB therapy may have CPA. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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10 pages, 743 KiB  
Article
Incidence and Risk Factors of Chronic Pulmonary Aspergillosis Development during Long-Term Follow-Up after Lung Cancer Surgery
by Sun Hye Shin, Bo-Guen Kim, Jiyeon Kang, Sang-Won Um, Hojoong Kim, Hong Kwan Kim, Jhingook Kim, Young Mog Shim, Yong Soo Choi and Byeong-Ho Jeong
J. Fungi 2020, 6(4), 271; https://doi.org/10.3390/jof6040271 - 09 Nov 2020
Cited by 9 | Viewed by 1994
Abstract
Lung resection surgery for non-small-cell lung cancer (NSCLC) is reportedly a risk factor for developing chronic pulmonary aspergillosis (CPA). However, limited data are available regarding the development of CPA during long-term follow-up after lung cancer surgery. This study aimed to investigate the cumulative [...] Read more.
Lung resection surgery for non-small-cell lung cancer (NSCLC) is reportedly a risk factor for developing chronic pulmonary aspergillosis (CPA). However, limited data are available regarding the development of CPA during long-term follow-up after lung cancer surgery. This study aimed to investigate the cumulative incidence and clinical factors associated with CPA development after lung cancer surgery. We retrospectively analyzed 3423 patients with NSCLC who (1) underwent surgical resection and (2) did not have CPA at the time of surgery between January 2010 and December 2013. The diagnosis of CPA was based on clinical symptoms, serological or microbiological evidences, compatible radiological findings, and exclusion of alternative diagnoses. The cumulative incidence of CPA and overall survival (OS) were estimated using the Kaplan–Meier method, and a multivariable Cox proportional hazard analysis was performed to identify factors associated with CPA development. Patients were followed-up for a median of 5.83 years with a 72.3% 5-year OS rate. Fifty-six patients developed CPA at a median of 2.68 years after surgery, with cumulative incidences of 0.4%, 1.1%, 1.6%, and 3.5% at 1, 3, 5, and 10 years, respectively. Lower body mass index (BMI), smoking, underlying interstitial lung disease, thoracotomy, development of postoperative pulmonary complications 30 days after surgery, and treatment with both chemotherapy and radiotherapy were independently associated with CPA development. The cumulative incidence of CPA after surgery was 3.5% at 10 years and showed a steadily increasing trend during long-term follow-up. Therefore, increased awareness regarding CPA development is needed especially in patients with risk factors. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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8 pages, 719 KiB  
Article
Aspergillus fumigatus and Aspergillus flavus-Specific IgG Cut-Offs for the Diagnosis of Chronic Pulmonary Aspergillosis in Pakistan
by Kauser Jabeen, Joveria Farooqi, Nousheen Iqbal, Khalid Wahab and Muhammad Irfan
J. Fungi 2020, 6(4), 249; https://doi.org/10.3390/jof6040249 - 26 Oct 2020
Cited by 5 | Viewed by 3245
Abstract
Despite a high burden of chronic pulmonary aspergillosis (CPA) in Pakistan, Aspergillus-specific IgG testing is currently not available. Establishing cut-offs for Aspergillus-specific IgG for CPA diagnosis is crucial due to geographical variation. In settings such as Pakistan, where non-Aspergillus fumigatus [...] Read more.
Despite a high burden of chronic pulmonary aspergillosis (CPA) in Pakistan, Aspergillus-specific IgG testing is currently not available. Establishing cut-offs for Aspergillus-specific IgG for CPA diagnosis is crucial due to geographical variation. In settings such as Pakistan, where non-Aspergillus fumigatus (mainly A. flavus) Aspergillus species account for the majority of CPA cases, there is a need to explore additional benefit of Aspergillus flavus-specific IgG detection along with A. fumigatus-specific IgG detection. This study was conducted at the Aga Khan University, Karachi, Pakistan after ethical approval. Serum for IgG detection were collected after informed consent from healthy controls (n = 21), diseased controls (patients with lung diseases, n = 18), and CPA patients (n = 21). A. fumigatus and A. flavus IgG were detected using Siemens immulite assay. The sensitivity and specificity of A. fumigatus-specific IgG were 80.95% and 82.05%, respectively at a cut-off of 20 mg/L. The sensitivity and specificity of A. flavus-specific IgG were 80.95% and 79.49% at a cut-off of 30 mg/L. We report, for the first time, performance of A. flavus-specific IgG for CPA diagnosis. Although there was no statistically significant difference between the performance of both antigens, it seems contextually relevant to include A. flavus IgG in the CPA diagnostic algorithm in regions with higher non-A. fumigatus CPA infections. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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8 pages, 249 KiB  
Article
Prevalence of Vitamin D Deficiency in Treatment-Naïve Subjects with Chronic Pulmonary Aspergillosis
by Inderpaul Singh Sehgal, Sahajal Dhooria, Kuruswamy Thurai Prasad, Valliappan Muthu, Naresh Sachdeva, Sanjay Kumar Bhadada, Ashutosh Nath Aggarwal, Mandeep Garg, Arunaloke Chakrabarti and Ritesh Agarwal
J. Fungi 2020, 6(4), 202; https://doi.org/10.3390/jof6040202 - 01 Oct 2020
Cited by 5 | Viewed by 2504
Abstract
The association of vitamin D deficiency in the pathogenesis of invasive and allergic pulmonary aspergillosis is known. Whether vitamin D deficiency is prevalent in chronic pulmonary aspergillosis (CPA) remains unknown. We evaluated the prevalence of vitamin D deficiency in subjects with CPA. We [...] Read more.
The association of vitamin D deficiency in the pathogenesis of invasive and allergic pulmonary aspergillosis is known. Whether vitamin D deficiency is prevalent in chronic pulmonary aspergillosis (CPA) remains unknown. We evaluated the prevalence of vitamin D deficiency in subjects with CPA. We compared the clinicoradiological features, microbiology, the immunological response, and the severity of CPA in those with or without vitamin D deficiency. We measured plasma vitamin D levels in 230 consecutive treatment-naïve subjects with CPA and 78 controls (28 with prior tuberculosis (TB); 50 healthy controls). We defined vitamin D deficiency as 25(OH)D3 level <20 ng/mL. The mean (95% confidence intervals (CI)) levels of plasma vitamin D levels were 19.5 (17.6–21.4), 18.6 (13.9–23.3), and 15.3 (12.6–17.9) ng/mL in subjects with CPA, diseased controls, and healthy controls, respectively; and the levels were not different between the groups. The prevalence of vitamin D deficiency in subjects with CPA was 65% (n = 150) and was also not different between healthy (70%) or diseased (61%) controls. We did not find any difference in the clinicoradiological features, microbiology, immunological response, and severity of CPA between vitamin D sufficient and deficient groups. The prevalence of vitamin D deficiency is high in subjects with CPA, albeit similar to controls. Vitamin D deficiency does not affect the disease severity in subjects with CPA. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
12 pages, 273 KiB  
Article
CPAnet Registry—An International Chronic Pulmonary Aspergillosis Registry
by Christian B. Laursen, Jesper Rømhild Davidsen, Lander Van Acker, Helmut J.F. Salzer, Danila Seidel, Oliver A. Cornely, Martin Hoenigl, Ana Alastruey-Izquierdo, Christophe Hennequin, Cendrine Godet, Aleksandra Barac, Holger Flick, Oxana Munteanu and Eva Van Braeckel
J. Fungi 2020, 6(3), 96; https://doi.org/10.3390/jof6030096 - 29 Jun 2020
Cited by 16 | Viewed by 3041
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)

Review

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19 pages, 1076 KiB  
Review
Molecular Epidemiology of Aspergillus fumigatus in Chronic Pulmonary Aspergillosis Patients
by Mireille H. van der Torre, Hongwei Shen, Riina Rautemaa-Richardson, Malcolm D. Richardson and Lilyann Novak-Frazer
J. Fungi 2021, 7(2), 152; https://doi.org/10.3390/jof7020152 - 20 Feb 2021
Cited by 7 | Viewed by 3170
Abstract
Molecular fungal genotyping techniques developed and employed for epidemiological studies have understandably concentrated on establishing the genetic diversity of Aspergillus fumigatus in invasive aspergillosis due to its severity, the urgency for treatment, and the need to demonstrate possible sources. Some early studies suggested [...] Read more.
Molecular fungal genotyping techniques developed and employed for epidemiological studies have understandably concentrated on establishing the genetic diversity of Aspergillus fumigatus in invasive aspergillosis due to its severity, the urgency for treatment, and the need to demonstrate possible sources. Some early studies suggested that these strains were phenotypically, if not genotypically, different from others. However, with improved discrimination and evaluations, incorporating environmental as well as clinical isolates from other Aspergillus conditions (e.g., chronic pulmonary aspergillosis and cystic fibrosis), this premise is no longer upheld. Moreover, with the onset of increased global triazole resistance, there has been a concerted effort to incorporate resistance profiling into genotyping studies and the realisation that the wider population of non-immunocompromised aspergillosis patients are at risk. This review summarises the developments in molecular genotyping studies that incorporate resistance profiling with attention to chronic pulmonary aspergillosis and an example of our UK experience. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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10 pages, 858 KiB  
Review
Chronic Pulmonary Aspergillosis Following Nontuberculous Mycobacterial Infections: An Emerging Disease
by Pakpoom Phoompoung and Methee Chayakulkeeree
J. Fungi 2020, 6(4), 346; https://doi.org/10.3390/jof6040346 - 08 Dec 2020
Cited by 12 | Viewed by 3239
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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27 pages, 4914 KiB  
Review
A Collaborative Tale of Diagnosing and Treating Chronic Pulmonary Aspergillosis, from the Perspectives of Clinical Microbiologists, Surgical Pathologists, and Infectious Disease Clinicians
by Paige M. K. Larkin, Ashrit Multani, Omer E. Beaird, Ayrton J. Dayo, Gregory A. Fishbein and Shangxin Yang
J. Fungi 2020, 6(3), 106; https://doi.org/10.3390/jof6030106 - 11 Jul 2020
Cited by 6 | Viewed by 4590
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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18 pages, 1535 KiB  
Review
Chronic Pulmonary Aspergillosis: Notes for a Clinician in a Resource-Limited Setting Where There Is No Mycologist
by Felix Bongomin, Lucy Grace Asio, Joseph Baruch Baluku, Richard Kwizera and David W. Denning
J. Fungi 2020, 6(2), 75; https://doi.org/10.3390/jof6020075 - 02 Jun 2020
Cited by 31 | Viewed by 9191
Abstract
Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 [...] Read more.
Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 million individuals worldwide. Its diagnostic approach requires a thorough Clinical, Radiological, Immunological and Mycological (CRIM) assessment. The diagnosis of CPA requires (1) demonstration of one or more cavities with or without a fungal ball present or nodules on chest imaging, (2) direct evidence of Aspergillus infection or an immunological response to Aspergillus species and (3) exclusion of alternative diagnoses, although CPA and mycobacterial disease can be synchronous. Aspergillus antibody is elevated in over 90% of patients and is the cornerstone for CPA diagnosis. Long-term oral antifungal therapy improves quality of life, arrests haemoptysis and prevents disease progression. Itraconazole and voriconazole are alternative first-line agents; voriconazole is preferred for patients with contra-indications to itraconazole and in those with severe disease (including large aspergilloma). In patients co-infected with tuberculosis (TB), it is not possible to treat TB with rifampicin and concurrently administer azoles, because of profound drug interactions. In those with pan-azole resistance or intolerance or progressive disease while on oral triazoles, short-term courses of intravenous liposomal amphotericin B or micafungin is used. Surgery benefits patients with well-circumscribed simple aspergillomas and should be offered earlier in low-resource settings. Full article
(This article belongs to the Special Issue Chronic Pulmonary Aspergillosis)
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