Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation

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.

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Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.21.0034 ◽

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.

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

10.1101/2021.04.25.21256062 ◽

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.

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

Thorax ◽

10.1136/thoraxjnl-2020-216464 ◽

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.

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

Journal of Medical Case Reports ◽

10.1186/s13256-021-02721-9 ◽

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.

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Chronic Pulmonary Aspergillosis Misdiagnosed as Smear-Negative Pulmonary Tuberculosis in a TB Clinic in Nigeria

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2018/41816 ◽

2018 ◽

Vol 26 (10) ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Titilola Gbaja-Biamila ◽

Felix Bongomin ◽

Nicholas Irurhe ◽

Augustina Nwosu ◽

Rita Oladele

Keyword(s):

Pulmonary Tuberculosis ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis ◽

Smear Negative

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Diagnostic Aspects of Chronic Pulmonary Aspergillosis: Present and New Directions

Current Fungal Infection Reports ◽

10.1007/s12281-019-00361-7 ◽

2019 ◽

Vol 13 (4) ◽

pp. 292-300 ◽

Cited By ~ 1

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.

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Impact of high baseline Aspergillus-specific IgG levels on weight and quality-of-life outcomes of patients with chronic pulmonary aspergillosis

Medical Mycology ◽

10.1093/mmy/myaa026 ◽

2020 ◽

Vol 58 (7) ◽

pp. 1000-1004

Author(s):

Felix Bongomin ◽

Tomaz Garcez ◽

David W Denning

Keyword(s):

Quality Of Life ◽

Antifungal Treatment ◽

Weight Changes ◽

Pulmonary Aspergillosis ◽

Group A ◽

Chronic Pulmonary Aspergillosis ◽

Specific Igg ◽

Group B ◽

The Impact

Abstract This study aimed to evaluate the impact of quantitative baseline Aspergillus-specific immunoglobulin G (IgG) serum levels on weight changes of patients with chronic pulmonary aspergillosis (CPA) under antifungal treatment. We retrospectively reviewed data of patients diagnosed with CPA between April 2015 and March 2018 at the National Aspergillosis Centre (Manchester, UK). All patients were on continued antifungal treatment for 12 months. Data on Aspergillus-specific IgG levels, St George's quality of life (SGQoL) variables and weight at baseline, 6 months and 12 months were extracted. We defined a high serum Aspergillus-specific IgG as ≥ 200 mg/l (Group A) and low level < 200 mg/l (Group B). Forty-nine patients (37 male; 12 female), median age 65 years (range: 29–86) were studied. Overall, 33% (n = 16) of the patients were in Group A. The baseline characteristics between the two groups were similar. The median Charlson comorbidity index was 4 (range: 0–5) and 3 (range: 0–9) for Group A and Group B, respectively (P = .543). There was a sustained decline in median Aspergillus IgG levels from baseline, through 6 month to 12 months of continues therapy from 170 (range: 20–1110) to 121 (range: 20–1126), and finally 107 (15–937) mg/l, respectively (P < .001). Group A patients gained more weight at 6 months (9/15 [60%] vs. 7/33 [21%], P = .012) and at 12 months of treatment (9/15 [60%] vs. 7/33 [22%]), and more patients in Group B lost weight ((13/33 [41%] vs. 1/15 [7%]), P = .015). However, there was no difference in QoL outcomes across groups at 6 (P = .3) and 12 (P = .7) months. A very high Aspergillus IgG may confer a higher likelihood of weight gain as a key, objective marker of clinical response, if patients can tolerate 12 months of antifungal therapy.

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Haemoptysis in a female with diabetes mellitus: a unique presentation of chronic pulmonary aspergillosis, pulmonary tuberculosis, and Klebsiella peumoniae co‐infection

Clinical Case Reports ◽

10.1002/ccr3.542 ◽

2016 ◽

Vol 4 (4) ◽

pp. 432-436 ◽

Cited By ~ 3

Author(s):

Chinonso Ekwueme ◽

Akaninyene Asuquo Otu ◽

Sunny Chinenye ◽

Chioma Unachukwu ◽

Reginald N. Oputa ◽

...

Keyword(s):

Diabetes Mellitus ◽

Pulmonary Tuberculosis ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

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Mapping of Chronic Pulmonary Aspergillosis in Africa

Journal of Fungi ◽

10.3390/jof7100790 ◽

2021 ◽

Vol 7 (10) ◽

pp. 790

Author(s):

Ronald Olum ◽

Iriagbonse Iyabo Osaigbovo ◽

Joseph Baruch Baluku ◽

Jannik Stemler ◽

Richard Kwizera ◽

...

Keyword(s):

Risk Factor ◽

Pulmonary Tuberculosis ◽

Case Reports ◽

Case Series ◽

Important Risk Factor ◽

Chronic Obstructive ◽

Extensive Literature ◽

African Countries ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis

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.

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Evaluation of LDBio Aspergillus ICT Lateral Flow Assay for IgG and IgM Antibody Detection in Chronic Pulmonary Aspergillosis

Journal of Clinical Microbiology ◽

10.1128/jcm.00538-19 ◽

2019 ◽

Vol 57 (9) ◽

Cited By ~ 7

Author(s):

Elizabeth Stucky Hunter ◽

Malcolm D. Richardson ◽

David W. Denning

Keyword(s):

United Kingdom ◽

Line Intensity ◽

Test Line ◽

Lateral Flow ◽

Lateral Flow Assay ◽

Antibody Detection ◽

Resource Constrained ◽

Pulmonary Aspergillosis ◽

Chronic Pulmonary Aspergillosis ◽

Specific Igg

ABSTRACT Detecting Aspergillus-specific IgG is critical to diagnosing chronic pulmonary aspergillosis (CPA). Existing assays are often cost- and resource-intensive and not compatible with resource-constrained laboratory settings. LDBio Diagnostics has recently commercialized a lateral flow assay based on immunochromatographic technology (ICT) that detects Aspergillus antibodies (IgG and IgM) in less than 30 min, requiring minimal laboratory equipment. A total of 154 CPA patient sera collected at the National Aspergillosis Centre (Manchester, United Kingdom) and control patient sera from the Peninsula Research Bank (Exeter, United Kingdom) were evaluated. Samples were applied to the LDBio Aspergillus ICT lateral flow assay, and results were read both visually and digitally. Results were compared with Aspergillus IgG titers in CPA patients, measured by ImmunoCAP-specific IgG assays. For proven CPA patients versus controls, sensitivity and specificity for the LDBio Aspergillus ICT were 91.6% and 98.0%, respectively. In contrast, the routinely used ImmunoCAP assay exhibited 80.5% sensitivity for the same cohort (cutoff value, 40 mg of antigen-specific antibodies [mgA]/liter). The assay is easy to perform but challenging to read when only a very faint band is present (5/154 samples tested). The ImmunoCAP Aspergillus IgG titer was also compared with the Aspergillus ICT test line intensity or rate of development, with weak to moderate correlations. The Aspergillus ICT lateral flow assay exhibits excellent sensitivity for serological diagnosis of CPA. Quantifying IgG from test line intensity measurements is not reliable. Given the short run time, simplicity, and limited resources needed, the LDBio Aspergillus ICT is a suitable diagnostic tool for CPA in resource-constrained settings.

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