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

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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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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Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation

European Respiratory Journal ◽

10.1183/13993003.01184-2018 ◽

2019 ◽

Vol 53 (3) ◽

pp. 1801184 ◽

Cited By ~ 24

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.

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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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Effect of routine iron–folic acid supplementation among rural pregnant women living in low- and high-groundwater-iron areas in Bangladesh

Public Health Nutrition ◽

10.1017/s1368980019001617 ◽

2019 ◽

Vol 22 (15) ◽

pp. 2844-2855 ◽

Cited By ~ 1

Author(s):

Faruk Ahmed ◽

Moududur Rahman Khan ◽

Ireen Akhtar Chowdhury ◽

Rubhana Raqib ◽

Anjan Kumar Roy ◽

...

Keyword(s):

Folic Acid ◽

Pregnant Women ◽

Significant Proportion ◽

Significant Risk ◽

Folic Acid Supplementation ◽

Fe Deficiency ◽

Prospective Longitudinal Study ◽

Iron Folic Acid ◽

Hb Concentration ◽

Prospective Longitudinal

AbstractObjective:The present study investigated the risks and benefits of routine Fe–folic acid (IFA) supplementation in pregnant women living in low- and high-groundwater-Fe areas in Bangladesh.Design:A case-controlled prospective longitudinal study design was used to compare the effect of daily Fe (60 mg) and folic acid (400 μg) supplementation for 3·5 months.Setting:A rural community in Bangladesh.Participants:Pregnant women living in low-groundwater-Fe areas (n 260) and high-groundwater-Fe areas (n 262).Results:Mean Hb and serum ferritin concentrations at baseline were significantly higher in pregnant women in the high-groundwater-Fe areas. After supplementation, the mean change in Hb concentration in the women in the low-groundwater-Fe areas (0·10 mg/dl) was higher than that in the pregnant women in the high-groundwater-Fe areas (–0·08 mg/dl; P = 0·052). No significant changes in the prevalence of anaemia or Fe deficiency (ID) in either group were observed after IFA supplementation; however, the prevalence of Fe-deficiency anaemia (IDA) decreased significantly in the women in the low-groundwater-Fe areas. The risk of anaemia, ID and IDA after supplementation did not differ significantly between the groups. None of the participants had Fe overload. However, a significant proportion of the women in the high- and low-groundwater-Fe areas remained anaemic and Fe-deficient after supplementation.Conclusion:IFA supplementation significantly increased the Hb concentration in pregnant women living in the low-groundwater-Fe areas. Routine supplementation with 60 mg Fe and 400 μg folic acid does not pose any significant risk of haemoconcentration or Fe overload. Further research to identify other nutritional and non-nutritional contributors to anaemia is warranted to prevent and treat anaemia.

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Severity of gastric intestinal metaplasia predicts the risk of gastric cancer: a prospective multicentre cohort study (GCEP)

Gut ◽

10.1136/gutjnl-2021-324057 ◽

2021 ◽

pp. gutjnl-2021-324057

Author(s):

Jonathan W J Lee ◽

Feng Zhu ◽

Supriya Srivastava ◽

Stephen KK Tsao ◽

Christopher Khor ◽

...

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Significant Risk ◽

Incidence Rates ◽

Endoscopic Surveillance ◽

Smoking History ◽

Operating Characteristics ◽

Gastric Intestinal Metaplasia ◽

Risk Patients ◽

Prospective Longitudinal

ObjectiveTo investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC.MethodsA prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN).ResultsThere were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III–IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III–IV developed within 2 years (range: 12.7–44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III–IV if they are negative for H. pylori. Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV.ConclusionsWe suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.

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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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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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Aspergillus fumigatus and Aspergillus flavus-Specific IgG Cut-Offs for the Diagnosis of Chronic Pulmonary Aspergillosis in Pakistan

Journal of Fungi ◽

10.3390/jof6040249 ◽

2020 ◽

Vol 6 (4) ◽

pp. 249

Author(s):

Kauser Jabeen ◽

Joveria Farooqi ◽

Nousheen Iqbal ◽

Khalid Wahab ◽

Muhammad Irfan

Keyword(s):

Aspergillus Fumigatus ◽

Sensitivity And Specificity ◽

Aspergillus Flavus ◽

Diagnostic Algorithm ◽

Pulmonary Aspergillosis ◽

Significant Difference ◽

Ethical Approval ◽

Chronic Pulmonary Aspergillosis ◽

Specific Igg ◽

First Time

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.

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