Case Of Chronic Pulmonary Aspergillosis Research Articles

A case of chronic pulmonary aspergillosis due to pulmonary infarction, mimicking cryptogenic organising pneumonia

A patient initially treated with corticosteroids for cryptogenic organising pneumonia following pulmonary infarction, developed a worsening condition with progressive cavitary formations in both lower lung lobes. Contrast-enhanced chest computed tomography revealed a pulmonary embolism, and serum anti-Aspergillus IgG antibody analysis yielded a strong positive result. Consequently, the patient was diagnosed with pulmonary infarction with Aspergillus infection; organising pneumonia in surrounding areas reflected the repair process. Following treatment with anticoagulants and antifungal agents, the patient was successfully discharged. Hence, pulmonary infarction should be considered in cases of refractory lung lesions.

Incidence and prevalence of chronic pulmonary aspergillosis in patients with post-tuberculosis lung abnormality: Results from a community survey in North India.

Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for developing chronic pulmonary aspergillosis (CPA). However, the prevalence and incidence of CPA in PTLA patients in India remain unknown. We aimed to ascertain the incidence and prevalence of CPA in subjects with PTLA. We identified a cohort of pulmonary tuberculosis who completed anti-tuberculosis therapy (ATT) before November 2019 from the records of the 12 tuberculosis treatment centers attached to the national program. We recorded the clinical and demographic details. We performed computed tomography (CT) of the chest and estimated serum A. fumigatus-specific IgG. We categorised subjects as PTLA with or without CPA using a composite of clinical, radiological, and microbiological features. We resurveyed the subjects at 6 months (or earlier) for the presence of new symptoms. We calculated the prevalence and the incidence rate (per 100-person years) of CPA. We included 117 subjects with PTLA, with a median of 3 years after ATT completion. Eleven subjects had CPA in the initial survey, and one additional case developed CPA during the second survey. The prevalence of CPA in PTLA subjects was 10.3% (12/117). The total observation period was 286.7 person-years. The median (interquartile range) time to develop CPA after ATT completion was 12.5 (5-36.7) months. We found the CPA incidence rate (95% confidence interval) of 4.2 (1.8-6.5) per 100-person years. Chronic pulmonary aspergillosis complicates 10% of PTLA subjects after successful outcomes with ATT. Four new CPA cases may develop per 100-persons years of observation after ATT completion. We suggest screening patients with PTLA who develop new symptoms for CPA.

Prevalence of Chronic Pulmonary Aspergillosis in Two (2) Tuberculosis Treatment Clinics in Lagos, Nigeria: A Prospective Longitudinal Study.

Chronic pulmonary aspergillosis (CPA) is an underrecognized but common complication of pulmonary tuberculosis. In Nigeria, a tuberculosis-endemic country, there is currently no provision to monitor the development of CPA in patients treated for tuberculosis. This study determined the prevalence and incidence of CPA in Lagos, Nigeria. A prospective longitudinal study of patients with previously managed tuberculosis was conducted between June 2021 and May 2022. The study cohorts were assessed at 3-month intervals, and the following were collected: sociodemographic data, chest radiographic findings, sputum samples for fungal culture, and venous blood samples for Aspergillus immunoglobulin G estimation. CPA cases were determined using the case definition for resource-constrained countries. Descriptive and inferential statistics were used, and significance was set at a probability of 5% (P < .05). Of the 141 patients recruited, 79 (56.0%) were in the retreatment and 62 (44.0%) in the posttreatment tuberculosis group. The median age (interquartile range) was 40 (30-52) years, with a male-to-female ratio of 1.1:1. Ninety-seven patients (69%) had a GeneXpert test done, of whom 63 (64.9%) were GeneXpert negative. Cough was the most common symptom, with 15 (11%) patients having hemoptysis. The rate of CPA increased steadily as the study progressed: 44 (31.2%) at commencement, 45 (34.9%) at 3 months, 49 (42.6%) at 6 months, and 51 (54.3%) at 9 months. Thus, the overall prevalence of CPA was 49.7%, and the incidence was 6.1%. CPA is common in Nigeria and its true burden may still be underestimated. Increased awareness of CPA as a posttuberculosis lung disease is advocated. Evaluation for CPA should be incorporated in patients' work-up for tuberculosis.

Clinical utility of intrabronchial antifungal instillation in a complicated case of chronic pulmonary aspergillosis: case report and systematic review of literature

Clinical utility of intrabronchial antifungal instillation in a complicated case of chronic pulmonary aspergillosis: case report and systematic review of literature

Role of serum procalcitonin in the diagnosis and monitoring of treatment response in treatment-naïve subjects with chronic pulmonary aspergillosis

BackgroundInterferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA. MethodsWe extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study’s primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy. ResultsWe included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5–7.4%) and 100 (91.2–100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39–0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects. ConclusionPlasma procalcitonin has poor performance in diagnosing and following subjects with CPA.

The estimated burden of fungal diseases in Mali.

Mali is a developing country facing several health challenges with a high rate of tuberculosis (TB) and a moderate HIV infection burden. Little is known or done about fungal diseases, yet they represent a significant public health problem in certain populations. The aim of this study was to estimate the national burden of fungal disease, and summarize data, diagnostic and treatment gaps. We used national demographics and PubMed searches to retrieve articles on published data on these infections and at-risk populations (pulmonary TB, HIV/AIDS patients, patients receiving critical care etc.) in Mali. The estimated Malian population was 21,251,000 in 2020 (UN), of which 45% were children <14 years. Among HIV patients, we estimate an annual incidence of 611 cryptococcosis, 1393 Pneumocystis pneumonia, 180 histoplasmosis and >5,700 esophageal candidiasis and some microsporidiosis cases. Our prevalence estimates for tinea capitis are 2.3 million, for recurrent vulvovaginal candidiasis 272,460, ∼60,000 fungal asthma and 7,290 cases of chronic pulmonary aspergillosis (often mistaken for TB). Less common acute fungal infections are probably invasive aspergillosis (n=1230), fungal keratitis (n=2820), candidaemia (>1,060) and mucormycosis (n=43). Histoplasmin was found in 6% in general population. A few cases of mycetoma are described in Mali. Many WHO Essential medicines and Diagnostics are not available in Mali. This shows a marked disparity in documented and estimated cases of fungal diseases in Mali. These infections are underestimated due to the lack of accurate diagnosis tools and lack of support for fungal diseases diagnosis and management.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

The minimal important difference of six-minute walk test in subjects with chronic pulmonary aspergillosis treated with six-months of oral itraconazole.

P408 Evaluation of fungal serum biomarkers in the diagnosis and for monitoring patients with post tuberculosis chronic pulmonary aspergillosis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectivesThe evaluation of serum β-D-glucan, galactomannan, and Aspergillus fumigatus specific IgG in the diagnosis and clinical management of patients with chronic pulmonary aspergillosis.MethodsConsecutive patients with a past history of pulmonary tuberculosis (PTB) with clinical suspicion of chronic pulmonary aspergillosis (CPA) attending the outpatient services of PGIMER, Chandigarh were included from August 2019 to August 2021, and CPA was defined as described by Denning et al. including both radiological and mycological evidence. Age and sex-matched post-PTB individuals selected from a population attending the chest clinic were enrolled as controls. Serum samples were obtained from all participants and testing for serum β-D-glucan (Fungitell, CapeCod), galactomannan (Platelia, BioRad) and Aspergillus fumigatus specific IgG (ImmunoCAP, Phadia) was performed as per manufacturer's instructions.ResultsA total of 105 post-TB patients with CPA and 11 controls were enrolled. Aspergillus fumigatus (n = 8) was the most commonly isolated species, followed by A. flavus (n = 4), and A. niger (n = 2). The mean A. fumigatus specific IgG levels, serum galactomannan index and BDG levels were higher among CPA cases vs. controls at 101.4 mgA/l vs. 11.8 mgA/l, P-value: .0001; 0.73 vs. 0.35, P-value: .3134; and 133.7 pg/ml vs. 32.37 pg/ml, P-value: .012, respectively (Figs. 1a, b, c). The serum BDG had an area under curve 0.834 ± 0.044 (95% CI: 0.748-0.920) on the ROC curve with a sensitivity of 57.1% and specificity of 100% at the kit cut-off of 80 pg/ml (Fig. 2a). Comparison between CPA patients with multiple (n = 38) versus single lobe (n = 67) involvement showed comparable A. fumigatus specific IgG levels (112.3 vs. 93.8; P-value: .133 respectively) while galactomannan index and BDG levels were higher in cases with multiple vs. single lobe involvement (0.94 vs. 0.57, P-value: .117), and (174.3 vs. 105.3, P-value: .0071), respectively (Fig. 1d, e, f). There was a significant association of BDG value with the severity of dyspnea (P-value: .002) and a trend of higher A. fumigatus specific IgG was also seen to correlate with the severity of dyspnea (Fig. 2b and 2c).ConclusionBDG assay can serve as an adjunct in the diagnosis of patients with CPA. An association of higher levels of BDG with multiple lobe involvement and severe dyspnea could be due to more extensive tissue damage associated with a greater release of antigen in circulation during progressive disease. More studies with a larger number of control samples, preferably with multi-center coordination can further improve our understanding of this test's applicability in routine practice.

Serum total IgE may be a biomarker among chronic pulmonary aspergillosis patients with elevated serum total IgE levels: A cohort study with pathological evaluations.

High serum total IgE levels are common in chronic pulmonary aspergillosis. This novel study indicated that serum total IgE is a possible biomarker of the disease activity in the aforementioned condition. Immunofluorescence staining indicated a possible role of IgE in disease pathogenesis.

Mapping of Chronic Pulmonary Aspergillosis in Africa.

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.

Pulmonary aspergillosis: reports of two cases from a primary care center of Bangladesh

Pulmonary aspergillosis is an uncommon condition and at the same time very much challenging to diagnose and difficult to treat. Here, we present two cases of chronic pulmonary aspergillosis, who presented with with chronic low-grade fever, refractory and distressing cough and haemoptysis. The first patient was diagnosed as having aspergilloma in a pre-existing healed tubercular cavity and the second one with subacute necrotizing pulmonary aspergillosis, which simulated as bronchial carcinoma.&#x0D; BIRDEM Med J 2021; 11(3): 227-230

Pulmonary TB and chronic pulmonary aspergillosis: clinical differences and similarities.

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.

Effect of patient immunodeficiencies on the diagnostic performance of serological assays to detect Aspergillus-specific antibodies in chronic pulmonary aspergillosis

BackgroundPrevalence of chronic pulmonary aspergillosis (CPA) is ~3 million patients worldwide, and detection of Aspergillus-specific antibody is a critical diagnostic component. Some patients with CPA have subtle immune deficits possibly contributing to poor Aspergillus antibody production and false negative results. Materials/methodsWe analyzed patient data from 167 cases of clinically confirmed CPA previously evaluated by ImmunoCAP Aspergillus-specific IgG EIA, Bordier ELISA and LDBio Aspergillus IgG/IgM ICT lateral flow assay, to identify deficiencies in: mannose binding lectin (MBL), IgG, IgA, IgM, IFN gamma, IL12 or IL17 production, and/or low cell marker counts (CD4, CD19, CD56). We defined patients as ‘sero-negative’ if ImmunoCAP Aspergillus IgG was consistently and repeatedly negative (<40 mg A/L). ‘Sero-positive’ was defined as all other CPA cases. ResultsWe found the rate of false negatives by ImmunoCAP Aspergillus IgG EIA (n = 23) to be more prevalent in patients with immunodeficiency markers, especially multiple defects. MBL deficiency combined with low CD19 cells (p < 0.001), pneumococcal antibody levels (p = 0.043), IgM (p = 0.047) or three combined (p = 0.001–0.018) or all four together (p = 0.018) were significant. The performance LDBio Aspergillus IgG/IgM ICT appears to be relatively unaffected by immunodeficiency (92.7% of ImmunoCap sero-negatives were positive). The Bordier assay performed significantly better than the ImmunoCAP assay (P = 0.0016) for sero-negative CPA cases. ConclusionsIn select cases of CPA, ImmunoCAP EIA yields a false negative result, making serological diagnosis difficult. ImmunoCAP false negatives are more prevalent in patients with multiple immunological defects, who may still be positive with the LDBio Aspergillus ICT or Bordier EIA.

A Case of Chronic Pulmonary Aspergillosis with Non-specific Radiological Findings

A Case of Chronic Pulmonary Aspergillosis with Non-specific Radiological Findings

The burden of serious fungal infections in Azerbaijan.

Background:Azerbaijan is an upper middle-income country in South Caucasus with an area of 86,600 km2 and a total population of 10 million people and gross domestic product of US $4480 per capita. The aim of this research is to estimate fungal infection burden and highlight the problem at national and international levels.Methods:Fungal infection burden was estimated using data from epidemiological papers and population at risk and LIFE (Leading International Fungal Education) modelling.Results:The number of people living with human immunodeficiency virus (PLHIV) in 2018 was 6193, 29% of them not receiving antiretroviral therapy. Based on 90% and 20% rates of oral and oesophageal candidiasis in patients with CD4 cell count <200 µl–1 we estimate 808 and 579 patients with oral and oesophageal candidiasis, respectively. The annual incidences of cryptococcal meningitis and Pneumocystis pneumonia are 5 and 55 cases, respectively. We estimated 2307 cases of chronic pulmonary aspergillosis (CPA), 4927 patients with allergic bronchopulmonary aspergillosis (ABPA), and 6504 with severe asthma with fungal sensitization (SAFS). Using data on chronic obstructive pulmonary diseases (COPD), lung cancer, acute myeloid leukaemia rates, and number of transplantations, we estimated 693 cases of invasive aspergillosis following these conditions. Using a low-European rate for invasive candidiasis, we estimated 499 and 75 patients with candidemia and intra-abdominal candidiasis respectively. The number of adult women (15–55 years) in Azerbaijan is ~2,658,000, so it was estimated that 159,490 women suffer from recurrent vulvovaginal candidiasis (rVVC).Discussion:In total, the estimated number of people suffering from fungal diseases in Azerbaijan is 225,974 (2.3% of the population). However, the fungal rate is underestimated due to lack of epidemiological data. The most imminent need is improvement in diagnostic capabilities. This aim should be achieved via establishing a reference laboratory and equipping major clinical centers with essential diagnostics assays.

The burden of serious fungal infections in Sierra Leone: a national estimate.

Sierra Leone is a small, resource-limited country that has a low national prevalence of human immunodeficiency virus (HIV) and a very high burden of tuberculosis (TB). Fungal diseases are probably common, but poorly documented. In this article, we reviewed the existing literature on fungal epidemiology in Sierra Leone using national, regional, and international data, identified knowledge gaps, and propose solutions to address the challenges on the prevention and control of fungal diseases in Sierra Leone and similar countries. In advanced HIV disease, we estimate 300 cryptococcal meningitis, 640 Pneumocystis pneumonia, and over 4000 esophageal candidiasis cases annually. Chronic lung disease is common, with an estimated 6000 cases of chronic pulmonary aspergillosis, many mistaken for TB, 5000 adults with allergic bronchopulmonary aspergillosis complicating asthma, and probably over 6600 cases of severe asthma with fungal sensitization. Invasive aspergillosis is estimated at 478 cases. None of these diagnoses are made in Sierra Leone at present. Major burdens are recurrent vulvovaginal candidiasis (85,400) and tinea capitis in children (266,450). Improvement in fungal disease diagnosis in Sierra Leone will enable better estimates to be made and reduce morbidity and mortality.

Standardization of Aspergillus IgG diagnostic cutoff in Nigerians.

Background and objectives:Commercial Aspergillus IgG antibody assays have become pivotal in the current diagnosis of chronic pulmonary aspergillosis (CPA). However, diagnostic cutoffs have been found to vary from manufactures’ recommendations in different settings. This study aimed to establish the Aspergillus IgG reference range among Nigerians and determine a diagnostic cutoff for CPA.Methods:Sera from 519 prospectively recruited healthy blood donors and 39 previously confirmed cases of CPA were analysed for Aspergillus IgG levels using the Bordier test kit (Bordier Affinity Products SA, Crissier, Switzerland). Accuracy versus cutoff profile and receiver operating characteristics (ROC) curve were analysed for both CPA cases and controls using the R-Studio (2020), (Window desktop, version 4.0.2 software with R packages “nnet” and “ROCR”).Results:Among healthy blood donors, 141 (27.2%) were aged 16–25 years with median (interquartile range, IQR) of 22 (20–24) years; 304 (58.6%) were aged 26–40 years with median (IQR) of 32 (29–36) years; while 74 (14.2%) were aged 41–60 years with median (IQR) of 46 (44–49.75). Median IgG level in respective age groups were 0.069 (0.009–0.181), 0.044 (0.014–0.202) and 0.056 (0.01–0.265) with no significant difference found in the three age categories (p = 0.69). The overall diagnostic cutoff for the diagnosis of CPA was 0.821 with an accuracy of 97.1% and area under the curve (AUC) = 0.986.Conclusion:The optimal diagnostic cutoff for diagnosing CPA in Nigerians using the Bordier kit was 0.821 which is lower than the manufacturer’s recommended cutoff of 1.0. The determination of this cutoff among Nigerians will significantly enhance accurate identification of CPA and assessment of its true burden in Nigeria.

Case of chronic pulmonary aspergillosis, pulmonary tuberculosis, and Klebsiella peumoniae co-infection in an Indian diabetic male- A first of its type case report in the pandemic of COVID-19 from Asia

Case of chronic pulmonary aspergillosis, pulmonary tuberculosis, and Klebsiella peumoniae co-infection in an Indian diabetic male- A first of its type case report in the pandemic of COVID-19 from Asia - IJIRM- Print ISSN No: - 2581-4214 Online ISSN No:- 2581-4222 Article DOI No:- 10.18231/j.ijirm.2020.069, IP Indian Jo

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

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.

Chronic pulmonary aspergillosis – chronic cavitary pulmonary aspergillosis: a case report

Background: Chronic pulmonary aspergillosis (CPA) includes several disease manifestations. Almost all cases of CPA are caused by A. fumigatus. There are several underlying diseases that predispose patients to CPA. Treatment is often individualised depending on underlying disease process and the patient’s pulmonary status.Case presentation: A 57-year-old male with a history of renal transplant in the year 2006, routine on immunosuppressants, pulmonary tuberculosis relapse on anti-tuberculosis medications, aspergillosis on long term voriconazole, and DM type 2 presented with dyspnea, massive hemoptysis and productive cough 3 months before admission. Patient was diagnosed with aspergillosis in October 2012 through bronchoscopy. Microbiology result showed Aspergillus flavus. Enhanced thoracal CT result showed a cavitating nodule with soft tissue lesion in upper right lung, with fibrotic changes in the right lung and mild tubular bronchiectasis, with bilateral pleural thickening. Patient was then planned for lung resection due to the persistent pulmonary cavity. However, his clinical condition worsened and the patient passed away a few days before surgery.Conclusion: Diagnosing chronic pulmonary aspergillosis can often be challenging. The diagnosis of CPA can be inferred from a single chest radiograph. Despite this, detailed and sequentially acquired radiographic data may be required to observe both the typical radiographic features and the very slow progression of this disease. Treatment is often individualised. Azoles are the antifungal drug of choice when required.