Chronic Pulmonary Aspergillosis Patients Research Articles

Impact of Respiratory Bacterial Findings on Patients with Chronic Pulmonary Aspergillosis.

Distinct bacterial strains may affect the prognosis of patients with chronic respiratory diseases. However, little is known about the clinical significance of respiratory bacteria in patients with chronic pulmonary aspergillosis (CPA), a progressive and debilitating disease caused by Aspergillus spp. This study aimed to analyze data obtained from CPA patients and their sputum or bronchial washing samples and investigate the prevalence and composition of respiratory bacteria and clinical implications. Patients and Methods. We retrospectively reviewed the data of patients diagnosed with CPA between March 2019 and February 2023 in a tertiary referral hospital. We assessed the clinical characteristics and overall and pneumonia-specific survival rates of patients with CPA based on the presence of bacteria. Results and Conclusions. We included 142 patients with CPA. The most commonly identified bacteria were Klebsiella pneumoniae (22.5%), followed by Pseudomonas aeruginosa (21.8%) and Escherichia coli (4.2%). Patients with isolated bacteria had a higher prevalence of older age, female sex, diabetes, and a history of extrathoracic malignancy than those without isolated bacteria (P = 0.024, 0.013, 0.021, and 0.034, respectively). Furthermore, over a median follow-up of 11 (4-21) months, the pneumonia-specific mortality rate was 13.4% (19/142), which was higher in patients with isolated bacteria than in those without (P = 0.045, log-rank test). Particularly, patients with the presence of P. aeruginosa had a significantly higher mortality rate from pneumonia than those without the presence of P. aeruginosa (adjusted hazard ratio, 3.34; P = 0.015). In conclusion, CPA patients with isolated bacteria, especially P. aeruginosa, showed higher mortality rates due to pneumonia. Performing tests to identify bacteria in the lower respiratory tract of patients with CPA may be helpful in predicting future prognosis. Further studies are required to validate these findings in diverse ethnic groups.

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.

Impact of Ascaris lumbricoides infection on the development of chronic pulmonary aspergillosis in patients with COPD.

The aetiopathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear. The aim of our study was to determine the possible influence of Ascaris lumbricoides on the development of chronic pulmonary aspergillosis (CPA) in patients with COPD. The prevalence of A. lumbricoides in patients with COPD with CPA (19.05%) was significantly higher than that in those without (9.20%) and controls (4.9%) (p < 0.05). Trends in levels of Interleukin-1β and of tumour necrosis factor α suggest ascariasis increases susceptibility to Aspergillus sp. in patients with COPD and can be considered an additional risk factor for CPA.

Clinical Impact of Chronic Pulmonary Aspergillosis in Patients with Nontuberculous Mycobacterial Pulmonary Disease and Role of Computed Tomography in the Diagnosis.

Objective Chronic pulmonary aspergillosis (CPA) is an important complication of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnosis is challenging, as both CPA and NTM-PD present as chronic cavitary disease. The present study evaluated the impact of CPA on the survival of patients with NTM-PD and revealed the key computed tomography findings for a prompt diagnosis. Methods We retrospectively reviewed patients newly diagnosed with NTM-PD in Tenri Hospital (Tenri City, Nara Prefecture, Japan) between January 2009 and March 2018; the patients were followed up until May 2021. Clinical and radiological characteristics were assessed, and patients with CPA were identified. Results A total of 611 patients were diagnosed with NTM-PD. Among them, 38 (6.2%), 102 (17%), and 471 (77%) patients were diagnosed with NTM-PD with CPA, cavitary NTM-PD without CPA, and non-cavitary NTM-PD without CPA, respectively. The 5-year survival rate of the NTM-PD with CPA group (42.8%; 95% confidence interval: 28.7%-64.0%) was lower than that of the cavitary NTM-PD without CPA group (74.4%; 95% confidence interval: 65.4%-84.6%). A multivariate analysis revealed that fungal balls and cavities with adjacent extrapleural fat were significant predictive factors for NTM-PD with CPA. Conclusion NTM-PD with CPA patients exhibited a worse prognosis than cavitary NTM-PD without CPA patients. Therefore, an unerring diagnosis of CPA is essential for managing patients with NTM-PD. Computed tomography findings, such as fungal balls and cavities with adjacent extrapleural fat, may be valuable diagnostic clues when CPA is suspected in patients with NTM-PD.

Feasibility and safety of uniportal thoracoscopy for chronic pulmonary aspergillosis

Surgery plays a crucial role in the treatment of patients with chronic pulmonary aspergillosis (CPA). However, there is currently limited information available regarding the use of uniportal thoracoscopy (Uni-VATS) in CPA patients. To address this gap, we conducted a retrospective analysis of surgical procedures performed at a single center, aiming to demonstrate the feasibility and safety of Uni-VATS for patients with CPA. We collected basic information and surgical data from patients who underwent surgery for CPA at our hospital between January 2018 and June 2022. All patients received voriconazole antifungal medication for 3–6 months post-surgery and were monitored for a minimum of 6 months. A total of 110 patients, comprising 59 cases in the traditional open chest incision group and 51 cases in the Uni-VATS group, met the inclusion criteria. Among those who underwent surgery, 70% were male (77/110). The median age (IQR) of all enrolled patients was 55 (46–62) years. There were no statistically significant differences in general information, such as age, sex, comorbidities, BMI, FEV1, FVC, clinical symptoms, location of the disease, and duration of voriconazole antifungal medication, between the OS group and the Uni-VATS group (p > 0.05). The postoperative complication rates were 40.7% (24/59) for the traditional open chest incision group and 17.6% (9/51) for the Uni-VATS group. Through univariate analysis, we identified sex and operative approach as risk factors for postoperative complications. Multivariate logistic analysis confirmed that male and OS procedures were the independent risk factors for postoperative complications. There were statistically significant differences in operative time, intraoperative blood loss volume, postoperative drainage volume, pain scores, postoperative drainage tube removal time, postoperative hospital stay time between the OS group and the Uni-VATS group (p < 0.05). Uni-VATS is a feasible and safe surgical procedure for patients with CPA, and we recommend it as a preferred option for selected patients with CPA.

Prevalence and predictors of Aspergillus seropositivity and chronic pulmonary aspergillosis in an urban tertiary hospital in Sierra Leone: A cross-sectional study.

In the World Health Organization Global Tuberculosis (TB) Report 2022, 37% of pulmonary TB patients were clinically diagnosed and thus many people were treated for TB without evidence of the disease. Probably the most common TB misdiagnosis is chronic pulmonary aspergillosis (CPA). In this study, we aimed to assess the prevalence and predictors of Aspergillus seropositivity and CPA in patients with chronic respiratory symptoms in an urban tertiary hospital in Sierra Leone. We used a cross-sectional study design to recruit adults (≥18 years) from the Chest Clinic of Connaught Hospital, Freetown between November 2021 and July 2022. Aspergillus antibody was detected using LDBio Aspergillus IgM/IgG. Logistic regression was performed to assess the independent predictors of Aspergillus seropositivity and CPA. Of the 197 patients with chronic respiratory symptoms, 147 (74.6%) were male. Mean age was 47.1 ± 16.4 years. More than half (104, 52.8%) had been diagnosed with TB in the past, while 53 (26.9%) were on TB treatment at the time of recruitment. Fifty-two (26.4%) patients were HIV positive, 41 (20.8%) were seropositive for Aspergillus and 23 (11.6%) had CPA, 2 (3.8%) with current TB and 18 (17.3%) with past TB. Common radiologic abnormalities reported were localized fibrotic changes 62 (31.5%), consolidation 54 (27.4%), infiltrates 46 (23.4%), hilar adenopathy 40 (20.3%) and pleural effusion 35 (17.85) and thickening 23 (11.7%). Common symptoms were weight loss 144 (73.1%), cough 135 (68.5%), fever 117 (59.4%) and dyspnea 90 (45.7%). Current or past TB infection {aOR 3.52, 95% CI (1.46, 8.97); p = 0.005} was an independent predictor of Aspergillus seropositivity and CPA. We report a high prevalence of Aspergillus antibody seropositivity and CPA, underscoring the need to integrate the prevention and management of pulmonary fungal infections with TB services and asthma care in order to reduce unnecessary morbidity and mortality.

The Impact of Chronic Pulmonary Aspergillosis Co-infection on the Health-Related Quality of Life of Patients with Pulmonary Tuberculosis in Uganda.

Both pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) significantly affect health-related quality of life (HR-QoL). We aimed to determine the impact of CPA co-infection on the HR-QoL of Ugandans with PTB. We conducted a prospective study as part of a larger study among participants with PTB with persistent pulmonary symptoms after 2months of anti-TB treatment at Mulago Hospital, Kampala, Uganda between July 2020 and June 2021. HR-QoL was assessed using St. George Respiratory Questionnaire (SGRQ) at enrollment and at the end of PTB treatment (4months apart). SGRQ scores range from 0 to 100, with higher score representing a poorer HR-QoL. Of the 162 participants enrolled in the larger study, 32 (19.8%) had PTB + CPA and 130 (80.2%) had PTB. The baseline characteristics of the two groups were comparable. Regarding overall health, a higher proportion of the PTB group rated their HR-QoL as "very good" compared to those who had PTB + CPA (68 [54.0%] versus 8 [25.8%]). At enrollment, both groups had comparable median SGRQ scores. However, at follow up, the PTB group had statistically significantly better SGRQ scores (interquartile range); symptoms (0 [0-12.4] versus 14.4 [0-42.9], p < 0.001), activity ((0 [0-17.1] versus 12.2 [0-35.5], p = .03), impact (0 [0-4.0] versus 3.1 [0-22.5], p = 0.004), and total scores ((0 [0-8.5] versus 7.6[(0-27.4], p = 0.005). CPA co-infection impairs HR-QoL of people with PTB. Active screening and management of CPA in patients with PTB is recommended to improve HR-QoL of these individuals.

Diagnostic Laboratory Features and Performance of an Aspergillus IgG Lateral Flow Assay in a Chronic Pulmonary Aspergillosis Cohort.

Chronic pulmonary aspergillosis (CPA) is a chronic and progressive fungal disease with high morbidity and mortality. Avoiding diagnostic delay and misdiagnosis are concerns for CPA patients. However, diagnostic practice is poorly evaluated, especially in resource-constrained areas where Aspergillus antibody testing tools are lacking. This study aimed to investigate the diagnostic laboratory findings in a retrospective CPA cohort and to evaluate the performance of a novel Aspergillus IgG lateral flow assay (LFA; Era Biology, Tianjin, China). During January 2016 and December 2021, suspected CPA patients were screened at the Center for Infectious Diseases at Huashan Hospital. A total of 126 CPA patients were enrolled. Aspergillus IgG was positive in 72.1% with chronic cavitary pulmonary aspergillosis, 75.0% with chronic necrotizing pulmonary aspergillosis, 41.7% with simple aspergilloma, and 30.3% with Aspergillus nodule(s). The cavitary CPA subtypes had significantly higher levels of Aspergillus IgG. Aspergillus IgG was negative in 52 patients, who were finally diagnosed by histopathology, respiratory culture, and metagenomic next-generation sequencing (mNGS). Sputum culture was positive in 39.3% (42/107) of patients and Aspergillus fumigatus was the most common species (69.0%, 29/42). For CPA cohort versus controls, the sensitivity and specificity of the LFA were 55.6% and 92.7%, respectively. In a subgroup analysis, the LFA was highly sensitive for A. fumigatus-associated chronic cavitary pulmonary aspergillosis (CCPA; 96.2%, 26/27). Given the complexity of the disease, a combination of serological and non-serological tests should be considered to avoid misdiagnosis of CPA. The novel LFA has a satisfactory performance and allows earlier screening and diagnosis of CPA patients. IMPORTANCE There are concerns on avoiding diagnostic delay and misdiagnosis for chronic pulmonary aspergillosis due to its high morbidity and mortality. A proportion of CPA patients test negative for Aspergillus IgG. An optimal diagnostic strategy for CPA requires in-depth investigation based on real-world diagnostic practice, which has been rarely discussed. We summarized the clinical and diagnostic laboratory findings of 126 CPA patients with various CPA subtypes. Aspergillus IgG was the most sensitive test for diagnosing CPA. However, it was negative in 52 patients, who were finally diagnosed by non-serological tests, including biopsy, respiratory culture, and metagenomic next-generation sequencing. We also evaluated a novel Aspergillus IgG lateral flow assay, which showed a satisfactory performance in cavitary CPA patients and was highly specific to Aspergillus fumigatus. This study gives a full picture of the diagnostic practice for CPA patients in Chinese context and calls for early diagnosis of CPA with combined approaches.

Serum Cytokine Biomarkers for Use in Diagnosing Pulmonary Tuberculosis versus Chronic Pulmonary Aspergillosis.

Aspergillus fumigatus-induced chronic pulmonary aspergillosis (CPA), the most common pulmonary tuberculosis (TB) sequela, tends to occur after pulmonary infection with the intracellular pathogen Mycobacterium tuberculosis (Mtb). Timely and accurate detection of A. fumigatus infection of pulmonary TB patients would undoubtedly greatly improve patient prognosis. Currently, the galactomannan (GM) antigen test is commonly used to detect A. fumigatus infection but has poor sensitivity that renders this assay inadequate for use in clinical practice. Given the fact CPA and TB induce different host immune responses, we evaluated serum cytokine level profiles of CPA, TB patients and patients with both diseases (CPA-TB) for multiple cytokines and cytokine combinations. The results revealed significantly higher serum levels of numerous proinflammatory cytokines, including IL-1β, IL-6, IL-8, IL-12p70, IFN-α, IFN-γ and TNF-α, in peripheral blood of CPA-TB patients versus that of TB patients. IL-8 levels alone provided the best discriminatory performance for distinguishing between TB and either CPA-TB patients (AUC = 0.949) or CPA patients (AUC = 0.964). Moreover, both IL-8 and TNF-α (AUC = 0.996) levels could be used to distinguish between TB and CPA-TB patients. Likewise, IL-8, TNF-α and IL-6 levels together could be used to distinguish between CPA-TB and TB patients. In this study, multiple cytokines were identified that may serve as potential biomarkers for use in detecting TB patients with CPA. Furthermore, our results should enhance understanding of how immune system dysfunctions influence susceptibility to Mtb and/or A. fumigatus infections.

Prevalence of chronic pulmonary aspergillosis in fibrocavitary pulmonary tuberculosis patients.

Tuberculosis (TB) is still a global health issue. While the lungs are the most commonly affected, infections can also affect other organs. Because of the rise in immunocompromised hosts, the number of opportunistic infections has skyrocketed. In instances of aspergilloma and chronic pulmonary aspergillosis (CPA), pulmonary tuberculosis (PTB) is the most usually linked condition. The current cross-sectional study was conducted on 42 study participants from January 2018 to June 2019. Aspergilloma was observed in two participants (4.8%) of the study population. Candida growth was observed in five participants (11.9%) of the study population on sputum fungal culture. Aspergillus growth and Candida growth was observed in three (7.1%) and two (4.8%) participants of the study population, respectively, on bronchoalveolar lavage (BAL) fungal culture. Aspergillus IgG antibody was positive in four particpants (9.5%) of study population. Out of the 42 participants, four were diagnosed with CPA. Since CPA and PTB patients present similar symptoms, it is virtually impossible to distinguish between the two unless serological test is performed. There has been a significant burden of patients with CPA, especially in post tuberculosis fibro-cavitation. CPA patients requires long-term anti-fungal therapy; hence an improved case detection should be undertaken.

Loss to follow-up associated factors in patients with chronic pulmonary aspergillosis and its impact on the disease prognosis.

Pulmonary aspergillosis is a rare but challenging pulmonary disease. The conditions of patients with chronic pulmonary aspergillosis (CPA) can be even more complicated. The mortality rate of CPA remains high, and the prognostic factors are not well established due to a high proportion of loss to follow-up. In this study, we aim to explore factors associated with loss to follow-up in CPA patients and their impact on the disease prognosis after withdrawing anti-fungal treatments. Patients with confirmed CPA, who were admitted to the Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University from March 2017 to November 2019, were enrolled in this prospective study. The enrolled patients were followed up for 6 months after discharge. For loss to follow-up patients, the reasons for loss to follow-up and their prognosis after withdrawing anti-fungal treatments during loss to follow-up were recorded by telephone communication. Multivariate logistic regression analysis was performed to determine factors associated with loss to follow-up. The 199 out of 298 screened patients were included in the study. Except for 67 cases with regular follow-up, the rest 132 cases were lost to follow-up. Factors, including age > 60 years (OR = 2.036, P = 0.03), monthly income ≤ $583 (OR = 5.568, P = 0.0001), education ≤ 6 years (OR = 7.474, P = 0.0001), and non-local residence (OR = 5.893, P = 0.0001) were associated with the loss to follow-up according to multivariate logistic regression analysis. The most common reasons for loss to follow-up were economic factors and clinic visit distance. The overall case fatality rate (CFR) within 180 days in patients with regular follow-up and patients who stopped anti-fungal treatment during the loss to follow-up was 0% and 19.65%, respectively. The proportion of loss to follow-up in CPA patients remained high. Age (>60 years), poor financial status, low education, and non-local residence were the key factors associated with the loss to follow-up in this study. Our study reveals the need to optimize the follow-up procedures and improve the patients understanding about the benefits and limitations of follow-up to reduce the CFR.

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.

P203 Chronic pulmonary aspergillosis (CPA) in post tuberculosis sequele— aclinical experience from tertiary care

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMIntroductionChronic pulmonary aspergillosis (CPA) is a spectrum of illnesses clinically presenting as a persistent cough, dyspnea, hemoptysis, fatigue, and weight loss and radiologically can range from single aspergilloma, Aspergillus nodule, or chronic cavitary pulmonary aspergillosis (CCPA) which can progress to chronic fibrosing pulmonary aspergillosis if left untreated.1 CPA has high morbidity, burden in India estimated to be in a 5-year prevalence of 24/100 000.2 The commonly used criteria for diagnosing CPA include cough or hemoptysis for 1 month, raised Aspergillus-specific IgG, absence of positive GeneXpert test for Mycobacterium tuberculosis and either paracavitary fibrosis or a fungal ball on imaging of the thorax or progressive cavitation (either new cavitation or deterioration of pre-existing cavitation) on serial chest radiographs. Pulmonary tuberculosis (PTB) is the important predisposing risk factor for CPA,3 India being an endemic country, incidence of CPA may be underestimated or it may be misdiagnosed as smear-negative tuberculosis. Microbiologically, diagnosis by direct confirmation of Aspergillus spp infection (microscopy or culture from respiratory samples) may not be always positive, in such a scenario the immune response to Aspergillus spp. by measuring Aspergillus specific Immunoglobulin Ig G in clinically suspected cases may be used for diagnosis of CPA.MethodThis is a cross-sectional conducted in a tertiary care hospital, New Delhi, India. The patients with previous history of pulmonary tuberculosis who presented with symptoms of cough, hemoptysis, fever, shortness of breath, chest pain, and weight loss of ˃12-week duration were enrolled in the study. Relevant investigations including blood tests, chest imaging, sputum examination for bacterial infections, fungal (KOH mount), and tuberculosis (AFB smear, CBNAAT, mycobacterial cultures) were done. Microbiological evidence included a positive Aspergillus-specific IgG (cut off >8 units/ml) or positive serum galactomannan index (GMI) (cut off >1 according to EORTC/MSG guidelines) or KOH mount on sputum showing branching hyaline septate hyphae morphologically suggestive of Aspergillus spp. Patients who were diagnosed with CPA according to criteria were treated and followed up.ResultsA total of 15 patients were screened in the study, 4 patients who had concurrently detected pulmonary tuberculosis detected by Genexpert, were excluded from the study. Majority of patients presented with complaints of recurrent episodes of cough and hemoptysis. Imaging features included cavitation, bronchiectasis, pleural thickening, and fungal ball. Sputum microscopy for fungal elements was positive only in 10 patients. The serum Aspergillus Ig G (values ranged from 19.8-200 u/mL) was raised in all patients while serum GMI above cut-off was present in only 5 patients. All confirmed CPA patients were managed with voriconazole for 4 months. Following 4 months of treatment, all patients had favorable outcomes in terms of radiological improvement and clinical cure.ConclusionCPA is an underestimated post-PTB sequel and should be considered as differentials in patients with respiratory symptoms in post TB patients. Aspergillus Ig G and chest imaging are recommended as initial diagnostic tools for diagnosing CPA.Sources:Denning DW, Cadranel J, Beigelman-Aubry C et al. European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016; 47(1): 45-68.Agarwal R, Denning DW, Chakrabarti A. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS One. 2014; 9(12): e114745.Page ID, Byanyima R, Hosmane S et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. Eur Respir J. 2019; 53: 1801184

Cytomegalovirus viral interleukin-10 in patients with Aspergillus infection and effects on clinical outcome.

Human cytomegalovirus (CMV) is associated with aspergillosis, but the simultaneous presence of CMV viral interleukin-10 (cmvIL-10) and aspergillosis has never been investigated. CmvIL-10 is produced by CMV-infected cells and acts as an immune modulator during CMV infection. The aim of this study was to evaluate cmvIL-10 levels in peripheral blood and its influence on the clinical outcomes of Aspergillus infection. Patients who visited or were admitted to the hospital with suspected Aspergillus infection, including invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA), were prospectively enrolled. The cmvIL-10, human IL-10 (hIL-10), IL-1B, IL-6, IL-8, IFN-γ, and TNF-α levels in peripheral blood were measured. Patients with Aspergillus infection had a higher level of cmvIL-10 than the control group (158 ± 305 vs 27.9 ± 30.4pg/ml, p < .05). The level of cmvIL-10 was not correlated with CMV viremia or end-organ disease. The cmvIL-10 but not hIL-10 level was positively correlated with the IFN-γ level (p < .05) and marginally negatively correlated with IL-1B and IL-8 levels (p < .1). In patients with CPA, a high level of cmvIL-10 (≥100 pg/ml) was a poor prognostic factor for long-term survival (p < .05). In contrast, CMV viremia or end-organ disease was associated with poor survival in patients with IA (p=.05). Aspergillus infection was associated with CMV coinfection with cmvIL-10 in blood. A cmvIL-10 concentration ≥100 pg/ml was a predictor for unfavourable outcome in CPA patients.

Prevalence of chronic pulmonary aspergillosis regarding time of tuberculosis diagnosis in Brazil.

Data on the prevalence of chronic pulmonary aspergillosis (CPA) in patients with active or cured tuberculosis (TB) are scarce, mainly due to diagnostic difficulties. The diagnosis of CPA is based on pulmonary symptoms and chest computed tomography (CT) scans and is considered confirmed when there is microbiological or serological evidence of Aspergillus spp. To estimate the prevalence of CPA in patients treated or undergoing treatment for PTB, seen in two referral hospitals in Mato Grosso do Sul, Brazil. A total of 193 consecutive patients who were treated or previously treated for pulmonary tuberculosis underwent prospective evaluation: (a) clinical evaluation; (b) chest CT scan; (c) sputum examination-culture for fungi and smears for direct mycology; (d) detection of anti-Aspergillus fumigatus antibodies using an enzyme-linked immunosorbent assay Platelia® test; and (e) anti-Aspergillus spp. antibodies were assessed via a DID test. The global prevalence of CPA was 10.9% (95% confidence interval, 7.2%-16.1%), but it increased with the time of TB diagnosis. The variables independently associated with CPA were previous pulmonary tuberculosis over 4 years ago and haemoptysis. Cavities, pleural thickening and the presence of a fungal ball were the most frequent tomographic findings in patients with CPA. The high prevalence observed and its increase over time suggest the need for continuous surveillance of CPA in patients with active or previous pulmonary tuberculosis and throughout life, with clinical, tomographic and serological evaluations (ELISA) for a timely diagnosis and a better prognosis.

Chronic pulmonary aspergillosis in patients with active pulmonary tuberculosis with persisting symptoms in Uganda.

The occurrence of chronic pulmonary aspergillosis (CPA) among drug sensitive pulmonary tuberculosis (PTB) patients on optimal therapy with persistent symptoms was investigated. We consecutively enrolled participants with PTB with persistent pulmonary symptoms after 2months of anti-TB treatment at Mulago Hospital, Kampala, Uganda, between July 2020 and June 2021. CPA was defined as a positive Aspergillus-specific IgG/IgM immunochromatographic test (ICT), a cavity with or without a fungal ball on chest X-ray (CXR), and compatible symptoms >3months. We enrolled 162 participants (median age 30years; IQR: 25-40), 97 (59.9%) were male, 48 (29.6%) were HIV-infected and 15 (9.3%) had prior PTB. Thirty-eight (23.4%) sputum samples grew A.niger and 13 (8.0%) A.fumigatus species complexes. Six (3.7%) participants had intracavitary fungal balls and 52 (32.1%) had cavities. Overall, 32 (19.8%) participants had CPA. CPA was associated with prior PTB (adjusted odds ratio [aOR]: 6.61, 95% CI: 1.85-23.9, p=.004), and far advanced CXR changes (aOR: 4.26, 95% CI: 1.72-10.52, p=.002). The Aspergillus IgG/IgM ICT was positive in 10 (31.3%) participants with CPA. Chronic pulmonary aspergillosis may cause persistent respiratory symptoms in up to one-fifth of patients after intensive treatment for PTB. The Aspergillus IgG/IgM ICT positivity rate was very low and may not be used alone for the diagnosis of CPA in Uganda.

Unravelling the Molecular Identification and Antifungal Susceptibility Profiles of Aspergillus spp. Isolated from Chronic Pulmonary Aspergillosis Patients in Jakarta, Indonesia: The Emergence of Cryptic Species.

Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial β-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients.

Incidence of Chronic Pulmonary Aspergillosis in Patients with Suspected or Confirmed NTM and TB-A Population-Based Retrospective Cohort Study.

Chronic pulmonary aspergillosis (CPA) is a severe and underdiagnosed pulmonary fungal infection with a significant overlap in symptoms and imaging findings of mycobacterium tuberculosis (TB) and non-tuberculous mycobacterium (NTM). Infection with TB or NTM is a predisposing underlying condition for CPA in approximately one-third of patients. A previously published study from Uganda showed increased incidence and complication rate of CPA with respect to pre-existing radiographic cavitation in a post-treatment TB population. The aim of this study was to investigate the incidence of CPA in a low-endemic population of confirmed or suspected TB and NTM patients. We manually reviewed 172 patients referred on suspicion or for treatment of TB or NTM at the Department of Respiratory Medicine, Odense University Hospital during the period of 1 January 2018 to 31 December 2020. We found no CPA amongst TB patients as opposed to an incidence of 8.2% (n = 4) in NTM-infected patients. We identified possible investigatory differences in Aspergillus blood sample screening protocols depending on NTM or TB, initiated at the Department of Respiratory Medicine at Odense University Hospital. A focused screening and investigatory protocol in NTM patients with persisting or developing symptoms is warranted in relation to suspected CPA.

Prevalence of Chronic Pulmonary Aspergillosis in Patients Suspected of Chest Malignancy.

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening fungal lung infection, and recent research suggests CPA to be more common than previously considered. Although CPA mimics other lung diseases including pulmonary cancer, awareness of this disease entity is still sparse. This study aimed to investigate the prevalence of CPA in a population of patients under suspicion of having lung cancer. We conducted a retrospective cohort study of 1200 patients and manually collected individual health record data from previous cancer examinations, with retrospective CPA status assessment using international criteria. Among 992 included patients, 16 (1.6%) fulfilled diagnostic criteria for CPA retrospectively, of whom 15 were undiscovered at initial lung cancer examination. The prevalence of CPA in this study population was 50 times higher than the reported prevalence of the overall European population. Our findings indicate that CPA is often missed in patients suspected of malignancy in the chest. Therefore, CPA should be kept in mind as a significant differential diagnosis.