Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can't undergo surgeryIntracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don't work well because they can't reach high enough concentrations in the cavities. Surgery is usually the best option, but it's risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We've treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can't have surgery.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities.

BACKGROUND: Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%-25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. METHODS: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. RESULTS: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets. CONCLUSION: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.

Chronic pulmonary aspergillosis incidence in newly detected pulmonary tuberculosis cases during follow-up.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is known to complicate patients with post-tubercular lung disease. However, some evidence suggests that CPA might co-exist in patients with newly-diagnosed pulmonary tuberculosis (P.TB) at diagnosis and also develop during therapy. The objective of this study was to confirm the presence of CPA in newly diagnosed P.TB at baseline and at the end-of-TB-therapy. MATERIALS AND METHODS: This prospective longitudinal study included newly diagnosed P.TB patients, followed up at third month and end-of-TB-therapy with symptom assessment, anti-Aspergillus IgG antibody and imaging of chest for diagnosing CPA. RESULTS: We recruited 255 patients at baseline out of which 158 (62%) completed their follow-up. Anti-Aspergillus IgG was positive in 11.1% at baseline and 27.8% at end-of-TB-therapy. Overall, proven CPA was diagnosed in 7% at baseline and 14.5% at the end-of-TB-therapy. Around 6% patients had evidence of aspergilloma in CT chest at the end-of-TB-therapy. CONCLUSIONS: CPA can be present in newly diagnosed P.TB patients at diagnosis and also develop during anti-tubercular treatment. Patients with persistent symptoms or developing new symptoms during treatment for P.TB should be evaluated for CPA. Whether patients with concomitant P.TB and CPA, while receiving antitubercular therapy, need additional antifungal therapy, needs to be evaluated in future studies.

Analysis of cases with co-infection of COVID-19 and pulmonary aspergillosis.

The objective of this study was to investigate the risk factors and diagnosis measure of COVID-19-associated pulmonary aspergillosis (CAPA). This study included 201 COVID-19 patients from December 1, 2022, to January 31, 2023; 7 (3.5%) were diagnosed with CAPA. The main risk factors were age, MV, ICU admission and COPD, and the presence of comorbidities such as ARDS and hypoproteinemia in COVID-19 patients, more susceptible to Aspergillus infection. In addition to specimen culture in the lower respiratory tract, the 1,3-ß-D-glucan antigen test can serve as an important screening indicator for early CAPA diagnosis in non-granulocytopenia patients.

Native-lung complications following single-lung transplantation for interstitial lung disease: an in-depth analysis.

BACKGROUND: Interstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood. METHODS: A retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups. RESULTS: Our study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients. CONCLUSIONS: This study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation.

The incidence and prevalence of serious fungal diseases in Tunisia.

With increasing concern about the negative health impact of fungal disease, there is a need to survey what is and is not known about the epidemiology of these infections in Tunisia. We have estimated the incidence and prevalence of the most serious fungal diseases in Tunisia for the first time. Using published literature from Tunisia, or if absent other countries, we have estimated the burden of life-threatening fungal infections and those causing significant morbidity, using deterministic modeling, based on populations at greatest risk. An estimated 250,494 (2.12% of the Tunisian population) are affected by a serious fungal disease annually. Invasive and chronic pulmonary aspergillosis are relatively common with 708 and 2090 patients affected, partly linked to the prevalence of chronic obstructive pulmonary disease (COPD). Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization) have an estimated prevalence of 38,264 (5.8% of the adult asthma population). Fungal keratitis probably affects 1,761 eyes annually, often leading to uniocular blindness. Candidaemia and Candida peritonitis probably affect at least 680 people annually, with a high mortality. Recurrent vulvovaginal candidiasis probably affects over 200,000 women. While fungal diseases are regularly diagnosed in Tunisia, epidemiological studies with denominators are uncommon. Some fungal diseases are poorly addressed with the current diagnostic portfolio, and surveillance is lacking. Studies on these diseases and the implementation of a national program of surveillance are required.

COVID-19-associated pulmonary aspergillosis (CAPA) in hematological patients: Could antifungal prophylaxis be necessary? A nationwide study.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. METHODS: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. FINDINGS: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p < 0.001]. B-cell malignancies - specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia - showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. CONCLUSION: COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted.

Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. MATERIALS AND METHODS: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. RESULTS: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort. CONCLUSION: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

A 65-Year-Old Man with Refractory Hemoptysis Associated with Chronic Progressive Pulmonary Aspergillosis Who Failed to Respond to Combined Endobronchial Occlusion and Bronchial Artery Embolization: A Case Report and Literature Review.

BACKGROUND Hemoptysis due to airway hemorrhage is treated with hemostatic agents, bronchial artery embolization (BAE), or surgical resection. We present the case of a 65-year-old man with refractory hemoptysis associated with chronic progressive pulmonary aspergillosis (CPPA) who failed to respond to combined endobronchial occlusion (EBO) with endobronchial Watanabe spigot (EWS) and BAE. CASE REPORT A 63-year-old man was diagnosed with CPPA in the right upper lung and presented to our hospital 2 years later for hemoptysis at age 65. He developed severe hemoptysis during an outpatient visit, and was urgently admitted, intubated, and ventilated to prevent choking on blood clots. Chest computed tomography showed a large mass in the apical portion of the right lung, constituting apical pleural thickening and an encapsulated pleural effusion, and dilatation in the bronchial artery supplying the right upper lung lobe. Bronchoscopy revealed the right upper lobe B1-B3 as the bleeding source. The patient had recurrent hemoptysis that was not controlled by BAE or 6 EBO+EWS procedures, and he ultimately died of hypoxemia.In the literature review, EBO+EWS can effectively control hemoptysis in appropriate cases, without the need for BAE or surgical lung resection. It is less invasive, is associated with fewer adverse events than BAE or surgery, and can achieve temporary hemostasis for severe hemoptysis. CONCLUSIONS BAE and EBO+EWS were ineffective in controlling recurrent hemoptysis caused by CPPA in this case. However, a multidisciplinary approach such as attempting hemostasis with combined EBO+EWS and BAE may be a viable treatment option in severe cases of hemoptysis.

Aspergillus nodules: Natural history and the effect of antifungals.

BACKGROUND: Aspergillus nodules are classified as a subset of chronic pulmonary aspergillosis. The optimal management approach is not known as their natural evolution following biopsy, the rate of progression to chronic cavitary pulmonary aspergillosis (CCPA) and the effect of antifungal treatment have not been described. OBJECTIVES: To describe the clinical course of patients diagnosed with Aspergillus nodules and the effect of antifungal treatment. PATIENTS/METHODS: We present a series of 23 patients with histologically confirmed Aspergillus nodules and describe serial imaging, antifungal treatment and progression to other diagnoses. RESULTS: Thirteen patients were diagnosed after a CT-guided biopsy and 10 after surgical resection. Among those who had CT-guided biopsy, 8 did not receive antifungal treatment; the nodule was stable or smaller in all cases on subsequent CT scan after a mean of 15.5 months. However, one patient developed squamous cell carcinoma after 16 months and another developed CCPA after 7 months. Among the 5 patients who received antifungals for at least 4 weeks, the nodule was smaller in 1 and stable in 4. One patient developed CCPA 3 years after the biopsy. No patient who had a surgical resection subsequently had a CCPA diagnosis. CONCLUSION: Most Aspergillus nodules remained stable or improved following biopsy, irrespective of the effect of antifungals. However, CCPA can develop occasionally in patients with Aspergillus nodules and ongoing radiological follow-up may be warranted when the nodule is not resected.

Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza.

The complex interaction between viruses and fungi has profound implications, especially given the significant impact of these microorganisms on human health. While well-known examples such as HIV, influenza, and SARS-CoV-2 are recognized as risk factors for invasive fungal diseases, the relationship between viruses and fungi remains largely underexplored outside of these cases. Fungi and viruses can engage in symbiotic or synergistic interactions. Remarkably, some viruses, known as mycoviruses, can directly infect fungi, may influencing their phenotype and potentially their virulence. In addition, viruses and fungi can coexist within the human microbiome, a complex ecosystem of microorganisms. Under certain conditions, viral infection might predispose the host to an invasive fungal infection, as observed with influenza-associated pulmonary aspergillosis or COVID-19 associated pulmonary aspergillosis. We aim in this review to highlight potential connections between fungi and viruses (CMV and other herpesviruses, HTLV-1 and respiratory viruses), excluding SARS-CoV-2 and influenza.

The link between invasive fungal diseases and certain viruses (HIV, SARS-CoV-2 and influenza) is now well established. For other viruses, however, the relationship remains uncertain. In this review, we aim to highlight associations between fungi and viruses, except HIV, SARS-CoV-2 and influenza.

[Well Differentiated Liposarcoma of a Lung:Report of a Case].

A 61-year-old woman was referred for further evaluation of an intracystic nodule in her left upper lung. Computed tomography( CT) showed a 15 mm nodule in a pulmonary cyst adjacent to aortic arch and mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET)-CT showed little uptake of FDG in the lesion. No abnormality was found in the bronchoscopy findings. On imaging findings, the possibility of pulmonary aspergilloma was considered, but the serological findings were inconsistent, and surgical resection of the lesion was performed for both diagnosis and treatment. The final pathohistological diagnosis was well differentiated liposarcoma. No adjuvant therapy was performed and the patient has been well without recurrence for 2 years after the surgery. We report a rare case of well differentiated liposarcoma of a lung mimicking pulmonary aspergilloma.

Pulmonary scedosporiosis in an intractable immunocompetent host: A case report and literature review.

Pulmonary scedosporiosis is a rare pulmonary infection that often presents with nonspecific symptoms and radiological findings. In this report, we present a case of localized pulmonary scedosporiosis in an immunocompetent patient and analyze a total of 25 immunocompetent patients with pulmonary scedosporiosis. Through this case and the literature, we highlight the importance of considering pulmonary scedosporiosis in patients with nonspecific clinical symptoms and radiological findings resembling aspergilloma. This case and the literature further emphasize the significance of surgical intervention. Regardless of the use of antifungal drugs, surgery should be conducted as soon as possible.

Comparison of influenza- and COVID-19-associated pulmonary aspergillosis in China.

PURPOSE: We conducted a monocentric retrospective study using the latest definitions to compare the demographic, clinical, and biological characteristics of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA). METHODS: The study retrospectively enrolled 180 patients, including 70 influenza/IPA patients (with positive influenza A/B and Aspergillus) and 110 COVID-19/IPA patients (with positive SARS-CoV-2 and Aspergillus). Among them, 42 (60%) and 30 (27.3%) patients fulfilled the definitions of IAPA and CAPA, respectively. RESULTS: The CAPA patients had significantly higher in-hospital mortality (13/31, 41.9%) than IAPA patients (8/42, 19%) with a P-value of 0.033. Kaplan-Meier survival curve also showed significantly higher 30-day mortality for CAPA patients (P = 0.025). Additionally, the CAPA patients were older, though insignificantly, than IAPA patients (70 (60-80) vs. 62 (52-72), P = 0.075). A lower percentage of chronic pulmonary disease (12.9 vs. 40.5%, P = 0.01) but higher corticosteroids use 7 days before and after ICU admission (22.6% vs. 0%, P = 0.002) were found in CAPA patients. Notably, there were no significant differences in the percentage of ICU admission or ICU mortality between the two groups. In addition, the time from observation to Aspergillus diagnosis was significantly longer in CAPA patients than in IAPA patients (7 (2-13) vs. 0 (0-4.5), P = 0.048). CONCLUSION: Patients infected with SARS-CoV-2 and Aspergillus during the concentrated outbreak of COVID-19 in China had generally higher in-hospital mortality but a lower percentage of chronic pulmonary disease than those infected with influenza and Aspergillus. For influenza-infected patients who require hospitalization, close attention should be paid to the risk of invasive aspergillosis upfront.

Estimated burden of fungal infections in Panama.

Data published on Panamanian fungal disease are scarce, mostly case reports. To date, there is no paper that compiles the burden of fungal disease Here we estimate for the first time the incidence and prevalence of fungal diseases in Panama. Data on fungal disease were obtained from different search engines: PubMed, Google Scholar, Scielo and Lilacs. For population and at risk diseases, we used statistics from worldometer, UNAIDS, and WHO. Incidence, prevalence, and absolute numbers were calculated based on the population at risk. Panamanian population in 2022 was 4,429,739. We estimated that 85,530 (1.93 %) people suffer from fungal diseases. The most frequent fungal infection was recurrent Candida vaginitis (3285/100,000). There are 31,000 HIV-infected people in Panama and based on the number of cases not receiving anti-retroviral therapy (14,570), and previous reports of prevalence of opportunistic infections, we estimated annual incidences of 4.0/100,000 for cryptococcal meningitis, 29.5/100,000 for oral candidiasis, 23.1/100,000 for esophageal candidiasis, 29.5/100,000 for Pneumocystis pneumonia, 15.1/100,000, and for histoplasmosis. For chronic pulmonary aspergillosis (CPA) and fungal asthma we used data from Guatemala and Colombia to estimate COPD and asthma prevalence and WHO report for tuberculosis. We estimated annual incidences of 6.1/100,000 for invasive aspergillosis and prevalence of 31.5/100,000 for CPA, 60.2/100,000 for allergic bronchopulmonary aspergillosis, and 79.5/100,000 for severe asthma with fungal sensitisation. Other incidence estimates were 5.0/100,000 for candidaemia, 0.20/100,000 for mucormycosis, and 4.97/100,000 for fungal keratitis. Even though this report on burden of fungal disease is a forward step, more epidemiological studies to validate these estimates are needed.