Epidemiology of chronic pulmonary aspergillosis: A nationwide descriptive study.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has recently gained attention owing to its substantial health burden. However, the precise epidemiology and prognosis of the disease are still unclear due to the lack of a nationwide descriptive analysis. This study aimed to elucidate the epidemiology of patients with CPA and to investigate their prognosis. METHODS: Using a national administrative database covering >99% of the population in Japan, we calculated the nationwide incidence and prevalence of CPA from 2016 to 2022. Additionally, we clarified the survival rate of patients diagnosed with CPA and identified independent prognostic factors using multivariate Cox proportional hazard analysis. RESULTS: During the study period, while the prevalence of CPA remained stable at 9.0-9.5 per 100,000 persons, its incidence declined to 2.1 from 3.5 per 100,000 person-years. The 1-, 3-, and 5-year survival rates were 65%, 48%, and 41%, respectively. During the year of CPA onset, approximately 50% of patients received oral corticosteroids (OCS) at least once, while about 30% underwent frequent OCS treatment (≥4 times per year) within the same timeframe. Increased mortality was independently associated with older age (>65 years) (hazard ratio [HR], 2.65; 95% confidence interval (CI), 2.54-2.77), males (1.24; 1.20-1.29), a history of chronic obstructive pulmonary disease (1.05; 1.02-1.09), lung cancer (1.12; 1.06-1.18); and ILD (1.19; 1.14-1.24); and frequent OCS use (1.13; 1.09-1.17). Conversely, decreased mortality was associated with a history of tuberculosis (HR, 0.81; 95% CI, 0.76-0.86), non-tuberculous mycobacteria (0.91; 0.86-0.96), and other chronic pulmonary diseases (0.89; 0.85-0.92). CONCLUSIONS: The incidence of CPA decreased over the past decade, although the prevalence was stable and much higher than that in European countries. Moreover, the patients' prognosis was poor. Physicians should be vigilant about CPA onset in patients with specific high-risk underlying pulmonary conditions.

Damping excessive viral-induced IFN-γ rescues the impaired anti-Aspergillus host immune response in influenza-associated pulmonary aspergillosis.

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) is a severe fungal superinfection in critically ill influenza patients that is of incompletely understood pathogenesis. Despite the use of contemporary therapies with antifungal and antivirals, mortality rates remain unacceptably high. We aimed to unravel the IAPA immunopathogenesis as a means to develop adjunctive immunomodulatory therapies. METHODS: We used a murine model of IAPA to investigate how influenza predisposes to the development of invasive pulmonary aspergillosis. Immunocompetent mice were challenged with an intranasal instillation of influenza on day 0 followed by an orotracheal inoculation with Aspergillus 4 days later. Mice were monitored daily for overall health status, lung pathology with micro-computed tomography (µCT) and fungal burden with bioluminescence imaging (BLI). At endpoint, high parameter immunophenotyping, spatial transcriptomics, histopathology, dynamic phagosome biogenesis assays with live imaging, immunofluorescence staining, specialized functional phagocytosis and killing assays were performed. FINDINGS: We uncovered an early exuberant influenza-induced interferon-gamma (IFN-γ) production as the major driver of immunopathology in IAPA and delineated the molecular mechanisms. Specifically, excessive IFN-γ production resulted in a defective Th17-immune response, depletion of macrophages, and impaired killing of Aspergillus conidia by macrophages due to the inhibition of NADPH oxidase-dependent activation of LC3-associated phagocytosis (LAP). Markedly, mice with partial or complete genetic ablation of IFN-γ had a restored Th17-immune response, LAP-dependent mechanism of killing and were fully protected from invasive fungal infection. INTERPRETATION: Together, these results identify exuberant viral induced IFN-γ production as a major driver of immune dysfunction in IAPA, paving the way to explore the use of excessive viral-induced IFN-γ as a biomarker and new immunotherapeutic target in IAPA. FUNDING: This research was funded by the Research Foundation Flanders (FWO), project funding under Grant G053121N to JW, SHB and GVV; G057721N, G0G4820N to GVV; 1506114 N to KL and GVV; KU Leuven internal funds (C24/17/061) to GVV, clinical research funding to JW, Research Foundation Flanders (FWO) aspirant mandate under Grant 1186121N/1186123 N to LS, 11B5520N to FS, 1SF2222N to EV and 11M6922N/11M6924N to SF, travel grants V428023N, K103723N, K217722N to LS. FLvdV was supported by a Vidi grant of the Netherlands Association for Scientific Research. FLvdV, JW, AC and GC were supported by the Europeans Union's Horizon 2020 research and innovation program under grant agreement no 847507 HDM-FUN. AC was also supported by the Fundação para a Ciência e a Tecnologia (FCT), with the references UIDB/50026/2020, UIDP/50026/2020, PTDC/MED-OUT/1112/2021 (https://doi.org/10.54499/PTDC/MED-OUT/1112/2021), and 2022.06674.PTDC (http://doi.org/10.54499/2022.06674.PTDC); and the "la Caixa" Foundation under the agreement LCF/PR/HR22/52420003 (MICROFUN).

Timing of recurrence after treatment of pulmonary TB.

Pulmonary TB (PTB) may recur due to reinfection or relapse after initial successful treatment. Based on microbiologically documented cases, we searched Embase, PubMed, Web of Science, and Medline for PTB recurrence. The timeframe of overall recurrences, relapse, reinfection, and risk factors were assessed. We compared the time to recurrence, relapse, and reinfection from treatment completion and plotted this using Kaplan-Meier curves. This systematic review included 23 articles describing 2,153 PTB recurrences in 75,224 treated people across all continents. Genotyping data to distinguish relapse from reinfection was available for 402 recurrences. The cumulative recurrence percentage was 2.9% over 5 years, and the median time for recurrence was 18 months (95% CI 16.99-19.0). Most recurrences (93%) were in HIV-negative people. Relapse occurred earlier than reinfection at 12 months (95% CI 10.86-13.14) vs 24 months (95% CI 21.61-26.39) (P < 0.001, χ2 59.89). In low TB burden settings, recurrences were mainly caused by relapse (85%), whereas in high-burden settings, relapses comprised 56% of recurrences. Recurrences occurred slightly earlier in HIV-positive patients (P = 0.038, χ2 4.30). The emergence of resistance to one or more first-line anti-TB agents was documented in 40 of 421 cases (9.5%). Early recurrences are mainly relapses, while late recurrences are mainly reinfections.

La TB pulmonaire (TBP) peut récidiver en raison d'une réinfection ou d'une rechute après un premier traitement réussi. En nous basant sur des cas documentés sur le plan microbiologique, nous avons mené une recherche dans les bases de données Embase, PubMed, Web of Science et Medline concernant la récurrence de la TBP. Nous avons évalué le calendrier des récidives globales, des rechutes, des réinfections ainsi que des facteurs de risque associés. De plus, nous avons comparé les délais de récurrence, de rechute et de réinfection à partir de la fin du traitement, en les illustrant à l'aide de courbes de Kaplan-Meier. Cette analyse systématique a examiné 23 études rapportant 2 153 cas de récidive de TBP parmi 75 224 individus traités à l'échelle mondiale. Des informations de génotypage permettant de différencier les rechutes des réinfections étaient accessibles pour 402 cas de récidive. Le taux cumulé de récidive s'élevait à 2,9% sur une période de 5 ans, avec un délai médian de récidive de 18 mois (IC à 95% 16,99­19,0). La majorité des récidives (93%) concernait des individus séronégatifs. Les rechutes se sont produites plus rapidement que les réinfections, à 12 mois (IC 95% 10,86­13,14) contre 24 mois (IC 95% 21,61­26,39 ; P < 0,001 ; χ2 59,89). Dans les environnements où le fardeau de la TB est faible, les récidives étaient principalement attribuées à des rechutes (85%), tandis que dans les contextes à fardeau élevé, les rechutes représentaient 56% des récidives. Les récidives se sont manifestées légèrement plus tôt chez les patients séropositifs (P = 0,038, χ2 4,30). L'apparition d'une résistance à un ou plusieurs médicaments anti-TB de première ligne a été observée dans 40 cas sur 421, soit 9,5%. Les récidives précoces sont majoritairement des rechutes, tandis que les récidives tardives sont principalement dues à des réinfections.

Diagnostic value and clinical use of metagenomic next-generation sequencing for invasive pulmonary aspergillosis.

OBJECTIVE: To compare the diagnostic efficacy of metagenomic next generation sequencing (mNGS) with traditional fungal culture, (1,3)-ß-D glucan (G) test, and galactomannan (GM) test in diagnosing invasive pulmonary aspergillosis (IPA) and to explore the advantages and disadvantages of mNGS for IPA diagnosis. METHODS: A retrospective analysis was conducted on 136 patients admitted to the Department of Respiratory and Critical Care Medicine of Affiliated Hospital of Putian University from March 2018 to March 2020. Among them, there were 66 patients with IPA (IPA group) and 70 without (non-IPA group). Baseline data, inflammatory factors, cytokines, and specimens such as bronchoalveolar lavage fluid (BALF) and blood of these patients were collected. Fungal culture test, G test, GM test and mNGS test were performed. Information included for analysis encompassed patients' host factors, clinical features, chest scanning images, laboratory test results, and treatment outcome. RESULTS: There was no statistical difference in the baseline data or inflammatory factors in patients between the IPA group and the non-IPA group. Further analysis showed that the sensitivity of mNGS in diagnosing IPA was 53.03%, which was higher than that of traditional fungal culture test (27.27%), G test (31.82%), and GM test (34.85%). Notably, when combining fungal culture, G test, GM test, and mNGS, the sensitivity increased to 69.70%, with a specificity of 97.14%. The sensitivity of the combined test was higher than that any of the tests alone for diagnosing IPA. CONCLUSION: mNGS test offers superior diagnostic performance for IPA in comparison to traditional tests, particularly for testing samples like bronchoalveolar lavage fluid and bronchial secretions. The test result remains valuable even after aspergillus treatment. In addition, the use of mNGS in conjunction with other traditional tests, such as fungal culture test, G test, and GM test, can enhance the diagnostic efficacy for IPA.

Invasive Tracheobronchial Aspergillosis: A Fatal Complication in a Patient With Treated Mediastinal Lung Adenocarcinoma.

Invasive tracheobronchial aspergillosis (ITBA) is a rare but severe form of invasive aspergillosis. This report presents a fatal case of ITBA in a 75-year-old man with a complex medical history including mediastinal lung adenocarcinoma, radiation pneumonitis, and pulmonary nocardiosis. The patient was admitted with worsening dyspnea and chest imaging revealed severe airway stenosis. Initially suspected to be cancer recurrence, post-mortem examination confirmed ITBA caused by Aspergillus penicillioides. Histopathological findings showed fungal invasion of the tracheobronchial tree with destruction, obstruction, and perforation of the airways. Multiple risk factors likely contributed to the development of ITBA in this patient, including diabetes, chronic obstructive pulmonary disease (COPD), long-term steroid use, prior COVID-19 infection, and a history of radiation therapy. This case highlights the diagnostic challenges of ITBA, particularly in patients with multiple comorbidities and a history of malignancy. It emphasizes the importance of considering fungal infections in the differential diagnosis of airway obstruction in high-risk patients.

The top 10 papers on the treatment of invasive fungal infections, 2018-2023.

Background: Invasive fungal infections are responsible for a large number of infections in hospitalized patients annually and are responsible for high morbidity and mortality. Familiarity with novel agents or strategies in this area can be challenging. Objectives: To identify the top 10 manuscripts on the treatment of invasive fungal infections from 2018 to 2023. Design: Modified Delphi consensus-building technique. Methods: A three-stage consensus-building approach was used comprised of (1) identifying relevant articles; (2) voting by a panel of experts to establish consensus on the importance of these articles; and (3) finalizing the list of top articles by a small group. Members of the Southeastern Research Group Endeavor network served as content experts. Publications from 2018 to 2023 were evaluated if articles met the following inclusion criteria: (1) published between 2018 and 2023, (2) contained content related to fungal infections, and (3) included an actionable intervention. Results: A total of 6518 potential publications were assessed. After applying inclusion and exclusion criteria, 82 articles were reviewed. The top 10 publications related to invasive fungal infections, selected by a panel of experts, are summarized in this manuscript and include publications related to the treatment of invasive aspergillosis, candidiasis, and cryptococcosis. Conclusion: This article highlights the selected publications and may serve as a key resource for teaching and training. Clinicians may also employ these reported interventions to identify new opportunities to optimize antifungal therapeutic strategies within one's institution.

Top papers in antifungal literature 2018-2023 Fungi live in the environment and in the intestinal tract of humans, and infections caused by fungi can be deadly. Knowing what has been studied in the medical literature can give medical personnel information to best treat these infections. This paper sought to use scientific methods to review and choose the top 10 papers from 2018-2023 that make a difference in treatment of these potentially deadly fungal infections. Infections covered include those caused by yeasts (Candida and Cryptococcus) and molds (Aspergillus). Drugs covered include azole antifungals (isavuconazole, voriconazole, posaconazole, and fluconazole), echinocandins (caspofungin, micafungin), amphotericin, and new drugs (fosmanogepix and rezafungin). Strategies evaluated to improve patient care include dosing changes, empiric therapy choices, and therapeutic drug monitoring. This paper might help medical personnel better manage fungal infections.

[A case report of pulmonary aspergillosis secondary to occupational chronic formaldehyde toxic obstructive pulmonary disease].

Invasive pulmonary aspergillosis is the most common type of pulmonary aspergillosis. This paper reported a patient with pulmonary aspergillosis secondary to obstructive pulmonary disease and other underlying diseases. The clinical manifestations included wheezing, cough, fever and wheezing rale in the lungs. Diagnosis was ultimately confirmed through pathogens targeted next generation sequencing and pathological examination of respiratory coughs. Following comprehensive treatment that included antifungal therapy, the patient was cured and discharged with a good prognosis.

Three-Month Mortality in Nonhaematological Patients with Chronic Pulmonary Aspergillosis: Differences between Subtypes.

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0-9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0-9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis.

ProcCluster® and procaine hydrochloride inhibit the growth of Aspergillus species and exert antimicrobial properties during coinfection with influenza A viruses and A. fumigatus in vitro.

Introduction: Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine. Methods: Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay. Results: Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication. Discussion: This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens.

Exhaled Breath Condensate Surveillance for Aspergillus in Acute Leukemia-a Pilot Trial.

Invasive fungal infections in patients with leukemia carry a high mortality rate, but early diagnosis has the potential to modify this natural history. A novel screening method using Aspergillus droplet-digital polymerase chain reaction in exhaled breath condensate may have a similar performance to serum galactomannan screening. Larger studies, including other molds, are necessary.

Invasive pulmonary aspergillosis in patients with acute leukemia.

INTRODUCTION: Invasive pulmonary aspergillosis is a serious complication in hematology. AIM: Describe the prevalence, diagnostic aspects, therapeutic modalities, and evolution of the IPA cases occurring in patients with acute leukemia. METHODS: Our study was retrospective including patients with acute leukemia who developed invasive pulmonary aspergillosis during the period January 2009 and December 2020 at the hematology department in south Tunisia. The IPA was defined in three levels of probability according to the criteria of the EORTC / MSG 2019. RESULTS: We collected 127 patients who presented with Invasive pulmonary aspergillosis. Sixty-three percent of our patients had acute myeloid leukemia. The diagnosis of invasive pulmonary aspergillosis was during the induction course in 76% of cases. Twenty-seven of our patients had chest pain. The chest Computed tomography (CT) scan showed the Halo sign in 89% of cases. The Aspergillus galactomannan antigen was positive in 38% of cases. Extrapulmonary aspergillosis involvement was noted in 18% of cases: IPA was possible and probable respectively in 59% and 41% of cases. All patients treated with Voriconazole with a favorable response in 54% of cases. The mortality rate was 46%. The overall survival at week 12 was 56%. CONCLUSION: The morbidity and mortality of patients who developed invasive pulmonary aspergillosis with acute leukemia in our series were high. We need to improve our strategy for early diagnosis and management.

Retrospective Comparison of Two Aspergillus IgG Enzyme Immunoassays for Diagnosing Pulmonary Aspergillosis.

Aspergillus-specific antibodies are diagnostic indicators of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Tests for detecting Aspergillus-specific antibodies were not used clinically in Japan, and the production of the Aspergillus precipitin test was discontinued. Thus, alternative tests for diagnosing aspergillosis are urgently needed. We retrospectively evaluated 64 patients with suspected ABPA and CPA who underwent precipitin antibody testing. Serum Aspergillus IgG levels were measured and compared using the Bordier Aspergillus fumigatus ELISA and the Platelia Aspergillus IgG (Bio-Rad) kits. Of the participants, 18 were diagnosed with CPA, and 8 were diagnosed with ABPA. Both the Bordier and Bio-Rad kits showed high sensitivity and specificity for CPA and ABPA. The area under the receiver operating characteristic curves for the Bordier and Bio-Rad kits were 0.97 and 0.95, respectively, for CPA, and 0.89 and 0.91, respectively, for ABPA. In contrast to the Bordier kit, the Bio-Rad kit showed relatively low anti-Aspergillus IgG levels and lower sensitivity to non-fumigatus Aspergillus infections. The Aspergillus-specific IgG ELISA tests showed sufficient diagnostic accuracy. Therefore, these assays are recommended as alternatives to the precipitin kit for diagnosing aspergillosis in clinical settings in Japan.

Optimized Antifungal Therapy for Chronic Pulmonary Aspergillosis.

Chronic pulmonary aspergillosis (CPA) represents a spectrum of lung disorders caused by local proliferation of Aspergillus hyphae in individuals with non-systemic or mildly systemic immunodepression or altered pulmonary integrity due to underlying disease. While long-term systemic antifungal treatment is still the mainstay for management, surgery is considered mainly in rarer invasive disease manifestations such as sinusitis and osteomyelitis. Optimal application of existing antifungal agents with suitable pharmacokinetic properties is important for the treatment of diseases such as CPA, which requires long-term use. Appropriate management of side effects by therapeutic drug monitoring, maintenance of adherence, and assessment of drug resistance to Aspergillus can provide safe and effective treatment in the future. Most available antifungal agents for the management of mycoses in humans have disadvantages that can limit their use in clinical practice. By contrast, second generation antifungals such as triazoles have advantages of extended antifungal spectrum and availability in both oral and intravenous formulations. Isavuconazole, a new extended spectrum triazole, has been shown to be effective against Aspergillus. The safety profile and excellent pharmacokinetic characteristics of isavuconazole make it an attractive option for treatment of invasive fungal infections including CPA. With this drug now available in Japan, new evidence is expected to expand treatment options. This review focuses on the selection of antifungal agents based on national and international guidelines and the characteristics of each agent for their appropriate use in CPA.

Invasive Mediastinal Aspergillosis in an 18-Year-Old Immunocompetent Female Leading to Stroke.

We present a case of invasive pulmonary aspergillosis in an immunocompetent young female. An 18-year-old female presented with symptoms of a left-sided middle cerebral artery (MCA) stroke with right arm weakness and aphasia. Computed tomography (CT) brain confirmed the diagnosis of stroke. Further history revealed that the patient had been experiencing low-grade fevers with occasional shortness of breath for the past year. The blood work had eosinophilia at that time for which she was given mebendazole but saw little improvement. Chest X-rays showed upper lobe consolidation for which a tuberculosis (TB) workup was also done, which also came out negative. At the current presentation, she underwent further workup with echocardiography and eventual ultrasound-guided mediastinal biopsy that ultimately led to the correct diagnosis of aspergillosis. However, sadly, it was already too late for the patient who passed away one day after the commencement of the amphotericin B therapy. This paper hopes to decrease the threshold of clinical suspicion for invasive aspergillosis (IA) regardless of the immunity status of the patient, especially if they are presenting with an unrelenting mediastinal or pulmonary symptom complex in the setting of eosinophilia.

Clinical characteristics of pulmonary Mycobacterium avium complex disease in patients with interstitial lung disease.

OBJECTIVE: Mycobacterium avium complex pulmonary disease (MAC-PD) is occasionally complicated by interstitial lung disease (ILD) in clinical practice, but clinical studies are limited. This study aims to elucidate the clinical and imaging characteristics of MAC-PD in patients with ILD. METHODS: We retrospectively analyzed imaging and clinical data from medical records of 54 consecutive ILD patients diagnosed with MAC-PD from 2011 to 2021 at our institution. We compared the imaging and clinical data of these patients with 2218 ILD patients diagnosed at our institution. RESULTS: The mean age of the patients was 74 years, with 25 males and 29 females, and a mean body mass index (BMI) of 20.0 kg/m2. Compared to all ILD patients, ILD-associated MAC-PD had older ages, lower BMI. The most common underlying ILD diagnosis was unclassifiable interstitial pneumonia. MAC-PD imaging classification was nodular-bronchiectatic (NB) type in 17 patients, fibro-cavitary (FC) type in 15 patients, and unclassifiable (UC) type in 22 patients. Many UC types were difficult to diagnose due to the absence of clear findings indicative of MAC infection. Chronic pulmonary aspergillosis complication was 24.1 %. The mean survival of ILD-associated MAC-PD was 55.6 months, shorter than that of regular MAC-PD. The UC type had a shorter survival than the NB type, similar to the FC type. CONCLUSION: MAC-PD associated with ILD frequently complicates chronic pulmonary aspergillosis and has a poor prognosis. The most common imaging type, UC type, particularly has a shorter survival. Careful management is essential for MAC-PD associated with ILD.

High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide Population-Based Matched Cohort Study.

BACKGROUND: Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain. METHODS: We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA). RESULTS: During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25-1.76) and 90 days (aHR, 1.63; CI, 1.44-1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79-1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94-9.43). CONCLUSION: Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.

Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review.

BACKGROUND: Reports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians' understanding of the disease and to facilitate early diagnosis and treatment. CASE PRESENTATION: A 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. INFECTION: Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates. CONCLUSION: Our case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Investigation of risk factors for invasive pulmonary aspergillosis among patients with COVID-19.

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA.

Evaluation of the Dynamiker Quantitative Anti-Aspergillus Fumigatus Specific Detection for the Diagnosis of Different Kinds of Chronic Pulmonary Aspergillosis.

Background: Aspergillus-specific IgG antibody test is considered to be the most reliable method for diagnosing chronic pulmonary aspergillosis (CPA), while its diagnostic roles in different kinds of CPA are still uncertain and it is a challenge of having a threshold to interpret the IgG levels. Purpose: This study aimed to evaluate the diagnostic value of the Dynamiker quantitative Aspergillus fumigatus-specific IgG antibody in different types of CPA with the aim of providing a reference for clinical work. Methods: This prospective study collected the clinical data of patients with suspected CPA admitted to the hospital from January 2020 to December 2022 and divided them into two groups: CPA and non-CPA. The study analyzed clinical characteristics and Aspergillus-specific IgG antibody test's diagnostic value, and a receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy. Results: We enrolled 54 CPA patients and 132 non-CPA patients. The average admission age of the CPA group was 61.0 (43.8, 70.0) years, and the sex ratio was 32/22 (male/female). The level of Aspergillus fumigatus-specific IgG antibody in the CPA group was significantly higher than the non-CPA group (95.2 (31.3, 213.3) vs 47.5 (34.0, 80.3) AU/mL, p = 0.001). The area under the ROC curve was 0.653 (95% confidence interval [CI]: 0.580-0.721, p = 0.003). The cutoff with the best diagnostic efficacy was 87 AU/mL, and the sensitivity and specificity were 57.4% and 77.3%, respectively. There was no significant difference in the level of specific IgG antibody among the five CPA types (p = 0.543); however, it was relatively higher in chronic cavitary pulmonary aspergillosis (CCPA). Conclusion: Aspergillus-specific IgG antibody is valuable diagnostic marker for CPA, while its value in differential diagnosis among different types of CPA is limited.

Navigating Uncertainty: Managing Influenza-Associated Invasive Pulmonary Aspergillosis in an Intensive Care Unit.

We present a challenging case of a patient admitted to an intensive care unit with influenza-associated pulmonary aspergillosis (IAPA). The clinical course was characterised by refractory fungal pneumonia and tracheobronchitis, suspected drug-induced liver injury due to triazole antifungals, and secondary bacterial infections with multidrug-resistant microorganisms, resulting in a fatal outcome despite the optimisation of antifungal treatment through therapeutic drug monitoring. This case underscores the complexity that clinicians face in managing critically ill patients with invasive fungal infections.