Allergic bronchopulmonary mycosis due to Schizophyllum commune in a patient with chronic hepatitis B.

INTRODUCTION: Schizophyllum commune (S. commune) is an opportunistic pathogenic fungus and can cause infection of the respiratory system in immunocompromised hosts. Allergic bronchopulmonary mycosis (ABPM) is the major disease caused by S. commune. However, identification of S. commune using routine mycological diagnostic methods is difficult. It is easy to make mistakes in diagnosis and treatment, resulting in deterioration of the disease. We report the first case of ABPM due to S. commune in a Chinese patient with chronic hepatitis B. CASE PRESENTATION: The patient presented cough, sputum and dyspnea for six months. The pathogen was missed during routine laboratory workup. We performed bronchoscopy examination and bronchoalveolar lavage. S. commune was identified by metagenomic next-generation sequencing (mNGS) of bronchial alveolar lavage fluid (BALF). Hence, the patient was immediately treated with 200 mg voriconazole twice daily (intravenous infusion) and 20 mg prednisone once a day (oral therapy), along with oral entecavir for hepatitis B. There was no recurrence of infection after the medication was discontinued. CONCLUSIONS: S. commune infection should be considered in the diagnosis of patients with refractory cough, sputum and dyspnea, especially in immunocompromised individuals. The mNGS technique is an effective supplementary technique for the diagnosis of S. commune infection, enabling precise clinical decision-making and appropriate treatment. Most patients have good prognosis with a combination of proper antifungal therapy and hormonal therapy.

Improved diagnostic markers for invasive pulmonary aspergillosis in COPD patients.

Background: The prevalence of invasive pulmonary aspergillosis (IPA) among patients with chronic obstructive pulmonary disease (COPD) is steadily increasing, leading to high mortality. Although early diagnosis can significantly reduce mortality, the efficacy of current diagnostic methods is limited. Consequently, there is a need for novel approaches for early IPA detection. Methods: This retrospective study involved 383 hospitalized COPD patients with GOLD stages III and IV. The IPA group (67 patients) and non-IPA group (316 patients) were identified at the First Affiliated Hospital of Guangzhou Medical University between January 2016 and February 2022. We analyzed common serological indicators in our hospital to identify predictive indicators for the early diagnosis of IPA in COPD patients. Results: The sensitivity and specificity of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), lactate dehydrogenase (LDH), and ceruloplasmin (CER) for diagnosing IPA in COPD patients were as follows: CRP (91.2%, 57.7%), ESR (77.5%, 73.0%), PCT (60.5%, 71.4%), LDH (50.0%, 88.8%), and CER (60.7%, 74.3%). Combinations of biomarkers, such as CRP-ESR, CRP-LDH, ESR-LDH, ESR-CER, and LDH-CER, showed promising diagnostic potential, with larger area under the curve (AUC) values for IPA diagnosis in COPD patients. However, no statistically significant difference was observed between the diagnostic efficacy of single biomarkers and combined biomarkers. Notably, compared to those in the unassisted ventilation group, the patients in the assisted ventilation group (including noninvasive ventilation and tracheal intubation/incision-assisted ventilation group) exhibited significantly greater PCT and LDH levels, while the CER significantly decreased (p=0.021). There were no significant differences in biomarker levels between the ICU group and the non-ICU group. CRP (p<0.01), ESR (p=0.028), PCT (p<0.01), and CER (p<0.01) were positively correlated with hospitalization duration, whereas LDH was not correlated with hospitalization duration. Conclusion: Our study highlights the diagnostic potential of CRP, ESR, PCT, LDH, and CER for IPA in COPD patients. CRP and LDH can also initially predict the need for assisted ventilation, while CRP can initially estimate the length of hospitalization. This study represents the first report of the potential of CER for diagnosing IPA, suggesting its significance for further research.

Efficacy and safety of caspofungin for the treatment of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

OBJECTIVES: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA). METHODS: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro, and the safety of caspofungin. RESULTS: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants. CONCLUSIONS: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Baseline chest computed tomography for diagnosis of invasive aspergillosis in patients with acute myeloid leukaemia treated with intensive chemotherapy: A retrospective single-centre cohort study.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a relatively common infection in patients with acute myeloid leukaemia (AML), and is associated with high mortality rates. Optimising early detection is key to reduce the burden of IPA in this population. In this retrospective cohort study, we evaluated the added value of baseline chest CT before start of classical induction chemotherapy. METHODS: Adult patients receiving first-line intensive chemotherapy for AML were included if a baseline chest CT scan was available (±7 days). Data were collected from the electronic health record. IPA was classified using the EORTC/MSGERC 2020 consensus definitions. RESULTS: Between 2015 and 2019, 99 patients were included. During first-line treatment, 29/99 (30%) patients developed a probable IPA. Baseline chest CT was abnormal in 61/99 (62%) and 14/61 (23%) patients had typical radiological signs for IPA. An abnormal scan showed a trend towards higher risk for IPA (hazard ratio (HR): 2.12; 95% CI 0.95-4.84). Ground glass opacities were a strong predictor for developing IPA (HR 3.35: 95% CI 1.61-7.00). No probable/proven IPA was diagnosed at baseline; however, a bronchoalveolar lavage (BAL) at baseline was only performed in seven patients. Twelve-week mortality was higher in patients with IPA (7/26, 27% vs. 5/59, 8%; p = .024). CONCLUSION: Baseline chest CT scan could be an asset in the early diagnosis of IPA and contribute to risk estimation for IPA. In patients with an abnormal baseline CT, performing a BAL should be considered more frequently, and not only in patients with radiological findings typical for IPA.

Risk factors for short-term prognosis of end-stage liver disease complicated by invasive pulmonary aspergillosis.

BACKGROUND AND AIM: Patients with end-stage liver disease (ESLD) are susceptible to invasive pulmonary aspergillosis (IPA). This study aimed to investigate the risk factors affecting the occurrence and short-term prognosis of ESLD complicated by IPA. METHODS: This retrospective case-control study included 110 patients with ESLD. Of them, 27 ESLD-IPA received antifungal therapy with amphotericin B (AmB); 27 AmB-free-treated ESLD-IPA patients were enrolled through 1:1 propensity score matching. Fifty-six ESLD patients with other comorbid pulmonary infections were enrolled as controls. The basic features of groups were compared, while the possible risk factors affecting the occurrence and short-term outcomes of IPA were analyzed. RESULTS: Data analysis revealed invasive procedures, glucocorticoid exposure, and broad-spectrum antibiotic use were independent risk factors for IPA. The 54 patients with ESLD-IPA exhibited an overall treatment effectiveness and 28-d mortality rate of 50.00% and 20.37%, respectively, in whom patients treated with AmB-containing showed higher treatment efficacy than patients treated with AmB-free antifungal regimens (66.7% vs. 33.3%, respectively, χ2 = 6.000, P = 0.014). Multivariate logistic regression analysis revealed that the treatment regimen was the only predictor affecting patient outcomes, with AmB-containing regimens were 4.893 times more effective than AmB-free regimens (95% CI, 1.367-17.515; P = 0.015). The only independent predictors affecting the 28-d mortality rate were neutrophil-to-lymphocyte ratio and IPA diagnosis (OR = 1.140 and 10.037, P = 0.046 and 0.025, respectively). CONCLUSIONS: Glucocorticoid exposure, invasive procedures, and broad-spectrum antibiotic exposure increased the risk of IPA in ESLD patients. AmB alone or combined with other antifungals may serve as an economical, safe, and effective treatment option for ESLD-IPA.

Clinical characteristics and outcomes of pleural aspergillosis: a review of 13 cases.

Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), which mostly occurs in the immunocompromised host. The clinical condition is critical, especially to those who develop bronchopleural fistula. This study aimed to assess the characteristics and the prognosis of aspergillus pleurisy. Clinical data from 13 patients diagnosed with aspergillus pleurisy in our hospital from January 2000 to December 2022 were retrospectively studied. Thirteen patients with Aspergillus pleurisy were included. There were 10 males and 3 females, with a median age of 65 (range: 18-79) years. Bronchopleural fistula was present in eight patients. A proven diagnosis of Aspergillus pleurisy was based on positive pleural fluid culture in seven cases and histopathological examination of pleural biopsies in six cases. Four patients refused further treatment and were discharged from the hospital against medical advice. Nine cases recovered and were discharged after multiple antifungal treatments (systemic and topical antifungal therapies, pleural drainage and irrigation, and surgical repair). During follow-up, one patient, who suffered underlying bronchiectasis, died of massive hemoptysis 2 years after discharge. The remaining eight cases are still under close follow-up, with a median follow-up of 5.4 (range: 1.3-18.9) years. The prognosis of aspergillus pleurisy complicated with bronchopleural fistula is poor. Thoracic surgery, especially lung resection, is a risk factor associated with the incidence of Aspergillus pleurisy. Systemic antifungal therapy and adequate pleural irrigation could improve the prognosis. IMPORTANCE: Aspergillus pleurisy is a rare complication of invasive pulmonary aspergillosis (IPA), associated with a poor prognosis. The morbidity and mortality of this condition have not been thoroughly studied, and recent research on this topic is limited. The current study included 13 patients diagnosed with Aspergillus pleurisy, with the majority presenting concomitantly with a bronchopleural fistula. Among these patients, nine had a history of thoracic surgery, including lung transplantation and lobectomy. Four patients refused further treatment and were discharged against medical advice, while one patient succumbed to massive hemoptysis 2 years after discharge. This case series provides essential insights into Aspergillus pleurisy and evaluates the therapeutic strategy based on a limited cohort.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Diagnostic performance of serum galactomannan and ß-D-glucan for invasive aspergillosis in suspected patients: A meta-analysis.

BACKGROUND: Serum galactomannan (GM) and ß-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually. METHODS: A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone. RESULTS: Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40-0.66) vs 0.72 (95% CI 0.61-0.81) and a pooled specificity of 0.94 (95% CI 0.91-0.97) vs 0.82 (95% CI 0.73-0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87-0.92) vs 0.83 (95% CI 0.80-0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69-0.86) and 0.76 (95% CI 0.69-0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone. CONCLUSION: Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.

Invasive pulmonary and central nervous system aspergillosis in a child: A case report and literature review.

RATIONALE: Children with haematological malignancies have a higher risk of developing aggressive pulmonary aspergillosis and a higher mortality rate. The most common site of extrapulmonary aspergillosis in children is the central nervous system (CNS), and the death rate is higher when CNS is affected. Therefore, early diagnosis and treatment of invasive aspergillosis are essential for reducing mortality. PATIENT CONCERNS: We report a case of an 8-year-old girl with acute lymphoblastic leukaemia who developed invasive pulmonary aspergillosis complicated by CNS aspergillosis. Aspergillus was confirmed by metagenomic sequencing of pathogenic microorganisms. DIAGNOSES: Invasive pulmonary and central nervous system aspergillosis. INTERVENTIONS: The patient was treated with combined systemic antifungal agents (voriconazole and liposomal amphotericin B) and intrathecal injection of amphotericin B. OUTCOMES: The treatment was well tolerated and resulted in remarkable clinical and radiological head improvements. LESSONS: Invasive aspergillosis has a high mortality rate and requires early diagnosis and treatment. Pathogenic microbial metagenomic sequencing is a convenient method to assist in the early diagnosis of aspergillosis. Voriconazole is the drug of choice for the treatment of invasive aspergillosis. When CNS aspergillosis occurs, it can be combined with other systemic antifungal drugs and intrathecal injection of amphotericin B.

In vivo pharmacodynamic characterization of a next-generation polyene, SF001, in the invasive pulmonary aspergillosis mouse model.

SF001 is a next-generation polyene antifungal drug in development, designed to have increased specificity to fungal ergosterol, which is absent in humans, and decreased binding to cholesterol. SF001 demonstrates long-acting, potent, broad-spectrum fungicidal activity. The goal of the current study was to determine the pharmacodynamic index and target of SF001 in an immunocompromised mouse model of invasive pulmonary aspergillosis against six Aspergillus fumigatus isolates. Minimum inhibitory concentration (MIC) values ranged from 0.5 to 2.0 mg/L. Plasma and epithelial lining fluid (ELF) pharmacokinetics were performed following single intraperitoneal doses of 1, 4, 16, and 64 mg/kg. Treatment efficacy was assessed with each of the six fungal isolates using daily doses of SF001 ranging from 0.25 to 64 mg/kg/day over a 96-h treatment duration. Efficacy was assessed by A. fumigatus quantitative PCR of conidial equivalents from lung homogenates. Nonlinear regression analysis using the Hill equation demonstrated that the 24-h exposure-response relationships for both plasma and ELF area under the concentration/MIC and Cmax/MIC ratios were strong and relatively similar [coefficient of determination (R2) = 0.74-0.75). Exposure-response relationships included a median plasma 24-h Cmax/MIC target for stasis and 1-log kill endpoint of 0.5 and 0.6, respectively. The present studies demonstrated in vitro and in vivo SF001 potency against A. fumigatus. These results have potential relevance for SF001 clinical dose selection and evaluation of susceptibility breakpoints.

High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Different forms of pulmonary aspergillosis: A pictorial essay.

Pulmonary aspergillosis is a group of mycotic diseases affecting the lungs. The form of the disease mainly depends on the immune status of the patient and underlying conditions. Invasive pulmonary aspergillosis usually affects immunocompromised patients - angio-invasive and airway-invasive forms are possible. Chronic aspergillosis usually appears in mildly immunosuppressed or immunocompetent patients with underlying structural lung changes and may have diverse forms: simple aspergilloma, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, subacute invasive pulmonary aspergillosis, aspergillus nodules and endobronchial aspergilloma. Allergic bronchopulmonary aspergillosis is a hyper-reactivity reaction to Aspergillus species, and usually develops in asthma and cystic fibrosis patients. The aim of this article is to comprehensively overview different forms of aspergillosis, their symptoms and underlying conditions and to present imaging findings.

Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment.

Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by Aspergillus hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.

Clinical characteristics, bacterial coinfections and outcomes in COVID-19-associated pulmonary aspergillosis in a third-level Mexican hospital during the COVID-19 pre-vaccination era.

BACKGROUND: Damage due to respiratory viruses increases the risk of bacterial and fungal coinfections and superinfections. High rates of invasive aspergillosis are seen in severe influenza and COVID-19. This report describes CAPA cases diagnosed during the first wave in the biggest reference centre for severe COVID-19 in Mexico. OBJECTIVES: To describe the clinical, microbiological and radiological characteristics of patients with invasive pulmonary aspergillosis associated with critical COVID-19, as well as to describe the variables associated with mortality. METHODS: This retrospective study identified CAPA cases among individuals with COVID-19 and ARDS, hospitalised from 1 March 2020 to 31 March 2021. CAPA was defined according to ECMM/ISHAM consensus criteria. Prevalence was estimated. Clinical and microbiological characteristics including bacterial superinfections, antifungal susceptibility testing and outcomes were documented. RESULTS: Possible CAPA was diagnosed in 86 patients among 2080 individuals with severe COVID-19, representing 4.13% prevalence. All CAPA cases had a positive respiratory culture for Aspergillus species. Aspergillus fumigatus was the most frequent isolate (64%, n = 55/86). Seven isolates (9%, n = 7/80) were resistant to amphotericin B (A. fumigatus n = 5/55, 9%; A. niger, n = 2/7, 28%), two A. fumigatus isolates were resistant to itraconazole (3.6%, n = 2/55). Tracheal galactomannan values ranged between 1.2 and 4.05, while serum galactomannan was positive only in 11% (n = 3/26). Bacterial coinfection were documented in 46% (n = 40/86). Gram negatives were the most frequent cause (77%, n = 31/40 isolates), from which 13% (n = 4/31) were reported as multidrug-resistant bacteria. Mortality rate was 60% and worse prognosis was seen in older persons, high tracheal galactomannan index and high HbA1c level. CONCLUSIONS: One in 10 individuals with CAPA carry a resistant Aspergillus isolate and/or will be affected by a MDR bacteria. High mortality rates are seen in this population.

Effect of volume of instillate on the diagnostic utility of bronchoalveolar lavage galactomannan in patients with suspected chronic pulmonary aspergillosis-A pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) galactomannan (GM) is commonly used to diagnose Aspergillus-related lung diseases. However, unlike serum GM, which is measured in undiluted blood, BAL-GM is estimated using variable aliquots and cumulative volume of instillates during bronchoscopy. OBJECTIVE: Since different studies have reported varying diagnostic accuracy and cut-offs for BAL-GM in CPA, we hypothesized that the total volume of instillate and 'order/label' of aliquots significantly affects the BAL-GM values, which was evaluated as part of this study. PATIENTS & METHODS: We obtained 250 BAL samples from 50 patients (five from each) with suspected chronic pulmonary aspergillosis. BAL fluid was collected after instilling sequential volumes of 40 mL of normal saline each for the first four labels and a fifth label was prepared by mixing 1 mL from each of the previous labels. The GM level of each label was measured by PLATELIA™ ASPERGILLUS Ag enzyme immunoassay. This study measured the discordance, level of agreement, diagnostic characteristics (sensitivity, specificity and AUROC) and best cut-offs for BAL-GM in the different aliquots of lavage fluid. RESULTS: The study population, classified into CPA (28%) and non-CPA (72%) groups, based on ERS/ESCMID criteria (excluding BAL-GM) were not different with respect to clinico-radiological characteristics. The discordance of BAL-GM positivity (using a cut-off of >1) between the serial labels for the same patient ranged between 10% and 22%, while the discordance between classification using BAL-GM positivity (using a cut-off of ≥1) and clinic-radio-microbiological classification ranged between 18% and 30%. The level of agreement for serial labels was at best fair (<0.6 for all except one 'label'). The AUROC for the serial samples ranged between 0.595 and 0.702, with the '40 mL and the 'mix' samples performing the best. The best BAL-GM cut-off also showed significant variation between serial labels of varying dilutions (Range:1.01 - 4.26). INTERPRETATION: This study highlights the variation in BAL-GM measured and the 'positivity' between different 'labels' of aliquots of BAL, with the first aliquot and the mixed sample showing the best performances for diagnosis of CPA. Future studies should attempt to 'standardise' the instilled volume for BAL-GM estimation to standardise the diagnostic yield.

Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Invasive pulmonary aspergillosis following human metapneumovirus infection in solid-organ transplant recipients: Another virus to add to the list.

There is increasing recognition that respiratory viral infections such as influenza, respiratory syncytial virus, parainfluenza virus, adenovirus, and SARS-CoV-2 can promote the development of invasive fungal pulmonary coinfections, particularly invasive aspergillosis, both in immunocompetent and immunocompromised patients. To date, there are no case reports exploring the role of human metapneumovirus as a risk factor for fungal coinfection. Below, we describe the case of a 63-year-old woman who received a kidney transplant and developed invasive pulmonary aspergillosis after a human metapneumovirus infection and discuss the possible phenomena that could favor this association.

Lung and sinus fungal infection imaging in immunocompromised patients.

BACKGROUND: Imaging is a key diagnostic modality for suspected invasive pulmonary or sinus fungal disease and may help to direct testing and treatment. Fungal diagnostic guidelines have been developed and emphasize the role of imaging in this setting. We review and summarize evidence regarding imaging for fungal pulmonary and sinus disease (in particular invasive aspergillosis, mucormycosis and pneumocystosis) in immunocompromised patients. OBJECTIVES: We reviewed data on imaging modalities and findings used for diagnosis of invasive fungal pulmonary and sinus disease. SOURCES: References for this review were identified by searches of PubMed, Google Scholar, Embase and Web of Science through 1 April 1 2023. CONTENT: Computed tomography imaging is the method of choice for the evaluation of suspected lung or sinus fungal disease. Although no computed tomography radiologic pattern is pathognomonic of pulmonary invasive fungal disease (IFD) the halo sign firstly suggests an angio-invasive pulmonary aspergillosis while the Reversed Halo Sign is more suggestive of pulmonary mucormycosis in an appropriate clinical setting. The air crescent sign is uncommon, occurring in the later stages of invasive aspergillosis in neutropenic patients. In contrast, new cavitary lesions should suggest IFD in moderately immunocompromised patients. Regarding sinus site, bony erosion, peri-antral fat or septal ulceration are reasonably predictive of IFD. IMPLICATIONS: Imaging assessment of the lung and sinuses is an important component of the diagnostic work-up and management of IFD in immunocompromised patients. However, radiological features signs have sensitivity and specificity that often vary according to underlying disease states. Periodic review of imaging studies and diagnostic guidelines characterizing imaging findings may help clinicians to consider fungal infections in clinical care thereby leading to an earlier confirmation and treatment of IFD.

Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment.

Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration. Inspired by natural lung surfactants, dipalmitoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DPPC/DMPG) surface-modified lipid nanoparticles (LNPs) were scrutinized for pulmonary administration. DPPC/DMPG-VRZ-LNPs prepared using ultrasonication/thin film hydration were investigated for colloidal properties over 3-month shelf storage. They were stable with a slight change in entrapment efficiency. They provided a sustained VRZ release over 24 h, with a rapid initial release. In vitro aerosolization indicated higher percentages of VRZ deposited on stages corresponding to secondary bronchi and alveolar ducts. Moreover, intrapulmonary administration maintained high lung VRZ concentration (27 ± 1.14 µg/g) after 6 h. A preclinical study using a cyclophosphamide-induced neutropenic rat model demonstrated a 3-fold reduction in BALF-Galactomannan down to 0.515 ± 0.22 µg/L confirming DPPC/DMPG-VRZ-LNPs potential in hyphal growth inhibition. Histopathological examination of infected/nontreated lung sections exhibited dense fungal load inside alveoli and blood vessels indicating massive tissue and angio-invasiveness. Nevertheless, DPPC/DMPG-VRZ-LNPs-treated animals displayed minimal hyphae with no signs of invasiveness. The developed bioinspired nanoparticles serve as prospective bioactive nanocarrier candidates for pulmonary administration of VRZ in the management of IPA.